Mortality associated with low plasma concentration of beta carotene and the effect of oral supplementation

E. R. Greenberg, J. A. Baron, M. R. Karagas, T. A. Stukel, D. W. Nierenberg, M. M. Stevens, J. S. Mandel and R. W. Haile
Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH, USA.

OBJECTIVE: To examine the relationship between beta carotene plasma concentration and beta carotene supplementation and risk of death from major disease causes. DESIGN: Cohort study of plasma concentrations; randomized, controlled clinical trial of supplementation. SETTING: Medical school-affiliated dermatology practices. PATIENTS: A total of 1188 men and 532 women with mean age of 63.2 years, who had enrolled in a randomized clinical trial of beta carotene supplementation to prevent nonmelanoma skin cancer. INTERVENTION: Oral beta carotene, 50 mg per day for a median of 4.3 years. MAIN OUTCOME MEASURES: All-cause mortality and mortality from cardiovascular disease and cancer. RESULTS: During a median follow-up period of 8.2 years, there were 285 deaths. Persons whose initial plasma beta carotene concentrations were in the highest quartile (>0.52 micromol/L [27.7 microg/dL]) had a lower risk of death from all causes (adjusted relative rate [RR], 0.52; 95% confidence interval [CI] 0.44 to 0.87) and from cardiovascular diseases (adjusted RR, 0.57; 95% CI, 0.34 to 0.95) compared with persons with initial concentrations in the lowest quartile (<0.21 micromol/L [11.2 microg/dL]). Patients randomly assigned to beta carotene supplementation showed no reduction in relative mortality rates from all causes (adjusted RR, 1.03; 95% CI, 0.82 to 1.30) or from cardiovascular disease (adjusted RR, 1.16; 95% CI, 0.82 to 1.64). There was no evidence of lower mortality following supplementation among patients with initial beta carotene concentrations below the median for the study group. CONCLUSIONS: These analyses provide no support for a strong effect of supplemental beta carotene in reducing mortality from cardiovascular disease or other causes. Although the possibility exists that beta carotene supplementation produces benefits that are too small or too delayed to have been detected in this study, noncausal explanations should be sought for the association between plasma concentrations of beta carotene and diminished risk of death.

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