Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial

Smith AD, et al.

Published in PLoS One

Methodology

Randomised, double-blind, placebo-controlled trial of folic acid 0.8 mg, vitamin B12 0.5 mg and vitamin B6 20 mg daily for 24 months in adults 70+ with mild cognitive impairment, with serial volumetric MRI measuring whole-brain atrophy rate plus cognitive testing and homocysteine.

Key Findings

In VITACOG, 271 older adults with mild cognitive impairment took high-dose folic acid, vitamin B12 and B6 or placebo for two years; B vitamins lowered homocysteine by about 30% and slowed the rate of whole-brain atrophy by roughly 30% overall, with reductions up to 53% in participants with the highest baseline homocysteine, and slower atrophy correlated with better cognitive scores.

Conclusions

Homocysteine-lowering B vitamins slowed brain atrophy in mild cognitive impairment, with benefit concentrated in those with elevated baseline homocysteine - the strongest case yet for targeted rather than universal B vitamin use.

Limitations

Single-centre trial of modest size with brain atrophy as an imaging surrogate rather than dementia incidence; benefit largely confined to a high-homocysteine subgroup identified post hoc; results not replicated in larger cognitive trials; adequate baseline B12 status may be a prerequisite.