Prostate Cancer and Supplementation With α-Tocopherol and β-Carotene: Incidence and Mortality in a Controlled Trial

Abstract

Background: Epidemiologic studies have suggested that vitamin E and ␤-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of ␣-tocopherol (a form of vitamin E) and ␤-carotene supplementation, separately or together, on prostate cancer in male smokers. Methods: A total of 29 133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive ␣-tocopherol (50 mg), ␤-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. Results: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = −47% to −12%) in the incidence of prostate cancer was observed among the subjects receiving ␣-tocopherol (n = 14 564) compared with those not receiving it (n = 14 569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = −65% to −1%) among men receiving ␣-tocopherol. Among subjects receiving ␤-carotene (n = 14 560), prostate cancer incidence was 23% higher (95% CI = −4%-59%) and mortality was 15% higher (95% CI = −30%-89%) compared with those not receiving it (n = 14 573). Neither agent had any effect on the time interval between diagnosis and death. Conclusions: Long-term supplementation with ␣-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings. [J Natl Cancer Inst 1998;90:440-6]

Potential health risks of complementary alternative medicines in cancer patients

“…We also issued a qualified warning to one patient taking beta-carotene, who was known to be an occasional smoker. Beta-carotene may increase the risk of prostate and lung cancer in smokers through enhanced production of beta-carotene oxidation metabolites if they are not neutralised by other antioxidants such as vitamin C and E (Heinonen et al, 1998;Patrick, 2000). In addition, 18 (11.0 %) patients reported taking supplements higher than the recommended doses.…”

A case–control study of selenium in nails and prostate cancer risk in British men

“…However, smoking was not associated with risk in this study population and additional adjustment for smoking made no appreciable difference to the association between selenium concentration and cancer risk. The hypothesis that selenium and vitamin E intake may interact to influence prostate cancer risk has been largely derived from animal studies (Diplock, 1978) and from a randomised controlled trial that found a-tocopherol to be associated with a reduced risk of prostate cancer (Heinonen et al, 1998). Indeed, a trial specifically designed to test the joint efficacy of selenium and vitamin E for the prevention of prostate cancer is underway (Klein et al, 2003).…”

Impact of diet on prostate cancer: a review

“…This randomized, double-blind, placebo-controlled study in 29 133 male smokers found a 32% reduction in prostate cancer incidence and a 41% lower mortality in those receiving 50 mg of alpha-tocopherol daily for 5-8 y. 68 Analysis in the 6-year post-trial follow-up assessment found that the relative risk (RR) in the alpha-tocopherol group increased from 0.64 (95% CI, 0.44-0.94) during the trial to 0.73 (95% CI, 0.51-1.04) by 1996 and finally to 0.94 (95% CI, 0.72-1.24) by 1999. 69 As the RR returned toward 1.0, the post-intervention study concluded that the beneficial effects of alpha-tocopherol supplementation disappeared after the intervention, suggesting that benefit from vitamin E requires long-term supplement use.…”