High-Dose Vitamin D 3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults

Abstract

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 (P_{group × time} = .01) compared with placebo but did not change in the 250,000-IU D₃ group (P_{group × 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.