query: Treating Asthma With Plants vs. Supplements?

positive: Dietary polyphenols in the prevention and treatment of allergic diseases. Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.

positive: Dietary antioxidant intake, allergic sensitization and allergic diseases in young children. BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.

positive: Manipulating antioxidant intake in asthma: a randomized controlled trial. BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.

positive: Clinical efficacy of apple polyphenol for treating cedar pollinosis. A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.

positive: An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis. BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.

positive: Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete Background Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods A cross‐sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58‐item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.

positive: Diet, lung function, and lung function decline in a cohort of 2512 middle aged men BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.

positive: A prospective study of diet and adult-onset asthma. A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.

positive: Effect of fresh fruit consumption on lung function and wheeze in children BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.

positive: Vegan regimen with reduced medication in the treatment of bronchial asthma. Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.

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

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: 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: A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders. Today, tens of millions of elderly individuals worldwide suffer from dementia. While the pathogenesis of dementia is complex and incompletely understood, it may be, at least to a certain extent, the consequence of systemic vascular pathology. The metabolic syndrome and its individual components induce a proinflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic. Associations have been established between the metabolic syndrome, its constituents and dementia. A relationship has also been observed between certain dietary factors, such as constituents of the 'Mediterranean diet', and the metabolic syndrome; similar associations have been noted between these dietary factors and dementia. Fruit juices and extracts are under investigation as treatments for cognitive impairment. Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared. The benefits of fruit products are thought to be a result of its polyphenol content. A grape polyphenol found in grapes, resveratrol, now being studied in humans, and one in grapes and blueberries, pterostilbene, have been found to improve cognition in rodents. In the design of future human trials, one ought to consider the poor bioavailability of these products, the possible need to initiate the experimental therapy long before the onset of symptoms, and currently limited knowledge about the appropriate form (e.g. juice, powder or individual polyphenol) of treatment.

positive: Plant foods and brain aging: a critical appraisal. In the 21st century, human aging will be one of the biggest challenges for most societies throughout the world. The decline in human fitness is a typical hallmark of the aging process. Aside from the cardiovascular system, the brain most often suffers significantly from the life-long impact of stressors, such as reactive oxygen and nitrogen species. Oxytosis, i.e. oxidative stress-induced cell death, has been identified to play a major role in the development and onset of chronic diseases. Foods, especially of plant origin, are rich in antioxidants and numerous in vivo data suggest that a diet rich in fruits and vegetables supports the maintenance of animal and human health. These beneficial effects also extend to the central nervous system, which, due to the presence of the blood-brain barrier, tightly controls the influx of metabolites and nutrients. In earlier studies the impact of antioxidant vitamins, such as alpha-tocopherol and ascorbic acid, on brain health has been of interest. Recently, the focus moved to assessing the potential of unsaturated fatty acids and secondary plant metabolites, particularly of polyphenols, to act as neuroprotectants. Considerable experimental evidence suggests that polyphenols and other plant-derived bioactivities affect animal and human brain function not only by directly lowering oxidative stress load but also by modulating various signal transduction pathways.

positive: Dietary intake of berries and flavonoids in relation to cognitive decline Objective Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women. Methods Beginning in 1980, a semi-quantitative food frequency questionnaire was administered every four years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at two-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariable-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes. Results Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (e.g., for a global score averaging all six cognitive tests, for blueberries: p-trend=0.014 and mean difference=0.04 [95% CI=0.01, 0.07] comparing extreme categories of intake; for strawberries: p-trend= 0.022 and mean difference=0.03 [95% CI=0.00, 0.06] comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we find for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends= 0.015 and 0.053, respectively, for the global score). Interpretation Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.

positive: Blueberry Supplementation Improves Memory in Older Adults The prevalence of dementia is increasing with expansion of the older adult population. In the absence of effective therapy, preventive approaches are essential to address this public health problem. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with increased neuronal signaling in brain centers mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration. We investigated the effects of daily consumption of wild blueberry juice in a sample of nine older adults with early memory changes. At 12 weeks, we observed improved paired associate learning (p = 0.009) and word list recall (p = 0.04). In addition, there were trends suggesting reduced depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10). We also compared the memory performances of the blueberry subjects with a demographically-matched sample who consumed a berry placebo beverage in a companion trial of identical design and observed comparable results for paired associate learning. The findings of this preliminary study suggest that moderate-term blueberry supplementation can confer neurocognitive benefit and establish a basis for more comprehensive human trials to study preventive potential and neuronal mechanisms.

positive: Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry ... Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

positive: Concord grape juice supplementation and neurocognitive function in human aging. Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline.

positive: Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with CVD, and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In addition, preliminary animal data have indicated improvement in memory and motor function with grape juice supplementation, suggesting potential for cognitive benefit in ageing humans. In this initial investigation of neurocognitive effects, we enrolled twelve older adults with memory decline but not dementia in a randomised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. We observed significant improvement in a measure of verbal learning and non-significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with early memory decline and establish a basis for more comprehensive investigations to evaluate potential benefit and assess mechanisms of action.

positive: Blueberries and neuronal aging. As the population of people in the United States over the age of 65 years continues to increase, so too will the incidence of age-related pathologies, including decreases in cognitive and motor function. In cases of severe deficits in memory or motor function, hospitalization and/or custodial care would be a likely outcome. This means that unless some way is found to reduce these age-related decrements in neuronal function, health care costs will continue to rise exponentially. Evidence is accumulating that consumption of blueberries may be one strategy to forestall or even reverse age-related neuronal deficits, as well as their subsequent behavioral manifestations, in order to increase healthy aging. Research suggests that the polyphenolic compounds found in blueberries exert their beneficial effects either through their ability to lower oxidative stress and inflammation or directly by altering the signaling involved in neuronal communication. These interventions, in turn, may protect against age-related deficits in cognitive and motor function. Appropriately, the US Department of Agriculture has figured prominently in these discoveries, through the efforts of two USDA researchers who worked for the department 100 years apart. Copyright © 2012 S. Karger AG, Basel.

positive: Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells. Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.

positive: Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link? Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.

positive: Variations in product choices of frequently purchased herbs: caveat emptor. BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.

positive: The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity. PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.

positive: Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.

positive: Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis. Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.

positive: A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women. Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.

positive: Ultraviolet phototoxicity to the retina. OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.

positive: Goji berry effects on macular characteristics and plasma antioxidant levels. PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.

positive: Iris color and macular pigment optical density. The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.

positive: Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial. Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.

positive: Cataract is a self-defence reaction to protect the retina from oxidative damage. Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.

positive: Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma. AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.

positive: Dietary modification of human macular pigment density. PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight "retinal responders" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two "retinal nonresponders" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one "serum and retinal nonresponder" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.

positive: Randomised clinical trial: dried plums (prunes) vs. psyllium for constipation. BACKGROUND: Treatment of chronic constipation remains challenging with 50% of patients dissatisfied with current therapy. There is an unmet need for natural and safe alternatives. Dried plums (prunes) have been used traditionally for constipation but their efficacy is not known. Aim To assess and compare the effects of dried plums and psyllium in patients with chronic constipation. METHODS: Subjects were enrolled in an 8-week, single-blind, randomised cross-over study. Subjects received either dried plums (50 g b.d., fibre=6 gm/day) or psyllium (11 g b.d., fibre=6 gm/day) for 3 weeks each, in a crossover trial with a 1-week washout period. Subjects maintained a daily symptom and stool diary. Assessments included number of complete spontaneous bowel movements per week, global relief of constipation, stool consistency, straining, tolerability and taste. RESULTS: Forty constipated subjects (m/f=3/37, mean age=38 years) participated. The number of complete spontaneous bowel movements per week (primary outcome measure) and stool consistency scores improved significantly (P<0.05) with dried plums when compared to psyllium. Straining and global constipation symptoms did not differ significantly between treatments (P=N.S.). Dried plums and psyllium were rated as equally palatable and both were safe and well tolerated. CONCLUSION: Dried plums are safe, palatable and more effective than psyllium for the treatment of mild to moderate constipation, and should be considered as a first line therapy. © 2011 Blackwell Publishing Ltd.

positive: Nutrition and lifestyle in relation to bowel movement frequency: a cross-sectional study of 20630 men and women in EPIC-Oxford. OBJECTIVE: To investigate the relationships between nutritional and lifestyle factors and bowel movement frequency. DESIGN: Cross-sectional analysis using data from a prospective study. Mean numbers of bowel movements were calculated in relation to a range of factors. In addition, individuals were categorised according to frequency of bowel movements: fewer than 7 per week ('less than daily') versus 7 or more per week ('daily'), and odds ratios were calculated from logistic regression models. Results for each factor were adjusted for the other factors under consideration. SETTING: The European Prospective Investigation into Cancer and Nutrition, Oxford cohort (EPIC-Oxford), UK. PARTICIPANTS: In total, 20630 men and women aged 22-97 years at recruitment. Thirty per cent of the subjects were vegetarians or vegans. RESULTS: Women had fewer bowel movements on average than men, and were less likely to have daily bowel movements. Mean bowel movement frequency was higher in vegetarians (10.5 in men, 9.1 in women) and especially in vegans (11.6 in men, 10.5 in women) compared with participants who ate meat (9.5 in men, 8.2 in women). There were also significant positive associations between bowel movement frequency and body mass index (BMI), intakes of dietary fibre and non-alcoholic fluids, for both men and women. Vigorous exercise was positively associated with bowel movement frequency in women although results for men were less clear. Alcohol intake was positively associated with bowel movement frequency in men but not in women. CONCLUSION: Being vegetarian and especially vegan is strongly associated with a higher frequency of bowel movements. Moreover, having a high intake of dietary fibre and fluids and a high BMI are associated with an increase in frequency of bowel movements.

positive: Phytosterol composition of nuts and seeds commonly consumed in the United States. Phytosterols were quantified in nuts and seeds commonly consumed in the United States. Total lipid extracts were subjected to acid hydrolysis and then alkaline saponfication, and free sterols were analyzed as trimethylsilyl derivatives by capillary GC-FID and GC-MS. Delta5-Avenasterol was quantified after alkaline saponification plus direct analysis of the glucoside. Sesame seed and wheat germ had the highest total phytosterol content (400-413 mg/100 g) and Brazil nuts the lowest (95 mg/100 g). Of the products typically consumed as snack foods, pistachio and sunflower kernel were richest in phytosterols (270-289 mg/100 g). beta-Sitosterol, Delta5-avenasterol, and campesterol were predominant. Campestanol ranged from 1.0 to 12.7 mg/100 g. Only 13 mg/100 g beta-sitosterol was found in pumpkin seed kernel, although total sterol content was high (265 mg/100 g). Phytosterol concentrations were greater than reported in existing food composition databases, probably due to the inclusion of steryl glycosides, which represent a significant portion of total sterols in nuts and seeds.

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: Consumption of polyunsaturated fatty acids, fish, and nuts and risk of inflammatory disease mortality. BACKGROUND: n-3 (omega-3) Polyunsaturated fatty acids (PUFAs), fish, and nuts can regulate inflammatory processes and responses. OBJECTIVE: We investigated whether dietary intakes of PUFAs [n-3, n-6 (omega-6), and α-linolenic acid], fish, and nuts were associated with 15-y mortality attributed to noncardiovascular, noncancer inflammatory diseases. DESIGN: The analyses involved 2514 participants aged ≥49 y at baseline. Dietary data were collected by using a semiquantitative food-frequency questionnaire, and PUFA, fish, and nut intakes were calculated. Inflammatory disease mortality was confirmed from the Australian National Death Index. RESULTS: Over 15 y, 214 subjects died of inflammatory diseases. Women in the highest tertiles of total n-3 PUFA intake, compared with those in the lowest tertile of intake at baseline, had a 44% reduced risk of inflammatory disease mortality (P for trend = 0.03). This association was not observed in men. In both men and women, each 1-SD increase in energy-adjusted intake of α-linolenic acid was inversely associated with inflammatory mortality (hazard ratio: 0.83; 95% CI: 0.71, 0.98). Subjects in the second and third tertiles of nut consumption had a 51% and 32% reduced risk of inflammatory disease mortality, respectively, compared with those in the first tertile (reference). Dietary intakes of long-chain n-3 and n-6 PUFAs and fish were not associated with inflammatory disease mortality. CONCLUSIONS: We report on a novel link between dietary intake of total n-3 PUFA and risk of inflammatory disease mortality in older women. Furthermore, our data indicate a protective role of nuts, but not fish, against inflammatory disease mortality.

positive: Determinants of Inflammatory Markers in a Bi-ethnic Population Background Inflammation is a common pathophysiological pathway for a number of chronic diseases, and is strongly influenced by sociodemographic factors and lifestyle. Less is known about factors that may influence the inflammatory response in individuals of distinct ethnic backgrounds. Therefore, this study examined the relationship between ethnicity and blood levels of inflammatory markers in a sample of non-smoking church-goers. Methods In a cross-sectional investigation, 508 men and women (>35 years old, 62% White, 38% Black) participated in the Biopsy-chosocial Religion and Health substudy of the Adventist Health Study 2. The contribution of socioeconomic status (education level and difficulty meeting expenses for basic needs) and health covariates (exercise, vegetarian or other type of diet, body mass index, and presence of inflammatory conditions) toward serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was assessed with linear regression models. Levels of interleukin-10 (IL-10), an anti-inflammatory marker, were also assessed. Results Blacks showed higher levels of CRP and IL-6 than Whites. Controlling for socio-demographic and health variables attenuated the ethnic difference in CRP while IL-6 levels remained higher in Blacks than in Whites (β=.118; 95% confidence interval=.014–.206; P=.025). Ethnic differences in IL-10 and TNF-α were not found. Vegetarian diet was associated with lower CRP levels while exercise frequency was associated with higher IL-10 levels. Conclusion Higher susceptibility of Blacks to inflammatory diseases may reflect higher IL-6, which could be important in assessing health disparities among Blacks and Whites. Vegetarian diet and exercise may counteract effects of disparities.

positive: Adverse effects of concentrated green tea extracts. A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

positive: Bioavailability of natural carotenoids in human skin compared to blood. Skin functions and structure are significantly influenced by nutrients. Antioxidants protect the supportive layer of the skin against any damaging irradiation effects and the action of free radicals. A lack of suitable methods means that the pharmacokinetic properties of systemically applied carotenoids transferred into the skin remain poorly understood. In this study, a natural kale extract or placebo oil were given orally to 22 healthy volunteers for 4 weeks. Carotenoid bioaccessibility was evaluated using non-invasive resonance Raman spectroscopy on the palm and forehead skin. For the analysis of the blood serum, the standard HPLC method was used. The blood and skin levels of the carotenoids increased significantly during the study but compared to the blood serum values, increases in skin were delayed and depended on the dermal area as well as on the carotenoid. Lycopene, measured as being low in the extract, increases more in the skin compared to the blood indicating that the natural mixture of the extract stabilizes the antioxidative network in the skin. After supplementation had ended, the carotenoids decreased much faster in the blood than in the skin. The delayed decrease in the skin may indicate a peripheral buffer function of the skin for carotenoids. Copyright © 2010 Elsevier B.V. All rights reserved.

negative: Airway and circulating levels of carotenoids in asthma and healthy controls. BACKGROUND: Elevated oxidative stress and impaired antioxidant defences are increasingly recognised features of asthma. Carotenoids are potent dietary antioxidants that may protect against asthma by reducing oxidative damage. OBJECTIVES: This study aimed firstly, to characterise circulating and airway levels of carotenoids in asthma compared to healthy controls, in relation to dietary intake. Secondly, the study aimed to test whether airway lycopene defences can be improved using oral supplements. METHODS: Induced sputum and peripheral blood samples were collected from subjects with asthma (n = 15) and healthy controls (n = 16). Dietary carotenoid intakes were estimated using the 24-hour recall method and analysed using a modified version of the Foodworks 210 Nutrient Calculation Software. Another group of healthy controls (n = 9) were supplemented with 20 mg/day lycopene for 4 weeks. Carotenoids (beta-carotene, lycopene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin) were measured by HPLC. RESULTS: Despite similar dietary intake, whole blood levels of total carotenoids, lycopene, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene were significantly lower in asthma than controls. However, there were no differences in plasma or sputum carotenoid levels. Induced sputum carotenoid levels were significantly lower than plasma and whole blood levels, but correlated strongly with plasma levels (r = 0.798, p < 0.001). Although there were no overall increases in either plasma or sputum lycopene levels following supplementation, changes in airway lycopene levels correlated with changes in plasma levels (r = 0.908, p < 0.002). CONCLUSIONS: Whole blood, but not plasma or sputum, carotenoid levels are deficient in asthma. Plasma carotenoid levels reflect airway carotenoid levels and when plasma levels are improved using oral supplements this is reflected in the airways.

negative: Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.

negative: The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study. Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the individual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic sampling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude); however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29; 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87; 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations. © 2010 John Wiley & Sons A/S.

negative: Asthma induced by sulphur dioxide, benzoate and tartrazine contained in orange drinks. Of 272 patients with asthma, thirty (11%) gave a history of exacerbations occurring after ingestion, solutions of orange orange drinks. Fourteen of these were given provocation tests by drinking, on separate occasions of sulphur dioxide, sodium benzoate and tartrazine, which are present in all orange drinks. Eight reacted to sulphur dioxide with a fall in FEV1, four to sodium benzoate and one to tartrazine, and four did not react to any of these agents. Three of the benzoate patients were also sensitive to sulphur dioxide. The sulphur dioxide sensitive patients were predominantly young, with extrinsic asthma. The benzoate sensitive patients were predominantly middle-aged and the proportion with intrinsic asthma was higher. Prior inhalation of sodium cromoglycate by four patients inhibited the reaction to these substances. Sulphur dioxide has not previously been reported to cause exacerbations of asthma when ingested as a food preservative. It is used as a preservative in a wide range of acidic beverages and foods, and should be considered as possibly causal in patients suffering from apparently cryptogenic asthma, and asthma seemingly due to food allergy.

negative: The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.

negative: The burden of childhood asthma Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.

negative: An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. OBJECTIVE: To examine in overweight humans the short-term safety and efficacy for weight loss of an herbal supplement containing Ma Huang, Guarana and other ingredients. DESIGN: An 8 week randomized, double-blind placebo controlled study of a herbal dietary supplement (72 mg/day ephedrine alkaloids and 240 mg/day caffeine). SUBJECTS: Overweight men and women (body mass index, > or =29 and < or =35 kg/m2). MEASUREMENTS: The primary outcome variable was body weight change. Secondary variables included anthropometric, metabolic and cardiovascular changes. RESULTS: Sixty-seven subjects were randomized to either placebo (n=32) or active Ma Huang/Guarana (n=35). Twenty-four subjects in each group completed the study. Active treatment produced significantly (P<0.006) greater loss of weight (X+/-s.d.,-4.0+/-3.4 kg) and fat (-2.1+/-3.0% fat) over the 8-week treatment period than did placebo (-0.8+/-2.4 kg and 0.2+/-2.3% fat). Active treatment also produced greater reductions in hip circumference and serum triglyceride levels. Eight of the 35 actively treated subjects (23%) and none of the 32 placebo-treated control subjects withdrew from the protocol because of potential treatment-related effects. Dry mouth, insomnia and headache were the adverse symptoms reported most frequently by the herbal vs placebo group at the final evaluation visit. CONCLUSIONS: This herbal mixture of Ma Huang and Guarana effectively promoted short-term weight and fat loss. Safety with long-term use requires further investigation.

negative: Diet, infection and wheezy illness: lessons from adults. An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.

negative: Is the asthma epidemic still ascending? Asthma is a phenotypically heterogeneous disorder of multifactorial origins that affects 300 million people suffering from asthma and more than 250,000 asthma-related deaths each year. Although treatment for asthma has improved, its prevalence continues to increase, particularly in low and middle income countries, or in some ethnic groups in which prevalence was previously low. Observed spatio-temporal variations in the increased prevalence of asthma depend on exposure to environmental factors. Recently, several arguments are also in favor of the involvement of host susceptibility and stress in the observed increase of asthma prevalence. Further investigations are warranted to better understand mechanisms underlying asthma increase or stagnation. Copyright © 2012 Elsevier Inc. All rights reserved.

negative: Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition. The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.

negative: Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study. BACKGROUND: Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 µg per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases. OBJECTIVE: To investigate the association between cod liver oil intake and asthma development. METHODS: In the Nord-Trøndelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake ≥ 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up. RESULTS: Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for ≥ 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (< 40/≥ 40 years), sex (men/women), family history of asthma (yes/no) and BMI subgroups (< 25/≥ 25 kg/m(2)). CONCLUSIONS: Intake of cod liver oil with high vitamin A content was significantly associated with increased incidence of adult-onset asthma.

negative: Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know. Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.

negative: Polysaccharides Isolated from Açaí Fruit Induce Innate Immune Responses The Açaí (Acai) fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.

negative: Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and... Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data. Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6-7 and 13-14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995). The 13-14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13-14 yr olds and the ISAAC data for 6-7 yr olds showed similar patterns for these foods. A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.

negative: Maternal vaginal microflora during pregnancy and the risk of asthma hospitalization and use of antiasthma medication in early childhood. BACKGROUND: Infants with wheezing and allergic diseases have a microflora that differs from that of healthy infants. The fetus acquires microorganisms during birth when exposed to the maternal vaginal microflora. It is therefore conceivable that the maternal vaginal microflora might influence the establishment of the infant flora and, as a consequence, the development of wheezing and allergic diseases. OBJECTIVE: We sought to study the associations between the composition of the maternal vaginal microflora and the development of wheezing and asthma in childhood. METHODS: We performed a population-based cohort study in Denmark. Vaginal samples for bacterial analysis were obtained during pregnancy. A total of 2927 women (80% of the invited women) completed the study and had 3003 live infants. Infant wheezing was assessed as one or more hospitalizations for asthma between 0 and 3 years of age. Asthma was assessed as use of 3 or more packages of antiasthma medication between 4 and 5 years of age. RESULTS: Maternal vaginal colonization with Ureaplasma urealyticum during pregnancy was associated with infant wheezing (odds ratio [OR], 2.0; 95% CI, 1.2-3.6), but not with asthma, during the fifth year of life. Maternal colonization with staphylococci (OR, 2.2; 95% CI, 1.4-3.4) and use of antibiotics in pregnancy (OR, 1.7; 95% CI, 1.1-2.6) were associated with asthma during the fifth year of life. CONCLUSION: The composition of the maternal vaginal micro-flora might be associated with wheezing and asthma in the offspring up to 5 years of age.

negative: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis. This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. 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: Aloe versus silver sulfadiazine creams for second-degree burns: a randomized controlled study. PURPOSE: Burn injury is associated with a high incidence of death and disability; yet its management remains problematic and costly. We conducted this clinical study to evaluate the efficacy of aloe vera cream for partial thickness burn wounds and compare its results with those of silver sulfadiazine (SSD). METHODS: Thirty patients with similar types of second-degree burns at two sites on different parts of the body were included in this study. Each patient had one burn treated with topical SSD and one treated with aloe cream, randomly. RESULTS: The rate of re-epithelialization and healing of the partial thickness burns was significantly faster in the site treated with aloe than in the site treated with SSD (15.9 +/- 2 vs 18.73 +/- 2.65 days, respectively; P < 0.0001). The sites treated with aloe were completely healed in less than 16 days vs 19 days for the sites treated with SSD. CONCLUSION: These results clearly demonstrated the greater efficacy of aloe cream over SSD cream for treating second-degree burns.

negative: Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocy... Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.

negative: A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767

negative: Baker's yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women. OBJECTIVE: Several studies have shown a baker's yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. This study evaluated the effect of a specific beta-glucan supplement (Wellmune) on upper respiratory tract symptoms and psychological well-being in women with moderate levels of psychological stress. METHODS: Healthy women (38 ± 12 years old) prescreened for moderate levels of psychological stress, self-administered a placebo (n = 38) or 250 mg of Wellmune (n = 39) daily for 12 weeks. We used the Profile of Mood States (POMS) psychological survey to assess changes in mental/physical energy levels (vigor) and overall well-being (global mood state). A quantitative health perception log was used to track upper respiratory symptoms. RESULTS: Subjects in the Wellmune group reported fewer upper respiratory symptoms compared to placebo (10% vs 29%), better overall well-being (global mood state: 99 ± 19 vs 108 ± 23, p < 0.05), and superior mental/physical energy levels (vigor: 19.9 ± 4.7 vs 15.8 ± 6.3, p < 0.05). CONCLUSIONS: These data show that daily dietary supplementation with Wellmune reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors.

negative: 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.

negative: Radioprotection by plant products: present status and future prospects. The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.

negative: Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia. It has long been appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH). Prospective cohort data originating from recently published randomized trials on the medical treatment of BPH and prevention of prostate cancer have been invaluable. A growing body of evidence suggests that exercise and the intake of specific macronutrients and micronutrients through regular diet play a beneficial role. Most strikingly, the magnitude of these effects is similar to medical therapies using alpha-blockers and 5-alpha-reductase inhibitors. The use of supplements for prostate disease is a multibillion dollar business in the United States, and supplements are more commonly prescribed than medical therapy in many countries. In contrast to consumption of micronutrients through regular diet, supplemental intake of micronutrients and phytotherapies currently lack evidence to support their efficacy.

negative: Review of the efficacy of green tea, isoflavones and aloe vera supplements based on randomised controlled trials. We assess the evidence for health benefits of three commonly consumed plant food supplements (PFS), green tea, isoflavone and aloe vera, based on published systematic reviews of randomised controlled trials (RCTs). Whilst the potential benefits of green tea have been reported in a wide range of health areas, it is only in the area of the metabolic syndrome that the number of RCTs is approaching sufficient to judge such efficacy. Isoflavone supplements are widely used, and RCTs indicate that they affect bone resorption at lower doses in postmenopausal women undergoing estrogen-related bone loss, but this is only translated to attenuation of bone loss at higher doses of isoflavones. A systematic review on RCTs concluded that the effects of isoflavones on hot flashes in postmenopausal women were highly variable and no conclusions could be drawn. Despite the popularity of aloe vera as a PFS, the evaluation of its efficacy as a coadjuvant therapy for certain metabolic or digestive pathologies remains scarce; it constitutes a typical example of a naturally occurring ingredient whose efficacy in topical applications presupposes its efficacy in systemic applications. Nevertheless, its possible toxic effects on oral consumption call for caution in its utility as a PFS. Since 2007, efficacy evaluation of PFS in Europe has been covered by European Union Nutrition and Health Claims legislation. The European Food Safety Authority has adopted an approach relying on RCTs, while medicinal effects are accepted based on traditional use. In general, there are insufficient RCTs for claims to be made, and conclusive results on PFS should be obtained in the future by conducting studies with more homogeneous populations, by using supplements with optimised and measured bioavailability, and by conducting larger RCTs.

negative: The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century. It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.

negative: Acute dietary nitrate supplementation improves cycling time trial performance. PURPOSE: Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance. However, it is presently unknown whether it may enhance performance during simulated competition. The present study investigated the effects of acute dietary nitrate supplementation on power output (PO), VO2, and performance during 4- and 16.1-km cycling time trials (TT). METHODS: After familiarization, nine club-level competitive male cyclists were assigned in a randomized, crossover design to consume 0.5 L of beetroot juice (BR; containing ∼ 6.2 mmol of nitrate) or 0.5 L of nitrate-depleted BR (placebo, PL; containing ∼ 0.0047 mmol of nitrate), ∼ 2.5 h before the completion of a 4- and a 16.1-km TT. RESULTS: BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P < 0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P > 0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P < 0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P < 0.01). Consequently, BR improved 4-km performance by 2.8% (PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min, P < 0.05) and 16.1-km performance by 2.7% (PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min, P < 0.01). CONCLUSIONS: These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy, as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance.

negative: Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients. BACKGROUND: The contribution of ascorbate to urinary oxalate is controversial. The present study aimed to determine whether urinary oxalate and pH may be affected by vitamin C supplementation in calcium stone-forming patients. METHODS: Forty-seven adult calcium stone-forming patients received either 1 g (N=23) or 2 g (N=24) of vitamin C supplement for 3 days and 20 healthy subjects received 1 g. A 24-hour urine sample was obtained both before and after vitamin C for calcium, oxalate, magnesium, citrate, sodium, potassium, and creatinine determination. The Tiselius index was used as a calcium oxalate crystallization index. A spot fasting morning urine sample was also obtained to determine the urinary pH before and after vitamin C. RESULTS: Fasting urinary pH did not change after 1 g (5.8 +/- 0.6 vs. 5.8 +/- 0.7) or 2 g vitamin C (5.8 +/- 0.8 vs. 5.8 +/- 0.7). A significant increase in mean urinary oxalate was observed in calcium stone-forming patients receiving either 1 g (50 +/- 16 vs. 31 +/- 12 mg/24 hours) or 2 g (48 +/- 21 vs. 34 +/- 12 mg/24 hours) of vitamin C and in healthy subjects (25 +/- 12 vs. 39 +/- 13 mg/24 hours). A significant increase in mean Tiselius index was observed in calcium stone-forming patients after 1 g (1.43 +/- 0.70 vs. 0.92 +/- 0.65) or 2 g vitamin C (1.61 +/- 1.05 vs. 0.99 +/- 0.55) and in healthy subjects (1.50 +/- 0.69 vs. 0.91 +/- 0.46). Ancillary analyses of spot urine obtained after vitamin C were performed in 15 control subjects in vessels with or without ethylenediaminetetraacetic acid (EDTA) with no difference in urinary oxalate between them (28 +/- 23 vs. 26 +/- 21 mg/L), suggesting that the in vitro conversion of ascorbate to oxalate did not occur. CONCLUSION: These data suggest that vitamin C supplementation may increase urinary oxalate excretion and the risk of calcium oxalate crystallization in calcium stone-forming patients.

negative: 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.

negative: Immunity: plants as effective mediators. In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.

negative: Inhalation aromatherapy during radiotherapy: results of a placebo-controlled double-blind randomized trial. PURPOSE: To determine whether the inhalation of aromatherapy during radiotherapy reduces anxiety. PATIENTS AND METHODS: Three hundred thirteen patients undergoing radiotherapy were randomly assigned to receive either carrier oil with fractionated oils, carrier oil only, or pure essential oils of lavender, bergamot, and cedarwood administered by inhalation concurrently with radiation treatment. Patients underwent assessment by the Hospital Anxiety and Depression Scale (HADS) and the Somatic and Psychological Health Report (SPHERE) at baseline and at treatment completion. RESULTS: There were no significant differences in HADS depression or SPHERE scores between the randomly assigned groups. However, HADS anxiety scores were significantly lower at treatment completion in the carrier oil only group compared with either of the fragrant arms (P =.04). CONCLUSION: Aromatherapy, as administered in this study, is not beneficial.

negative: The marketing of dietary supplements in North America: the emperor is (almost) naked. BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail ("junk mail"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.