Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

Nutrients. 2016 Nov 23;8(11):741. doi: 10.3390/nu8110741.


Neural tube defects (NTDs) are a group of severe congenital malformations, induced by the combined effects of genes and the environment. The most valuable finding so far has been the protective effect of folic acid supplementation against NTDs. However, many women do not take folic acid supplements until they are pregnant, which is too late to prevent NTDs effectively. Long-term intake of folic acid-fortified food is a good choice to solve this problem, and mandatory folic acid fortification should be further promoted, especially in Europe, Asia and Africa. Vitamin B2, vitamin B-6, vitamin B-12, choline, betaine and n-3 polyunsaturated fatty acids (PUFAs) can also reduce the NTD risk by interacting with the one-carbon metabolism pathway. This suggest that multivitamin B combined with choline, betaine and n-3 PUFAs supplementation may have a better protective effect against NTDs than folic acid alone. Genetic polymorphisms involved in one-carbon metabolism are associated with NTD risk, and gene screening for women of childbearing age prior to pregnancy may help prevent NTDs induced by the risk allele. In addition, the consumption of alcohol, tea and coffee, and low intakes of fruit and vegetable are also associated with the increased risk of NTDs, and should be avoided by women of childbearing age.

Keywords: alcohol; betaine; choline; coffee; folate; neural tube defects; one-carbon metabolism; tea; vitamin B.

Publication types

  • Review

MeSH terms

  • Anencephaly / genetics
  • Anencephaly / metabolism*
  • Anencephaly / physiopathology
  • Anencephaly / prevention & control*
  • Animals
  • Carbon / metabolism*
  • Dietary Supplements*
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid Deficiency / metabolism
  • Folic Acid Deficiency / physiopathology
  • Folic Acid Deficiency / therapy*
  • Food, Fortified
  • Gene-Environment Interaction
  • Humans
  • Maternal Nutritional Physiological Phenomena*
  • Nutritional Status*
  • Nutritive Value
  • Pregnancy
  • Recommended Dietary Allowances
  • Risk Factors


  • Carbon
  • Folic Acid

Supplementary concepts

  • Neural tube defect, folate-sensitive