Risk of Mortality with Vitamin E Supplements: The Cache County Study

Purpose A recent meta-analysis reported increased mortality in clinical trial participants randomized to high-dose vitamin E. We sought to determine whether these mortality risks with vitamin E reflect adverse consequences of its use in the presence of cardiovascular disease. Methods In a defined population aged 65 years or older, baseline interviews captured self- or proxy-reported history of cardiovascular illness. A medicine cabinet inventory verified nutritional supplement and medication use. Three sources identified subsequent deaths. Cox proportional hazards methods examined the association between vitamin E use and mortality. Results After adjustment for age and sex, there was no association in this population between vitamin E use and mortality (adjusted hazard ratio [aHR] 0.93; 95% confidence interval [CI], 0.74-1.15). Predictably, deaths were more frequent with a history of diabetes, stroke, coronary artery bypass graft surgery, or myocardial infarction, and with the use of warfarin, nitrates, or diuretics. None of these conditions or treatments altered the null main effect with vitamin E, but mortality was increased in vitamin E users who had a history of stroke (aHR 3.64; CI, 1.73-7.68), coronary bypass graft surgery (aHR 4.40; CI, 2.83-6.83), or myocardial infarction (aHR 1.95; CI, 1.29-2.95) and, independently, in those taking nitrates (aHR 3.95; CI, 2.04-7.65), warfarin (aHR 3.71; CI, 2.22-6.21), or diuretics (aHR 1.83; CI, 1.35-2.49). Although not definitive, a consistent trend toward reduced mortality was seen in vitamin E users without these conditions or treatments. Conclusions In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without.