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An Editorial Update: Annus horribilis for Vitamin E
- Eliseo Guallar, MD, DrPH;
- Daniel F. Hanley, MD; and
- Edgar R. Miller III, MD, PhD
- From Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
In January 2005, we published a dose–response meta-analysis showing that high-dosage (≥400 IU/d) vitamin E supplementation was associated with a small but statistically significant increased risk for mortality (relative risk, 1.04 [95% CI, 1.01 to 1.07]) (1). The precise dosage of vitamin E at which the relative risk for mortality exceeded 1 and the magnitude of the risk increase were uncertain. However, the analysis showed that high-dosage vitamin E supplementation was likely to be harmful. Even in the best case, it offered no benefit in prolonging life. These findings were highly controversial: Together with our response, this issue of Annals includes 11 of more than 40 electronic rapid responses to the Annals Web site. Rather than summarizing this exchange of views, this editorial reports further developments in the vitamin E story.
Vitamin E and the Prevention of Cancer, Cardiovascular Disease, and Mortality
Recently, vitamin E has suffered several setbacks. The Women's Health Study (WHS), a 10-year, primary prevention trial that randomly assigned 39 876 healthy women to either 600 IU of vitamin E or placebo on alternate days, found that vitamin E did not reduce cardiovascular disease or cancer (2). Indeed, total mortality was slightly—although nonsignificantly—increased with vitamin E (relative risk, 1.04 [CI, 0.93 to 1.16]). The WHS was particularly important since its target population, healthy women, was underrepresented in the trials included in our meta-analysis.
The Heart Outcomes Prevention Evaluation–The Ongoing Outcomes (HOPE-TOO) study recently reported its findings (3). This report extended the follow-up of the original HOPE trial (4), in which 9541 patients with vascular disease or diabetes mellitus were randomly assigned to natural vitamin E (400 IU/d) or placebo. After 7 years of follow-up, the incidence of cancer, major cardiovascular events, and mortality was similar in both treatment groups (3). However, patients …
