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Cited by 1,137Antioxidant Activity and Oxidative StressNutritional Studies and DietVitamin D Research Studies

Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer: The Women’s Health Study: A Randomized Controlled Trial

Lee, I-Min, Cook, Nancy R., Gaziano, J. Michael, Gordon, David, Ridker, Paul M, Manson, JoAnn E., Hennekens, Charles H., Buring, Julie E.·2005·JAMA
DOI 10.1001/jama.294.1.56
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Abstract

CONTEXT: Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. OBJECTIVE: To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women. DESIGN, SETTING, AND PARTICIPANTS: In the Women's Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years. INTERVENTION: Administration of 600 IU of natural-source vitamin E on alternate days. MAIN OUTCOME MEASURES: Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer. RESULTS: During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53). CONCLUSIONS: The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.

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Authors
Lee, I.-M., Cook, N. R., Gaziano, J. M., Gordon, D., Ridker, P. M., Manson, J. E., Hennekens, C. H., & Buring, J. E.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Lee, I-Min
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2005-07-06
Volume
294
Issue
1
Pages
56
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.294.1.56
OpenAlex
W1995731966
Cited by
1,137
References
57
Citations by year
2026: 18 · 2025: 19 · 2024: 39 · 2023: 29 · 2022: 25 · 2021: 38 · 2020: 45 · 2019: 39 · 2018: 46 · 2017: 34 · 2016: 45 · 2015: 54 · 2014: 66 · 2013: 71 · 2012: 69
FWCI
53.06
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl043851-10)
  • National Heart, Lung, and Blood Institute (HL43851)
  • National Cancer Institute (CA-47988, R01CA047988)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
Keywords
vitamin E supplementation, primary prevention, cardiovascular disease, cancer prevention, Women's Health Study, myocardial infarction, stroke, cardiovascular mortality, breast cancer, aspirin, healthy women, cardiovascular events, cardiovascular risk factors, alcohol consumption, physical activity, body mass index, blood pressure
MeSH terms
Aged, Aspirin, Cardiovascular Diseases, Double-Blind Method, Drug Interactions, Female, Humans, Middle Aged, Mortality, Neoplasms, Primary Prevention, Risk Factors, Incidence, Dietary Supplements, alpha-Tocopherol

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