Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)
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CONTEXT: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. OBJECTIVE: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. INTERVENTIONS: Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer incidence. RESULTS: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. CONCLUSION: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00006392.
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Electron donors such as transition metal ions, amines, glutathione, vitamin C, vitamin E, NADH, and FADH2 split a dioxetane's O-O bond without C-C cleavage, yielding harmless diols.
“Electron donors such as transition metal ions, amines, glutathione, vitamin C, vitamin E, NADH, and FADH2 split the O–O bond of a dioxetane in a way that is not followed by the C–C cleavage and so yields harmless diols (276, 287, 65, 277, 278, 288).”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [287]
The Statistical Analysis and Results sections concern vitamin E supplementation and cancer outcomes, not dioxetane chemistry. Searches for dioxetane O–O and C–C bond cleavage, diols, and the listed electron donors found no passage addressing the claimed reaction. (LLM, conf=0.78)
Experimental — accuracy not yet measuredHuman and animal studies have not clearly shown that antioxidants prevent or suppress cancer.
“recent results from both human and animal studies have found no clear evidence of the benefit of antioxidant treatment in preventing or suppressing cancer development.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [17]
In patients, antioxidant use raised the risk of prostate and lung cancer.
“increase the risk of prostate and lung cancers in patients17–19”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [17]
Various clinical trials disproved the approach that cancer patients supplementing their diet with antioxidants may inhibit cancer progression.
“However, various clinical trials disproved this approach (Klein et al. 2011).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Klein et al. 2011
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References 37 · Cited by 1,787
Research works printed but not linked: 1
- [8]8. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statist Med. 1999; 18(6):695-706.
- Authors
- Klein, E. A., Thompson, I. M., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., Minasian, L. M., Ford, L. G., Parnes, H. L., Gaziano, J. M., Karp, D. D., Lieber, M. M., Walther, P. J., Klotz, L., Parsons, J. K., Chin, J. L., Darke, A. K., Lippman, S. M., Goodman, G. E., Meyskens, F. L., & Baker, L. H.
- Affiliations
- Cleveland Clinic (US)
- The University of Texas at San Antonio Health Science Center (US)
- Fred Hutch Cancer Center (US)
- University of Colorado Health (US)
- National Institutes of Health (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Mayo Clinic (US)
- Duke University (US)
- Sunnybrook Health Science Centre (CA)
- University of California San Diego (US)
- Western University (CA)
- The University of Texas MD Anderson Cancer Center (US)
- Swedish Medical Center (US)
- University of California, Irvine (US)
- University of Michigan (US)
- Corresponding author
- Klein, Eric A.
- ORCID
- Klein, Eric A.
- Thompson, Ian M.
- Tangen, Catherine M.
- Lucia, M. Scott
- Goodman, Phyllis J.
- Minasian, Lori M.
- Ford, Leslie G.
- Parnes, Howard L.
- Gaziano, J. Michael
- Karp, Daniel D.
- Walther, Philip J.
- Klotz, Laurence
- Parsons, J. Kellogg
- Chin, Joseph L.
- Darke, Amy K.
- Lippman, Scott M.
- Goodman, Gary E.
- Meyskens, Frank L.
- Baker, Laurence H.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2011-10-12
- Volume
- 306
- Issue
- 14
- Pages
- 1549
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC4169010
- OpenAlex
- W2140068099
- Semantic Scholar
- ce47bda9ee0e2b63f0b9a1134b7402323837f338
- Cited by
- 1,787
- References
- 37
- Citations by year
- 2026: 80 · 2025: 93 · 2024: 91 · 2023: 90 · 2022: 138 · 2021: 133 · 2020: 141 · 2019: 103 · 2018: 119 · 2017: 126 · 2016: 129 · 2015: 108 · 2014: 152 · 2013: 123 · 2012: 148
- FWCI
- 90.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- U.S. Department of Health and Human Services
- Amgen
- Pfizer
- Perrigo Company Charitable Foundation
- National Institutes of Health
- DSM Nutritional Products
- National Cancer Institute (CA 37429, U10CA037429)
- National Center for Complementary and Alternative Medicine
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- vitamin E, selenium, prostate cancer, prostate cancer incidence, dietary supplements, cancer prevention, long-term follow-up, hazard ratio, L-selenomethionine, alpha-tocopherol acetate, healthy men, Black men, older men, vitamin E toxicity, selenium toxicity, vitamin E deficiency, selenium deficiency
- MeSH terms
- Aged, Antioxidants, Follow-Up Studies, Humans, Male, Middle Aged, Prostatic Neoplasms, Risk, Selenium, Vitamin E, Incidence, Dietary Supplements
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