Sadeq A Quraishi1, Gennaro De Pascale, Joseph S Needleman, Harumasa Nakazawa, Masao Kaneki, Ednan K Bajwa, Carlos A Camargo, Ishir Bhan. 1. 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.
Abstract
OBJECTIVES: To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated withplacebo 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.
RCT Entities:
OBJECTIVES: To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICUpatients 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.
Authors: B Agerberth; J Charo; J Werr; B Olsson; F Idali; L Lindbom; R Kiessling; H Jörnvall; H Wigzell; G H Gudmundsson Journal: Blood Date: 2000-11-01 Impact factor: 22.113
Authors: Mitchell M Levy; Mitchell P Fink; John C Marshall; Edward Abraham; Derek Angus; Deborah Cook; Jonathan Cohen; Steven M Opal; Jean-Louis Vincent; Graham Ramsay Journal: Crit Care Med Date: 2003-04 Impact factor: 7.598
Authors: Gennaro Martucci; Fabio Tuzzolino; Antonio Arcadipane; Thomas R Pieber; Christian Schnedl; Tadeja Urbanic Purkart; Gerlies Treiber; Karin Amrein Journal: Intensive Care Med Date: 2017-05-26 Impact factor: 17.440
Authors: Jenny E Han; Jessica A Alvarez; Jennifer L Jones; Vin Tangpricha; Mona A Brown; Li Hao; Lou Ann S Brown; Greg S Martin; Thomas R Ziegler Journal: Nutrition Date: 2017-02-27 Impact factor: 4.008
Authors: Vin Tangpricha; Joshua Lukemire; Yuqing Chen; José Nilo G Binongo; Suzanne E Judd; Ellen S Michalski; Moon J Lee; Seth Walker; Thomas R Ziegler; Rabin Tirouvanziam; Susu M Zughaier; Supavit Chesdachai; Wendy A Hermes; James F Chmiel; Ruth E Grossmann; Amit Gaggar; Patricia M Joseph; Jessica A Alvarez Journal: Am J Clin Nutr Date: 2019-03-01 Impact factor: 7.045
Authors: Adit A Ginde; Roy G Brower; Jeffrey M Caterino; Lani Finck; Valerie M Banner-Goodspeed; Colin K Grissom; Douglas Hayden; Catherine L Hough; Robert C Hyzy; Akram Khan; Joseph E Levitt; Pauline K Park; Nancy Ringwood; Emanuel P Rivers; Wesley H Self; Nathan I Shapiro; B Taylor Thompson; Donald M Yealy; Daniel Talmor Journal: N Engl J Med Date: 2019-12-11 Impact factor: 91.245
Authors: Jonathan M Mansbach; Kohei Hasegawa; Nadim J Ajami; Joseph F Petrosino; Pedro A Piedra; Courtney N Tierney; Janice A Espinola; Carlos A Camargo Journal: Clin Infect Dis Date: 2017-09-15 Impact factor: 9.079
Authors: Gerard E Mullin; Berkeley Limektkai; Lin Wang; Patrick Hanaway; Loren Marks; Edward Giovannucci Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622