Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis

Abstract Context Elevated homocysteine levels are associated with brain atrophy and dementia, with B vitamin supplementation a possible low-cost intervention to help mitigate the deleterious impacts on brain health. However, prior meta-analyses have produced inconsistent results, with unexplained heterogeneity, while the quality of evidence has not been assessed. Objective This systematic review, meta-analysis, and meta-regression sought to quantify the effect of B vitamin supplementation on global cognitive function in older adults. Data Sources PubMed, Embase, PsychInfo, Scopus, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) from inception to June 20, 2024. Data Extraction Eligible RCTs were derived from populations aged ≥60 years, with interventions of 26 weeks or longer comprising vitamin(s) B6, B9, or B12 of any dose or administration route, compared with placebo or usual dementia care. Studies must also have quantified global cognitive function at baseline and at end of treatment. Data Analysis Seventeen RCTs, including 5275 participants, were identified. A small to moderate improvement (Hedges’ g = 0.423; 95% CI: 0.188 to 0.657) in global cognitive function after supplementation was observed with considerable heterogeneity (I2 = 92.71; Grading of Recommendations, Assessment, Development, and Evaluations [GRADE] = very low certainty). A meta-regression identified that statistical outliers and single-blinded studies contributed to the pooled g and heterogeneity. Omitting these studies resulted in a small effect (g = 0.110; 95% CI: 0.034 to 0.186), with negligible heterogeneity (I2 = 15.39; GRADE = high certainty). The effect size did not differ between classifications of cognitive impairment (ie, intact cognition, mild cognitive impairment, and dementia) in subgroup analysis (P = .729). Conclusion The pooled findings indicated there is high-certainty evidence that vitamin B6, B9, or B12 supplementation has a very small benefit on global cognitive function in older adults. Systematic Review Registration PROSPERO registration no. CRD42024553717.