The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (1985–1993) recruited 29,133 Finnish male cigarette smokers, finding that vitamin E supplementation had no overall effect on mortality. The authors of this paper found that the effect of vitamin E on respiratory infections in ATBC Study participants was modified by age, smoking, and dietary vitamin C intake; therefore, they examined whether the effect of vitamin E supplementation on mortality is modified by the same variables. During a median follow-up time of 6.1 years, 3,571 deaths occurred. Age and dietary vitamin C intake had a second-order interaction with vitamin E supplementation of 50 mg/day. Among participants with a dietary vitamin C intake above the median of 90 mg/day, vitamin E increased mortality among those aged 50–62 years by 19% (95% confidence interval: 5, 35), whereas vitamin E decreased mortality among those aged 66–69 years by 41% (95% CI: −56, −21). Vitamin E had no effect on participants who had a dietary vitamin C intake below the median. Smoking quantity did not modify the effect of vitamin E. This study provides strong evidence that the effect of vitamin E supplementation on mortality varies between different population groups. Further study is needed to confirm this heterogeneity
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