query: milk

positive: p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene. Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.

positive: Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA... BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.

positive: Alkylphenols in human milk and their relations to dietary habits in central Taiwan. The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.

positive: Xeno-estrogenic compounds in precipitation. The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.

positive: Nonylphenol and octylphenol in human breast milk. Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.

positive: Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.

positive: European bans on surfactant trigger transatlantic debate. U.S. and European regulators and researchers disagree over risks of a common class of surfactants.

positive: Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy). This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.

positive: Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7). A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.

positive: Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He... Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S

positive: Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

positive: Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment. The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.

positive: Effects of intestinal microflora and the environment on the development of asthma and allergy. The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.

positive: Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis. BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel

positive: Alkylphenols--potential modulators of the allergic response. The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.

positive: Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men. BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids.

positive: Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.

positive: Milk Intake in Early Life and Risk of Advanced Prostate Cancer The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002–2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.

positive: The experience of Japan as a clue to the etiology of breast and ovarian cancers: relationship between death from both malignancies and dietary prac... Although breast and ovarian cancers are rare in Japan compared with other developed countries, the death rates for both are increasing. In Japan, dramatic lifestyle changes occurred after World War II. Over the past 50 years (1947-1997), the age-standardized death rates of breast and ovarian cancers increased about 2- and 4-fold, respectively, and the respective intake of milk, meat, and eggs increased 20-, 10-, and 7-fold. The increase in the annual death rates from breast and ovarian cancers might be due to the lifestyle changes (increased consumption of animal-derived food) that occurred after 1945. Among the food, milk and dairy products should receive particular attention since they contain considerable amounts of estrogens.

positive: Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies. We have previously found a positive association between milk consumption and prostate cancer risk using meta-analysis to analyze published case-control studies. In the present study, further meta-analysis was conducted to estimate the summary relative risk (RR) between the consumption of milk and dairy products and prostate cancer from cohort studies published between 1966- 2006. We found 18 relevant articles and 13 independent studies were available for our analysis. The summary RR was 1.13 (95% confidence interval = 1.02-1.24) when comparing the highest with the lowest quantile of consumption. The summary RRs by study stratification showed a positive association. A dose-response relationship was identified when combining the studies that partitioned the consumption by quintiles. We also evaluated the effects of some limitations, such as dairy classification, prostate cancer stages and publication bias, in the present study. These findings, together with the previous study, suggest that the consumption of milk and dairy products increases the risk of prostate cancer. This is biologically plausible since milk contains considerable amounts of fat, hormones, and calcium that are associated with prostate cancer risk.

positive: Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies. Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further. Copyright 2004 Lawrence Erlbaum Associates, Inc.

positive: Milk stimulates growth of prostate cancer cells in culture. Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.

positive: Incidence and mortality of testicular and prostatic cancers in relation to world dietary practices. The incidence and mortality rates of testicular and prostatic cancers in 42 countries were correlated with the dietary practices in these countries using the cancer rates (1988-92) provided by the International Agency for Research on Cancer (IARC) and the food supply data (1961-90) provided by the Food and Agriculture Organization (FAO). Among the food items we examined, cheese was most closely correlated with the incidence of testicular cancer at ages 20-39, followed by animal fats and milk. The correlation coefficient (r) was highest (r = 0.804) when calculated for cheese consumed during the period 1961-65 (maternal or prepubertal consumption). Stepwise-multiple-regression analysis revealed that milk + cheese (1961-65) made a significant contribution to the incidence of testicular cancer (standardized regression coefficient [R] = 0.654). Concerning prostatic cancer, milk (1961-90) was most closely correlated (r = 0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk + cheese as a factor contributing to the incidence of prostatic cancer (R = 0.525). The food that was most closely correlated with the mortality rate of prostatic cancer was milk (r = 0.766), followed by coffee, cheese and animal fats. Stepwise-multiple-regression analysis revealed that milk + cheese was a factor contributing to mortality from prostatic cancer (R = 0.580). The results of our study suggest a role of milk and dairy products in the development and growth of testicular and prostatic cancers. The close correlation between cheese and testicular cancer and between milk and prostatic cancer suggests that further mechanistic studies should be undertaken concerning the development of male genital organ cancers. Copyright 2001 Wiley-Liss, Inc.

positive: Soy protein may alleviate osteoarthritis symptoms. Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.

positive: Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks. OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.

positive: Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

positive: Poppy seed foods and opiate drug testing--where are we today? Seeds of the opium poppy plant are legally sold and widely consumed as food. Due to contamination during harvesting, the seeds can contain morphine and other opiate alkaloids. The objective of this study is to review the toxicology of poppy seed foods regarding influence on opiate drug tests. Computer-assisted literature review resulted in 95 identified references. Normal poppy seed consumption is generally regarded as safe. During food processing, the morphine content is considerably reduced (up to 90%). The possibility of false-positive opiate drug tests after poppy food ingestion exists. There are no unambiguous markers available to differentiate poppy food ingestion from heroin or pharmaceutical morphine use. This is also a problem in heroin-assisted maintenance programs. A basic requirement in such substitution programs is the patients' abstinence from any other drugs, including additional illicit heroin. Also a lack of forensic ingestion trials was detected that consider all factors influencing the morphine content in biologic matrices after consumption. Most studies did not control for the losses during food processing, so that the initial morphine dosage was overestimated. The large reduction of the morphine content during past years raises questions about the validity of the "poppy seed defence." However, a threshold of food use that would not lead to positive drug tests with certainty is currently unavailable. Research is needed to prove if the morphine contents in today's foods still pose the possibility of influencing drug tests. Future trials should consider processing-related morphine losses.

positive: Morphine levels in urine subsequent to poppy seed consumption. Urine morphine levels after the consumption of poppy seeds were measured in two separate trials. Maximum levels of approximately 18 micrograms/ml were found using RIA, EMIT-ST and GC methodologies. Positive immunoassay results were seen up to 60 h post-ingestion. Several different lots of seeds from various sources were assayed for morphine and found to range from 4-200 mg/kg. Differentiation of poppy seed eaters from opiate users was not possible via the identification of minor alkaloid constituents of poppy seeds. It is, however, possible to analyse opiate urines with respect to 6-O-acetylmorphine. Below the level of approximately 5 micrograms/ml total opiates, GC/MS is the method of choice for this analysis.

positive: Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta... In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.

positive: Choline intake and risk of lethal prostate cancer: incidence and survival Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.

positive: Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.

positive: Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men.

positive: Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

positive: Choline and betaine intake and the risk of colorectal cancer in men Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.

positive: Alkaline diets favor lean tissue mass in older adults Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.

positive: Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.

positive: The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health? This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.

positive: Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores. OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.

positive: Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians. A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.

positive: Age and systemic acid-base equilibrium: analysis of published data. To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.

positive: Diet-induced metabolic acidosis. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

positive: Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia. The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.

positive: Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

positive: Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY

positive: Retinal arterial changes correlate with cerebral small-vessel disease. OBJECTIVE: To examine the relation between retinal artery disease and cerebral small-vessel disease (SVD). METHODS: In a prospective cohort of patients with symptomatic atherosclerotic disease, the authors performed retinal photographs and brain MRI. Two ophthalmologists, not aware of the MR results, independently assessed retinal arterial narrowing, crossings, sclerosis, and tortuosity according to standard scoring lists. Two observers independently assessed white matter lesions (WML) and lacunar infarcts on the MR images. Lesions were considered abnormal only when both ophthalmologists or MR raters agreed. Cerebral SVD was defined as the presence of WML or lacunar infarcts. RESULTS: In 179 patients, retinal photographs and brain MRI were performed. Of the 108 patients with MR signs of SVD, 92% had at least one retinal vascular abnormality; of the 71 patients without SVD, 77% had retinal pathology (p < 0.01). All types of retinal vascular pathology occurred more frequently in patients with SVD, but only retinal arterial narrowing and sclerosis differed significantly. In the 109 normotensive patients, the presence of any retinal vascular change correlated with signs of SVD (p = 0.01). CONCLUSION: Pathologic changes in the retinal arteries parallel changes in the small cerebral arteries that cause WML and lacunes, both in hypertensive and in normotensive patients.

positive: Effect of low saturated fat diet in early and late cases of multiple sclerosis. 144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.

positive: A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

positive: Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.

positive: Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer? Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.

positive: Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.

positive: Colorectal cancer screening with odour material by canine scent detection Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.

positive: Olfactory detection of human bladder cancer by dogs: proof of principle study Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.

positive: The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.

positive: Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment. BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.

positive: Association between organic dietary choice during pregnancy and hypospadias in offspring: a study of mothers of 306 boys operated on for hypospadias. PURPOSE: The etiology of hypospadias is poorly understood. Exposure to pesticides has been considered a risk factor, although findings are inconsistent. Diet constitutes a significant exposure route for pesticides, and pesticide residues are more frequently reported in conventional than organic food products. We examined the association between organic dietary choice during pregnancy and presence of hypospadias in the offspring. MATERIALS AND METHODS: Mothers of 306 boys operated on for hypospadias were frequency matched for geography and child birth year to 306 mothers of healthy boys in a case-control study. Telephone interviews were conducted regarding demographic and lifestyle factors, including intake and organic choice of selected food items (milk, dairy products, egg, fruit, vegetables and meat). Logistic regression models were constructed for dietary variables, and odds ratios were calculated controlling for maternal age, body mass index and alcohol consumption. RESULTS: Overall organic choice of food items during pregnancy was not associated with hypospadias in the offspring. However, frequent current consumption of high fat dairy products (milk, butter) while rarely or never choosing the organic alternative to these products during pregnancy was associated with increased odds of hypospadias (adjusted OR 2.18, 95% CI 1.09-4.36). CONCLUSIONS: This large case-control study of boys operated on for hypospadias suggests an association between hypospadias in the offspring and the mother not choosing the organic alternative, and having a high current intake of nonorganic butter and cheese. This finding could be due to chemical contamination of high fat dairy products. However, general lifestyle and health behavior related to choosing organic alternatives may also explain the finding. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

positive: Profiles of Organic Food Consumers in a Large Sample of French Adults: Results from the Nutrinet-Santé Cohort Study Background Lifestyle, dietary patterns and nutritional status of organic food consumers have rarely been described, while interest for a sustainable diet is markedly increasing. Methods Consumer attitude and frequency of use of 18 organic products were assessed in 54,311 adult participants in the Nutrinet-Santé cohort. Cluster analysis was performed to identify behaviors associated with organic product consumption. Socio-demographic characteristics, food consumption and nutrient intake across clusters are provided. Cross-sectional association with overweight/obesity was estimated using polytomous logistic regression. Results Five clusters were identified: 3 clusters of non-consumers whose reasons differed, occasional (OCOP, 51%) and regular (RCOP, 14%) organic product consumers. RCOP were more highly educated and physically active than other clusters. They also exhibited dietary patterns that included more plant foods and less sweet and alcoholic beverages, processed meat or milk. Their nutrient intake profiles (fatty acids, most minerals and vitamins, fibers) were healthier and they more closely adhered to dietary guidelines. In multivariate models (after accounting for confounders, including level of adherence to nutritional guidelines), compared to those not interested in organic products, RCOP participants showed a markedly lower probability of overweight (excluding obesity) (25≤body mass index<30) and obesity (body mass index ≥30): −36% and −62% in men and −42% and −48% in women, respectively (P<0.0001). OCOP participants (%) generally showed intermediate figures. Conclusions Regular consumers of organic products, a sizeable group in our sample, exhibit specific socio-demographic characteristics, and an overall healthy profile which should be accounted for in further studies analyzing organic food intake and health markers.

positive: Organically Grown Food Provides Health Benefits to Drosophila melanogaster The “organic food” market is the fastest growing food sector, yet it is unclear whether organically raised food is nutritionally superior to conventionally grown food and whether consuming organic food bestows health benefits. In order to evaluate potential health benefits of organic foods, we used the well-characterized fruit fly Drosophila melanogaster as a model system. Fruit flies were raised on a diets consisting of extracts of either conventionally or organically raised produce (bananas, potatoes, raisins, soy beans). Flies were then subjected to a variety of tests designed to assess overall fly health. Flies raised on diets made from organically grown produce had greater fertility and longevity. On certain food sources, greater activity and greater stress resistance was additionally observed, suggesting that organic food bestows positive effects on fly health. Our data show that Drosophila can be used as a convenient model system to experimentally test potential health effects of dietary components. Using this system, we provide evidence that organically raised food may provide animals with tangible benefits to overall health.

positive: Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.

positive: Pesticide exposure and serum organochlorine residuals among testicular cancer patients and healthy controls. The incidence of testicular cancer (TC) has been increasing worldwide during the last decades. The reasons of the increase remains unknown, but recent findings suggest that organochlorine pesticides (OPs) could influence the development of TC. A hospital-based case-control study of 50 cases and 48 controls was conducted to determine whether environmental exposure to OPs is associated with the risk of TC, and by measuring serum concentrations of OPs, including p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) isomer and hexachlorobenzene (HCB) in participants. A significant association was observed between TC and household insecticide use (odds ratio [OR] = 3.01, 95 % CI: 1.11-8.14; OR(adjusted) = 3.23, 95 % CI: 1.15-9.11). Crude and adjusted ORs for TC were also significantly associated with higher serum concentrations of total OPs (OR = 3.15, 95 % CI: 1.00-9.91; OR(adjusted) = 3.34, 95 % CI: 1.09-10.17) in cases compared with controls. These findings give additional support to the results of previous research that suggest that some environmental exposures to OPs may be implicated in the pathogenesis of TC.

positive: ATTENTION DEFICIT/HYPERACTIVITY DISORDER AND URINARY METABOLITES OF ORGANOPHOSPHATE PESTICIDES IN U.S. CHILDREN 8–15 YEARS Context Exposure to organophosphate (OP) pesticides is common, and although these compounds have known neurotoxic properties, few studies examined risks for children in the general population. Objective To examine the association between the concentrations of urinary dialkyl phosphate (DAP) metabolites of OPs and attention deficit/hyperactivity disorder (ADHD) in children age 8 to 15 years. Participants and Methods Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1,139 children representative of the general U.S. population. A structured interview with a parent was used to ascertain ADHD diagnostic status, based on slightly modified criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV. Results One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher concentrations of urinary DAPs, especially dimethyl alkylphosphates (DMAP), were more likely to be diagnosed with ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio (OR) of 1.55 (95% confidence intervals [CI], 1.14–2.10), after adjusting for sex, age, race/ethnicity, poverty-income ratio, fasting duration, and urinary creatinine concentration. For the most commonly detected DMAP metabolite, dimethylthiophosphate, children with levels higher than the median of detectable concentrations had double the odds of ADHD (adjusted OR, 1.93 [95% CI, 1.23–3.02]) compared with those with non-detectable levels. Conclusions These findings support the hypothesis that OP exposure, at levels common in U.S. children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal.

positive: Organic foods: health and environmental advantages and disadvantages. The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term "organic," reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.

positive: Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.

positive: A Prospective Study of Organochlorines in Adipose Tissue and Risk of Non-Hodgkin Lymphoma Background: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements. Objective: Our purpose was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL. Methods: We conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997. Within the cohort we identified 256 persons diagnosed with NHL in the population-based nationwide Danish Cancer Registry and randomly selected 256 subcohort persons. We measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Associations between the 18 organochlorines and NHL were analyzed in Cox regression models, adjusting for body mass index. Results: Incidence rate ratios and confidence intervals (CIs) for interquartile range increases in concentrations of dichlorodiphenyltrichlorethane (DDT), cis-nonachlor, and oxychlordane were 1.35 (95% CI: 1.10, 1.66), 1.13 (95% CI: 0.94, 1.36), and 1.11 (95% CI: 0.89, 1.38), respectively, with monotonic dose–response trends for DDT and cis-nonachlor based on categorical models. The relative risk estimates were higher for men than for women. In contrast, no clear association was found between NHL and PCBs. Conclusion: We found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.

positive: Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach. OBJECTIVE: To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. METHODS: United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. RESULTS: The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. CONCLUSIONS: Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences. Copyright © 2011 Wiley Periodicals, Inc.

positive: Skim milk, whey, and casein increase body weight and whey and casein increase the plasma C-peptide concentration in overweight adolescents. In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.

positive: Leucine signaling in the pathogenesis of type 2 diabetes and obesity Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.

positive: Milk Intake and Total Dairy Consumption: Associations with Early Menarche in NHANES 1999-2004 Background Several components of dairy products have been linked to earlier menarche. Methods/Findings This study assessed whether positive associations exist between childhood milk consumption and age at menarche or the likelihood of early menarche (<12 yrs) in a U.S sample. Data derive from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Two samples were utilized: 2657 women age 20–49 yrs and 1008 girls age 9–12 yrs. In regression analysis, a weak negative relationship was found between frequency of milk consumption at 5–12 yrs and age at menarche (daily milk intake β = −0.32, P<0.10; “sometimes/variable milk intake” β = −0.38, P<0.06, each compared to intake rarely/never). Cox regression yielded no greater risk of early menarche among those who drank milk “sometimes/varied” or daily vs. never/rarely (HR: 1.20, P<0.42, HR: 1.25, P<0.23, respectively). Among the 9–12 yr olds, Cox regression indicated that neither total dairy kcal, calcium and protein, nor daily milk intake in the past 30 days contributed to early menarche. Girls in the middle tertile of milk intake had a marginally lower risk of early menarche than those in the highest tertile (HR: 0.6, P<0.06). Those in the lowest tertiles of dairy fat intake had a greater risk of early menarche than those in the highest (HR: 1.5, P<0.05, HR: 1.6, P<0.07, lowest and middle tertile, respectively), while those with the lowest calcium intake had a lower risk of early menarche (HR: 0.6, P<0.05) than those in the highest tertile. These relationships remained after adjusting for overweight or overweight and height percentile; both increased the risk of earlier menarche. Blacks were more likely than Whites to reach menarche early (HR: 1.7, P<0.03), but not after controlling for overweight. Conclusions There is some evidence that greater milk intake is associated with an increased risk of early menarche, or a lower age at menarche.

positive: Do breast-feeding and delayed introduction of solid foods protect against subsequent obesity? To correct methodologic flaws (Type II error, confounding variables, and nonblinding) in previous studies relating infant feeding to later obesity, we conducted case-control studies of 639 patients 12 to 18 years of age attending our Adolescent Clinic, and 533 similarly aged healthy children attending a Montreal high school. Each subject was classified as either obese, overweight, or nonobese based on measurements of height, weight, and triceps and subscapular skinfolds. Feeding history, family history, and demographic data were later ascertained "blindly" by telephone interview. Analysis of the raw data revealed a significantly elevated estimated relative risk of not breast-feeding and a significant trend for rates of breast-feeding among the three weight groups. The magnitude of the protective effect appeared to rise slightly with increased duration of breast-feeding. Delayed introduction of solid foods provided little if any additional benefit. Several demographic and clinical variables proved to be confounding, but the significant protective effect of breast-feeding persisted even after controlling for confounders. We conclude that breast-feeding does protect against later obesity and attribute the conflicting results of previous studies to insufficient attention to methodologic standards.

positive: Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.

positive: Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.

positive: Relationship between funding sources and outcomes of obesity-related research. This study examined the relationship between funding sources and the outcomes of published obesity-related research. A list of funded projects for human nutrition research linking food intake to obesity in 2001-2005 was drawn from two distinct sources: (a) the federal government's semi-public generic commodity promotion or "checkoff" programs for Fluid Milk and Dairy and (b) the National Institutes of Health (NIH). The Principal Investigator for each funded project was determined. Published literature by that individual was located using an Ovid MEDLINE and PubMed author search. All articles related to both dairy and obesity were included. Financial sponsorship for each article and article conclusions were classified by independent groups of co-investigators. Seventy-nine relevant articles were included in the study. Of these, 62 were sponsored by the checkoff programs and 17 by the NIH. The study did not find consistent evidence that checkoff-funded projects were more likely to support an obesity prevention benefit from dairy consumption. The study did identify a new research methodology for the investigation of bias by source of sponsorship. Copyright © 2012 Elsevier Inc. All rights reserved.

positive: Milk intake and risk of hip fracture in men and women: a meta-analysis of prospective cohort studies. Milk contains calcium, phosphorus, and protein and is fortified with vitamin D in the United States. All these ingredients may improve bone health. However, the potential benefit of milk on hip fracture prevention is not well established. The objective of this study was to assess the association of milk intake with risk of hip fracture based on a meta-analysis of cohort studies in middle-aged or older men and women. Data sources for this study were English and non-English publications via Medline (Ovid, PubMed) and EMBASE search up to June 2010, experts in the field, and reference lists. The idea was to compare prospective cohort studies on the same scale so that we could calculate the relative risk (RR) of hip fracture per glass of milk intake daily (approximately 300 mg calcium per glass of milk). Pooled analyses were based on random effects models. The data were extracted by two independent observers. The results show that in women (6 studies, 195,102 women, 3574 hip fractures), there was no overall association between total milk intake and hip fracture risk (pooled RR per glass of milk per day = 0.99; 95% confidence interval [CI] 0.96-1.02; Q-test p = .37). In men (3 studies, 75,149 men, 195 hip fractures), the pooled RR per daily glass of milk was 0.91 (95% CI 0.81-1.01). Our conclusion is that in our meta-analysis of cohort studies, there was no overall association between milk intake and hip fracture risk in women but that more data are needed in men. Copyright © 2011 American Society for Bone and Mineral Research.

positive: Milk intake and risk of mortality and fractures in women and men: cohort studies Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.

positive: Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial. BACKGROUND: Short-term studies established that calcium influences bone accretion during growth. Whether long-term supplementation influences bone accretion in young adults is not known. OBJECTIVE: This study evaluated the long-term effects of calcium supplementation on bone accretion among females from childhood to young adulthood. DESIGN: A 4-y randomized clinical trial recruited 354 females in pubertal stage 2 and optionally was extended for an additional 3 y. The mean dietary calcium intake of the participants over 7 y was approximately 830 mg/d; calcium-supplemented persons received an additional approximately 670 mg/d. Primary outcome variables were distal and proximal radius bone mineral density (BMD), total-body BMD (TBBMD), and metacarpal cortical indexes. RESULTS: Multivariate analyses of the primary outcomes indicated that calcium-supplementation effects vary over time. Follow-up univariate analyses indicated that all primary outcomes were significantly larger in the supplemented group than in the placebo group at the year 4 endpoint. However, at the year 7 endpoint, this effect vanished for TBBMD and distal radius BMD. Longitudinal models for TBBMD and proximal radius BMD, according to the time since menarche, showed a highly significant effect of supplementation during the pubertal growth spurt and a diminishing effect thereafter. Post hoc stratifications by compliance-adjusted total calcium intake and by final stature or metacarpal total cross-sectional area showed that calcium effects depend on compliance and body frame. CONCLUSIONS: Calcium supplementation significantly influenced bone accretion in young females during the pubertal growth spurt. By young adulthood, significant effects remained at metacarpals and at the forearm of tall persons, which indicated that the calcium requirement for growth is associated with skeletal size. These results may be important for both primary prevention of osteoporosis and prevention of bone fragility fractures during growth.

positive: Milk Consumption During Teenage Years and Risk of Hip Fractures in Older Adults Importance Milk consumption during adolescence is recommended to promote peak bone mass and thereby reduce fracture risk in later life. However, its role in hip fracture prevention is not established and high consumption may adversely influence risk by increasing height. Objective To determine whether milk consumption during teenage years influences risk of hip fracture in older adults and to investigate the role of attained height in this association. Design Prospective cohort study over 22 years of follow-up Setting United States Participants Over 96,000 Caucasian postmenopausal women from the Nurses’ Health Study and men age 50 and older from the Health Professionals Follow-up Study Exposures Frequency of consumption of milk and other foods during ages 13–18 and attained height were reported at baseline. Current diet, weight, smoking, physical activity, medication use, and other risk factors for hip fractures were reported on biennial questionnaires. Main Outcome Measures Cox proportional hazards models were used to calculate relative risks (RR) of first incident hip fracture from low-trauma events per glass (8 fl oz or 240 mL) of milk consumed per day during teenage years. Results Over follow-up, 1226 hip fractures were identified in women and 490 in men. After controlling for known risk factors and current milk consumption, each additional glass of milk per day during teenage years was associated with a significant 9% higher risk of hip fracture in men (RR=1.09, 95% CI 1.01–1.17). The association was attenuated when height was added to the model (RR=1.06, 95% CI 0.98–1.14). Teenage milk consumption was not associated with hip fractures in women (RR=1.00, 95% CI 0.95–1.05 per glass per day). Conclusion and Relevance Greater milk consumption during teenage years was not associated with a lower risk of hip fracture in older adults. The positive association observed in men was partially mediated through attained height.

positive: Skeletal health in adult patients with classic galactosemia. SUMMARY: This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients. INTRODUCTION: Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia. METHODS: This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0 ± 11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers. RESULTS: There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm(2), p = 0.014). The percentage of subjects with BMD-Z <-2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r = 0.58, p < 0.05) and spine in men (r = 0.53, p < 0.05)]. In women, weight was also correlated with BMD-Z (r = 0.57, p < 0.05 at hip), and C-telopeptides (r = -0.59 at spine and -0.63 hip, p < 0.05) and osteocalcin (r = -0.71 at spine and -0.72 hip, p < 0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p = 0.017); serum calcium was a significant predictor of hip (p = 0.014) and spine (p = 0.013) BMD in both sexes. CONCLUSIONS: Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial.

positive: Role of insulin in the pathogenesis of free fatty acid-induced insulin resistance in skeletal muscle. Insulin resistance is a pathophysiological link of obesity to type 2 diabetes. The initial cause of insulin resistance is critical for prevention and treatment of type 2 diabetes. Lipotoxicity is a well-known concept in the explanation of initiation of insulin resistance. Although there are several prevailing hypotheses about the cellular/molecular mechanisms of lipotoxicity, such as inflammation, oxidative stress, hyperinsulinemia, and ER stress, the relative importance of these hypothesized events remains to be determined. The role of hyperinsulinemia is relatively under documented in the literature for the initiation of insulin resistance. In this review, an interaction of fatty acid and beta-cells, and a synergy between free fatty acids (FFAs) and insulin are emphasized for the role of hyperinsulinemia. This article presents the evidence about FFA-induced insulin secretion in vitro and in vivo, recent advances in the molecular mechanism of FFA action in beta-cells, a role of GPR40 in the development of insulin resistance, and the negative feedback loop of the insulin receptor signal pathway. The negative feedback loop is discussed in detail with a focus on IRS-1 serine kinases. This article provides a substantial support for the role of insulin in the early stages of FFA-associated insulin resistance. The hypothesis of insulin's role in lipotoxicity is referred to as the "insulin hypothesis" in this review. According to this hypothesis, prevention of increased beta-cell response to glucose may be a potential approach for early intervention of metabolic syndrome.

positive: Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. METHODS: The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E%). Here, insulin sensitivity was 12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).

positive: Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.

positive: Veganism and its relationship with insulin resistance and intramyocellular lipid. OBJECTIVE: To test the hypothesis that dietary factors in the vegan diet lead to improved insulin sensitivity and lower intramyocellular lipid (IMCL) storage. DESIGN: Case-control study. SETTING: Imperial College School of Medicine, Hammersmith Hospital Campus, London, UK. SUBJECTS: A total of 24 vegans and 25 omnivores participated in this study; three vegan subjects could not be matched therefore the matched results are shown for 21 vegans and 25 omnivores. The subjects were matched for gender, age and body mass index (BMI). INTERVENTIONS: Full anthropometry, 7-day dietary assessment and physical activity levels were obtained. Insulin sensitivity (%S) and beta-cell function (%B) were determined using the homeostatic model assessment (HOMA). IMCL levels were determined using in vivo proton magnetic resonance spectroscopy; total body fat content was assessed by bioelectrical impedance. RESULTS: There was no difference between the groups in sex, age, BMI, waist measurement, percentage body fat, activity levels and energy intake. Vegans had a significantly lower systolic blood pressure (-11.0 mmHg, CI -20.6 to -1.3, P=0.027) and higher dietary intake of carbohydrate (10.7%, CI 6.8-14.5, P<0.001), nonstarch polysaccharides (20.7 g, CI 15.8-25.6, P<0.001) and polyunsaturated fat (2.8%, CI 1.0-4.6, P=0.003), with a significantly lower glycaemic index (-3.7, CI -6.7 to -0.7, P=0.01). Also, vegans had lower fasting plasma triacylglycerol (-0.7 mmol/l, CI -0.9 to -0.4, P<0.001) and glucose (-0.4 mmol/l, CI -0.7 to -0.09, P=0.05) concentrations. There was no significant difference in HOMA %S but there was with HOMA %B (32.1%, CI 10.3-53.9, P=0.005), while IMCL levels were significantly lower in the soleus muscle (-9.7, CI -16.2 to -3.3, P=0.01). CONCLUSION: Vegans have a food intake and a biochemical profile that will be expected to be cardioprotective, with lower IMCL accumulation and beta-cell protective.

positive: A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Obesity and type 2 diabetes have been associated with a high-fat diet (HFD) and reduced mitochondrial mass and function. We hypothesized a HFD may affect expression of genes involved in mitochondrial function and biogenesis. To test this hypothesis, we fed 10 insulin-sensitive males an isoenergetic HFD for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarray analysis revealed 297 genes were differentially regulated by the HFD (Bonferonni adjusted P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS) decreased. Four were members of mitochondrial complex I: NDUFB3, NDUFB5, NDUFS1, and NDUFV1; one was SDHB in complex II and a mitochondrial carrier protein SLC25A12. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1) alpha and PGC1beta mRNA were decreased by -20%, P < 0.01, and -25%, P < 0.01, respectively. In a separate experiment, we fed C57Bl/6J mice a HFD for 3 weeks and found that the same OXPHOS and PGC1 mRNAs were downregulated by approximately 90%, cytochrome C and PGC1alpha protein by approximately 40%. Combined, these results suggest a mechanism whereby HFD downregulates genes necessary for OXPHOS and mitochondrial biogenesis. These changes mimic those observed in diabetes and insulin resistance and, if sustained, may result in mitochondrial dysfunction in the prediabetic/insulin-resistant state.

positive: Higher insulin sensitivity in vegans is not associated with higher mitochondrial density. BACKGROUND/OBJECTIVES: Vegans have a lower incidence of insulin resistance (IR)-associated diseases and a higher insulin sensitivity (IS) compared with omnivores. The aim of this study was to examine whether the higher IS in vegans relates to markers of mitochondrial biogenesis and to intramyocellular lipid (IMCL) content. SUBJECTS/METHODS: Eleven vegans and 10 matched (race, age, sex, body mass index, physical activity and energy intake) omnivorous controls were enrolled in a case-control study. Anthropometry, bioimpedance (BIA), ultrasound measurement of visceral and subcutaneous fat layer, parameters of glucose and lipid homeostasis, hyperinsulinemic euglycemic clamp and muscle biopsies were performed. Citrate synthase (CS) activity, mitochondrial DNA (mtDNA) and IMCL content were assessed in skeletal muscle samples. RESULTS: Both groups were comparable in anthropometric and BIA parameters, physical activity and protein-energy intake. Vegans had significantly higher glucose disposal (M-value, vegans 8.11±1.51 vs controls 6.31±1.57 mg/kg/min, 95% confidence interval: 0.402 to 3.212, P=0.014), slightly lower IMCL content (vegans 13.91 (7.8 to 44.0) vs controls 17.36 (12.4 to 78.5) mg/g of muscle, 95% confidence interval: -7.594 to 24.550, P=0.193) and slightly higher relative muscle mtDNA amount (vegans 1.36±0.31 vs controls 1.13±0.36, 95% confidence interval:-0.078 to 0.537, P=0.135). No significant differences were found in CS activity (vegans 18.43±5.05 vs controls 18.16±5.41 μmol/g/min, 95% confidence interval: -4.503 to 5.050, P=0.906). CONCLUSIONS: Vegans have a higher IS, but comparable mitochondrial density and IMCL content with omnivores. This suggests that a decrease in whole-body glucose disposal may precede muscle lipid accumulation and mitochondrial dysfunction in IR development.

positive: Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance.

positive: Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.

positive: Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy as... Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P < 0.01) but not in the tibialis anterior (P = 0.19), but showed a normal content of saturated/unsaturated carbons in the fatty acid chain of subcutaneous adipocytes. Stepwise regression analysis selected intramyocellular triglyceride soleus content and plasma free fatty acid levels as the main predictors of whole body insulin sensitivity. In conclusion, 1H and 13C NMR spectroscopy revealed intramyocellular abnormalities of lipid metabolism associated with whole body insulin resistance in subjects at high risk of developing diabetes, and might be useful tools for noninvasively monitoring these alterations in diabetes and prediabetic states.

positive: Free fatty acids and skeletal muscle insulin resistance. PURPOSE OF REVIEW: Acute exposure to fatty acids causes insulin resistance in muscle, and excess dietary lipid and obesity are also strongly associated with muscle insulin resistance. Relevant mechanisms, however, are still not fully elucidated. Here we examine the latest evidence as to why lipids might accumulate in muscle and the possible mechanisms for lipid-induced insulin resistance. RECENT FINDINGS: Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Crosstalk between inflammatory signalling pathways and insulin signalling pathways, mitochondrial dysfunction and oxidative stress have also been put forward as major contributors to the development or maintenance of lipid-induced insulin resistance in muscle. Several animal models with gene deletions in pathways of fatty acid synthesis and storage also show increased metabolic rate, reduced intramuscular lipid storage and improved insulin action when challenged with a high lipid load. SUMMARY: Studies in genetic and dietary obese animal models, genetically modified animals and humans with obesity or type 2 diabetes suggest plausible mechanisms for effects of fatty acids, lipid metabolites, inflammatory pathways and mitochondrial dysfunction on insulin action in muscle. Many of these mechanisms, however, have been demonstrated in situations in which lipid accumulation (obesity) already exists. Whether the initial events leading to muscle insulin resistance are direct effects of fatty acids in muscle or are secondary to lipid accumulation in adipose tissue or liver remains to be clarified.

positive: Effect of ingestion of meat on plasma cholesterol of vegetarians. In a controlled trial, 21 strict vegetarians were studied prospectively for eight weeks: a two-week control period of the usual vegetarian diet was followed by four weeks, during which 250 g of beef was added isocalorically to the daily vegetarian diet and then by two weeks of the control diet. Plasma high-density lipoprotein-cholesterol did not change during the study, whereas plasma total cholesterol rose significantly by 19% at the end of the meat-eating period. Systolic blood pressure (BP) increased significantly during the meat eating by 3% over control values, whereas diastolic BP showed no major changes. Plasma renin activity, prostaglandin A and E levels, and urinary kallikrein, norepinephrine, and epinephrine excretions were within normal limits and did not change notably throughout the trial. The study suggests an adverse effect of consumption of beef on plasma lipid and BP levels.

positive: Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.

positive: Developing actionable dietary guidance messages: dietary fat as a case study. Although consumers say they are concerned about nutrition and are aware that eating a healthful diet is important for good health, this knowledge does not always translate into healthful diet behaviors or motivate behavior change. In an effort to better understand consumer attitudes about nutrition and to explore alternatives for communicating dietary advice in language that is meaningful and motivates behavior change, the International Food Information Council (IFIC) conducted qualitative research with consumers (using focus groups) and registered dietitians (using telephone interviews) in 1998 and 1999. Results of the research are presented using dietary fat as a case study. Findings from the IFIC research were reported to the Dietary Guidelines Advisory Committee to assist the Committee in developing meaningful and action-oriented dietary advice related to dietary fat for inclusion in the 2000 Dietary Guidelines for Americans that would be motivating and easy for consumers to implement. The recommendation to moderate fat intake in the new dietary guideline, "Choose a diet that is low in saturated fat and cholesterol and moderate in total fat" is consistent with communication recommendations in the IFIC research. Further, the moderate fat message is empowering because it suggests an achievable dietary regimen and reduces guilt and worry about foods. It allows flexibility to enjoy desired foods and promotes using common sense when it comes to diet. Several issues emerged from the IFIC research that apply to general nutrition communications with consumers, whether it be through national nutrition recommendations or in one-on-one counseling situations: to be effective, messages to consumers about nutrition, and specifically dietary fat, must address sources of discomfort about dietary choices; they must engender a sense of empowerment; and they should motivate both by providing clear information that propels toward taking action and appeals to the need to make personal choices.

positive: Reduced or modified dietary fat for preventing cardiovascular disease. BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB s, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.

positive: Diet and serum cholesterol: do zero correlations negate the relationship? The confounding that results from the uncontrolled conditions under which most epidemiologic observations are made is sufficient to undermine their validity with respect to investigation of the relationship between diet and serum cholesterol. In this paper, the authors show, using both a mathematical model and referring to empirical data, that if certain variances are sufficiently great, even when there is cause and effect, correlation coefficients close to zero would be expected from the actual data of a cross-sectional study. Cross-sectional designs are therefore not suitable for studying this relationship.

positive: Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease Background: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. Objective: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Design: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. Results: During 5–23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. Conclusions: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.

positive: Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review... AIM: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO). METHODS: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes. RESULTS: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E. CONCLUSIONS: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.

positive: Recommended dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids: a systematic review. Dietary fat and its effects on health and disease has attracted interest for research and Public Health. Since the 1980s many bodies and organizations have published recommendations regarding fat intake. In this paper different sets of recommendations are analyzed following a systematic review process to examine dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids. A literature search was conducted in relevant literature databases along a search for suitable grey literature reports. Documents were included if they reported information on either recommended intake levels or dietary reference values or nutritional objectives or dietary guidelines regarding fat and/or fatty acids and/or cholesterol intake or if reported background information on the process followed to produce the recommendations. There is no standard approach for deriving nutrient recommendations. Recommendations vary between countries regarding the levels of intake advised, the process followed to set the recommendations. Recommendations on fat intake share similar figures regarding total fat intake, saturated fats and trans fats. Many sets do not include a recommendation about cholesterol intake. Most recent documents provide advice regarding specific n-3 fatty acids. Despite efforts to develop evidence based nutrient recommendations and dietary guidelines that may contribute to enhance health, there are still many gaps in research. It would be desirable that all bodies concerned remain transparent about the development of dietary recommendations. In order to achieve this, the type of evidence selected to base the recommendations should be specified and ranked. Regular updates of such recommendations should be planned.

positive: The sensitivity of the child to sex steroids: possible impact of exogenous estrogens. The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to estradiol and may respond with increased growth and/or breast development even at serum levels below the current detection limits; (iii) no threshold has been established, below which no hormonal effects can be seen in children exposed to exogenous steroids or endocrine disruptors; (iv) changes in hormone levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels.

positive: Obstetric complications of twin pregnancies. Advances in assisted reproductive technology and increases in the proportion of maternities in older women have both contributed to the steep increase in the incidence of twin pregnancies since the 1980s. Maternal and perinatal complications are higher in twins than in singleton pregnancies. A significant proportion of perinatal mortality and morbidity among twins is due to the high incidence of preterm delivery and the added complication of twin-to-twin transfusion syndrome (TTTS) in monochorionic twins. Monochorionic twins also have a much higher rate of perinatal mortality than dichorionic twins, the greatest risk being before fetal viability (<24 weeks gestation). Early diagnosis of twins and their chorionicity, close fetal surveillance, particularly of monochorionic twins, and prompt therapeutic intervention in TTS are necessary to reduce perinatal mortality. Intrapartum management in the hospital setting with anaesthetic and neonatal facilities, as well as critical assessment of mode of delivery, have led to better outcomes. Ultrasonography is a valuable tool in the management of twin pregnancy. This chapter briefly summarises these topics, with a particular focus on recent literature.

positive: Effects of twin gestation on maternal morbidity. As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Copyright © 2012 Elsevier Inc. All rights reserved.

positive: Evidence-based care of women with a multiple pregnancy. Women with a multiple pregnancy face greater risks for themselves and their infants than women pregnant with one child. Pre-pregnancy care should focus on avoiding multiple pregnancy. Early prenatal care centres on determining chorionicity and screening for fetal anomalies, with later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. The optimal timing and mode of birth are the focus of current multicentre, randomised, controlled trials. However, the data from such trials on care for women with a multiple pregnancy are limited. Many areas of care require better-quality information, including when using assisted reproductive techniques, the optimal number of embryos to be transferred, care after the diagnosis of chorionicity, and the benefits of specialised multiple pregnancy clinics. Better-quality information is required to inform clinical practice for women with complications of multiple pregnancy, including monoamniotic twin pregnancy, treatment of twin-to-twin transfusion syndrome, and care following single intrauterine fetal death.

positive: Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate. OBJECTIVE: To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning. STUDY DESIGN: In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered. RESULTS: Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores. CONCLUSION: The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.

positive: Reducing the incidence of twins and triplets. Multiple pregnancy rates remain high after assisted conception because of a misconceived assumption that transferring three or more embryos will maximize pregnancy rates. Maternal morbidity is sevenfold greater in multiple pregnancies than in singletons, perinatal mortality rates are fourfold higher for twins and sixfold higher for triplets, while cerebral palsy rates are 1-1.5% in twin and 7-8% in triplet pregnancies. Therefore, multiple pregnancies must be considered a serious adverse outcome of assisted reproductive techniques. Primary prevention of multiple pregnancies is the solution. The overwhelming evidence presented in this chapter demonstrates that limiting the embryo transfer in in vitro fertilization to two embryos would significantly reduce adverse maternal and perinatal outcomes by reducing the incidence of high order multiple pregnancies without reducing take-home-baby rates. Secondary prevention by multifetal pregnancy reduction is effective, but not acceptable to all patients. New developments in blastocyst culture, single embryo transfer, embryo cryopreservation and pre-implantation aneuploidy exclusion, should allow improvements in pregnancy rates without increasing multiple pregnancies.

positive: Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels. Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.

positive: Are oral contraceptives a significant contributor to the estrogenicity of drinking water? Recent observed feminization of aquatic animals has raised concerns about estrogenic compounds in water supplies and the potential for these chemicals to reach drinking water. Public perception frequently attributes this feminization to oral contraceptives (OCs) in wastewater and raises concerns that exposure to OCs in drinking water may contribute to the recent rise in human reproductive problems. This paper reviews the literature regarding various sources of estrogens, in surface, source and drinking water, with an emphasis on the active molecule that comes from OCs. It includes discussion of the various agricultural, industrial, and municipal sources and outlines the contributions of estrogenic chemicals to the estrogenicity of waterways and estimates that the risk of exposure to synthetic estrogens in drinking water on human health is negligible. This paper also provides recommendations for strategies to better understand all the potential sources of estrogenic compounds in the environment and possibilities to reduce the levels of estrogenic chemicals in the water supply.

positive: Occurrence of estrogen hormones in biosolids, animal manure and mushroom compost. The presence of natural estrogen hormones as trace concentrations in the environment has been reported by many researchers and is of growing concern due to its possible adverse effects on the ecosystem. In this study, municipal biosolids, poultry manure (PM) and cow manure (CM), and spent mushroom compost (SMC) were analyzed for the presence of seven estrogen hormones. 17α-estradiol, 17β-estradiol, 17α-dihydroequilin, and estrone were detected in the sampled biosolids and manures at concentrations ranging from 6 to 462 ng/g of dry solids. 17α-estradiol, 17β-estradiol, and estrone were also detected in SMC at concentrations ranging from 4 to 28 ng/g of dry solids. Desorption experiments were simulated in the laboratory using deionized water (milli-Q), and the aqueous phase was examined for the presence of estrogen hormones to determine their desorption potential. Very low desorption of 0.4% and 0.2% estrogen hormones was observed from municipal biosolids and SMC, respectively. An estimate of total estrogen contribution from different solid waste sources is reported. Animal manures (PM and CM) contribute to a significant load of estrogen hormones in the natural environment.

positive: Oestrogen levels in serum and urine of premenopausal women eating low and high amounts of meat. OBJECTIVE: Based on the hypothesis that high-meat diets may increase breast cancer risk through hormonal pathways, the present analysis compared oestrogens in serum and urine by meat-eating status. DESIGN: Intervention with repeated measures. SETTING: Two randomized soya trials (BEAN1 and BEAN2) among premenopausal healthy women. SUBJECTS: BEAN1 participants completed seven unannounced 24 h dietary recalls and donated five blood and urine samples over 2 years. BEAN2 women provided seven recalls and three samples over 13 months. Serum samples were analysed for oestrone (E₁) and oestradiol (E₂) using RIA. Nine oestrogen metabolites were measured in urine by LC-MS. Semi-vegetarians included women who reported consuming <30 g of red meat, poultry and fish daily, and pescatarians those who reported consuming <20 g of meat/poultry but >10 g of fish daily. All other women were classified as non-vegetarians. We applied mixed models to compute least-square means by vegetarian status adjusted for potential confounders. RESULTS: The mean age of the 272 participants was 41·9 (SD 4·5) years. Serum E₁ (85 v. 100 pg/ml, P = 0·04) and E₂ (140 v. 154 pg/ml, P = 0·04) levels were lower in the thirty-seven semi-vegetarians than in the 235 non-vegetarians. The sum of the nine urinary oestrogen metabolites (183 v. 200 pmol/mg creatinine, P = 0·27) and the proportions of individual oestrogens and pathways did not differ by meat-eating status. Restricting the models to the samples collected during the luteal phase strengthened the associations. CONCLUSIONS: Given the limitations of the study, the lower levels of serum oestrogens in semi-vegetarians than non-vegetarians need confirmation in larger populations.

positive: Occurrence, fate, and biodegradation of estrogens in sewage and manure. The estrogens estrone (E1), 17alpha-estradiol (E2alpha), 17beta-estradiol (E2beta), and estriol (E3) are natural sex hormones produced by humans and animals. In addition, there are some synthetic estrogens, such as 17alpha-ethinylestradiol (EE2), used for contraception purposes. These compounds are able to produce endocrine disruption in living organisms at nanogram-per-liter levels. In both humans and animals, estrogens are excreted in urine and feces, reaching the natural environment through discharge from sewage treatment plants (STP) and manure disposal units. In STPs, hormone removal depends on the type of treatment process and on different parameters such as the hydraulic and sludge retention times. Thus, hormone elimination rates vary from 0% to 90% in different STPs. Animals are also an important source of estrogens in the environment. Indeed, animals produce high concentrations of hormones which will end up in manure which is typically spread on land. Hence, waste-borne animal hormones may transfer these pollutants to the soil. The purpose of this review is to highlight the significance for both health and the environment of pollution by estrogens and critically review the existing knowledge on their fate and removal in different treatment processes. Relevant information on the microbial degradation of hormones and metabolic pathways is also included.

positive: An Assessment of Potential Exposure and Risk from Estrogens in Drinking Water Background Detection of estrogens in the environment has raised concerns in recent years because of their potential to affect both wildlife and humans. Objectives We compared exposures to prescribed and naturally occurring estrogens in drinking water to exposures to naturally occurring background levels of estrogens in the diet of children and adults and to four independently derived acceptable daily intakes (ADIs) to determine whether drinking water intakes are larger or smaller than dietary intake or ADIs. Methods We used the Pharmaceutical Assessment and Transport Evaluation (PhATE) model to predict concentrations of estrogens potentially present in drinking water. Predicted drinking water concentrations were combined with default water intake rates to estimate drinking water exposures. Predicted drinking water intakes were compared to dietary intakes and also to ADIs. We present comparisons for individual estrogens as well as combined estrogens. Results In the analysis we estimated that a child’s exposures to individual prescribed estrogens in drinking water are 730–480,000 times lower (depending upon estrogen type) than exposure to background levels of naturally occurring estrogens in milk. A child’s exposure to total estrogens in drinking water (prescribed and naturally occurring) is about 150 times lower than exposure from milk. Adult margins of exposure (MOEs) based on total dietary exposure are about 2 times smaller than those for children. Margins of safety (MOSs) for an adult’s exposure to total prescribed estrogens in drinking water vary from about 135 to > 17,000, depending on ADI. MOSs for exposure to total estrogens in drinking water are about 2 times lower than MOSs for prescribed estrogens. Depending on the ADI that is used, MOSs for young children range from 28 to 5,120 for total estrogens (including both prescribed and naturally occurring sources) in drinking water. Conclusions The consistently large MOEs and MOSs strongly suggest that prescribed and total estrogens that may potentially be present in drinking water in the United States are not causing adverse effects in U.S. residents, including sensitive subpopulations.

positive: Cardiovascular disease data to be standardized across Europe. ESC is to create an inventory of cardiovascular disease registries and a task force on data standardization

positive: Tea Consumption Enhances Endothelial-Dependent Vasodilation; a Meta-Analysis Background Tea consumption is associated with a lower risk of cardiovascular disease including stroke. Direct effects of tea components on the vasculature, particularly the endothelium, may partly explain this association. Objective We performed a meta-analysis of controlled human intervention studies on the effect of tea on flow-mediated dilation (FMD) of the brachial artery, a measurement of endothelial function, which is suggested to be associated with cardiovascular risk. Methods Human intervention studies were identified by systematic search of the databases Medline, Embase, Chemical s and Biosis through March 2009 and by hand-searching related articles. Studies were selected based on predefined criteria: intervention with tea as the sole experimental variable, placebo-controlled design, and no missing data on FMD outcome or its variability. A random effects model was used to calculate the pooled overall effect on FMD due to the intake of tea. The impact of various subject and treatment characteristics was investigated in the presence of heterogeneity. Results In total, 9 studies from different research groups were included with 15 relevant study arms. The overall absolute increase in FMD of tea vs. placebo was 2.6% of the arterial diameter (95% CI: 1.8-3.3%; P-value <0.001) for a median daily dose of 500 mL of tea (2–3 cups). This is a relative increase of approximately 40% compared to the average FMD of 6.3% measured under placebo or baseline conditions. There was significant heterogeneity between studies (P-value <0.001) that might partly be explained by the cuff position either distal or proximal to the area of FMD measurement. No indication for publication bias was found. Conclusion Moderate consumption of tea substantially enhances endothelial-dependent vasodilation. This may provide a mechanistic explanation for the reduced risk of cardiovascular events and stroke observed among tea drinkers.

positive: Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.

positive: Black tea increases coronary flow velocity reserve in healthy male subjects. Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.

positive: Caffeine enhances endothelial repair by an AMPK-dependent mechanism. OBJECTIVE: Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage. METHODS AND RESULTS: We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 micromol/L) induces migration of human EPCs as well as mature ECs. In patients with coronary artery disease (CAD), caffeinated coffee increased caffeine serum concentration from 2 micromol/L to 23 micromol/L, coinciding with a significant increase in migratory activity of patient-derived EPCs. Decaffeinated coffee neither affected caffeine serum levels nor migratory capacity of EPCs. Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery. The enhancement of reendothelialization by caffeine was significantly reduced in AMPK knockout mice compared to wild-type animals. Transplantation of wild-type and AMPK(-/-) bone marrow into wild-type mice revealed no difference in caffeine challenged reendothelialization. ECs which were depleted of mitochondrial DNA did not migrate when challenged with caffeine, suggesting a potential role for mitochondria in caffeine-dependent migration. CONCLUSIONS: These results provide evidence that caffeine enhances endothelial cell migration and reendothelialization in part through an AMPK-dependent mechanism, suggesting a beneficial role for caffeine in endothelial repair.

positive: Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease. Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation. Copyright © 2011 Elsevier Inc. All rights reserved.

positive: Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.

positive: Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls Background Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). Methodology/Principal Findings MBF was measured with 15O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58±13 years) and in CAD patients (n = 15, mean age 61±9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26±0.56 vs. 2.02±0.56, P<0.005), remote (2.40±0.70 vs. 1.78±0.46, P<0.001) and in stenotic segments (1.90±0.41 vs. 1.38±0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). Conclusions We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls.

positive: Dose-dependent effects of decaffeinated coffee on endothelial function in healthy subjects. BACKGROUND/OBJECTIVES: Coffee is known to contain antioxidant substances whose effects may be blunted because of caffeine that may unfavorably affect the cardiovascular system. This study was designed to investigate the acute dose-dependent effects of decaffeinated coffee (DC) on endothelial function measured by the brachial artery flow-mediated dilation (FMD). SUBJECTS/METHODS: A total of 15 (8 men and 7 women) healthy nonobese subjects underwent a single-blind, crossover study. Subjects ingested one and two cups of decaffeinated Italian espresso coffee in random order at 5- to 7-day intervals. RESULTS: In the hour following the ingestion of two cups of DC, FMD increased (mean+/-s.e.m.): 0 min, 7.4+/-0.7%; 30 min, 8.0+/-0.6%; 60 min, 10.8+/-0.8%; P<0.001) as compared to consumption of one cup of DC (0 min, 6.9+/-0.7%; 30 min, 8.4+/-1.2%; 60 min, 8.5+/-1.1%; 3 x 2 repeated-measures analysis of variance: P=0.037 for time x treatment effect). Blood pressure did not differ between groups, and basal heart rate was lower in the two-cup group at baseline and 60 min. CONCLUSIONS: The present study demonstrated a significant acute favorable dose-dependent effect of decaffeinated espresso coffee on endothelial function. Further studies are needed to investigate the effects of chronic use of DC especially with respect to caffeinated coffee and in subjects with cardiovascular diseases.

positive: Does a glass of red wine improve endothelial function? AIMS: To examine the acute effect of red wine and de-alcoholized red wine on endothelial function. METHODS AND RESULTS: High frequency ultrasound was used to measure blood flow and percentage brachial artery dilatation after reactive hyperaemia induced by forearm cuff occlusion in 12 healthy subjects, less than 40 years of age, without known cardiovascular risk factors. The subjects drank 250 ml of red wine with or without alcohol over 10 min according to a randomized procedure. Brachial artery dilatation was measured again 30 and 60 min after the subjects had finished drinking. The subjects were studied a second time within a week of the first study in a cross-over design. After the red wine with alcohol the resting brachial artery diameter, resting blood flow, heart rate and plasma-ethanol increased significantly. After the de-alcoholized red wine these parameters were unchanged. Flow-mediated dilatation of the brachial artery was significantly higher (P<0.05) after drinking de-alcoholized red wine (5.6+/-3.2%) than after drinking red wine with alcohol (3.6+/-2.2%) and before drinking (3.9+/-2.5%). CONCLUSION: After ingestion of red wine with alcohol the brachial artery dilated and the blood flow increased. These changes were not observed following the de-alcoholized red wine and were thus attributable to ethanol. These haemodynamic changes may have concealed an effect on flow-mediated brachial artery dilatation which did not increase after drinking red wine with alcohol. Flow-mediated dilatation of the brachial artery increased significantly after de-alcoholized red wine and this finding may support the hypothesis that antioxidant qualities of red wine, rather than ethanol in itself, may protect against cardiovascular disease. Copyright 2000 The European Society of Cardiology.

positive: Association of Coffee Drinking with Total and Cause-Specific Mortality Background Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear. Methods We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health–AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline. Results During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline. Conclusions In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.)

positive: The acute effect of green tea consumption on endothelial function in healthy individuals. BACKGROUND: Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet. DESIGN AND METHODS: We studied 14 healthy individuals (age 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FMD of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (Il-6) and 1b (Il-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention. RESULTS: Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P<0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, Il-6, Il-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress. CONCLUSION: Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.

positive: A new proposed guidance system for beverage consumption in the United States. The Beverage Guidance Panel was assembled to provide guidance on the relative health and nutritional benefits and risks of various beverage categories. The beverage panel was initiated by the first author. The Panel's purpose is to attempt to systematically review the literature on beverages and health and provide guidance to the consumer. An additional purpose of the Panel is to develop a deeper dialog among the scientific community on overall beverage consumption patterns in the United States and on the great potential to change this pattern as a way to improve health. Over the past several decades, levels of overweight and obesity have increased across all population groups in the United States. Concurrently, an increased daily intake of 150-300 kcal (for different age-sex groups) has occurred, with approximately 50% of the increased calories coming from the consumption of calorically sweetened beverages. The panel ranked beverages from the lowest to the highest value based on caloric and nutrient contents and related health benefits and risks. Drinking water was ranked as the preferred beverage to fulfill daily water needs and was followed in decreasing value by tea and coffee, low-fat (1.5% or 1%) and skim (nonfat) milk and soy beverages, noncalorically sweetened beverages, beverages with some nutritional benefits (fruit and vegetable juices, whole milk, alcohol, and sports drinks), and calorically sweetened, nutrient-poor beverages. The Panel recommends that the consumption of beverages with no or few calories should take precedence over the consumption of beverages with more calories.

positive: Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. BACKGROUND: Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. CONCLUSIONS: Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.

positive: Coffee and endothelial function: a battle between caffeine and antioxidants? Although coffee is largely consumed by adults in Western countries, controversy exists about its impact on the cardiovascular system. We recently demonstrated that caffeinated and decaffeinated espresso coffee have different acute effects on endothelial function in healthy subjects, measured using flow-mediated dilation (FMD) of the brachial artery. In this study, we measured the anti-oxidant capacity of two coffee substances in terms of free stable radical 2,2-diphenyl-1-picryl-hydrazyl 50% inhibition (I(50) DPPH). The caffeinated coffee had a slightly higher anti-oxidant capacity than decaffeinated espresso coffee (I(50) DPPH: 1.13±0.02 vs 1.30±0.03 μl; P<0.001). We suggest that the unfavourable effects observed after caffeinated coffee ingestion are due to caffeine and that the antioxidant activity is responsible for the increased FMD observed after decaffeinated coffee ingestion. Further clinical and epidemiological studies are needed to understand the chronic effects of coffee consumption on health.

positive: Consumption of a boiled Greek type of coffee is associated with improved endothelial function: the Ikaria study. OBJECTIVE: The association of coffee consumption with cardiovascular disease remains controversial. Endothelial function is associated with cardiovascular risk. We examined the association between chronic coffee consumption and endothelium function in elderly inhabitants of the island of Ikaria. METHODS: The analysis was conducted on 142 elderly subjects (aged 66-91 years) of the Ikaria Study. Endothelial function was evaluated by ultrasound measurement of flow-mediated dilation (FMD). Coffee consumption was evaluated based on a food frequency questionnaire and was categorized as 'low' (< 200 ml/day), 'moderate' (200-450 ml/day), or 'high' (> 450 ml/day). RESULTS: From the subjects included in the study, 87% consumed a boiled Greek type of coffee. Moreover, 40% had a 'low', 48% a 'moderate' and 13% a 'high' daily coffee consumption. There was a linear increase in FMD according to coffee consumption ('low': 4.33 ± 2.51% vs 'moderate': 5.39 ± 3.09% vs 'high': 6.47 ± 2.72%; p = 0.032). Moreover, subjects consuming mainly a boiled Greek type of coffee had a significantly higher FMD compared with those consuming other types of coffee beverages (p = 0.035). CONCLUSIONS: Chronic coffee consumption is associated with improved endothelial function in elderly subjects, providing a new connection between nutrition and vascular health.

positive: Meat intake and reproductive parameters among young men Background In the United States, anabolic sex steroids are administered to cattle for growth promotion. There is concern regarding the reproductive consequences of this practice for men who eat beef. We investigated whether meat consumption was associated with semen quality parameters and reproductive hormone levels in young men. Methods Semen samples were obtained from 189 men aged 18-22 years. Diet was assessed with a previously validated food frequency questionnaire. We used linear regression to analyze the cross-sectional associations of meat intake with semen quality parameters and reproductive hormones, while adjusting for potential confounders. Results There was an inverse relation between processed red meat intake and total sperm count. The adjusted relative differences in total sperm counts for men in increasing quartiles of processed meat intake were 0 (ref), −3 (95% confidence interval = −67 to 37), −14 (−82 to 28), and −78 (−202 to −5) million (test for trend, P = 0.01). This association was strongest among men with abstinence time less than 2 days and was driven by a strong inverse relation between processed red meat intake and ejaculate volume (test for trend, P =0.003). Conclusions In our population of young men, processed meat intake was associated with lower total sperm count. We cannot distinguish whether this association is due to residual confounding by abstinence time or represents a true biological effect.

positive: Lipid Concentrations and Semen Quality: The LIFE Study The decline in sperm count rates over the last 50 years appears to parallel the rising prevalence of obesity. As lipids levels are strongly associated with obesity, high lipids levels or hyperlipidemia may thus play an important role in the decline in fertility in addition to other environmental or lifestyle factors. The objective of this population based cohort study was to evaluate the association between men’s serum lipid concentrations and semen quality parameters among 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided prospectively up to two semen samples (94% of men provided one or more semen samples, and 77% of men provided a second sample approximately one month later). Linear mixed effects models were used to estimate the associations between baseline lipid concentrations and semen quality parameters, adjusted for age, body mass index, and race. We found that higher levels of serum total cholesterol, free cholesterol and phospholipids were associated with a significantly lower percentage of sperm with intact acrosome and smaller sperm head area and perimeter. Our results suggest that lipid concentrations may affect semen parameters, specifically sperm head morphology, highlighting the importance of cholesterol and lipid homeostasis for male fecundity.

positive: Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients. Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.

positive: Lipids and testicular function. We studied 19 male patients with primary hyperlipoproteinaemia, a control group of 28 healthy men and 44 infertile males before any treatment was undertaken. Spermiogram, seminal biochemical studies, measurements of plasma hormone levels and lipid determinations were carried out. Most hyperlipoproteinaemic patients showed abnormalities in the spermiograms and the mean values were lower than in the controls except for semen volume. Seminal biochemical determinations were normal in the majority and the hormone profile showed some abnormal values, mainly for E2. Lipid abnormalities were more common in azoospermic infertile men and mean lipid levels were higher. Correlation studies suggest that high levels of C and/or Tg are associated with poor semen quality and higher FSH levels. The results of our studies suggest that high lipid levels exert adverse direct effects at the testicular level.

positive: Dairy intake and semen quality among men attending a fertility clinic Objective To examine the relationship between dairy food intake and semen parameters Design Longitudinal study Setting Men attending academic medical center fertility clinic in Boston, MA Patients 155 men Interventions None Main Outcome Measures total sperm count, sperm concentration, progressive motility, and morphology Results Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22–3.54 servings/day) had 33% (95% confidence interval (CI) 1, 55) higher sperm concentration and 9.3 (95%CI 1.4, 17.2) percentage units higher sperm motility than men in the lowest quartile of intake (≤0.28 servings/day). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30% (95%CI 1,51) higher sperm concentration and 8.7 (95%CI 3.0, 14.4) percentage units higher sperm motility. Cheese intake was associated with lower sperm concentration among ever smokers. In this group, men in the highest tertile of intake (0.82–2.43 servings/day) had 53.2% (95%CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (<0.43 servings/day). Conclusions Our findings suggest that low-fat dairy intake, particularly low-fat milk, is related to higher sperm concentration and progressive motility, while cheese intake to lower sperm concentration among past or current smokers.

positive: Is milk responsible for male reproductive disorders? The role of environmental compounds with estrogenic activity in the development of male reproductive disorders has been a source of great concern. Among the routes of human exposure to estrogens, we are particularly concerned about cows' milk, which contains considerable amounts of estrogens. The major sources of animal-derived estrogens in the human diet are milk and dairy products, which account for 60-70% of the estrogens consumed. Humans consume milk obtained from heifers in the latter half of pregnancy, when the estrogen levels in cows are markedly elevated. The milk that we now consume may be quite unlike that consumed 100 years ago. Modern genetically-improved dairy cows, such as the Holstein, are usually fed a combination of grass and concentrates (grain/protein mixes and various by-products), allowing them to lactate during the latter half of pregnancy, even at 220 days of gestation. We hypothesize that milk is responsible, at least in part, for some male reproductive disorders. Copyright 2001 Harcourt Publishers Ltd.

positive: Role of environmental estrogens in the deterioration of male factor fertility. OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.

positive: Possible health impact of animal oestrogens in food. Oestrogens govern reproductive functions in vertebrates, and are present in all animal tissues. The theoretical maximum daily intake (TMDI) of oestradiol-17beta by consumption of cattle meat is calculated to be 4.3 ng. Following the use of oestradiol-containing growth-promoting agents, TMDI is increased by a factor of 4.6 to 20 ng oestradiol-17beta, assuming that single dosage and 'good animal husbandry' are observed. Pork and poultry probably contain similar amounts of oestrogens as untreated cattle. The mean concentration of oestradiol-17beta in whole milk is estimated at 6.4 pg/ml. Scarce data available on eggs report up to 200 pg/g oestradiol-17beta. The risk evaluation of oestrogenic growth-promoting agents is limited by analytical uncertainties. Residues of oestradiol-17alpha and the importance of oestrogen conjugates are widely unknown. The performance of mass spectrometry still needs to be improved for confirmation of oestrogen concentrations in most food. At present, the potential relevance of oestradiol acyl esters, the actual daily production rate of oestradiol in prepubertal children, and the role of oestradiol metabolites in cancer are obscure. The presence of different cytoplasmic oestrogen receptor subtypes and potential oestradiol effects in non-reproductive functions require further examination.

positive: Some observations on human semen analysis. Semen analysis of 66 unmarried medical students in the age group of 17-21 years was carried out. A higher liquefaction time pH, motility, lower sperm count and abnormal forms were observed compared to reported values. Liquefaction time, pH and sperm count was found significantly different in non-vegetarians and vegetarians, perhaps due to difference in their dietary proteins.

positive: High dietary intake of saturated fat is associated with reduced semen quality among 701 young Danish men from the general population. BACKGROUND: Saturated fat intake has been associated with both cardiovascular disease and cancer risk, and a newly published study found an association between saturated fat intake and a lower sperm concentration in infertile men. OBJECTIVE: The objective was to examine the association between dietary fat intake and semen quality among 701 young Danish men from the general population. DESIGN: In this cross-sectional study, men were recruited when they were examined to determine their fitness for military service from 2008 to 2010. They delivered a semen sample, underwent a physical examination, and answered a questionnaire comprising a quantitative food-frequency questionnaire to assess food and nutrient intakes. Multiple linear regression analyses were performed with semen variables as outcomes and dietary fat intakes as exposure variables, adjusted for confounders. RESULTS: A lower sperm concentration and total sperm count in men with a high intake of saturated fat was found. A significant dose-response association was found, and men in the highest quartile of saturated fat intake had a 38% (95% CI: 0.1%, 61%) lower sperm concentration and a 41% (95% CI: 4%, 64%) lower total sperm count than did men in the lowest quartile. No association between semen quality and intake of other types of fat was found. CONCLUSIONS: Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health.

positive: Dairy food intake in relation to semen quality and reproductive hormone levels among physically active young men STUDY QUESTION Is increased consumption of dairy foods associated with lower semen quality? SUMMARY ANSWER We found that intake of full-fat dairy was inversely related to sperm motility and morphology. These associations were driven primarily by intake of cheese and were independent of overall dietary patterns. WHAT IS KNOWN ALREADY It has been suggested that environmental estrogens could be responsible for the putative secular decline in sperm counts. Dairy foods contain large amounts of estrogens. While some studies have suggested dairy as a possible contributing factor for decreased semen quality, this finding has not been consistent across studies. STUDY DESIGN, SIZE, DURATION The Rochester Young Men's Study (n = 189) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS/MATERIALS, SETTING, METHODS Men aged 18–22 years were included in this analysis. Diet was assessed via food frequency questionnaire. Linear regression was used to analyze the relation between dairy intake and conventional semen quality parameters (total sperm count, sperm concentration, progressive motility, morphology and ejaculate volume) adjusting for age, abstinence time, race, smoking status, body mass index, recruitment period, moderate-to-intense exercise, TV watching and total calorie intake. MAIN RESULTS AND THE ROLE OF CHANCE Total dairy food intake was inversely related to sperm morphology (P-trend = 0.004). This association was mostly driven by intake of full-fat dairy foods. The adjusted difference (95% confidence interval) in normal sperm morphology percent was −3.2% (−4.5 to −1.8) between men in the upper half and those in the lower half of full-fat dairy intake (P < 0.0001), while the equivalent contrast for low-fat dairy intake was less pronounced [−1.3% (−2.7 to −0.07; P= 0.06)]. Full-fat dairy intake was also associated with significantly lower percent progressively motile sperm (P= 0.05). LIMITATIONS, REASONS FOR CAUTION As it was a cross-sectional study, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS Further research is needed to prove a causal link between a high consumption of full-fat dairy foods and detrimental effects on semen quality. If verified our findings would mean that intake of full-fat dairy foods should be considered in attempts to explain secular trends in semen quality and that men trying to have children should restrict their intake. STUDY FUNDING/COMPETING INTEREST(S) European Union Seventh Framework Program (Environment), ‘Developmental Effects of Environment on Reproductive Health’ (DEER) grant 212844. Grant P30 {"type":"entrez-nucleotide","attrs":{"text":"DK046200","term_id":"187635970","term_text":"DK046200"}}DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16 from the National Institutes of Health. None of the authors has any conflicts of interest to declare.

positive: A national survey of persistent, bioaccumulative, and toxic (PBT) pollutants in the United States milk supply. This study measured 21 persistent, bioaccumulative, and toxic (PBT) pollutants in the US milk supply. Since milk fat is likely to be among the highest dietary sources of exposure to PBTs, it is important to understand their levels in this food. Nationwide samples were collected from 45 dairy plants in July of 2000 and again in January 2001. The levels of all chemicals in the chlorobenzene, pesticide and other halogenated organic groups were determined to be below their detection limits in all samples. National averages were computed for 11 chemicals or chemical groups found above the detection limits. The national average CDD/CDF and PCB TEQ concentrations were 14.30 and 8.64 pg/l, respectively, for a total of 22.94 pg/l. These levels are about half the values found in a similar study conducted in 1996. If this difference is in fact indicative of declining milk levels and assuming exposure levels from nondairy pathways have remained the same over this time period, this would result in an overall decrease in adult background dioxin exposure of 14%. Six PAHs were detected with national averages ranging from 40 to 777 ng/l. Cadmium concentrations ranged from 150 to 870 ng/l with a national average of 360 ng/l. Lead concentrations were consistently higher than those of cadmium, ranging from 630 to 1950 ng/l with a national average of 830 ng/l. PAHs showed the strongest seasonal/geographic differences, with higher levels in winter than summer, north than south and east than west. Average adult daily intakes from total milk fat ingestion were computed for all detected compounds and compared to total intakes from all pathways: CDD/CDF/PCB TEQs: 8 vs. 55 pg/day, PAHs: 0.6 vs. 3 micro g/day, lead: 0.14 vs. 4-6 micro g/day, and cadmium: 0.06 vs. 30 micro g/day.

positive: Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine. The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the "chick edema factor" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.

positive: PCDD and PCDF contamination in catfish feed from Arkansas, USA. One combined catfish feed sample from Arkansas, USA, and its eight ingredients were analyzed for PCDDs and PCDFs. One of the ingredients, soybean meal, was highly contaminated by PCDDs, especially the toxic 2,3,7,8-substituted congeners, e.g., 7.3 pg/g dry weight or 370 pg/g lipid for the 2,3,7,8-tetra CDD. The I-TEQ value for the soybean meal was 11.4 pg/g dry weight or 576 pg/g fat. The corresponding values for the combined catfish feed concentrations were approximately 3 times lower. The congener pattern, the congener profile and the ratio sigma PCDDs/sigma PCDFs for the soybean meal were quite unique. We are not aware of any environmental sample or technical product with similar characteristics. As a result, natural formation of the PCDDs found in the soybean meal cannot be ruled out.

positive: Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake. Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, "dioxin") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.

positive: Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source. Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.

positive: PCDD, PCDF, and PCB in farm-raised catfish from southeast United States--concentrations, sources, and CYP1A induction. Nine catfish fillets, three catfish nuggets, two feed samples, and one pond sediment were analyzed for PCDD, PCDF, and PCB. Farm-raised catfish from Mississippi, Alabama, and Arkansas contained significant levels of 2,3,7,8-substituted PCDD and PCDF. In addition, a large number of non-2,3,7,8-substituted congeners were present in all samples. The catfish fillets and catfish nuggets also contained high concentrations of dioxin-like PCB, as well as a number of non-dioxin-like PCB. The TEQ based on PCDD and PCDF ranged from 9.5 to 43.0 pg/g lipid and the TEQ based on PCB ranged from 0.45 to 4.9 pg/g lipid for all catfish samples. The dioxin-like PCB contributed 4-16% to the total TEQ (PCDD/PCDF/PCB) for the catfish samples. The major source for the PCDD, PCDF, and PCB appears to be from feed and not from pond sediment. Immunoreactive CYP1A protein was elevated 2.5 fold in the pond-raised catfish compared to the aquarium-raised one. The results of this study suggest that the PCDD/PCDF are more important than the PCB in the CYP1A induction.

positive: Reducing exposure to dioxins and related compounds through foods in the next generation. Dioxins and related compounds are undesirable and unintended contaminants in the food supply, and dietary intake is the major route of exposure. Reducing dietary exposure to dioxins among the most vulnerable segments of the population (i.e., pregnant women, infants, and young girls) is an effective strategy for reducing body burdens in future generations. Exposure to dioxins through foods can be minimized by selecting lower-fat versions of meats, poultry, and dairy products. Consuming all foods, including fatty fish, in recommended amounts is congruent with the goal of reducing dioxin intake exposure and maintaining good health.

positive: The concentration and distribution of 2,3,7,8-dibenzo-p-dioxins/-furans in chickens. The concentrations of the 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid adjusted basis for each tissue. While there is a marked difference in the concentration of the 2,3,7,8-dibenzo-p-dioxins in the edible tissues expressed on a whole weight basis, the lipid-adjusted concentrations of the individual dioxins were not statistically different in the various tissues. This validates the use of lipid adjusted concentrations of 2,3,7,8-PCDDs/PCDFs in abdominal fat for the determination of the presence of these compounds in different tissues.

positive: Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/PCDF) in food samples collected in southern Mississippi, USA. In 1994, we analyzed 43 foodstuff samples from local supermarkets in southern Mississippi, USA, for PCDD/PCDF. 2,3,7,8-Cl4DD could be quantified in 31 of these samples. On a lipid basis, levels in meat (0.53-1.10 pg I-TEQ/g) and dairy products (0.42-1.10 pg I-TEQ/g) were slightly lower than those reported from other industrialized countries. While levels in dairy samples from the United States and Europe are comparable, there is a difference in the contribution of individual congeners to the I-TEQ: for example, in milk samples from Germany approximately 40% of the I-TEQ is due to the presence of 2,3, 4,7,8-Cl5DF while in the Mississippi samples this congener only contributes 16%. The highest concentrations of PCDD/PCDF in our study were detected in the farm-raised catfish (10.2-27.8 pg I-TEQ/g). A unique finding was that in addition to the 2,3,7,8-substituted PCDD/PCDF the catfish samples contained many non-2,3,7,8-substituted congeners. This is unusual because vertebrate animals selectively eliminate or metabolize the non-2,3,7,8-substituted congeners.

positive: The early treatment of type 2 diabetes. The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.

positive: Attained height of lacto-ovo vegetarian children and adolescents. The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.

positive: Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.

positive: Management of type 2 diabetes mellitus in children and adolescents. OBJECTIVE: Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, "Management of Type 2 Diabetes Mellitus in Children and Adolescents," and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.

positive: Pediatrician's role in screening and treatment: bullying, prediabetes, oral health. PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.

positive: Strategies for preventing type 2 diabetes: an update for clinicians Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.

positive: Intensive versus conventional glucose control in critically ill patients. BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society

positive: Plant foods and plant-based diets: protective against childhood obesity? The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.

positive: Prediabetes: A high-risk state for developing diabetes Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.

positive: Type 2 diabetes mellitus in children and adolescents Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.

positive: Prediabetes and type 2 diabetes in youth: an emerging epidemic disease? PURPOSE OF REVIEW: The prevalence of obesity in youth is increasing alarmingly among children and adolescents in the United States. The problem falls disproportionately on African-American and Hispanic children. Many of the metabolic and cardiovascular complications associated with obesity are already present during childhood and are closely linked to the concomitant insulin resistance/hyperinsulinemia and degree of obesity. Moreover, these co-morbidities persist into adulthood. RECENT FINDINGS: The progression from normal glucose tolerance to type 2 diabetes mellitus involves an intermediate stage known as prediabetes or impaired glucose regulation. Prediabetes is characterized by peripheral insulin-resistance and impaired glucose sensitivity of first-phase insulin secretion. On the other hand, in overt type 2 diabetes mellitus beta-cell failure becomes fully manifested. Progression from prediabetes to type 2 diabetes mellitus in youth is characterized by marked weight gain and further reduction in insulin secretion and insulin resistance. SUMMARY: Reverting obesity through lifestyle modification, that involves nutrition education, behavior modification and exercise, is an important step to prevent the progression to diabetes.

positive: The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food? Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.

positive: Childhood obesity and type 2 diabetes mellitus. Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.

positive: Vegetarian diets and childhood obesity prevention. The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.

positive: Non-celiac gluten sensitivity: clinical relevance and recommendations for future research. BACKGROUND: There has been increasing interest in the entity of Non-Celiac Gluten Sensitivity (NCGS) in recent years; however, it still remains a controversial topic and its pathogenesis is not well understood. Celiac Disease, in contrast, is a well-studied condition that has become increasingly recognized as a prevalent condition arising from a heightened immunological response to gluten. Wheat allergy is an IgE-mediated condition capable of causing a variety of gastrointestinal symptoms. However, the number of patients who have neither celiac disease nor wheat allergy, but appear to derive benefit from a gluten-free diet, is also increasing substantially. The use of the term NCGS as a way of describing this condition has become increasingly prevalent in recent years. PURPOSE: In this review, we will focus on gastrointestinal manifestations of NCGS and discuss the evidence for the condition and its putative pathogenesis. We will discuss areas of controversy and areas for potential future research. © 2013 John Wiley & Sons Ltd.

positive: Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. OBJECTIVES: Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers. METHODS: We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001-2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls. RESULTS: Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in "in vitro" assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients. CONCLUSIONS: Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.

positive: Non-celiac gluten sensitivity: literature review. BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.

positive: Nonceliac gluten sensitivity: sense or sensibility? Recent studies support the existence of a new condition, nonceliac gluten sensitivity, which manifests as intestinal or extraintestinal symptoms that improve or disappear after gluten withdrawal in individuals with normal small-bowel mucosa and negative results on serum antitransglutaminase and antiendomysial antibody testing. Although the clinical value of this concept is under debate, the prevalence of nonceliac gluten sensitivity in the general population is supposed to be many times higher than that of celiac disease. The lack of an unambiguous definition of nonceliac gluten sensitivity, a major pitfall, is primarily related to the heterogeneous cause of this condition, whose symptoms are presumed to be caused by different mechanisms. If nonceliac gluten sensitivity is an etiologically heterogeneous syndrome, then management options should vary according to the predominant or concomitant underlying pathogenic pathways.

positive: Gluten-sensitive diarrhea without evidence of celiac disease. Eight adult female patients suffering from abdominal pain and chronic diarrhea which was often incapacitating and frequently nocturnal, had dramatic relief on a gluten-free diet and return of symptoms after gluten challenge. Previous nonspecific measures and a milk-free diet were ineffective. Multiple jejunal biopsies showed minor, but significant changes in cellularity which returned to normal on the gluten-free diet. Apart from a slight increase in jejunal cellularity, no immunological abnormalities were found after gluten challenge. Steatorrhea or other biochemical defects, common in celiac disease, were not found. It was concluded that these patients had a gluten-sensitive diarrhea, but had no evidence of celiac disease.

positive: Sensitivity-related illness: the escalating pandemic of allergy, food intolerance and chemical sensitivity. The prevalence of allergic-related diseases, food intolerance, and chemical sensitivities in both the pediatric and adult population has increased dramatically over the last two decades, with escalating rates of associated morbidity. Conditions of acquired allergy, food intolerance and chemical hypersensitivity are frequently the direct sequelae of a toxicant induced loss of tolerance (TILT) in response to a significant initiating toxic exposure. Following the primary toxicant insult, the individuals become sensitive to low levels of diverse and unrelated triggers in their environment such as commonly encountered chemical, inhalant or food antigens. Among sensitized individuals, exposure to assorted inciting stimuli may precipitate diverse clinical and/or immune sequelae as may be evidenced by clinical symptoms as well as varied lymphocyte, antibody, or cytokine responses in some cases. Recently recognized as a mechanism of disease development, TILT and resultant sensitivity-related illness (SRI) may involve various organ systems and evoke wide-ranging physical or neuropsychological manifestations. With escalating rates of toxicant exposure and bioaccumulation in the population-at-large, an increasing proportion of contemporary illness is the direct result of TILT and ensuing SRI. Avoidance of triggers will preclude symptoms, and desensitization immunotherapy or immune suppression may ameliorate symptomatology in some cases. Resolution of SRI generally occurs on a gradual basis following the elimination of bioaccumulated toxicity and avoidance of further initiating adverse environmental exposures. As has usually been the case throughout medical history whenever new evidence regarding disease mechanisms emerges, resistance to the translation of knowledge abounds. Copyright © 2010 Elsevier B.V. All rights reserved.

positive: Non-celiac gluten sensitivity. Is it in the gluten or the grain? Celiac disease is an immune-mediated inflammatory disorder of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals. Over the past several years, the concept of non-celiac gluten sensitivity (NCGS) has gained significant interest from the scientific community and mass media and the number of individuals embracing a gluten-free diet is rapidly growing. This condition is characterized by gastrointestinal or extraintestinal symptoms that respond to gluten withdrawal without evidence for underlying celiac disease or wheat allergy. Symptoms display significant overlap with the irritable bowel syndrome. Many important factors regarding this relatively novel condition remain to be elucidated; no discriminative markers to support a diagnosis of gluten sensitivity have been identified yet and its pathogenesis remains obscure. Here we review the current knowledge on NCGS, and outline potential pathogenic pathways of different gluten related disorders in order to gain clues about the pathophysiology of this novel condition.

positive: Absence of somatization in non-coeliac gluten sensitivity. OBJECTIVE: In contrast to coeliac disease (CD), the mechanism behind non-coeliac gluten sensitivity (NCGS) is unclear. The aims of the study were to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals compared with CD patients and healthy controls, and to compare the response to gluten challenge between NCGS and CD patients. MATERIAL AND METHODS: We examined 22 CD patients and 31 HLA-DQ2+ NCGS patients without CD, all on a gluten-free diet. All but five CD patients were challenged orally for 3 days with gluten; symptom registration was performed during challenge. A comparison group of 40 healthy controls was included. Patients and healthy controls completed questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life. RESULTS: The NCGS patients reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after gluten challenge than CD patients. There were no significant differences between CD and NCGS patients regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. The somatization level was low in CD and NCGS groups. Symptom increase after gluten challenge was not related to personality in NCGS patients. CONCLUSIONS: NCGS patients did not exhibit a tendency for general somatization. Personality and quality of life did not differ between NCGS and CD patients, and were mostly at the same level as in healthy controls. NCGS patients reported more symptoms than CD patients after gluten challenge.

positive: Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity - an exploratory clinical study. BACKGROUND: Current evidence suggests that many patients with self-reported non-coeliac gluten sensitivity (NCGS) retain gastrointestinal symptoms on a gluten-free diet (GFD) but continue to restrict gluten as they report 'feeling better'. AIM: To investigate the notion that a major effect of gluten in those with NCGS is on mental state and not necessarily on gastrointestinal symptoms. METHODS: Twenty-two subjects (24-62 years, five male) with irritable bowel syndrome who had coeliac disease excluded but were symptomatically controlled on a GFD, undertook a double-blind cross-over study. Participants randomly received one of three dietary challenges for 3 days, followed by a minimum 3-day washout before crossing over to the next diet. Challenge gluten-free food was supplemented with gluten (16 g/day), whey (16 g/day) or not supplemented (placebo). End-points included mental state as assessed by the Spielberger State Trait Personality Inventory (STPI), cortisol secretion and gastrointestinal symptoms. RESULTS: Gluten ingestion was associated with higher overall STPI state depression scores compared to placebo [M = 2.03, 95% CI (0.55-3.51), P = 0.010] but not whey [M = 1.48, 95% CI (-0.14 to 3.10), P = 0.07]. No differences were found for other STPI state indices or for any STPI trait measures. No difference in cortisol secretion was identified between challenges. Gastrointestinal symptoms were induced similarly across all dietary challenges. CONCLUSIONS: Short-term exposure to gluten specifically induced current feelings of depression with no effect on other indices or on emotional disposition. Gluten-specific induction of gastrointestinal symptoms was not identified. Such findings might explain why patients with non-coeliac gluten sensitivity feel better on a gluten-free diet despite the continuation of gastrointestinal symptoms. © 2014 John Wiley & Sons Ltd.

positive: Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. METHODS: A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. RESULTS: A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. CONCLUSIONS: "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.

positive: Coeliac Disease - New Pathophysiological Findings and Their Implications for Therapy. in English, German Die Zöliakie ist weltweit eine der häufigsten Erkrankungen, die aus einer Kombination von Umwelt-(Gluten) und genetischen (humanes Leukozyten-Antigen (HLA) und Nicht-HLA-Gene) Faktoren resultiert. Abhängig von der geographischen Lage, wird die Prävalenz der Zöliakie auf etwa 0,5-1% der Bevölkerung geschätzt. Die einzige Behandlung, die derzeit bei Zöliakie verfügbar ist, besteht in einer glutenfreien Diät (GFD), die glutenhaltige Getreide wie Weizen, Roggen und Gerste sowie andere Lebensmittel mit natürlichem oder zugesetztem Gluten ausschließt. Die Complianceraten und die Akzeptanz durch die Patienten sind jedoch oft schlecht. Weiterhin kann die Diät selbst bei Patienten, die diese vollständig einhalten, möglicherweise nicht zu einer klinischen oder histologischen Verbesserung führen. Daher ist es nicht verwunderlich, dass Studien zeigen, dass Zöliakie-Patienten sehr an nichtdiätetischen Alternativen interessiert sind. Die folgende Übersicht konzentriert sich auf aktuelle pathophysiologische Konzepte der Zöliakie, bei denen jene Signalwege herausgestellt werden, die als mögliche neue, nichtdiätetische therapeutische Ansatzpunkte in der Behandlung der Zöliakie dienen könnten. Coeliac disease (CD) is one of the most common diseases worldwide, resulting from a combination of environmental (gluten) and genetic (human leucocyte antigen (HLA) and non-HLA genes) factors. Depending on the geographical location, the prevalence of CD has been estimated to approximate 0.5-1%. The only treatment currently available for CD is a gluten-free diet (GFD) excluding gluten-containing cereals such as wheat, rye, and barley, and other foodstuffs with natural or added gluten. However, adherence rates and patient acceptance are often poor. Moreover, even in fully adherent patients, the diet may fail to induce clinical or histological improvement. Hence, it is unsurprising that studies show CD patients to be highly interested in non-dietary alternatives. The following review focuses on current pathophysiological concepts of CD, spotlighting those pathways which may serve as new possible, non-dietary therapeutic targets in the treatment of CD.

positive: Cow's-milk-free diet as a therapeutic option in childhood chronic constipation. OBJECTIVES: It has been reported that a number of children with constipation respond to a diet free of cow's-milk (CM) proteins, although evidence is lacking to support an immunoglobulin E-mediated mechanism. PATIENTS AND METHODS: We performed an open-label crossover study comparing CM and rice milk in 69 children who fulfilled Rome III criteria for chronic constipation. Clinical, physical, and immunologic parameters of patients who responded (R) and who did not respond (NR) to a CM-free diet were compared. RESULTS: Thirty-five of the 69 children (51%) improved during the first CM-free diet phase, 8 of these did not develop constipation when CM was reintroduced, and 27 children (39%) developed constipation during the CM challenge and improved during the second CM-free diet phase (R group). Thirty-four children (49%) did not improve during the first CM-free diet phase (NR group). Bowel movements per week among R children significantly increased compared with NR children (R: 2.8-7.7 vs NR: 2.6-2.7) (P < 0.001). Seventy-eight percent of the children with developmental delay responded to the CM-free diet (P = 0.007). No significant statistical difference was found between the R and NR children in terms of fiber and milk consumption; atopic or allergic history; full-blood eosinophil count and percentage, and lymphocyte populations; immunoglobulins, immunoglobulin (Ig)G subclasses, total IgE; and serum-specific immunoglobulin E for CM proteins. CONCLUSIONS: A clear association between CM consumption and constipation has been found in more than one third of children. However, analytical parameters do not demonstrate an immunoglobulin E-mediated immunologic mechanism.

positive: Prevalence, symptoms and outcome of constipation in infants and toddlers. OBJECTIVE: To determine the prevalence of constipation in children <or=2 years, describe the symptoms of constipation, and review how often specific interventions were effective. STUDY DESIGN: Retrospective chart review. RESULTS: Of 4,157 children <2 years of age, 185 children had constipation. The prevalence rate for constipation in the first year of life was 2.9%, and in the second year of life, the rate was 10.1%. Functional constipation was the cause in 97% of the children. Boys and girls were affected with equal frequency. Constipation was caused by an underlying organic disease in 1.6% of cases, and 97% of the children had functional constipation. Dietary changes and corn syrup were the initial treatment suggestions for 116 children; 93% of these children underwent follow-up examinations, and the constipation resolved in 25% of the children. Of 100 children treated with milk of magnesia or polyethylene glycol 3350 without electrolytes, 93 children underwent follow-up examinations, and the constipation was resolved with treatment in 92% of the children. CONCLUSIONS: Dietary changes, corn syrup, or both resolved constipation in 25% of children, and laxatives resolved constipation in 92% of children. Both milk of magnesia and polyethylene glycol were efficient and safe in infants and toddlers.

positive: Intolerance of cow's milk and chronic constipation in children. BACKGROUND: Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow's milk among children. On the basis of a prior open study, we hypothesized that intolerance of cow's milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children. METHODS: We performed a double-blind, crossover study comparing cow's milk with soy milk in 65 children (age range, 11 to 72 months) with chronic constipation (defined as having one bowel movement every 3 to 15 days). All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success; 49 had anal fissures and perianal erythema or edema. After 15 days of observation, the patients received cow's milk or soy milk for two weeks. After a one-week washout period, the feedings were reversed. A response was defined as eight or more bowel movements during a treatment period. RESULTS: Forty-four of the 65 children (68 percent) had a response while receiving soy milk. Anal fissures and pain with defecation resolved. None of the children who received cow's milk had a response. In all 44 children with a response, the response was confirmed with a double-blind challenge with cow's milk. Children with a response had a higher frequency of coexistent rhinitis, dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1 of 21, P=0.05); they were also more likely to have anal fissures and erythema or edema at base line (40 of 44 vs. 9 of 21, P<0.001), evidence of inflammation of the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P=0.008), and signs of hypersensitivity, such as specific IgE antibodies to cow's-milk antigens (31 of 44 vs. 4 of 21, P<0.001). CONCLUSIONS: In young children, chronic constipation can be a manifestation of intolerance of cow's milk.

positive: Cow's Milk Allergy Is a Major Contributor in Recurrent Perianal Dermatitis of Infants Background. Recurrent perianal inflammation has great etiologic diversity. A possible cause is cow's milk allergy (CMA). The aim was to assess the magnitude of this cause. Subjects and Methods. This follow up clinical study was carried out on 63 infants with perianal dermatitis of more than 3 weeks with history of recurrence. Definitive diagnosis was made for each infant through medical history taking, clinical examination and investigations including stool analysis and culture, stool pH and reducing substances, perianal swab for different cultures and staining for Candida albicans. Complete blood count and quantitative determination of cow's milk-specific serum IgE concentration were done for all patients. CMA was confirmed through an open withdrawal-rechallenge procedure. Serum immunoglobulins and CD markers as well as gastrointestinal endoscopies were done for some patients. Results. Causes of perianal dermatitis included CMA (47.6%), bacterial dermatitis (17.46%), moniliasis (15.87%), enterobiasis (9.52%) and lactose intolerance (9.5%). Predictors of CMA included presence of bloody and/or mucoid stool, other atopic manifestations, anal fissures, or recurrent vomiting. Conclusion. We can conclude that cow's milk allergy is a common cause of recurrent perianal dermatitis. Mucoid or bloody stool, anal fissures or ulcers, vomiting and atopic manifestations can predict this etiology.

positive: The Role of Cow's Milk Allergy in Pediatric Chronic Constipation: A Randomized Clinical Trial Objective Cow's milk allergy has different presentations in children and can cause functional bowel symptoms such as chronic constipation. The aims of this study were to investigate the role of cow's milk allergy as a cause of chronic constipation and effect of cow's milk free diet (CMFD) on its treatment in children. Methods We performed a randomized clinical study comparing CMFD with cow's milk diet (CMD) in two groups each consisting of 70 patients (age range, 1-13 years) with chronic functional constipation (defined as Rome III criteria). All subjects had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives for at least 3 months without success; also all 140 patients performed skin prick test. The case group received CMFD for 4 weeks. After that they received CMD for 2 extra weeks. The control group received CMD for whole 6 weeks. A response was defined as decreased in signs and symptoms that not fulfilled Rome III criteria after 4 weeks of CMFD and came back to Rome III criteria after 2 weeks of CMD challenge. Findings After 4 weeks 56 (80%) patients of the case group responded in comparison to 33 (47.1%) patients in the control group (P=0.0001). In the case group after 2 weeks challenge 24 out of 56 (42.8%) responders developed constipation according to Rome III criteria. With other words, the frequency of cow's milk allergy among constipated patients was 80%. Only one patient had positive skin prick test. Conclusion In children, chronic constipation can be a manifestation of cow's milk allergy. At present, although several aspects must be further investigated, a therapeutic attempt with elimination diet is advisable in all children with constipation unresponsive to correct laxative treatment.

positive: Cows milk consumption in constipation and anal fissure in infants and young children. OBJECTIVE: To examine daily cows milk consumption and duration of breastfeeding in infants and young children with anal fissure and constipation. METHODS: Two groups of 30 consecutive children aged between 4 months and 3 years were evaluated retrospectively. Group I comprised children with chronic constipation and anal fissure in whom surgical causes were excluded, and group II comprised normal children. The daily consumption of cows milk, duration of breastfeeding and other clinical features of the children were investigated RESULTS: The mean daily consumption of cows milk was significantly higher in group I (756 mL, range 200-1500 mL) than group II (253 mL, range 0-1000 mL) (P < 0.001). Group I children were breastfed for a significantly shorter period (5.8 months, range 0-18 months) than group II (10.1 months, range 2-24 months) (P < 0.006). The odds ratios for the two factors - children consuming more than 200 mL of cows milk per day (25 children in group I, 11 children in group II) and breastfeeding for less than 4 months (16 children in group I, 5 children in group II) - were calculated to be 8.6 (95% confidence interval [CI]: 0.23-0.74, P = 0.0005) and 5.7 (95% CI: 0.37-0.66, P = 0.007), respectively. CONCLUSIONS: Infants and young children with chronic constipation and anal fissure may consume larger amounts of cows milk than children with a normal bowel habit. Additionally, shorter duration of breastfeeding and early bottle feeding with cows milk may play a role in the development of constipation and anal fissure in infants and young children.

positive: Review article: Chronic constipation and food hypersensitivity--an intriguing relationship. BACKGROUND: Chronic constipation is common in the general population. Some studies have shown that in children cow's milk protein hypersensitivity can cause chronic constipation unresponsive to laxative treatment. AIMS: To review the literature and summarize the data that point to a relationship between refractory chronic constipation and food hypersensitivity, and to discuss the hypothesis that the pathogenesis of constipation due to food hypersensitivity. METHODS: A search in the U.S. National Library of Medicine was performed, matching the key words 'chronic constipation, food intolerance and allergy'. RESULTS: Thirty-three papers were found but only 19 of them were related to the topic of this review. Most of the data indicated a relationship between constipation and food allergy in a subgroup of paediatric patients with 'idiopathic' constipation unresponsive to laxative treatment. There was only one study in adults that demonstrated the resolution of chronic constipation on hypoallergenic diet in four patients. CONCLUSIONS: An increasing number of reports suggest a relationship between refractory chronic constipation and food allergy in children. Similar data in adults are scarce and need to be confirmed. Further studies should be performed to obtain firmer evidence for the role of allergy in constipation and clarify the pathogenetic mechanisms involved.

positive: Cow's milk protein intolerance and chronic constipation in children. Cow's milk protein (CMP) allergy was investigated in 25 children (age-range 3 months to 11 years) with chronic constipation. A diagnosis of constipation was made on the basis of a history of painful elimination of hard stools for at least 1 month, whether or not associated with a reduced frequency of stools or soiling. The children were evaluated using clinical parameters and the following laboratory tests: total serum immunoglobulin E (IgE); specific IgE (radioallergosorbent test [RAST]) for whole cow's milk, alpha-lactoalbumin, beta-lactoglobulin, and a food group; and skin-prick tests with whole milk, alpha-lactoalbumin, beta-lactoglobulin, and casein. Following the evaluation, the children were submitted to a CMP-free diet for a period of 4 weeks. In seven patients (28%), constipation disappeared during the CMP-free diet and reappeared within 48-72 h following challenge with cow's milk. In two infants a rectal biopsy revealed allergic colitis and they therefore did not undergo the challenge. High serum levels of total IgE were observed in five of the children who showed a clinical improvement (71%), a positive skin-test in two (29%), and detectable specific IgE in two (29%). These results suggest that CMP allergy or intolerance should be considered as a cause of chronic refractory constipation in children, although the underlying mechanism still require further investigation.

positive: Chronic constipation as a symptom of cow milk allergy. Twenty-seven consecutive infants (mean age, 20.6 months) with chronic "idiopathic" constipation were studied to investigate the possible relation between constipation and cow milk protein allergy (CMPA). The infants were initially observed on an unrestricted diet, and the number of stools per day was recorded. Subsequently the infants were put on a diet free of cow milk protein (CMP) for two periods of 1 month each, separated by two challenges with CMP. During the CMP-free diet, there was a resolution of symptoms in 21 patients; during the two consecutive challenges, constipation reappeared within 48 to 72 hours. In another six patients the CMP-free diet did not lead to improvement of constipation. Only four of the patients who improved on the CMP-free diet had concomitant symptoms of suspected CMPA, but a medical history of CMPA was found in 15 of the 21 patients cured and in only one of the six patients whose condition had not improved (p < 0.05); in addition, in 15 of the 21 cured patients, results of one or more laboratory tests (specific IgE, IgG, anti-beta-lactoglobulin, circulating eosinophils) were positive at the time of diagnosis, indicating hypersensitivity, compared with one of the six patients whose condition did not improve (p < 0.05). The endoscopic and histologic findings at the time of diagnosis showed proctitis with monocytic infiltration in two patients cured with the CMP-free diet; after 1 month on this diet, they were completely normal. We conclude that constipation in infants may have an allergic pathogenesis.

positive: Oligo-antigenic diet in the treatment of chronic anal fissures. Evidence for a relationship between food hypersensitivity and anal fissures. OBJECTIVES: Patients with chronic constipation due to food hypersensitivity (FH) had an elevated anal sphincter resting pressure. No studies have investigated a possible role of FH in anal fissures (AFs). We aimed to evaluate (1) the effectiveness of diet in curing AFs and to evaluate (2) the clinical effects of a double-blind placebo-controlled (DBPC) challenge, using cow's milk protein or wheat. METHODS: One hundred and sixty-one patients with AFs were randomized to receive a "true-elimination diet" or a "sham-elimination diet" for 8 weeks; both groups also received topical nifedipine and lidocaine. Sixty patients who were cured with the "true-elimination diet" underwent DBPC challenge in which cow's milk and wheat were used. RESULTS: At the end of the study, 69% of the "true-diet group" and 45% of the "sham-diet group" showed complete healing of AFs (P<0.0002). Thirteen of the 60 patients had AF recurrence during the 2-week cow's milk DBPC challenge and 7 patients had AF recurrence on wheat challenge. At the end of the challenge, anal sphincter resting pressure significantly increased in the patients who showed AF reappearance (P<0.0001), compared with the baseline values. The patients who reacted to the challenges had a significantly higher number of eosinophils in the lamina propria and intraepithelial lymphocytes than those who did not react to the challenges. CONCLUSIONS: An oligo-antigenic diet combined with medical treatment improved the rate of chronic AF healing. In more than 20% of the patients receiving medical and dietary treatment, AFs recurred on DBPC food challenge.

positive: Food intolerance and chronic constipation: manometry and histology study. BACKGROUND: Chronic constipation in children can be caused by cows' milk intolerance (CMI), but its pathogenesis is unknown. AIMS: To evaluate the histology and manometry pattern in patients with food intolerance-related constipation. PATIENTS AND METHODS: Thirty-six consecutive children with chronic constipation were enrolled. All underwent an elimination diet and successive double-blind food challenge. All underwent rectal biopsy and anorectal manometry. RESULTS: A total of 14 patients were found to be suffering from CMI and three from multiple food intolerance. They had a normal stool frequency on elimination diet, whereas constipation recurred on food challenge. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, and the number of intra-epithelial lymphocytes and eosinophils. The rectal mucous gel layer showed that the food-intolerant patients had a significantly lower thickness of mucus than the other subjects studied. Manometry showed a higher anal sphincter resting pressure and a lower critical volume in food intolerance patients than in the others suffering from constipation unrelated to food intolerance. Both histology and manometry abnormalities disappeared on the elimination diet. CONCLUSIONS: Food intolerance-related constipation is characterized by proctitis. Increased anal resting pressure and a reduced mucous gel layer can be considered to be contributory factors in the pathogenesis of constipation.

positive: Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne Acne in adolescents of developed countries is an epidemic skin disease and has currently been linked to the Western diet (WD). It is the intention of this viewpoint to discuss the possible impact of WD-mediated nutrient signalling in the pathogenesis of acne. High glycaemic load and dairy protein consumption both increase insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) that is superimposed on elevated IGF-1 signalling of puberty. The cell's nutritional status is primarily sensed by the forkhead box transcription factor O1 (FoxO1) and the serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1). Increased IIS extrudes FoxO1 into the cytoplasm, whereas nuclear FoxO1 suppresses hepatic IGF-1 synthesis and thus impairs somatic growth. FoxO1 attenuates androgen signalling, interacts with regulatory proteins important for sebaceous lipogenesis, regulates the activity of innate and adaptive immunity, antagonizes oxidative stress and most importantly functions as a rheostat of mTORC1, the master regulator of cell growth, proliferation and metabolic homoeostasis. Thus, FoxO1 links nutrient availability to mTORC1-driven processes: increased protein and lipid synthesis, cell proliferation, cell differentiation including hyperproliferation of acroinfundibular keratinocytes, sebaceous gland hyperplasia, increased sebaceous lipogenesis, insulin resistance and increased body mass index. Enhanced androgen, TNF-α and IGF-1 signalling due to genetic polymorphisms promoting the risk of acne all converge in mTORC1 activation, which is further enhanced by nutrient signalling of WD. Deeper insights into the molecular interplay of FoxO1/mTORC1-mediated nutrient signalling are thus of critical importance to understand the impact of WD on the promotion of epidemic acne and more serious mTORC1-driven diseases of civilization.

positive: Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam... Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

positive: Turning acne on/off via mTORC1 Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.

positive: Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis. Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.

positive: Acne vulgaris: a disease of Western civilization. BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.

positive: ACNE AND RISK OF PROSTATE CANCER In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for four or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used “tetracycline for at least two months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for four or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR=1.70, 95% CI:1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.

positive: Dietary intervention in acne The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.

positive: Metabolic disorders and breast cancer risk (United States). OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.

positive: Acne: risk indicator for increased body mass index and insulin resistance. Acne appears to represent a visible indicator disease of over-activated mTORC1 signalling, an unfavour-able metabolic deviation on the road to serious common Western diseases of civilisation associated with increased body mass index and insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the association of acne with increased body mass index, insulin resistance, and early onset of menarche. Both, a high glycaemic load and increased consumption of milk and milk products, staples of Western diet, aggravate mammalian target of rapamycin complex 1 signalling. This review of the literature summarises present evidence for an association between acne, increased body mass index, insulin resistance and Western diet. By dietary intervention with a Palaeolithic-type diet, the dermatologist has the chance to attenuate patients' increased mTORC1 signalling by reducing glycaemic load and milk consumption, which may not only improve acne but may delay the march to more serious mTORC1-driven diseases of civilisation.

positive: The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.

positive: Nutrient Signaling to mTOR and Cell Growth The mammalian target of rapamycin (mTOR) is a conserved protein kinase involved in a multitude of cellular processes including cell growth. Increased mTOR activation is observed in multiple human cancers and inhibition of mTOR has proven efficacious in numerous clinical trials. mTOR comprises two complexes, termed mTORC1 and mTORC2. Both complexes respond to growth factors, whereas only mTORC1 is controlled by nutrients, such as glucose and amino acids. Since the discovery of mTOR, extensive studies have intricately detailed the molecular mechanisms by which mTORC1 is regulated. Somewhat paradoxically, amino acid induced mTORC1 activation—arguably the most essential stimulus leading to mTORC1 activation—is the least understood. Here we review the current knowledge of nutrient dependent regulation of mTORC1.

positive: Sirolimus for Kaposi's sarcoma in renal-transplant recipients. BACKGROUND: Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treatment with immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have antitumor effects. METHODS: We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy-proven Kaposi's sarcoma and began sirolimus therapy. All patients underwent an excisional biopsy of the lesion and one biopsy of normal skin at the time of diagnosis. A second biopsy was performed at the site of a previous Kaposi's sarcoma lesion six months after sirolimus therapy was begun. We examined biopsy specimens for vascular endothelial growth factor (VEGF), Flk-1/KDR protein, and phosphorylated Akt and p70S6 kinase, two enzymes in the signaling pathway targeted by sirolimus. RESULTS: Three months after sirolimus therapy was begun, all cutaneous Kaposi's sarcoma lesions had disappeared in all patients. Remission was confirmed histologically in all patients six months after sirolimus therapy was begun. There were no acute episodes of rejection or changes in kidney-graft function. Levels of Flk-1/KDR and phosphorylated Akt and p70S6 kinase were increased in Kaposi's sarcoma cells. The expression of VEGF was increased in Kaposi's sarcoma cells and even more so in normal skin cells around the Kaposi's sarcoma lesions. CONCLUSIONS: Sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while providing effective immunosuppression. Copyright 2005 Massachusetts Medical Society.

positive: Amino acid sensing mechanisms: an Achilles heel in cancer? The act of increasing mass, either in non-dividing cells or in dividing cells seeking to provide new material for daughter cells, depends upon the continued presence of extracellular nutrients in order to conserve mass. For amino acid nutrients, it appears that their insufficiency for new protein synthesis is actively monitored by both prokaryotic and eukaryotic cells, eliciting appropriate cellular responses that may depend not only on bulk nutrient supply, but also on the abundance of specific amino acids. © 2012 The Author Journal compilation © 2012 FEBS.

positive: Deconvoluting mTOR biology In metazoans, TOR is an essential protein that functions as a master regulator of cellular growth and proliferation. Over the past decade, there has been an explosion of information about this critical master kinase, ranging from the composition of the TOR protein complex to its ability to act as an integrator of numerous extracellular signals. Unfortunately, this plethora of information has also raised numerous questions regarding TOR function. Currently, the prevailing view is that mammalian TOR (mTOR) exists in at least two molecular complexes, mTORC1 and mTORC2, which are largely defined by the presence of either RAPTOR or RICTOR. However, additional co-factors have been identified for each complex, and their importance in mediating mTOR signals has been incompletely elucidated. Similarly, there are differences in mTOR function that reflect the tissue of origin. In this review, we present an alternative view to mTOR complex formation and function, which envisions mTOR regulation and signal propagation as a reflection of cell type- and basal state-dependent conditions. The re-interpretation of mTOR biology in this framework may facilitate the design of therapies most likely to effectively inhibit this central regulator of cell behavior.

positive: mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ... Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

positive: mTORC1 signaling: what we still don't know. The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected. mTORC1 regulates diverse cellular functions. Several mTORC1 substrates are now known, although in several cases their physiological roles are poorly or incompletely understood. In the case of several processes, although it is clear that they are regulated by mTORC1, it is not known how mTORC1 does this. Lastly, mTORC1 is implicated in ageing, but again it is unclear what mechanisms account for this. Given the importance of mTORC1 signaling both for cellular functions and in human disease, it is a high priority to gain further insights into the control of mTORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.

positive: mTOR is a key modulator of ageing and age-related disease Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.

positive: mTOR and cancer therapy. Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of the targets of the mTOR kinase, are overexpressed or mutated in cancer. Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo. Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer. The sporadic responses from the initial clinical trials, based on the hypothesis of general translation inhibition of cancer cells are now beginning to be understood owing to a more complete understanding of the dynamics of mTOR regulation and the function of mTOR in the tumor microenvironment. This review will summarize the preclinical and clinical data and recent discoveries of the function of mTOR in cancer and growth regulation.

positive: Fisetin regulates obesity by targeting mTORC1 signaling. Fisetin, a flavonol present in vegetables and fruits, possesses antioxidative and anti-inflammatory properties. In this study, we have demonstrated that fisetin prevents diet-induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis. To evaluate whether fisetin regulates mTORC1 signaling, we investigated the phosphorylation and kinase activity of the 70-kDa ribosomal protein S6 kinase 1 (S6K1) and mTORC1 in 3T3-L1 preadipocytes. Fisetin treatment of preadipocytes reduced the phosphorylation of S6K1 and mTORC1 in a time- and concentration-dependent manner. To further our understanding of how fisetin negatively regulates mTORC1 signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells. The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt-dependent manner. Recent studies have shown that adipocyte differentiation is dependent on mTORC1 activity. Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of fisetin on mTOR. The inhibitory effect of fisetin on adipogenesis is dependent of mTOR activity, suggesting that fisetin inhibits adipogenesis and the accumulation of intracellular triglycerides during adipocyte differentiation by targeting mTORC1 signaling. Fisetin supplementation in mice fed a high-fat diet (HFD) significantly attenuated HFD-induced increases in body weight and white adipose tissue. We also observed that fisetin efficiently suppressed the phosphorylation of Akt, S6K1 and mTORC1 in adipose tissue. Collectively, these results suggest that inhibition of mTORC1 signaling by fisetin prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice. Therefore, fisetin may be a useful phytochemical agent for attenuating diet-induced obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

positive: Rapalogs in cancer prevention Common cancer is an age-related disease. Slow aging is associated with reduced and delayed carcinogenesis. Calorie restriction (CR), the most studied anti-aging intervention, prevents cancer by slowing down the aging process. Evidence is emerging that CR decelerates aging by deactivating MTOR (Target of Rapamycin). Rapamycin and other rapalogs suppress cellular senescence, slow down aging and postpone age-related diseases including cancer. At the same time, rapalogs are approved for certain cancer treatments. Can cancer prevention be explained by direct targeting of cancer cells? Or does rapamycin prevent cancer indirectly through slowing down the aging process? Increasing evidence points to the latter scenario.

positive: Caloric restriction and incidence of breast cancer. CONTEXT: Restricting caloric intake is one of the most effective ways to extend lifespan and to reduce spontaneous tumor occurrence in experimental animals, but whether similar associations hold in humans has not been appropriately studied. OBJECTIVE: To determine whether caloric restriction in early life reduces the risk of invasive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using data from the Swedish Inpatient Registry, the Swedish Cancer Registry, the Swedish Death Registry, and the Swedish Fertility Registry. Participants were 7303 Swedish women hospitalized for anorexia nervosa prior to age 40 years between 1965 and 1998. Women were excluded (n = 31) if they were diagnosed with cancer prior to their first discharge from hospitalization for anorexia nervosa. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer. RESULTS: Compared with the Swedish general population, women hospitalized for anorexia nervosa prior to age 40 years had a 53% (95% confidence interval [CI], 3%-81%) lower incidence of breast cancer; nulliparous women with anorexia nervosa had a 23% (95% CI, 79% higher to 75% lower) lower incidence, and parous women with anorexia nervosa had a 76% (95% CI, 13%-97%) lower incidence. CONCLUSIONS: Severe caloric restriction in humans may confer protection from invasive breast cancer. Low caloric intake prior to first birth followed by a subsequent pregnancy appears to be associated with an even more pronounced reduction in risk.

positive: Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer. The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.

positive: Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans. Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans. Copyright © 2012 Elsevier Inc. All rights reserved.

positive: Evaluation of Antiradical Activity of Different Cocoa and Chocolate Products: Relation with Lipid and Protein Composition Chocolate antioxidant properties are often claimed; however, they are frequently different from the parent natural sources due to the industry or artisan transformation. In particular, antioxidant property of chocolate and cocoa are not adequately taken into consideration by consumers who normally make use of this food just for its flavor and taste properties. In this study, we have investigated the antioxidant capacity and total phenolic content of cocoa nibs, cocoa masses, and corresponding chocolate bars with different percentages of cocoa from different origins. The antioxidant capacity of the different samples was measured by two different assays [1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and ferric reducing antioxidant of potency (FRAP) tests]. The Folin–Ciocalteu reagent was used to assess the total phenolic content. The masses showed a higher antioxidant power than the nibs, and this has been attributed to the fact that in the nibs is still present the lipid part, which will form the cocoa butter. The influence of milk, whey, and soy proteins was also investigated. Our results showed that the extra dark cocoa bar, 100% cocoa chocolate, is the best in terms of total polyphenol content and in terms of antioxidant capacity according to the DPPH and FRAP tests. In addition, the bars of organic dark chocolate 80%, dark Tanzania 80%, and Trinidad 80% products are well performing in all respects. As highlighted by us, the antiradical properties of cocoa products are higher than many antioxidant supplements in tablets.

positive: Dark chocolate improves coronary vasomotion and reduces platelet reactivity. BACKGROUND: Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. METHODS AND RESULTS: We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. CONCLUSIONS: Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.

positive: Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers. BACKGROUND: Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). METHODS: Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. RESULTS: The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. CONCLUSION: This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

positive: Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

positive: Chocolate--guilty pleasure or healthy supplement? Dark chocolate and other cocoa products are popular in the population as a whole, but their overall health benefit remains controversial. Observations from the Kuna Indian population have shown an impressive cardiovascular health benefit from cocoa. For various reasons, this benefit has not been as robust as in other populations. Additionally, several mechanisms have been proposed that might confer cocoa's possible health benefit, but no consensus has been reached on cocoa's physiologic role in promoting cardiovascular health. Flavanols, as well as theobromine, may contribute to enhancements in endothelial function and subsequent improvements in various contributors to cardiovascular disease (CVD) including hypertension, platelet aggregation and adhesion, insulin resistance, and hypercholesterolemia. While the benefits of cocoa may be altered at the various stages of growth, development, and production, it appears that for many people "healthy" dark chocolate may, indeed, provide a pleasurable role in CVD risk reduction. The objectives of this review are to discuss the associations of cocoa with decreased blood pressure and improved CVD risk, to describe the possible mechanisms for these potential benefits, and to highlight considerations for the use of cocoa as a dietary supplement.

positive: Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. BACKGROUND: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). OBJECTIVE: The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. DESIGN: We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. RESULTS: We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. CONCLUSIONS: We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.

positive: Food prices and blood cholesterol. Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.

positive: Agricultural policies, food and public health A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.

positive: Dietary exposure to xenoestrogens in New Zealand. Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.

positive: Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.

positive: Human exposure to endocrine disrupters: carcinogenic risk assessment. Human exposure to endocrine disrupters (EDs) is widespread and is considered to pose a growing threat to human health. Recent advances in molecular and genetic research and better understanding of mechanisms of blastic cell transformation have led to efforts to improve cancer risk assessment for populations exposed to this family of xenobiotics. In risk assessment, low dose extrapolation of cancer incidence data from both experimental animals and epidemiology studies has been largely based on models assuming linear correlation at low doses, despite existence of evidence showing otherwise. Another weakness of ED risk assessment is poor exposure data in ecological studies. Those are frequently rough estimates derived from contaminated items of local food basket surveys. Polyhalogenated hydrocarbons are treated as examples. There is growing sense of urgency to develop a biologically based dose response model of cancer risk, integrating emerging data from molecular biology and epidemiology to provide more realistic data for risk assessors, public, public health managers and environmental issues administrators.

positive: Inadvertent exposure to xenoestrogens. Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.

positive: Endocrine disrupting nonylphenols are ubiquitous in food. 4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.

positive: The experience of Japan as a clue to the etiology of testicular and prostatic cancers. In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.

positive: Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8

positive: Optimized LC/MS/MS analysis of morphine and codeine in poppy seed and evaluation of their fate during food processing as a basis for risk analysis. The opiate alkaloids present in poppy seed intended for use in food recently have raised major concerns. An efficient method for routine analysis of morphine and codeine using liquid chromatography in combination with tandem mass spectrometry on a triple quadrupole instrument (LC/MS/MS) was therefore developed. The optimal sample preparation was found to be cold extraction of 10 g of unground poppy seed with 30 mL of methanol containing 0.1% acetic acid for 60 min shaken at 250 rpm. The fate of morphine during food processing was also studied. All experiments led to a significant reduction of morphine and codeine. For poppy cake only 16-50% of the morphine was recovered, and in poppy buns at the highest temperature (220 degrees C) only 3% of the original morphine content was found. Ground poppy seed showed significantly lower recoveries than untreated seed. Morphine elimination during food processing has to be taken into account in the current discussion about its maximum limits in poppy seed.

positive: 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

positive: One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites. PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.

positive: Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria. This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.

positive: Fish odour syndrome Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria

positive: Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.

positive: Dietary protein and bone health: harmonizing conflicting theories. A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.

positive: Dietary protein and bone health: a systematic review and meta-analysis. BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.

positive: Excess dietary protein can adversely affect bone. The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.

positive: Low protein intake: the impact on calcium and bone homeostasis in humans. Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.

positive: The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.

positive: Protein intake, calcium balance and health consequences. High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.

positive: A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m... Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.

positive: The molecular basis of nutritional intervention in multiple sclerosis: a narrative review. It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

positive: Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals. Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.

positive: The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.

positive: Chitin synthesis and degradation as targets for pesticide action. Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.

positive: Methionine dependency and cancer treatment. Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.

positive: Targeting methionine auxotrophy in cancer: discovery & exploration. INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.

positive: Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i... Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.

positive: Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.

positive: Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.

positive: Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption? Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.

positive: Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.

positive: Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study. Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.

positive: Recent fat intake modulates fat taste sensitivity in lean and overweight subjects. OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.

positive: Desire to eat high- and low-fat foods following a low-fat dietary intervention. OBJECTIVE: This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. DESIGN: Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. SETTING: University clinic, Memphis, Tennessee. PARTICIPANTS: 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. INTERVENTION: A 16-week cognitive-behavioral program for obesity. VARIABLES MEASURED: Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. ANALYSIS: Analysis of variance, multiple regression, and paired t tests. RESULTS: The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. CONCLUSIONS AND IMPLICATIONS: Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.

positive: The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.

positive: The color red reduces snack food and soft drink intake. Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright Â© 2012 Elsevier Ltd. All rights reserved.

positive: Are free fatty acids effective taste stimuli in humans? Presented at the symposium "The Taste for Fat: New Discoveries on the Role of Fat in Sensor... The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional "primary" or "basic" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®

positive: Oral sensitivity to oleic acid is associated with fat intake and body mass index. BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

positive: You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.

positive: Antigenotoxic activity of watercress extract in an in vitro mammalian system using comet assay. Watercress (Cruciferae), an integral part of Mediterranean diets, is a nutritive food which is used in the treatment of several diseases. Oxidative DNA damage seems to play a crucial role in chronic, aging-related diseases and it is considered an important and probably carcinogenic factor. The aim of this work was to determine the impact of watercress extract on cell viability and its potential antigenotoxic properties against induced oxidative damage, using a comet assay and peripheral blood cells as an in vitro model. An aqueous extract of the leaves was prepared using a juice processor, centrifuged, filtered and preserved at -20 °C. Two concentrations of the aqueous extract (13.2 and 26.4 mg/mL) were assayed. No differences were found in cell viability between the control and treated groups at any time. Significant antigenotoxic effects were observed for both concentrations, expressed as the damage index (p = 0.005 at 30 min; p < 0.001 at 60 and 90 min), the percentage reductions in damage being similar between them (67.1-75.2% respectively). These results suggest that the consumption watercress in the diet is a powerful tool for improving health and the quality of life. Copyright © 2011 John Wiley & Sons, Ltd.

positive: Exercise-induced oxidative stress:myths, realities and physiological relevance. Although assays for the most popular markers of exercise-induced oxidative stress may experience methodological flaws, there is sufficient credible evidence to suggest that exercise is accompanied by an increased generation of free radicals, resulting in a measurable degree of oxidative modifications to various molecules. However, the mechanisms responsible are unclear. A common assumption that increased mitochondrial oxygen consumption leads per se to increased reactive oxygen species (ROS) production is not supported by in vitro and in vivo data. The specific contributions of other systems (xanthine oxidase, inflammation, haem protein auto-oxidation) are poorly characterised. It has been demonstrated that ROS have the capacity to contribute to the development of muscle fatigue in situ, but there is still a lack of convincing direct evidence that ROS impair exercise performance in vivo in humans. It remains unclear whether exercise-induced oxidative modifications have little significance, induce harmful oxidative damage, or are an integral part of redox regulation. It is clear that ROS play important roles in numerous physiological processes at rest; however, the detailed physiological functions of ROS in exercise remain to be elucidated.

positive: Could a vegetarian diet reduce exercise-induced oxidative stress? A review of the literature. Oxidative stress is a natural physiological process that describes an imbalance between free radical production and the ability of the antioxidant defence system of the body to neutralize free radicals. Free radicals can be beneficial as they may promote wound healing and contribute to a healthy immune response. However, free radicals can have a detrimental impact when they interfere with the regulation of apoptosis and thus play a role in the promotion of some cancers and conditions such as cardiovascular disease. Antioxidants are molecules that reduce the damage associated with oxidative stress by counteracting free radicals. Regular exercise is a vital component of a healthy lifestyle, although it can increase oxidative stress. As a typical vegetarian diet comprises a wide range of antioxidant-rich foods, it is plausible that the consumption of these foods will result in an enhanced antioxidant system capable of reducing exercise-induced oxidative stress. In addition, a relationship between a vegetarian diet and lower risks of cardiovascular disease and some cancers has been established. This review explores the current available evidence linking exercise, vegetarians, antioxidants, and oxidative stress.

positive: Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation? Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.

positive: Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.

positive: Endurance exercise results in DNA damage as detected by the comet assay. To determine if 6 weeks of supplementation with antioxidants could alleviate exercise-induced DNA damage, we studied 21 runners during a 50 km ultramarathon. Subjects were randomly assigned to one of two groups: (1) placebos (PL) or (2) antioxidants (AO) (1000 mg vitamin C and 400 IU RRR-alpha-tocopheryl acetate). The comet assay was used to assess DNA damage in circulating leukocytes at selected time points: pre-, mid-, and 2 h postrace and daily for 6 days postrace. All subjects completed the race: run time 7.1 +/- 0.1 h, energy expenditure 5008 +/- 80 kcal for women (n = 10) and 6932 +/- 206 kcal for men (n = 11). Overall, the percentage DNA damage increased at midrace (p <.02), but returned to baseline by 2 h postrace, indicating that the exercise bout induced nonpersistent DNA damage. There was a gender x treatment x time interaction (p <.01). One day postrace, women taking AO had 62% less DNA damage than women taking PL (p <.0008). In contrast, there were no statistically significant differences between the two treatment groups of men at any time point. Thus, endurance exercise resulted in DNA damage as shown by the comet assay and AO seemed to enhance recovery in women but not in men.

positive: Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation. Exercise-induced deoxyribonucleic acid (DNA) damage is often associated with an increase in free radicals; however, there is a lack of evidence examining the two in parallel. This study tested the hypothesis that high-intensity exercise has the ability to produce free radicals that may be capable of causing DNA damage. Twelve apparently healthy male subjects (age: 23 ± 4 years; stature: 181 ± 8 cm; body mass: 80 ± 9 kg; and VO(2max) : 49 ± 5 ml/kg/min) performed three 5 min consecutive and incremental stages (40, 70, and 100% of VO(2max) ) of aerobic exercise with a 15-min period separating each stage. Blood was drawn after each bout of exercise for the determination of ex vivo free radicals, DNA damage, protein carbonyls, lipid hydroperoxide (LOOH) concentration, and a range of lipid-soluble antioxidants. Lipid-derived oxygen-centered free radicals (hyperfine coupling constants a(Nitrogen) = 13.7 Gauss (G) and aβ(Hydrogen) = 1.8 G) increased as a result of acute moderate and high-intensity exercise (P < 0.05), while DNA damage was also increased (P < 0.05). Systemic changes were observed in LOOH and for lipid-soluble antioxidants throughout exercise (P < 0.05); however, there was no observed change in protein carbonyl concentration (P > 0.05). These findings identify lipid-derived free radical species as possible contributors to peripheral mononuclear cell DNA damage in the human exercising model. This damage occurs in the presence of lipid oxidation but in the absence of any change to protein carbonyl concentration. The significance of these findings may have relevance in terms of immune function, the aging process, and the pathology of carcinogenesis. Copyright © 2010 Wiley-Liss, Inc.

positive: Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation. Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation.

positive: Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise. Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.

positive: Does physical activity induce DNA damage? The single cell gel electrophoresis (SCG) assay (comet assay) is a sensitive technique for detecting the presence of DNA strand-breaks and alkali-labile damage in individual cells. This technique was used to study peripheral blood cells from three volunteers after physical activity. The test subjects had to run on a treadmill and were checked for blood pressure and ECG, lactate concentration and creatine kinase activity. Blood was taken before and several times during and after the run. In a first multiple step test, the volunteers ran as long as possible with increasing speed. In a second test they had to run for 45 min with a fixed individual speed which was defined to ensure an aerobic metabolism. In the first test, the white blood cells of all subjects showed increased DNA migration in the SCG assay. The effect was seen 6 h after the end of the exercise and reached its maximum 24 h later. After 72 h, DNA migration decreased to about control level. The distribution of DNA migration among cells clearly demonstrated that the majority of white blood cells exhibited increased DNA migration and that the effect was not only due to a small fraction of damaged cells. From the same blood samples, blood cultures were set up to study a possible effect on the frequency of sister chromatid exchanges (SCE), another indicator for genotoxic effects. However, there was no significant increase in SCE in any of the cultures. In the second exercise, during aerobic metabolism, the effect on DNA migration was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)

positive: Antioxidant diet supplementation enhances aerobic performance in amateur sportsmen. The effects of antioxidant diet supplements on blood lactate concentration and on the aerobic and anaerobic thresholds and their adaptations to training were analysed. Fifteen amateur male athletes were randomly assigned to either a placebo group or an antioxidant-supplemented group (90 days supplementation with 500 mg x day(-1) of vitamin E and 30 mg x day(-1) of beta-carotene, and the last 15 days also with 1 g x day(-1) of vitamin C). Before and after the antioxidant supplements, the sportsmen performed a maximal exercise test on a cycle ergometer and maximal and submaximal physiological parameters were assessed together with blood lactate concentration. Maximal oxygen uptake (VO(2max)), maximal blood lactate concentration, and the maximal workload attained rose significantly in both groups after the 3 months of training. At the end of the study, maximal blood lactate concentration was lower in the group that took supplements than in the placebo group. The percentage of VO(2max) attained at the anaerobic threshold rose significantly in both groups after 3 months of training, although the final value in the supplemented group was higher than that in the placebo group. Antioxidant diet supplements induced lower increases in blood lactate concentration after a maximal exercise test and could improve the efficiency in which aerobic energy is obtained.

positive: Orange juice improved lipid profile and blood lactate of overweight middle-aged women subjected to aerobic training. OBJECTIVE: This study investigated how consumption of orange juice associated with aerobic training affected serum lipids and physical characteristics of overweight, middle-aged women. METHODS: The experimental group consisted of 13 women who consumed 500 mL/d of orange juice and did 1h aerobic training 3 times a week for 3 months. The control group consisted of another 13 women who did the same aerobic training program but did not consume orange juice. RESULTS: At the end of the experiment, the control group lost an average of 15% of fat mass (P<0.05) and 2.5% of weight (P<0.05), whereas the experimental group lost 11% of fat mass and 1.2% of weight (P<0.05). Consumption of orange juice by the experimental group was associated with increased dietary intake of vitamin C and folate by 126% and 61% respectively. Serum LDL-C decreased 15% (P<0.05) and HDL-C increased 18% (P<0.05) in the experimental group, but no significant change was observed in the control group. Both groups improved the anaerobic threshold by 20% (P<0.05), but blood lactate concentration decreased 27% in the experimental group compared to the 17% control group, suggesting that experimental group has less muscle fatigue and better response to training. CONCLUSIONS: The consumption of 500 mL/d of orange juice associated with aerobic training in overweight women decreased cardiovascular disease risk by reducing LDL-C levels and increasing HDL-C levels. This association also decreased blood lactate concentration and increased anaerobic threshold, showing some improvement in the physical performance. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

positive: Postprandial glycemic response to orange juice and nondiet cola: is there a difference? The purpose of this study was to compare the effects of unsweetened fruit juice and regular, decaffeinated soda on postprandial serum glucose levels in individuals with non-insulin-dependent diabetes mellitus (NIDDM) when these liquids are ingested separately as part of mixed meals. Eighteen individuals with NIDDM consumed three test breakfasts calculated using the diabetic exchange meal-planning system. Foods were identical in each of the breakfasts except for foods in the fruit exchange. Carbohydrate-equivalent amounts of fresh orange slices, unsweetened orange juice, and regular, decaffeinated Coke were consumed in breakfasts 1, 2, and 3, respectively. Serum glucose samples were drawn at fasting and 1, 2, and 3 hours postprandially. No difference was found in the postprandial serum glucose response when Coke versus orange juice was consumed in the breakfast. These findings question the appropriateness of using unsweetened fruit juices in routine meal planning for individuals with NIDDM.

positive: Pancreatic lipase inhibitors from natural sources: unexplored potential. The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer approaches for the treatment of obesity have involved inhibition of dietary triglyceride absorption via inhibition of pancreatic lipase (PL) as this is the major source of excess calories. Natural products provide a vast pool of PL inhibitors that can possibly be developed into clinical products. This article reviews various extracts and secondary metabolites from plants and microbial origin with PL inhibitory activity that can be focused for drug development programs.

positive: HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. BACKGROUND: Orange juice-a rich source of vitamin C, folate, and flavonoids such as hesperidin-induces hypocholesterolemic responses in animals. OBJECTIVE: We determined whether orange juice beneficially altered blood lipids in subjects with moderate hypercholesterolemia. DESIGN: The sample consisted of 16 healthy men and 9 healthy women with elevated plasma total and LDL-cholesterol and normal plasma triacylglycerol concentrations. Participants incorporated 1, 2, or 3 cups (250 mL each) of orange juice sequentially into their diets, each dose over a period of 4 wk. This was followed by a 5-wk washout period. Plasma lipid, folate, homocyst(e)ine, and vitamin C (a compliance marker) concentrations were measured at baseline, after each treatment, and after the washout period. RESULTS: Consumption of 750 mL but not of 250 or 500 mL orange juice daily increased HDL-cholesterol concentrations by 21% (P: < 0.001), triacylglycerol concentrations by 30% (from 1.56 +/- 0.72 to 2.03 +/- 0.91 mmol/L; P: < 0.02), and folate concentrations by 18% (P: < 0.01); decreased the LDL-HDL cholesterol ratio by 16% (P: < 0.005); and did not affect homocyst(e)ine concentrations. Plasma vitamin C concentrations increased significantly during each dietary period (2.1, 3.1, and 3.8 times, respectively). CONCLUSIONS: Orange juice (750 mL/d) improved blood lipid profiles in hypercholesterolemic subjects, confirming recommendations to consume >/=5-10 servings of fruit and vegetables daily.

positive: Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line--a comparative study. Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance. Copyright Â© 2011 Elsevier Ltd. All rights reserved.

positive: Reducing the fat content in ground beef without sacrificing quality: a review. Americans are becoming more health conscious in their food choices and many are interested in reducing dietary fat intake. Fat replacers can affect meat flavor both by adding flavors of their own, by reducing the original aroma-generating substrate (fat) and by altering release of aroma compounds. When fat is removed from meat, water is generally added to replace it. Water-binding compounds can be added to prevent the added water from cooking out or evaporating and to prevent patty shrinkage. Fat replacers are generally classified by their composition: protein-based replacers including whey, soy and collagen, lipid-based substances such as soy lecithin which function as emulsifiers maintaining the fat that is retained distributed in the product, and carbohydrate-based substances including flours (wheat, soy, oat), starches (potato, modified corn starch, tapioca) and gums (carrageenan, xanthin). Duplication of the characteristics contributed by fat often requires a combination of replacers to address juiciness and texture (firmness) without negatively impacting flavor. Published by Elsevier Ltd.

positive: Exposure to common food additive carrageenan leads to reduced sulfatase activity and increase in sulfated glycosaminoglycans in human epithelial cells The commonly used food additive carrageenan, including lambda (λ), kappa (κ) and iota (ι) forms, is composed of galactose disaccharides linked in alpha-1,3 and beta-1,4 glycosidic bonds with up to three sulfate groups per disaccharide residue. Carrageenan closely resembles the endogenous galactose or N-acetylgalactosamine-containing glycosaminoglycans (GAGs), chondroitin sulfate (CS), dermatan sulfate (DS), and keratan sulfate. However, these GAGs have beta-1,3 and beta-1,4 glycosidic bonds, in contrast to the unusual alpha-1,3 glycosidic bond in carrageenan. Since sulfatase activity is inhibited by sulfate, and carrageenan is so highly sulfated, we tested the effect of carrageenan exposure on sulfatase activity in human intestinal and mammary epithelial cell lines and found that carrageenan exposure significantly reduced the activity of sulfatases, including N-acetylgalactosamine-4-sulfatase, galactose-6-sulfatase, iduronate sulfatase, steroid sulfatase, arylsulfatase A, SULF-1,2, and heparan sulfamidase. Consistent with the inhibition of sulfatase activity, following exposure to carrageenan, GAG content increased significantly and showed marked differences in disaccharide composition. Specific changes in CS disaccharides included increases in di-sulfated disaccharide components of CSD (2S6S) and CS-E (4S6S), with declines in CS-A (4S) and CS-C (6S). Specific changes in heparin-heparan sulfate disaccharides included increases in 6S disaccharides, as well as increases in NS and 2S6S disaccharides. Study results suggest that carrageenan inhibition of sulfatase activity leads to re-distribution of the cellular GAG composition with increase in di-sulfated CS and with potential consequences for cell structure and function.

positive: Pro-inflammatory NF-κB and early growth response gene 1 regulate epithelial barrier disruption by food additive carrageenan in human intestinal epi... The widely used food additive carrageenan (CGN) has been shown to induce intestinal inflammation, ulcerative colitis-like symptoms, or neoplasm in the gut epithelia in animal models, which are also clinical features of human inflammatory bowel disease. In this study, the effects of CGN on pro-inflammatory transcription factors NF-κB and early growth response gene 1 product (EGR-1) were evaluated in terms of human intestinal epithelial barrier integrity. Both pro-inflammatory transcription factors were elevated by CGN and only NF-κB activation was shown to be involved in the induction of pro-inflammatory cytokine interleukin-8. Moreover, the integrity of the in vitro epithelial monolayer under the CGN insult was maintained by both activated pro-inflammatory transcription factors NF-κB and EGR-1. Suppression of NF-κB or EGR-1 aggravated barrier disruption by CGN, which was associated with the reduced gene expression of tight junction component zonula occludens 1 and its irregular localization in the epithelial monolayer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

positive: Evaluation of certain food additives and contaminants. This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The Committee also evaluated the risk posed by two food contaminants, with the aim of deriving tolerable intakes where appropriate and advising on risk management options for the purpose of public health protection. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of and assessment of dietary exposure to food additives and contaminants. A summary follows of the Committee's evaluations of technical, toxicological and dietary exposure data for certain food additives (aluminium-containing food additives, Benzoe Tonkinensis, glycerol ester of gum rosin, glycerol ester of tall oil rosin, glycerol ester of wood rosin, octenyl succinic acid modified gum arabic, polydimethyl siloxane, Ponceau 4R, pullulan, pullulanase from Bacillus deromificans expressed in Bacillus licheniformis, Quinoline Yellow and Sunset Yellow FCF) and two food contaminants (cyanogenic glycosides and fumonisins). Specifications for the following food additives were revised: aluminium lakes of colouring matters; beta-apo-8'-carotenal; beta-apo-8'-carotenoic acid ethyl ester; beta-carotene, synthetic; hydroxypropyl methyl cellulose; magnesium silicate, synthetic; modified starches; nitrous oxide; sodium carboxymethyl cellulose; and sucrose monoesters of lauric, palmitic or stearic acid. Annexed to the report are tables summarizing the Committee's recommendations for dietary exposures to and toxicological evaluations of the food additives and contaminants considered.

positive: Dietary acrylamide exposure of the French population: results of the second French Total Diet Study. Acrylamide is a heat-induced carcinogen compound that is found in some foods consequently to cooking or other thermal processes. In the second French Total Diet Study (TDS), acrylamide was analysed in 192 food samples collected in mainland France to be representative of the population diet and prepared "as consumed". Highest mean concentrations were found in potato chips/crisps (954 μg/kg), French fries and other fried potatoes (724 μg/kg), and salted biscuits other than potato chips (697 μg/kg). Exposure of general adult and child populations was assessed by combining analytical results with national consumption data. Mean acrylamide exposure was assessed to be 0.43±0.33 μg/kg of body weight (bw) per day for adults and 0.69±0.58 μg/kg bw/day for children. Although the exposure assessed is lower than in previous evaluations, the calculated margins of exposure, based on benchmark dose limits defined for carcinogenic effects, remain very low especially for young children (below 100 at the 95th percentile of exposure), indicating a health concern. It is therefore advisable to continue efforts in order to reduce dietary exposure to acrylamide. Copyright Â© 2012 Elsevier Ltd. All rights reserved.

positive: Carrageenans and their use in meat products. Carrageenans are sulfated linear polysaccharides of D-galactose and 3,6-anhydro-D-galactose extracted from red seaweeds. They have been used by the food industry for their gelling, thickening, and stabilizing properties, and more recently by the meat industry for reduced fat products. Meat is a complex system of muscle tissue, connective tissue, fat, and water; during processing, numerous interactions occur among all these components. These interactions are responsible for the functional properties of the meat system. In meat products, carrageenans contribute to gel formation and water retention. Their addition is of special interest in low-fat meat products because fat reduction often leads to unacceptable, tough textures. When carrageenans are incorporated in these formulations, they improve the textural characteristics of the product by decreasing toughness and increasing juiciness. Although carrageenan interactions with milk proteins have been studied extensively, the mechanism by which carrageenans interact with meat proteins and the other meat components is not fully understood.

positive: Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro. Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1-10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1-8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6-8 d of CGN exposure, the percentage of cells reentering G0-G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology.

positive: Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. Carrageenan is a high molecular weight sulfated polygalactan used to improve the texture of commercial food products. Its use increased markedly during the last half century, although carrageenan is known to induce inflammation in rheumatological models and in intestinal models of colitis. We performed studies to determine its direct effects on human intestinal cells, including normal human intestinal epithelial cells from colonic surgeries, the normal intestinal epithelial cell line NCM460, and normal rat ileal epithelial cells. Cells were treated with high molecular weight lambda-carrageenan at a concentration of 1 mug/ml for 1-96 h. IL-8, IL-8 promoter activity, total and nuclear NF-kappaB, IkappaBalpha, phospho-IkappaBalpha, and Bcl10 were assessed by immunohistochemistry, Western blot, ELISA, and cDNA microarray. Increased Bcl10, nuclear and cytoplasmic NF-kappaB, IL-8 promoter activation, and IL-8 secretion were detected following carrageenan exposure. Knockdown of Bcl10 by siRNA markedly reduced the increase in IL-8 that followed carrageenan exposure in the NCM460 cells. These results show, for the first time, that exposure of human intestinal epithelial cells to carrageenan triggers a distinct inflammatory pathway via activation of Bcl10 with NF-kappaB activation and upregulation of IL-8 secretion. Since Bcl10 contains a caspase-recruitment domain, similar to that found in NOD2/CARD15 and associated with genetic predisposition to Crohn's disease, the study findings may represent a link between genetic and environmental etiologies of inflammatory bowel disease. Because of the high use of carrageenan as a food additive in the diet, the findings may have clinical significance.

positive: Review of harmful gastrointestinal effects of carrageenan in animal experiments. In this article I review the association between exposure to carrageenan and the occurrence of colonic ulcerations and gastrointestinal neoplasms in animal models. Although the International Agency for Research on Cancer in 1982 identified sufficient evidence for the carcinogenicity of degraded carrageenan in animals to regard it as posing a carcinogenic risk to humans, carrageenan is still used widely as a thickener, stabilizer, and texturizer in a variety of processed foods prevalent in the Western diet. I reviewed experimental data pertaining to carrageenan's effects with particular attention to the occurrence of ulcerations and neoplasms in association with exposure to carrageenan. In addition, I reviewed from established sources mechanisms for production of degraded carrageenan from undegraded or native carrageenan and data with regard to carrageenan intake. Review of these data demonstrated that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Although in 1972, the U.S. Food and Drug Administration considered restricting dietary carrageenan to an average molecular weight > 100,000, this resolution did not prevail, and no subsequent regulation has restricted use. Because of the acknowledged carcinogenic properties of degraded carrageenan in animal models and the cancer-promoting effects of undegraded carrageenan in experimental models, the widespread use of carrageenan in the Western diet should be reconsidered.

positive: The spermicidal potency of Coca-Cola and Pepsi-Cola. The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.

positive: Dietary fat and semen quality among men attending a fertility clinic BACKGROUND The objective of this study was to examine the relation between dietary fats and semen quality parameters. METHODS Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders. RESULTS Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62–14%) lower total sperm count and 38% (95% CI: 58–10%) lower sperm concentration than men in the lowest third (Ptrend = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= −0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4–3.5%) higher normal morphology than men in the lowest third (Ptrend = 0.02). CONCLUSIONS In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.

positive: The question of declining sperm density revisited: an analysis of 101 studies published 1934-1996. In 1992 Carlsen et al. reported a significant global decline in sperm density between 1938 and 1990 [Evidence for Decreasing Quality of Semen during Last 50 Years. Br Med J 305:609-613 (1992)]. We subsequently published a reanalysis of the studies included by Carlsen et al. [Swan et al. Have Sperm Densities Declined? A Reanalysis of Global Trend Data. Environ Health Perspect 105:1228-1232 (1997)]. In that analysis we found significant declines in sperm density in the United States and Europe/Australia after controlling for abstinence time, age, percent of men with proven fertility, and specimen collection method. The declines in sperm density in the United States (approximately 1.5%/year) and Europe/Australia (approximately 3%/year) were somewhat greater than the average decline reported by Carlsen et al. (approximately 1%/year). However, we found no decline in sperm density in non-Western countries, for which data were very limited. In the current study, we used similar methods to analyze an expanded set of studies. We added 47 English language studies published in 1934-1996 to those we had analyzed previously. The average decline in sperm count was virtually unchanged from that reported previously by Carlsen et al. (slope = -0.94 vs. -0.93). The slopes in the three geographic groupings were also similar to those we reported earlier. In North America, the slope was somewhat less than the slope we had found for the United States (slope = -0.80; 95% confidence interval (CI), -1.37--0.24). Similarly, the decline in Europe (slope = -2.35; CI, -3.66--1.05) was somewhat less than reported previously. As before, studies from other countries showed no trend (slope = -0.21; CI, -2.30-1.88). These results are consistent with those of Carlsen et al. and our previous results, suggesting that the reported trends are not dependent on the particular studies included by Carlsen et al. and that the observed trends previously reported for 1938-1990 are also seen in data from 1934-1996.

positive: Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility Background Many studies have examined whether caffeine, alcohol, or specific beverages containing these affect fertility in women. However most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases. Methods We followed 18,555 married women without a history of infertility for 8 years as they attempted to become (or became) pregnant. Diet was measured twice during this period and prospectively related to the incidence of ovulatory disorder infertility. Results There were 438 incident report of ovulatory disorder infertility during follow-up. Intakes of alcohol and caffeine were unrelated to the risk of ovulatory disorder infertility. The multivariate-adjusted relative risk (RR), 95% confidence interval (CI), P for trend comparing the highest to lowest categories of intake were 1.11 (0.76–1.64; 0.78) for alcohol and 0.86 (0.61–1.20; 0.44) for total caffeine. However, intake of caffeinated soft drinks was positively related to ovulatory disorder infertility. The multivariate-adjusted RR 95% CI, and P for trend comparing the highest to lowest categories of caffeinated soft drink consumption were 1.47 (1.09–1.98; 0.01). Similar associations were observed for noncaffeinated, sugared, diet and total soft drinks. Conclusions Our findings do not support the hypothesis that alcohol and caffeine impair ovulation to the point of decreasing fertility. The association between soft drinks and ovulatory disorder infertility appears not to be attributable to their caffeine or sugar content, and deserves further investigation.

positive: Food intake and its relationship with semen quality: a case-control study. OBJECTIVE: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN: An observational, analytical case-control study. SETTING: Private fertility clinics. PATIENT(S): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S): We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S): Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.

positive: Male reproductive organs are at risk from environmental hazards Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction, infertility, cryptorchidism, hypospadias and testicular cancer. Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However, the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation, radiant heat and a number of known toxicants. So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane, ethylendibromide and DDT/DDE, some heavy metals as inorganic lead and mercury) and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures, but millions of workers in less affluent countries are at risk from reproductive toxicants. New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world. For other toxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates, bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones. Finally, there are data indicating a particular vulnerability of the fetal testis to toxicants—for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.

positive: Perinatal Exposure to Low Doses of Dioxin Can Permanently Impair Human Semen Quality Background In recent decades, young men in some industrialized areas have reportedly experienced a decrease in semen quality. Objective We examined effects of perinatal dioxin exposure on sperm quality and reproductive hormones. Methods We investigated sperm quality and hormone concentrations in 39 sons (mean age, 22.5 years) born between 1977 and 1984 to mothers exposed to dioxin after the accident in Seveso, Italy (1976), and 58 comparisons (mean age, 24.6 years) born to mothers exposed only to background dioxin. Maternal dioxin levels at conception were extrapolated from the concentrations measured in 1976 serum samples. Results The 21 breast-fed sons whose exposed mothers had a median serum dioxin concentration as low as 19 ppt at conception had lower sperm concentration (36.3 vs. 86.3 million/mL; p = 0.002), total count (116.9 vs. 231.1; p = 0.02), progressive motility (35.8 vs. 44.2%; p = 0.03), and total motile count (38.7 vs. 98 million; p = 0.01) than did the 36 breast-fed comparisons. The 18 formula-fed exposed and the 22 formula-fed and 36 breast-fed comparisons (maternal dioxin background 10 ppt at conception) had no sperm-related differences. Follicle-stimulating hormone was higher in the breast-fed exposed group than in the breast-fed comparisons (4.1 vs. 2.63 IU/L; p = 0.03) or the formula-fed exposed (4.1 vs. 2.6 IU/L; p = 0.04), and inhibin B was lower (breast-fed exposed group, 70.2; breast-fed comparisons, 101.8 pg/mL, p = 0.01; formula-fed exposed, 99.9 pg/mL, p = 0.02). Conclusions In utero and lactational exposure of children to relatively low dioxin doses can permanently reduce sperm quality.

positive: Heavy metals in commercial fish in New Jersey. Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. While attention has focused on self-caught fish, most of the fish eaten by the American public comes from commercial sources. We sampled 11 types of fish and shellfish obtained from supermarkets and specialty fish markets in New Jersey and analyzed them for arsenic, cadmium, chromium, lead, manganese, mercury, and selenium. We test the null hypothesis that metal levels do not vary among fish types, and we consider whether the levels of any metals could harm the fish themselves or their predators or pose a health risk for human consumers. There were significant interspecific differences for all metals, and no fish types had the highest levels of more than two metals. There were few significant correlations (Kendall tau) among metals for the three most numerous fish (yellowfin tuna, bluefish, and flounder), the correlations were generally low (below 0.40), and many correlations were negative. Only manganese and lead positively were correlated for tuna, bluefish, and flounder. The levels of most metals were below those known to cause adverse effects in the fish themselves. However, the levels of arsenic, lead, mercury, and selenium in some fish were in the range known to cause some sublethal effects in sensitive predatory birds and mammals and in some fish exceeded health-based standards. The greatest risk from different metals resided in different fish; the species of fish with the highest levels of a given metal sometimes exceeded the human health guidance or standards for that metal. Thus, the risk information given to the public (mainly about mercury) does not present a complete picture. The potential of harm from other metals suggests that people not only should eat smaller quantities of fish known to accumulate mercury but also should eat a diversity of fish to avoid consuming unhealthy quantities of other heavy metals. However, consumers should bear in mind that standards have a margin of safety.

positive: Correlation of lead, cadmium and mercury levels in tissue and liver samples with age in cattle. The aim of this study was to determine the accumulation of selected heavy metals (Pb, Cd, Hg, As) in meat and liver of cattle. The animals were divided into four age-groups which allowed the analysis of statistical-mathematical correlations between the age of the animals and contamination of meat. The research material for determination of heavy metal levels was taken from the longissimus back muscle (m. longissimus dorsi) and samples from the tail lobe of the liver. Analysis showed that contamination by Cd and Pb is clearly dependent on the age of the animal.

positive: Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy. BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of "high beef consumers" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of "high beef consumers" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.

positive: Heavy Metals and Couple Fecundity, the LIFE Study The effect of heavy metals at environmentally relevant concentrations on couple fecundity has received limited study despite ubiquitous exposure. In 2005–2009, couples (n=501) desiring pregnancy and discontinuing contraception were recruited and asked to complete interviews and to provide blood specimens for the quantification of cadmium (μg/L), lead (μg/dL) and mercury (μg/L) using inductively coupled plasma-mass spectrometry. Couples completed daily journals on lifestyle and intercourse along with menstruation and pregnancy testing for women. Couples were followed for 12 months or until pregnant. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated adjusting for age, body mass index, cotinine, and serum lipids in relation to female then male exposures. FORs <1 denote a longer time to pregnancy. In adjusted models, reduced FORs were observed for both female cadmium (0.78; 95% CI 0.63–0.97) and male lead (0.85; 95% CI 0.73–0.98) concentrations. When jointly modeling couples’ exposures, only male lead concentration significantly reduced the FOR (0.82; 95% CI 0.68, 0.97), though the FOR remained <1 for female cadmium (0.80; 95% CI 0.64, 1.00). This prospective couple based cohort with longitudinal capture of time to pregnancy is suggestive of cadmium and lead’s reproductive toxicity at environmentally relevant concentrations.

positive: Physical activity, obesity and eating habits can influence assisted reproduction outcomes. OBJECTIVE: To determine if eating habits, physical activity and BMI can influence assisted reproduction outcomes. MATERIAL AND METHODS: This study analyzed 436 patients undergoing intracytoplasmic sperm injection cycles. Patients answered a questionnaire and regression analysis examined the relationship between lifestyle and BMI with the intracytoplasmic sperm injection cycles outcomes. RESULTS: No influence of lifestyle and obesity was observed on the number of oocytes recovered. Obesity reduced the normal fertilization rate (coefficient [Coef.]: -16.0; p = 0.01) and increased the risk of miscarriage (OR: 14.3; p = 0.03). Physical activity positively affected implantation (Coef.: 9.4; p = 0.009), increased the chance of pregnancy (OR: 1.83; p = 0.013) and tended to decrease the risk of miscarriage (OR: 0.30; p = 0.068). In addition, an inverse correlation was found between physical activity and BMI, and a direct correlation was found between soft-drink consumption and BMI. CONCLUSIONS: Eating habits, physical activity and obesity could affect clinical outcomes of assisted reproduction.

positive: Trans Fat Consumption and Aggression Background Dietary trans fatty acids (dTFA) are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. Methodolgy/Prinicpal Findings We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999–2004) were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking). Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld with adjustment for confounders, was preserved across sex, age, and ethnicity strata, and held cross-sectionally and prospectively. Conclusions/Significance This study provides the first evidence linking dTFA with behavioral irritability and aggression. While confounding is always a concern in observational studies, factors including strength and consistency of association, biological gradient, temporality, and biological plausibility add weight to the prospect of a causal connection. Our results may have relevance to public policy determinations regarding dietary trans fats. Clinicaltrials.gov # NCT00330980

positive: A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD. Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.

positive: Updated estimate of trans fat intake by the US population. The dietary intake of industrially-produced trans fatty acids (IP-TFA) was estimated for the US population (aged 2 years or more), children (aged 2-5 years) and teenage boys (aged 13-18 years) using the 2003-2006 National Health and Nutrition Examination Survey (NHANES) food consumption database, market share information and trans fat levels based on label survey data and analytical data for packaged and in-store purchased foods. For fast foods, a Monte Carlo model was used to estimate IP-TFA intake. Further, the intake of trans fat was also estimated using trans fat levels reported in the US Department of Agriculture (USDA) National Nutrient Database for Standard Reference, Release 22 (SR 22, 2009) and the 2003-2006 NHANES food consumption database. The cumulative intake of IP-TFA was estimated to be 1.3 g per person per day (g/p/d) at the mean for the US population. Based on this estimate, the mean dietary intake of IP-TFA has decreased significantly from that cited in the 2003 US Food and Drug Administration (FDA) final rule that established labelling requirements for trans fat (4.6 g/p/d for adults). Although the overall intake of IP-TFA has decreased as a result of the implementation of labelling requirements, individuals with certain dietary habits may still consume high levels of IP-TFA if certain brands or types of food products are frequently chosen.

positive: 210Po in the marine environment with emphasis on its behaviour within the biosphere. The distribution and behaviour of the natural-series alpha-emitter polonium-210 in the marine environment has been under study for many years primarily due to its enhanced bioaccumulation, its strong affinity for binding with certain internal tissues, and its importance as a contributor to the natural radiation dose received by marine biota as well as humans consuming seafoods. Results from studies spanning nearly 5 decades show that (210)Po concentrations in organisms vary widely among the different phylogenic groups as well as between the different tissues of a given species. Such variation results in (210)Po concentration factors ranging from approximately 10(3) to over 10(6) depending upon the organism or tissue considered. (210)Po/(210)Pb ratios in marine species are generally greater than unity and tend to increase up the food chain indicating that (210)Po is preferentially taken up by organisms compared to its progenitor (210)Pb. The effective transfer of (210)Po up the food chain is primarily due to the high degree of assimilation of the radionuclide from ingested food and its subsequent strong retention in the organisms. In some cases this mechanism may lead to an apparent biomagnification of (210)Po at the higher trophic level. Various pelagic species release (210)Po and (210)Pb packaged in organic biodetrital particles that sink and remove these radionuclides from the upper water column, a biogeochemical process which, coupled with scavenging rates of this radionuclide pair, is being examined as a possible proxy for estimating downward organic carbon fluxes in the sea. Data related to preferential bioaccumulation in various organisms, their tissues, resultant radiation doses to these species, and the processes by which (210)Po is transferred and recycled through the food web are discussed. In addition, the main gaps in our present knowledge and proposed areas for future studies on the biogeochemical behaviour of (210)Po and its use as a tracer of oceanographic processes are highlighted in this review. Copyright © 2010 Elsevier Ltd. All rights reserved.

positive: Pacific bluefin tuna transport Fukushima-derived radionuclides from Japan to California The Fukushima Dai-ichi release of radionuclides into ocean waters caused significant local and global concern regarding the spread of radioactive material. We report unequivocal evidence that Pacific bluefin tuna, Thunnus orientalis, transported Fukushima-derived radionuclides across the entire North Pacific Ocean. We measured γ-emitting radionuclides in California-caught tunas and found 134Cs (4.0 ± 1.4 Bq kg−1) and elevated 137Cs (6.3 ± 1.5 Bq kg−1) in 15 Pacific bluefin tuna sampled in August 2011. We found no 134Cs and background concentrations (∼1 Bq kg−1) of 137Cs in pre-Fukushima bluefin and post-Fukushima yellowfin tunas, ruling out elevated radiocesium uptake before 2011 or in California waters post-Fukushima. These findings indicate that Pacific bluefin tuna can rapidly transport radionuclides from a point source in Japan to distant ecoregions and demonstrate the importance of migratory animals as transport vectors of radionuclides. Other large, highly migratory marine animals make extensive use of waters around Japan, and these animals may also be transport vectors of Fukushima-derived radionuclides to distant regions of the North and South Pacific Oceans. These results reveal tools to trace migration origin (using the presence of 134Cs) and potentially migration timing (using 134Cs:137Cs ratios) in highly migratory marine species in the Pacific Ocean.

positive: Radioactive fallout in the United States due to the Fukushima nuclear plant accident. The release of radioactivity into the atmosphere from the damaged Fukushima Daiichi nuclear power plant started on March 12th, 2011. Among the various radionuclides released, iodine -131 ((131)I) and cesium isotopes ((137)Cs and (134)Cs) were transported across the Pacific Ocean and reached the United States on 17-18 March 2011. Consequently, an elevated level of fission products (131)I, (132)I, (132)Te, (134)Cs and (137)Cs were detected in air, water, and milk samples collected across the United States between March 17 and April 4, 2011. The continuous monitoring of activities over a period of 25 days and spatial variations across more than 100 sampling locations in the United States made it possible to characterize the contaminated air masses. For the entire period, the highest detected activity values ranged from less than 1 m Bq m(-3) to 31 m Bq m(-3) for the particulate (131)I, and up to 96 m Bq m(-3) for the gaseous (131)I fraction.

positive: Increase of 210Po levels in human semen fluid after mussel ingestion. Polonium-210 ((210)Po) radioactive concentrations were determined in human semen fluid of vasectomized non-smoker volunteers. The (210)Po levels ranged from 0.10 to 0.39 mBq g(-1) (mean: 0.23 ± 0.08 mBq g(-1)). This value decreased to 0.10 ± 0.02 mBq g(-1) (range from 0.07 to 0.13 mBq g(-1)) after two weeks of a controlled diet, excluding fish and seafood. Then, volunteers ate during a single meal 200 g of the cooked mussel Perna perna L., and (210)Po levels were determined again, during ten days, in semen fluid samples collected every morning. Volunteers continued with the controlled diet and maintained sexual abstinence through the period of the experiment. A 300% increase of (210)Po level was observed the day following mussel consumption, with a later reduction, such that the level returned to near baseline by day 4. Copyright © 2011 Elsevier Ltd. All rights reserved.

positive: An unexpected mortality increase in the United States follows arrival of the radioactive plume from Fukushima: is there a correlation? The multiple nuclear meltdowns at the Fukushima plants beginning on March 11, 2011, are releasing large amounts of airborne radioactivity that has spread throughout Japan and to other nations; thus, studies of contamination and health hazards are merited. In the United States, Fukushima fallout arrived just six days after the earthquake, tsunami, and meltdowns. Some samples of radioactivity in precipitation, air, water, and milk, taken by the U.S. government, showed levels hundreds of times above normal; however, the small number of samples prohibits any credible analysis of temporal trends and spatial comparisons. U.S. health officials report weekly deaths by age in 122 cities, about 25 to 35 percent of the national total. Deaths rose 4.46 percent from 2010 to 2011 in the 14 weeks after the arrival of Japanese fallout, compared with a 2.34 percent increase in the prior 14 weeks. The number of infant deaths after Fukushima rose 1.80 percent, compared with a previous 8.37 percent decrease. Projecting these figures for the entire United States yields 13,983 total deaths and 822 infant deaths in excess of the expected. These preliminary data need to be followed up, especially in the light of similar preliminary U.S. mortality findings for the four months after Chernobyl fallout arrived in 1986, which approximated final figures.

positive: Semen quality of male idiopathic infertile smokers and nonsmokers: an ultrastructural study. This retrospective study was aimed at evaluating the effects of cigarette consumption on semen parameters in a group of men with idiopathic infertility. The semen quality of 2 groups of men with idiopathic infertility, smokers (n = 118) and nonsmokers (n = 153), were compared. Conventional semen analysis was performed and sperm morphology was assessed by transmission electron microscopy (TEM). TEM data were elaborated by means of a mathematical formula based on a Bayesian technique able to furnish a fertility index (FI), and the percentages of sperm apoptosis, necrosis, and immaturity. Values of normality recommended by World Health Organization guidelines were used as a control for conventional semen analysis, and values from sperm of 25 men of proven fertility were used for TEM indices. Infertile smoker and nonsmoker patients showed similar sperm parameters, although sperm motility and TEM analysis values in both groups were significantly impaired compared with controls. Smoker patients were then classified as mild (>or=1 and <or=10 cigarettes/d), moderate (>10 and <20 cigarettes/day), or heavy smokers (>or=20 cigarettes/d). Sperm concentration and FI were significantly (P < .05) different among the 3 considered smoker classes. Comparing the pairs of smoker classes, sperm concentration and FI in heavy smokers were significantly lower (P < .05) than that observed in mild smoker and nonsmoker groups. Although semen quality in males with idiopathic infertility seems not to be dramatically affected by cigarette consumption, heavy smokers show significantly lower sperm concentration and FI: another strong reason to stop smoking.

positive: Cigarette smoke radioactivity and lung cancer risk. INTRODUCTION: To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers. METHODS: Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998. RESULTS: The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential "cancerous growth" in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant "nicotine kick" sensation. CONCLUSIONS: The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.

positive: Wet deposition of fission-product isotopes to North America from the Fukushima Dai-ichi incident, March 2011. Using the infrastructure of the National Atmospheric Deposition Program (NADP), numerous measurements of radionuclide wet deposition over North America were made for 167 NADP sites before and after the Fukushima Dai-ichi Nuclear Power Station incident of March 12, 2011. For the period from March 8 through April 5, 2011, wet-only precipitation samples were collected by NADP and analyzed for fission-product isotopes within whole-water and filterable solid samples by the United States Geological Survey using gamma spectrometry. Variable amounts of (131)I, (134)Cs, or (137)Cs were measured at approximately 21% of sampled NADP sites distributed widely across the contiguous United States and Alaska. Calculated 1- to 2-week individual radionuclide deposition fluxes ranged from 0.47 to 5100 Becquerels per square meter during the sampling period. Wet deposition activity was small compared to measured activity already present in U.S. soil. NADP networks responded to this complex disaster, and provided scientifically valid measurements that are comparable and complementary to other networks in North America and Europe.

positive: Death by polonium-210: lessons learned from the murder of former Soviet spy Alexander Litvinenko. The medical response to radiation--whether the result of radiological warfare, terrorist deployment of improvised radiation dispersal weapons, political assassination, occupational or industrial accidents or the medically radiated patient remains one of the least taught among all disciplines within medical education. In the aftermath of 9/11 among medical vulnerabilities to toxicant threats, of all the categories of weapons of mass destruction (WMD)--whether using the CBRNE (chemical, biological, radiological, nuclear, explosive) or NBC (nuclear, biological, chemical) acronym--radiation is the least taught in professional schools, responder cultures or civil preparedness organizations. To date, few health care professionals (HCP) possess the fundamental knowledge or skills to identify and diagnose, let alone treat a radiation victim; this vulnerability made even more obvious in the aftermath of the high profile assassination of former Russian agent Alexander Litvinenko. He was poisoned with Polonium210. Radioactive substances are ubiquitous with radiation sources being in or transported through virtually every region nationwide. It is essential to increase preparedness among community and rural health care facilities as well as urban and university hospitals. Managing radiation injuries effectively requires access to specialized equipment and expertise. Radiation sickness is progressive and may require acute, critical and long-term care throughout the course of illness. Regardless of the source, preparedness rests upon acknowledging a threat exists and dedicating the resources to address the risks including the enhancement of training and equipment. Mass or individual exposures to radiation present unique challenges to the entire response continuum from law enforcement, first responders and emergency medical care. Increased education about and practice in responding to radiological threats is essential to enhance preparedness.

positive: Nutrient profiling of foods: creating a nutrient-rich food index. Nutrient profiling of foods, described as the science of ranking foods based on their nutrient content, is fast becoming the basis for regulating nutrition labels, health claims, and marketing and advertising to children. A number of nutrient profile models have now been developed by research scientists, regulatory agencies, and by the food industry. Whereas some of these models have focused on nutrients to limit, others have emphasized nutrients known to be beneficial to health, or some combination of both. Although nutrient profile models are often tailored to specific goals, the development process ought to follow the same science-driven rules. These include the selection of index nutrients and reference amounts, the development of an appropriate algorithm for calculating nutrient density, and the validation of the chosen nutrient profile model against healthy diets. It is extremely important that nutrient profiles be validated rather than merely compared to prevailing public opinion. Regulatory agencies should act only when they are satisfied that the scientific process has been followed, that the algorithms are transparent, and that the profile model has been validated with respect to objective measures of a healthy diet.

positive: The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. OBJECTIVES: Bacterial vaginosis (BV), a disturbance of vaginal microflora, is a common cause of vaginal symptoms and is associated with an increased risk of acquisition of sexually transmitted infections, HIV, and with adverse pregnancy outcomes. We determined prevalence and associations with BV among a representative sample of women of reproductive age in the United States. STUDY DESIGN: Women aged 14-49 years participating in the National Health and Nutrition Examination Survey 2001-2004 were asked to submit a self-collected vaginal swab for Gram staining. BV, determined using Nugent's score, was defined as a score of 7-10. RESULTS: The prevalence of BV was 29.2% (95% confidence interval 27.2%-31.3%) corresponding to 21 million women with BV; only 15.7% of the women with BV reported vaginal symptoms. Prevalence was 51.4% among non-Hispanic blacks, 31.9% among Mexican Americans, and 23.2% among non-Hispanic whites (P <0.01 for each comparison). Although BV was also associated with poverty (P <0.01), smoking (P <0.05), increasing body mass index (chi2 P <0.0001 for trend), and having had a female sex partner (P <0.005), in the multivariate model, BV only remained positively associated with race/ethnicity, increasing lifetime sex partners (chi2 P <0.001 for trend), increasing douching frequency (chi2 P for trend <0.001), low educational attainment (P <0.01), and inversely associated with current use of oral contraceptive pills (P <0.005). CONCLUSION: BV is a common condition; 84% of women with BV did not report symptoms. Because BV increases the risk of acquiring sexually transmitted infections, BV could contribute to racial disparities in these infections.

positive: A Longitudinal Study of Vaginal Douching and Bacterial Vaginosis—A Marginal Structural Modeling Analysis The etiology of bacterial vaginosis is unknown, and there are no long-term therapies for preventing this frequently recurring condition. Vaginal douching has been reported to be associated with bacterial vaginosis in observational studies. However, this association may be due to confounding by indication—that is, confounding by women douching in response to vaginal symptoms associated with bacterial vaginosis. The authors used marginal structural modeling to estimate the causal effect of douching on bacterial vaginosis risk while controlling for this confounding effect. In 1999–2002, nonpregnant women (n = 3,620) were recruited into a prospective study when they visited one of 12 public health clinics in Birmingham, Alabama, for routine care. Participants were assessed quarterly for 1 year. Bacterial vaginosis was based on a Nugent's Gram stain score of 7 or higher. Thirty-two percent of participants douched in every study interval, and 43.0% never douched. Of the 12,349 study visits, 40.2% were classified as involving bacterial vaginosis. The relative risk for regular douching as compared with no douching was 1.21 (95% confidence interval: 1.08, 1.38). These findings indicate that douching confers increased risk of disruption of vaginal flora. In the absence of a large randomized trial, these findings provide the best evidence to date for a risk of bacterial vaginosis associated with douching.

positive: Bacterial Vaginosis Is Associated with Variation in Dietary Indices Bacterial vaginosis (BV) is a common condition of unknown etiology and has been linked to adverse reproductive and obstetric health outcomes. Prior dietary research on BV has focused on specific macro- and micronutrients, but not dietary indices. We assessed the relationship between BV and selected dietary indicators among a cohort of 1735 nonpregnant women ages 15–44 y from Birmingham, Alabama. Annual intake was assessed with the Block98 FFQ, and the glycemic index, glycemic load (GL), and Healthy Eating Index were calculated by the Block Dietary Data System. The Naturally Nutrient Rich (NNR) score was also calculated. Vaginal flora was evaluated using Nugent Gram-stain criteria. Crude OR and adjusted OR were determined by multinomial and logistic regression in cross-sectional and prospective analyses, respectively. Participants were predominantly African American (85.5%) aged 25.3 ± 6.8 y (mean ± SD). Per 10-unit increase, GL was positively (adjusted OR = 1.01, 95% CI = 1.00–1.03) and NNR was negatively (adjusted OR = 0.93, 95% CI = 0.88–0.99) associated with BV compared to normal vaginal flora. In prospective analyses, only GL was associated with BV progression (adjusted OR = 1.03, 95% CI = 1.00–1.05) and persistence (adjusted OR = 1.02, 95% CI = 1.01–1.04) after adjustment. Both GL and NNR were associated with greater BV prevalence and GL was associated with an increase in BV persistence and acquisition. These results suggest that diet composition may contribute to vaginal flora imbalances and be important for elucidating the etiology of BV.

positive: The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Commercial literature on various probiotic products suggests that they can be taken before meals, during meals or after meals or even without meals. This has led to serious confusion for the industry and the consumer. The objective of our study was to examine the impact of the time of administration with respect to mealtime and the impact of the buffering capacity of the food on the survival of probiotic microbes during gastrointestinal transit. We used an in vitro Digestive System (IViDiS) model of the upper gastrointestinal tract to examine the survival of a commercial multi-strain probiotic, ProtecFlor®. This product, in a capsule form, contains four different microbes: two lactobacilli (Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011), Bifidobacterium longum R0175 and Saccharomyces cerevisiae boulardii. Enumeration during and after transit of the stomach and duodenal models showed that survival of all the bacteria in the product was best when given with a meal or 30 minutes before a meal (cooked oatmeal with milk). Probiotics given 30 minutes after the meal did not survive in high numbers. Survival in milk with 1% milk fat and oatmeal-milk gruel were significantly better than apple juice or spring water. S. boulardii was not affected by time of meal or the buffering capacity of the meal. The protein content of the meal was probably not as important for the survival of the bacteria as the fat content. We conclude that ideally, non-enteric coated bacterial probiotic products should be taken with or just prior to a meal containing some fats.

positive: Placebos in clinical practice: comparing attitudes, beliefs, and patterns of use between academic psychiatrists and nonpsychiatrists. Controversial and ethically tenuous, the use of placebos is central to medicine but even more pivotal to psychosocial therapies. Scholars, researchers, and practitioners largely disagree about the conceptualization of placebos. While different professionals often confound the meanings of placebo effects with placebo responses, physicians continue to prescribe placebos as part of clinical practice. Our study aims to review attitudes and beliefs concerning placebos outside of clinical research. Herein we compare patterns of placebo use reported by academic psychiatrists with those reported by physicians from different specialties across Canadian medical schools. Using a web-based tool, we circulated an online survey to all 17 Canadian medical schools, with a special emphasis on psychiatry departments therein and in university-affiliated teaching hospitals. A variation on earlier efforts, our 5-minute, 21-question survey was anonymous. Among the 606 respondents who completed our online survey, 257 were psychiatrists. Our analysis revealed that psychiatrists prescribed significantly more subtherapeutic doses of medication than physicians in other specialties, although about 20% of both psychiatrists and nonpsychiatrists prescribed placebos regularly as part of routine clinical practice. However, compared with 6% of nonpsychiatrists, only 2% of psychiatrists deemed placebos of no clinical benefit. In addition, more than 60% of psychiatrists either agreed or strongly agreed that placebos had therapeutic effects relative to fewer than 45% of other practitioners. Findings from this pan-Canadian survey suggest that, compared with other physicians, psychiatrists seem to better value the influence placebos wield on the mind and body and maintain more favourable beliefs and attitudes toward placebo phenomena.

positive: Bach flower remedies: a systematic review of randomised clinical trials. Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos.

positive: Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003). Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients.

positive: Questionnaire survey on use of placebo Objectives To gauge the frequency and circumstances of use of placebo in clinical practice and the attitudes towards its use among those who administer it. Design Retrospective questionnaire. Setting Two large hospitals and various community clinics in the Jerusalem area. Participants 31 physicians working in hospital inpatient and outpatient departments, 31 head nurses working in hospital inpatient departments, and 27 family physicians working in community clinics. Main outcome measures Self report of frequency and circumstances of, and attitudes towards, use of placebo. Results Among the 89 respondents, 53 (60%) used placebos (95% confidence interval 49% to 70%). Among users, 33 (62%) prescribed a placebo as often as once a month or more; 36 (68%) told patients they were receiving actual medication; 15 (28%) considered that placebos were a diagnostic tool; and 48/51 (94%) reported that they found placebos generally or occasionally effective. Conclusion Most practitioners questioned in this study continue to use placebos. Used wisely, placebos might have a legitimate place in therapeutics. Wider recognition of the practice and debate about its implications are imperative.

positive: What's in placebos: who knows? Analysis of randomized, controlled trials. BACKGROUND: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting. PURPOSE: To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials. DATA SOURCES: 4 English-language general and internal medicine journals with high impact factors. STUDY SELECTION: 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009. DATA EXTRACTION: Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus. DATA SYNTHESIS: Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002). LIMITATION: Journals with high impact factors may not be representative. CONCLUSION: Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.

positive: A survey of placebo use in a general hospital. Two hundred thirty registered nurses and seventy physicians participated in a retrospective study scrutinizing placebo effects, prescribing patterns, and staff attitudes in a university-based general hospital setting. Despite copious experimental literature devoted to placebo effects over the past thirty years, the medical and surgical use of placebos seems to disregard experimental data. Although 80% of the staff had used placebos in the hospital, their knowledge of placebo effects was in many respects deficient. Within the hospital, 89% of placebo use was directed toward the amelioration of "pain"; the authors believe that emphasis should be placed on the education of staff to perceive emotional, social, and physiological concomitants of pain rather than resorting to a purely physicalistic approach. A need to acknowledge staff conflicts over the ethical use of placebos should be a significant part of this educational approach.

positive: Can deceiving patients be morally acceptable? Daniel K Sokol argues that on rare occasions benignly deceiving patients can be morally acceptable, and he has devised a decision checklist to help doctors facing such a dilemma

positive: Placebos and general practice: attitudes to, and the use of, the placebo effect. The present study surveyed Dunedin general practitioners to determine whether they would deliberately use placebo treatments, under what conditions they would do so, their basic understanding of the placebo effect, and their perception of their use of placebos relative to that of their colleagues. Results indicated that almost all GPS surveyed would deliberately use a placebo treatment under some circumstances. However, there was a clear and statistically significant tendency to understate their use relative to that of their colleagues. It was also clear that a significant number of those surveyed felt placebo treatments to be more appropriate for "imaginary illnesses". Results are discussed in comparison with overseas studies and in regard to their implications for medical training.

positive: A duty to deceive: placebos in clinical practice. Among medical researchers and clinicians the dominant view is that it is unethical to deceive patients by prescribing a placebo. This opinion is formalized in a recent policy issued by the American Medical Association (AMA [Chicago, IL]). Although placebos can be shown to be always safe, often effective, and sometimes necessary, doctors are now effectively prohibited from using them in clinical practice. I argue that the deceptive administration of placebos is not subject to the same moral objections that face other forms of deception in clinical practice and medical research. Although deception is normally objectionable on the grounds that it limits autonomy and breaches trust, these grounds do not apply to placebos when they are prescribed within appropriate ethical limits. Patients have reason to prefer that doctors can prescribe placebos in ethically responsible ways. Hence, the AMA has an obligation to endorse and to promote the responsible use of deceptive placebos in clinical practice.

positive: A systematic review of systematic reviews of homeopathy Homeopathy remains one of the most controversial subjects in therapeutics. This article is an attempt to clarify its effectiveness based on recent systematic reviews. Electronic databases were searched for systematic reviews/meta-analysis on the subject. Seventeen articles fulfilled the inclusion/exclusion criteria. Six of them related to re-analyses of one landmark meta-analysis. Collectively they implied that the overall positive result of this meta-analysis is not supported by a critical analysis of the data. Eleven independent systematic reviews were located. Collectively they failed to provide strong evidence in favour of homeopathy. In particular, there was no condition which responds convincingly better to homeopathic treatment than to placebo or other control interventions. Similarly, there was no homeopathic remedy that was demonstrated to yield clinical effects that are convincingly different from placebo. It is concluded that the best clinical evidence for homeopathy available to date does not warrant positive recommendations for its use in clinical practice.

positive: Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists Objective To describe the attitudes and behaviours regarding placebo treatments, defined as a treatment whose benefits derive from positive patient expectations and not from the physiological mechanism of the treatment itself. Design Cross sectional mailed survey. Setting Physicians’ clinical practices. Participants 1200 practising internists and rheumatologists in the United States. Main outcome measures Investigators measured physicians’ self reported behaviours and attitudes concerning the use of placebo treatments, including measures of whether they would use or had recommended a “placebo treatment,” their ethical judgments about the practice, what they recommended as placebo treatments, and how they typically communicate with patients about the practice. Results 679 physicians (57%) responded to the survey. About half of the surveyed internists and rheumatologists reported prescribing placebo treatments on a regular basis (46-58%, depending on how the question was phrased). Most physicians (399, 62%) believed the practice to be ethically permissible. Few reported using saline (18, 3%) or sugar pills (12, 2%) as placebo treatments, while large proportions reported using over the counter analgesics (267, 41%) and vitamins (243, 38%) as placebo treatments within the past year. A small but notable proportion of physicians reported using antibiotics (86, 13%) and sedatives (86, 13%) as placebo treatments during the same period. Furthermore, physicians who use placebo treatments most commonly describe them to patients as a potentially beneficial medicine or treatment not typically used for their condition (241, 68%); only rarely do they explicitly describe them as placebos (18, 5%). Conclusions Prescribing placebo treatments seems to be common and is viewed as ethically permissible among the surveyed US internists and rheumatologists. Vitamins and over the counter analgesics are the most commonly used treatments. Physicians might not be fully transparent with their patients about the use of placebos and might have mixed motivations for recommending such treatments.

positive: The use of placebo interventions in medical practice--a national questionnaire survey of Danish clinicians. The authors sent a questionnaire to 772 randomly selected Danish clinicians and asked them about their use of placebo interventions. Sixty-five percent responded. Among the general practitioners, 86% (95% confidence interval 81-91) reported to have used placebo interventions at least once, and 48% (41-55) to have used placebo interventions more than ten times, within the last year. Hospital-based doctors and private specialists reported to have used placebo interventions less frequently (p < .001). The most important reason for the use of placebo interventions was to avoid a confrontation with the patient. Typical placebos were antibiotics for viral infections. Approximately 30% (28-36) of the clinicians believed in an effect of placebo interventions on objective outcomes, and 46% (42-50) found clinical placebo interventions generally ethically acceptable.

positive: General practice consultations: is there any point in being positive? A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were randomly selected for one of four consultations: a consultation conducted in a "positive manner," with and without treatment, and a consultation conducted in a "non-positive manner," called a negative consultation, with and without treatment. Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups. Similarly, 64% of those receiving a positive consultation got better, compared with 39% of those who received a negative consultation (p = 0.001) and 53% of those treated got better compared with 50% of those not treated (p = 0.5).

positive: Energy density, nutrient adequacy, and cost per serving can provide insight into food choices in the lower Mississippi Delta. OBJECTIVE: To compare differences across food groups for food cost, energy, and nutrient profiles of 100 items from a cross-sectional survey of 225 stores in 18 counties across the Lower Mississippi Delta of Arkansas, Louisiana, and Mississippi. METHODS: Energy, nutrient, and cost profiles for food items were calculated by using Naturally Nutrient Rich methodology and converting price per 100 g edible portion to price per serving. Foods were grouped into 6 food groups. Mean differences were compared with ANOVA. RESULTS: Significant differences existed by food group for each measure. Energy density was highest for fats/oils/sweets, whereas nutrient density was highest for vegetables. Price per serving was lowest for fats/oils/sweets and highest for meats. CONCLUSIONS AND IMPLICATIONS: Educational messages focusing on a complete diet should consider the role of food costs and provide specific recommendations for increasing nutrient-dense foods by replacing a portion of the meat serving at meals with culturally acceptable lower-cost nutrient-dense foods. Copyright Â© 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

positive: The cost of US foods as related to their nutritive value Background: Comparisons of the cost of different foods relative to their energy and nutritive value were conducted in the 1800s by the US Department of Agriculture (USDA). Objective: The objective was to reestablish the relations between food cost, energy, and nutrients by using contemporary nutrient composition and food prices data from the USDA. Design: The USDA Food and Nutrient Database for Dietary Studies 1.0 (FNDDS 1.0) and the Center for Nutrition Policy and Promotion food prices database were used for analysis. For 1387 foods, key variables were as follows: energy density (kcal/g), serving size (g), unit price ($/100 g), serving price ($/serving), and energy cost ($/kcal). A regression model tested associations between nutrients and unit price ($/100 g). Comparisons between food groups were tested by using one-factor analyses of variance. Relations between energy density and price within food groups were tested by using Spearman's correlations. Results: Grains and fats food groups supplied the lowest-cost dietary energy. The energy cost for vegetables was higher than that for any other food group except for fruit. Serving sizes increased with water content and varied inversely with energy density of foods. The highest prices per serving were for meats, poultry, and fish, and the lowest prices per serving were for the fats category. Although carbohydrates, sugar, and fat were associated with lower price per 100 g, protein, fiber, vitamins, and minerals were associated with higher price per 100 g, after adjustment for energy. Conclusions: Grains and sugars food groups were cheaper than vegetables and fruit per calorie and were cheaper than fruit per serving. These price differentials may help to explain why low-cost, energy-dense foods that are nutrient poor are associated with lower education and incomes.

positive: What is the cell hydration status of healthy children in the USA? Preliminary data on urine osmolality and water intake. OBJECTIVE: Hyperosmotic stress on cells limits many aspects of cell function, metabolism and health. International data suggest that schoolchildren may be at risk of hyperosmotic stress on cells because of suboptimal water intake. The present study explored the cell hydration status of two samples of children in the USA. DESIGN: Cross-sectional study describing the urine osmolality (an index of hyperosmotic cell shrinkage) and water intake of convenience samples from Los Angeles (LA) and New York City (NYC). SETTING: Each participant collected a urine sample at an outpatient clinic on the way to school on a weekday morning in spring 2009. Each was instructed to wake, eat, drink and do as usual before school, and complete a dietary record form describing the type and amounts of all foods and beverages consumed after waking, before giving the sample. SUBJECTS: The children (9-11 years) in LA (n 337) and NYC (n 211) considered themselves healthy enough to go to school on the day they gave the urine sample. RESULTS: Elevated urine osmolality (>800 mmol/kg) was observed in 63 % and 66 % of participants in LA and NYC, respectively. In multivariable-adjusted logistic regression models, elevated urine osmolality was associated with not reporting intake of drinking water in the morning (LA: OR = 2·1, 95 % CI 1·2, 3·5; NYC: OR = 1·8, 95 % CI 1·0, 3·5). Although over 90 % of both samples had breakfast before giving the urine sample, 75 % did not drink water. CONCLUSIONS: Research is warranted to confirm these results and pursue their potential health implications.

positive: Hydration and cognitive performance. A clinical link exists between severe dehydration and cognitive performance. Using rapid and severe water loss induced either by intense exercise and/or heat stress, initial studies suggested there were alterations in short-term memory and cognitive function related to vision, but more recent studies have not all confirmed these data. Some studies argue that water loss is not responsible for the observations made, and studies compensating water losses have failed to prevent the symptoms. Studies in children have suggested that drinking extra water helps cognitive performance, but these data rely on a small number of children. In older adults (mean age around 60) the data are not strong enough to support a relationship between mild dehydration and cognitive function. Data on frail elderly and demented people are lacking. Methodological heterogeneity in these studies are such that the relationship between mild dehydration and cognitive performance cannot be supported.

positive: Mild dehydration impairs cognitive performance and mood of men. The present study assessed the effects of mild dehydration on cognitive performance and mood of young males. A total of twenty-six men (age 20·0 (sd 0·3) years) participated in three randomised, single-blind, repeated-measures trials: exercise-induced dehydration plus a diuretic (DD; 40 mg furosemide); exercise-induced dehydration plus placebo containing no diuretic (DN); exercise while maintaining euhydration plus placebo (EU; control condition). Each trial included three 40 min treadmill walks at 5·6 km/h, 5 % grade in a 27·7°C environment. A comprehensive computerised six-task cognitive test battery, the profile of mood states questionnaire and the symptom questionnaire (headache, concentration and task difficulty) were administered during each trial. Paired t tests compared the DD and DN trials resulting in >1 % body mass loss (mean 1·59 (sd 0·42) %) with the volunteer's EU trial (0·01 (sd 0·03) %). Dehydration degraded specific aspects of cognitive performance: errors increased on visual vigilance (P = 0·048) and visual working memory response latency slowed (P = 0·021). Fatigue and tension/anxiety increased due to dehydration at rest (P = 0·040 and 0·029) and fatigue during exercise (P = 0·026). Plasma osmolality increased due to dehydration (P < 0·001) but resting gastrointestinal temperature was not altered (P = 0·238). In conclusion, mild dehydration without hyperthermia in men induced adverse changes in vigilance and working memory, and increased tension/anxiety and fatigue.

positive: Should children drink more water?: the effects of drinking water on cognition in children. While dehydration has well-documented negative effects on adult cognition, there is little research on hydration and cognitive performance in children. We investigated whether having a drink of water improved children's performance on cognitive tasks. Fifty-eight children aged 7-9 years old were randomly allocated to a group that received additional water or a group that did not. Results showed that children who drank additional water rated themselves as significantly less thirsty than the comparison group (p=0.002), and they performed better on visual attention tasks (letter cancellation, p=0.02; spot the difference memory tasks, ps=0.019 and 0.014).

positive: Effects of drinking supplementary water at school on cognitive performance in children. We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

positive: Does having a drink help you think? 6-7-Year-old children show improvements in cognitive performance from baseline to test after having a drink of ... Little research has examined the effect of water consumption on cognition in children. We examined whether drinking water improves performance from baseline to test in twenty-three 6-7-year-old children. There were significant interactions between time of test and water group (water/no water), with improvements in the water group on thirst and happiness ratings, visual attention and visual search, but not visual memory or visuomotor performance. These results indicate that even under conditions of mild dehydration, not as a result of exercise, intentional water deprivation or heat exposure, children's cognitive performance can be improved by having a drink of water.

positive: Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.

positive: Recommendations for the prevention of chronic disease: the application for breast disease. Experimental and epidemiological evidence suggest that a diet with dietary fat as low as 20% of kcal may be necessary to reduce the risk of breast cancer. Two groups of women, postmenopausal women treated for breast cancer and premenopausal women with cystic breast disease accompanied by cyclical mastaligia, participated in an intervention program to determine the feasibility of such a low-fat diet. After 3 mo of intervention both groups were consuming a low-fat diet; in the premenopausal groups serum estrogen levels decreased in response to the fat reduction. Other nutrition-education programs in research institutions, restaurants, and schools are attempting to influence the public's knowledge and behavior regarding the importance of dietary fat reduction.

positive: Serum prolactin and oestradiol levels in women with cyclical mastalgia. Basal serum prolactin and serum oestradiol-17-beta concentrations were measured four times during one menstrual cycle in 20 women with severe cyclical mastalgia and normal to slightly fibroadenotic breasts. A group of 10 normal women who had never experienced mastalgia served as controls. Basal serum prolactin was significantly elevated in patients compared to normals, although within the normal range. Serum oestradiol concentrations did not differ in the two groups and were also within the normal range. A significant positive correlation between oestradiol and prolactin was found in patients and normals, but with larger prolactin levels in patients. The results point towards a prolactin secretory hypersensitivity for oestradiol in patients with cyclical mastalgia. Prolactin is considered a central factor in the eliciting of cyclical mastalgia.

positive: Global study of women's experiences of premenstrual symptoms and their effects on daily life. OBJECTIVES: To determine cross-cultural and other effects on women's experiences of premenstrual symptoms and their impact on activities of daily life (ADL). STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R = 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Women's knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. CONCLUSIONS: Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of women's experiences of these symptoms across countries and regions. Women's knowledge of PMS terms is highly dependent on the country in which they live.

positive: Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.

positive: Mastalgia: a review of management. Mastalgia affects up to two-thirds of women at some time during their reproductive lives. It is usually benign, but thefear of underlying breast cancer is why many women present for evaluation. Mastalgia can be associated with premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and, rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie syndrome, present as mastalgia. A thorough clinical evaluation is required to assess the cause. The majority of women can be reassured after a clinical evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast support; a low-fat, high-carbohydrate diet; and topical nonsteroidal antiinflammatory agents are reasonable first-line treatments. Hormonal agents, such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in the treatment of mastalgia. Side effects, however, limit their extensive use. Danazol is the only FDA-approved hormonal treatment and is best used in cyclic form to limit the adverse effects. Lisuride maleate is a new agent recently studied for the treatment of mastalgia. Initial data on this medication are encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of cases.

positive: Effect of flax seed ingestion on the menstrual cycle. Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.

positive: A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease. A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.

positive: Influence of dietary fat on self-reported menstrual symptoms. The Moos Menstrual Distress Questionnaire (MMDQ) was completed by thirty healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40% energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20% energy from fat). There were no significant differences in self-reported menstrual symptoms between the two P/S groups. During both menses and the premenstrual week of the low fat dietary period there were significant decreases in self-reported symptoms associated with water retention. A decrease in symptoms in the group labelled "arousal" during the rest of the menstrual cycle was also reported.

positive: Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial Modifiable factors, including diet, might alter breast cancer risk. We used the WHI Dietary Modification (DM) trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of and considered to be on the pathway to invasive breast cancer. The WHI DM trial was a randomized, controlled, primary prevention trial conducted in 40 US clinical centers from 1993–2005. 48,835 postmenopausal women, aged 50–79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the DM intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/day and intake of grain products to ≥6 servings/day, but resulted in smaller, albeit significant changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between DM and benign proliferative breast disease was 1.09 (95%CI, 0.98–1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake does not alter the risk of benign proliferative breast disease.

positive: Mastalgia. OBJECTIVE: To review the current management of women with breast pain. OPTIONS: The effect of various treatment modes and health practices, including medications, was considered for the management of both cyclical and noncyclical breast pain. OUTCOMES: Effective and timely management of the woman with breast pain and improved quality of life. EVIDENCE: A literature search was performed to identify reports published in English between 1975 and July 2003 using MEDLINE and Cochrane Database of Systematic Reviews. VALUES: Levels of evidence, as outlined, have been determined using the criteria outlined by the Canadian Task Force on the Periodic Health Examination. Participants were the principal authors: a clinical dietitian, a surgeon oncologist, and a nurse. BENEFITS, HARMS, AND COSTS: Utilizing the information will increase knowledge, enabling a consistent approach, which will reduce the number of ineffective interventions and ensure appropriate use medications. VALIDATION: Comparison has been made with management protocols in the literature, but no clinical guidelines have been located. No formal clinical testing has taken place. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada (SOGC). Work on these guidelines was initiated by team members to fill a need for practice guidelines at Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, MB. RECOMMENDATIONS: 1. Education and reassurance is an integral part of the management of mastalgia and should be the first-line treatment. (II-1 A) 2. The use of a well-fitting bra that provides good support should be considered for the relief of cyclical and noncyclical mastalgia. (II-3 B) 3. A change in dose, formulation, or scheduling should be considered for women on HRT. HRT may be discontinued if appropriate. (III C) 4. Women with breast pain should not be advised to reduce caffeine intake. (1 E) 5. Vitamin E should not be considered for the treatment of mastalgia. (1 E) 6. There is presently insufficient evidence to recommend the use of evening primrose oil (EPO) in the treatment of breast pain. (II-2 C) 7. Flaxseed should be considered as a first-line treatment for cyclical mastalgia. (I A) 8. Topical non-steroidal anti-inflammatory gel, such as diclofenac 2% in pluronic lethicin organogel, should be considered for pain control for localized treatment of mastalgia. (I A) 9. Tamoxifen 10 mg daily or danazol 200 mg daily should be considered when first-line treatments are ineffective. (I A) 10. Mastectomy or partial mastectomy should not be considered an effective treatment for mastalgia. (III E).

positive: Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy. 21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.

positive: A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease. This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.

positive: Protein redistribution diet and antiparkinsonian response to levodopa. Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.

positive: Caffeine for treatment of Parkinson disease Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.

positive: Plasma levels of amino acids correlate with motor fluctuations in parkinsonism. Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.

positive: Habitual intake of dietary flavonoids and risk of Parkinson disease Objective: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). Methods: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. Results: We identified 805 participants (438 men and 367 women) who developed PD during 20–22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Conclusions: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.

positive: Intake of Japanese and Chinese teas reduces risk of Parkinson's disease. Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

positive: Pilot dietary study with normoproteic protein-redistributed plant-food diet and motor performance in patients with Parkinson's disease. Although a plant-based diet can provide some benefits in Parkinson's disease (PD), no study to date has evaluated the effectiveness of a plant-food diet in the management of the disease. In this pilot study, we compared the effect of a plant-food menu (PFD) and of a omnivorous menu on motor performance of 25 PD patients, 12 in the intervention group (PDi) and 13 in the control group (PDc). After 4 weeks, the PDi group showed a significant reduction (Mann-Whitney test) in the Unified Parkinson's Disease Rating Scale, total score (47.67 vs. 74.46, P = 0.008) and sub-score III motor performances (25.42 vs. 46.46, P = 0.001), and the modified Hoehn and Yahr Staging Scale (1.96 vs. 3.15, P = 0.005). These data suggest that PFD may be useful in the management of PD patients by improving their motor performances. Additional studies are needed in order to confirm these preliminary results.

positive: Caffeine and risk of Parkinson disease in a large cohort of men and women Background Caffeine consumption has been associated with a reduced risk of Parkinson disease. The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy. We sought to confirm these findings using data on Parkinson disease incidence in the CPS II Nutrition Cohort, a large prospective study of men and women. Methods We conducted a prospective study of caffeine intake and risk of PD within the Cancer Prevention Study II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, smoking and alcohol consumption. Results After adjustment for age, smoking and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The relative risk comparing the 5th to the 1st quintile of caffeine intake was 0.43 (CI: 0.26, 0.71, p-trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; p for trend =0.05) in women. Among women, this association was stronger among never users of hormone replacement therapy (RR=0.32) than among ever users (RR=0.81, p-interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Conclusion Findings from this large prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of hormone replacement therapy in women.

positive: Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease. In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.

positive: Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies. The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.

positive: Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007 Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.

positive: Elevated Serum Pesticide Levels and Risk of Parkinson Disease Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.

positive: Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books. BACKGROUND: The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. METHODS: A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. RESULTS: Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called "the magic potion". CONCLUSIONS: Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).

positive: Association between polychlorinated biphenyls and Parkinson’s disease neuropathology Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.

positive: Hospital Admissions for Traumatic Brain Injuries, 2004: Statistical Brief #27 Excerpt This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) on the treatment of TBI in U.S. hospitals in 2004. Hospital utilization and costs for TBI admissions are compared with hospital stays for all other injuries. Additionally, trends in hospital stays for TBI and differences in the distribution of TBI admissions by various patient characteristics are examined. Finally, common causes of TBIs resulting in hospital admission, as well as the coexisting conditions often associated with these injuries, are described. All differences between estimates noted in the text are statistically significant at the 0.05 level or better.

positive: Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.

positive: Influence of water and food consumption on inadvertent antibiotics intake among general population. Antibiotic entry into the water environment has been of growing concern. However, few investigations have been performed to examine the potential for indirect human exposure to environmental antibiotic residues. We evaluated the contribution of drinking water and major food consumption to inadvertent intake of antibiotic residues among general human population in Korea. We estimated daily human intake of six antibiotics, i.e., sulfamethazine (SMZ), sulfamethoxazole (SMX), sulfathiazole (STZ), trimethoprim (TMP), enrofloxacin (EFX), and roxithromycin (RTM), by measuring the concentrations of the antibiotics and their major metabolites in urine from general population in Korea (n=541). In addition, we measured antibiotics from source water of drinking water as well as in tap water samples, and surveyed water consumption rates among the study population. To assess the contribution of dietary factor, we also surveyed consumption pattern for several major foods which are suspected of antibiotics residue. SMZ, Sulfamethazine-N4-acetyl (SMZ-N4), TMP, EFX, ciprofloxacin (CFX), and RTM were detected up to 448, 6210, 11,900, 6970, 32,400, and 151pg/ml in the urine samples, respectively. Estimates of daily intake of major antibiotics did not appear to be related with consumption of drinking water although antibiotics were frequently detected in source waters (10-67ng/l). Consumption of several foods correlated significantly with urinary excretion of several antibiotics. Daily intake estimates of EFX and CFX were associated with consumption of beef, pork, and dairy products; those of SMZ and TMP associated with pork and dairy products; and that of TMP related with raw fish. Daily antibiotics intake estimates however did not exceed the acceptable daily intake levels. Copyright 2010 Elsevier Inc. All rights reserved.

positive: Influence of a five-day vegetarian diet on urinary levels of antibiotics and phthalate metabolites: a pilot study with "Temple Stay" participants. Diet is purported to be means of exposure to many environmental contaminants. The purpose of this study is to understand the influence of dietary change on the levels of exposure to several environmental chemicals - in particular, antibiotics and phthalates. For this purpose, we examined the extent to which short-term changes in diet influenced the inadvertent exposure levels to these chemicals in an adult population. We recruited participants (n=25) of a five-day 'Temple Stay' program in Korea and collected urine samples before and after the program. We also conducted a questionnaire survey on participants' dietary patterns prior to their participation. During the program, participants followed the daily routines of Buddhist monks and maintained a vegetarian diet. Urinary levels of three antibiotics and their major metabolites, metabolites of four major phthalates, and malondialdehyde (MDA) as an oxidative stress biomarker were analyzed. The frequency and levels of detection for antibiotics and phthalates noticeably decreased during the program. Urinary MDA levels were significantly lower than before program participation (0.16 versus 0.27mg/g creatinine). Although the exposure to target compounds might be influenced by other behavioral patterns, these results suggest that even short-term changes in dietary behavior may significantly decrease inadvertent exposure to antibiotics and phthalates and hence may reduce oxidative stress levels. Copyright 2010 Elsevier Inc. All rights reserved.

positive: Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. Perfluorooctanesulfonyl fluoride based compounds have been used in a wide variety of consumer products, such as carpets, upholstery, and textiles. These compounds degrade to perfluorooctanesulfonate (PFOS), a persistent metabolite that accumulates in tissues of humans and wildlife. Previous studies have reported the occurrence of PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) in human sera collected from the United States. In this study, concentrations of PFOS, PFHxS, PFOA, and PFOSA were measured in 473 human blood/serum/plasma samples collected from the United States, Colombia, Brazil, Belgium, Italy, Poland, India, Malaysia, and Korea. Among the four perfluorochemicals measured, PFOS was the predominant compound found in blood. Concentrations of PFOS were the highest in the samples collected from the United States and Poland (>30 ng/mL); moderate in Korea, Belgium, Malaysia, Brazil, Italy, and Colombia (3 to 29 ng/mL); and lowest in India (<3 ng/mL). PFOA was the next most abundant perfluorochemical in blood samples, although the frequency of occurrence of this compound was relatively low. No age- or gender-related differences in the concentrations of PFOS and PFOA were found in serum samples. The degree of association between the concentrations of four perfluorochemicals varied, depending on the origin of the samples. These results suggested the existence of sources with varying levels and compositions of perfluorochemicals, and differences in exposure patterns to these chemicals, in various countries. In addition to the four target fluorochemicals measured, qualitative analysis of selected blood samples showed the presence of other perfluorochemicals such as perfluorodecanesulfonate (PFDS), perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorododecanoic acid (PFDoA), and perfluoroundecanoic acid (PFUnDA) in serum samples, at concentrations approximately 5- to 10-fold lower than the concentration of PFOS. Further studies should focus on identifying sources and pathways of human exposure to perfluorochemicals.

positive: Perfluorochemicals in meat, eggs and indoor dust in China: assessment of sources and pathways of human exposure to perfluorochemicals. In this study, 10 perfluorochemicals (PFCs) were measured in meat, meat products, and eggs, and in indoor dust, collected in China. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the most frequently detected PFCs in these samples. Mean concentrations of PFOS and PFOA in foodstuffs were in the range of 0.05-1.99 ng/g fresh wt and 0.06-12.5 ng/g fresh wt, respectively. The mean concentrations of PFOA, perfluoroheptanoic acid (PFHpA), and PFOS in indoor dust were 205, 14.0, and 4.86 ng/g, dry wt, respectively. The estimated daily intake of PFOS and PFOA from meat, meat products and eggs (EDI(meat&eggs)) ranged from 6.00 to 9.64 ng/d and from 254 to 576 ng/d, respectively, when the values below the limit of quantitation (LOQ) were assigned as 0, and from 8.80 to 15.0 ng/d and from 255 to 577 ng/d, respectively, when the values below the LOQ were set at 1/2LOQ. The EDI(meat&eggs) of PFOS and PFOA increased with increasing family income. The estimated daily intake of PFOS and PFOA through inhalation of dust (EDI(dust)) ranged from 0.23 to 0.31 ng/d and from 9.68 to 13.4 ng/d, respectively. The daily intakes of PFOS and PFOA from the consumption of meat, meat products, and eggs, and from dust ingestion, as calculated from our samples in this study, were compared with estimated daily intake of PFCs reported from the concentrations in drinking water, fish and seafood from China. Our calculations indicate that dietary sources (EDI(dietary)) account for the overwhelming proportion of (>99% for PFOS and 98% for PFOA) total daily intake (TDI) in adults. The analyzed foodstuffs (meat, meat products, and eggs) were not the major contributors to dietary exposure to PFOS, whereas, meat was the primary contributor to dietary exposure to PFOA.

positive: Perfluorooctanesulfonate and related fluorochemicals in human blood samples from China. Perfluorooctanesulfonylfluoride (POSF)-based compounds have been manufactured and used in a variety of industrial applications. These compounds degrade to perfluorooctanesulfonate (PFOS) which is regarded as a persistent end-stage metabolite and is found to accumulate in tissues of humans and wildlife. PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) have been found in human sera from the United States. In this study, concentrations of PFHxS, perfluorobutanesulfonate (PFBS), PFOS, perfluorohexanoic acid (PFHxA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and PFOSA were measured in 85 samples of whole human blood collected from nine cities (eight provinces) in China, including Shenyang (Liaoning), Beijing (Hebei), Zhengzhou (Henan), Jintan (Jiangsu), Wuhan (Hubei), Zhoushan (Zhejiang), Guiyang (Guizhou), Xiamen (Fujian), and Fuzhou (Fujian). Among the 10 perfluorinated compounds (PFCs) measured, PFOS was the predominant compound. The mean concentration of PFOS was greatest in samples collected from Shenyang (79.2 ng/mL) and least in samples from Jintan (3.72 ng/mL). PFHxS was the next most abundant perfluorochemical in the samples. No age-related differences in the concentrations of PFOA, PFOS, PFOSA, and PFHxS were observed. Gender-related differences were found,with males higher for PFOS and PFHxS, and females higher in PFUnDA. Concentrations of PFHxS were positively correlated with those of PFOS, while concentrations of PFNA, PFDA, and PFUnDA were positively correlated with those of PFOA. There were differences in the concentration profiles (percentage composition) of various PFCs in the samples among the nine cities.

positive: Variability in Pesticide Deposition and Source Contributions to Snowpack in Western US National Parks Fifty-six seasonal snowpack samples were collected at remote alpine, sub-arctic, and arctic sites in eight Western US national parks during three consecutive years (2003–2005). Four current-use pesticides (CUPs) (dacthal (DCPA), chlorpyrifos, endosulfan, and γ-hexachlorocyclohexane (HCH)) and four historic-use pesticides (HUPs) (dieldrin, α-HCH, chlordane, and hexachlorobenzene (HCB)) were commonly measured at all sites, during all years. The mean coefficient of variation for pesticide concentrations was 15% for site replicate samples, 41% for intra-park replicate samples, and 59% for inter-annual replicate samples. The relative pesticide concentration profiles were consistent from year to year but unique for individual parks, indicating a regional source effect. HUP concentrations were well-correlated with regional cropland intensity when the effect of temperature on snow-air partitioning was considered. The mass of individual CUPs used in regions located one-day upwind of the parks was calculated using air mass back trajectories and this was used to explain the distribution of CUPs among the parks. The percent of the snowpack pesticide concentration due to regional transport was high (>75%) for the majority of pesticides in all parks. These results suggest that the majority of pesticide contamination in US national parks is due to pesticide use in North America.

positive: Chronic dietary risk characterization for pesticide residues: a ranking and scoring method integrating agricultural uses and food contamination data. A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales. Copyright © 2011 Elsevier Ltd. All rights reserved.

positive: Pesticides in rain in four agricultural watersheds in the United States. Rainfall samples were collected during the 2003 and 2004 growing seasons at four agricultural locales across the USA in Maryland, Indiana, Nebraska, and California. The samples were analyzed for 21 insecticides, 18 herbicides, three fungicides, and 40 pesticide degradates. Data from all sites combined show that 7 of the 10 most frequently detected pesticides were herbicides, with atrazine (70%) and metolachlor (83%) detected at every site. Dacthal, acetochlor, simazine, alachlor, and pendimethalin were detected in more than 50% of the samples. Chlorpyrifos, carbaryl, and diazinon were the only insecticides among the 10 most frequently detected compounds. Of the remaining pesticide parent compounds, 18 were detected in fewer than 30% of the samples, and 13 were not detected. The most frequently detected degradates were deethylatrazine; the oxygen analogs (OAs) of the organophosphorus insecticides chlorpyrifos, diazinon, and malathion; and 1-napthol (degradate of carbaryl). Deethylatrazine was detected in nearly 70% of the samples collected in Maryland, Indiana, and Nebraska but was detected only once in California. The OAs of chlorpyrifos and diazinon were detected primarily in California. Degradates of the acetanilide herbicides were rarely detected in rain, indicating that they are not formed in the atmosphere or readily volatilized from soils. Herbicides accounted for 91 to 98% of the total pesticide mass deposited by rain except in California, where insecticides accounted for 61% in 2004. The mass of pesticides deposited by rainfall was estimated to be less than 2% of the total applied in these agricultural areas.

positive: Polybrominated diphenyl ethers in U.S. Meat and poultry from two statistically designed surveys showing trends and levels from 2002 to 2008. Polybrominated diphenyl ether (PBDE) body burdens in the general U.S. population have been linked to the consumption of red meat and poultry. Exposure estimates have also indicated that meat products are a major contributor to PBDE dietary intake. To establish solid estimates of PBDE concentrations in domestic meat and poultry, samples from two statistically designed surveys of U.S. meat and poultry were analyzed for PBDEs. The two surveys were conducted in 2002-2003 and 2007-2008, between which times the manufacturing of penta-BDE and octa-BDE formulations had ceased in the United States (December 2004). Thus, the data provided an opportunity to observe prevalence and concentration trends that may have occurred during this time frame and to compare the mean PBDE levels among the meat and poultry industries. On the basis of composite samples, the average sum of the seven most prevalent PBDEs (BDE-28, -47, -99, -100, -153, -154, and -183) decreased by >60% from 1.95 ng/g lipid in 2002-2003 to 0.72 ng/g lipid in 2007-2008 for meat and poultry. PBDEs measured in individual samples in 2008 showed that beef samples had the lowest PBDE levels followed by hogs and chickens and then by turkeys. The PBDE congener pattern was the same for both surveys and resembled the penta-BDE formulation with BDE-47 and -99 accounting for 30 and 40% of the total, respectively. On the basis of the data from the two surveys, it appears that PBDE levels in U.S. meat and poultry have declined since manufacturing ceased; however, exposure pathways of PBDEs to livestock are still not known.

positive: Flame retardants in the serum of pet dogs and in their food. A previous study from our laboratory showed that pet cats had much higher serum levels of flame retardants compared to humans, despite sharing the same household environment. Dogs, on the other hand, are expected to have lower serum levels of flame retardants because they are metabolically better equipped to degrade these compounds. Thus, we hypothesized that dogs might be more similar to humans in their response to these environmental stressors and be better indicators of human exposures to these contaminants. Serum samples and their food were collected from 18 dogs and analyzed for PBDEs and other emerging flame retardants. The concentrations of PBDEs in dog serum and dog food averaged 1.8 ± 0.4 ng/g wet weight (ww) and 1.1 ± 0.2 ng/g ww, respectively. While the dog serum samples were dominated by the tetra to hepta BDE congeners, BDE-209 was the most abundant congener in the dog food. This difference in congener pattern was analyzed in terms of half-lives. Assuming food as the main exposure source, the average half-life in dog serum was 450 ± 170 days for the less brominated congeners and 2.3 ± 0.5 days for BDE-209. Dust was also considered as an additional exposure source, giving unreasonable residence times. In addition to PBDEs, other flame retardants, including Dechlorane Plus, decabromodiphenylethane, and hexabromocyclododecane, were identified in these samples.

positive: Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets. Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the "vegetarian" than in the "mixed" diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r = -0.74; p less than 0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r = -0.52; p less than 0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.

positive: Brain serotonin content: physiological regulation by plasma neutral amino acids. When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.

positive: Effect of nutrient intake on premenstrual depression. We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.

positive: Higher bioaccessibility of iron and zinc from food grains in the presence of garlic and onion. Bioavailability of micronutrients iron and zinc is particularly low from plant foods. Hence there is a need to evolve a food-based strategy to improve the same to combat widespread deficiencies of these minerals in a population dependent on plant foods. Dietary sulfur-containing amino acids have been reported to improve the mineral status of experimental animals. Our objective was to examine whether sulfur compound-rich Allium spices have a similar potential of beneficially modulating the mineral bioavailability. In this context, we examined the influence of exogenously added garlic and onion on the bioaccessibility of iron and zinc from food grains. Two representative cereals and pulses each were studied in both raw and cooked condition employing two levels of garlic (0.25 and 0.5 g/10 g of grain) and onion (1.5 and 3 g/10 g of grain). The enhancing effect of these two spices on iron bioaccessibility was generally evidenced in the case of both the cereals (9.4-65.9% increase) and pulses (9.9-73.3% increase) in both raw and cooked conditions. The two spices similarly enhanced the bioaccessibility of zinc from the food grains, the extent of increase in cereals ranging from 10.4% to 159.4% and in pulses from 9.8% to 49.8%. Thus, both garlic and onion were evidenced here to have a promoting influence on the bioaccessibility of iron and zinc from food grains. This novel information has the potential application in evolving a food-based strategy to improve the bioavailability of trace minerals and hence contributes to the human health benefit.

positive: Anti-inflammatory effects of plant-based foods and of their constituents. Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.

positive: Assessment of atherosclerosis: the role of flow-mediated dilatation. Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensive.

positive: Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits. Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.

positive: Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol. We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.

positive: Evidence for acne-promoting effects of milk and other insulinotropic dairy products. Acne vulgaris, the most common skin disease of western civilization, has evolved to an epidemic affecting more than 85% of adolescents. Acne can be regarded as an indicator disease of exaggerated insulinotropic western nutrition. Especially milk and whey protein-based products contribute to elevations of postprandial insulin and basal insulin-like growth factor-I (IGF-I) plasma levels. It is the evolutional principle of mammalian milk to promote growth and support anabolic conditions for the neonate during the nursing period. Whey proteins are most potent inducers of glucose-dependent insulinotropic polypeptide secreted by enteroendocrine K cells which in concert with hydrolyzed whey protein-derived essential amino acids stimulate insulin secretion of pancreatic β-cells. Increased insulin/IGF-I signaling activates the phosphoinositide-3 kinase/Akt pathway, thereby reducing the nuclear content of the transcription factor FoxO1, the key nutrigenomic regulator of acne target genes. Nuclear FoxO1 deficiency has been linked to all major factors of acne pathogenesis, i.e. androgen receptor transactivation, comedogenesis, increased sebaceous lipogenesis, and follicular inflammation. The elimination of the whey protein-based insulinotropic mechanisms of milk will be the most important future challenge for nutrition research. Both, restriction of milk consumption or generation of less insulinotropic milk will have an enormous impact on the prevention of epidemic western diseases like obesity, diabetes mellitus, cancer, neurodegenerative diseases and acne. Copyright © 2011 S. Karger AG, Basel.

positive: High school dietary dairy intake and teenage acne. BACKGROUND: Previous studies suggest possible associations between Western diet and acne. We examined data from the Nurses Health Study II to retrospectively evaluate whether intakes of dairy foods during high school were associated with physician-diagnosed severe teenage acne. METHODS: We studied 47,355 women who completed questionnaires on high school diet in 1998 and physician-diagnosed severe teenage acne in 1989. We estimated the prevalence ratios and 95% confidence intervals of acne history across categories of intakes. RESULTS: After accounting for age, age at menarche, body mass index, and energy intake, the multivariate prevalence ratio (95% confidence intervals; P value for test of trend) of acne, comparing extreme categories of intake, were: 1.22 (1.03, 1.44; .002) for total milk; 1.12 (1.00, 1.25; .56) for whole milk; 1.16 (1.01, 1.34; .25) for low-fat milk; and 1.44 (1.21, 1.72; .003) for skim milk. Instant breakfast drink, sherbet, cottage cheese, and cream cheese were also positively associated with acne. CONCLUSION: We found a positive association with acne for intake of total milk and skim milk. We hypothesize that the association with milk may be because of the presence of hormones and bioactive molecules in milk.

positive: Milk consumption and acne in adolescent girls. There has been a remarkable paucity of evidence for an association between diet and acne. Our previous studies suggest that there is an association between milk intake and teenage acne. This is a prospective cohort study to evaluate that relationship. We studied 6,094 girls, aged 9-15 years in 1996, who reported dietary intake on up to three food frequency questionnaires from 1996 to 1998. Presence and severity of acne was assessed by questionnaire in 1999. We computed multivariate prevalence ratios (PR) and 95 percent confidence intervals for acne. After accounting for age at baseline, height and energy intake, the multivariate PRs (95 % CI; p-value for test of trend) for acne comparing highest (2 or more servings per day) to lowest (<1 per week) intake categories in 1996, were 1.20 (1.09, 1.31; <0.001) for total milk, 1.19 (1.06, 1.32; <0.001) for whole milk, 1.17 (1.04, 1.31; 0.002) for low fat milk and 1.19 (1.08, 1.31; <0.001) for skim milk. This result did not change appreciably when we excluded girls who reported use of contraceptives and when we restricted our analysis to those younger than 11 years of age at baseline. We found a positive association between intake of milk and acne. This finding supports earlier studies and suggests that the metabolic effects of milk are sufficient to elicit biological responses in consumers.

positive: Milk consumption and acne in teenaged boys Objective We sought to examine the association between dietary dairy intake and teenaged acne among boys. Methods This was a prospective cohort study. We studied 4273 boys, members of a prospective cohort study of youths and of lifestyle factors, who reported dietary intake on up to 3 food frequency questionnaires from 1996 to 1998 and teenaged acne in 1999. We computed multivariate prevalence ratios and 95% confidence intervals for acne. Results After adjusting for age at baseline, height, and energy intake, the multivariate prevalence ratios (95% confidence interval; P value for test of trend) for acne comparing highest (>2 servings/d) with lowest (<1/wk) intake categories in 1996 were 1.16 (1.01, 1.34; 0.77) for total milk, 1.10 (0.94, 1.28; 0.83) for whole/2% milk, 1.17 (0.99, 1.39; 0.08) for low-fat (1%) milk, and 1.19 (1.01, 1.40; 0.02) for skim milk. Limitations Not all members of the cohort responded to the questionnaire. Acne assessment was by self-report and boys whose symptoms might have been part of an underlying disorder were not excluded. We did not adjust for steroid use and other lifestyle factors that may affect occurrence of acne. Conclusion We found a positive association between intake of skim milk and acne. This finding suggests that skim milk contains hormonal constituents, or factors that influence endogenous hormones, in sufficient quantities to have biological effects in consumers.

positive: Beta-casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Casomorphins are the most important during the first year of life, when postnatal formation is most active and milk is the main source of both nutritive and biologically active material for infants. This study was conducted on a total of 90 infants, of which 37 were fed with breast milk and 53 were fed with formula containing cow milk. The study has firstly indicated substances with immunoreactivity of human (irHCM) and bovine (irBCM) beta-casomorphins-7 in blood plasma of naturally and artificially fed infants, respectively. irHCM and irBCM were detected both in the morning before feeding (basal level), and 3h after feeding. Elevation of irHCM and irBCM levels after feeding was detected mainly in infants in the first 3 months of life. Chromatographic characterization of the material with irBCM has demonstrated that it has the same molecular mass and polarity as synthetic bovine beta-casomorphin-7. The highest basal irHCM was observed in breast-fed infants with normal psychomotor development and muscle tone. In contrast, elevated basal irBCM was found in formula-fed infants showing delay in psychomotor development and heightened muscle tone. Among formula-fed infants with normal development, the rate of this parameter directly correlated to basal irBCM. The data indicate that breast feeding has an advantage over artificial feeding for infants' development during the first year of life and support the hypothesis for deterioration of bovine casomorphin elimination as a risk factor for delay in psychomotor development and other diseases such as autism.

positive: The influence of μ-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs). Milk is one of the main source of biologically-active peptides that may function as regulatory substances called food hormones. After passing the gut-blood barrier, the μ-opioid receptor agonist and antagonist peptides may become the new factors influencing various functions of the human organism. The aim of the conducted research was to determine the influence of μ-opioid receptor agonist peptides: human and bovine β-casomorphin-7 (h/bBCM-7) and antagonistic peptides: casoxin-6 and- D (CXN-6/D) on proliferation and cytokine secretion of human peripheral blood mononuclear cells (PBMCs). The PBMCs proliferation was measured by the use of the BrdU test, which assesses the DNA synthesis activity and the WST-1 test which assesses the activity of mitochondrial dehydrogenase enzymes. The influence of all the investigated peptides on secretion of IL-4, IL-8, IL-13 and IFN-γ was determined by the use of the ELISA tests. Incubating the cells with the peptides has not caused any changes to their enzymatic activity, which has been proved by a WST-1 test. When using a BrdU test, however, it has been observed that there appear changes to proliferation of PBMCs correlated to amounts of bromodeoxyuridine incorporated into the cellular DNA. Moreover, changes to secretion of IL-4 and IL-13 by the cells under the influence of agonists were detected, as well as changes to secretion of IFN-gamma under the influence of all the examined substances. The obtained results provide information on immunomodulatory effects of food-derived opioid peptides, which may be of clinical significance especially in the case of allergic diseases in newborns. Copyright © 2010 Elsevier Inc. All rights reserved.

positive: Relation of beta-casomorphin to apnea in sudden infant death syndrome. Sudden infant death syndrome (SIDS) is the most common cause of death in infants and its pathogenesis is complex and multifactorial. The aim of this review is to summarize recent novel findings regarding the possible association of beta-casomorphin (beta-CM) to apnea in SIDS, which has not been widely appreciated by pediatricians and scientists. beta-CM is an exogenous bioactive peptide derived from casein, a major protein in milk and milk products, which has opioid activity. Mechanistically, circulation of this peptide into the infant's immature central nervous system might inhibit the respiratory center in the brainstem leading to apnea and death. This paper will review the possible relationship between beta-CM and SIDS in the context of passage of beta-CM through the gastrointestinal tract and the blood-brain barrier (BBB), permeability of the BBB to peptides in infants, and characterization of the casomorphin system in the brain.

positive: Post-diagnosis dietary factors and survival after invasive breast cancer Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.

positive: Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.

positive: Manufactured uncertainty: protecting public health in the age of contested science and product defense. The strategy of "manufacturing uncertainty" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called "product defense" or "litigation support." As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.

positive: Some subgroups of reproductive age women in the United States may be at risk for iodine deficiency. Consuming an adequate amount of iodine during pregnancy is critical for fetal neurologic development. Even a mild deficiency can impair cognitive ability. Important sources of iodine in the United States include dairy products and iodized salt. Although the U.S. population has traditionally been considered iodine sufficient, median urinary iodine concentrations (UIC) have decreased 50% since the 1970s. We analyzed 2001-2006 NHANES data from urine iodine spot tests for pregnant (n = 326), lactating (n = 53), and nonpregnant, nonlactating (n = 1437) women of reproductive age (15-44 y). We used WHO criteria to define iodine sufficiency (median UIC: 150-249 microg/L among pregnant women; >or=100 microg/L among lactating women; and 100-199 microg/L among nonpregnant, nonlactating women). The iodine status of pregnant women was borderline sufficient (median UIC = 153 microg/L; 95% CI = 105-196), while lactating (115 microg/L; 95% CI = 62-162) and nonpregnant, nonlactating (130 microg/L; 95% CI = 117-140) women were iodine sufficient. Dairy product consumption was an important contributor to iodine status among both pregnant and nonpregnant, nonlactating women, and those who do not consume dairy products may be at risk for iodine deficiency. Although larger samples are needed to confirm these findings, these results raise concerns about the iodine status of pregnant women and women of reproductive age who are not consuming dairy products. Iodine levels among U.S. women should be monitored, particularly among subgroups at risk for iodine deficiency.

positive: Iodine Status and Thyroid Function of Boston-Area Vegetarians and Vegans Context: Adequate dietary iodine is required for normal thyroid function. The iodine status and thyroid function of U.S. vegetarians and vegans have not been previously studied. Environmental perchlorate and thiocyanate (inhibitors of thyroid iodine uptake) exposures may adversely affect thyroid function. Objective: The objective of the study was to assess the iodine status and thyroid function of U.S. vegetarians (consume plant based products, eggs, milk; abstain from meat, poultry, fish, shellfish) and vegans (avoid all animal products) and whether these may be affected by environmental perchlorate and thiocyanate exposures. Design and Setting: This was a cross-sectional assessment of urinary iodine, perchlorate, and thiocyanate concentrations and serum thyroid function in Boston-area vegetarians and vegans. Subjects: One hundred forty-one subjects (78 vegetarians, 63 vegans) were recruited; one vegan was excluded. Results: Median urinary iodine concentration of vegans (78.5 μg/liter; range 6.8–964.7 μg/liter) was lower than vegetarians (147.0 μg/liter; range 9.3–778.6 μg/liter) (P < 0.01). Adjusted for cigarette smoking (confirmed by urinary cotinine levels) and thiocyanate-rich food consumption, median urinary thiocyanate concentration of vegans (630 μg/liter; range 108-3085 μg/liter) was higher than vegetarians (341 μg/liter; range 31–1963 μg/liter) (P < 0.01). There were no between-group differences in urinary perchlorate concentrations (P = 0.75), TSH (P = 0.46), and free T4 (P = 0.77). Urinary iodine, perchlorate, and thiocyanate levels were not associated with TSH (P = 0.59) or free T4 (P = 0.14), even when adjusted for multiple variables. Conclusions: U.S. vegetarians are iodine sufficient. U.S. vegans may be at risk for low iodine intake, and vegan women of child-bearing age should supplement with 150 μg iodine daily. Environmental perchlorate and thiocyanate exposures are not associated with thyroid dysfunction in these groups.

positive: Association between isolation of Staphylococcus aureus one week after calving and milk yield, somatic cell count, clinical mastitis, and culling th... Cows with isolation of Staphylococcus aureus approximately 1 week after calving and milk yield, somatic cell count (SCC), clinical mastitis (CM), and culling risk through the remaining lactation were assessed in 178 Norwegian dairy herds. Mixed models with repeated measures were used to compare milk yield and SCC, and survival analyses were used to estimate the hazard ratio for CM and culling. On average, cows with an isolate of Staph. aureus had a significantly higher SCC than culture-negative cows. If no post-milking teat disinfection (PMTD) was used, the mean values of SCC were 42,000, 61,000, 68,000 and 77,000 cells/ml for cows with no Staph. aureus isolate, with Staph. aureus isolated in 1 quarter, in 2 quarters and more than 2 quarters respectively. If iodine PMTD was used, SCC means were 36,000; 63,000; 70,000 and 122,000, respectively. Primiparous cows testing positive for Staph. aureus had the same milk yield curve as culture-negative cows, except for those with Staph. aureus isolated in more than 2 quarters. They produced 229 kg less during a 305-d lactation. Multiparous cows with isolation of Staph. aureus in at least 1 quarter produced 94-161 kg less milk in 2nd and >3rd parity, respectively, and those with isolation in more than 2 quarters produced 303-390 kg less than multiparous culture-negative animals during a 305-d lactation. Compared with culture-negative cows, the hazard ratio for CM and culling in cows with isolation of Staph. aureus in at least 1 quarter was 2.0 (1.6-2.4) and 1.7 (1.5-1.9), respectively. There was a decrease in the SCC and in the CM risk in culture-negative cows where iodine PMTD had been used, indicating that iodine PMTD has a preventive effect on already healthy cows. For cows testing positive for Staph. aureus in more than 2 quarters at calving, iodine PMTD had a negative effect on the CM risk and on the SCC through the remaining lactation.

positive: Cretinism revisited. Endemic cretinism includes two syndromes: a more common neurological disorder with brain damage, deaf mutism, squint and spastic paresis of the legs and a less common syndrome of severe hypothyroidism, growth retardation and less severe mental defect. Both conditions are due to dietary iodine deficiency and can be prevented by correction of iodine deficiency before pregnancy. Endemic cretinism is now included in the spectrum of the effects of iodine deficiency in a population termed the 'iodine deficiency disorders (IDDs)', which also includes a wide range of lesser degrees of cognitive defect that can be prevented by the correction of iodine deficiency. Iodine deficiency is now recognised by the World Health Organization (WHO) as the most common preventable cause of brain damage with in excess of 2 billion at risk from 130 countries. A global United Nations (UN) programme of prevention has achieved 68% household usage of iodised salt by the year 2000 compared with less than 20% prior to 1990. Copyright 2009 Elsevier Ltd. All rights reserved.

positive: Does milk increase mucus production? Excessive milk consumption has a long association with increased respiratory tract mucus production and asthma. Such an association cannot be explained using a conventional allergic paradigm and there is limited medical evidence showing causality. In the human colon, beta-casomorphin-7 (beta-CM-7), an exorphin derived from the breakdown of A1 milk, stimulates mucus production from gut MUC5AC glands. In the presence of inflammation similar mucus overproduction from respiratory tract MUC5AC glands characterises many respiratory tract diseases. beta-CM-7 from the blood stream could stimulate the production and secretion of mucus production from these respiratory glands. Such a hypothesis could be tested in vitro using quantitative RT-PCR to show that the addition of beta-CM-7 into an incubation medium of respiratory goblet cells elicits an increase in MUC5AC mRNA and by identifying beta-CM-7 in the blood of asthmatic patients. This association may not necessarily be simply cause and effect as the person has to be consuming A1 milk, beta-CM-7 must pass into the systemic circulation and the tissues have to be actively inflamed. These prerequisites could explain why only a subgroup of the population, who have increased respiratory tract mucus production, find that many of their symptoms, including asthma, improve on a dairy elimination diet. (c) 2009 Elsevier Ltd. All rights reserved.

positive: Calcium absorption in Australian osteopenic post-menopausal women: an acute comparative study of fortified soymilk to cows' milk. Calcium loss after menopause increases the risk of osteoporosis in aging women. Soymilk is often consumed to reduce menopausal symptoms, although in its native form, it contains significantly less calcium than cow's milk. Moreover, when calcium is added as a fortificant, it may not be absorbed efficiently. This study compares calcium absorption from soymilk fortified with a proprietary phosphate of calcium versus absorption from cow's milk. Preliminary studies compared methods for labelling the calcium fortificant either before or after its addition to soymilk. It was established that fortificant labelled after it was added to soymilk had a tracer distribution pattern very similar to that shown by fortificant labelled before adding to soymilk, provided a heat treatment (90?C for 30 min) was applied. This method was therefore used for further bioavailability studies. Calcium absorption from fortified soy milk compared to cow's milk was examined using a randomised single-blind acute cross-over design study in 12 osteopenic post-menopausal women aged (mean +/- SD) 56.7+/-5.3 years, with a body mass index of 26.5+/-5.6 kg/m2. Participants consumed 20 mL of test milk labelled after addition of fortificant with 185 kBq of 45Ca in 44 mg of calcium carrier, allowing the determination of the hourly fractional calcium absorption rate (alpha) using a single isotope radiocalcium test. The mean hourly fractional calcium absorption from fortified soymilk was found to be comparable to that of cows' milk: alpha = 0.65+/-0.19 and alpha =0.66+/-0.22, p>0.05, respectively.

positive: Vegetarian diets and public health: biomarker and redox connections. Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.

positive: The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.

positive: Acne, dairy and cancer A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.

positive: Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows. BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.

positive: Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women. The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.

positive: Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence. OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.

positive: Consumption of animal products, their nutrient components and postmenopausal circulating steroid hormone concentrations. BACKGROUND/OBJECTIVES: Little is known about nutritional factors that influence circulating concentrations of steroid hormones, which are consistently associated with risk of breast cancer for postmenopausal women. We aimed to investigate the association between consumption of animal products and the plasma concentrations of steroid hormones and sex hormone-binding globulin (SHBG). SUBJECTS/METHODS: Cross-sectional analysis was conducted on plasma from 766 naturally postmenopausal women. We measured plasma concentrations of steroid hormones and SHBG, and estimated dietary intakes using a 121-item food frequency questionnaire. Log-transformed values of hormone concentrations were regressed on quartiles of intake of meat and dairy products among food items, and fats, proteins and cholesterol among nutrient intake. RESULTS: Total red and fresh red meat consumption was negatively associated with SHBG levels (P for trend=0.04 and <0.01, respectively). Mean SHBG concentrations were approximately 8% and 13% lower for women in the highest quartile compared with the lowest quartile of total red and fresh red meat consumption, respectively. Positive associations were observed between dairy product consumption and total and free estradiol concentrations (P for trend=0.02 and 0.03, respectively). Mean concentrations of total and free estradiol were 15 and 14% higher for women in the highest quartile of dairy product consumption than for those in the lowest quartile, respectively. No associations were observed with consumption of processed meat, chicken, fish, eggs, cholesterol, fats or protein. CONCLUSIONS: Our study suggests that greater consumption of total red and fresh red meat and dairy products might influence circulating concentrations of SHBG and estradiol, respectively. Confirmation and further investigation is required.

positive: Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal. BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.

positive: Humoral immunity to cow's milk proteins and gliadin within the etiology of recurrent aphthous ulcers? OBJECTIVES: The goal of this study was to determine the incidence of serum antibodies to gliadin and to cow's milk proteins (CMP) using ELISA test, within patients who have recurrent aphthous ulcers (RAU). SUBJECTS AND METHODS: Fifty patients with recurrent aphthous ulcers and fifty healthy people were included in this research. Levels of serum IgA and IgG antibodies to gliadin and IgA, IgG and IgE to CMP were determined using ELISA. RESULTS: The levels of serum antigliadin IgA and IgG antibodies were not significantly higher in patients with RAU in comparison with the controls (P = 0.937 and P = 0.1854 respectively). The levels of serum anti-CMP IgA, IgG and IgE antibodies were significantly higher in patients with RAU in comparison with the controls (P < 0.005, P < 0.002 and P < 0.001 respectively). In general, the increased humoral (IgA or IgG) immunoreactivity to CMP was found in 32 of 50 patients, while 17 of them showed the increased levels of both IgA and IgG immunoreactivity to CMP. At the same time, 16 out of 50 patients had IgA, IgG and IgE immunoreactivity to CMP. CONCLUSION: These results indicate the strong association between high levels of serum anti-CMP IgA, IgG and IgE antibodies and clinical manifestations of recurrent aphthous ulcers.

positive: Veganism, bone mineral density, and body composition: a study in Buddhist nuns. SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P < 0.001); however, there was no significant correlation between dietary calcium and BMD. Further analysis suggested that whole body BMD, but not lumbar spine or femoral neck BMD, was positively correlated with the ratio of animal protein to vegetable protein. CONCLUSION: These results suggest that, although vegans have much lower intakes of dietary calcium and protein than omnivores, veganism does not have adverse effect on bone mineral density and does not alter body composition.

positive: Milk consumption: aggravating factor of acne and promoter of chronic diseases of Western societies. Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies.

positive: Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.

positive: Quantitative measurement of endogenous estrogen metabolites, risk-factors for development of breast cancer, in commercial milk products by LC-MS/MS. Increased levels of estrogen metabolites (EM) are associated with cancers of the reproductive system. One potential dietary source of EM is milk. In this study, the absolute quantities of unconjugated (free) and unconjugated plus conjugated (total) EM were measured in a variety of commercial milks (whole, 2%, skim, and buttermilk). The results show that the milk products tested contain considerable levels of EM; however, the levels of unconjugated EM in skim milk were substantially lower than that observed in whole milk, 2% milk, and buttermilk. Whole milk contained the lowest overall levels of EM while buttermilk contained the highest. As anticipated, soy milk did not contain the mammalian EM measured using this method. The relatively high levels of catechol estrogens detected in milk products support the theory that milk consumption is a source of EM and their ingestion may have a dietary influence on cancer risk.

positive: Recent advances in berry supplementation and age-related cognitive decline. PURPOSE OF REVIEW: To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. RECENT FINDINGS: Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effects of berries on the central nervous system, recent studies have demonstrated the bioavailability of berry polyphenols in several animal models. These studies have revealed that flavonoids and polyphenols from berries do accumulate in the brain following long-term consumption. Finally, several compelling studies have revealed that berries can influence cell-signaling cascades both in vivo and in cell culture systems. These studies underscore the developing theory that berries and antioxidant-rich foods may be acting as more than just oxygen radical neutralizers in the aging central nervous system. SUMMARY: Antioxidant-rich berries consumed in the diet can positively impact learning and memory in the aged animal. This effect on cognition is thought to be due to the direct interaction of berry polyphenols with aging neurons, reducing the impact of stress-related cellular signals and increasing the capacity of neurons to maintain proper functioning during aging.

positive: Antioxidant status in humans after consumption of blackberry (Rubus fruticosus L.) juices with and without defatted milk. The present study was designed to evaluate the possible effect of the consumption of blackberry juices (BJ) prepared with water (BJW) and defatted milk (BJM) on the plasma antioxidant capacity and the enzymatic and nonenzymatic antioxidants. A significant (p < 0.05) increase in the ascorbic acid content in the plasma was observed after intake of both BJs. However, no changes were observed in the plasma urate and alpha-tocopherol levels. An increase on the plasma antioxidant capacity, by ORAC assay, was observed only after consumption of BJW but not statistically significant. Plasma antioxidant capacity had a good positive correlation with ascorbic acid (r = 0.93) and a negative correlation with urate level (r = -0.79). No correlation was observed between antioxidant capacity and total cyanidin or total ellagic acid contents. Further, it was observed that plasma catalase increased following intake of BJ's. No change was observed on the plasma and erythrocyte CAT and glutathione peroxidase activities. A significant decrease (p < 0.05) in the urinary antioxidant capacity between 1 and 4 h after intake of both BJs was observed. A good correlation was observed between total antioxidant capacity and urate and total cyanidin levels. These results suggested association between anthocyanin levels and CAT and a good correlation between antioxidant capacity and ascorbic acid in the human plasma after intake of BJs. Follow-up studies investigating the antioxidant properties and health benefits are necessary to demonstrate the health benefits of polyphenols.

positive: Addition of milk prevents vascular protective effects of tea. AIMS: Experimental and clinical studies indicate that tea exerts protection against cardiovascular diseases. However, a question of much debate is whether addition of milk modifies the biological activities of tea. We studied the vascular effects of tea, with or without milk, in humans and elucidated the impact of individual milk proteins in cell culture experiments, with isolated rat aortic rings and by HPLC analysis. METHODS AND RESULTS: A total of 16 healthy female volunteers consumed either 500 mL of freshly brewed black tea, black tea with 10% skimmed milk, or boiled water as control. Flow-mediated dilation (FMD) was measured by high-resolution vascular ultrasound before and 2 h after consumption. Black tea significantly improved FMD in humans compared with water, whereas addition of milk completely blunted the effects of tea. To support these findings, similar experiments were performed in isolated rat aortic rings and endothelial cells. Tea induced vasorelaxation in rat aortic rings and increased the activity of endothelial nitric oxide synthase by phosphorylation of the enzyme in endothelial cells. All effects were completely inhibited by the addition of milk to tea. Of the various kinds of milk proteins, the caseins accounted for these inhibiting effects of milk, probably by formation of complexes with tea catechins. CONCLUSION: Milk counteracts the favourable health effects of tea on vascular function. This finding indicates the need for particular awareness in the interpretation and design of studies comprising nutritional flavonoids.

positive: Antioxidant activity of blueberry fruit is impaired by association with milk. The antioxidant properties of dietary phenolics are believed to be reduced in vivo because of their affinity for proteins. In this study we assessed the bioavailability of phenolics and the in vivo plasma antioxidant capacity after the consumption of blueberries (Vaccinium corymbosum L.) with and without milk. In a crossover design, 11 healthy human volunteers consumed either (a) 200 g of blueberries plus 200 ml of water or (b) 200 g of blueberries plus 200 ml of whole milk. Venous samples were collected at baseline and at 1, 2, and 5 h postconsumption. Ingestion of blueberries increased plasma levels of reducing and chain-breaking potential (+6.1%, p<0.001; +11.1%, p<0.05) and enhanced plasma concentrations of caffeic and ferulic acid. When blueberries and milk were ingested there was no increase in plasma antioxidant capacity. There was a reduction in the peak plasma concentrations of caffeic and ferulic acid (-49.7%, p<0.001, and -19.8%, p<0.05, respectively) as well as the overall absorption (AUC) of caffeic acid (p<0.001). The ingestion of blueberries in association with milk, thus, impairs the in vivo antioxidant properties of blueberries and reduces the absorption of caffeic acid.

positive: Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain. Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.

positive: The environmental and public health risks associated with arsenical use in animal feeds. Arsenic exposures contribute significantly to the burden of preventable disease worldwide, specifically related to increased risks of cancer, diabetes, and cardiovascular disease. Most exposures are associated with natural contamination of groundwater, which is difficult to mitigate when these sources are used for drinking water. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China, among many countries. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals. Land disposal of these wastes can contaminate surface and ground water, and the conversion of animal wastes into fertilizer pellets for home use as well as the introduction of animal waste incinerators may increase opportunities for exposure. As an intentional additive to animal feed, use of arsenical drugs is a preventable source of human exposure. The domestic practice of using these drugs in poultry production has been the subject of media attention and limited research, though the use of these drugs in domestic swine production and in the rapidly growing foreign animal production industry remains largely uncharacterized. This continued expansion of arsenical drug use may likely increase the burden of global human arsenic exposure and risk.

positive: PCBs Enhance Collagen I Expression from Human Peritoneal Fibroblasts Objective To test the effect of four polychlorinated biphenyl congeners (PCB-77, PCB-105, PCB 153 and PCB 180) on expression of three adhesion markers, TGF-β1, VEGF, and type I collagen in normal human peritoneal and adhesion fibroblasts Design Cell culture study Settings University Research Laboratory Patients Primary cultures of normal peritoneal and adhesion fibroblasts were established from three patients. Interventions Fibroblasts were treated with PCB-77, PCB-105, PCB-153 or PCB-180, 20 ppm for 24 hours. Total RNA was extracted from each treatment and subjected to real-time RT/PCR. Main Outcome and Measures mRNA levels of type I collagen, VEGF and TGF-β1. Results Normal human peritoneal fibroblasts expressed type I collagen, VEGF and TGF-β1. Exposure of normal human fibroblasts to PCB-77, PCB-105, PCB-153 or PCB-180 did not affect mRNA levels of β-actin, the house keeping gene used to normalized RNA levels for the real-time RT/PCR, nor did it affect cell viability as assessed by trypan blue exclusion. PCB treatments, compared to control, resulted in no significant change for TGF-β1 or VEGF mRNA levels, in normal peritoneal and adhesion fibroblasts. In marked contrast, type I collagen mRNA levels were markedly increased in response to the brief 24 hrs exposure to each PCB, treatment each (P<0.0001) in both cell types. Conclusion The finding that PCB-77, PCB-105, PCB-153 or PCB-180 increased the expression of type I collagen in human normal peritoneal and adhesion fibroblasts is the first demonstration of involvement of organochlorines in the pathogenesis of tissue fibrosis. This may implicate organochlorine exposure as an etiologic factor in a wide variety of previously unlinked human ailments characterized by fibrosis.

positive: Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis. Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.

positive: 2,3,7,8-Tetrachlorodibenzo-p-dioxin in maternal breast milk and newborn head circumference. Dioxins are known to affect infant growth and neurodevelopment in both humans and animals. In this study, we examined the relationship between neonatal head circumference, which is related to fetal brain development, and the concentration of dioxins in breast milk as an indicator of maternal exposure. A total of 42 milk samples were obtained on the fifth to eighth postpartum day from mothers in Japan exposed to dioxins in the environment. The levels of seven dioxins and 10 furan isomers were measured in each milk sample using an HR-GC/MS system. The relationships between the concentration of each dioxin isomer and newborn size, including head circumference, were then investigated after adjustment for confounding factors. The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin isomer, negatively correlated with newborn head circumference, even after adjustment for gestational age, infant sex, parity and other confounding factors. However, there were no significant relationships between the concentration of other dioxin and furan isomers in maternal breast milk and infant height, weight and chest circumference at birth. These facts suggested that fetal brain development might be influenced by maternal exposure to TCDD in the environment.

positive: Dioxin May Promote Inflammation-Related Development of Endometriosis Laboratory and population-based studies suggest that exposure to environmental toxicants may be one of several triggers for the development of endometriosis. We discuss evidence that modulation of the endometrial endocrine-immune interface could mechanistically link toxicant exposure to the development of this disease. Capsule Summary: Environmental toxicant exposure induces an inflammatory-like endometrial response that may promote the development of endometriosis.

positive: Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey. The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.

positive: Genistein inhibits differentiation of primary human adipocytes. Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.

positive: Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford. BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.

positive: Diet and acne. Acne is caused by the action of dihydrotestosterone, derived from endogenous and exogenous precursors, likely acting synergistically with insulin-like growth factor-1. These sources and interactions are discussed. Both a mechanism of action and recommended dietary changes that limit ingestion and production of these hormones are proposed.

positive: Effective Heat Inactivation of Mycobacterium avium subsp. paratuberculosis in Raw Milk Contaminated with Naturally Infected Feces The effectiveness of high-temperature, short holding time (HTST) pasteurization and homogenization with respect to inactivation of Mycobacterium avium subsp. paratuberculosis was evaluated quantitatively. This allowed a detailed determination of inactivation kinetics. High concentrations of feces from cows with clinical symptoms of Johne's disease were used to contaminate raw milk in order to realistically mimic possible incidents most closely. Final M. avium subsp. paratuberculosis concentrations varying from 102 to 3.5 × 105 cells per ml raw milk were used. Heat treatments including industrial HTST were simulated on a pilot scale with 22 different time-temperature combinations, including 60 to 90°C at holding (mean residence) times of 6 to 15 s. Following 72°C and a holding time of 6 s, 70°C for 10 and 15 s, or under more stringent conditions, no viable M. avium subsp. paratuberculosis cells were recovered, resulting in >4.2- to >7.1-fold reductions, depending on the original inoculum concentrations. Inactivation kinetic modeling of 69 quantitative data points yielded an Ea of 305,635 J/mol and an lnk0 of 107.2, corresponding to a D value of 1.2 s at 72°C and a Z value of 7.7°C. Homogenization did not significantly affect the inactivation. The conclusion can be drawn that HTST pasteurization conditions equal to 15 s at ≥72°C result in a more-than-sevenfold reduction of M. avium subsp. paratuberculosis.

positive: Microbial and sensory changes throughout the ripening of Prato cheese made from milk with different levels of somatic cells. The objective of this research was to evaluate the effects of 2 levels of raw milk somatic cell count (SCC) on the composition of Prato cheese and on the microbiological and sensory changes of Prato cheese throughout ripening. Two groups of dairy cows were selected to obtain low-SCC (<200,000 cells/mL) and high-SCC (>700,000 cells/mL) milks, which were used to manufacture 2 vats of cheese. The pasteurized milk was evaluated according to the pH, total solids, fat, total protein, lactose, standard plate count, coliforms at 45 degrees C, and Salmonella spp. The cheese composition was evaluated 2 d after manufacture. Lactic acid bacteria, psychrotrophic bacteria, and yeast and mold counts were carried out after 3, 9, 16, 32, and 51 d of storage. Salmonella spp., Listeria monocytogenes, and coagulase-positive Staphylococcus counts were carried out after 3, 32, and 51 d of storage. A 2 x 5 factorial design with 4 replications was performed. Sensory evaluation of the cheeses from low- and high-SCC milks was carried out for overall acceptance by using a 9-point hedonic scale after 8, 22, 35, 50, and 63 d of storage. The somatic cell levels used did not affect the total protein and salt:moisture contents of the cheeses. The pH and moisture content were higher and the clotting time was longer for cheeses from high-SCC milk. Both cheeses presented the absence of Salmonella spp. and L. monocytogenes, and the coagulase-positive Staphylococcus count was below 1 x 10(2) cfu/g throughout the storage time. The lactic acid bacteria count decreased significantly during the storage time for the cheeses from both low- and high-SCC milks, but at a faster rate for the cheese from high-SCC milk. Cheeses from high-SCC milk presented lower psychrotrophic bacteria counts and higher yeast and mold counts than cheeses from low-SCC milk. Cheeses from low-SCC milk showed better overall acceptance by the consumers. The lower overall acceptance of the cheeses from high-SCC milk may be associated with texture and flavor defects, probably caused by the higher proteolysis of these cheeses.

positive: Methanol extract of the seaweed Gloiopeltis furcata induces G2/M arrest and inhibits cyclooxygenase-2 activity in human hepatocarcinoma HepG2 cells. It was previously reported that a methanol extract of Gloiopeltis furcata (MEGF), a kind of edible seaweed, inhibited the growth of several human cancer cell lines. In the present study, the effect of MEGF on the growth of human hepatocarcinoma HepG2 cells and its effect on the cyclooxygenases (COXs) expression were investigated. MEGF markedly reduced the viability of HepG2 cells and induced the G2/M arrest of the cell cycle in a concentration dependent manner. These effects were associated with the down-regulation of cyclin A, up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) and dephosphorylation of Cdc25C. Furthermore, it was found that MEGF decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E(2) (PGE(2)) synthesis. These findings indicate that MEGF may have a possible therapeutic potential in hepatoma cancer patients.

positive: Arsenic in seaweed--forms, concentration and dietary exposure. This study has measured the content of total and inorganic forms of arsenic in seaweed available on retail sale for consumption, to provide data for dietary exposure estimates and to support advice to consumers. A total of 31 samples covering five varieties of seaweed were collected from various retail outlets across London and the internet. All of the samples were purchased as dried product. For four of the five varieties, soaking was advised prior to consumption. The recommended method of preparation for each individual sample was followed, and total and inorganic arsenic were analysed both before and after preparation. The arsenic remaining in the water used for soaking was also measured. Arsenic was detected in all samples with total arsenic at concentrations ranging from 18 to 124 mg/kg. Inorganic arsenic, which can cause liver cancer, was only found in the nine samples of hijiki seaweed that were analysed, at concentrations in the range 67-96 mg/kg. Other types of seaweed were all found to contain less than 0.3mg/kg inorganic arsenic, which was the limit of detection for the method used. Since consumption of hijiki seaweed could significantly increase dietary exposure to inorganic arsenic, the UK Food Standards Agency (FSA) issued advice to consumers to avoid eating it.

positive: Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford. OBJECTIVE: To compare fracture rates in four diet groups (meat eaters, fish eaters, vegetarians and vegans) in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). DESIGN: Prospective cohort study of self-reported fracture risk at follow-up. SETTING: The United Kingdom. SUBJECTS: A total of 7947 men and 26,749 women aged 20-89 years, including 19,249 meat eaters, 4901 fish eaters, 9420 vegetarians and 1126 vegans, recruited by postal methods and through general practice surgeries. METHODS: Cox regression. RESULTS: Over an average of 5.2 years of follow-up, 343 men and 1555 women reported one or more fractures. Compared with meat eaters, fracture incidence rate ratios in men and women combined adjusted for sex, age and non-dietary factors were 1.01 (95% CI 0.88-1.17) for fish eaters, 1.00 (0.89-1.13) for vegetarians and 1.30 (1.02-1.66) for vegans. After further adjustment for dietary energy and calcium intake the incidence rate ratio among vegans compared with meat eaters was 1.15 (0.89-1.49). Among subjects consuming at least 525 mg/day calcium the corresponding incidence rate ratios were 1.05 (0.90-1.21) for fish eaters, 1.02 (0.90-1.15) for vegetarians and 1.00 (0.69-1.44) for vegans. CONCLUSIONS: In this population, fracture risk was similar for meat eaters, fish eaters and vegetarians. The higher fracture risk in the vegans appeared to be a consequence of their considerably lower mean calcium intake. An adequate calcium intake is essential for bone health, irrespective of dietary preferences. SPONSORSHIP: The EPIC-Oxford study is supported by The Medical Research Council and Cancer Research UK.

positive: Effect of a Daily Supplement of Soy Protein on Body Composition and Insulin Secretion in Postmenopausal Women Objective: To determine if a supplement of soy protein improves body composition, body fat distribution, and glucose and insulin metabolism in non-diabetic postmenopausal women compared to an isocaloric casein placebo. Design: Randomized, double-blind, placebo-controlled 3-month trial Setting: Clinical Research Center Patients: 15 postmenopausal women Interventions: CT scans at L4/L5, dual energy x-ray absorptiometry (DXA), hyperglycemic clamps Main outcome measures: Total fat, total abdominal fat, visceral fat, subcutaneous abdominal fat, and insulin secretion. Results: Weight by DXA did not change between groups (+1.38 ± 2.02 kg for placebo vs. +0.756 ± 1.32 kg for soy, p=0.48, means ± S.D.). Total and subcutaneous abdominal fat increased more in the placebo compared to the soy group (for differences between groups in total abdominal fat: +38.62 ± 22.84 cm2 for placebo vs. −11.86 ± 31.48 cm2 for soy, p=0.005; subcutaneous abdominal fat: +22.91 ± 28.58 cm2 for placebo vs. −14.73 ± 22.26 cm2 for soy, p=0.013). Insulin secretion, visceral fat, total body fat, and lean mass did not differ between groups. Isoflavone levels increased more in the soy group. Conclusion: A daily supplement of soy protein prevents the increase in subcutaneous and total abdominal fat observed with an isocaloric casein placebo in postmenopausal women.

positive: Meat intake and bladder cancer risk in 2 prospective cohort studies. BACKGROUND: Nitrosamines, which are known bladder carcinogens, or their precursors are found in certain meat items, and concentrations of these compounds are especially high in bacon. Only 3 cohort studies, all with <100 case subjects, have examined the relation between meat intake and bladder cancer, and few studies have examined the relation of different meat types with bladder cancer. OBJECTIVE: The aim was to examine the association between specific meat items and bladder cancer in 2 large prospective studies. DESIGN: We analyzed data from 2 cohorts with up to 22 y of follow-up and 808 incident bladder cancer cases. Detailed data on meat were obtained from multiple food-frequency questionnaires administered over time. Multivariate relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards models with control for potential confounders, including detailed smoking history. RESULTS: Men and women with a high intake of bacon (>/=5 servings/wk) had an elevated risk of bladder cancer compared with those who never ate bacon (multivariate RR = 1.59; 95% CI = 1.06, 2.37), although the overall association was not statistically significant (P for trend = 0.06). However, the association with bacon was stronger and became statistically significant after the removal of individuals who indicated having "greatly" changed their red meat (men) or bacon (women) intake during the 10 y before baseline (multivariate RR = 2.10; 95% CI = 1.24, 3.55; P for trend = 0.006). A positive association was also detected for intake of chicken without skin, but not for chicken with skin or for other meats, including processed meats, hot dogs, and hamburgers. CONCLUSIONS: In these 2 cohorts combined, frequent consumption of bacon was associated with an elevated risk of bladder cancer. Other studies with data on specific meat items are necessary to confirm our findings.

positive: Adolescent milk fat and galactose consumption and testicular germ cell cancer. Recent case-control studies suggested that dairy product consumption is an important risk factor for testicular cancer. We examined the association between consumption of dairy products, especially milk, milk fat, and galactose, and testicular cancer in a population-based case-control study including 269 case and 797 controls (response proportions of 76% and 46%, respectively). Dietary history was assessed by food frequency questions for the index persons and through their mothers including diet 1 year before interview and diet at age 17 years. We used conditional logistic regression to calculate odds ratios as estimates of the relative risk (RR), 95% confidence intervals (95% CI), and to control for social status and height. The RR of testicular cancer was 1.37 (95% CI, 1.12-1.68) per additional 20 servings of milk per month (each 200 mL) in adolescence. This elevated overall risk was mainly due to an increased risk for seminoma (RR, 1.66; 95% CI, 1.30-2.12) per additional 20 milk servings per month. The RR for seminoma was 1.30 (95% CI, 1.15-1.48) for each additional 200 g milk fat per month and was 2.01 (95% CI, 1.41-2.86) for each additional 200 g galactose per month during adolescence. Our results suggest that milk fat and/or galactose may explain the association between milk and dairy product consumption and seminomatous testicular cancer.

positive: Dietary Mutagen Exposure and Risk of Pancreatic Cancer To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5—f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (Ptrend= 0.024). Ahigher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. Apossible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, Pinteraction= 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

positive: Animal food intake and cooking methods in relation to endometrial cancer risk in Shanghai We evaluated animal food intake and cooking methods in relation to endometrial cancer risk in a population-based case–control study in Shanghai, China. A validated food frequency questionnaire was used to collect the usual dietary habits of 1204 cases and 1212 controls aged 30–69 years between 1997 and 2003. Statistical analyses were based on an unconditional logistic regression model adjusting for potential confounders. High intake of meat and fish was associated with an increased risk of endometrial cancer, with adjusted odds ratios for the highest vs the lowest quartile groups being 1.7 (95% confidence interval: 1.3–2.2) and 2.4 (1.8–3.1), respectively. The elevated risk was observed for all types of meat and fish intake. Intake of eggs and milk was not related to risk. Cooking methods and doneness levels for meat and fish were not associated with risk, nor did they modify the association with meat and fish consumption. Our study suggests that animal food consumption may play an important role in the aetiology of endometrial cancer, but cooking methods have minimal influence on risk among Chinese women.

positive: A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland). High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.

positive: Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease. BACKGROUND: The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial. OBJECTIVE: We aimed to explore biomarkers of dairy fat intake in plasma and erythrocytes and to assess the hypothesis that higher concentrations of these biomarkers are associated with a greater risk of IHD in US women. DESIGN: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989-1990, 166 incident cases of IHD were ascertained between baseline and 1996. These cases were matched with 327 controls for age, smoking, fasting status, and date of blood drawing. RESULTS: Among controls, correlation coefficients between average dairy fat intake in 1986-1990 and 15:0 and trans 16:1n-7 content were 0.36 and 0.30 for plasma and 0.30 and 0.32 for erythrocytes, respectively. In multivariate analyses, with control for age, smoking, and other risk factors of IHD, women with higher plasma concentrations of 15:0 had a significantly higher risk of IHD. The multivariate-adjusted relative risks (95% CI) from the lowest to highest tertile of 15:0 concentrations in plasma were 1.0 (reference), 2.18 (1.20, 3.98), and 2.36 (1.16, 4.78) (P for trend = 0.03). Associations for other biomarkers were not significant. CONCLUSIONS: Plasma and erythrocyte contents of 15:0 and trans 16:1n-7 can be used as biomarkers of dairy fat intake. These data suggest that a high intake of dairy fat is associated with a greater risk of IHD.

positive: Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr cohort. BACKGROUND: Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link between cancer risk and dairy consumption in adulthood is increasing, but associations with childhood dairy consumption have not been studied adequately. OBJECTIVE: We investigated whether dairy consumption in childhood is associated with cancer incidence and mortality in adulthood. DESIGN: From 1937 through 1939, some 4,999 children living in England and Scotland participated in a study of family food consumption, assessed from 7-d household food inventories. The National Health Service central register was used to ascertain cancer registrations and deaths between 1948 and 2005 in the 4,383 traced cohort members. Per capita household intake estimates for dairy products and calcium were used as proxy for individual intake. RESULTS: During the follow-up period, 770 cancer registrations or cancer deaths occurred. High childhood total dairy intake was associated with a near-tripling in the odds of colorectal cancer [multivariate odds ratio: 2.90 (95% CI: 1.26, 6.65); 2-sided P for trend = 0.005] compared with low intake, independent of meat, fruit, and vegetable intakes and socioeconomic indicators. Milk intake showed a similar association with colorectal cancer risk. High milk intake was weakly inversely associated with prostate cancer risk (P for trend = 0.11). Childhood dairy intake was not associated with breast and stomach cancer risk; a positive association with lung cancer risk was confounded by smoking behavior during adulthood. CONCLUSIONS: A family diet rich in dairy products during childhood is associated with a greater risk of colorectal cancer in adulthood. Confirmation of possible underlying biological mechanisms is needed.

positive: Meat consumption and risk of breast cancer in the UK Women's Cohort Study We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86–1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86–1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14–2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer.

positive: Dairy products and risk of Parkinson’s disease The authors prospectively investigated the association between dairy intake and risk of Parkinson’s disease among 57,689 men and 73,175 women from the Cancer Prevention Study II Nutrition Cohort from the American Cancer Society. A total of 250 men and 138 women with Parkinson’s disease were identified during the follow-up (1992–2001). Dairy consumption was positively associated with the risk of Parkinson’s disease: compared with the lowest intake quintile, the corresponding relative risks (RRs) for quintiles 2–5 were 1.4, 1.4, 1.4, and 1.6 (95 percent confidence interval (CI): 1.1–2.2; p for trend=0.05). A higher risk among dairy consumers was found in both men and women, although the association in women appeared non-linear. The meta-analysis of all prospective studies confirmed a moderately elevated risk of Parkinson’s disease among individuals with high dairy consumption: the RRs between extreme intake categories were 1.6 (95 percent CI: 1.3–2.0) for men and women combined, 1.8 for men (95 percent CI: 1.4–2.4), and 1.3 for women (95 percent CI: 0.8–2.1). These data suggest that dairy consumption may increase the risk of Parkinson’s disease, particularly in men. More studies are needed to further examine these findings and to explore the underlying mechanisms.

positive: Cooked meat and risk of breast cancer--lifetime versus recent dietary intake. BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.

negative: Prevalence and public health significance of aluminum residues in milk and some dairy products. Sixty random samples of bulk farm milk, market milk, locally manufactured processed cheese, and milk powder were collected to be analyzed for aluminum (Al) concentration using graphite furnace atomic absorption spectrometry (GFAAS). The results were compared with provisional acceptable permissible limits (PAPLs). The maximum estimated dietary intake (MEDI) of Al for the examined samples was calculated. In addition, an experimental study was conducted to determine the possible leaching of Al from cookware in milk during boiling. The obtained results showed that Al concentration in examined bulk farm milk samples was found to be negligible. In contrast, market milk revealed higher concentration, 65.0% of the examined samples were above the PAPLs. The results revealed significant difference of Al concentration among them. The Al levels in processed cheese wrapped in Al foil were significantly higher than those found in samples packed in glass containers with a significant difference of Al concentration between them. Also, 20% of the examined milk powder samples exceeded the PAPLs (0.01 to 0.4 mg/kg). The MEDI for Al in bulk farm milk, control market milk, market milk boiled in Al cookware, market milk boiled in stainless-steel cookware, processed cheese wrapped in Al foil, processed cheese packed in glass containers, and milk powder were calculated as 3.0%, 61.0%, 63.0%, 61.0%, 428.0%, 220.0%, and 166.0% from "PTDI," respectively. The results of the experimental study showed no marked significant differences of Al concentration between market milk (control group) and those boiled in Al cookware, as well as to those boiled in stainless-steel cookware. PRACTICAL APPLICATION:   The results of the present study indicate that Al level in milk kept in Al containers and dairy products packed in Al foil is beyond the permissible limits, suggesting health hazard. Therefore, all milk cans should be constructed of stainless steel, prevent the entrance of tap water into milk, and the processed cheese should be packed in glass containers and not wrapped in Al foil. Leaching of Al increased to a significant percent more during storage than during boiling, so milk should be kept in stainless steel or glass containers in the refrigerator.

negative: Cow's milk allergy in Thai children. Cow's milk allergy (CMA) is nowadays a common problem in Thai children. We reviewed medical records of patients with CMA from the Department of Pediatrics at King Chulalongkom Memorial Hospital of the past 10 years, from 1998 to 2007. The criteria for the diagnosis of CMA included: elimination of cow's milk formula resulting in improvement of symptoms, and: recurrence of symptoms after reintroduction of cow's milk by oral challenge or by accidental ingestion. Of the 382 children with a diagnosis of CMA, 168 were girls and 214 were boys. The average age at the time of diagnosis was 14.8 months (7 days-13 years). The average duration of symptoms before diagnosis was 9.2 months. A family history of atopic diseases was found in 64.2% of the patients. All of the mothers reported an increased consumption of cow's milk during their pregnancy. The most common symptoms were respiratory (43.2%) followed by gastrointestinal (GI) (22.5%) and skin manifestations (20.1%). Less common symptoms included failure to thrive (10.9%), anemia (2.8%), delayed speech due to chronic serous otitis media (0.2%) and anaphylactic shock (0.2%). A prick skin test with cow milk extract was positive in 61.4%. Exclusively breast-fed was found in 13.2% of the patients. Successful treatment included elimination of cow's milk and milk products and substitution with soy formula in 42.5%, partial hydrolysate formula (pHF) in 35.7%, extensive hydrolysate formula (eHF) in 14.2%, and amino acid formula in 1.7%. Continued breast feeding was successful in 5.9% (with maternal restriction of cow's milk and milk products). Our study demonstrates the variety of clinical manifestations of CMA in Thai children especially respiratory symptoms which are usually overlooked.

negative: Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial. OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.

negative: Beef, pork, and milk allergy (cross reactivity with each other and pet allergies). OBJECTIVE: The purposes of this study were to examine milk allergic patients to determine concomitant reactivity between milk, beef, pork and cat and dog dander and other common inhalant allergens. METHODS: 19 patients were selected according to their Immuno-CAP results, which had increased Ig-E levels against milk, pork or beef. Patients were also tested against Johnson grass, short ragweed, cat/dog dander and d. farina. RESULTS: Pearson's test revealed strong correlation between beef and pork, beef and milk, pork and milk Ig-E counts (consecutively r2 = 0.89, r2 = 0.81, r2 = 0.60 and p < 0.01. All cat allergic patients also appeared to be allergic to either beef/pork meat or milk. The correlation between pork and dog dander Ig-E counts was also significant (r2 = 0.38, p < 0.01). No correlation detected between milk-meat-pet and grass-weed-dust allergies. DISCUSSION AND CONCLUSION: Patients who are known to have pet allergies may need to be screened for meat and milk allergy. Milk allergic patients may also need to avoid cows and pork meat.

negative: A systematic review and meta-analysis of the effects of pasteurization on milk vitamins, and evidence for raw milk consumption and other health-rel... Pasteurization of milk ensures safety for human consumption by reducing the number of viable pathogenic bacteria. Although the public health benefits of pasteurization are well established, pro-raw milk advocate organizations continue to promote raw milk as "nature's perfect food." Advocacy groups' claims include statements that pasteurization destroys important vitamins and that raw milk consumption can prevent and treat allergies, cancer, and lactose intolerance. A systematic review and meta-analysis was completed to summarize available evidence for these selected claims. Forty studies assessing the effects of pasteurization on vitamin levels were found. Qualitatively, vitamins B12 and E decreased following pasteurization, and vitamin A increased. Random effects meta-analysis revealed no significant effect of pasteurization on vitamin B6 concentrations (standardized mean difference [SMD], -2.66; 95% confidence interval [CI], -5.40, 0.8; P = 0.06) but a decrease in concentrations of vitamins B1 (SMD, -1.77; 95% CI, -2.57, -0.96; P < 0.001), B2 (SMD, -0.41; 95% CI, -0.81, -0.01; P < 0.05), C (SMD, -2.13; 95% CI, -3.52, -0.74; P < 0.01), and folate (SMD, -11.99; 95% CI, -20.95, -3.03; P < 0.01). The effect of pasteurization on milk's nutritive value was minimal because many of these vitamins are naturally found in relatively low levels. However, milk is an important dietary source of vitamin B2, and the impact of heat treatment should be further considered. Raw milk consumption may have a protective association with allergy development (six studies), although this relationship may be potentially confounded by other farming-related factors. Raw milk consumption was not associated with cancer (two studies) or lactose intolerance (one study). Overall, these findings should be interpreted with caution given the poor quality of reported methodology in many of the included studies.

negative: Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the milk of healthy women. An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.

negative: Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets. The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.

negative: Iodine toxicity from soy milk and seaweed ingestion is associated with serious thyroid dysfunction. We report a series of cases of thyroid dysfunction in adults associated with ingestion of a brand of soy milk manufactured with kombu (seaweed), and a case of hypothyroidism in a neonate whose mother had been drinking this milk. We also report two cases of neonatal hypothyroidism linked to maternal ingestion of seaweed made into soup. These products were found to contain high levels of iodine. Despite increasing awareness of iodine deficiency, the potential for iodine toxicity, particularly from sources such as seaweed, is less well recognised.

negative: The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers. The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that "man has been drinking cows' milk for around 2000 years without apparent harm." However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.

negative: PCDD/Fs and dioxin-like PCBs in human milk and estimation of infants' daily intake: a review. This paper reviews the recent scientific literature on PCDDs, PCDFs and dioxin-like PCBs in human milk. All the papers reporting levels of these contaminants in human breast milk published from January 2000 to January 2009 and available on the www.sciencedirect.com web site were identified and included. The aim was (1) to study levels of PCDDs, PCDFs and PCBs in human milk in mothers from different geographical areas and assess infant exposure to these contaminants; (2) to study the effect of variables such as the mother's age, number of deliveries, dietary and smoking habits and her own nutrition in infancy, and the environment, on levels of the contaminants in breast milk; (3) to study time patterns, and (4) to identify data gaps. Copyright © 2011 Elsevier Ltd. All rights reserved.

negative: Cow's milk allergy is associated with recurrent otitis media during childhood. To determine whether cow's milk allergy (CMA) in infancy is associated with recurrent otitis media (ROM) or other chronic ear infections, we conducted a cohort study by enrolling 56 milk-allergic and 204 control schoolchildren. We also studied the association between ear problems and different atopic manifestations. A higher proportion of children with CMA had had ROM. defined as at least 15 acute otitis media episodes by the age of 10 years (27%, vs 12%, p = 0.009), and had undergone adenoidectomy and or tympanostomy compared with the controls (48%, vs 28%, p = 0.005). However, this was only true of the children who had developed respiratory atopy. Asthma and/or allergic rhinitis, but not atopic dermatitis, posed a significant risk for ROM, while all the three atopic manifestations enhanced the risk for secretory otitis media. Positive skin prick tests with food, but not with inhaled allergens, tended to be associated with ear problems. In conclusion, we found that children with CMA in infancy, even when properly treated, had experienced significantly more ROM, the risk associating with concomitant development of respiratory atopy.

negative: Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.

negative: Comparisons of a chicken-based formula with soy-based formula in infants with cow milk allergy. OBJECTIVE: To determine whether chicken-based formula can replace soy-based formula in infants with cow milk allergy. SUBJECTS AND METHODS: Thirty-eight infants with cow's milk allergy, aged between 2-24 months of age were randomized to receive either chicken-based formula or soy-based formula for 14 days. RESULTS: In the group of soy-based formula, 12 out of 18 infants had evidence of intolerance and could not continue with the formula. However, only 4 out of 20 infants in the chicken-based formula group had evidence of clinical intolerance. All other 16 infants were fed the chicken-based formula with success. The number of infants who were intolerant to chicken formula was significantly lower than the number of those fed soy-based formula (p = 0.009). CONCLUSION: Chicken-based formula can be used more effectively than soy-based formula in infants with cow milk allergy.

negative: Differences among total and in vitro digestible phosphorus content of meat and milk products. OBJECTIVE: Meat and milk products are important sources of dietary phosphorus (P) and protein. The use of P additives is common both in processed cheese and meat products. Measurement of in vitro digestible phosphorus (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected meat and milk products and to compare amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP contents of 21 meat and milk products were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). In DP analysis, samples were digested enzymatically, in principle, in the same way as in the alimentary canal before the analyses. The most popular national brands of meat and milk products were chosen for analysis. RESULTS: The highest TP and DP contents were found in processed and hard cheeses; the lowest, in milk and cottage cheese. TP and DP contents in sausages and cold cuts were lower than those in cheeses. Chicken, pork, beef, and rainbow trout contained similar amounts of TP, but slightly more variation was found in their DP contents. CONCLUSIONS: Foods containing P additives have a high content of DP. Our study confirms that cottage cheese and unenhanced meats are better choices than processed or hard cheeses, sausages, and cold cuts for chronic kidney disease patients, based on their lower P-to-protein ratios and sodium contents. The results support previous findings of better P absorbability in foods of animal origin than in, for example, legumes. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

negative: Human exposure to PBDEs: associations of PBDE body burdens with food consumption and house dust concentrations. This study was designed to determine the body burden of polybrominated diphenyl ethers (PBDEs) among first-time mothers in the Greater Boston, Massachusetts area and to explore key routes of exposure. We collected breast milk samples from 46 first-time mothers, 2-8 weeks after birth. We also sampled house dust from the homes of a subset of participants by vacuuming commonly used areas. Data on personal characteristics, diet, home furniture, and electrical devices were gathered from each participant using a questionnaire. Breast milk and dust samples were analyzed for PBDEs using gas chromatography/ mass spectrometry. PBDE concentrations were log-normally distributed in breast milk and dust. We found statistically significant, positive associations between PBDE concentrations in breast milk and house dust (r = 0.76, p = 0.003, not including BDE-209), as well as with reported dietary habits, particularly the consumption of dairy products (r = 0.41, p = 0.005) and meat (r = 0.37, p = 0.01). Due to low detection rates, it was not possible to draw conclusions about the association between BDE-209 in milk and dust. Our results support the hypothesis that the indoor environment and diet both play prominent roles in adult human exposure to PBDEs.

negative: Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001. OBJECTIVE: To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). DESIGN: A three stage, pre-post intervention trial, spanning nine weeks. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). INTERVENTIONS: Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. MEASURES OF OUTCOME: In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. RESULTS: Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. CONCLUSIONS: Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.

negative: Chronic disease and infant nutrition: is it significant to public health? OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.

negative: To breastfeed or not to breastfeed: a review of the impact of lactational exposure to polychlorinated biphenyls (PCBs) on infants. Researchers have long debated the adverse effects of exposure to polychlorinated biphenyls (PCBs) on children versus the benefits of breastfeeding. In this article, the authors provide an overview of the known health effects of PCBs in children and examine the level of evidence regarding the risk of postnatal exposure via breastfeeding. The major source of PCBs is environmental, with over 90% of human exposure through the food chain. PCB exposure in infants is predominantly via breast milk, but limited evidence exists of significant toxicity associated with this mode of transmission. Breastfeeding should, therefore, continue to be encouraged on the basis of evidence of the benefits derived from human milk coupled with inconclusive proof that lactational PCB exposure has major detrimental effects on the overall health and development of infants.

negative: From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.

negative: Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream–based milkshake Background: Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. Objective: We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream–based milkshake and examined the influence of adipose tissue and the specificity of this relation. Design: Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Results: Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Conclusions: Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.

negative: Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. BACKGROUND: The aging process can lead to a decline in cellular immunity. Therefore, the elderly could benefit from safe and effective interventions that restore cellular immune functions. OBJECTIVE: We determined whether dietary supplementation with the known immunostimulating probiotic Bifidobacterium lactis HN019 could enhance aspects of cellular immunity in elderly subjects. DESIGN: Thirty healthy elderly volunteers (age range: 63-84 y; median: 69 y) participated in a 3-stage dietary supplementation trial lasting 9 wk. During stage 1 (run-in), subjects consumed low-fat milk (200 mL twice daily for 3 wk) as a base-diet control. During stage 2 (intervention), they consumed milk supplemented with B. lactis HN019 in a typical dose (5 x 10(10) organisms/d) or a low dose (5 x 10(9) organisms/d) for 3 wk. During stage 3 (washout), they consumed low-fat milk for 3 wk. Changes in the relative proportions of leukocyte subsets and ex vivo leukocyte phagocytic and tumor-cell-killing activity were determined longitudinally by assaying peripheral blood samples. RESULTS: Increases in the proportions of total, helper (CD4(+)), and activated (CD25(+)) T lymphocytes and natural killer cells were measured in the subjects' blood after consumption of B. lactis HN019. The ex vivo phagocytic capacity of mononuclear and polymorphonuclear phagocytes and the tumoricidal activity of natural killer cells were also elevated after B. lactis HN019 consumption. The greatest changes in immunity were found in subjects who had poor pretreatment immune responses. In general, the 2 doses of B. lactis HN019 had similar effectiveness. CONCLUSION: B. lactis HN019 could be an effective probiotic dietary supplement for enhancing some aspects of cellular immunity in the elderly.

negative: [Consequences of exclusive breast-feeding in vegan mother newborn--case report]. We report on the case of an infant who was hospitalized because of failure to thrive, megaloblastic anemia, and delayed psychomotor development. He was 10 months old and had been exclusively breast-fed by his vegan mother. Investigations showed vitamin B(12) deficiency with hematocytopenia and pervasive developmental disorders as well as vitamin K and vitamin D deficiencies. The infant's mother presented the same deficiencies. Introduction of vitamin supplementation normalized the biological disorders, and the infant showed weight gain and neurological improvement. This case highlights that a vegan diet during pregnancy followed by exclusive breast-feeding can induce nutritional deficiencies in the newborn, with clinical consequences. Detecting mother and child vitamin deficiencies and preventing them is essential.

negative: Humans have antibodies reactive with Bovine leukemia virus. Bovine leukemia virus (BLV) is an oncogenic retrovirus that commonly infects cattle and causes B cell leukosis in 1-5% of infected cattle. BLV-infected cells are present in marketed beef and dairy products. In the decade after the discovery of BLV in 1969, studies using agar gel immunodiffusion and complement fixation assays failed to find antibodies to BLV in human sera. This led to the prevailing opinion that exposure of humans to BLV and/or the potential for infection are not significant and therefore the virus is not a public health hazard. We reexamined this issue using more sensitive immunological techniques available today. Using immunoblotting to test the sera of 257 humans for antibodies of four isotypes (IgG1, IgM, IgA, and IgG4) to the BLV capsid antigen (p24), we detected at least one antibody isotype reactive with BLV in 74% of the human sera tested. The specificity of the reactivity was strongly suggested by competition studies and by ruling out cross-reacting antibodies to other chronic human viruses. Our results suggest that antibodies reactive with the BLV capsid antigen may serve as a biomarker for exposure to BLV and this exposure may be widespread. The results do not necessarily mean that humans are actually infected with BLV; the antibodies could be a response to heat-denatured BLV antigens consumed in food. They do, however, suggest that further studies in this area could be important.

negative: The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study. Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.

negative: American Academy of Pediatrics recommendations on the Effects of Early Nutritional Interventions on the Development of Atopic Disease Purpose of review This article reviews the AAP’s statement on early nutritional interventions on the development of atopic disease in infants and children. Recent findings Recent findings suggest that restriction of maternal diet during pregnancy and lactation does not play a major role in the development of allergic disease. In high risk infants exclusive breastfeeding for at least 4 months prevents or delays atopic dermatitis, cow milk allergy, and wheezing early in life. There is evidence that supplementing breastfeeding with a hydrolyzed formula protects against atopic disease, especially atopic dermatitis in at risk infants. Finally there is little evidence that delaying the introduction of complimentary foods beyond 4 to 6 months of age has any protective effect against allergy. There is insufficient data that any dietary intervention beyond 4 to 6 months of age has any protective effect against developing atopic disease. Summary In high risk infants there is evidence for exclusive breastfeeding for at least 4 months and delaying of complimentary foods until 4 to 6 months prevents the development of allergy. There is some evidence that supplementing hydrolyzed formulas in high risk infants may delay or prevent allergic disease. There is no convincing evidence that maternal manipulation of diet during pregnancy or lactation, use of soy products, or infant dietary restrictions beyond 4 to 6 months has any effect on the development of atopic disease.

negative: Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: a common practice in some Asian cultures to promote breast milk s... Mild iodine deficiency is a recognised problem in Australia and New Zealand. However, iodine excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of excess dietary iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of consuming seaweed soup to promote breast milk supply. Although most attention recently has been on the inadequacy of iodine in Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is desirable. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

negative: Diet promotes sleep duration and quality. Sleep, much like eating, is an essential part of life. The mechanisms of sleep are only partially clear and are the subject of intense research. There is increasing evidence showing that sleep has an influence on dietary choices. Both cross-sectional and epidemiologic studies have demonstrated that those who sleep less are more likely to consume energy-rich foods (such as fats or refined carbohydrates), to consume fewer portions of vegetables, and to have more irregular meal patterns. In this narrative review, we pose the opposite question: can ingested food affect sleep? The purpose of this review is to discuss the evidence linking diet and sleep and to determine whether what we eat and what kind of nutrients we obtain from the food consumed before bedtime matter. In addition, scientific evidence behind traditional sleep-promoting foods such as milk and some herbal products is briefly described. These are reviewed using data from clinical trials, mostly in healthy subjects. In addition, we discuss the possible mechanisms behind these observations. Lastly, we summarize our findings that emerging evidence confirms a link between diet and sleep. Overall, foods impacting the availability of tryptophan, as well as the synthesis of serotonin and melatonin, may be the most helpful in promoting sleep. Although there are clear physiological connections behind these effects, the clinical relevance needs to be studied further. Copyright © 2012 Elsevier Inc. All rights reserved.

negative: Body fat and animal protein intakes are associated with adrenal androgen secretion in children. BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes. CONCLUSIONS: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.

negative: Caffeine in pregnancy. Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Because of its wide consumption at different levels by most segments of the population, the public and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. Reproductive-aged and pregnant women are 'at risk' subgroups of the population who may require specific advice on moderating their daily caffeine intake. This article highlights the implications of caffeine intake in pregnancy, reviews the latest evidence-based information available on this subject, and offers recommendations (practical advice) for the obstetrician-gynecologists proving peripartum care to these potentially complicated pregnancies.

negative: Effects of meals and meal times on uptake of lead from the gastrointestinal tract in humans. Twenty three adults ingested 203Pb as lead acetate on the 12th hour of a 19 h fast. Retention measured 7 days later in a whole-body counter was 61% and whole-body turnover rates suggested that initial uptake had been considerably greater. Balanced meals eaten with 203Pb reduced lead uptake to 4% and the influence of the food lasted for up to 3 h. The effects of phytate, ethylene-diaminetetra acetate (EDTA), caffeine, alcohol, glucose, a liquid meal and a light snack were tested separately with intermediate results. The effect of a meal was probably largely due to its content of calcium and phosphate salts but lead uptake was probably further reduced by phytate which is plentiful in whole cereals and it was probably increased by a factor in milk. Uptake with skimmed milk was the same as with whole milk and we suggested that the factor was not fat. Comestibles with low mineral and phytate contents reduced lead uptake by intermediate amounts, possibly by stimulation of digestive secretions. The avid uptake of lead during a fast, the large reduction of lead uptake with meals and the likelihood of variations in gastric-emptying rates and dietary habits may be major causes of variation in body burdens of lead in the population.

negative: Intake of Small-to-Medium-Chain Saturated Fatty Acids Is Associated with Peripheral Leukocyte Telomere Length in Postmenopausal Women Dietary factors, including dietary fat, may affect the biological aging process, as reflected by the shortening of telomere length (TL), by affecting levels of oxidative stress and inflammatory responses. We examined the direct relations of total and types of dietary fats and fat-rich foods to peripheral leukocyte TL. In 4029 apparently healthy postmenopausal women who participated in the Women’s Health Initiative, intakes of total fat, individual fatty acids, and fat-rich foods were assessed by a questionnaire. TL was measured by quantitative polymerase chain reaction. Intake of short-to-medium-chain saturated fatty acids (SMSFAs; aliphatic tails of ≤12 carbons) was inversely associated with TL. Compared with participants in other quartiles of SMSFA intake, women who were in the highest quartile (median: 1.29% of energy) had shorter TLs [mean: 4.00 kb (95% CI: 3.89, 4.11 kb)], whereas women in the lowest quartile of intake (median: 0.29% of energy) had longer TLs [mean: 4.13 kb (95% CI: 4.03, 4.24 kb); P-trend = 0.046]. Except for lauric acid, all other individual SMSFAs were inversely associated with TL (P < 0.05). In isoenergetic substitution models, the substitution of 1% of energy from SMSFAs with any other energy source was associated with 119 bp longer TLs (95% CI: 21, 216 bp). Intakes of nonskim milk, butter, and whole-milk cheese (major sources of SMSFAs) were all inversely associated with TL. No significant associations were found with long-chain saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. In conclusion, we found that higher intakes of SMSFAs and SMSFA-rich foods were associated with shorter peripheral leukocyte TL among postmenopausal women. These findings suggest the potential roles of SMSFAs in the rate of biological aging.

negative: Intake of dioxins and related compounds from food in the U.S. population. The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.