Subclinical cobalamin deficiency

Curr Opin Gastroenterol. 2012 Mar;28(2):151-8. doi: 10.1097/MOG.0b013e3283505852.


Purpose of review: This review focuses on recent developments and controversies in the diagnosis, consequences, and management of subclinical cobalamin deficiency (SCCD), which affects many elderly persons.

Recent findings: Diagnosis of SCCD depends exclusively on biochemical tests whose individual limitations suggest that combinations of tests are needed, especially in epidemiologic research. The causes of SCCD are unknown in more than 60% of cases, which limits prognostic predictions and identification of health consequences. After years of varying, often inconclusive associations, new clinical trials suggest that homocysteine reduction by high doses of folic acid, cobalamin, and pyridoxine may reduce progression of structural brain changes and cognitive impairment, especially in predisposed individuals. The causative or contributory roles, if any, of SCCD itself in cognitive dysfunction require direct study. If the findings are confirmed, high-dose supplementation with three vitamins will probably be more effective than fortification of the diet.

Summary: The story of SCCD, which is severalfold times more common in the elderly than clinical cobalamin deficiency but also differs from it in arising only infrequently from severe malabsorption and thus being less likely to progress, continues to evolve. Preventive benefits need to be confirmed and expanded, and will require fuller understanding of SCCD pathophysiology, natural history, and health consequences.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Asymptomatic Diseases / therapy
  • Cognition Disorders / complications
  • Dietary Supplements*
  • Folic Acid
  • Food, Fortified
  • Humans
  • Vitamin B 12 / adverse effects
  • Vitamin B 12 / therapeutic use*
  • Vitamin B 12 Deficiency / complications
  • Vitamin B 12 Deficiency / diagnosis*
  • Vitamin B 12 Deficiency / drug therapy*
  • Vitamin B 12 Deficiency / etiology
  • Vitamins / adverse effects
  • Vitamins / therapeutic use*


  • Vitamins
  • Folic Acid
  • Vitamin B 12