Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration

Abstract

Background: Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown.

Objective: We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D₃ administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation.

Design: Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D₃ (250,000IU vitamin D₃ bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D₃ supplementation.

Results: Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways-predominantly representing amino acid pathways-differed between the vitamin D₃- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D₃ treatment.

Conclusions: Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D₃ supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D₃ in this clinical setting.

Keywords: Cholecalciferol; Cystic fibrosis; Metabolomics; Pulmonary exacerbation; Vitamin D.