Vitamin B—Can it prevent cognitive decline? A systematic review and meta-analysis

Design: randomized, placebo-controlled trials (RCTs). Participants: cognitively unimpaired adults; majority elderly (often ≥60 years), with some middle-aged and younger adults; both sexes overall, though some trials included only women or only men; populations included healthy individuals and those with risk factors for cognitive decline (elevated homocysteine, vitamin B deficiency, cardiovascular disease, chronic kidney disease, diabetes). Total across 20 trials: 12,697 participants.

Oral vitamin B regimens using folic acid with vitamins B6 and B12, administered in single or combination formulations; treatment durations ranged from 5 weeks to 6.6 years; taken orally.

Oral vitamin B supplementation did not significantly prevent cognitive decline in cognitively unimpaired adults. Global cognition showed no meaningful improvement (pooled effect near zero; 95% CI includes 0; p > 0.05; sensitivity analysis with reduced heterogeneity also non-significant). Some secondary cognitive domains showed isolated significant effects in individual trials, but findings were inconsistent across populations and may reflect chance or bias. No evidence that any particular population group benefits more; results apply only to oral administration and to cognitively unimpaired individuals; no established preventive benefit for cognitive decline. No conclusions about non-oral administration or treatment of cognitive impairment. Overall certainty for the primary outcome is high.

High heterogeneity across trials (differences in populations, interventions, durations, and cognitive outcomes); reliance on MMSE/TICS-m for global cognition in many studies with known limitations; many trials had small samples and some risk of bias; broad array of cognitive tests limits comparability; potential publication and language biases; results limited to oral vitamin B formulations and to cognitively unimpaired individuals.