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Editorial
February 4, 1998

Homocysteine, Folate, Vitamin B6, and Cardiovascular Disease

Author Affiliations

From the Department of Veterans Affairs Medical Center, Providence, RI.

JAMA. 1998;279(5):392-393. doi:10.1001/jama.279.5.392

The importance of hyperhomocysteinemia in the pathogenesis of arteriosclerosis was first recognized by study of vascular pathology in children with homocystinuria caused by 2 different enzymatic abnormalities of homocysteine metabolism.1 Homocystinuria caused by deficiency of cystathionine synthase, a pyridoxal phosphate-dependent enzyme, is characterized by vascular abnormalities and frequent arterial and venous thromboses.2 In 1968 a 2-month-old boy with a rare form of homocystinuria caused by deficiency of methyltetrahydrofolate homocysteine methyl transferase, a cobalamin-dependent enzyme, was discovered to have rapidly progressive arteriosclerosis.1 Because of the different metabolic patterns caused by these 2 enzymatic abnormalities, it was suggested that homocysteine causes arteriosclerotic plaques by a direct effect on the cells and tissues of the arteries. A third enzyme abnormality leading to homocystinuria, deficiency of methylenetetrahydrofolate reductase, a folate-dependent enzyme, was found to cause arteriosclerotic plaques,3 also supporting the conclusion that homocysteine is atherogenic. This interpretation 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. The atherogenic effect of homocysteine was subsequently demonstrated experimentally by parenteral and alimentary administration of the amino acid to rabbits4,5 and baboons.6

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