Adverse effects of increased dietary folate. Relation to measures to reduce the incidence of neural tube defects

Clin Invest Med. 1994 Jun;17(3):244-52.


Folate given in the periconceptional period reduced the numbers of births with neural tube defects (NTD) by 75%. Extension of these observations to all those at risk requires an increase in dietary folate, which can only be achieved by fortification of food. This will result in increased folate consumption by the whole population. Folate in excess of 1 mg daily can have adverse effects in patients with untreated cobalamin deficiency, usually undiagnosed pernicious anaemia (PA). In such patients, the anaemia is ameliorated with a return of normoblastic haemopoiesis, but in about half the patients neuropathy progresses or will develop for the first time. If continued long enough, such neuropathy is not reversed by subsequent cobalamin therapy. The lowest dose of folate that proved effective in preventing NTDs was 0.36 mg daily. This amount, added to a diet that already supplies about 0.2 mg folate, will give an average folate intake of 0.56 mg daily. To avoid exceeding this amount of folate significantly, folate should no longer be added to multivitamin preparations or the amount added should be considerably curtailed. Close surveillance should be set up to determine whether adverse effects are produced as a result of folate fortification of food. This surveillance should identify patients developing cobalamin neuropathy in the absence of anaemia and usually with a normoblastic marrow, a situation that is rare at the present time.

Publication types

  • Review

MeSH terms

  • Anemia, Pernicious / complications
  • Diet
  • Dose-Response Relationship, Drug
  • Female
  • Folic Acid / adverse effects*
  • Folic Acid / therapeutic use*
  • Humans
  • Incidence
  • Nervous System Diseases / chemically induced*
  • Neural Tube Defects / epidemiology
  • Neural Tube Defects / prevention & control*
  • Pregnancy
  • Vitamin B 12 Deficiency / complications


  • Folic Acid