Vitamin D Metabolism Is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease

Am J Respir Crit Care Med. 2020 Aug 1;202(3):371-382. doi: 10.1164/rccm.201909-1867OC.


Rationale: Vitamin D deficiency is common in patients with asthma and chronic obstructive pulmonary disease (COPD). Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions.Objectives: To determine whether vitamin D metabolism is altered in asthma or COPD.Methods: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D3, 25(OH)D3, and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined presupplementation and postsupplementation in 93 adults with asthma, COPD, or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed 14 datasets to compare expression of 1α,25(OH)2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD versus control subjects.Measurements and Main Results: The mean postsupplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in control subjects (39.8 nmol/L; P = 0.001). Compared with control subjects, patients with asthma and COPD had lower molar ratios of 25(OH)D3-to-vitamin D3 and higher molar ratios of 1α,25(OH)2D3-to-25(OH)D3 both presupplementation and postsupplementation (P ≤ 0.005). Intergroup differences in 1α,25(OH)2D3-inducible gene expression signatures were modest and variable if statistically significant.Conclusions: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-to-vitamin D3 and increased molar ratios of 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.

Keywords: 1α,25-dihydroxyvitamin D; 24R,25-dihydroxyvitamin D; 4,β25-dihydroxyvitamin D; vitamin D 1α-hydroxylase; vitamin D 25-hydroxylase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Asthma / metabolism*
  • Calcifediol / metabolism*
  • Calcitriol / metabolism*
  • Case-Control Studies
  • Cholecalciferol / metabolism*
  • Cholecalciferol / pharmacokinetics
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P450 Family 2 / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Polymorphism, Single Nucleotide
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Randomized Controlled Trials as Topic
  • Vitamin D-Binding Protein / genetics
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamins / metabolism*
  • Vitamins / pharmacokinetics


  • GC protein, human
  • Vitamin D-Binding Protein
  • Vitamins
  • Cholecalciferol
  • Cytochrome P-450 CYP3A
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • CYP3A4 protein, human
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase
  • Calcitriol
  • Calcifediol