Vitamin B6, B12, and Folic Acid Supplementation and Cognitive Function

A Systematic Review of Randomized Trials

Ethan M. Balk, MD, MPH; Gowri Raman, MD; Athina Tatsioni, MD; Mei Chung, MPH; Joseph Lau, MD; Irwin H. Rosenberg, MD

Arch Intern Med. 2007;167(1):21-30.

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 B6”), cyanocobalamin or hydroxycobalamin (hereinafter “vitamin B12”), 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 B6 and/or B12 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 B6 and 6 of vitamin B12 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 B6 or B12 or folic acid supplementation, alone or in combination, on cognitive function testing in people with either normal or impaired cognitive function.

Author Affiliations: Tufts-New England Medical Center Evidence-based Practice Center, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center (Drs Balk, Raman, Tatsioni, and Lau and Ms Chung), and Nutrition and Neurocognition Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University (Dr Rosenberg), Boston, Mass.