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Am Fam Physician. 1999;59(10):2904

Recent developments in understanding the process of atherosclerosis have led to the consideration that antioxidants may play a role in primary or secondary prevention. Specifically, antioxidants have been proposed as inhibitors of atherogenic and thrombotic events in the coronary arterial wall. Vitamin C, vitamin E and beta carotene are the dietary antioxidants that have received the most attention. Tribble, for the Nutrition Committee of the American Heart Association, reviewed evidence concerning the role of dietary antioxidants in coronary disease prevention and pointed out issues that need to be resolved before prophylactic use of antioxidants can be recommended.

The author states that support for the importance of dietary antioxidants in the prevention of coronary heart disease has mostly come from observational studies. In cohort and case-control studies, increased antioxidant intake was associated with a reduced risk of major coronary disease. The largest of these cohort studies was the Nurses' Health Study, in which 85,000 participants were followed for up to eight years. The risk of coronary disease was lowest in women with a vitamin E intake achievable only by supplementation. This study was reported in 1993.

In another study, a lower risk of major coronary events was reported in men who had a high intake of beta carotene. Subgroup analyses, however, revealed that this relationship was only significant in current and former smokers. A relationship between vitamin C intake and disease risk has not been reported in observational studies.

Direct experimental evidence that antioxidants prevent coronary disease is lacking. For example, no evidence of a benefit from beta carotene on cardiovascular disease was observed in the Physicians' Health Study, which involved 22,000 American male physicians. Similarly, the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study evaluated the effects of 50 IU of vitamin E, 20 mg of beta carotene or both, but did not demonstrate any reduction in the risk of lung cancer or major coronary events with the use of these antioxidants.

The author states that the results of secondary prevention trials have been more supportive of the potential benefits of antioxidants. For example, the Cambridge Heart Antioxidant Study showed a reduction in the risk of cardiovascular events with high dosages (400 or 800 IU) of vitamin E. The combined results of the two dosage levels showed that the risk of myocardial infarction was reduced by 77 percent and the risk of all cardiovascular events by 47 percent.

The author concludes that evidence in support of the potential health benefits of dietary antioxidants is insufficient. Thus, a general recommendation for supplementation cannot be endorsed. According to the AHA, the most prudent and scientifically supportable recommendation for the general population is to consume a balanced diet with emphasis on antioxidant-rich fruits and vegetables and whole grains. Although diet alone may not provide the levels of vitamin E intake that have been associated with a lowest risk in a few observational studies, the absence of efficacy and safety data from randomized trials precludes the establishment of a population-wide recommendation for vitamin E supplementation. In the case of secondary prevention, the results from clinical trials of vitgamin E have been encouraging and, if further studies confirm these findings, consideration of the merits of vitamin E supplementation in individuals with cardiovascular disease would be warranted.

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