Circulating vitamin E levels and Alzheimer's disease: a Mendelian randomization study

Alzheimer's disease (AD) is the leading cause of dementia in older adults. It is more than 50 years since vitamin E was recognized as critical for optimal neurological health. Clinical studies have yielded inconsistent findings on the effect of vitamin E on AD risk. Thus, it remains unclear whether vitamin E levels are genetically associated with AD risk. We performed a Mendelian randomization study to investigate association of circulating vitamin E levels with AD using large-scale vitamin E genome-wide association study data set (N = 7781 individuals of European descent) and AD genome-wide association study data set (N = 54,162 individuals [including 17,008 AD cases and 37,154 controls of European descent]). Mendelian randomization-Egger intercept test showed no significant pleiotropy (β = -0.113; p = 0.296). Inverse-variance weighted (odds ratio = 0.96, 95% confidence interval: 0.47-1.94, p = 0.936) and weighted median analyses (odds ratio = 1.13, 95% confidence interval: 0.35-3.69, p = 0.836) showed no significant association between vitamin E and AD. Together with previous literature, this suggests that vitamin E supplementation may not forestall AD in the general population.