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Unmetabolized Folic Acid in the Cord Blood of Most Infants: Implications for Future Health

Onusic, Sylvia P
Advances in nutrition 2016 v.7 no.1 pp. 45A
autoantibodies, blood, blood flow, brain, breast milk, childhood, children, diet, dihydrofolate reductase, folate receptors, folate-binding proteins, folic acid, grain products, mothers, neonates, neural tube defects, pre-eclampsia, pregnancy, pregnant women, risk factors, umbilical cord, vitamin B deficiency, vitamin B12, Canada, United States
Pregnant women today are ingesting much higher amounts of synthetic folic acid (FA) from prenatal vitamins and diet. In 1998, the United States and Canada instituted mandatory fortification of all grain products with FA solely to prevent neural tube defects (NTDs). FA is not successful in reducing NTDs among high-risk groups and 30–40% of women do not metabolize FA. At certain levels, occurring even at 200 micrograms (ug), the dihydrofolate reductase enzyme can become saturated allowing un-metabolized folic acid (UMFA) to pass into the blood stream by passive diffusion. UMFA has been detected in cord blood in the newborn baby's umbilical cord of mothers who did and did not take prenatal vitamins. In 2005, MR Sweeney and colleagues found UMFA in the cord blood of all the 4 d old infants they tested and since then other groups have replicated the results. Breast milk contains amounts of natural folate (5-MTHF) but researchers found UMFA in breast milk in both supplemented and non-supplemented mothers, and a down-regulation of the natural folate binding protein needed to take the folate into the breast milk. FA “masks” vitamin B-12 deficiency, and low vitamin B-12 with high FA concentrations are risk factors for NTDs, preeclampsia, placental abruption, pregnancy loss, hyperhomocysteinemia, and intrauterine growth restriction. The folate receptor in the brain has an affinity for FA. It is unknown if UMFA could block the transport of folate into the brain or pass into the brain itself. Cerebral folate deficiency (CFD), a condition among some autistic children, occurs when autoantibodies to the folate receptor prevent folate from entering the brain. Does UMFA play a role in the formation of auto-antibodies? A review of PubMed for the terms “unmetabolized folic acid,” showed few citations, several dealing with infant and childhood effects of FA, but none dealing with UMFA and brain effects.