Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial
Open accessAbstract
BACKGROUND: Observational studies suggested that a diet high in fruits and vegetables, both of which are rich with antioxidants, may prevent cancer development. However, findings from randomized trials of the association between antioxidant use and cancer risk have been mostly negative. METHODS: From 8171 women who were randomly assigned in the Women's Antioxidant Cardiovascular Study, a double-blind, placebo-controlled 2 x 2 x 2 factorial trial of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of alpha-tocopherol every other day), and beta carotene (50 mg every other day), 7627 women who were free of cancer before random assignment were selected for this study. Diagnoses and deaths from cancer at a specific site were confirmed by use of hospital reports and the National Death Index. Cox proportional hazards regression models were used to assess hazard ratios (represented as relative risks [RRs]) of common cancers associated with use of antioxidants, either individually or in combination. Subgroup analyses were conducted to determine if duration of use modified the association of supplement use with cancer risk. All statistical tests were two-sided. RESULTS: During an average 9.4 years of treatment, 624 women developed incident invasive cancer and 176 women died from cancer. There were no statistically significant effects of use of any antioxidant on total cancer incidence. Compared with the placebo group, the RRs were 1.11 (95% confidence interval [CI] = 0.95 to 1.30) in the vitamin C group, 0.93 (95% CI = 0.79 to 1.09) in the vitamin E group, and 1.00 (95% CI = 0.85 to 1.17) in the beta carotene group. Similarly, no effects of these antioxidants were observed on cancer mortality. Compared with the placebo group, the RRs were 1.28 (95% CI = 0.95 to 1.73) in the vitamin C group, 0.87 (95% CI = 0.65 to 1.17) in the vitamin E group, and 0.84 (95% CI = 0.62 to 1.13) in the beta carotene group. Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death. CONCLUSIONS: Supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality.
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Clinical trials using antioxidants to scavenge ROS have consistently failed, and in some cases, actually increased mortality.
“This line of thinking has led to multiple clinical trials using antioxidants to scavenge ROS, yet these trials have consistently failed, and in some cases, actually increased mortality 84–87.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [86]
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- Authors
- Lin, J., Cook, N. R., Albert, C., Zaharris, E., Gaziano, J. M., Van Denburgh, M., Buring, J. E., & Manson, J. E.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-12-30
- Volume
- 101
- Issue
- 1
- Pages
- 14-23
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC2615459
- OpenAlex
- W2144053989
- Cited by
- 309
- References
- 73
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 18 · 2021: 19 · 2020: 17 · 2019: 10 · 2018: 4 · 2017: 9 · 2016: 21 · 2015: 15 · 2014: 22 · 2013: 26 · 2012: 27
- FWCI
- 15.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 46959, R01HL046959)
- National Cancer Institute (CA126846, K07CA112529, CA112529, R01CA126846)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- vitamin E, beta-carotene, antioxidant supplementation, cancer risk, cancer incidence, cancer mortality, women, dietary antioxidants, fruit and vegetable intake, duration of supplementation, cancer prevention, factorial trial
- MeSH terms
- Adult, Aged, Antioxidants, Ascorbic Acid, Cardiovascular Diseases, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Middle Aged, Neoplasms, Primary Prevention, Risk Factors, United States, Vitamin E, Incidence, Proportional Hazards Models, Risk Assessment, beta Carotene, Dietary Supplements
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 ›
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