on August 22, 2002
Published online before print August 22, 2002, doi: 10.1161/01.ATV.0000034706.24149.95
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Submitted on July 15, 2002
Accepted on July 29, 2002
Antioxidant Vitamins and Lipid Therapy. End of a Long Romance?
B. Greg Brown *;
From the Department of Medicine, Divisions of Cardiology (B.G.B., A.C.L., X.-Q.Z.) and Metabolism, Endocrinology, and Nutrition (M.C.C., A.C.), University of Washington School of Medicine, Seattle.
* To whom correspondence should be addressed. E-mail: bgbrown{at}u.washington.edu.
Abstract—During the past decade, the perception flourished that lipid and antioxidant therapy were 2 independent avenues for cardiovascular protection. However, studies have shown that commonly used antioxidant vitamin regimens do not prevent cardiovascular events. We found that the addition of antioxidant vitamins to simvastatin-niacin therapy substantially blunts the expected rise in the protective high density lipoprotein (HDL)2 cholesterol and lipoprotein(A-I) subfractions of HDL, with apparent adverse effects on the progression of coronary artery disease. To better understand this effect, 12 apolipoproteins, receptors, or enzymes that contribute to reverse cholesterol transport have been examined in terms of their relationship to HDL2 and lipoprotein(A-I) levels and the potential for antioxidant modulation of their gene expression. Three plausible candidate mechanisms are identified: (1) antioxidant stimulation of cholesteryl ester transfer protein expression/activity, (2) antioxidant suppression of macrophage ATP binding cassette transmembrane transporter A1 expression, and/or (3) antioxidant suppression of hepatic or intestinal apolipoprotein A-I synthesis or increase in apolipoprotein A-I catabolism. In summary, antioxidant vitamins E and C and ß-carotene, alone or in combination, do not protect against cardiovascular disease. Their use for this purpose may create a diversion away from proven therapies. Because these vitamins blunt the protective HDL2 cholesterol response to HDL cholesterol-targeted therapy, they are potentially harmful in this setting. We conclude that they should rarely, if ever, be recommended for cardiovascular protection.
Key words: antioxidant vitamins • lipid therapy • atherosclerosis
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