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

• Published in: Metabolism, clinical and experimental Vol. 70; pp. 31 - 41
• Main Authors: Alvarez, Jessica A., Chong, Elizabeth Y., Walker, Douglas I., Chandler, Joshua D., Michalski, Ellen S., Grossmann, Ruth E., Uppal, Karan, Li, Shuzhao, Frediani, Jennifer K., Tirouvanziam, Rabindra, Tran, ViLinh T., Tangpricha, Vin, Jones, Dean P., Ziegler, Thomas R.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.05.2017
• Subjects: Cholecalciferol; Cystic fibrosis; Endocrinology & Metabolism; Metabolomics; Pulmonary exacerbation; Vitamin D; FEV1%predicted; Metabolomics; HRM; CF; Cholecalciferol; HCA; Cystic fibrosis; Human Metabolomics Database; PCA; TCA; Vitamin D; FDR; LIMMA; 25(OH)D; NIST SRM; Pulmonary exacerbation; BMI; hierarchical cluster analysis; amino acids; pulmonary exacerbation; metabolomics; cystic fibrosis; cholecalciferol; false discovery rate; National Institute of Standards and Technology Standard Reference Material; HMDB; percentage of predicted forced expiratory volume in 1 s; tricarboxylic acid; 25-hydroxyvitamin D; vitamin D; body mass index; linear models for microarray data; high-resolution metabolomics; principal component analysis
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2017.02.006

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. 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. 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. 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. 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.