High-Dose Vitamin D 3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial

JPEN J Parenter Enteral Nutr. 2018 Jan;42(1):87-94. doi: 10.1177/0148607116678197. Epub 2017 Dec 11.


Background: Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high-dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults.

Materials and methods: Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double-blind, randomized, placebo-controlled trial of high-dose vitamin D3 (D3 ) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3 , or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3 , respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed-effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time.

Results: At enrollment, >75% of participants in all groups had plasma 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000-IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000-IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000-IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000-IU D3 group.

Conclusion: In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high-dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.

Keywords: anemia; critical illness; hemoglobin; hepcidin; vitamin D.

Publication types

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

MeSH terms

  • Aged
  • Cholecalciferol / therapeutic use*
  • Critical Care / methods*
  • Critical Illness
  • Double-Blind Method
  • Female
  • Hemoglobins / drug effects*
  • Hepcidins / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Respiration, Artificial*
  • Vitamins / therapeutic use*


  • Hemoglobins
  • Hepcidins
  • Vitamins
  • Cholecalciferol