Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers

Chest. 2004 Feb;125(2):557-65. doi: 10.1378/chest.125.2.557.


Background: Vitamin E and beta-carotene affect various measures of immune function and accordingly might influence the predisposition of humans to infections. However, only few controlled trials have tested this hypothesis.

Study objective: To examine whether vitamin E or beta-carotene supplementation affects the risk of pneumonia in a controlled trial.

Design and setting: The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study, a randomized, double-blind, placebo-controlled trial that examined the effects of vitamin E, 50 mg/d, and beta-carotene, 20 mg/d, on lung cancer using a 2 x 2 factorial design. The trial was conducted in the general community in southwestern Finland in 1985 to 1993; the intervention lasted for 6.1 years (median). The hypothesis being tested in the present study was formulated after the trial was closed.

Participants: ATBC study cohort of 29,133 men aged 50 to 69 years, who smoked at least five cigarettes per day, at baseline.

Main outcome measure: The first occurrence of hospital-treated pneumonia was retrieved from the national hospital discharge register (898 cases).

Results: Vitamin E supplementation had no overall effect on the incidence of pneumonia (relative risk [RR], 1.00; 95% confidence interval [CI], 0.88 to 1.14) nor had beta-carotene supplementation (RR, 0.98; 95% CI, 0.85 to 1.11). Nevertheless, the age of smoking initiation was a highly significant modifying factor. Among subjects who had initiated smoking at a later age (> or =21 years; n = 7,469 with 196 pneumonia cases), vitamin E supplementation decreased the risk of pneumonia (RR, 0.65; 95% CI, 0.49 to 0.86), whereas beta-carotene supplementation increased the risk (RR, 1.42; 95% CI, 1.07 to 1.89).

Conclusions: Data from this large controlled trial suggest that vitamin E and beta-carotene supplementation have no overall effect on the risk of hospital-treated pneumonia in older male smokers, but our subgroup finding that vitamin E seemed to benefit subjects who initiated smoking at a later age warrants further investigation.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Community-Acquired Infections / epidemiology
  • Community-Acquired Infections / immunology
  • Community-Acquired Infections / therapy
  • Confidence Intervals
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Follow-Up Studies
  • Hospitalization / statistics & numerical data
  • Humans
  • Lung Neoplasms / prevention & control*
  • Male
  • Middle Aged
  • Pneumonia / epidemiology
  • Pneumonia / immunology
  • Pneumonia / therapy*
  • Probability
  • Risk Assessment
  • Severity of Illness Index
  • Smoking / adverse effects*
  • Treatment Outcome
  • Vitamin E / administration & dosage*
  • beta Carotene / administration & dosage*


  • beta Carotene
  • Vitamin E