Antioxidant micronutrients have been reported to be associated with an improvement in the blood profile, but the results are not consistent. The aim of the present study was to assess the effects of antioxidant supplementation on changes in the serum lipid profile of adult participants in the SU.VI.MAX study. French adults (n = 12,741: 7,713 females aged 35-60 yr, and 5,028 males aged 45-60 yr) received daily antioxidant supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium, and 20 mg zinc) or a matching placebo. Median follow-up time was 7.5 yr. After 7.5 yr, no effect of supplementation on total cholesterol was observed in men or women after adjusting for baseline total cholesterol levels and lipid-lowering medications. The prevalence of hypercholesterolemia (> or =6.5 mmol/L) showed a trend toward being higher in women who received supplements compared with those who received the placebo (P= 0.06). In both sexes, the group receiving supplements exhibited higher mean serum TG concentrations than did the placebo group (P= 0.06 in men; P= 0.05 in women). The prevalence of hypertriglyceridemia (> or =2.3 mmol/L) was also significantly higher in men who received supplements (P= 0.03), but not in women. Our results suggest than long-term daily supplementation with low doses of beta-carotene, vitamins C and E, selenium, and zinc does not result in an improved lipid profile and could even adversely affect some blood lipids, possibly with a higher risk of hyperlipidemia in women.