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Randomized Controlled Trial
. 2018 Jan;42(1):87-94.
doi: 10.1177/0148607116678197. Epub 2017 Dec 11.

High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial

Ellen M Smith  1 , Jennifer L Jones  2 , Jenny E Han  3 , Jessica A Alvarez  1   2 , John H Sloan  4 , Robert J Konrad  4 , Susu M Zughaier  5 , Greg S Martin  3 , Thomas R Ziegler  1   2 , Vin Tangpricha  1   2   6
Affiliations
Randomized Controlled Trial

High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial

Ellen M Smith et al. JPEN J Parenter Enteral Nutr. 2018 Jan.

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 (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.

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Conflict of interest statement

Conflicts of interest: JHS and RJK are employed by Eli Lilly and Company and performed the hepcidin assay. Eli Lilly and Company played no role in the study design or the decision to publish.

Figures

Figure 1
Figure 1
Geometric mean hemoglobin concentrations with corresponding 95% confidence intervals in critically ill adults. Hemoglobin concentrations are reported across time and by treatment group. Hemoglobin concentrations increased significantly over time in the group that received 500,000 IU D3 compared to the placebo group; there was no significant change in the 250,000 IU D3 group. By three weeks, hemoglobin concentrations in the 500,000 IU D3 group differed significantly from the placebo group; there were no statistically significant differences between groups at other time points. *P<0.05; group*time, group-by-time interaction. Sample sizes in the placebo, 250,000 IU D3, and 500,000 IU D3 groups, respectively: enrollment n = 10, 9, 11; 1 week n = 9, 9, 9; 2 weeks n = 8, 6, 5; 3 weeks n = 5, 4, 2; 4 weeks n = 2, 2, 1.
Figure 2
Figure 2
Geometric mean hepcidin concentrations with corresponding 95% confidence intervals in critically ill adults. Hepcidin concentrations are reported across time and by treatment group. There were no significant differences over time in hepcidin concentrations in either vitamin D-treated group relative to placebo. Hepcidin concentrations in the 500,000 IU D3 group differed significantly from the placebo group one week after dosing; there were no statistically significant differences between groups at other time points. *P<0.05; group*time, group-by-time interaction. Sample sizes in the placebo, 250,000 IU D3, and 500,000 IU D3 groups, respectively: enrollment n = 10, 9, 11; 1 week n = 9, 6, 9; 2 weeks n = 8, 6, 5; 3 weeks n = 4, 4, 2.
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