Summary:
This systematic review and meta-analysis examined whether taking B-vitamin supplements improves overall cognitive ability. Dementia is expected to increase worldwide as populations age, including in Australia, where more than six million people are forecast to develop dementia in the next 40 years. Elevated homocysteine, a marker related to inflammation and oxidative stress, has been linked with higher risks of cardiovascular disease and dementia. Research has associated high homocysteine with changes in brain structure and function, including neuron damage and temporal lobe shrinkage. B-vitamins (B6, B9, and B12) help break down homocysteine, so supplements have been proposed as a way to slow cognitive decline. This study searched five major databases for randomised controlled trials in adults aged 60 years or older. Eligible trials used B6, B9, or B12 supplements for at least 26 weeks and measured cognition at both the start and end of the intervention. Seventeen trials, including 5,275 participants, met the criteria. The study found that long-term supplementation with vitamin B6, B9, or B12 produces an improvement in cognitive function in older adults, and that the benefit appears consistent regardless of baseline cognitive status.
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.
Article Publication Date: 12/9/2025
DOI: x10.1093/nutrit/nuaf155
