This Article Full Text Full Text (PDF) All Versions of this Article: 22/10/1535    most recent 01.ATV.0000034706.24149.95v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, B. G. Articles by Chait, A. Search for Related Content PubMed PubMed Citation Articles by Brown, B. G. Articles by Chait, A. Related Collections Nutrition Primary prevention Lipid and lipoprotein metabolism Oxidant stress

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1535.)
© 2002 American Heart Association, Inc.

Brief Reviews

Antioxidant Vitamins and Lipid Therapy

End of a Long Romance?

B. Greg Brown; Marian C. Cheung; Andrew C. Lee; Xue-Qiao Zhao; Alan Chait

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.

Correspondence to B. Greg Brown, MD, PhD, Cardiology, Box 356422, Health Sciences Building, Room A509, 1959 NE Pacific St, Seattle, WA 98195. E-mail bgbrown{at}u.washington.edu

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

This article has been cited by other articles:

				S. Blum, U. Milman, C. Shapira, R. Miller-Lotan, L. Bennett, M. Kostenko, M. Landau, S. Keidar, Y. Levy, A. Khemlin, et al. Dual Therapy With Statins and Antioxidants Is Superior to Statins Alone in Decreasing the Risk of Cardiovascular Disease in a Subgroup of Middle-Aged Individuals With Both Diabetes Mellitus and the Haptoglobin 2-2 Genotype Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): e18 - e20. [Full Text] [PDF]

				A. Pirillo, P. Uboldi, G. Pappalardo, H. Kuhn, and A. L. Catapano Modification of HDL3 by mild oxidative stress increases ATP-binding cassette transporter 1-mediated cholesterol efflux Cardiovasc Res, August 1, 2007; 75(3): 566 - 574. [Abstract] [Full Text] [PDF]

				M. Torzewski, V. Ochsenhirt, A. L. Kleschyov, M. Oelze, A. Daiber, H. Li, H. Rossmann, S. Tsimikas, K. Reifenberg, F. Cheng, et al. Deficiency of Glutathione Peroxidase-1 Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 850 - 857. [Abstract] [Full Text] [PDF]

				U. Singh, J. Otvos, A. Dasgupta, J. A. de Lemos, S. Devaraj, and I. Jialal High-Dose {alpha}-Tocopherol Therapy Does Not Affect HDL Subfractions in Patients with Coronary Artery Disease on Statin Therapy Clin. Chem., March 1, 2007; 53(3): 525 - 528. [Abstract] [Full Text] [PDF]

				P. J. Gillies and E. S. Krul Using Genetic Variation to Optimize Nutritional Preemption J. Nutr., January 1, 2007; 137(1): 270S - 274S. [Abstract] [Full Text] [PDF]

				B. Fletcher, K. Berra, P. Ades, L. T. Braun, L. E. Burke, J. L. Durstine, J. M. Fair, G. F. Fletcher, D. Goff, L. L. Hayman, et al. Managing Abnormal Blood Lipids: A Collaborative Approach Circulation, November 15, 2005; 112(20): 3184 - 3209. [Abstract] [Full Text] [PDF]

				A. H. Lichtenstein and R. M. Russell Essential Nutrients: Food or Supplements?: Where Should the Emphasis Be? JAMA, July 20, 2005; 294(3): 351 - 358. [Abstract] [Full Text] [PDF]

				B. G. Brown and J. Crowley Is There Any Hope for Vitamin E? JAMA, March 16, 2005; 293(11): 1387 - 1390. [Full Text] [PDF]

				T. S. E. Albert, P. N. Duchateau, S. S. Deeb, C. R. Pullinger, M. H. Cho, D. C. Heilbron, M. J. Malloy, J. P. Kane, and B. G. Brown Apolipoprotein L-I is positively associated with hyperglycemia and plasma triglycerides in CAD patients with low HDL J. Lipid Res., March 1, 2005; 46(3): 469 - 474. [Abstract] [Full Text] [PDF]

				J. W Anderson Whole grains and coronary heart disease: the whole kernel of truth Am. J. Clinical Nutrition, December 1, 2004; 80(6): 1459 - 1460. [Full Text] [PDF]

				C. Gouedard, R. Barouki, and Y. Morel Induction of the Paraoxonase-1 Gene Expression by Resveratrol Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2378 - 2383. [Abstract] [Full Text] [PDF]

				F. Krotz, H.-Y. Sohn, and U. Pohl Reactive Oxygen Species: Players in the Platelet Game Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1988 - 1996. [Abstract] [Full Text] [PDF]

				P. M. Kris-Etherton, A. H. Lichtenstein, B. V. Howard, D. Steinberg, J. L. Witztum, and for the Nutrition Committee of the American Heart Antioxidant Vitamin Supplements and Cardiovascular Disease Circulation, August 3, 2004; 110(5): 637 - 641. [Full Text] [PDF]

				A. P. Levy, P. Friedenberg, R. Lotan, P. Ouyang, M. Tripputi, L. Higginson, F. R. Cobb, J.-C. Tardif, V. Bittner, and B. V. Howard The Effect of Vitamin Therapy on the Progression of Coronary Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women Diabetes Care, April 1, 2004; 27(4): 925 - 930. [Abstract] [Full Text] [PDF]

				J. L. Anderson and J. F. Carlquist Genetic polymorphisms of hepatic lipase and cholesteryl ester transfer protein, intermediate phenotypes, and coronary risk: Do they add up yet? J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1990 - 1993. [Full Text] [PDF]

				B. F. Asztalos, M. Batista, K. V. Horvath, C. E. Cox, G. E. Dallal, J. S. Morse, G. B. Brown, and E. J. Schaefer Change in {alpha}1 HDL Concentration Predicts Progression in Coronary Artery Stenosis Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 847 - 852. [Abstract] [Full Text] [PDF]

				N. R. Matthan, A. Giovanni, E. J. Schaefer, B. G. Brown, and A. H. Lichtenstein Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL J. Lipid Res., April 1, 2003; 44(4): 800 - 806. [Abstract] [Full Text] [PDF]