Cystic Fibrosis exacerbation reduced by Vitamin D (250,000 IU) – RCT May 2017

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

Metabolism. 2017 May;70:31-41. doi: 10.1016/j.metabol.2017.02.006. Epub 2017 Feb 11.

Alvarez JA1, Chong EY2, Walker DI3, Chandler JD4, Michalski ES5, Grossmann RE6, Uppal K3, Li S3, Frediani JK5, Tirouvanziam R7, Tran VT3, Tangpricha V 8, Jones DP3, Ziegler TR8.

• 1 Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: jessica.alvarez at emory.edu.
• 2 Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
• 3 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
• 4 Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
• 5 Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Nutrition and Health Sciences Graduate Program, Laney Graduate School, Emory University, Atlanta, GA, USA.
• 6 College of Nursing, The University of Iowa, Ames, IA, USA.
• 7 Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
• 8 Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Section of Endocrinology, Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.

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.

PMID: 28403943 DOI: 10.1016/j.metabol.2017.02.006

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