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Effects of long-term antioxidant supplementation and association of serum antioxidant concentrations with risk of metabolic syndrome in adults^1,2,3

¹ From the Nutritional Epidemiology Research Unit-UMR U557 INSERM, U1125 INRA, CNAM, PARIS 13 University, Bobigny, France (SC, A-CV, PG, and SH); the Public Health Department, Avicenne Hospital, Bobigny, France (SC and SH); the Biologie Intégrée Department, CHU de Grenoble, Grenoble, France (JA, AF, and HF); INSERM, U884, Bioénergétique Fondamentale et Appliquée Laboratory, and Grenoble University, UFR de Biologie, Médecine, Pharmacie et APS, Grenoble, France (JA and AF); The George Institute for International Health, University of Sydney, Sydney, Australia (RH); and INSERM U558, Epidemiology and Public Health Analyses, Faculty of Medicine, University Paul Sabatier III, Toulouse, France (NA).

² The SU.VI.MAX Study was approved by the National Ethical Committee (CCPPRB number 706).

³ Address correspondence to S Czernichow, Nutritional Epidemiology Research Unit-UMR U557 INSERM, U1125 INRA, CNAM, PARIS 13 University, CRNH-IdF, 74 rue Marcel Cachin, 93017 Bobigny, France. E-mail: czernichow{at}uren.smbh.univ-paris13.fr.

Background: Limited observational evidence suggests lower antioxidant concentrations in individuals with the metabolic syndrome (MetS); few randomized controlled trials have addressed the effect of multiple antioxidants on the risk of MetS.

Objective: The objective was to examine the effect of antioxidant supplementation for 7.5 y on the incidence of MetS and the epidemiologic association between baseline serum antioxidant concentrations and the prospective risk of MetS.

Design: Adults (n = 5220) participating in the SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) primary prevention trial were randomly assigned to receive a supplement containing a combination of antioxidants (vitamins C and E, β-carotene, zinc, and selenium) at nutritional doses or a placebo. Subjects were free of MetS at baseline and were followed for 7.5 y.

Results: Antioxidant supplementation for 7.5 y did not affect the risk of MetS. Baseline serum antioxidant concentrations of β-carotene and vitamin C, however, were negatively associated with the risk of MetS; the adjusted odds ratios (and 95% CIs) for the highest compared with the lowest tertile were 0.34 (0.21, 0.53; P for trend = 0.0002) and 0.53 (0.35, 0.80; P for trend = 0.01), respectively. Baseline serum zinc concentrations were positively associated with the risk of developing MetS; the adjusted odds ratio (and 95% CI) for the highest compared with the lowest tertile was 1.81 (1.20, 2.72; P for trend = 0.01).

Conclusions: The experimental finding of no beneficial effects of antioxidant supplementation in a generally well-nourished population is consistent with recent reports of a lack of efficacy of antioxidant supplements. However, the relations observed between the risk of MetS and baseline serum antioxidant concentrations, which probably reflect associations with overall dietary patterns, do support the current recommendations to consume antioxidant-rich foods. This trial was registered at clinicaltrials.gov as NCT00272428.