Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial

Cancer. 2007 Mar 1;109(5):891-8. doi: 10.1002/cncr.22482.


Background: Although smoking and alcohol consumption are the major risk factors for upper aerodigestive tract cancers, observational studies indicate a protective role for fruits, vegetables, and antioxidant nutrients.

Methods: The authors examined whether daily supplementation with 50 mg dl alpha-tocopheryl acetate and/or 20 mg beta-carotene reduced the incidence of or mortality from oral/pharyngeal, esophageal, and laryngeal cancers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a double-blind, placebo-controlled primary prevention trial conducted in southwestern Finland. A total of 29,133 male smokers, aged 50-69 years and free of cancer at baseline, were randomized in a 2 x 2 factorial design to the supplementation regimen for 5-8 years (median, 6.1 years). Incident cancers of the oral cavity and pharynx (n = 65), esophagus (n = 24), and larynx (n = 56) were identified through the Finnish Cancer Registry. Intervention effects were assessed using survival analysis and proportional hazards models.

Results: There was no effect of either agent on the overall incidence of any upper aerodigestive tract cancer. For larynx, however, exploratory subgroup analyses were suggestive of a protective effect of beta-carotene supplementation on the incidence of early stage malignancies (stage I, relative risk [RR], 0.28, 95% confidence interval [CI]: 0.10-0.75). Neither agent affected mortality from these neoplasms.

Conclusions: The results do not provide support for a protective effect of vitamin E or beta-carotene supplementation on upper aerodigestive tract cancers, although beta-carotene supplementation may impact the incidence of some subtypes of laryngeal tumors.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Dietary Supplements
  • Double-Blind Method
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / prevention & control*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Primary Prevention
  • Smoking / adverse effects
  • Vitamins / therapeutic use*
  • alpha-Tocopherol / therapeutic use*
  • beta Carotene / therapeutic use*


  • Vitamins
  • beta Carotene
  • alpha-Tocopherol