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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 V8, 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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