Vitamin B12 for cognition.

Systematic review of 3 small randomized trials in older adults, mainly people with dementia, cognitive impairment, or low/subnormal serum vitamin B12 levels. Included participants were mostly community-dwelling or hospitalized older adults; one trial involved 5 active-arm participants with moderate Alzheimer disease, another enrolled older patients with subnormal B12 concentrations, and another studied previously untreated vitamin B12 deficiency.

Vitamin B12 was given in several regimens across the included trials: 1000 microgram injections daily for 5 days, then one injection monthly for 5 months; oral cyanocobalamin 10 microgram daily for 1 month; oral cyanocobalamin 50 microgram daily for 1 month; and 1 mg cyanocobalamin injections weekly for 4 weeks. Comparators were placebo or no treatment in the individual trials.

Overall, vitamin B12 supplementation did not show convincing improvement in cognitive function in older adults with dementia or low B12. The clearest trial results were null for ADAS-Cog in Alzheimer disease (MD 0.04, 95% CI -5.95 to 6.03, p=0.99) and null for MMSE after 1 month with oral cyanocobalamin 10 microgram daily (MD -1.60, 95% CI -3.99 to 0.79, p=0.19) or 50 microgram daily (MD -0.60, p=0.63). In the 3-month deficiency trial, CAMCOG was also null (MD -0.6, 95% CI -2.2 to 0.9, p=0.43) and MMSE was unchanged (MD 0.1, 95% CI -0.6 to 0.8, p=0.70), with no adverse events reported. A borderline result favored treatment for 12-word delayed recall (MD -0.50, 95% CI -1.0 to 0.0, p=0.05), but the overall evidence remained insufficient to support benefit.

The evidence base was very small, with only 3 trials and limited active-arm sample sizes, including one arm with N=5. Trials were short, populations and B12 deficiency definitions were heterogeneous, and cognitive outcomes varied, limiting comparability and generalizability. No trials in healthy older adults were found, and the review was underpowered to detect modest benefits or harms.