This mendelian randomization approach found increased stroke in those with the TT genotype (OR for stroke, 1.26; 95% CI, 1.11 1.43) without significant between-study heterogeneity or evidence of publication bias.776 The B complex vitamins pyridoxine (B6 ), cobalamin (B12 ), and folic acid lower homocysteine levels. Folic acid intake is associated with reduced risk of ischemic stroke in some epide- miological studies but not in others.777 780 In a clinical trial of healthy adults without diabetes mellitus and CVD, B complex vitamin supplementation compared with placebo decreased carotid IMT in the group of participants whose baseline plasma homocysteine was 9.1 mol/L but not in those whose homo- cysteine levels were lower.781 A meta-analysis of 10 random- ized trials of folic acid similarly found that treatment decreased IMT but with substantial heterogeneity resulting from larger effects at higher baseline IMTs or with greater reductions in A substudy of the Vitamins to Prevent Stroke (VITATOPS) trial, however, reported that B complex vitamins did not slow the progression of carotid IMT.783 Most trials of patients with established atherosclerotic vas- cular disease have found no benefit of homocysteine lower- ing by B complex vitamin therapy on clinical cardiovascular end points. In the Vitamin Intervention for Stroke Prevention (VISP) trial, therapy with high doses of vitamin B6 , vitamin , and folic acid did not affect the risk of recurrent isch- emic stroke compared with a low-dose formulation of these B complex vitamins. 