Does folic acid harm people with vitamin B12 deficiency?

QJM. 1995 May;88(5):357-64.


Oral folic acid given before and during pregnancy can prevent about 75% of fetal neural tube defects. Even in large dose (20 mg daily) folic acid has never been shown to harm normal people, but it has acquired a bad reputation in pernicious anaemia. Before 1930, if untreated patients survived the anaemia, they succumbed to peripheral neuritis, subacute combined degeneration of the spinal cord, and death. The speed of this progression was extremely variable. From 1947 onwards, there were many reports of rapid neurological deterioration during administration of folic acid as sole therapy to people with pernicious anaemia. However, a review of clinical studies published before the introduction of liver and vitamin B12 therapy shows that neurological deterioration was often quite as rapid and severe in untreated patients. Oral folic acid can usually correct or prevent the anaemia of pernicious anaemia. Thus it could mask the underlying disease, and allow the development or progression of neurological deterioration, if diagnosis depended on the presence of anaemic symptoms. This possibility can readily be overcome by adequate education of doctors, so that a macrocytic anaemia is not regarded as a necessary accompanying sign of the neurological disorder. The hypothetical and avoidable side-effects of food fortification with folic acid have to be balanced against the certain benefit of preventing neural tube defects in unplanned pregnancies, and also against the probability that adults may be spared the neuropsychiatric and other ill-effects which result from inadequate dietary folic acid.

Publication types

  • Review

MeSH terms

  • Aged
  • Anemia, Pernicious / complications
  • Anemia, Pernicious / diagnosis*
  • Anemia, Pernicious / drug therapy
  • Clinical Trials as Topic
  • Diagnostic Errors
  • Female
  • Folic Acid / adverse effects*
  • Folic Acid / therapeutic use
  • Food, Fortified
  • Humans
  • Male
  • Nervous System Diseases / etiology*
  • Pregnancy
  • Vitamin B 12 Deficiency / drug therapy*


  • Folic Acid