Reply to J Hathcock

Johns Hopkins Medical Institutions
Welch Center for Prevention, Epidemiology and Clinical Research
2024 E Monument Street
Baltimore, MD 21205-2223
E-mail: eguallar{at}jhsph.edu

Dear Sir:

We thank Hathcock for his interest in our analysis of the currently available literature on vitamin-mineral supplementation and the progression of atherosclerosis (1). After a systematic review of all available randomized controlled trials, we concluded that there is no clear evidence to support the use of antioxidant vitamin and B vitamin supplements to reduce the progression of atherosclerosis.

Hathcock argues that, because of the small number of trials, the statistical power to detect intervention effects was small. For antioxidant vitamins, several trials were of high quality and of sufficient size to identify clinically relevant effects. For instance, the HDL-Atherosclerosis Treatment Study (HATS) tested both simvastatin plus niacin and vitamin E, vitamin C, selenium, and ß-carotene in a 2-by-2 factorial design. Simvastatin plus niacin provided a marked angiographic benefit in terms of the progression of atherosclerosis, but antioxidant vitamins did not (2). Likewise, the Study to Evaluate Carotid Ultrasound changes in patients treated with ramipril and vitamin E (SECURE) tested ramipril and vitamin E in a 2-by-2 factorial design. Again, ramipril showed a beneficial effect, but vitamin E did not (3). The overall lack of effect of antioxidants on the progression of atherosclerosis in subjects who did not undergo percutaneous transluminal coronary angioplasty likely did not result from a lack of power.

Although there is less scientific evidence available on the effects of B vitamins on the progression of atherosclerosis and on the effects of vitamin-mineral supplements in patients undergoing percutaneous transluminal coronary angioplasty, our meta-analysis provided a transparent and systematic appraisal of the current evidence. Overall, there is no convincing evidence that vitamin-mineral supplements reduce the progression of atherosclerosis.

Hathcock also cites the results of the Women's Health Study to support a beneficial effect of vitamin E supplements on cardiovascular disease mortality. The conclusions of this study, based on all cardiovascular events, however, were sobering: "These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women" (4).

Antioxidant vitamin and B vitamin supplements have been extensively studied for a presumed beneficial effect in the prevention of clinical cardiovascular events in large, high-quality, randomized controlled trials, with disappointing results. In view of the randomized evidence, the epidemiologic evidence discussed by Hathcock cannot be used as grounds for supporting the use of these vitamin supplements to prevent cardiovascular disease. Therefore, there is currently no sound evidence to support the use of antioxidant vitamin and B vitamin supplements to prevent clinical cardiovascular events or the progression of atherosclerosis.

ACKNOWLEDGMENTS

None of the authors had a conflict of interest.

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