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Author Notes:

Corresponding author: Jessica A. Alvarez, 101 Woodruff Cr NE, WMRB 1313, Atlanta, GA 30329, Phone: (404) 727-1390; jessica.alvarez@emory.edu

Author contributions were as follows: conception and design of the study (JAA, VT, TRZ); acquisition of data (JAA, REG, VTT, DIW, KU, SL); analysis and interpretation of data (JAA, EYC, DIW, EMS, JKF, JDC, RT, DPJ, TRZ); drafting the article (JAA); and critical revisions for important intellectual content (EYC, DIW, JDC, EMS, REG, JKF, RT, VTT, KU, SL, VT, DPJ, TRZ). All authors read and approved the final manuscript.

None of the authors have a conflict of interest to declare.

The funding sources had no involvement in the study design; collection, analysis, or interpretation of data; the writing of the manuscript; or the decision to submit the article for publication.


Research Funding:

This work was supported, in part, by the National Institutes of Health [grants K01 DK102851 (JAA), K24 DK096574 (TRZ), K01 GM109309 (REG), T32 DK007734 (EMS), R01 HL126603 (RT), and UL1 TR000454 (Atlanta Clinical and Translational Science Institute)]; and the Cystic Fibrosis Foundation [grants TANGPR11A0 (VT), CHANDL16F0 (JDC) and a Student Trainee Award (REG)].


  • Science & Technology
  • Life Sciences & Biomedicine
  • Endocrinology & Metabolism
  • Cystic fibrosis
  • Vitamin D
  • Cholecalciferol
  • Metabolomics
  • Pulmonary exacerbation
  • Amino acids

Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D-3 administration

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Journal Title:



Volume 70


, Pages 31-41

Type of Work:

Article | Post-print: After Peer Review


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 D 3 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 D 3 (250,000 IU vitamin D 3 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 D 3 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 D 3 - 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 D 3 treatment. Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D 3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D 3 in this clinical setting.

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