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Randomized Controlled Trial
. 2025 May;155(5):1417-1428.
doi: 10.1016/j.tjnut.2025.02.003. Epub 2025 Feb 6.

Vitamin D Supplementation, Chronic Obstructive Lung Disease and Asthma Exacerbations, and Lung Function Decline

Diane R Gold  1 , Vincent J Carey  2 , Craig P Hersh  2 , Emily Wan  3 , Carlos A Camargo Jr  4 , I-Min Lee  5 , Nancy R Cook  5 , Nicholas Nassikas  6 , Julie E Buring  5 , JoAnn E Manson  5 , Heike Luttmann-Gibson  7
Affiliations
Randomized Controlled Trial

Vitamin D Supplementation, Chronic Obstructive Lung Disease and Asthma Exacerbations, and Lung Function Decline

Diane R Gold et al. J Nutr. 2025 May.

Abstract

Background: It remains unclear whether supplementation with vitamin D reduces risk of acute exacerbations of chronic obstructive lung disease (COPD) or asthma, major contributors to the world-wide burden of disease.

Objectives: To compare effects of vitamin D with placebo supplementation for the prespecified primary endpoints 1) acute exacerbations of COPD and 2) decline in pulmonary function measures of airflow obstruction. Prespecified secondary endpoints included asthma exacerbations and control.

Methods: Lung VITamin D and OmegA-3 TriaL (VITAL) is an ancillary study of VITAL, a United States nationwide, randomized, placebo-controlled trial with a 2-by-2 factorial design of vitamin D3 (2000 IU/d) and marine n-3 fatty acids (1 g/d) among men 50 y and women 55 y of age or older. Of 25,871 randomly divided participants, 3632 at risk for respiratory exacerbations, including 1977 with COPD by diagnosis or symptoms and 1654 with self-reported asthma diagnosis, were followed annually for 5 y by self-administered respiratory questionnaire. Spirometry was performed at baseline and 2 y after randomization by 1648 participants from 12 urban centers. Decline in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity was measured between baseline and follow-up.

Results: Supplementation with vitamin D was not associated with lower risk of any primary or secondary end point. Over the 5-y follow-up, the number of COPD exacerbations was 0.27/y in the vitamin D group and 0.25/y in the placebo group (rate ratio 1.10; 95% confidence interval, 0.93, 1.29). Over the 2-y follow-up, supplementation was not associated with slower decline (mL/y) in FEV1.

Conclusions: Supplementation with vitamin D, compared with placebo, did not result in a lower rate of COPD exacerbations or improved pulmonary function in community-dwelling adults not selected for vitamin D deficiency. This trial was registered at Lung VITAL clinicaltrials.gov as NCT01728571 with Protocol ID 2010-P-000622 (https://prevention.cancer.gov/clinical-trials/clinical-trials-search/nct01728571).

Keywords: COPD; asthma; pulmonary function; spirometry; vitamin D; vitamin supplement.

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Conflict of interest statement

Conflict of interest DRG, VJC, CH, CAC, I-ML, NN, JEB, JEM, and HL-G reported grants from National Institutes of Health (NIH) during the conduct of the study. CH reports grant support from The National Heart, Lung, and Blood Institute, Alpha-1 Foundation, Bayer, Boehringer Ingelheim, and Vertex, and consulting fees from Chiesi, Sanofi, and Takeda, unrelated to this manuscript. EW reports grant funding from the United States Department of Veterans Affairs and has served on a scientific advisory board for Verona Pharma, outside the current work. NN has received payments from Industrial Economics, Inc for consulting work and honoraria from Harvard University, Columbia University, Stanford University, and Rhode Island Thoracic Society, unrelated to this work. JEB reports that during the trial, her spouse was on the Scientific Advisory Board of Pharmavite, which provided the vit D/placebo for the VITAL trial. NRC reports no conflict of interest.

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