Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials

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#cognition #cognition-disorders #dietary-supplements #folic-acid #humans

Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials

Balk et al., 2007 | Arch Intern Med | Systematic Review

Citation

Balk Ethan M, Raman Gowri, ... Rosenberg Irwin H. Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med. 2007-Jan-08;167(1):21-30

Abstract

BACKGROUND: Despite their important role in cognitive function, the value of B vitamin supplementation is unknown. A systematic review of the effect of pyridoxine hydrochloride (hereinafter "vitamin B(6)"), cyanocobalamin or hydroxycobalamin (hereinafter "vitamin B(12)"), and folic acid supplementation on cognitive function was performed. METHODS: Literature search conducted in MEDLINE with supplemental articles from reviews and domain experts. We included English language randomized controlled trials of vitamins B(6) and/or B(12) and/or folic acid supplementation with cognitive function outcomes. RESULTS: Fourteen trials met our criteria; most were of low quality and limited applicability. Approximately 50 different cognitive function tests were assessed. Three trials of vitamin B(6) and 6 of vitamin B(12) found no effect overall in a variety of doses, routes of administration, and populations. One of 3 trials of folic acid found a benefit in cognitive function in people with cognitive impairment and low baseline serum folate levels. Six trials of combinations of the B vitamins all concluded that the interventions had no effect on cognitive function. Among 3 trials, those in the placebo arm had greater improvements in a small number of cognitive tests than participants receiving either folic acid or combination B-vitamin supplements. The evidence was limited by a sparsity of studies, small sample size, heterogeneity in outcomes, and a lack of studies that evaluated symptoms or clinical outcomes. CONCLUSION: The evidence does not yet provide adequate evidence of an effect of vitamin B(6) or B(12) or folic acid supplementation, alone or in combination, on cognitive function testing in people with either normal or impaired cognitive function.

Key Findings

Fourteen trials met our criteria; most were of low quality and limited applicability. Approximately 50 different cognitive function tests were assessed. Three trials of vitamin B(6) and 6 of vitamin B(12) found no effect overall in a variety of doses, routes of administration, and populations. One of 3 trials of folic acid found a benefit in cognitive function in people with cognitive impairment and low baseline serum folate levels. Six trials of combinations of the B vitamins all concluded that

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 3
Age Range See abstract
Condition cognitive

MeSH Terms

  • Cognition
  • Cognition Disorders
  • Dietary Supplements
  • Folic Acid
  • Humans
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Vitamin B 12
  • Vitamin B 6
  • Vitamin B Complex

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Research Support, U.S. Gov't, P.H.S., Systematic Review
  • Vertical: vitamin-b6

Provenance

  • PMID: 17210874
  • DOI: (not available)
  • PMCID: Not in PMC
  • Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09