Design of physicians' health study II - A randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials

PURPOSE: To assess the balance of benefits and risks of supplementation wit h beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiov ascular (CVD), and eye diseases. DESIGN: Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PI-IS II will utilize a 2 X 2 X 2 X 2 factorial de sign to test alternate day beta-carotene, alternate day vitamin E, daily vi tamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degener ation. PRIOR RESULTS: The final results of the recently completed Physicians' Heal th Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplement ation (50 mg on alternate days) had no significant benefit or harm on cance r or CVD during more than 12 years of treatment and follow-up. In regards t o cancer, there were possible benefits on total and prostate cancer in thos e with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-c arotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplem entation on subsequent vascular events among a small subgroup of 333 men wi th prior angina or revascularization. The currently available data from ran domized trials of primary prevention are sparse and inconsistent for vitami n E and non-existent for vitamin C and multivitamins. For eye diseases, nam ely cataract and age-related macular degeneration, there are no completed l arge-scale randomized trials of antioxidant vitamins. CONCLUSIONS: PHS II is unique in several respects. PHS II is the only prima ry prevention trial in apparently healthy men testing the balance of benefi ts and risks of vitamin E on cancer and CVD. In addition, PHS II is the onl y primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins,as well as any single antio xidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PI-IS II is the only trial testing a priori the hypotheses that b eta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, P HS II will add unique as well as importantly relevant and complementary inf ormation to the totality of evidence from other completed and ongoing large -scale randomized trials on the balance of benefits and risks of beta-carot ene, vitamin E, vitamin C, and multivitamins alone and in combination on pr evention of cancer, CVD and eye diseases. (C) 2000 Elsevier Science Inc. Al l rights reserved.