期刊
METABOLITES
卷 12, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/metabo12030207
关键词
sex; metabolomics; women; vitamin D; acylcarnitine; bioenergesis
资金
- National Institutes of Health [R01 GM115774]
- European Society for Clinical Nutrition and Metabolism (ESPEN)
- Austrian National Bank (Jubilaumsfonds) [14143]
- Medizinischen Universitat Graz
- Fresenius Kabi (Germany)
The metabolomics study revealed sex-specific differences in the metabolic response to high-dose oral vitamin D-3 intervention among critically ill patients. Women showed lower absorption of vitamin D-3 despite receiving higher doses, with distinct metabolite associations in females and males. These sex-specific pharmacometabolomics differences may have implications for personalized medicine.
Pharmacological interventions are essential for the treatment and management of critical illness. Although women comprise a large proportion of the critically ill, sex-specific pharmacological properties are poorly described in critical care. The sex-specific effects of vitamin D-3 treatment in the critically ill are not known. Therefore, we performed a metabolomics cohort study with 1215 plasma samples from 428 patients from the VITdAL-ICU trial to study sex-specific differences in the metabolic response to critical illness following high-dose oral vitamin D-3 intervention. In women, despite the dose of vitamin D-3 being higher, pharmacokinetics demonstrated a lower extent of vitamin D-3 absorption compared to men. Metabolic response to high-dose oral vitamin D-3 is sex-specific. Sex-stratified individual metabolite associations with elevations in 25(OH)D following intervention showed female-specific positive associations in long-chain acylcarnitines and male-specific positive associations in free fatty acids. In subjects who responded to vitamin D-3 intervention, significant negative associations were observed in short-chain acylcarnitines and branched chain amino acid metabolites in women as compared to men. Acylcarnitines and branched chain amino acids are reflective of fatty acid B oxidation, and bioenergesis may represent notable metabolic signatures of the sex-specific response to vitamin D. Demonstrating sex-specific pharmacometabolomics differences following intervention is an important movement towards the understanding of personalized medicine.
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