Glossary

Term · Pregnancy: Eating

unmetabolized folic acid

Also: UMFA, free folic acid, unconverted folic acid

Folic acid from supplements and fortified foods that is still in the blood unchanged, because the body converts it to active folate slowly. Its effects are debated.

In plain words

is the synthetic form of used in prenatal vitamins and . The body turns it into active folate, the form used in cell division and early development. At high intakes, some folic acid reaches the blood without being converted. That is unmetabolized folic acid. Researchers have seen it in the blood of many adults who take supplements daily, and they have not agreed on what it does. Some studies link it to changes in immune cells. No clear harm has been shown at usual prenatal intakes. Prenatal vitamins contain folic acid, and providers can say what fits a person's intake.

The deeper version

Human (DHFR) has low hepatic activity, so folic acid conversion is slow and saturable. Bailey and Ayling (2009) showed that DHFR activity varies widely between individuals and that unmetabolized folic acid appears in plasma at high intakes. Troen et al. (2006) associated circulating unmetabolized folic acid with reduced natural killer cell cytotoxicity in older women, a finding not replicated consistently. The Institute of Medicine's folate (1998) set the tolerable upper intake for synthetic folate from fortification and supplements, and the clinical significance of unmetabolized folic acid for pregnancy outcomes remains unproven. The main controversy is whether the rising share of folic acid in fortified foods and supplements matters for population health.

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Sources

  • Bailey SW, Ayling JE — The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. PNAS 2009
  • Troen AM et al. — Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. Journal of Nutrition 2006
  • Institute of Medicine — Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, 1998

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