LACK OF EFFECT OF LONG-TERM SUPPLEMENTATION WITH BETA-CAROTENE ON THEINCIDENCE OF MALIGNANT NEOPLASMS AND CARDIOVASCULAR-DISEASE

Background. Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower ri sks of cancer and cardiovascular disease, and earlier basic research s uggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducte d a trial of beta carotene supplementation. Methods. In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alte rnate days), we enrolled 22,071 male physicians, 40 to 84 years of age , in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By Decembe r 31, 1995, the scheduled end of the study, fewer than 1 percent had b een lost to follow-up, and compliance was 78 percent in the group that received beta carotene. Results. Among 11,036 physicians randomly ass igned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall inci dence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neop lasm (except nonmelanoma skin cancer), as compared with 1293 in the pl acebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the pla cebo group); the number of deaths from cancer (386 vs. 380), deaths fr om any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of t he previous three end points (967 vs. 972). Among current and former s mokers, there were also no significant early or late differences in an y of these end points. Conclusions. In this trial among healthy men, 1 2 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovasc ular disease, or death from all causes. (C) 1996, Massachusetts Medica l Society.