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Am Fam Physician. 2003;68(8):1613-1614

Clinical Question: Are antioxidants effective in preventing heart disease?

Setting: Various (meta-analysis)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: Many years ago, Herbert pointed out that the term antioxidants was misleading because the purported agents must oxidize one substrate to reduce another (Herbert V. The antioxidant supplement myth. Am J Clin Nutr 1994;60:157–8). After discovering that the name is problematic, it is not surprising that people have wondered whether we have the function right, not to mention the effect.

In this study, investigators searched MEDLINE to identify randomized trials of vitamin E and beta-carotene in the primary and secondary prevention of heart disease. They do not describe searching for unpublished data. To minimize the effect of publication bias, the investigators excluded trials with fewer than 1,000 subjects. They also included only studies from developed countries to reduce the potential effects of nutrient-poor diets. Two investigators independently determined study eligibility, but they do not describe their methods of data extraction or of resolving conflict, and they do not report the rate of concordance among the reviewers.

The investigators identified 12 studies; eight used beta-carotene, and seven used vitamin E. Of the 12 studies, seven were for primary prevention and five for secondary prevention (in patients with established cardiovascular disease). More than 130,000 patients participated in the studies of beta-carotene, in which all-cause mortality was 7.4 percent in the actively treated patients and 7 percent in the control patients (P = .003; number needed to kill [NNK] = 250). A similarly small but significant increase in cardiovascular mortality was seen among patients receiving beta-carotene (3.4 versus 3.1 percent; NNK = 334; P = .003). Beta-carotene had no effect on stroke events (2.3 percent for treated and control patients). The data were homogeneous across studies for these end points.

More than 81,000 patients participated in studies of vitamin E. All-cause mortality was the same in treated patients (11.3 percent) and control patients (11.1 percent; P = .42). The event rate also was the same for cardiovascular mortality in treated and control patients (6 percent; P = .94) and for stroke rate (3.6 percent in treated patients and 3.5 percent in control patients; P = .70).

Finally, the investigators combined all end points and found that the likelihood of any bad outcome was identical in patients receiving vitamin E or placebo (9.8 percent; P = .93). These data also were homogeneous across studies.

Bottom Line: Beta-carotene and vitamin E offer no protection against all-cause mortality, cardiovascular mortality, or stroke. (Level of Evidence: 1a–)

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