Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study

Observational studies have reported a cardioprotective effect of vitamin E whereas intervention trials failed to confirm its beneficial effects, and even some reported adverse effects of vitamin E supplements on coronary artery disease (CAD). To clarify, we conducted a two-sample mendelian randomization study to investigate causal association of vitamin E with the risk of CAD. Three single nucleotide polymorphisms (SNPs) identified in a genome-wide analysis study including 7781 individuals of European descent, rs964184, rs2108622, and rs11057830 were used as the genetic instruments for vitamin E. Data for CAD/myocardial infarction (MI) were available from Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics consortium. The effect of each SNP on CAD/myocardial infarction (MI) was weighted by its effect on serum vitamin E (mg/L), and results were pooled to give a summary estimates for the effect of increased vitamin E on risk of CAD/MI. Based on 3 SNPs each 1 mg/L increase in vitamin E was significantly associated with CAD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.03-1.06), MI (OR 1.04, 95% CI 1.03-1.05), elevated low-density lipoprotein cholesterol (0.021 standard deviations (SD), 95% CI 0.016, 0.027), triglycerides (0.026 SD, 95% CI 0.021, 0.031), and total cholesterol (0.043 SD, 95% CI 0.038, 0.048) and lower levels of high-density lipoprotein cholesterol (-0.019 SD 95% CI -0.024, -0.014). Our findings indicate that higher vitamin E may increase the risk of CAD/MI and the safety and efficacy of vitamin E supplementation use should be reevaluated.