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

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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

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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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Uche, U. I., Suzuki, S., Fulda, K. G., & Zhou, Z. (2020) · Environmental Research · doi:10.1016/j.envres.2020.110109 · Cited by 21
Preventing Alzheimer’s Disease
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Effect of Acute Myocardial Infarction on Erythrocytic Glutathione Peroxidase 1 Activity and Plasma Vitamin E Levels
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Expert Report: Making Decisions about the Risks of Chemicals in Foods with Limited Scientific Information
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Vitamin E and Mast Cells
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The Efficacy of Vitamins in the Prevention and Treatment of Cardiovascular Disease
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“…that vitamin E alone or in combination with other agents was not beneﬁcial and was not associated with all-cause and cardiovascular mortality [202]. of vitamin E did not prevent major cardiovascular The ineffectiveness of vitamin E could be explained on the basis that these study…”
Background
In Situ Conversion of Atherosclerotic Plaques’ Iron into Nanotheranostics
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Abnormal Ca 2+ Cycling in Failing Ventricular Myocytes: Role of NOS1-Mediated Nitroso-Redox Balance
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“While antioxidant therapy (either scavenging ROS or inhibiting a source of ROS) has beneﬁcial effects in small animal models of HF (4, 76, 117, 128, 147), clinical trials have been disappointing (21, 69, 108, 116).”
Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations
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“However, more research on this molecule is needed, mainly focusing on the long-term use of high-dose vitamin E supplementation, which may increase the risk of developing heart disease [264] and prostate cancer [265].”
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A review of clinical studies on angiotensin II receptor blockers and risk of cancer
Dézsi, C. A. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.11.031 · Cited by 17
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“Unfortunately, scavenging the ROS by exogenous antioxidants, such as vitamin E or C, has been shown to be of limited therapeutic efficacy against cardiovascular events, including MF [10] and even can increase the risk of heart failure in some clinical trials [11].”
Background
An Objective Appraisal of the Free Radical Theory of Aging
Lustgarten, M. S., Müller, F. L., & Remmen, H. V. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-378638-8.00008-7 · Cited by 18
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D’Amato, A., Cestiè, C., Ferranti, F., Segato, C., Prosperi, S., Germanò, R., Myftari, V., Bartimoccia, S., Castellani, V., Badagliacca, R., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26115165 · Cited by 16
“In fact, the large-scale HOPE trial [72] evaluated long-term supplementation with 400 IU of vitamin E daily in individuals at high cardiovascular risk.”
Chrono-modulated effects of external stressors on oxidative stress and damage in humans: A scoping review on night shift work
Makris, K. C., Heibati, B., & Narui, S. Z. (2023) · Environment International · doi:10.1016/j.envint.2023.108048 · Cited by 16
“For example, several double-blind interventional trials in humans showed that a treatment with free-radical-scavenging antioxidants presented with limited evidence for human health benefits (Lonn et al. 2005; Omenn et al. 1996; Williams and Fisher 2005).”
Diet, exercise, and supplements: what is their role in the management of the metabolic dysfunction-associated steatotic liver disease in children?
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Ulbricht, C. E., Basch, E., Chao, W., Conquer, J. A., Costa, D., Culwell, S., Flanagan, K. E., Guilford, J., Hammerness, P. G., Hashmi, S., et al. (2012) · Journal of Dietary Supplements · doi:10.3109/19390211.2012.736721 · Cited by 16
“(350) conducted a systematic review and meta-analysis of 12 RCTs (311,134,162,171,188,190,251,261,263,273,285,480,509) to assess the effects of antioxidant supplements on colorectal cancer and/or adenoma prevention (N = 164,460).”
Background
Recent advances in the determination of tocopherols in biological fluids: from sample pretreatment and liquid chromatography to clinical studies
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Chemical Youth
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Reactive Oxygen/Nitrogen Species and the Myocardial Cell Homeostasis: An Ambiguous Relationship
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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: bronze
doi.org
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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Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer: A Randomized Controlled Trial

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