Vitamin D supplementation in chronic obstructive pulmonary disease patients with low serum vitamin D: a randomized controlled trial

Abstract

Background Vitamin D deficiency is frequently found in patients with Chronic Obstructive Pulmonary Disease (COPD). Vitamin D has antimicrobial, anti-inflammatory and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients. Objectives To assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD Study design and Methods We performed a multi-center, double-blind, randomized controlled trial. COPD patients with one or more exacerbations in the preceding year and a vitamin D deficiency (15–50 nmol/L) were randomly allocated in a 1:1 ratio to receive either vitamin D3 16.800 IU or placebo once a week during 1 year. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbation, time to first and second hospitalization, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life. Results The intention-to-treat population consisted of 155 participants. Mean (SD) serum 25-hydroxyvitamine D (25(OH)D) concentrations after one year was 112 (34) nmol/L in the vitamin D group, compared to 42 (17) nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate (incidence rate ratio (IRR):0.90; 95%-confidence interval (95%-CI): 0.67,1.21). In a prespecified subgroup analysis in participants with 25(OH)D levels 15–25 nmol/L (n = 31) no effect of vitamin D supplementation was found (IRR:0.91; 95%-CI:0.43,1.93). No relevant differences were found between the intervention and placebo group in secondary outcomes. Conclusion Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.

Vitamin D deficiency in chronic obstructive pulmonary disease

“…Lokesh et al [17] found a positive correlation between serum 25(OH)D 3 levels and 6-min walk test (6MWT) distance in patients with COPD but not in healthy controls, suggesting that there may be an additional role of vitamin D in the musculoskeletal system for patients with COPD. However, Rafiq et al [21 ▪▪ ] found that vitamin D supplementation did not improve 6MWT distance in COPD patients.…”

“…The reported relationship between VDD and COPD exacerbations has prompted some investigators to study the impacts of vitamin D replacement on exacerbations (Table 1). In one recent randomized control trial (RCT), 155 COPD patients were randomized to receive 16 800 units of vitamin D 3 oral weekly or placebo but there was no difference in the rate of exacerbations between the treatment arms despite improvement in serum 25(OH)D 3 levels [serum 25(OH)D 3 levels 38 ± 15 to 112 ± 34 nmol/l in the treatment group compared with 40 ± 17 to 42 ± 17 nmol/l in placebo] [21 ▪▪ ]. Another recent RCT found no benefit of vitamin D replacement on the rate of exacerbations in the treatment group overall, but there was a significant benefit in the subgroup of patients with serum 25(OH)D 3 levels less than 25 ng/ml when given vitamin D 3 100 000 units oral monthly compared with placebo (hazard ratio 0.11, 95% CI 0.01–0.51) [28 ▪▪ ].…”

“…Whether treatment of VDD in COPD improves lung function has been studied in RCTs (Table 1). One recent placebo-controlled RCT found no effect of vitamin D supplementation on lung function, including in the subgroup with severe VDD although this represented only one-fifth of the participants [21 ▪▪ ]. A second recent RCT found a significant increase in FEV 1 and forced vital capacity (FVC) after 4 weeks of vitamin D supplementation in combination with an aerobic exercise intervention, but not with vitamin D supplementation alone [33].…”

Recent advances in vitamin D implications in chronic respiratory diseases

“…, the effects of vitamin D supplementation in COPD patients with vitamin D deficiency was investigated. Their findings failed to show any preventive or positive effects of vitamin D supplementation on lung exacerbations [ 46 ]. They mentioned several factors contributing to their results.…”

“…Collectively, they concluded no effect of vitamin D supplementation on reducing exacerbations in COPD patients with vitamin D supplementation. Nonetheless, they highlighted the need of supplementing COPD patients with a serum 25(OH)D concentration < 124.8 ng/ml, as COPD patients having low vitamin D are diagnosed with osteoporosis and bone fractures [ 46 , 47 , 51 , 52 ]. By contrast, other RCT studies that aimed similar clinical outcomes [ 53 , 54 ], showed that vitamin D supplementation was associated with a decrease in COPD exacerbations, increase in FEV 1 [ 53 ] and increase in serum 25(OH)D levels [ 54 ].…”