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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1261.)
© 2001 American Heart Association, Inc.

Brief Review

Is the Emperor Wearing Clothes?

Clinical Trials of Vitamin E and the LDL Oxidation Hypothesis

Jay W. Heinecke

From the Departments of Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Mo.

Correspondence to Dr Jay W. Heinecke, Division of Atherosclerosis, Nutrition and Lipid Research, Box 8046, 660 S Euclid Ave, St. Louis, MO 63110. E-mail heinecke{at}im.wustl.edu

Abstract—— A wealth of evidence indicates that oxidized low density lipoprotein (LDL) may be of central importance in animal models of atherogenesis. In recent clinical trials, however, dietary vitamin E supplements have not consistently prevented cardiac events in humans with established coronary artery disease. Such mixed results have led many to question the role of LDL oxidation in human atherosclerosis, although this interpretation assumes that the doses of vitamin E used in the studies inhibited lipid oxidation in vivo. In fact, there is remarkably little evidence indicating that those particular regimens effectively inhibit lipid peroxidation in healthy humans. Moreover, evidence of increased oxidative stress was not a criterion for inclusion in the trials; therefore, vitamin E may have benefited only a subset of the participants. These uncertainties raise doubts about the ability of vitamin E to augment antioxidant defense mechanisms in vivo and leave many questions about LDL oxidation and atherosclerosis unanswered.

Key Words: atherosclerosis • antioxidant • lipid peroxidation • oxidative stress • oxidized LDL

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