Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial

Am J Clin Nutr. 2006 Aug;84(2):361-70. doi: 10.1093/ajcn/84.1.361.

Abstract

Background: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive.

Objective: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency.

Design: In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function.

Results: Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains.

Conclusion: Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Cognition / drug effects*
  • Cognition / physiology
  • Cognition Disorders / etiology
  • Cognition Disorders / prevention & control*
  • Dietary Supplements
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Folic Acid / pharmacology*
  • Folic Acid / therapeutic use
  • Homocysteine / blood
  • Humans
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Methylmalonic Acid / blood
  • Psychomotor Performance / drug effects
  • Transcobalamins / analysis
  • Transcobalamins / metabolism
  • Vitamin B 12 / pharmacology*
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / complications
  • Vitamin B 12 Deficiency / drug therapy*

Substances

  • Transcobalamins
  • Homocysteine
  • Methylmalonic Acid
  • Folic Acid
  • Vitamin B 12