Antioxidants—Yes or No?

Abstract & Commentary

Synopsis: There is no clear evidence that antioxidants provided by dietary intake or by the addition of oral agents in the form of vitamin supplements can reduce the risk of developing atherosclerosis.

Source: McQuillan BM, et al. J Am Coll Cardiol. 2001;38(7): 1788-1794.

Preventative therapies aimed at reducing the incidence of cardiovascular diseases, the single major cause of mortality and morbidity worldwide, have improved dramatically over the past decade. For many years, substantial interest has been focused on the potential benefits of antioxidant vitamins in cardiovascular disease prevention.

McQuillan and his associates from the Heart Research Institute of Western Australia studied 1111 subjects (558 men and 553 women) whose mean age was approximately 52 years by measuring dietary vitamin intake, fasting plasma levels of vitamins A, C, and E, lycopene, and alpha- and beta-carotene. In addition, they performed bilateral carotid artery B-Mode ultrasound imaging. After adjustment for age and conventional risk factors, they found a progressive decrease in intima-media wall thickness (IMT). Dietary vitamin E levels accounted for only 1% of the variants in measured IMT in men and, in fact, there was an inverse association between carotid artery mean IMT and plasma lycopene in women but not in men. They concluded that the study provided limited support for the hypothesis that increased dietary intake of vitamin E and increased plasma lycopene may decrease the risk of atherosclerosis but they found no support for the widespread concept that supplemental antioxidant vitamins will protect against the development of atherosclerotic CAD.

Comment by Harold L. Karpman, MD, FACC, FACP

It is now commonly accepted that oxidation of low-density lipoprotein (LDL) is important in the development of early atherosclerosis because oxidized LDL possesses a number of biological properties that may promote atherogenesis.1,2 Animal studies have long suggested that administration of antioxidants may inhibit lipid oxidation and reduce the development of atherosclerosis.3,4 Despite these encouraging laboratory findings, the many epidemiological studies that have investigated the relationship between antioxidant vitamins and the occurrence of vascular disease have yielded results that often were in conflict with randomized clinical trial findings.5

McQuillan et al’s study of a large number of subjects with an equal gender ratio and broad age range provided no support for the long-held hypothesis that higher dietary consumption of the antioxidant vitamin E may reduce or prevent the development of early atherosclerosis. A number of epidemiologic studies are currently ongoing and hopefully will more clearly elucidate whether combinations of antioxidants and/or longer-term use of these agents in various populations will prevent early atherosclerosis in the normal population or even in the population of those individuals who are more susceptible to developing early vascular disease however, thus far, there certainly is no clear evidence that antioxidants provided by dietary intake or by the addition of oral agents in the form of vitamin supplements can reduce the risk of developing atherosclerosis. Until the results of these epidemiologic studies have been reported, physicians should focus their efforts on proven methods (ie, cigarette smoking cessation, exercise, lipid control, blood pressure lowering, counseling patients on avoidance of stress, weight reduction, etc.) and drug therapy (ie, aspirin, statins, beta blockers, angiotensin-converting enzyme inhibitors, etc.) for preventing symptomatic CAD and/or stroke and should not emphasize the alleged benefits of vitamin supplements or other alternative medicines until they have been clinically proven by well mounted, randomized studies.

References

1. Steinberg D, et al. N Engl J Med. 1989;320:915-924.

2. Esterbauer H, et al. Adv Pharmacol. 1997;38:425-486.

3. Carew TE, et al. Proc Natl Acad Sci USA. 1987;84: 7727-7729.

4. Verlangieri AJ, Bush MJ. Am Coll Nutr. 1992;11: 131-138.

5. Steinberg D. Lancet. 1995;346:36-38.

Dr. Karpman, Clinical Professor of Medicine, UCLA School of Medicine, is Associate Editor of Internal Medicine Alert.