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Cited by 2,397Antioxidant Activity and Oxidative StressNutritional Studies and DietVitamin C and Antioxidants Research

Lack of Effect of Long-Term Supplementation with Beta Carotene on the Incidence of Malignant Neoplasms and Cardiovascular Disease

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Hennekens, Charles H., Buring, Julie E., Manson, JoAnn E., Stampfer, Meir, Rosner, Bernard, Cook, Nancy R., Belanger, Charlene, LaMotte, Frances +4 more·1996·New England Journal of Medicine
DOI 10.1056/nejm199605023341801
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Abstract

BACKGROUND: Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation. METHODS: In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene. RESULTS: Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points. CONCLUSIONS: In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes.

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  • In 1996, a trial of 12 years supplementation with β-carotene (50 mg on alternate days) in healthy men did not show any protective effect from melanoma insurgence.

    “In 1996, a trial was reported on 12 years of supplementation with β-carotene (50 mg on alternate days) on healthy men but did not show any protective effect from melanoma insurgence [109].”

    From Antioxidants from Plants Protect against Skin Photoaging (2018) · cites this paper as [109]

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Authors
Hennekens, C. H., Buring, J. E., Manson, J. E., Stampfer, M., Rosner, B., Cook, N. R., Belanger, C., LaMotte, F., Gaziano, J. M., Ridker, P. M., Willett, W., & Peto, R.
Affiliations
  • Brigham and Women's Hospital (US)
  • University of Oxford (GB)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1996-05-02
Volume
334
Issue
18
Pages
1145-1149
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199605023341801
OpenAlex
W2315403385
Cited by
2,397
References
23
Citations by year
2026: 8 · 2025: 19 · 2024: 19 · 2023: 24 · 2022: 24 · 2021: 25 · 2020: 34 · 2019: 32 · 2018: 34 · 2017: 45 · 2016: 40 · 2015: 45 · 2014: 67 · 2013: 90 · 2012: 87
FWCI
109.95
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL 26490)
  • National Cancer Institute (R01CA040360, CA 34944, CA 40360)
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 › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords
beta-carotene supplementation, vitamin A, cancer incidence, cardiovascular disease, lung cancer, myocardial infarction, stroke, mortality, smokers, physicians, long-term supplementation, non-melanoma skin cancer, fruit and vegetable intake, vitamin A toxicity, retinol, tocopherols, tocotrienols, tocopheryl nicotinate, tocopheryl succinate
MeSH terms
Adult, Aged, Aged, 80 and over, Antioxidants, Cardiovascular Diseases, Carotenoids, Double-Blind Method, Humans, Male, Middle Aged, Mortality, Neoplasms, Risk, Incidence, Proportional Hazards Models, beta Carotene

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