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A Randomized, Placebo-Controlled Trial of the Health Effects of Antioxidant Vitamins and Minerals

Serge Hercberg, MD, PhD; Pilar Galan, MD, PhD; Paul Preziosi, MD; Sandrine Bertrais, PhD; Louise Mennen, PhD; Denis Malvy, MD, PhD; Anne-Marie Roussel, PhD; Alain Favier, PhD; Serge Briançon, MD

Arch Intern Med. 2004;164:2335-2342.

Background  It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population.

Methods  The Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 µg of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years.

Results  No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found (P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval {CI}, 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction).

Conclusions  After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.

Author Affiliations: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité de Recherche Médicale INSERM/Institut National de la Recherche Argronomique/Conservatoire National des Ants et Métiers (CNAM) (Drs Hercberg, Galan, Preziosi, Bertrais, and Mennen), and Unité de Surveillance et d’Épidémiologie Nutritionnelle (Drs Hercberg and Mennen), InVS/CNAM, Paris, France; Centre René-Labusquière, Université Victor Segalen, Bordeaux, France (Dr Malvy); Laboratoires Nutrition, Vieillissement et Maladies Cardiovasculaires (Dr Roussel) and Lésions des Acides Nucléiques (Dr Favier), Université Joseph Fourier, Grenoble, France; and Département d’Épidémiologie Clinique,École de Santé Publique, Faculté de Médecine, Centre Hospitalier Universitaire (CHU) Nancy, Nancy, France (Dr Briançon).

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