Metabolomic Profiling of Recombinant Erythropoietin (rHuEpo) in Trained Caucasian Athletes

Giscard Lima, Jonathan Shurlock, Guan Wang, Antonia Karanikolou, Shaun Sutehall, Yannis P. Pitsiladis*, Angelo D'alessandro

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

2 Citations (Scopus)

Abstract

Objective: Recombinant human erythropoietin (rHuEpo) is prohibited by the World Anti-Doping Agency but remains the drug of choice for many cheating athletes wishing to evade detection using current methods. The aim of this study was to identify a robust metabolomics signature of rHuEpo using an untargeted approach in blood (plasma and serum) and urine.

Design: Longitudinal study.

Setting: University of Glasgow.

Participants: Eighteen male participants regularly engaged in predominantly endurance-based activities, such as running, cycling, swimming, triathlon, and team sports, were recruited.

Interventions: Each participant received 50 IU·kg-1 body mass of rHuEpo subcutaneously every 2 days for 4 weeks. Samples were collected at baseline, during rHuEpo administration (over 4 weeks) and after rHuEpo administration (week 7-10). The samples were analyzed using hydrophilic interaction liquid chromatography mass spectrometry.

Main Outcome Measures: Significant metabolic signatures of rHuEpo administration were identified in all biofluids tested in this study.

Results: Regarding metabolomics data, 488 plasma metabolites, 694 serum metabolites, and 1628 urinary metabolites were identified. Reproducible signatures of rHuEpo administration across all biofluids included alterations of pyrimidine metabolism (orotate and dihydroorotate) and acyl-carnitines (palmitoyl-carnitine and elaidic carnitine), metabolic pathways that are associated with erythropoiesis or erythrocyte membrane function, respectively.

Conclusions: Preliminary metabolic signatures of rHuEpo administration were identified. Future studies will be required to validate these encouraging results in independent cohorts and with orthogonal techniques, such as integration of our data with signatures derived from other "omics"analyses of rHuEpo administration (eg, transcriptomics).

Original languageEnglish
Pages (from-to)E123-E134
Number of pages12
JournalClinical Journal of Sport Medicine
Volume33
Issue number5
DOIs
Publication statusPublished - Sept 2023

Scopus Subject Areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

User-Defined Keywords

  • anti-doping
  • mass spectrometry
  • metabolic signatures
  • metabolomics
  • plasma
  • rHuEpo
  • serum
  • urine

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