Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase

From: http://www.annals.org/content/142/1/37.full.pdf

Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase
All-Cause Mortality
Edgar R. Miller III, MD, PhD; Roberto Pastor-Barriuso, PhD; Darshan Dalal, MD, MPH; Rudolph A. Riemersma, PhD, FRCPE;
Lawrence J. Appel, MD, MPH; and Eliseo Guallar, MD, DrPH
Background: Experimental models and observational studies
suggest that vitamin E supplementation may prevent cardiovascular
disease and cancer. However, several trials of high-dosage
vitamin E supplementation showed non–statistically significant increases
in total mortality.
Purpose: To perform a meta-analysis of the dose–response relationship
between vitamin E supplementation and total mortality
by using data from randomized, controlled trials.
Patients: 135 967 participants in 19 clinical trials. Of these trials,
9 tested vitamin E alone and 10 tested vitamin E combined with
other vitamins or minerals. The dosages of vitamin E ranged from
16.5 to 2000 IU/d (median, 400 IU/d).
Data Sources: PubMed search from 1966 through August 2004,
complemented by a search of the Cochrane Clinical Trials Database
and review of citations of published reviews and metaanalyses.
No language restrictions were applied.
Data Extraction: 3 investigators independently abstracted
study reports. The investigators of the original publications were
contacted if required information was not available.
Data Synthesis: 9 of 11 trials testing high-dosage vitamin E
(>400 IU/d) showed increased risk (risk difference > 0) for allcause
mortality in comparisons of vitamin E versus control. The
pooled all-cause mortality risk difference in high-dosage vitamin E
trials was 39 per 10 000 persons (95% CI, 3 to 74 per 10 000
persons; P 0.035). For low-dosage vitamin E trials, the risk
difference was 16 per 10 000 persons (CI, 41 to 10 per 10 000
persons; P > 0.2). A dose–response analysis showed a statistically
significant relationship between vitamin E dosage and all-cause
mortality, with increased risk of dosages greater than 150 IU/d.
Limitations: High-dosage (>400 IU/d) trials were often small
and were performed in patients with chronic diseases. The generalizability
of the findings to healthy adults is uncertain. Precise
estimation of the threshold at which risk increases is difficult.
Conclusion: High-dosage (>400 IU/d) vitamin E supplements
may increase all-cause