Fifty patients (mean age, 60 years) with carotid intima-media thickness (IMT)  1 mm, which is associated with an increased risk of cerebral ischemia, were randomly assigned to receive daily, in double-blind fashion, either 1) 2.5 mg of folic acid, 25 mg of vitamin B6, and 0.5 mg of vitamin B12, or 2) placebo for 1 year. In the active-treatment group, the mean plasma homocysteine concentration decreased from 10.50 to 6.56 micromol/L (p < 0.0001), but remained unchanged in the placebo group (10.76 vs. 10.45 micromol/L). Mean IMT in the active-treatment group decreased from 1.50 to 1.42 mm (p = 0.034), a change suggestive of a regression of atherosclerosis. In contrast, mean IMT increased from 1.47 to 1.54 mm in the placebo group (< 0.02 for the difference in the change between groups).

Comment: In this study, supplementation with folic acid, vitamin B6, and vitamin B12 significantly reduced carotid intima-media thickness in patients at risk of cerebral ischemia. While some of this improvement may have been due to a reduction in homocysteine levels, the effect appeared to be at least partly independent of both baseline plasma homocysteine concentrations and the change in homocysteine levels during treatment. Vitamin B6, in particular, has actions unrelated to homocysteine metabolism that might be expected to improve vascular health, such as enhancement of endothelial-tissue integrity and inhibition of platelet aggregation.

Till U, et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, vitamins B6 and B12. Atherosclerosis 2005;181:131-135.