Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial

JAMA. 2002 Aug 14;288(6):715-21. doi: 10.1001/jama.288.6.715.


Context: Immune response in elderly individuals has been reported to improve after micronutrient supplementation. However, efficacy trials evaluating infectious diseases as outcomes are scarce and inconclusive.

Objective: To investigate the effect of daily multivitamin-mineral and vitamin E supplementation on incidence and severity of acute respiratory tract infections in elderly individuals.

Design: A randomized, double blind, placebo-controlled, 2 x 2 factorial trial.

Setting and participants: A total of 652 noninstitutionalized individuals aged 60 years or older enrolled from 2 community-based sampling strategies in the Wageningen area of the Netherlands, conducted from 1998 to 2000. At baseline, 6% of participants had suboptimal ascorbic acid and 1.3% had suboptimal alpha-tocopherol plasma concentration.

Intervention: Physiological doses of multivitamin-minerals, 200 mg of vitamin E, both, or placebo.

Main outcome measures: Incidence and severity of self-reported acute respiratory tract infections at 15 months, as assessed by a nurse (telephone contact), home visits, and microbiological and serological testing in subsets of patients.

Results: During a median observation period of 441 days, 443 (68%) of 652 participants recorded 1024 respiratory tract infection episodes. The incidence rate ratio of acute respiratory tract infection for multivitamin-mineral supplementation was 0.95 (95% confidence interval, 0.75-1.15; P =.58) and for vitamin E supplementation, 1.12 (95% confidence interval, 0.88-1.25; P =.21). Severity of infections was not influenced by multivitamin-mineral supplementation. For vitamin E vs no vitamin E, severity was worse: median (interquartile range) for illness-duration was 19 (9-37) vs 14 (6-29) days, P =.02; number of symptoms, 6 (3-8) vs 4 (3-8), P =.03; presence of fever, 36.7% vs 25.2%, P =.009; and restriction of activity, 52.3% vs 41.1%, P =.02.

Conclusions: Neither daily multivitamin-mineral supplementation at physiological dose nor 200 mg of vitamin E showed a favorable effect on incidence and severity of acute respiratory tract infections in well-nourished noninstitutionalized elderly individuals. Instead we observed adverse effects of vitamin E on illness severity.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Minerals / therapeutic use*
  • Respiratory Tract Infections / classification
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / prevention & control*
  • Severity of Illness Index
  • Treatment Failure
  • Vitamin E / therapeutic use*
  • Vitamins / therapeutic use*


  • Minerals
  • Vitamins
  • Vitamin E