Clinical Question: Does vitamin E supplementation reduce the risk of cancer and cardiovascular disease?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Results of observational studies report an association between a decrease in cardiovascular risk and an increase in vitamin E in the diet. Results of published short-term controlled trials, however, report a neutral effect of vitamin E supplementation on cardiovascular disease risk. To assess whether longer treatment duration is effective, the current investigators extended the Heart Outcomes Prevention Evaluation (HOPE) trial, which initially evaluated the effects of vitamin E supplementation on patients at high risk for cardiovascular events.

Of the original 9,541 patients who participated in the HOPE trial for a mean of 4.5 years, 4,723 agreed to participate in an extension study for seven years. Patients were randomized initially in a double-blind fashion to receive vitamin E (400 IU daily) or matched placebo. Complete follow-up occurred for more than 99 percent of participants in the extension trial. Outcomes were assessed by persons blinded to treatment group assignment.

Using intention-to-treat analysis, no significant differences were noted between the vitamin E supplementation group and the control group in the incidence of cancer or deaths related to cancer. There also were no differences in the main composite of cardiovascular outcomes including death or rehospitalization. A significant increased risk in heart failure and related complications occurred in the vitamin E group (number needed to treat to harm = 61 for seven years; 95% confidence interval, 35 to 235). These results are supported by a recent meta-analysis that found no benefit and a slightly higher rate of death in patients taking high-dose vitamin E (Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37–46).

Bottom Line: Vitamin E supplementation does not reduce the risk of cancer or major cardiovascular events in patients at high risk for vascular disease, and may increase the risk of heart failure. (Level of Evidence: 1b)