title: Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial.
abstract: OBJECTIVE
  To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol.
  
  
  METHODS
  Randomized, placebo-controlled, trial.
  
  
  METHODS
  Medical and surgical ICUs of a single teaching hospital in Boston, MA.
  
  
  METHODS
  Thirty adult ICU patients.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: 1Harvard Medical School, Boston, MA. 2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA. 3Shriners Hospital for Children, Boston, MA. 4Department of Medicine, Massachusetts General Hospital, Boston, MA. 5Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA. 6Harvard School of Public Health, Boston, MA.
authors.forename: Sadeq A
authors.initials: SA
authors.lastname: Quraishi
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Pascale
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Needleman
authors.forename: Harumasa
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.forename: Ednan K
authors.initials: EK
authors.lastname: Bajwa
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.forename: Ishir
authors.initials: I
authors.lastname: Bhan
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers; D002097:C-Reactive Protein; D002112:Calcifediol / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000097:blood*; D012709:Serum Albumin; D012772:Shock, Septic / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D012709:Serum Albumin; D014807:Vitamin D; D002762:Cholecalciferol; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D; D002112:Calcifediol; D054804:Cathelicidins