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Author Notes:

Correspondence: Jenny E. Han, MD, MSc, Emory University School of Medicine, Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, 49 Jesse Hill Jr. Drive SE, Atlanta, GA 30303, jehan2@emory.edu; Phone: 404-616-0821; Fax: 404-616-8455

Statement of Authorship: Conception, design, conduct of trial, analysis, and interpretation, drafting and revising manuscript: JEH, JAA, JLJ, LAB, VT, GSM, TRZ

Conduct of trial, interpretation, drafting work of intellectual content: MAB, LH

Analysis and interpretation and drafting work of intellectual content: JEH, JAA, LAB, JLJ, VT, GSM, TRZ.

We would like to acknowledge Frank Harris for his technical assistance.

Conflict of Interest Statement: The authors have no conflicts of interest to disclose.


Research Funding:

Supported, in part, by National Institutes of Health grants: NIH R21 HL110044 (GSM, TRZ), K24 DK096574 (TRZ), UL1 TR000454 (JEH, GSM, TRZ, VT), K01 DK102851 (JAA), T32 DK007298 (JLJ), T32 AA013528 (JEH).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Nutrition & Dietetics
  • Antimicrobial peptides
  • Critical care
  • LL-37
  • Respiratory failure
  • Vitamin D

Impact of high-dose vitamin D-3 on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults


Journal Title:

Nutrition in Clinical Practice


Volume 38


, Pages 102-108

Type of Work:

Article | Post-print: After Peer Review


Objectives High-dose vitamin D3increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. Methods In a double blind, randomized controlled trial, critically ill ventilator-dependent adults (N = 30) received enteral vitamin D3(250,000 or 500,000 IU total over 5 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Results Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P < 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). Conclusions The present study found a dose-related increase in plasma free-25(OH)D levels, which was associated with increasing circulating mRNA expression of hCAP18 over time. There were no correlations between changes in total and free 25(OH)D against plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3administration on endogenous AMPs.

Copyright information:

© 2017 Elsevier Inc.

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