Treatment response variations to a single large bolus of enteral cholecalciferol in vitamin D deficient critically Ill children: Metabolomic insights for precision nutrition.

The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2025 Jun; Vol. 250, pp. 106720. Date of Electronic Publication: 2025 Mar 09.

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Philip Britz-Mckibbin reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Philip Britz-Mckibbin reports financial support was provided by Genome Canada. Philip Britz-Mckibbin reports financial support was provided by Canada Foundation for Innovation. Dayre McNally reports financial support was provided by Canadian Institutes of Health Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper
Vitamin D deficiency (VDD) is prevalent globally and in pediatric intensive care units, where it represents a modifiable risk factor that may impact patient recovery during hospitalization. Herein, we performed a retrospective analysis of serum samples from a phase-II randomized placebo-controlled trial involving a single large bolus of 10,000 IU/kg vitamin D3 ingested by critically ill children with VDD (25-OH-D < 50 nmol/L). Targeted and untargeted methods were used to comprehensively measure 6 vitamin D metabolites, 239 lipids, 68 polar metabolites, and 4 electrolytes using a multi-step data workflow for compound authentication. Complementary statistical methods classified circulating metabolites/lipids associated with vitamin D repletion following high-dose vitamin D3 intake (n = 20) versus placebo (n = 11) comprising an optional standard of care maintenance dose (< 1000 IU/day). There was a striking increase in median serum concentrations of 25-OH-D3 (4.7-fold), 3-epi-25-OH-D3 (24-fold) and their C3-epimer ratio (6.7-fold) in treated patients on day 3, whereas serum vitamin D3 peaked on day 1 (128-fold) unlike placebo. Treatment response differences were attributed to D3 bioavailability and C3-epimerase activity without evidence of hypercalcemia. For the first time, we report the detection of circulating 3-epi-D3 that was strongly correlated with vitamin D3 uptake (r = 0.898). Metabolomic studies revealed that vitamin D sufficiency (serum 25-OH-D >75 nmol/L) coincided with lower circulating levels of 3-methylhistidine, cystine, S-methylcysteine, uric acid, and two lysophosphatidylcholines 7 days after treatment. Rapid correction of VDD was associated with indicators of lower oxidative stress, inflammation, and muscle protein turn-over that may contribute clinical benefits in high-risk critically ill children.
(Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

English

Publisher: Pergamon Country of Publication: England NLM ID: 9015483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1220 (Electronic) Linking ISSN: 09600760 NLM ISO Abbreviation: J Steroid Biochem Mol Biol Subsets: MEDLINE

Vitamin D Deficiency*/drug therapy , Vitamin D Deficiency*/blood , Vitamin D Deficiency*/metabolism , Vitamin D Deficiency*/diet therapy , Cholecalciferol*/administration & dosage , Cholecalciferol*/therapeutic use , Cholecalciferol*/blood , Vitamins*/administration & dosage , Enteral Nutrition*, Humans ; Critical Illness/therapy ; Female ; Male ; Child ; Child, Preschool ; Retrospective Studies ; Metabolomics ; Infant ; Precision Medicine ; Adolescent ; Intensive Care Units, Pediatric

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