The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals.
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 Supplementation en Vitamines et Mineraux 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 mug 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.
Hercberg
Serge
S
Institut National de la Santé et de la Recherche Médicale, Unité de Recherche Médicale INSERM/Institut National de la Recherche Agronomique/Conservatoire National des Ants et Métiers (CNAM), Paris, France.
Galan
Pilar
P
Preziosi
Paul
P
Bertrais
Sandrine
S
Mennen
Louise
L
Malvy
Denis
D
Roussel
Anne-Marie
AM
Favier
Alain
A
Briançon
Serge
S
D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D019587:Dietary Supplements; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control*; D009369:Neoplasms / Q000517:prevention & control*; D012643:Selenium / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use; D015032:Zinc / Q000627:therapeutic use; D019207:beta Carotene / Q000627:therapeutic use
D000975:Antioxidants; D019207:beta Carotene; D014810:Vitamin E; D012643:Selenium; D015032:Zinc; D001205:Ascorbic Acid