Maternal oversupplementation with folic acid and its impact on neurodevelopment of offspring

Nutr Rev. 2018 Sep 1;76(9):708-721. doi: 10.1093/nutrit/nuy025.


Folic acid, a B vitamin, is vital for early neurodevelopment and is well known for its protective effect against neural tube defects. Various national health agencies worldwide recommend that women of childbearing age take approximately 0.4 to 1 mg of supplemental folic acid daily to reduce the risk of neural tube defects in offspring. Several countries have tried to promote folic acid intake through mandatory fortification programs to reduce neural tube defects. Supplementation combined with mandatory fortification of foods has led to high levels of folic acid and related metabolites in women of childbearing age. Recent studies have reported that oversupplementation, defined as exceeding either the recommended dietary allowance or the upper limit of the daily reference intake of folic acid, may have negative effects on human health. This review examines whether maternal oversupplementation with folic acid affects the neurodevelopment of offspring. Data from animal studies suggest there are behavioral, morphological, and molecular changes in the brain of offspring. Additional studies are required to determine both the dosage of folic acid and the timing of folic acid intake needed for optimal neurodevelopment in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dietary Supplements / adverse effects*
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / adverse effects*
  • Food, Fortified
  • Humans
  • Infant, Newborn
  • Male
  • Neural Tube Defects / prevention & control
  • Neurodevelopmental Disorders / chemically induced*
  • Overnutrition / etiology*
  • Pregnancy
  • Pregnancy Complications / etiology*
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Recommended Dietary Allowances


  • Folic Acid