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Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus. [ABSTRACT FROM PUBLISHER]

Background/Objectives:As low folate status has been implicated in depression, high folate intake, in the form of supplements, during pregnancy might offer protection against depression during pregnancy and postpartum.Subjects/Methods:We examined the association between change in self-reported depressive symptoms (Edinburgh Postnatal Depression Scale) at different timepoints during and following pregnancy and self-reported folic acid supplementation during pregnancy in a prospective cohort of 6809 pregnant women. We also tested whether there was a main effect of methylenetetrahydrofolate reductase (MTHFR) C677T genotype (which influences folate metabolism and intracellular levels of folate metabolites and homocysteine) on change in depression scores, and carried out our analysis of folic acid supplementation and depression stratifying by genotype.Results:We found no strong evidence that folic acid supplementation reduced the risk of depression during pregnancy and up to 8 months after pregnancy. However, we did find evidence to suggest that folic acid supplements during pregnancy protected against depression 21 months postpartum, and that this effect was more pronounced in those with the MTHFR C677T TT genotype (change in depression score from 8 months to 21 months postpartum among TT individuals was 0.66 (95% CI=0.31-1.01) among those not taking supplements, compared with −1.02 (95% CI=−2.22-0.18) among those taking supplements at 18 weeks pregnancy, Pdifference=0.01).Conclusions:Low folate is unlikely to be an important risk factor for depression during pregnancy and for postpartum depression, but may be a risk factor for depression outside of pregnancy, especially among women with the MTHFR C677T TT genotype. [ABSTRACT FROM AUTHOR]

Folic acid is important because supplementation around the time of conception has been proven to lower the risk of having offspring with a neural-tube defect. Furthermore, both dietary folate and folic acid decrease plasma total homocysteine concentrations. Elevated plasma homocysteine concentrations are considered to be an independent risk factor for cardiovascular disease. The aim of the present review is to give an overview of factors influencing bioavailability and bioefficacy (the proportion of ingested nutrient converted to its active form) of food folate and folic acid, and to discuss the functional bioefficacy of folate and folic acid in decreasing plasma homocysteine concentrations. We use the mnemonic SLAMENGHI to group factors influencing bioavailability and bioefficacy: Species of folate; Linkage at molecular level; Amount of folate and folic acid consumed; Matrix; Effect modifiers; Nutrient status; Genetic factors; Host-related factors; mathematical Interactions between the various factors. Bioefficacy of folate from some foods is <50 % that of folic acid. This factor is most probably explained by the matrix factors, encapsulation and binding. However, often such effects cannot be distinguished from factors such as species, chain length of folate in food, effect modifiers and the amount of folate consumed in a meal. Folic acid provided as a supplement is well absorbed. However, the homocysteine-lowering capacity of doses of folic acid >500 μg is limited. It is unclear whether unmetabolised folic acid poses health risks. This factor is of importance, because food fortification is now implemented in many countries and folic acid supplements are freely available. In particular circumstances host-related factors, such as gastrointestinal illness and pH of the jejunum, can influence bioavailability. Genetic factors also deserve attention for future research, because polymorphisms may influence folate bioavailability.
Folate: Folic acid: Bioavailability: Bioefficacy: Homocysteine [ABSTRACT FROM AUTHOR]

Investigates the total homocysteine (tHcy) and methylmalonic acid (MMA) levels as markers of functional cobalamin and folate status in pregnant Nepali women. Associations between serum tHcy, MMA, cobalamin and folate in the pregnant women studied; Determinants of functional cobalamin and folate deficiencies; Link between serum tHcy values and complications of pregnancy.

From a public health perspective, some of the new insights into folic acid nutrition are of significance. Folate intake recommendations vary under different conditions. Intake of 350 ??g is required to maintain plasma homocysteine levels, 650 ??g for those with elevated plasma homocysteine, about 400 ??g for women planning to become pregnant and 4000 ??g for those with history of neural tube defect affected pregnancy. This raises the question whether the folate intake is adequate for the general population, particularly in the vulnerable groups or whether there is a need for scientists to take a fresh view of the requirements, recommended dietary intakes, and consider intervention measures which will have impact on the folate nutritional status. The recommendations should provide a margin of safety to allow for decreased intake, increased requirements, individual variability and bioavailability of natural food folates. The folate intake and nutriture in relation to India and other developing countries needs careful consideration to reduce anemia, neural tube defects and possibly impact on the high incidence of cardiovascular diseases. [ABSTRACT FROM PUBLISHER]