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Cited by 4,737Antioxidant Activity and Oxidative StressHead and Neck Cancer StudiesLung Cancer Diagnosis and Treatment

The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers

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The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group·1994·New England Journal of Medicine
DOI 10.1056/nejm199404143301501
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Abstract

BACKGROUND: Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer. METHODS: We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years. RESULTS: Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha-tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease. CONCLUSIONS: We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.

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  • 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 [19]

  • Human 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 [19]

  • Beta-carotene has been shown to increase the risk of lung cancers.

    “However, this formulation is not recommended for smokers because beta-carotene has been shown to increase the risk of lung cancers.148,149”

    From Age-related macular degeneration (2008) · cites this paper as [148]

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Research works printed but not linked: 2

  1. [2]2. National Research Council. Diet, nutrition, and cancer. Washington, D.C.: National Academy Press, 1982.
  2. [28]28. Buring JE, Hennekens CH. The Women's Health Study: summary of the study design. J Myocardial Ischemia 1992;4:27-9.

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Authors
The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group
Corresponding author
The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1994-04-14
Volume
330
Issue
15
Pages
1029-1035
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199404143301501
OpenAlex
W1525444530
Cited by
4,737
References
25
Citations by year
2026: 63 · 2025: 51 · 2024: 63 · 2023: 72 · 2022: 104 · 2021: 87 · 2020: 94 · 2019: 77 · 2018: 83 · 2017: 95 · 2016: 91 · 2015: 105 · 2014: 135 · 2013: 120 · 2012: 160
FWCI
154.01
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (n01cn045165-030)
  • National Cancer Institute (N01 CN 45165)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
vitamin E, alpha-tocopherol, beta-carotene, lung cancer, cancer prevention, smokers, dietary supplementation, prostate cancer, hemorrhagic stroke, all-cause mortality, ischemic heart disease
MeSH terms
Aged, Carotenoids, Cause of Death, Double-Blind Method, Finland, Humans, Lung Neoplasms, Male, Middle Aged, Smoking, Vitamin E, Incidence, beta Carotene

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