High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial

Ann Intern Med. 2012 Jan 17;156(2):105-14. doi: 10.7326/0003-4819-156-2-201201170-00004.


Background: Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis.

Objective: To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations.

Design: Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367)

Setting: University Hospitals Leuven, Leuven, Belgium.

Patients: 182 patients with moderate to very severe COPD and a history of recent exacerbations.

Intervention: 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year.

Measurements: The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death.

Results: Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042).

Limitation: This was a single-center study with a small sample size.

Conclusion: High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations.

Primary funding source: Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).

Publication types

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

MeSH terms

  • Aged
  • Antimicrobial Cationic Peptides / blood
  • Cathelicidins
  • Cause of Death
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis / prevention & control
  • Phagocytosis
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quality of Life
  • Recurrence
  • Sputum / microbiology
  • Treatment Outcome
  • Vitamin D / administration & dosage*
  • Vitamin D / adverse effects
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood


  • Antimicrobial Cationic Peptides
  • Vitamin D
  • 25-hydroxyvitamin D
  • Cathelicidins

Associated data

  • ClinicalTrials.gov/NCT00666367