Effect of Folic Acid, with or Without Other B Vitamins, on Cognitive Decline: Meta-analysis of Randomized Trials

Purpose: We aimed to quantify the effect of folic acid supplementation on the prevention of cognitive decline.

Methods: We conducted a meta-analysis of 9 placebo-controlled randomized trials (2835 participants, median duration 6 months) of folic acid, with or without other B vitamins, on cognitive function. Standardized mean differences in cognitive function test scores were calculated between folic acid and placebo-treated groups.

Results: The standardized mean difference in cognitive function test scores was 0.01 (95% confidence interval [95% CI], -0.08 to 0.10), or an increase of 1% (95% CI, -8% to 10%) of 1 standard deviation. The results were similar within each of the 4 categories of cognitive function (memory, speed, language, and executive function); standardized mean differences were 0.01 (95% CI, -0.08 to 0.09), -0.01 (95% CI, -0.10 to 0.13), -0.05 (95% CI, -0.15 to 0.04), and 0.03 (95% CI, -0.13 to 0.19), respectively.

Conclusion: Randomized trials show no effect of folic acid, with or without other B vitamins, on cognitive function within 3 years of the start of treatment. Trials of longer duration, recording the incidence of dementia, as well as cognitive decline, are needed.