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Better Health Store News: Do Antioxidants Reduce the Effectiveness of Cholesterol-Lowering Drugs?
By Jeremy Appleton, ND

Healthnotes Newswire — Antioxidants may blunt the effectiveness of a cholesterol-lowering drug regimen, according to a new study in Atherosclerosis, Thrombosis and Vascular Biology,1 a journal of the American Heart Association.

Patients with coronary artery disease and extremely low HDL (“good”) cholesterol were given a combination of the cholesterol-lowering agents simvastatin (Zocor®) and niacin (vitamin B3), this same combination plus antioxidant supplements (beta-carotene, vitamin C, vitamin E and selenium), the antioxidants alone, or a placebo. The simvastatin-niacin group and the simvastatin-niacin plus antioxidants group had similar reductions in total cholesterol, LDL (“bad”) cholesterol, and triglycerides.

The simvastatin-niacin group, however, had greater increases in HDL cholesterol, and greater reductions in a less well-known heart disease risk factor (called lipoprotein A-I) than did those taking the combination of simvastatin-niacin and antioxidants. The authors concluded that the antioxidants blunted the favorable response to simvastatin-niacin. An accompanying editorial called for a halt to recommendations of antioxidants for the prevention and treatment of cardiovascular disease.2 However, when the totality of evidence is considered, the conclusion of that editorial appears unwise.

If antioxidants do blunt one of the effects of simvastatin-niacin therapy, that does not necessarily mean that the net effect of antioxidants is negative. By analogy, supplementation with niacin has been shown to raise blood levels of homocysteine, an effect which would be expected to increase the risk of heart disease.3 Yet, niacin therapy has been shown to reduce heart disease-related mortality.4 Evidently, the beneficial effects of niacin on cholesterol levels and other cardiac risk factors such as fibrinogen outweigh any potential adverse effect on homocysteine levels.5

Antioxidants have numerous positive effects on the cardiovascular system that are unrelated to cholesterol regulation. For example, vitamins E and C each inhibit platelet aggregation and prevent the oxidation of LDL cholesterol, effects which are believed to prevent the development of cardiovascular disease.6 7 8 9 Moreover, there is direct clinical evidence that vitamin E may prevent heart attacks,10 although research in this area is conflicting.11 In addition, there are some apparently beneficial interactions between antioxidants and simvastatin and related drugs. For example, in one study, eight weeks of simvastatin plus vitamin E (300 IU per day) improved markers of blood vessel elasticity more than simvastatin alone.12 In a double-blind trial, lovastatin (a drug similar to simvastatin) was found to increase oxidative damage to LDL cholesterol (which might increase blood vessel damage), but this effect was partially blocked by vitamin E.13

It is important not to draw conclusions about any particular therapy solely on the basis of how that treatment affects individual laboratory values. For example, even though estrogen-replacement therapy lowers serum cholesterol levels in postmenopausal women,14 it does not reduce their risk of heart disease.15 The reported interaction between simvastatin-niacin and antioxidants does not appear to be sufficient reason for people to deprive themselves of the potentially beneficial effects of antioxidant supplements.

References
1. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of hdl to simvastatin-niacin therapy in patients with coronary artery disease and low hdl. Arterioscler Thromb Vasc Biol 2001;21:1320–6.
2. Kuller LH. A time to stop prescribing antioxidant vitamins to prevent and treat heart disease? Arterioscler Thromb Vasc Biol 2001;21:1253.
3. Garg R, Malinow M, Pettinger M. Niacin treatment increases plasma homocyst(e)ine levels. Am Heart J 1999;138:1082–7.
4. Horwitz N. Link niacin to longevity after an MI. Med Tribune 1985(April 24):1.
5. Philipp CS, Cisar LA, Saidi P, Kostis JB. Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease. Am J Cardiol 1998;82:697–9.
6. Mabile L, Bruckdorfer KR, Rice-Evans C. Moderate supplementation with natural alpha-tocopherol decreases platelet aggregation and low-density lipoprotein oxidation. Atherosclerosis 1999;147:177–85.
7. Arrol S, Mackness MI, Durrington PN. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity. Atherosclerosis 2000;150:129–34.
8. Wilkinson IB, Megson IL, MacCallum H, et al. Oral vitamin C reduces arterial stiffness and platelet aggregation in humans. J Cardiovasc Pharmacol 1999;34:690–3.
9. Jialal I, Vega GL, Grundy SM. Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis 1990;82:185–91.
10. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781–6.
11. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000;342:154–60.
12. Neunteufl T, Kostner K, Katzenschlager R, et al. Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol 1998;32:711–6.
13. Palomäki A, Malminiemi K, Malminiemi O, Solakivi T. Effects of lovastatin therapy on susceptibility of LDL to oxidation during alpha-tocopherol supplementation. Arterioscler Thromb Vasc Biol 1999;19:1541–8.
14. The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1995;273:199–208.
15. Mitka M. New advice for women patients about hormone therapy and the heart. JAMA 2001;286:907. [News report]

Jeremy Appleton, ND,is a licensed naturopathic physician, writer, and educator in the field of evidence-based complementary and alternative medicine. Dr. Appleton is Chair of Nutrition at the National College of Naturopathic Medicine.

This article is provided by Healthnotes for theBetterHealthStore. Copyright © 2001 Healthnotes, Inc. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.




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