Canadian researchers assessed whether or not a supplementation with low doses of antioxidant vitamins and minerals could reduce the occurrence of prostate cancer and influence biochemical markers. The SU.VI.MAX trial comprised 5141 men randomised to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years. Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrolment and at the end of follow-up from 3616 men. Cox regression models were used to estimate the hazard ratio and related 95% CI of prostate cancer associated with the supplementation and to examine whether or not the effect differed among predetermined susceptible subgroups. During the follow-up, 103 cases of prostate cancer were diagnosed. Overall, there was a moderate non-significant reduction in prostate cancer rate associated with the supplementation (hazard ratio = 0.88; 95% CI = 0.60–1.29). However, the effect differed significantly between men with normal baseline PSA (< 3 μg/l) and those with elevated PSA. Among men with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements (hazard ratio = 0.52; 95% CI = 0.29–0.92). In men with elevated PSA at baseline, the supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (hazard ratio = 1.54; 95% CI = 0.87–2.72). The supplementation had no effect on PSA or IGF levels.