Published in Cancer Detection and Prevention 2001; 25(5):479-485.

Effect of Two Years' Supplementation with Natural Antioxidants on Vitamin and Trace Element Status Biomarkers: Preliminary Data of the Su.Vi.Max Study

Denis J-M Malvy MD, PhD,a A lain Favier, PhD,b Henri Faure, PhD,b Paul Preziosi, MD,c Pilar Galan, MD, PhD,c Josiane Arnaud, PhD,b Anne-Marie Roussel, PhD,b Serge Briançon, MD,d and Serge Hercberg, MD, PhDc

aINSERM U330 and Centre René Labusquiére, University Victor Segalen Bordeaux 2, Bordeaux, bLaboratory of Biochemistry, University Hospital Centre of Grenoble, Grenoble, cInstitute Scientifique et Technique de Ia Nutrition et de l'Alimentation/CNAM, Paris, and d School of Public Health, Faculty of Medicine, Nancy, France.

Address all correspondence and reprint requests to Denis Malvy, MD, PhD, Centre René Labusquière, Université Victor Segalen Bordeaux 2, 146 Rue Léo Saignat, F-33076 Bordeaux Cedex, France.

ABSTRACT: The "Supplementation en Vitamins et Minéraux AntioXidants" (SU.VI.MAX) study is a randomized double-blind, placebo controlled, primary-prevention trial designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 µg; and zinc, 20 mg) at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of cancers and cardiovascular diseases. The study involves 12,735 eligible subjects (women aged 35-60 years, men aged 45-60 years) included in 1994 in France. They will be followed up for 8 years. The targeted population is the general population. The aim of this specific analysis is to assess the effect of 2 years-supplementation on biochemical indicators of vitamin and trace element on a subsample of 1000 subjects. The mean (± standard deviation) concentrations of plasma beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc among participants who were randomly assigned to receive a daily supplementation with beta-carotene, vitamin E, vitamin C, selenium and zinc for 2 years were significantly higher than those who were assigned to receive placebo. Specifically, the mean concentrations among men in the intervention group were 0.86 ± 0.70 µmol/L for beta-carotene, 35.3 ± 9.3 µmol/L for alpha-tocopherol, 11.5 ± 4.7 µg/mL for vitamin C, 1.65 + 0 33 µmol/L for selenium, and 16.2 ± 3.9 µmol/L for zinc. The mean concentrations among women in the intervention were 1.25 ± 0.90 µmol/L for beta-carotene, 34.9 ± 8.4 µmol/L for alphatocopherol, 12.6 ± 4.0 µg/mL for vitamin C, 1.68 ± 0.37 µmol/L for selenium, and 15.3 ± 3.9 µmol/L for zinc. The values observed for beta-carotene and vitamin E in the supplementation group after 2 years of intervention are those that have been associated with the lowest risk of cancer in observational studies. They are definitely lower than concentrations reported in intervention studies showing an apparent negative effect of high levels of beta-carotene supplementation on the lung cancer incidence rate in high-risk subjects (initial level multiplied by 12-18). Data from the follow-up will ascertain if any plausible reduction in the incidence rate of cancers may be associated with such amounts of antioxidant agents.

KEY WORDS: antioxidants, cancers, prevention trial, trace elements, vitamins.