Those with Asthma or COPD had half the response to Vitamin D – March 2020

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

Am J Respir Crit Care Med. 2020 Mar 18, DOI: 10.1164/rccm.201909-1867OC
David A Jolliffe 1, Christos Stefanidis 1, Zhican Wang 2, Nazanin Z Kermani 3, Vassil Dimitrov 4, John H White 5, John E McDonough 6, Wim Janssens 7, Paul Pfeffer 8, Christopher J Griffiths 9, Andrew Bush 10, Yike Guo 3, Stephanie Christenson 11, Ian M Adcock 12, Kian Fan Chung 13, Kenneth E Thummel 2, Adrian R Martineau 14

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Rationale: Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions.

Objective: 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 one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation 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 fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls.

Measurements and main results:
The mean post-supplementation 25(OH)D increase in participants with

• asthma (20.9 nmol/L) and
• COPD (21.5 nmol/L) was lower than in
• controls (39.8 nmol/L; P=0.001).

Compared with controls, 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 pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where 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.