Elevated total plasma
homocysteine has been linked to the development of
cognitive impairment and
dementia in later life and this can be reliably lowered by the daily supplementation of
vitamin B6, B12, and
folic acid. We performed a systematic review and meta-analysis of 19 English language randomized, placebo-controlled trials of
homocysteine lowering
B-vitamin supplementation of individuals with and without
cognitive impairment at the time of study entry. We standardized scores to facilitate comparison between studies and to enable us to complete a meta-analysis of randomized trials. In addition, we stratified our analyses according to the
folate status of the country of origin.
B-vitamin supplementation did not show an improvement in cognitive function for individuals with (SMD = 0.10, 95%CI -0.08 to 0.28) or without (SMD = -0.03, 95%CI -0.1 to 0.04) significant
cognitive impairment. This was irrespective of study duration (SMD = 0.05, 95%CI -0.10 to 0.20 and SMD = 0, 95%CI -0.08 to 0.08), study size (SMD = 0.05, 95%CI -0.09 to 0.19 and SMD = -0.02, 95%CI -0.10 to 0.05), and whether participants came from countries with low
folate status (SMD = 0.14, 95%CI -0.12 to 0.40 and SMD = -0.10, 95%CI -0.23 to 0.04). Supplementation of
vitamins B12, B6, and
folic acid alone or in combination does not appear to improve cognitive function in individuals with or without existing
cognitive impairment. It remains to be established if prolonged treatment with
B-vitamins can reduce the risk of
dementia in later life.