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

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.