Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial

Gennaro De Pascale, Sadeq A. Quraishi, Joseph S. Needleman, Harumasa Nakazawa, Masao Kaneki, Ednan K. Bajwa, Carlos A. Camargo, Ishir Bhan

Risultato della ricerca: Contributo in rivistaArticolo in rivista

77 Citazioni (Scopus)


To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol. Design: Randomized, placebo-controlled, trial. Setting: Medical and surgical ICUs of a single teaching hospital in Boston, MA. Patients: Thirty adult ICU patients. Interventions: Placebo (n = 10) versus 200,000 IU cholecalciferol (n = 10) versus 400,000 IU cholecalciferol (n = 10), within 24 hours of new-onset severe sepsis or septic shock. Measurements and Main Results: Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D, as well as vitamin D-binding protein and albumin to calculate bioavailable 25-hydroxyvitamin D. Plasma LL-37 and high-sensitivity C-reactive protein levels were also measured. At baseline, median (interquartile range) plasma 25-hydroxyvitamin D was 17 ng/mL (13-22 ng/mL) and peaked by day 5 in both intervention groups. Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for placebo, 200,000 IU cholecalciferol, and 400,000 IU cholecalciferol groups, respectively, were as follows: 1) total 25-hydroxyvitamin D, 3% (-3% to 8%), 49% (30-82%), and 69% (55-106%) (p < 0.001); 2) bioavailable 25-hydroxyvitamin D, 4% (-8% to 7%), 45% (40-70%), and 96% (58-136%) (p < 0.01); and 3) LL-37:-17% (-9% to-23%), 4% (-10% to 14%), and 30% (23-48%) (p = 0.04). Change in high-sensitivity C-reactive protein levels did not differ between groups. A positive correlation was observed between bioavailable 25-hydroxyvitamin D and LL-37 (Spearman ρ = 0.44; p = 0.03) but not for total 25-hydroxyvitamin D and LL-37. Conclusions: High-dose cholecalciferol supplementation rapidly and safely improves 25-hydroxyvitamin D and bioavailable 25-hydroxyvitamin D levels in patients with severe sepsis or septic shock. Changes in bioavailable 25-hydroxyvitamin D are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.
Lingua originaleEnglish
pagine (da-a)1928-1937
Numero di pagine10
RivistaCritical Care Medicine
Stato di pubblicazionePubblicato - 2015


  • 25-hydroxyvitamin
  • Adult
  • Antimicrobial Cationic Peptides
  • Biomarkers
  • C-Reactive Protein
  • Calcifediol
  • Cholecalciferol
  • Dietary Supplements
  • Female
  • Hospitals, Teaching
  • Humans
  • Intensive Care Units
  • LL-37
  • Male
  • Middle Aged
  • Sepsis
  • Serum Albumin
  • Shock, Septic
  • Vitamin D
  • cathelicidin
  • cholecalciferol
  • intensive care unit


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