The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer: The Women’s Health Study: A Randomized Controlled Trial
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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“Some trials, in fact, have documented potential harm, including an increased risk of lung cancer from beta-carotene supplements in smokers and an increased risk of heart failure 70 and the possibility of increased total mortality 71 from high-dose vitamin E supplements.”
From Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement From the American Heart Association Nutrition Committee (2006) · cites this paper as [71]
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“Evidence of a direct cardiovascular health benefit from consuming soy protein products instead of dairy or other proteins or of isoflavone supplements is minimal.71,72”
From Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement From the American Heart Association Nutrition Committee (2006) · cites this paper as [71]
In the citing paper
“The WHS is a completed randomized trial (1992-2004) testing aspirin and vitamin E for preventing cardiovascular disease and cancer among 39,876 healthy women, ≥45 years, living throughout the US.[32-34]”
From Using accelerometers to measure physical activity in large-scale epidemiological studies: issues and challenges (2014) · cites this paper as [33]
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Free radicals, antioxidants, and human disease: curiosity, cause, or consequence?
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Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality
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A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease
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Vitamin E Consumption and the Risk of Coronary Heart Disease in Men
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Self-citationStephens, N. G., Parsons, A., Brown, M. J., Schofield, P. M., Kelly, F., Cheeseman, K., & Mitchinson, M. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90866-1 · Cited by 2,148
Vitamin E Consumption and the Risk of Coronary Disease in Women
Stampfer, M. J., Hennekens, C. H., Manson, J. E., Colditz, G. A., ROSNER, B. A., & Willett, W. C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282003 · Cited by 2,085
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Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P. V., Azzini, E., Peluso, I., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00694 · Cited by 1,971
Metadata
- 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
- 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 (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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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