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(Circulation. 2001;103:1006.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Supplementation of Atherogenic Diet With B Vitamins Does Not Prevent Atherosclerosis or Vascular Dysfunction in Monkeys

Steven R. Lentz, MD, PhD; Donald J. Piegors, MBA; M. René Malinow, MD; Donald D. Heistad, MD

From the Veterans Affairs Medical Center (S.R.L., D.D.H.) and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, and the Oregon Regional Primate Research Center (M.R.M.), Beaverton.

Correspondence to Steven R. Lentz, MD, PhD, Department of Internal Medicine, C303 GH, University of Iowa, Iowa City, IA 52242. E-mail steven-lentz{at}uiowa.edu

Background—Hyperhomocysteinemia is associated with increased risk of atherosclerotic and thrombotic vascular disease. In many patients, hyperhomocysteinemia can be treated or prevented by dietary supplementation with B vitamins, but the clinical benefit of B vitamins for the prevention of vascular disease has not been proven.

Methods and Results—Using an atherogenic diet that produces both hyperhomocysteinemia and hypercholesterolemia, we tested the hypothesis that dietary supplementation with B vitamins (folic acid, vitamin B₁₂, and vitamin B₆) would prevent hyperhomocysteinemia, vascular dysfunction, and atherosclerotic lesions in monkeys. After 17 months, plasma total homocysteine increased from 3.6±0.3 to 11.8±1.7 µmol/L in monkeys fed an unsupplemented atherogenic diet (P<0.01) but did not increase in monkeys fed an atherogenic diet supplemented with B vitamins (3.8±0.3 µmol/L). Serum cholesterol increased from 122±7 to 550±59 mg/dL in the unsupplemented group (P<0.001) and from 118±5 to 492±55 mg/dL in the supplemented group (P<0.001). Responses to endothelium-dependent vasodilators, both in resistance vessels in vivo and in the carotid artery ex vivo, were impaired to a similar extent in groups that did and did not receive vitamin supplements. Anticoagulant responses to the infusion of thrombin were also impaired to a similar extent in both groups. Vitamin supplementation failed to prevent intimal thickening in the carotid or iliac arteries.

Conclusions—These findings demonstrate that supplementation with B vitamins prevents hyperhomocysteinemia but is not sufficient to prevent the development of vascular dysfunction or atherosclerotic lesions in monkeys with marked hypercholesterolemia, even in the absence of preexisting atherosclerosis.

Key Words: atherosclerosis • cholesterol • endothelium • homocysteine • thrombin

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