Homocysteine

Abstract

The authors of the much publicized though not yet published Norwegian Vitamin Study (NORVIT)1 of vitamin therapy in coronary artery disease, are widely quoted as saying that vitamin therapy for lowering plasma total homocysteine (tHcy) was harmful, and that “homocysteine is dead.” However, the slides of their presentation1 do not show the B12 status of the participants, nor do they indicate whether B12 injections were given to participants with low levels of B12. Commentators2 have called NORVIT “the largest trial to date to test the hypothesis that folate supplementation reduces risk of cardiovascular disease,” but because there were 4 treatment arms in NORVIT, each with 900 participants, the number of patients randomized to folate/B12 or folate/B12/B6 was essentially the same as that in the Vitamin Intervention for Stroke Prevention (VISP) trial3 (≈1800). They used a much higher dose of B6 than other studies and cannot exclude the possibility that their results were driven by that choice. As did VISP, they also used a dose of B12 that, as has recently become apparent, was too low for adequate absorption of B12 in elderly subjects (discussed below). In this issue of Stroke , a substudy of the Vitamins to Prevent Stroke (VITATOPS) trial4 reports that in Singapore, treatment with 2.5 mg folic acid, 0.5 mg vitamin B12, and 25 mg B6 reduced levels of tHcy by 3.8 μmol/L compared with placebo.5 The authors also studied 2 polymorphism …