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

Crit Care Med. 2015 Sep;43(9):1928-37. doi: 10.1097/CCM.0000000000001148.

Abstract

Objectives: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antimicrobial Cationic Peptides / blood*
  • Biomarkers
  • C-Reactive Protein
  • Calcifediol / blood
  • Cathelicidins
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / therapeutic use*
  • Dietary Supplements*
  • Female
  • Hospitals, Teaching
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Sepsis / blood*
  • Serum Albumin
  • Shock, Septic / blood
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • Antimicrobial Cationic Peptides
  • Biomarkers
  • Serum Albumin
  • Vitamin D
  • Cholecalciferol
  • C-Reactive Protein
  • 25-hydroxyvitamin D
  • Calcifediol
  • Cathelicidins