query: folic acid

positive: Antioxidant status and its association with elevated depressive symptoms among US adults: National Health and Nutrition Examination Surveys 2005–06 We examined the relationship of elevated depressive symptoms with antioxidant status. Cross-sectional data from the National Health and Nutrition Examination Surveys 2005–06 on US adults aged 20–85 years were analyzed. Depressive symptoms were measured using the Patient Health Questionnaire with a score cutpoint of 10 to define “elevated depressive symptoms”. Serum antioxidant status was measured by serum levels of carotenoids, retinol (free and retinyl esters), vitamin C and vitamin E. The main analyses consisted of multiple logistic and zero-inflated poisson regression models, taking into account sampling design complexity. The final sample consisted of 1,798 US adults with complete data. Higher total carotenoid serum level was associated with lower likelihood of elevated depressive symptoms with a reduction in the odds by 37% overall with each SD increase in exposure, and by 34% among women (p<0.05). A dose-response relationship was observed when serum total carotenoids were expressed as quartiles [Q4 (1.62–10.1 μmol/L) vs. Q1(0.06–0.86 μmol/L): OR=0.41; 95% CI: 0.23–0.76, P<0.001; p-value for trend=0.035], though no significant associations were found with other antioxidant levels. Among carotenoids, β-carotene (men and women combined) and lutein+zeaxanthins (women only, after control for dietary lutein+zeaxanthin intake and supplement use) had an independent inverse association with elevated depressive symptoms among US adults. None of the other serum antioxidants had a significant association with depressive symptoms, independently of total carotenoids and other covariates. In conclusion, total carotenoids (mainly β-carotene and lutein+zeaxanthins) in serum were associated with reduced levels of depressive symptoms among community-dwelling US adults.

positive: Dietary pattern and depressive symptoms in middle age Background Studies of diet and depression have focused primarily on individual nutrients. Aims To examine the association between dietary patterns and depression using an overall diet approach. Method Analyses were carried on data from 3486 participants (26.2% women, mean age 55.6 years) from the Whitehall II prospective cohort, in which two dietary patterns were identified: ‘whole food’ (heavily loaded by vegetables, fruits and fish) and ‘processed food’ (heavily loaded by sweetened desserts, fried food, processed meat, refined grains and high-fat dairy products). Self-reported depression was assessed 5 years later using the Center for Epidemiologic Studies – Depression (CES–D) scale. Results After adjusting for potential confounders, participants in the highest tertile of the whole food pattern had lower odds of CES–D depression (OR = 0.74, 95% CI 0.56–0.99) than those in the lowest tertile. In contrast, high consumption of processed food was associated with an increased odds of CES–D depression (OR = 1.58, 95% CI 1.11–2.23). Conclusions In middle-aged participants, a processed food dietary pattern is a risk factor for CES–D depression 5 years later, whereas a whole food pattern is protective.

positive: Fruit, Vegetable and Antioxidant Intakes are Lower in Older Adults with Depression Studies have shown an association between depression and both antioxidant levels and oxidant stress, but generally have not included intakes of antioxidants and antioxidant-rich fruits and vegetables. The present study examined the cross-sectional associations between clinically-diagnosed depression and intakes of antioxidants, fruits and vegetables in a cohort of older adults. Antioxidant, fruit and vegetable intakes were assessed in 278 elderly participants (144 with depression, 134 without depression) using a Block 1998 food frequency questionnaire, which was administered between 1999 and 2007. All participants were age 60 years or over. Vitamin C, lutein and cryptoxanthin intakes were significantly lower among depressed individuals than in comparison participants (p<0.05). In addition, fruit and vegetable consumption, a primary determinant of antioxidant intake, was lower in depressed individuals. In multivariable models, controlling for age, sex, education, vascular comorbidity score, body mass index, total dietary fat, and alcohol, vitamin C, cryptoxanthin, fruits and vegetables remained significant. Antioxidants from dietary supplements were not associated with depression. Antioxidant, fruit and vegetable intakes were lower in individuals with late-life depression than in comparison participants. These associations may partially explain the elevated risk of cardiovascular disease among older depressed individuals. In addition, these findings point to the importance of antioxidant food sources rather than dietary supplements.

positive: High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. BACKGROUND: Ascorbic acid (AA) modulates catecholaminergic activity, decreases stress reactivity, approach anxiety and prolactin release, improves vascular function, and increases oxytocin release. These processes are relevant to sexual behavior and mood. METHODS: In this randomized double-blind, placebo-controlled 14 day trial of sustained-release AA (42 healthy young adults; 3000 mg/day Cetebe) and placebo (39 healthy young adults), subjects with partners recorded penile-vaginal intercourse (FSI), noncoital partner sex, and masturbation in daily diaries, and also completed the Beck Depression Inventory before and after the trial. RESULTS: The AA group reported greater FSI (but, as hypothesized, not other sexual behavior) frequency, an effect most prominent in subjects not cohabiting with their sexual partner, and in women. The AA but not placebo group also experienced a decrease in Beck Depression scores. CONCLUSIONS: AA appears to increase FSI, and the differential benefit to noncohabitants suggests that a central activation or disinhibition, rather than peripheral mechanism may be responsible.

positive: A tomato-rich diet is related to depressive symptoms among an elderly population aged 70 years and over: a population-based, cross-sectional analysis. BACKGROUND: Enhanced oxidative stress or defective anti-oxidant defenses are related to the pathogenesis of depressive symptoms. Lycopene is the most powerful antioxidant amongst the carotenoids. The aim of this study was to investigate the relationship between different vegetables, including tomatoes/tomato products (a major source of lycopene), and depressive symptoms in a community-based elderly population. METHODS: We analyzed a cross-sectional survey including 986 community-dwelling elderly Japanese individuals aged 70 years and older. Dietary intake was assessed using a valid self-administered diet-history questionnaire, and depressive symptoms were evaluated using the 30-item Geriatric Depression Scale with 2 cut-off points: 11 (mild and severe) and 14 (severe) or use of anti-depressive agents. RESULTS: The prevalence of mild and severe and severe depressive symptoms was 34.9% and 20.2%, respectively. After adjustments for potentially confounding factors, the odds ratios of having mild and severe depressive symptoms by increasing levels of tomatoes/tomato products were 1.00, 0.54, and 0.48 (p for trend <0.01). Similar relationships were also observed in the case of severe depressive symptoms. In contrast, no relationship was observed between intake of other kinds of vegetables and depressive symptoms. LIMITATIONS: This is a cross-sectional study, and not for making a clinical diagnosis of depressive episodes. CONCLUSIONS: This study demonstrated that a tomato-rich diet is independently related to lower prevalence of depressive symptoms. These results suggest that a tomato-rich diet may have a beneficial effect on the prevention of depressive symptoms. Further studies are needed to confirm these findings. Copyright © 2012 Elsevier B.V. All rights reserved.

positive: Antioxidants as potential therapeutics for neuropsychiatric disorders Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders.

positive: Dietary folate and the risk of depression in Finnish middle-aged men. A prospective follow-up study. BACKGROUND: Several cross-sectional studies have focused on the low blood folate levels of depressive patients. Nevertheless, no prospective studies have been published on the association between dietary folate and depression. METHODS: We studied the association between dietary folate and cobalamin and receiving a discharge diagnosis of depression in a prospective follow-up setting. Our cohort was recruited between 1984 and 1989 and followed until the end of 2000, and it consisted of 2,313 men aged between 42 and 60 years from eastern Finland. RESULTS: The mean intake of folate in the whole cohort was 256 microg/day (SD=76). Those below the median of energy-adjusted folate intake had higher risk of getting discharge diagnosis of depression (RR 3.04, 95% CI: 1.58, 5.86) during the follow-up period than those who had a folate intake above the median. This excess risk remained significant after adjustment for current socioeconomic status, the baseline HPL depression score, the energy-adjusted daily intake of fibre and vitamin C, and the total fat intake. CONCLUSIONS: A low dietary intake of folate may be a risk factor for severe depression. This also indicates that nutrition may have a role in the prevention of depression.

positive: Is low folate a risk factor for depression? A meta‐analysis and exploration of heterogeneity Low folate has been causatively linked to depression, but research is contradictory. An association may arise due to chance, bias, confounding or reverse causality. A systematic review of observational studies which examined the association between depression and folate was conducted. 11 relevant studies (15 315 participants; three case–control studies, seven population surveys and one cohort study) examining the risk of depression in the presence of low folate were found. Pooling showed a significant relationship between folate status and depression (odds ratio (OR)pooled unadjusted = 1.55; 95% CI 1.26 to 1.91). This relationship remained after adjustment for potential confounding (OR)pooled adjusted = 1.42; 95% CI 1.10 to 1.83). Folate levels were also lower in depression. There is accumulating evidence that low folate status is associated with depression. Much of this evidence comes from case–control and cross‐sectional studies. Cohort studies and definitive randomised‐controlled trials to test the therapeutic benefit of folate are required to confirm or refute a causal relationship.

positive: Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial. BACKGROUND: Clinical mood disorders often become clinically manifest in the later teenage years and early twenties and can be associated with a poor long-term prognosis. The primary prevention of these disorders would therefore have great public health value. Nutritional supplements are a feasible intervention for primary prevention and several epidemiological studies have indicated links between low folate status and depressive symptomatology in the general population. METHOD: A randomised, double blind, parallel group, placebo-controlled trial in which participants, aged 14-24 years, at increased familial risk of mood disorder, were randomised to folic acid (2.5 mg daily) or identical placebo liquid for a maximum of 36 months. Primary outcome data (the onset of a DSM-IV mood disorder) were collected from 112 participants; 56 per group. RESULTS: The incidence of mood disorder in the folic acid and placebo groups were 14.3% and 17.9% respectively, a non-significant difference. However, there was post-hoc evidence that folic acid delayed the time to onset of mood disorder in those participants who became unwell. LIMITATIONS: Small sample size and rate of onset of mood disorders lower than expected. CONCLUSIONS: Although long term folic acid supplementation was well tolerated, with high levels of adherence, there was no evidence that it reduced the incidence of mood disorder compared to those taking placebo. Copyright © 2014 Elsevier B.V. All rights reserved.

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: Vitamin D: extraskeletal health. Vitamin D deficiency is the most common nutritional deficiency and likely the most common medical condition in the world. The major cause of vitamin D deficiency has been the lack of appreciation that the body requires 5- to 10-fold higher intakes than is currently recommended by health agencies. There is now overwhelming and compelling scientific and epidemiologic data suggesting that the human body requires a blood level of 25(OH)D above 30 ng/mL for maximum health. To increase the blood level to the minimum 30 ng/mL requires the ingestion of at least 1000 IU of vitamin D per day for adults. In general, there is no downside to increasing either a child's or adult's vitamin D intake. Copyright 2010 Elsevier Inc. All rights reserved.

positive: From the Cover: The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake Numerous clinical trials using folic acid for prevention of cardiovascular disease, stroke, cognitive decline, and neural tube defects have been completed or are underway. Yet, all functions of folate are performed by tetrahydrofolate and its one-carbon derivatives. Folic acid is a synthetic oxidized form not significantly found in fresh natural foods; to be used it must be converted to tetrahydrofolate by dihydrofolate reductase (DHFR). Increasing evidence suggests that this process may be slow in humans. Here we show, using a sensitive assay we developed, that the reduction of folic acid by DHFR per gram of human liver (n = 6) obtained from organ donors or directly from surgery is, on average, less than 2% of that in rat liver at physiological pH. Moreover, in contrast to rats, there was almost a 5-fold variation of DHFR activity among the human samples. This limited ability to activate the synthetic vitamer raises issues about clinical trials using high levels of folic acid. The extremely low rate of conversion of folic acid suggests that the benefit of its use in high doses will be limited by saturation of DHFR, especially in individuals possessing lower than average activity. These results are also consistent with the reports of unmetabolized folic acid in plasma and urine.

negative: Safety considerations and potential interactions of vitamins: should vitamins be considered drugs? OBJECTIVE: To examine adverse effects, adverse events, and potential interactions of vitamins in light of their current prevalence of use, and to discuss whether vitamins should be considered over-the-counter drugs or natural health products/dietary supplements. DATA SOURCES: We performed a MEDLINE/PubMed search, explored 4 online databases (Medline Plus, Drug Digest, Natural Medicine Comprehensive Database, and the database of the University of Maryland), and examined reference lists of included studies published from 1966 through October 2009. STUDY SELECTION AND DATA EXTRACTION: The studies were reviewed, with an emphasis on randomized controlled clinical trials. We included articles with the most clinically important information with regard to adverse events and interactions. DATA SYNTHESIS: Vitamins are used by over one third of the North American population. Vitamins have documented adverse effects and toxicities, and most have documented interactions with drugs. While some vitamins (biotin, pantothenic acid, riboflavin, thiamine, vitamin B(12), vitamin K) have minor and reversible adverse effects, others, such as fat-soluble vitamins (A, E, D), can cause serious adverse events. Two water-soluble vitamins, folic acid and niacin, can also have significant toxicities and adverse events. CONCLUSIONS: Our recommendation is that vitamins A, E, D, folic acid, and niacin should be categorized as over-the-counter medications. Labeling of vitamins, especially those intended for children and other vulnerable groups, should include information on possible toxicities, dosing, recommended upper intake limits, and concurrent use with other products. Vitamin A should be excluded from multivitamin supplements and food fortificants.

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

negative: Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Elevated total plasma homocysteine has been linked to the development of cognitive impairment and dementia in later life and this can be reliably lowered by the daily supplementation of vitamin B6, B12, and folic acid. We performed a systematic review and meta-analysis of 19 English language randomized, placebo-controlled trials of homocysteine lowering B-vitamin supplementation of individuals with and without cognitive impairment at the time of study entry. We standardized scores to facilitate comparison between studies and to enable us to complete a meta-analysis of randomized trials. In addition, we stratified our analyses according to the folate status of the country of origin. B-vitamin supplementation did not show an improvement in cognitive function for individuals with (SMD = 0.10, 95%CI -0.08 to 0.28) or without (SMD = -0.03, 95%CI -0.1 to 0.04) significant cognitive impairment. This was irrespective of study duration (SMD = 0.05, 95%CI -0.10 to 0.20 and SMD = 0, 95%CI -0.08 to 0.08), study size (SMD = 0.05, 95%CI -0.09 to 0.19 and SMD = -0.02, 95%CI -0.10 to 0.05), and whether participants came from countries with low folate status (SMD = 0.14, 95%CI -0.12 to 0.40 and SMD = -0.10, 95%CI -0.23 to 0.04). Supplementation of vitamins B12, B6, and folic acid alone or in combination does not appear to improve cognitive function in individuals with or without existing cognitive impairment. It remains to be established if prolonged treatment with B-vitamins can reduce the risk of dementia in later life.

negative: Essentials of Healthy Eating: A Guide Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.

negative: Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.

negative: The role of phytic acid in legumes: antinutrient or beneficial function? This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.

negative: Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ... BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

negative: Effect of the vegetarian diet on non-communicable diseases. A vegetarian diet generally includes plenty of vegetables and fruits, which are rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe³⁺, folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol, total fat and saturated fatty acid, sodium, Fe²⁺, zinc, vitamin A, B₁₂ and D, and especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and circulatory and cerebrovascular diseases was significantly lower in vegetarians than in omnivorous populations. Compared with omnivores, the incidence of cancer and type 2 diabetes was also significantly lower in vegetarians. However, vegetarians have a number of increased risk factors for non-communicable diseases such as increased plasma homocysteine, mean platelet volume and platelet aggregability compared with omnivores, which are associated with low intake of vitamin B₁₂ and n-3 PUFA. Based on the present data, it would seem appropriate for vegetarians to carefully design their diet, specifically focusing on increasing their intake of vitamin B₁₂ and n-3 PUFA to further reduce already low mortality and morbidity from non-communicable diseases. © 2013 Society of Chemical Industry.

negative: Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis. The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.

negative: Dietary citric acid enhances absorption of aluminum in antacids. Ten healthy men ingested, twice daily between meals, during each of the seven-day experimental periods: (a) citric acid (as lemon juice), (b) Al(OH)3, or (c) Al(OH)3 + citric acid. Whole blood sampled after each dietary period was analyzed electrothermally after digestion with nitric acid. Moderate, but significant, increases in mean Al concentrations as compared with pretreatment values [5 (SD 3) micrograms of Al per liter] were seen after ingestion of either citric acid or Al(OH)3: 9 (SD 4) and 12 (SD 3) micrograms/L, respectively. Ingestion of both Al(OH)3 and citric acid resulted in a more pronounced, highly significant (p less than 0.001) increase in Al concentrations, to 23 (SD 2) micrograms Al/L, probably owing to formation and absorption of Al-citrate complexes.

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

negative: Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Obesity is associated with complications during pregnancy and increased health risks in the newborn. The objective of the present study was to establish possible relationships between gut microbiota, body weight, weight gain and biochemical parameters in pregnant women. Fifty pregnant women were classified according to their BMI in normal-weight (n 34) and overweight (n 16) groups. Gut microbiota composition was analysed by quantitative real-time PCR in faeces and biochemical parameters in plasma at 24 weeks of pregnancy. Reduced numbers of Bifidobacterium and Bacteroides and increased numbers of Staphylococcus, Enterobacteriaceae and Escherichia coli were detected in overweight compared with normal-weight pregnant women. E. coli numbers were higher in women with excessive weight gain than in women with normal weight gain during pregnancy, while Bifidobacterium and Akkermansia muciniphila showed an opposite trend. In the whole population, increased total bacteria and Staphylococcus numbers were related to increased plasma cholesterol levels. Increased Bacteroides numbers were related to increased HDL-cholesterol and folic acid levels, and reduced TAG levels. Increased Bifidobacterium numbers were related to increased folic acid levels. Increased Enterobacteriaceae and E. coli numbers were related to increased ferritin and reduced transferrin, while Bifidobacterium levels showed the opposite trend. Therefore, gut microbiota composition is related to body weight, weight gain and metabolic biomarkers during pregnancy, which might be of relevance to the management of the health of women and infants.

negative: Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption. The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.

negative: Low vitamin B-12 status and risk of cognitive decline in older adults. BACKGROUND: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE: We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. DESIGN: Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995. RESULTS: Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant. CONCLUSIONS: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.

negative: Steam cooking significantly improves in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage. Bile acid binding capacity has been related to the cholesterol-lowering potential of foods and food fractions. Lowered recirculation of bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of cancer. Bile acid binding potential has been related to lowering the risk of heart disease and that of cancer. Previously, we have reported bile acid binding by several uncooked vegetables. However, most vegetables are consumed after cooking. How cooking would influence in vitro bile acid binding of various vegetables was investigated using a mixture of bile acids secreted in human bile under physiological conditions. Eight replicate incubations were conducted for each treatment simulating gastric and intestinal digestion, which included a substrate only, a bile acid mixture only, and 6 with substrate and bile acid mixture. Cholestyramine (a cholesterol-lowering, bile acid binding drug) was the positive control treatment and cellulose was the negative control. Relative to cholestyramine, in vitro bile acid binding on dry matter basis was for the collard greens, kale, and mustard greens, 13%; broccoli, 10%; Brussels sprouts and spinach, 8%; green bell pepper, 7%; and cabbage, 5%. These results point to the significantly different (P < or = .05) health-promoting potential of collard greens = kale = mustard greens > broccoli > Brussels sprouts = spinach = green bell pepper > cabbage as indicated by their bile acid binding on dry matter basis. Steam cooking significantly improved the in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage compared with previously observed bile acid binding values for these vegetables raw (uncooked). Inclusion of steam-cooked collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage in our daily diet as health-promoting vegetables should be emphasized. These green/leafy vegetables, when consumed regularly after steam cooking, would lower the risk of cardiovascular disease and cancer, advance human nutrition research, and improve public health.

negative: Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. BACKGROUND & AIMS: Increasing evidence suggests that a low folate intake and impaired folate metabolism may be implicated in the development of gastrointestinal cancers. We conducted a systematic review with meta-analysis of epidemiologic studies evaluating the association of folate intake or genetic polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism, with risk of esophageal, gastric, or pancreatic cancer. METHODS: A literature search was performed using MEDLINE for studies published through March 2006. Study-specific relative risks were weighted by the inverse of their variance to obtain random-effects summary estimates. RESULTS: The summary relative risks for the highest versus the lowest category of dietary folate intake were 0.66 (95% confidence interval [CI], 0.53-0.83) for esophageal squamous cell carcinoma (4 case-control), 0.50 (95% CI, 0.39-0.65) for esophageal adenocarcinoma (3 case-control), and 0.49 (95% CI, 0.35-0.67) for pancreatic cancer (1 case-control, 4 cohort); there was no heterogeneity among studies. Results on dietary folate intake and risk of gastric cancer (9 case-control, 2 cohort) were inconsistent. In most studies, the MTHFR 677TT (variant) genotype, which is associated with reduced enzyme activity, was associated with an increased risk of esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, noncardia gastric cancer, gastric cancer (all subsites), and pancreatic cancer; all but one of 22 odds ratios were >1, of which 13 estimates were statistically significant. Studies of the MTHFR A1298C polymorphism were limited and inconsistent. CONCLUSIONS: These findings support the hypothesis that folate may play a role in carcinogenesis of the esophagus, stomach, and pancreas.

negative: An impact of the diet on serum fatty acid and lipid profiles in Polish vegetarian children and children with allergy. BACKGROUND/OBJECTIVES: Vegetarian diet has become an increasing trend in western world and in Poland. The frequency of allergies is growing, and the effectiveness of vegetarian diet in allergic diseases is a concern for research. We aimed to study an effect of vegetarian diet on lipid profile in serum in a group of Polish children in Poland and to investigate lipid parameters in healthy vegetarian children and in omnivorous children with diagnosed atopic disease. SUBJECTS/METHODS: Serum lipid profiles (triglycerides, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, fatty acids) were assessed in groups of children: healthy vegetarians (n=24) and children with diagnosed atopic diseases (n=16), with control group of healthy omnivores (n=18). Diet classification was assessed by a questionnaire. RESULTS: No differences were observed in serum triglycerides, LDL cholesterol and saturated and monounsaturated fatty acids level in all groups. In the group of Polish vegetarian children, we recorded high consumption of vegetable oils rich in monounsaturated fatty acid, and sunflower oil containing linoleic acid. This observation was associated with higher content of linoleic acid in serum in this group. Among polyunsaturated n-6 fatty acids, linoleic acid revealed significantly (P<0.05) lower levels in allergy vs vegetarian groups. In case of eicosapentaenoic acid (n-3 fatty acid), the allergy group showed higher levels of this compound in comparison to vegetarians. CONCLUSIONS: Significantly higher concentration of linoleic acid in vegetarian children in comparison to allergy group indicated possible alternative path of lipid metabolism in studied groups, and in consequence, some elements of vegetarian diet may promote protection against allergy.

negative: Rarity of colon cancer in Africans is associated with low animal product consumption, not fiber. OBJECTIVE: To investigate whether the rarity of colon cancer in black Africans (prevalence, < 1:100,000) can be accounted for by dietary factors considered to reduce risk, and by differences in colonic bacterial fermentation. METHODS: Samples of the adult black South African population were drawn from several rural and urban regions. Food consumption was assessed by home visits, food frequency questionnaires, computerized analysis of 72-h dietary recall, and blood sampling. Colonic fermentation was measured by breath H2 and CH4 response to a traditional meal, and to 10-g of lactulose. Cancer risk was estimated by measurement of epithelial proliferation indices (Ki-67 and BrdU) in rectal mucosal biopsies. Results were evaluated by comparison to measurements in high-risk white South Africans (prevalence, 17:100,000). RESULTS: Epithelial proliferation was significantly lower in rural and urban blacks than whites. The diets of all the black subgroups were characterized by a low animal product and high boiled maize-meal content, whereas whites consumed more fresh animal products, cheese, and wheat products. Blacks consumed below RDA quantities of fiber (43% of RDA), vitamin A (78%), C (62%), folic acid (80%) and calcium (67%), whereas whites consumed more animal protein (177% of RDA) and fat (153%). Fasting and food-induced breath methane production was two to three times higher in blacks. CONCLUSIONS: The low prevalence of colon cancer in black Africans cannot be explained by dietary "protective" factors, such as, fiber, calcium, vitamins A, C and folic acid, but may be influenced by the absence of "aggressive" factors, such as excess animal protein and fat, and by differences in colonic bacterial fermentation.

negative: Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Trial Registration Controlled-Trials.com ISRCTN94410159

negative: How free fatty acids inhibit glucose utilization in human skeletal muscle. Rat muscle studies suggest competition between free fatty acids (FFA) and glucose for oxidation, resulting in glucose-6-phosphate accumulation. However, FFA decrease glucose-6-phosphate in human skeletal muscle, indicating direct inhibition of glucose transport/phosphorylation. This mechanism could redirect glucose from muscle to brain during fasting and explain the insulin resistance associated with high-lipid diets and obesity.

negative: A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. BACKGROUND: Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans (prebiotics). Results have been inconsistent; however, and no studies have been conducted to determine whether this effect persists with long-term use. OBJECTIVE: The objective was to assess the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y of supplementation with an inulin-type fructan. DESIGN: Pubertal adolescents were randomly assigned to receive 8 g/d of a mixed short and long degree of polymerization inulin-type fructan product (fructan group) or maltodextrin placebo (control group). Bone mineral content and bone mineral density were measured before randomization and after 1 y. Calcium absorption was measured with the use of stable isotopes at baseline and 8 wk and 1 y after supplementation. Polymorphisms of the Fok1 vitamin D receptor gene were determined. RESULTS: Calcium absorption was significantly greater in the fructan group than in the control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1 genotype was present such that subjects with an ff genotype had the least initial response to fructan. After 1 y, the fructan group had a greater increment in both whole-body bone mineral content (difference: 35 +/- 16 g; P = 0.03) and whole-body bone mineral density (difference: 0.015 +/- 0.004 g/cm(2); P = 0.01) than did the control group. CONCLUSION: Daily consumption of a combination of prebiotic short- and long-chain inulin-type fructans significantly increases calcium absorption and enhances bone mineralization during pubertal growth. Effects of dietary factors on calcium absorption may be modulated by genetic factors, including specific vitamin D receptor gene polymorphisms.

negative: Association between dietary fiber intake and the folate status of a group of female adolescents. The main objective of this study was to assess the association between dietary fiber intake and the folate status of Canadian female adolescents. We also assessed dietary folate intakes and evaluated the prevalence of biochemical folate deficiency in these subjects. Female adolescents aged 14-19 y (n = 224) were recruited and fasting blood samples were collected. Dietary intakes (3-d food record) were recorded and participants were classified as lactoovovegetarians, semivegetarians, or omnivores on the basis of food-consumption patterns assessed with food-frequency questionnaires. Fourteen percent, 17%, and 26% of lactoovovegetarians, semivegetarians, and omnivores, respectively, had dietary folate intakes below their predicted requirements; 1%, 4%, and 23%, respectively, had serum folate concentrations indicative of deficiency. Despite low dietary folate intakes and serum folate concentrations, few subjects had homocysteine concentrations indicative of deficiency, suggesting that the degree of folate depletion had not yet produced functional consequences. Most important, results suggest that the consumption of nonstarch polysaccharide is significantly associated with serum folate concentrations (P < 0.001). For each 1-g increase in nonstarch polysaccharide intake, a 1.8% increase in serum folate concentration is expected. In summary, we propose that an increase in nonstarch polysaccharide intake may promote the intestinal biosynthesis of folate, providing a complementary strategy to enhance the folate nutriture of humans.

negative: A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyalgia symptoms and promoted toxic-element deto... BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of a modified elimination diet and a supplemental medical food on clinical symptoms of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ), metallothionein mRNA expression, and urinary toxic element excretion. METHODS: Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a sequential design. During the initial 4-week Program A (control), participants consumed a modified US Department of Agriculture food pyramid diet and a rice protein powder supplement that provided basic macronutrient support. During the second 4-week Program B (intervention), participants consumed a modified elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to baseline, both programs showed trends toward lower mean FIQ total score, MSQ total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest headaches score. Compared to Program A, Program B resulted in a significant decrease (P< .05) in the FIQpain score and stiffness score. Participants also had better pain tolerance at five tender points during Program B than during Program A. Higher metallothionein mRNA expression was observed during Program B. An increase in creatinine-adjusted mercury excretion and suggestive increase in creatinine-adjusted arsenic excretion were noted when Program B was compared to baseline. Urinary mercury/arsenic concentrations were inversely associated with FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and efficacious botanically derived medical food treatment program for the amelioration of FM symptoms.

negative: Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. BACKGROUND AND AIM: Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. However, to what degree these effects are mediated by steatosis extent is unknown. METHODS: We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated. RESULTS: Concurrent with PPARgamma and SREBP-1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPARalpha expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid. CONCLUSIONS: Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.

negative: The link between erectile and cardiovascular health: the canary in the coal mine. Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.

negative: Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients. OBJECTIVE: Alpha-linolenic acid (ALA) is the natural precursor of the cardioprotective long-chain n-3 fatty acids. Available data indicate a possible beneficial effect of ALA on cardiovascular disease (CVD), but the response of various CVD risk factors to increased ALA intake is not well characterized. The purpose of the present study was to examine the effect of increased ALA intake on blood pressure in man. DESIGN, SETTING, SUBJECTS AND INTERVENTIONS: We used a prospective, two-group, parallel-arm design to examine the effect of a 12-week dietary supplementation with flaxseed oil, rich in ALA (8 g/day), on blood pressure in middle-aged dyslipidaemic men (n=59). The diet of the control group was supplemented with safflower oil, containing the equivalent n-6 fatty acid (11 g/day linoleic acid (LA); n=28). Arterial blood pressure was measured at the beginning and at the end of the dietary intervention period. RESULTS: Supplementation with ALA resulted in significantly lower systolic and diastolic blood pressure levels compared with LA (P=0.016 and P=0.011, respectively, from analysis of variance (ANOVA) for repeated measures). CONCLUSIONS: We observed a hypotensive effect of ALA, which may constitute another mechanism accounting in part for the apparent cardioprotective effect of this n-3 fatty acid.

negative: Micronutrients intake is associated with improved sperm DNA quality in older men. OBJECTIVE: To investigate whether lifestyle factors such as increased dietary intake of micronutrients reduce the risks of sperm DNA damage, and whether older men benefit more than younger men. DESIGN: Cross-sectional study design with equalized assignments into age groups. SETTING: National laboratory and university. PATIENT(S): Nonclinical group of 22-80-year-old nonsmoking men (n = 80) who reported no fertility problems. MAIN OUTCOME MEASURE(S): Sperm DNA damage measured by alkaline and neutral DNA electrophoresis (i.e., sperm Comet assay). RESULT(S): Sociodemographics, occupational exposures, medical and reproductive histories, and lifestyle habits were determined by questionnaire. The average daily dietary and supplement intake of micronutrients (vitamin C, vitamin E, b-carotene, zinc, and folate) was determined using the 100-item Modified Block Food Frequency Questionnaire (FFQ). Men with the highest intake of vitamin C had approximately 16% less sperm DNA damage (alkaline sperm Comet) than men with the lowest intake, with similar findings for vitamin E, folate, and zinc (but not β-carotene). Older men (>44 years) with the highest vitamin C intake had approximately 20% less sperm DNA damage compared with older men with the lowest intake, with similar findings for vitamin E and zinc. The older men with the highest intake of these micronutrients showed levels of sperm damage that were similar to those of the younger men. However, younger men (<44 years) did not benefit from higher intakes of the micronutrients surveyed. CONCLUSION(S): Men with higher dietary and supplement intake of certain micronutrients may produce sperm with less DNA damage, especially among older men. This raises the broader question of how lifestyle factors, including higher intakes of antioxidants and micronutrients, might protect somatic as well as germ cells against age-associated genomic damage. Copyright © 2012. Published by Elsevier Inc.

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

negative: Risk factors and preventive interventions for Alzheimer disease: state of the science. BACKGROUND: Numerous studies have investigated risk factors for Alzheimer disease (AD). However, at a recent National Institutes of Health State-of-the-Science Conference, an independent panel found insufficient evidence to support the association of any modifiable factor with risk of cognitive decline or AD. OBJECTIVE: To present key findings for selected factors and AD risk that led the panel to their conclusion. DATA SOURCES: An evidence report was commissioned by the Agency for Healthcare Research and Quality. It included English-language publications in MEDLINE and the Cochrane Database of Systematic Reviews from 1984 through October 27, 2009. Expert presentations and public discussions were considered. STUDY SELECTION: Study inclusion criteria for the evidence report were participants aged 50 years and older from general populations in developed countries; minimum sample sizes of 300 for cohort studies and 50 for randomized controlled trials; at least 2 years between exposure and outcome assessment; and use of well-accepted diagnostic criteria for AD. DATA EXTRACTION: Included studies were evaluated for eligibility and data were abstracted. Quality of overall evidence for each factor was summarized as low, moderate, or high. DATA SYNTHESIS: Diabetes mellitus, hyperlipidemia in midlife, and current tobacco use were associated with increased risk of AD, and Mediterranean-type diet, folic acid intake, low or moderate alcohol intake, cognitive activities, and physical activity were associated with decreased risk. The quality of evidence was low for all of these associations. CONCLUSION: Currently, insufficient evidence exists to draw firm conclusions on the association of any modifiable factors with risk of AD.

negative: Plasma deoxycholic acid concentration is elevated in postmenopausal women with newly diagnosed breast cancer. OBJECTIVE: High concentrations of plasma deoxycholic acid (DCA) are found in human breast cyst fluid and it has been hypothesised that this may be related to risk of breast cancer. The aim of this pilot study was to ascertain whether plasma bile acid concentrations were greater in women with breast cancer. DESIGN: A case-control study comparing postmenopausal women with breast cancer with healthy controls was conducted. SUBJECTS: Twenty Caucasian postmenopausal breast cancer patients were recruited at the time of diagnosis together with 20 healthy controls matched for age and body mass index. Exclusion criteria included any treatment for breast cancer, use of hormone replacement therapy in the last 12 months, diabetes mellitus, a history of liver or gall bladder disease or abnormal liver function. MEASUREMENTS: Fasting plasma bile acid concentrations were determined by gas-liquid chromatography/mass spectrometry. RESULTS: The mean plasma DCA concentration was 52% higher (P=0.012) in patients with breast cancer compared with controls. CONCLUSION: These results support the hypothesis that DCA may be involved in the aetiology of breast cancer.

negative: Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.

negative: Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. Mild to moderate hyperhomocysteinemia is a risk factor for neurodegenerative diseases. Human studies suggest that homocysteine (Hcy) plays a role in brain damage, cognitive and memory decline. Numerous studies in recent years investigated the role of Hcy as a cause of brain damage. Hcy itself or folate and vitamin B12 deficiency can cause disturbed methylation and/or redox potentials, thus promoting calcium influx, amyloid and tau protein accumulation, apoptosis, and neuronal death. The Hcy effect may also be mediated by activating the N-methyl-D-aspartate receptor subtype. Numerous neurotoxic effects of Hcy can be blocked by folate, glutamate receptor antagonists, or various antioxidants. This review describes the most important mechanisms of Hcy neurotoxicity and pharmacological agents known to reverse Hcy effects.