Homocysteine, B Vitamins, and Atherosclerosis

Abstract

To the Editor: The conclusion by Folsom et al1 that raised homocysteine concentrations in the blood may be a consequence, not a cause, of coronary artery disease has serious clinical implications. As McCully2 pointed out in his recent editorial, arteriosclerosis in hyperhomocysteinemia may result from 3 different enzymatic abnormalities: deficiency of cystathionine synthase, which is a pyridoxal phosphate–dependent enzyme; deficiency of methyltetrahydrofolate homocysteine methyl transferase, which is a cobalamin-dependent enzyme; and deficiency of methylene tetrahydrofolate reductase, which is a folate-dependent enzyme. The last enzymatic abnormality explains the origin of arteriosclerosis observed in vitamin B6–deficient monkeys and choline-deficient rats, 2 important animal models in which hyperhomocysteinemia also leads to atherogenesis.2 Although I agree with Folsom et al1 that randomized trials are needed to better clarify the interrelationships of homocysteine, B vitamins, …