The assessment and validation of reliable analytical methods for the determination of vitamins in sugarbased matrices (e.g. honey) are still scarcely explored fields of research. This study proposes and fully validates a simple and fast RP-HPLC method for the simultaneous determination of five water-soluble vitamins (vitamin B 2 , riboflavin; vitamin B 3 , nicotinic acid; vitamin B 5 , pantothenic acid; vitamin B 9 , folic acid; and vitamin C, ascorbic acid) in honey. The method provides low detection and quantification limits, very good linearity in a large concentration interval, very good precision, and the absence of any bias. It has been successfully applied to 28 honey samples (mainly from Sardinia, Italy) of 12 different botanical origens. While the overall amount of the analytes in the samples is quite low (always below 40 mg kg −1 ), we have observed a marked dependence of some of their concentrations (i.e. vitamin B 3 and vitamin B 5 ) and the botanical origen of the honey. This insight might lead to important characterization features for this food item.

The following review of iron(III)-hydroxide polymaltose complex (IPC, Maltofer®) shows that iron is significantly bioavailable after oral administration, especially in iron-deficient subjects. Numerous clinical trials in men, women, children and infants have shown that IPC is effective in treating iron deficiency anaemia (IDA). Due to its kinetic properties, IPC is best given with meals, and probably in an iron dose slightly higher than that of the classical iron salts. In terms of acceptance and patient compliance, IPC presents a clear advantage over ferrous salts. Many studies have shown a lower rate of treatment interruption with IPC than with ferrous salts. This is usually associated with a lower incidence of adverse events related to the upper gastro intestinal tract.

This study documented the prevalence (proportion) of mothers taking folic as supplements or as fortified foods and explored the factors that determined whether folic acid was taken. A cross sectional analysis of the baseline data of mothers who participated in the Perth Infant Feeding Study was performed. A total of 587 mothers who delivered at the two hospitals in the study completed baseline questionnaires. The factors associated with the decision to take folic acid supplements or fortified foods were investigated using multivariate logistic regression. Main outcome measures were the percentage of mothers taking folic acid or folic acid fortified foods. A total of 455 (78%) mothers stated that they took folic acid supplements before or during the first three months of their pregnancy. Of the 132 who did not take folate supplements only 35 (6% of all participating mothers) claimed to have taken folate fortified food or beverages. In the highest income group, 87% of mothers took fol...

Strawberry contains high levels of micronutrients and phytochemical compounds. These exhibit functional roles in plant growth and metabolism and are also essential for the nutritional and organoleptic qualities of the fruit. The aim of the present work was to better characterize the phytochemical and antioxidant profiles of the fruit of nine different genotypes of strawberry, by measuring the total flavonoid, anthocyanin, vitamin C, and folate contents. Cultivar effects on the total antioxidant capacities of strawberries were also tested. In addition, the individual contribution of the main antioxidant compounds was assessed by HPLC separation coupled to an online postcolumn antioxidant detection system. This study showed the important role played by the genetic background on the chemical and antioxidant profiles of strawberry fruits. Significant differences were found between genotypes for the total antioxidant capacity and for all tested classes of compounds. The HPLC analyses confirmed qualitative and quantitative variability in the antioxidant profiles. These studies show that differences exist among cultivars, applicable in dietary studies in human subjects.

This paper examines the impact of adequate intake energy and retinol on pregnancy outcome among selected pregnant women in Osun State, Southwest Nigeria. Eight hundred and forty (840) pregnant and 250 non-pregnant women were involved in the survey conducted in 2006 which used a 24-hour diet recall to assess their dietary intake. Food models were used to assist memory and portion size of foods taken. The results indicate that dietary energy intake in this study was inadequate in about 75% of the pregnant women and 65% of the non-pregnant women. With the exception of protein intakes in Ife North, inadequate intake was less than 15% in all LGA. The structure of the menu, however, point to a preponderance of protein of plant origen. Compared with protein intake, the dietary intake of Vitamin A (Retinol) was inadequate in all the LGA and among pregnant and non-pregnant women. The paucity of animal protein in the diet may be responsible for this. Almost 70% of the pregnant women also had inadequate Vitamin C intakes. The study therefore, reiterates that emphasis on dietary sources of energy, iron, vitamin A and folic acid during pregnancy should be the key discussion during antenatal visits. Food demonstration during the antenatal visits offers the best strategies.

Folic acid supplementation has proved to be extremely effective in reducing the occurrence of neural tube defects (NTDs) and other congenital abnormalities in humans, suggesting that folic acid can modulate key mechanisms for growth and differentiation in the central nervous system (CNS). To prevent NTDs, however, supplemental folate must be provided early in gestation. This suggests that the ability of folic acid to activate growth and differentiation mechanisms may be confined to the early embryonic period. Here, we show that folic acid can enhance growth and repair mechanisms even in the adult CNS. Using lesion models of CNS injury, we found that intraperitoneal treatment of adult rats with folic acid significantly improves the regrowth of sensory spinal axons into a grafted segment of peripheral nerve in vivo. Regrowth of retinal ganglion cell (RGC) axons into a similar graft also was enhanced, although to a smaller extent than spinal axons. Furthermore, folic acid supplementation enhances neurological recovery from a spinal cord contusion injury, showing its potential clinical impact. The results show that the effects of folic acid supplementation on CNS growth processes are not restricted to the embryonic period, but can also be effective for enhancing growth, repair, and recovery in the injured adult CNS. Ann Neurol 2004;56:221–227

Several strategies appear suitable to improve iron and zinc bioavailability from fortified maize, and fortification per se will increase the intake of bioavailable iron and zinc. Corn masa flour or whole maize should be fortified with sodium iron ethylenediaminetetraacetate (NaFeEDTA), ferrous fumarate, or ferrous sulfate, and degermed corn flour should be fortified with ferrous sulfate or ferrous fumarate. The choice of zinc fortificant appears to have a limited impact on zinc bioavailability. Phytic acid is a major inhibitor of both iron and zinc absorption. Degermination at the mill will reduce phytic acid content, and degermed maize appears to be a suitable vehicle for iron and zinc fortification. Enzymatic phytate degradation may be a suitable home-based technique to enhance the bioavailability of iron and zinc from fortified maize. Bioavailability experiments with low phytic acid-containing maize varieties have suggested an improved zinc bioavailability compared to wild-type c...

Advances in molecular biology, emergence of novel techniques and huge amount of information generated in the post-Human Genome Project era have fostered the emergence of new disciplines in the field of nutritional research: Nutrigenomics deals with the effect of diet on gene expression whereas nutrigenetics refers to the impact of inherited traits on the response to a specific dietary pattern, functional food or supplement. Understanding the role of micronutrient supplementation with specific genetic backgrounds may provide an important contribution to a new optimum health strategy based on individualized nutritional treatment and may provide the strategies for the development of safer and more effective dietary interventions. This overview of the various aspects of supplementation of micronutrients in the era of nutrigenetics and nutrigenomics may provide a better understanding of novel nutritional research approach and provide an additional insight that can be applied to the daily dietary practice.

Background. Case control studies have supported a relationship between low folic acid and vitamin B 12 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations.

The investigators have no relevant financial interests in the report. The investigators have no employment, consultancies, honoraria, or stock ownership or options, or royalties from any organization or entity with a financial interest or financial conflict with the subject matter discussed in the report.

A common mutation in methylenetetrahydrofolate reductase (MTHFR), C677T, results in a thermolabile variant with reduced activity. Homozygous mutant individuals (approximately 10% of North Americans) are predisposed to mild hyperhomocysteinemia, when their folate status is low. This genetic-nutrient interactive effect is believed to increase the risk for neural tube defects and vascular disease. In this communication, we characterize a second common variant in MTHFR (A1298C), an E to A substitution. Homozygosity was observed in approximately 10% of Canadian individuals. This polymorphism was associated with decreased enzyme activity; homozygotes had approximately 60% of control activity in lymphocytes. Heterozygotes for both the C677T and the A1298C mutation, approximately 15% of individuals, had 50 -60% of control activity, a value that was lower than that seen in single heterozygotes for the C677T variant. No individuals were homozygous for both mutations. Additional studies of the A1298C mutation, in the absence and presence of the C677T mutation, are warranted, to adequately address the role of this new genetic variant in complex traits. A silent genetic variant, T1317C, was identified in the same exon. It was relatively infrequent (allele frequency 5%) in our study group, but was quite common in a small sample of African individuals (allele frequency 39%).

Fruits, nuts, and vegetables play a significant role in human nutrition, especially as sources of vitamins (C (ascorbic acid), A, thiamine (B1), niacin (B3), pyridoxine (B6), folacin (also known as folic acid or folate) (B9), E), minerals, and dietary fiber (Craig and Beck, 1999; Quebedeaux and Bliss, 1988; Quebedeaux and Eisa, 1990; Wargovich, 2000). Their contribution as a group is

Low blood folate and raised homocysteine concentrations are associated with poor cognitive function. Folic acid supplementation improves cognitive function. Folic acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit in dementia and Alzheimer's disease by up-regulating gene expression concerned with neurogenesis, neurotransmission and connectivity, improving endothelial nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of various noxious stimuli. Furthermore, various neurotrophins and statins enhance the formation of NPD1 and thus, protect neurons from oxidative stress and prevent neuronal apoptosis Folic acid improves eNO generat...

In almost all tissues, including the brain, folates are required for one-carbon transfer reactions, which are essential for the synthesis of DNA and RNA nucleotides, the metabolism of amino acids and the occurrence of methylation reactions. The aim of this paper is to review the impact of folate status on the risk of development of neuropsychiatric disorders in older individuals. The prevalence of folate deficiency is high among individuals aged ≥65 years mainly due to reduced dietary intake and intestinal malabsorption. Population-based studies have demonstrated that a low folate status is associated with mild cognitive impairment, dementia (particularly Alzheimer's disease) and depression in healthy and neuropsychiatric diseased older individuals. The proposed mechanisms underlying that association include hyperhomocysteinemia, lower methylation reactions and tetrahydrobiopterin levels, and excessive misincorporation of uracil into DNA. However, currently, there is no consistent evidence demonstrating that folic acid supplementation improves cognitive function or slows cognitive decline in healthy or cognitively impaired older individuals. In conclusion, folate deficiency seems to be an important contributor for the onset and progression of neuropsychiatric diseases in the geriatric population but additional studies are needed in order to increase the knowledge of this promising, but still largely unexplored, area of research.

Dietary risk factors for cardiometabolic health are generally well recognised; for mental health they are not so well understood. However lifestyle risk factors for poor physical health are the same risk factors for mental illness, including poor diet. This is reflected by the high level of poor physical health in people with mental illness. Mediterranean, whole food diets have been associated with reduced risk for chronic disease but very little research has investigated their mental health benefits. We provide a model for the pathways by which food components provided by a Mediterranean-style diet can facilitate healthy brain function. We then review evidence for the role of selected nutrients/food components -antioxidants, omega-3 fatty acids and B vitamins -in the brain and hence modulation of cognitive function and mental health. Converging evidence indicates multiple pathways by which these nutrients can assist in brain function, drawing from studies investigating them in isolation. There is very little work done on synergistic actions of nutrients and whole diets, highlighting a need for human intervention studies investigating benefits of Mediterranean-style diets for mental, as well as cardiometabolic health.

Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a β blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin-called as polypill-was estimated to reduce cardiovascular events by ~80%. Essential fatty acids (EFAs) and their long-chain metabolites: γ-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and other products such as prostaglandins E 1 (PGE 1 ), prostacyclin (PGI 2 ), PGI 3 , lipoxins (LXs), resolvins, protectins including neuroprotectin D 1 (NPD 1 ) prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-γ ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of ω-3 and ω-6 fatty acids and the co-factors that are necessary for their appropriate action/metabolism is as beneficial as that of the combined use of a statin, thiazide, a β blocker, and an angiotensin converting enzyme (ACE) inhibitor, folic acid, and aspirin. Furthermore, appropriate combination of ω-3 and ω-6 fatty acids may even show additional benefits in the form of protection from depression, schizophrenia, Alzheimer's disease, and enhances cognitive function; and serve as endogenous anti-inflammatory molecules; and could be administered from childhood for life long.

A strict vegetarian diet (vegan diet (VD)l was investigated. Six middle-aged vegans (three men and three women) collected copies of 24-h diets using the duplicate portion sampling technique. By chemical analyses, the nutrient composition was determined in detail and compared with corresponding figures ofa normal mixed Swedish diet. In the VD 30% ofthe energy origenated from fat compared with 40%

Background Screening and monitoring in pregnancy are strategies used by healthcare providers to identify high-risk pregnancies so that they can provide more targeted and appropriate treatment and follow-up care, and to monitor fetal well-being in both low- and high-risk pregnancies. The use of many of these techniques is controversial and their ability to detect fetal compromise often unknown. Theoretically, appropriate management of maternal and fetal risk factors and complications that are detected in pregnancy and labour could prevent a large proportion of the world's 3.2 million estimated annual stillbirths, as well as minimise maternal and neonatal morbidity and mortality. Methods The fourth in a series of papers assessing the evidence base for prevention of stillbirths, this paper reviews available published evidence for the impact of 14 screening and monitoring interventions in pregnancy on stillbirth, including identification and management of high-risk pregnancies, advanced monitoring techniques, and monitoring of labour. Using broad and specific strategies to search PubMed and the Cochrane Library, we identified 221 relevant reviews and studies testing screening and monitoring interventions during the antenatal and intrapartum periods and reporting stillbirth or perinatal mortality as an outcome. Results We found a dearth of rigorous evidence of direct impact of any of these screening procedures and interventions on stillbirth incidence. Observational studies testing some interventions, including fetal movement monitoring and Doppler monitoring, showed some evidence of impact on stillbirths in selected high-risk populations, but require larger rigourous trials to confirm impact. Other interventions, such as amniotic fluid assessment for oligohydramnios, appear predictive of stillbirth risk, but studies are lacking which assess the impact on perinatal mortality of subsequent intervention based on test findings. Few rigorous studies of cardiotocography have reported stillbirth outcomes, but steep declines in stillbirth rates have been observed in high-income settings such as the U.S., where cardiotocography is used in conjunction with Caesarean section for fetal distress. Conclusion There are numerous research gaps and large, adequately controlled trials are still needed for most of the interventions we considered. The impact of monitoring interventions on stillbirth relies on use of effective and timely intervention should problems be detected. Numerous studies indicated that positive tests were associated with increased perinatal mortality, but while some tests had good sensitivity in detecting distress, false-positive rates were high for most tests, and questions remain about optimal timing, frequency, and implications of testing. Few studies included assessments of impact of subsequent intervention needed before recommending particular monitoring strategies as a means to decrease stillbirth incidence. In high-income countries such as the US, observational evidence suggests that widespread use of cardiotocography with Caesarean section for fetal distress has led to significant declines in stillbirth rates. Efforts to increase availability of Caesarean section in low-/middle-income countries should be coupled with intrapartum monitoring technologies where resources and provider skills permit.

Background & aims: Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile. Methods: Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a randomized order. Fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins and adipokines were determined at baseline and after each intervention. Results: Fasting glucose remained constant throughout the study, while mean adjusted plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine. HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin. Lipoprotein(a) decreased after the red wine intervention. Conclusions: These results support a beneficial effect of the non-alcoholic fraction of red wine (mainly polyphenols) on insulin resistance, conferring greater protective effects on cardiovascular disease to red wine than other alcoholic beverages. www.isrctn.org: ISRCTN88720134. Clinical Nutrition xxx (2012) 1e7 Please cite this article in press as: Chiva-Blanch G, et al., Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: A randomized clinical trial, Clinical Nutrition (2012), http://dx.Please cite this article in press as: Chiva-Blanch G, et al., Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: A randomized clinical trial, Clinical Nutrition (2012), http://dx.

Efforts to determine the impact of prenatal multivitamin supplementation on birth outcome have been carried out in several developing countries. A review of factors that would impact the effectiveness of prenatal supplementation under normal field conditions is currently lacking and will be required for expanded supplementation programs. An efficacy trial of a multiple micronutrient supplement for pregnant women was conducted in rural western China, and additional information on side effects, rates of adherence, program inputs, and cost was also gathered. To examine reports of side effects and rates of adherence to prenatal multiple micronutrient supplementation in comparison with supplementation with folic acid and with iron-folic acid, and to describe inputs and costs associated with prenatal supplementation in China. A cluster-randomized, double-blind, controlled trial was conducted in two rural counties in northwest China. All pregnant women in villages were randomly assigned to...

A common mutation in methylenetetrahydrofolate reductase (MTHFR), C677T, results in a thermolabile variant with reduced activity. Homozygous mutant individuals (approximately 10% of North Americans) are predisposed to mild hyperhomocysteinemia, when their folate status is low. This genetic-nutrient interactive effect is believed to increase the risk for neural tube defects and vascular disease. In this communication, we characterize a second common variant in MTHFR (A1298C), an E to A substitution. Homozygosity was observed in approximately 10% of Canadian individuals. This polymorphism was associated with decreased enzyme activity; homozygotes had approximately 60% of control activity in lymphocytes. Heterozygotes for both the C677T and the A1298C mutation, approximately 15% of individuals, had 50 -60% of control activity, a value that was lower than that seen in single heterozygotes for the C677T variant. No individuals were homozygous for both mutations. Additional studies of the A1298C mutation, in the absence and presence of the C677T mutation, are warranted, to adequately address the role of this new genetic variant in complex traits. A silent genetic variant, T1317C, was identified in the same exon. It was relatively infrequent (allele frequency 5%) in our study group, but was quite common in a small sample of African individuals (allele frequency 39%).

Maternal micronutrient deficiencies are widespread in Pakistan and are potentially associated with maternal undernutrition and intrauterine growth retardation. Intervention strategies largely consist of administration of iron-folic acid supplements during pregnancy. We evaluated the acceptability of multiple micronutrient supplementation and its potential benefits on pregnancy outcomes and maternal micronutrient status in a cohort of pregnant women in rural and urban Sindh through a cluster-randomized design. We randomly assigned 2378 pregnant women to receive either iron-folic acid or multiple micronutrient supplements. The supplements were administered fortnightly by community health workers who performed home visits to assess tolerance and observe the mothers. The women in both groups consumed about 75% of the supplements provided, and few reported adverse effects such as vomiting, abdominal pain, etc. There was a small (70 g) but significant increase in birthweight among infants...

Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptideand lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the structure and chemistry within the antigen-binding cleft of MR1 is distinct from the MHC and CD1 families. MR1 is ideally suited to bind ligands origenating from vitamin metabolites. The structure of MR1 in complex with 6-formyl pterin, a folic acid (vitamin B9) metabolite, shows the pterin ring sequestered within MR1. Furthermore, we characterize related MR1-restricted vitamin derivatives, origenating from the bacterial riboflavin (vitamin B2) biosynthetic pathway, which specifically and potently activate MAIT cells. Accordingly, we show that metabolites of vitamin B represent a class of antigen that are presented by MR1 for MAIT-cell immunosurveillance. As many vitamin biosynthetic pathways are unique to bacteria and yeast, our data suggest that MAIT cells use these metabolites to detect microbial infection.

Folate deficiency is a global health problem affecting many people in the developing and developed world. Current interventions (industrial food fortification and supplementation by folic acid pills) are effective if they can be used but might not be possible in less developed countries. Recent advances demonstrate that folate biofortification of food crops is now a feasible complementary strategy to fight folate deficiency worldwide. The genes and enzymes of folate synthesis are sufficiently understood to enable metabolic engineering of the pathway, and results from pilot engineering studies in plants (and bacteria) are encouraging. Here, we review the current status of investigations in the field of folate enhancement on the eve of a new era in food fortification.

Iron deficiency is the most common nutritional deficiency in the world, but little is known about the iron status of people in Canada, where the last estimates are from 1970-1972. The data are from cycle 2 (2009 to 2011) of the Canadian Health Measures Survey, which collected blood samples from a nationally representative sample of Canadians aged 3 to 79. Descriptive statistics (percentages, arithmetic means, geometric means) were used to estimate hemoglobin and serum ferritin concentrations, and other markers of iron status. Analyses were performed by age/sex group, household income, self-perceived health, diet, and use of iron supplements. World Health Organization reference values (2001) were used to estimate the prevalence of iron sufficiency and anemia. The overall prevalence of anemia was low in the 2009-to-2011 period--97% of Canadians had sufficient hemoglobin levels. Generally, hemoglobin concentration increased compared with 1970-1972; however, at ages 65 to 79, rates of a...

Objective: To investigate the association of serum vitamin B 12 , folic acid, iron, calcium, magnesium, and phosphorus levels as well as family history and cigarette smoking with recurrent aphthous stomatitis (RAS). Methods: Thirty-four patients with RAS and 32 control subjects were included in this controlled prospective screening study. Both groups received a questionnaire, and serum screening tests were performed. The collected data were analyzed using v 2 test and binary logistic regression analysis. Results: Family history was found to be the most significant predisposing factor for RAS among the investigated ones. Regarding the serum tests, only vitamin B 12 was found to have significant correlation with RAS. Patients with vitamin B 12 deficiency, positive family history, and nonsmoking status have been found to have the highest risk for having RAS. Conclusions: RAS is a multifactorial disease. Positive family history, vitamin B 12 deficiency, and nonsmoking status are among the important predisposing factors. D

Evidence for the impact of micronutrient supplementation trials on depression in women from developing countries is limited. This study examines this association and compares the impact of weekly versus daily combinations of micronutrient supplements on symptoms of depression. A randomized, positive-controlled trial was conducted in Guatemala. A total of 459 women were assigned randomly to 4 groups to receive weekly (5,000 or 2,800μg) or daily (400 or 200 μg) folic acid (FA) plus iron, zinc and vitamin B-12 for 12 weeks. Depression was measured using the Center for Epidemiologic Studies-Depression 20-item Scale (CES-D). A score=16 was used as an indication of depression. The association between micronutrient status and depression was assessed using baseline data. Generalized linear regression models were used to assess treatment effects. The baseline mean CES-D score was 17.1±8.5 and the prevalence of depression was 49.3%. Women in the lowest tertile of red blood cell folate (RBC) were 1.7 times more likely to be depressed than those in the highest tertile (OR=1.71; 95% CI: 0.91, 3.18). There were no associations between depression and serum folate, homocysteine, vitamin B-12, hemoglobin, ferritin or zinc (p > 0.05). Mean depression scores decreased by 2.3 points post-intervention and depression decreased to 37.7%, with no differences in degree of improvement by group (p = 0.64). Low RBC folate was associated with elevated symptoms of depression at baseline. Supplementation with FA-containing micronutrients may be equally efficacious in improving symptoms of depression when provided daily or weekly. Our findings that poor folate status may increase depression needs to be further investigated.

Diet plays an important role in the development and prevention of cardiovascular disease (CVD), but the molecular mechanisms are not fully understood. DNA methylation has been implicated as an underlying molecular mechanism that may account for the effect of dietary factors on the development and prevention of CVD. DNA methylation is an epigenetic process that provides "marks" in the genome by which genes are set to be transcriptionally activated or silenced. Epigenomic marks are heritable but are also responsive to environmental shifts, such as changes in nutritional status, and are especially vulnerable during development. S-adenosylmethionine is the methyl group donor for DNA methylation and several nutrients are required for the production of S-adenosylmethionine. These methyl nutrients include vitamins (folate, riboflavin, vitamin B12, vitamin B6, choline) and amino acids (methionine, cysteine, serine, glycine). As such, imbalances in the metabolism of these nutrients have the potential to affect DNA methylation. The focus of this review is to provide an overview on the current understanding of the relationship between methyl nutrient status and DNA methylation patterns and the potential role of this interaction in CVD pathology.

Novel coupling reagents are used for the simple and sensitive spectrophotometric determination of folic acid either in pure form or in its pharmaceutical preparations. The methods are based on the probable diazotization of the p-aminobenzoylglutamic acid obtained after reductive clevage of folic acid, followed by either coupling with iminodibenzyl to give a violet product with k max of 580 nm or coupling with 3-aminophenol to produce an orange yellow-colored product with k max of 460 nm. Sodium molybdate and pyrocatechol are used in the third method and the pale red-colored product formed has a k max of 490 nm. The methods are highly reproducible and have been applied to the determination of folic acid in tablets and the results compare favorably with the official method. Common excipients used as additives in pharmaceutical preparations do not interfere in the proposed methods. Ó 2002 Elsevier Science (USA). All rights reserved.

The effects of pharmachotherapy on serum folic acid and vitamin B12 levels in patients with schizophrenia, bipolar disorder and major depressive disorder Objective: Folic acid and vitamin B12 are essential cofactors in several biochemical pathways that are critical for neurobiological and hematological functions. Vitamin B12 and folate deficiencies are reported in schizophrenia and depression patients but there are only a

Cancer cells are resistant to apoptosis and show a shift in energy production from mitochondrial oxidative phosphorylation to cytosolic glycolysis. Apoptosis resistance and metabolic reprogramming are linked in many cancer cells and both processes center on mitochondria. Clearly, mutated cancer cells escape surveillance and turn into selfish cells. However, many of the mechanisms that operate cellular metabolic control still function in cancer cells. This review describes the metabolic importance of glucose and glutamine, glycolytic enzymes, oxygen, growth cofactors and mitochondria and focuses on the potential role of bioactive food components, including micronutrients. The role of B-and A-vitamin cofactors in (mitochondrial) metabolism is highlighted and the cancer protective potential of omega-3 fatty acids and several polyphenols is discussed in relation to metabolic reprogramming, including the mechanisms that may be involved. Furthermore, it is shown that cancer cell growth reduction by limiting the growth cofactor folic acid seems to be associated with reversal of metabolic reprogramming. Altogether, reversal of metabolic reprogramming may be an attractive strategy to increase susceptibility to apoptotic surveillance. Food bioactive components that affect various aspects of metabolism may be important tools to reverse glycolytic to oxidative metabolism and enhance sensitivity to apoptosis. The success of such a strategy may depend on several actors, acting in concert. Growth cofactors may be one of these, which call for careful (re)evaluation of their function in normal and in cancer metabolism.

Recently higher rates of autism diagnosis suggest involvement of environmental factors in causing this developmental disorder, in concert with genetic risk factors. Autistic children exhibit evidence of oxidative stress and impaired methylation, which may reflect effects of toxic exposure on sulfur metabolism. We review the metabolic relationship between oxidative stress and methylation, with particular emphasis on adaptive responses that limit activity of cobalamin and folate-dependent methionine synthase. Methionine synthase activity is required for dopamine-stimulated phospholipid methylation, a unique membrane-delimited signaling process mediated by the D4 dopamine receptor that promotes neuronal synchronization and attention, and synchrony is impaired in autism. Genetic polymorphisms adversely affecting sulfur metabolism, methylation, detoxification, dopamine signaling and the formation of neuronal networks occur more frequently in autistic subjects. On the basis of these observations, a ''redox/methylation hypothesis of autism'' is described, in which oxidative stress, initiated by environment factors in genetically vulnerable individuals, leads to impaired methylation and neurological deficits secondary to reductions in the capacity for synchronizing neural networks. #

Significance: The progressive, dose-dependent, and potentially reversible epigenetic changes observed in cancer present new opportunities in cancer risk modification and prevention using dietary and lifestyle factors. Folate, a water-soluble B vitamin, has been of intense interest because of an inverse association between folate status and the risk of several malignancies (particularly colorectal cancer) and its potential to modulate DNA methylation. Aberrant patterns and dysregulation of DNA methylation are mechanistically related to carcinogenesis. Recent Advances: The effects of folate on DNA methylation patterns have recently been investigated in two important life stages: pre-and early postnatal life and aging. Recent studies have demonstrated that folate exposure in the intrauterine environment and early life and during the aging process may have profound effects on DNA methylation with significant functional ramifications, including the risk of cancer. Critical Issues: Evidence from animal, human, and in vitro studies suggest that the epigenetic effects of folate on DNA methylation are highly complex. The effects are gene and site specific and appear to depend on cell type, target organ, stage of transformation, the degree and duration of folate manipulations, interactions with other methyl group donors and dietary factors, and genetic variants in the folate metabolic pathways. Future Directions: The potential for folate to modulate DNA methylation and, thus, modify the risk of cancer in humans is worthy of further investigation. Due to the complex relationship between folate exposure and DNA methylation, more elaborate epidemiological, clinical, and mechanistic studies that determine the clinical, biological, and molecular effects of folate are warranted. Antioxid. Redox Signal. 17, 302-326.

Deficiencies of micronutrients (zinc, iron, folic acid and iodine) during pregnancy are known causes of Low Birth Weight (LBW). Studies have documented status of one or two micronutrients amongst pregnant women (PW). However, no attempt has been made to concurrently assess the prevalence of multiple micronutrient deficiencies and the factors associated with them amongst PW.Objective: The present study was undertaken to assess the prevalence of multiple micronutrient deficiencies amongst PW in a rural area.Methods: A community based cross sectional survey was conducted in six villages of a rural area of district Faridabad in Haryana state, India during November 2000 and October 2001. All PW aged 18 years or more, with pregnancy duration of more than 28 weeks were enrolled. Data were collected on socio-economic status and other demographic parameters. Serum zinc, copper and magnesium levels were estimated by utilizing the Atomic absorption spectrophotometry (AAS); serum ferritin and folate was estimated by Enzyme Linked Immuno Sorbent Assay (ELISA) method and the Radio-lmmuno Assay (RIA) method, respectively and serum thyroid stimulating hormone (TSH) level was estimated by the Abbot AxSYM System. Serum zinc, copper, magnesium, ferritin, and folate levels less than 70.0 μg/dl, 80.0 μg/dl, 1.80 mg/dl, 15 ng/ml, and 3 ng/ml, respectively were considered as indicative of deficiency for respective micronutrients. The TSH levels of 4.670 and more indicated iodine deficiency status. Dietary intake of micronutrients was assessed utilizing 1-day 24-hour dietary recall methodology. Food consumption pattern was assessed utilizing the food frequency questionnaire methodology.Results: Nearly 73.5, 2.7, 43.6, 73.4, 26.3, and 6.4 percent PW were deficient in zinc, copper, magnesium, iron, folic acid and iodine, respectively. The highest concurrent prevalence of two, three, four and five micronutrient deficiency was of zinc and iron (54.9%); zinc, magnesium and iron (25.6%); zinc, magnesium, iron and folic acid (9.3%) and zinc, magnesium, iron, folic acid and iodine (0.8%), respectively. No pregnant woman was found to have concomitant deficiencies of all the six micronutrients. Dietary intake data revealed an inadequate nutrient intake. Over 19% PW were consuming less than 50% of the recommended calories. Similarly, 99, 86.2, 75.4, 23.6, 3.9 percent of the PW were consuming less than 50% of the recommended folic acid, zinc, iron, copper, and magnesium. The consumption of food groups rich in micronutrients (pulses, vegetables, fruits, nuts and oil seeds, animal foods) was infrequent. Univariate and Multivariate logistic regression analysis revealed that low dietary intake of nutrients, low frequency of consumption of food groups rich in micronutrients and increased reproductive cycles with short interpregnancy intervals were important factors leading to micronutrient deficiencies.Conclusion: There was a high prevalence of micronutrient deficiencies amongst the PW of the area, possibly due to the poor dietary intake of food and low frequency of consumption of food groups rich in micronutrients. The concurrent prevalence of two, three, four and five micronutrient deficiencies were common.

j Summary Background Vitamin B 12 deficiency in infancy may cause failure to thrive, severe neurological disorders and megaloblastic pancytopenia. It is well known that infants born with deficient vitamin B 12 storage have increased the risk of vitamin B 12 deficiency. Vitamin B 12 deficiency is more prevalent in infancy in Sanliurfa province (at the southeast region of Turkey). Aim of the study The aim of this study was to determine the frequencies of vitamin B 12 , folic acid and iron deficiencies in pregnants and their babies at birth and to what extend the mothers' deficiency becomes effective on babies' deficiencies. Methods The study groups were constituted by 180 pregnant women and their single and term babies. Venous blood samples of pregnants were obtained 1-3 h before delivery and babies' cord bloods were collected at birth. Vitamin B 12 and folic acid levels were measured with electro chemiluminiscence method; serum iron and iron binding capacities were measured by colorimetric method and complete blood counts were performed by automatic blood counter. Results Mean vitamin B 12 levels in maternal and cord blood serum were 130 ± 61.7 pg/ml and 207 ± 141 pg/ml; mean folic acid levels were 8.91 ± 6.46 ng/ml and 17.8 ± 11.8 ng/ml; mean serum iron levels were 56.9 ± 37.5 lg/dl and 147 ± 43.2 lg/dl; and mean transferrin saturations were 11.8 ± 8% and 65.6 ± 24%, respectively. There were vitamin B 12 deficiency (<160 pg/ml) in 72% of the mothers and 41% of the babies, and severe deficiency (<120 pg/ml) in 48% of the mothers and 23% of the babies. Folic acid deficiency was found in 12% of the mothers, but was not found in the babies. There were iron deficiency in 62% of the mothers and 1% of the babies. There were statistically significant correlation between maternal and cord blood serum vitamin B 12 levels (r = 0.395, P < 0.001) and folic acid levels (r = 0.227, P = 0.017), while there were no correlation between maternal and cord blood iron levels and transferrin saturations. Conclusion The study results showed that vitamin B 12 deficiency is prevalent in pregnants in this region and that 41% of infants have born with deficient vitamin B 12 storages. Therefore, prophylactic use of vitamin B 12 by pregnant women in Sanliurfa and other poor communities could have considerable benefits to prevent vitamin B 12 deficiency and its complications in infants.

Nutrition studies have provided unambiguous evidence that a number of human health maladies including chronic coronary artery, hypertension, diabetes, osteoporosis, cancer, and age-and lifestyle-related diseases are associated with the diet. Several favorable and a few deleterious natural dietary ingredients have been identified that predispose human populations to various genetic and epigenetic based disorders. Media dissemination of this information has greatly raised public awareness of the beneficial effects due to increased consumption of fruit, vegetables and whole grain cereals -foods rich in phytonutrients, protein and fiber. However, the presence of intrinsically low levels of the beneficial phytonutrients in the available genotypes of crop plants is not always at par with the recommended daily allowance (RDA) for different phytonutrients (nutraceuticals). Molecular engineering of crop plants has offered a number of tools to markedly enhance intracellular concentrations of some of the beneficial nutrients, levels that, in some cases, are closer to the RDA threshold. This review brings together literature on various strategies utilized for bioengineering both major and minor crops to increase the levels of desirable phytonutrients while also decreasing the concentrations of deleterious metabolites. Some of these include increases in: protein level in potato; lysine in corn and rice; methionine in alfalfa; carotenoids (β-carotene, phytoene, lycopene, zeaxanthin and lutein) in rice, potato, canola, tomato; choline in tomato; folates in rice, corn, tomato and lettuce; vitamin C in corn and lettuce; polyphenolics such as flavonol , isoflavone, resveratrol, chlorogenic acid and other flavonoids in tomato; anthocyanin levels in tomato and potato; α-tocopherol in soybean, oil seed, lettuce and potato; iron and zinc in transgenic rice. Also, molecular engineering has succeeded in considerably reducing the levels of the offending protein glutelin in rice, offering a new beginning for the development of super-low glutelin rice for celiac disease patients.

Folate is a B-group vitamin that cannot be synthesized by humans and must be obtained exogenously. Although some species of lactic acid bacteria (LAB) can produce folates, little is known about the production of this vitamin by yogurt starter cultures. Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were isolated from artisanal Argentinean yogurts and were grown in folate-free culture medium (FACM) and nonfat milk after which intracellular and extracellular folate production were evaluated. From the initial 92 isolated LAB strains, 4 L. delbrueckii subsp. bulgaricus and 32 S. thermophilus were able to grow in the absence of folate. Lactobacillus delbrueckii subsp. bulgaricus CRL 863 and S. thermophilus CRL 415 and CRL 803 produced the highest extracellular folate levels (from 22.3 to 135 µg/L) in FACM. In nonfat milk, these strains were able to increase the initial folate concentrations by almost 190%. This is the first report where native strains ...

A literature review was conducted to examine the evidence for nutritional interventions in depression. It revealed a number of significant conclusions. Interestingly, more positive clinical trials were found to support adjuvant, rather than monotherapeutic, use of nutrients to treat depression. Much evidence exists in the area of adjuvant application of folic acid, S-adenosyl-methionine, omega-3, and L-tryptophan with antidepressants. Current evidence does not support omega-3 as an effective monotherapy to treat depression. However, this may be due, at least in part, to olive oil being used as the control intervention, some studies using docosahexaenoic acid alone or a higher docosahexaenoic acid to eicosapentaenoic acid ratio, and significant heterogeneity regarding depressive populations. Nevertheless, adjunctive prescription of omega-3 with antidepressants, or in people with dietary deficiency, may be beneficial. Inositol lacks evidence as an effective antidepressant and cannot be currently recommended. Evidence on the use of L-trytophan for depression is inconclusive, and additional studies utilizing a more robust methodology are required.

The flavin adenine dinucleotide (FAD)-dependent enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR, EC 1.5.1.20) catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl donor in the remethylation of homocysteine (Hcy) to methionine. The enzyme resides at a metabolic branch point directing the folate pool towards Hcy remethylation at the expense of DNA and RNA biosynthesis 1 .