The HOPE and HOPE-TOO Trial Investigators (2005) Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 293: 1338–1347

Epidemiological and experimental studies have pointed to a role for vitamin E in cancer and cardiovascular disease prevention. A daily dose of this antioxidant produced no benefit, however, in the Heart Outcomes Prevention Evaluation (HOPE) trial, which randomized patients with diabetes mellitus or vascular disease to vitamin E supplementation or placebo over a median period of 4.5 years. To determine whether a benefit might be observed over the longer term, the study was extended; results from the HOPE—The Ongoing Outcomes (HOPE-TOO) trial extension have recently been published.

The trial extension included approximately half of the 9,541 patients who participated in the original study. A total of 3,994 participants continued to take the study intervention, whereas 738 were followed up passively. After a median follow-up of 7.0 years for the whole study population, and 7.2 years for those included in the HOPE-TOO extension, there were no significant differences between the placebo and vitamin E groups in the incidence of cancer or cancer-related deaths, or in the incidence of major cardiovascular events. As shown in the initial HOPE study, however, there was an unexpected increase in the rate of heart failure, and hospitalization for heart failure, among patients receiving vitamin E supplementation.

In summary, the study indicated that long-term vitamin E supplementation does not protect against major cardiovascular events or cancer. The observed increased risk of heart failure warrants further study, say the investigators, and in the meantime they recommend that vitamin E supplements “should not be used in patients with vascular disease or diabetes mellitus”.