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Cited by 1,209Antioxidant Activity and Oxidative StressNutritional Studies and DietVitamin D Research Studies

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer: A Randomized Controlled Trial

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The HOPE and HOPE-TOO Trial Investigators·2005·JAMA
DOI 10.1001/jama.293.11.1338
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Abstract

CONTEXT: Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. OBJECTIVE: To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. INTERVENTION: Daily dose of natural source vitamin E (400 IU) or matching placebo. MAIN OUTCOME MEASURES: Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. RESULTS: Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. CONCLUSION: In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.

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Research works printed but not linked: 18

  1. Verlangieri AJ, Bush MJ. Effects of d-␣-tocopherol supplementation on experimentally induced primate atherosclerosis. J Am Coll Nutr. 1992;11:131-138.
  2. Meydani M. Vitamin E. Lancet. 1995;345:170-175.
  3. Skyrme-Jones RA, O'Brien RC, Berry KL, Meredith IT. Vitamin E supplementation improves endothelial function in type 1 diabetes mellitus: a randomized, pla- cebo-controlled study. J Am Coll Cardiol. 2000;36:94- 100.
  4. Sigounas G, Anagnostou A, Steiner M. dl-alpha- Tocopherol induces apoptosis in erythroleukemia, pros- tate, and breast cancer cells. Nutr Cancer. 1997;28:30- 35.
  5. Ziegler RG, Mayne ST, Swanson CA. Nutrition and lung cancer [review]. Cancer Causes Control. 1996;7:157- 177.
  6. Longnecker MP, Martin-Moreno JM, Knekt P, et al. Serum alpha-tocopherol concentration in relation to sub- sequent colo-rectal cancer: pooled data from five cohorts. J Natl Cancer Inst. 1992;84:430-445.
  7. Ocke MC, Bueno-de-Mesquita HB, Feskens EJ, van Staveren WA, Kromhout D. Repeated measurements of vegetables, fruits, beta-carotene, and vitamins C and E in relation to lung cancer: the Zutphen Study. Am J Epidemiol. 1997;145:358-365.
  8. Klein EA, Thompson IM, Lippman SM, et al. SELECT: the next prostate cancer prevention trial: Selenium and Vitamin E Cancer Prevention Trial. J Urol. 2001;166:1311- 1315.
  9. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with ␣-tocopherol and ␤-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998;90:440-446.
  10. Li J-Y, Taylor PR, Li B, et al. Nutrition intervention trials in China: multiple incidence and disease-specific mor- tality among adults with esophageal dysplasia. J Natl Can- cer Inst. 1993;85:1492-1498.
  11. The Alpha-Tocopherol, Beta Carotene Cancer Pre- vention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other can- cers in male smokers. N Engl J Med. 1994;330: 1029-1035.
  12. Steinberg D, Witzum JL. Is the oxidative modifi- cation hypothesis relevant to human atherosclerosis: do the antioxidant trials conducted to date refute the hypothesis? Circulation. 2002;105:2107-2111.
  13. The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardio- vascular events in high-risk patients. N Engl J Med. 2000;342:154-160.
  14. Lonn E, Shaikholeslami R, Yi Q, et al. Effects of ramipril on left ventricular mass and function in car- diovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction: a sub- study of the HOPE trial. J Am Coll Cardiol. 2004;43: 2200-2206.
  15. GISSI-Prevenzione Investigators (Gruppo Itali- ano per lo Studio della Sopravvivenza nell'Infracto Miocardico). Dietary supplementation with n-e poly- unsaturated fatty acids and vitamin E after myocar- dial infarction: results of the GISSI-Prevenzione Trial. Lancet. 1999;354:447-455.
  16. Age-Related Eye Disease Study Group. A ran- domized, placebo-controlled, clinical trial of high-dose supplementation with vitamin C and E and beta-carotene for age-related cataract and vi- sion loss: AREDS Report No. 9. Arch Ophthalmol. 2001; 119:1439-1452.
  17. Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet. 2001;342:154-160.
  18. Bowry VW, Ingold KU, Stocker R. Vitamin E in human low-density lipoproteins: when and how this antioxidant becomes a pro-oxidant. Biochem J. 1992; 288:341-344.

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Metadata

Authors
The HOPE and HOPE-TOO Trial Investigators
Affiliations
Population Health Research Institute (CA)
Corresponding author
The HOPE and HOPE-TOO Trial Investigators
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2005-03-16
Volume
293
Issue
11
Pages
1338
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.293.11.1338
OpenAlex
W1678920698
Cited by
1,209
References
20
Citations by year
2026: 26 · 2025: 26 · 2024: 31 · 2023: 35 · 2022: 35 · 2021: 34 · 2020: 45 · 2019: 37 · 2018: 22 · 2017: 44 · 2016: 48 · 2015: 56 · 2014: 95 · 2013: 70 · 2012: 87
FWCI
58.51
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical Research Council Canada
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, long-term supplementation, cancer incidence, cancer mortality, cardiovascular events, myocardial infarction, stroke, cardiovascular mortality, heart failure, unstable angina, revascularization, older adults, vascular disease, diabetes mellitus
MeSH terms
Aged, Antioxidants, Cardiovascular Diseases, Diabetes Mellitus, Double-Blind Method, Female, Humans, Male, Middle Aged, Neoplasms, Risk, Vascular Diseases, Dietary Supplements, alpha-Tocopherol

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