Challenges in understanding the relationship between vitamin supplementation and secondary stroke prevention stem from limitations in trial design, for example, including patients with both cardiovascular and and enrollment from countries with varying levels of folate supplementa- tion of foods. Although meta-analyses of patients with vascular disease, including some with cere- brovascular disease, suggest a small but significant reduction in subsequent stroke risk among those receiving supplementation, assessment of factors that may modify this relationship (including genetic variants in folate metabolism, preexisting homocys- teine level, use of antiplatelet medications, renal function, and dose of B vitamin supplementation) is inconsistent among studies.609,629 637 Although 1 pri- mary prevention study among hypertensive patients with high homocysteine found that the addition of folic acid to enalapril was more effective in reducing first stroke among those with the methylenetetrahy- drofolate reductase C677T CC/CT polymorphism,637 it remains unknown whether folic acid or vitamin B supplementation in a specific subgroup of patients with recent stroke or TIA may be beneficial in reduc- ing the risk of secondary stroke. Recommendation-Specific Supportive Text 1. Results from VITATOPS (Vitamins to Prevent and VISP (Vitamin Intervention for did not show a significant reduction in risk of secondary stroke among patients with recent stroke who were randomized CLINICAL STATEMENTS AND GUIDELINES Kleindorfer to receive various doses of folic acid and vitamin B supplementation. Knowledge Gaps and Future Research Questions remain to be addressed about whether there are specific subgroups of stroke patients in whom B vitamin supplementation reduces secondary stroke risk. Randomized trials of B vitamins for secondary stroke prevention are needed in patients with stroke or TIA who do not consume folate-fortified foods. 