The Vitamin Intervention for Stroke Prevention (VISP) trial did not show efficacy of high-dose vitamin therapy (2.5 mg of folic acid, 25 mg of pyridoxine, and 400 mcg of vitamin B12 daily) as compared with low-dose vitamin therapy (20 mcg of folic acid, 200 mcg of vitamin B6, and 6 mcg of vitamin B12 daily) with respect to recurrent vascular events in patients with a history of a stroke.

In a new study, the data from the VISP trial were re-analyzed, after exclusion of patients with low and very high vitamin B12 levels at baseline (< 250 and > 637 pmol/L, representing the 25th and 95th percentiles). Patients with very low vitamin B12 levels (< 150 pmol/L) in both study arms were receiving parenteral vitamin B12 injections outside of the study, and those with moderately low levels may have been vitamin B12 malabsorbers, and therefore less likely to benefit from oral supplementation. Patients below the tenth percentile of renal function were also excluded. The criteria for this subgroup were defined before any data analysis. In all, 59% of the initial study group was included in the subgroup analysis. For the combined end point of ischemic stroke, coronary disease, or death, there was a 21% reduction in the risk of events in the high-dose group compared with the low-dose group (unadjusted p = 0.049; adjusted for age, sex, blood pressure, smoking, and vitamin B12 level, p = 0.056).

Comment: The results of this study suggest that relatively large doses of vitamin B12 may be necessary for some patients to maximize the benefits of B-vitamin therapy with respect to cardiovascular disease prevention. The failure to use large doses of vitamin B12 in some homocysteine-lowering trials might explain the conflicting results obtained in these studies. Patients with chronic renal failure on hemodialysis are known to require frequent parenteral doses of vitamin B12 in order to achieve the maximum homocysteine-lowering effect. Perhaps some patients with cardiovascular disease also have a higher-than-normal requirement for vitamin B12.

Spence JD, et al. Vitamin Intervention For Stroke Prevention trial: an efficacy analysis. Stroke. 2005;36:2404-2409.