Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer: A Randomized Controlled Trial
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Vitamin E did not improve cardiovascular outcomes in a large multicenter trial and actually increased congestive heart failure.
“However, despite this, vitamin E did not improve cardiovascular outcomes in a large multicenter trial and actually increased congestive heart failure (201).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [201]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Part of this paper’s reference list could not be split into single entries.
Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease
Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F. L., Valanis, B., Williams, J. H., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605023341802 · Cited by 3,638 · see citing works
Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality
Miller, E. R., Pastor-Barriuso, R., Dalal, D., Riemersma, R. A., Appel, L. J., & Guallar, E. (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-142-1-200501040-00110 · Cited by 2,577 · see citing works
Brown, B. G., Zhao, X.-Q., Chait, A., Fisher, L. D., Cheung, M. C., Morse, J. S., Dowdy, A. A., Marino, E. K., Bolson, E. L., Alaupovic, P., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011090 · Cited by 1,979 · see citing works
Vivekananthan, D. P., Penn, M. S., Sapp, S. K., Hsu, A., & Topol, E. J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13637-9 · Cited by 1,083 · see citing works
Bjelaković, G., Nikolova, D., Simonetti, R. G., & Gluud, C. N. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17138-9 · Cited by 612 · see citing works
Vitamin E in Humans: Demand and Delivery
Traber, M. G., & Sies, H. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nu.16.070196.001541 · Cited by 502 · see citing works
Jha, P., Flather, M., Lonn, E., Farkouh, M., & Yusuf, S. (1995) · Annals of Internal Medicine · doi:10.7326/0003-4819-123-11-199512010-00009 · Cited by 399 · see citing works
SERUM VITAMIN E AND RISK OF CANCER AMONG FINNISH MEN DURING A 10-YEAR FOLLOW-UP
Knekt, P., Aromaa, A., Maatela, J., Aaran, R., Nikkari, T., Hakama, M., Hakulinen, T. R., Peto, R., Saxén, E., & Teppo, L. (1988) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a114788 · Cited by 233 · see citing works
Clinical trials of antioxidants in atherosclerosis: are we doing the right thing?
Steinberg, D. H. (1995) · The Lancet · doi:10.1016/s0140-6736(95)92657-7 · Cited by 178 · see citing works
Huang, H.-Y. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwf210 · Cited by 173 · see citing works
Vitamin Supplement Use and Reduced Risk of Oral and Pharyngeal Cancer
Gridley, G., McLaughlin, J. K., Block, G., Blot, W. J., Gluch, M., & Fraumeni, J. F. (1992) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a116208 · Cited by 140 · see citing works
Recent Developments in Vitamin E and Immune Response
Meydan, S. N., & Beharka, A. A. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1998.tb01644.x · Cited by 135 · see citing works
Vitamin E and cancer prevention: recent advances and future potentials.
Prasad, K. N., & Edwards‐Prasad, J. (1992) · Journal of the American College of Nutrition · doi:10.1080/07315724.1992.10718253 · Cited by 130 · see citing works
SELECT: the Selenium and Vitamin E Cancer Prevention Trial: rationale and design
Klein, E., Thompson, I. M., Lippman, S., Goodman, P., Albanes, D., Taylor, P., & Coltman, C. A. (2000) · Prostate Cancer and Prostatic Diseases · doi:10.1038/sj.pcan.4500412 · Cited by 108 · see citing works
Influence of vitamin E on platelet function in humans.
Steiner, M. J. (1991) · Journal of the American College of Nutrition · doi:10.1080/07315724.1991.10718173 · Cited by 98 · see citing works
Serum -Tocopherol and Subsequent Risk of Lung Cancer Among Male Smokers
Woodson, K. G., Tangrea, J. A., Barrett, M. J., Virtamo, J. R. K., Taylor, P. R., & Albanes, D. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.20.1738 · Cited by 92 · see citing works
Vitamin E inhibits experimental carcinogenesis and tumour angiogenesis
Shklar, G., & SCHWARTZ, J. L. (1996) · European Journal of Cancer Part B Oral Oncology · doi:10.1016/0964-1955(95)00077-1 · Cited by 85 · see citing works
Bursell, S., & King, G. L. (1999) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(99)00047-9 · Cited by 80 · see citing works
Wiklund, R. A. (2000) · Survey of Anesthesiology · doi:10.1097/00132586-200012000-00021 · Cited by 42 · see citing works
Vitamin E in Humans: Demand and Delivery
Traber, M. G. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.16.1.321 · Cited by 26 · see citing works
the Heart Protection Study Collaborative Group (2002) · ACC Current Journal Review · doi:10.1016/s1062-1458(02)00921-2 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 18
- Verlangieri AJ, Bush MJ. Effects of d-␣-tocopherol supplementation on experimentally induced primate atherosclerosis. J Am Coll Nutr. 1992;11:131-138.
- Meydani M. Vitamin E. Lancet. 1995;345:170-175.
- 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.
- 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.
- Ziegler RG, Mayne ST, Swanson CA. Nutrition and lung cancer [review]. Cancer Causes Control. 1996;7:157- 177.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Cited by
Sorted by citations
Progress and challenges in translating the biology of atherosclerosis
Libby, P., Ridker, P. M., & Hansson, G. K. (2011) · Nature · doi:10.1038/nature10146 · Cited by 4,010 · see citing works
“Well-powered randomized clinical trials have consistently shown that antioxidant vitamins, such as vitamins E and C, do not reduce cardiovascular events over the timescale and doses studie”
Method2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.12.012 · Cited by 2,862 · see citing works
Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, M., Daniels, S., Franch, H. A., Franklin, B., Kris-Etherton, P., Harris, W. S., Howard, B., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.176158 · Cited by 2,705 · see citing works
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001063 · Cited by 4,922 · see citing works
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2007) · JAMA · doi:10.1001/jama.297.8.842 · Cited by 2,275 · see citing works
Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers
Lippman, S. M., Klein, E. A., Goodman, P. J., Lucia, M. S., Thompson, I. M., Ford, L. G., Parnes, H. L., Minasian, L. M., Gaziano, J. M., Hartline, J. A., et al. (2008) · JAMA · doi:10.1001/jama.2008.864 · Cited by 2,120 · see citing works
Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853 · see citing works
Jones, D. P. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.1865 · Cited by 1,726 · see citing works
“titative measures of disease outcome (11, 14, 19, 41, 42, 49 55, 62, 67).”
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001168 · Cited by 1,598 · see citing works
Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury
Murphy, E., & Steenbergen, C. (2008) · Physiological Reviews · doi:10.1152/physrev.00024.2007 · Cited by 1,472 · see citing works
“Antioxidants such as vitamins C and E have also been suggested to scavenge ROS and reduce ischemic injury (199), although the result of clinical trials do not suggest reduced overall mortality with vitamin E supplementation (1, 151, 285).”
BackgroundAge-related macular degeneration
Jager, R. D., Mieler, W. F., & Miller, J. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0801537 · Cited by 1,379 · see citing works
Mitochondrial energetics in the kidney
Bhargava, P., & Schnellmann, R. G. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.107 · Cited by 1,363 · see citing works
Biomarkers of Oxidative Damage in Human Disease
Dalle-Donne, I., Rossi, R., Colombo, R., Giustarini, D., & Milzani, A. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2005.061408 · Cited by 1,703 · see citing works
American Cancer Society guidelines on nutrition and physical activity for cancer prevention
Kushi, L. H., Doyle, C., McCullough, M. L., Rock, C. L., Demark‐Wahnefried, W., Bandera, E. V., Gapstur, S. M., Patel, A. V., Andrews, K. S., & Gansler, T. S. (2012) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20140 · Cited by 1,331 · see citing works
“Heart failure rates were actually higher among those taking vitamin E supplements.(376) Vitamin E supplementation is not recommended for the prevention of cancer or chronic diseases, although foods containing vitamin E, including nuts and some unsaturated oils, can be healthy and have been demonstrated to lower the ri…”
BackgroundMethodMente, A., de Koning, L., Shannon, H. S., & Anand, S. S. (2009) · Archives of Internal Medicine · doi:10.1001/archinternmed.2009.38 · Cited by 1,267 · see citing works
Oxidative stress and heart failure
Tsutsui, H., Kinugawa, S., & Matsushima, S. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00554.2011 · Cited by 1,246 · see citing works
Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases
Tan, B. L., Norhaizan, M. E., Liew, W.-P.-P., & Rahman, H. S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01162 · Cited by 1,182 · see citing works
Lee, I.-M., Cook, N. R., Gaziano, J. M., Gordon, D., Ridker, P. M., Manson, J. E., Hennekens, C. H., & Buring, J. E. (2005) · JAMA · doi:10.1001/jama.294.1.56 · Cited by 1,137 · see citing works
Cardiac Metabolism in Heart Failure
Doenst, T., Nguyễn, T. D., & Abel, E. D. (2013) · Circulation Research · doi:10.1161/circresaha.113.300376 · Cited by 1,104 · see citing works
Lockhart, P. B., Bolger, A. F., Papapanou, P. N., Osinbowale, O., Trevisan, M., Levison, M. E., Taubert, K. A., Newburger, J. W., Gornik, H. L., Gewitz, M. H., et al. (2012) · Circulation · doi:10.1161/cir.0b013e31825719f3 · Cited by 1,038 · see citing works
The immunology of atherosclerosis
Gisterå, A., & Hansson, G. K. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.51 · Cited by 982 · see citing works
Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training
Gomez-Cabrera, M.-C., Domenech, E., & Viña, J. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.02.001 · Cited by 1,020 · see citing works
“[45] Lonn, E.”
ResultBjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007176.pub2 · Cited by 924 · see citing works
Sesso, H. D. (2008) · JAMA · doi:10.1001/jama.2008.600 · Cited by 913 · see citing works
Cardiac Metabolism and its Interactions With Contraction, Growth, and Survival of Cardiomyocytes
Kolwicz, S. C., Purohit, S., & Tian, R. (2013) · Circulation Research · doi:10.1161/circresaha.113.302095 · Cited by 810 · see citing works
The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K. B., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 814 · see citing works
“For example, vitamin E was associated with heart failure in patients with vascular disease or diabetes mellitus in the Heart Outcomes Prevention Evaluation Study (Lonn et al., 2005) and increased prostate cancer after 7 years in the Selenium and Vitamin E Cancer Prevention Trial (Klein et al., 2011).”
BackgroundRistow, M., & Zarse, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.014 · Cited by 789 · see citing works
“Accordingly, other studies show that antioxidant supplements may be disease-promoting and/or may even reduce lifespan in humans (Albanes et al., 1996; Omenn et al., 1996; Vivekananthan et al., 2003; Lonn et al., 2005; Bjelakovic et al., 2007; Ward et al., 2007; Lippman et al., 2009).”
BackgroundAlam, M. A., Subhan, N., Rahman, M., Uddin, S. J., Reza, H. M., & Sarker, S. D. (2014) · Advances in Nutrition · doi:10.3945/an.113.005603 · Cited by 792 · see citing works
Nitric oxide and oxidative stress in vascular disease
Förstermann, U. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0808-2 · Cited by 780 · see citing works
López‐Alarcón, C., & Denicola, A. (2012) · Analytica Chimica Acta · doi:10.1016/j.aca.2012.11.051 · Cited by 782 · see citing works
Role of Oxidative Stress in Cardiac Hypertrophy and Remodeling
Takimoto, E., & Kass, D. A. (2006) · Hypertension · doi:10.1161/01.hyp.0000254415.31362.a7 · Cited by 772 · see citing works
Reactive oxygen species in cardiovascular disease
Sugamura, K., & Keaney (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.004 · Cited by 769 · see citing works
Sivitz, W. I., & Yorek, M. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2531 · Cited by 742 · see citing works
“However, despite this, vitamin E did not improve cardiovascular outcomes in a large multicenter trial and actually increased congestive heart failure (201).”
Extending life span by increasing oxidative stress
Ristow, M., & Schmeisser, S. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.010 · Cited by 718 · see citing works
Duell, P. B., Welty, F. K., Miller, M., Chait, A., Hammond, G., Ahmad, Z., Cohen, D. E., Horton, J. D., Pressman, G. S., Toth, P. P., et al. (2022) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atv.0000000000000153 · Cited by 727 · see citing works
Oxidative Stress in Cardiovascular Diseases
Dubois‐Deruy, E., Peugnet, V., Turkieh, A., & Pinet, F. (2020) · Antioxidants · doi:10.3390/antiox9090864 · Cited by 667 · see citing works
“Unfortunately, most of these clinical studies failed to show an improvement of vitamins supplementation at the cardiovascular level [57,83,84] or even reported an increased incidence of chronic congestive heart failure in humans [85,86].”
BackgroundYun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626 · see citing works
Dysken, M. W., Sano, M., Asthana, S., Vertrees, J. E., Pallaki, M., Llorente, M., Love, S., Schellenberg, G. D., McCarten, J. R., Malphurs, J., et al. (2014) · JAMA · doi:10.1001/jama.2013.282834 · Cited by 628 · see citing works
The Role of Vitamin E in Human Health and Some Diseases
Rizvi, S., Raza, S. T., Ahmed, F., Ahmad, A., Abbas, S., & Mahdi, F. (2014) · Sultan Qaboos University Medical Journal · doi:10.18295/2075-0528.1566 · Cited by 624 · see citing works
Impact of Oxidative Stress on the Heart and Vasculature
Münzel, T. F., Camici, G. G., Maack, C., Bonetti, N. R., Fuster, V., & Kovacic, J. C. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.05.035 · Cited by 623 · see citing works
Involvement of oxidative stress in Alzheimer disease
Nunomura, A., Castellani, R. J., Zhu, X., Moreira, P. I., Perry, G., & Smith, M. A. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000228136.58062.bf · Cited by 611 · see citing works
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.04.003 · Cited by 596 · see citing works
Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies
Förstermann, U. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1211 · Cited by 576 · see citing works
“In fact, evidence from large, well-designed studies indicates that the use of vitamin E in primary prevention of cardiovascular disease should actively be discouraged”
BackgroundAggarwal, B. B., Sundaram, C., Prasad, S., & Kannappan, R. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.07.043 · Cited by 567 · see citing works
Huynh, K., Bernardo, B. C., McMullen, J. R., & Ritchie, R. H. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.01.003 · Cited by 552 · see citing works
Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)
Ristow, M., & Schmeisser, K. (2014) · Dose-Response · doi:10.2203/dose-response.13-035.ristow · Cited by 534 · see citing works
“…promotion of cancer growth or induction of diseases with negative impact on human lifespan (Albanes et al. 1996, Omenn et al. 1996, Vivekananthan et al. 2003, Lonn et al. 2005, Bjelakovic et al. 2007, Ward et al. 2007, Lippman et al. 2009, Schipper 2004, DeNicola et al. 2011, Abner et al. 2011).”
BackgroundOxidative stress in prostate cancer
Khandrika, L., Kumar, B., Koul, S., MARONI, P. D., & Koul, H. K. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.12.011 · Cited by 528 · see citing works
“These studies did not provide strong support for population-wide implementation of high dose antioxidant supplementation for the prevention of prostate cancer [18–20].”
BackgroundRapa, S. F., Iorio, B. R. D., Campiglia, P., Heidland, A., & Marzocco, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010263 · Cited by 524 · see citing works
Oxidative stress and left ventricular remodelling after myocardial infarction
Hori, M., & Nishida, K. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn335 · Cited by 525 · see citing works
Vitamins E and C in the Prevention of Prostate and Total Cancer in Men
Gaziano, J. M., Glynn, R. J., Christen, W. G., Kurth, T., Belanger, C. F., MacFadyen, J. G., Bubes, V. Y., Manson, J. E., Sesso, H. D., & Buring, J. E. (2008) · JAMA · doi:10.1001/jama.2008.862 · Cited by 519 · see citing works
Obesity-Associated Oxidative Stress: Strategies Finalized to Improve Redox State
Savini, I., Catani, M. V., Evangelista, D., Gasperi, V., & Avigliano, L. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140510497 · Cited by 514 · see citing works
Targeting antioxidants for cancer therapy
Glasauer, A., & Chandel, N. S. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.07.017 · Cited by 502 · see citing works
Cook, N. R. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.15.1610 · Cited by 483 · see citing works
Drugs That May Cause or Exacerbate Heart Failure
Page, R. L., II, O’Bryant, C. L., Cheng, D., Dow, T. J., Ky, B., Stein, C. M., Spencer, A. P., Trupp, R. J., & Lindenfeld, J. M. (2016) · Circulation · doi:10.1161/cir.0000000000000426 · Cited by 474 · see citing works
Oxidative Stress and Hypertension
Harrison, D. G., & Góngora, M. C. (2009) · Medical Clinics of North America · doi:10.1016/j.mcna.2009.02.015 · Cited by 451 · see citing works
Nonalcoholic Fatty Liver Disease and the Heart
Stahl, E. P., Dhindsa, D. S., Lee, S. K., Sandesara, P. B., Chalasani, N., & Sperling, L. S. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.050 · Cited by 445 · see citing works
Oxidative stress and human diseases: Origin, link, measurement, mechanisms, and biomarkers
Giustarini, D., Dalle‐Donne, I., Tsikas, D., & Rossi, R. (2009) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408360903142326 · Cited by 443 · see citing works
The role of oxidative stress in the pathophysiology of hypertension
Rodrigo, R., González, J., & Paoletto, F. (2011) · Hypertension Research · doi:10.1038/hr.2010.264 · Cited by 436 · see citing works
The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes
Dzau, V. J., Antman, E. M., Black, H. R., Hayes, D. L., Manson, J. E., Plutzky, J., Popma, J. J., & Stevenson, W. G. (2006) · Circulation · doi:10.1161/circulationaha.106.655688 · Cited by 440 · see citing works
McCrindle, B. W., Urbina, E. M., Dennison, B. A., Jacobson, M. S., Steinberger, J., Rocchini, A. P., Hayman, L. L., & Daniels, S. R. (2007) · Circulation · doi:10.1161/circulationaha.107.181946 · Cited by 418 · see citing works
Vitamin E for Alzheimer's dementia and mild cognitive impairment
Farina, N., Llewellyn, D. J., Isaac, M. G. E. K. N., & Tabet, N. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002854.pub5 · Cited by 421 · see citing works
Vitamin E Regulatory Mechanisms
Traber, M. G. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.27.061406.093819 · Cited by 414 · see citing works
Role of Diet in Prostate Cancer Development and Progression
Chan, J. M., Gann, P. H., & Giovannucci, E. L. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.1492 · Cited by 413 · see citing works
Münzel, T., Gori, T., Keaney, J. F., Maack, C., & Daiber, A. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv305 · Cited by 394 · see citing works
Dietary Antioxidants and the Long-term Incidence of Age-Related Macular Degeneration
Tan, J. S. L., Wang, J. J., Flood, V., Rochtchina, E., Smith, W., & Mitchell, P. (2008) · Ophthalmology · doi:10.1016/j.ophtha.2007.03.083 · Cited by 381 · see citing works
The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor
D’Oria, R., Schipani, R., Leonardini, A., Natalicchio, A., Perrini, S., Cignarelli, A., Laviola, L., & Giorgino, F. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/5732956 · Cited by 387 · see citing works
Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol
Peh, H. Y., Tan, W. S. D., Liao, W., & Wong, W. S. F. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.12.003 · Cited by 351 · see citing works
Aimo, A., Castiglione, V., Borrelli, C., Saccaro, L. F., Franzini, M., Masi, S., Emdin, M., & Giannoni, A. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319870344 · Cited by 362 · see citing works
“045).(94) Similar findings were reported in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)Prevenzione cohort, enrolling patients with previous myocardial infarction.”
ResultSummary of American Heart Association Diet and Lifestyle Recommendations Revision 2006
Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, M., Daniels, S., Franch, H. A., Franklin, B., Kris-Etherton, P., Harris, W. S., Howard, B., et al. (2006) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000238352.25222.5e · Cited by 345 · see citing works
Effects of antioxidant supplementation on the aging process.
Fusco, D., Colloca, G. A., Monaco, M. R. L., & Cesari, M. (2007) · PubMed Central · Cited by 340 · see citing works
Male infertility testing: reactive oxygen species and antioxidant capacity
Ko, E., Sabanegh, E. S., & Agarwal, A. K. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.10.020 · Cited by 336 · see citing works
Pharmacological potential of tocotrienols: a review
Ahsan, H., Ahad, A., Iqbal, J., & Siddiqui, W. A. (2014) · Nutrition & Metabolism · doi:10.1186/1743-7075-11-52 · Cited by 330 · see citing works
The Evidence for Dietary Prevention and Treatment of Cardiovascular Disease
Horn, L. V., McCoin, M., Kris‐Etherton, P. M., Burke, F., Carson, J. A. S., Champagne, C. M., Karmally, W., & Sikand, G. (2008) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2007.10.050 · Cited by 322 · see citing works
Drager, L. F., Polotsky, V. Y., & Lorenzi-Filho, G. (2011) · Chest · doi:10.1378/chest.10-2223 · Cited by 322 · see citing works
Cognitive symptoms of Alzheimer’s disease: clinical management and prevention
Joe, E., & Ringman, J. M. (2019) · BMJ · doi:10.1136/bmj.l6217 · Cited by 325 · see citing works
Common risk factors for heart failure and cancer
Meijers, W. C., & de Boer, R. A. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz035 · Cited by 323 · see citing works
The Role of Oxidized Low-Density Lipoproteins in Atherosclerosis: The Myths and the Facts
Maiolino, G., Rossitto, G., Caielli, P., Bisogni, V., Rossi, G. P., & Calò, L. A. (2013) · Mediators of Inflammation · doi:10.1155/2013/714653 · Cited by 315 · see citing works
Antioxidant Supplementation during Exercise Training: Beneficial or Detrimental?
Peternelj, T.-T., & Coombes, J. S. (2011) · Sports Medicine · doi:10.2165/11594400-000000000-00000 · Cited by 314 · see citing works
Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial
Lin, J., Cook, N. R., Albert, C., Zaharris, E., Gaziano, J. M., Van Denburgh, M., Buring, J. E., & Manson, J. E. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn438 · Cited by 309 · see citing works
Evans, J. R., & Lawrenson, J. G. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000254.pub4 · Cited by 335 · see citing works
Okamura, T., Tsukamoto, K., Arai, H., Fujioka, Y., Ishigaki, Y., Koba, S., Ohmura, H., Shoji, T., Yokote, K., Yoshida, H., et al. (2023) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2022 · Cited by 317 · see citing works
Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets
Dewanjee, S., Das, S., Das, A. K., Bhattacharjee, N., Dihingia, A., Dua, T. K., Kalita, J., & Manna, P. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.06.034 · Cited by 300 · see citing works
The role of oxidative stress on breast cancer development and therapy
Hecht, F., Pessôa, C. F., Gentile, L. B., Rosenthal, D., de Carvalho, D. P., & Fortunato, R. S. (2016) · Tumor Biology · doi:10.1007/s13277-016-4873-9 · Cited by 304 · see citing works
Antioxidant Supplementation in the Treatment of Aging-Associated Diseases
Conti, V., Izzo, V., Corbi, G., Russomanno, G., Manzo, V., Lise, F. D., Donato, A. D., & Filippelli, A. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00024 · Cited by 296 · see citing works
“Two large randomized trials (Yusuf et al., 2000; Lonn et al., 2005) investigated the impact of vitamin E supplementation on CVDs and cardiovascular events in patients at high risk.”
BackgroundMethodInfluentialBjelaković, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. N. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007176 · Cited by 307 · see citing works
Role of oxidative stress and nitric oxide in atherothrombosis
Lubos, E. (2008) · Frontiers in bioscience · doi:10.2741/3084 · Cited by 290 · see citing works
“Despite an initial small study demonstrating a therapeutic benefit of vitamin E on reducing non-fatal myocardial infarction, more recent, placebo-controlled, large-scale trials of antioxidants have been disappointing and have found no clinically benefical effects of long term vitamin E supplementation (110-113).”
BackgroundMilman, U., Blum, S., Shapira, C., Aronson, D., Miller‐Lotan, R., Anbinder, Y., Alshiek, J., Bennett, L. N., Kostenko, M., Landau, M., et al. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.153965 · Cited by 281 · see citing works
Regulation of Weibel–Palade Body Exocytosis
Lowenstein, C. J., Morrell, C. N., & Yamakuchi, M. (2005) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2005.09.005 · Cited by 278 · see citing works
Lee, J. H., Park, A., Oh, K., Lee, S. C., Kim, W. K., & Bae, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194924 · Cited by 270 · see citing works
“In patients with vascular diseases, antioxidant supplementation for several years did not prevented overall cardiovascular events and may increase the risk for heart failure [144].”
BackgroundMultivitamins in the Prevention of Cancer in Men
Gaziano, J. M., Sesso, H. D., Christen, W. G., Bubes, V. Y., Smith, J. P., MacFadyen, J. G., Schvartz, M., Manson, J. E., Glynn, R. J., & Buring, J. E. (2012) · JAMA · doi:10.1001/jama.2012.14641 · Cited by 271 · see citing works
The relationship between dose of vitamin E and suppression of oxidative stress in humans
Roberts, L. J., Oates, J. A., Linton, M. F., Fazio, S., Meador, B. P., Gross, M., Shyr, Y., & Morrow, J. D. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.06.019 · Cited by 263 · see citing works
Reactive oxygen species and insulin resistance: the good, the bad and the ugly
Tiganis, T. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.11.006 · Cited by 256 · see citing works
Clinical trials of antioxidants as cancer prevention agents: Past, present, and future
Goodman, M. G., Bostick, R. M., Küçük, Ö., & Jones, D. P. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.018 · Cited by 255 · see citing works
Diminished Autophagy Limits Cardiac Injury in Mouse Models of Type 1 Diabetes
Xu, X., Kobayashi, S., Chen, K., Timm, D. J., Volden, P. A., Huang, Y., Gulick, J. M., Yue, Z., Robbins, J. M., Epstein, P. N., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.474650 · Cited by 251 · see citing works
Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure
Dey, S., DeMazumder, D., Sidor, A., Foster, D. B., & O'Rourke, B. P. (2018) · Circulation Research · doi:10.1161/circresaha.118.312708 · Cited by 245 · see citing works
Antioxidants in Central Nervous System Diseases: Preclinical Promise and Translational Challenges
Kamat, C. D., Gadal, S., Mhatre, M., Williamson, K. S., Pye, Q. N., & Hensley, K. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15314 · Cited by 237 · see citing works
“, vitamin E [24,61,91,103], and more likely produce only a prophylactic(or preventive)effect rather than a “therapeutic” effect.”
The role of vitamin E and oxidative stress in diabetes complications
Pazdro, R., & Burgess, J. R. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.03.005 · Cited by 236 · see citing works
“, 2009) or in diabetic patients (Lonn et al., 2005), but a higher vitamin E status has been found to be associated with a lower risk for pancreatic cancer (Stolzenberg-Solomon et al.”
InfluentialVascular NADPH oxidases as drug targets for novel antioxidant strategies
Guzik, T. J., & Harrison, D. G. (2006) · Drug Discovery Today · doi:10.1016/j.drudis.2006.04.003 · Cited by 234 · see citing works
“R eiew s P O S T S C R E E N 25 Lonn, E. et al. (2005) Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.”
BackgroundFardet, A., & Rock, E. (2014) · Advances in Nutrition · doi:10.3945/an.114.006122 · Cited by 238 · see citing works
Antioxidants in Translational Medicine
Schmidt, H. H. H. W., Stocker, R., Vollbracht, C., Paulsen, G., Riley, D. P., Daiber, A., & Cuadrado, A. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6393 · Cited by 231 · see citing works
“Yet, it remains puzzling why so many in vivo animal studies that have shown beneficial effects of antioxidants were later not translatable into the clinic because they failed to show benefit or in some studies, HOPE (95, 157), HOPE-TOO (89), a prospective study with vitamin C in postmenopausal women with diabetes mell…”
Result
- 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
- 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 › 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, 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
