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Public Policy and Folic Acid Fortification: Great Harm or Help?

Onusic, Sylvia P
Advances in nutrition 2016 v.7 no.1 pp. 25A
DNA methylation, animal models, asthma, autism, blood serum, children, diet, dihydrofolate reductase, eczema, folic acid, food fortification, gene expression, genetic polymorphism, grain products, health policy, insulin resistance, metabolism, mothers, neonates, neural tube defects, phenotype, pregnancy, public policy, risk factors, vitamin B12, women, Canada, Spain, United States
Since the 1900s, public policy worldwide recommends supplementation with folic acid (FA) for all women of child-bearing age and during pregnancy to prevent neural tube defects (NTDs). Since late 1998, the United States and Canada mandated fortification of all grain products with FA. Fortification reduced the incidence of NTDs by 60–70%. However 30–40% of cases remain nonresponsive because of inability to metabolize FA because of genetic polymorphisms (MTHFR) or a deficiency of dihydrofolate reductase. In Spain, the prevalence of MTHFR has doubled since FA supplements for women in early pregnancy were introduced in 1982. Both MTHFR polymorphisms have been associated with decreased levels of DNA methylation. However, more is not better. A “folic acid-adverse effects” search on PubMed produced 463 citations dealing with negative outcomes of infants whose mothers consumed FA through prenatal vitamins and diet. Higher concentrations of FA in serum of women can precipitate changes in a number of phenotypic outcomes in the offspring positively associated with autism, asthma, allergy-related respiratory impairment in children, an 85% greater risk of eczema, insulin resistance in age 6 y, modification in hepatic metabolism and vascular function, and other phenomena, even twinning. FA is known to mask vitamin B-12 deficiency, another factor in the development of NTDs. Although findings vary in human studies, animal models clearly show a consistent effect of FA on gene expression in the offspring. In lieu of the harms of FA to the unborn and newborn, is it time to seriously re-evaluate current public health policy on food fortification with FA and medical recommendations for prenatal vitamins?