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ORIGINAL RESEARCH COMMUNICATION |
1 From the Nutritional Epidemiology Branch (MEW, KAL, SJW, and DA) and the Genetic Epidemiology Branch (PRT), Division of Cancer Epidemiology and Genetics, and the Cancer Prevention Fellowship Program, Division of Cancer Prevention (KAL), National Cancer Institute, National Institutes of Health, Bethesda, MD, and the Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland (PP and JV)
Background: A meta-analysis of 19 trials suggested a small increase in the risk of all-cause mortality with high-dose vitamin E supplementation. Little is known, however, about the relation between mortality and circulating concentrations of vitamin E resulting from dietary intake, low-dose supplementation, or both.
Objective: We examined whether baseline serum 
-tocopherol concentrations are associated with total and cause-specific mortality.
Design: A prospective cohort study of 29 092 Finnish male smokers aged 50–69 y who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was carried out. Fasting serum -tocopherol was measured at baseline by using HPLC. Only 10% of participants reported vitamin E supplement use at baseline, and thus serum concentrations of vitamin E mainly reflected dietary intake and other host factors. Risks of total and cause-specific mortality were estimated by using proportional hazards models.
Results: During up to 19 y of follow-up, 13 380 deaths (including 4518 and 5776 due to cancer and cardiovascular disease, respectively) were identified. Men in the higher quintiles of serum -tocopherol had significantly lower risks of total and cause-specific mortality than did those in the lowest quintile [relative risk (RR) = 0.82 (95% CI: 0.78, 0.86) for total mortality and 0.79 (0.72, 0.86), 0.81 (0.75, 0.88), and 0.70 (0.63, 0.79) for deaths due to cancer, cardiovascular disease, and other causes, respectively; P for trend for all < 0.0001]. Cubic regression spline analysis of continuous serum -tocopherol values indicated greater risk reductions with increasing concentrations up to 
13–14 mg/L, after which no further benefit was noted.
Conclusion: Higher circulating concentrations of -tocopherol within the normal range are associated with significantly lower total and cause-specific mortality in older male smokers.
Key Words: Antioxidants • -tocopherol • cancer • cardiovascular disease • cohort study • mortality • smokers
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