Folic acid supplementation in pregnancy and implications in health and disease

Subit Barua, Salomon Kuizon, Mohammed A Junaid, Subit Barua, Salomon Kuizon, Mohammed A Junaid

Abstract

Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies.

Figures

Figure 1
Figure 1
Summary of folate metabolism (simplified). The schematic diagram shows that after entry of synthetic FA or natural dietary folates through receptors/carriers in cell membrane, the intracellular folate/ FA pass through series of biochemical reactions, and alter DNA methylation. Abbreviations: DHFR, dihydrofolate reductase; DHF, dihydrofolate; THF, tetrahydrofolate; SHMT, serine-hydroxymethyltransferase; 5,10-methenyl- THF, 5,10-methenyl-tetrahydrofolate; MTHFR, 5,10-methylenetetrahydrofolate reductase; 5-methyl THF, 5-methyltetrahydrofolate; MS, methionine synthase; B12, vitamin B-12; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; DNMT, DNA methyltransferase; MT, methyltransferases.
Figure 2
Figure 2
A representative integrative model of possible epigenetic influence on pregnancy outcomes. Maternal intake of FA may result in epigenetic modulation in the offspring brain methylome with overall or site specific alterations of methylation in genomic DNA, non-coding RNA and histone modifications. These effects may alter gene expression of several imprinted, candidate autism susceptibility and key developmental genes. Such changes may impact other biological processes, and associate with the overall developmental outcome. Scientific artwork adapted from [137],[138].

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Source: PubMed

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