A role for metabolomics in the antidoping toolbox?

Abstract

Evidence of the continuous rise of novel doping agents and novel doping strategies calls for the development of more accurate multi‐target screening methods. Direct multi‐target screening approaches are restricted to the targeted substances and their turnover. The development of effective “indirect” screening methods requires a priori a deep understanding of the metabolism of the substance. The biological passport has been demonstrated to be very effective, but it is limited to about 20 indirect parameters. The standard antidoping analytical methods are hence targeted and do not aim directly to identify unknown substances. Also, the detection of doping agents is limited by the excretion of the substance. This study considers metabolomics for the screening of performance enhancing hormone abuse by athletes, based on the following pieces of evidence: (1) hormones have a strong influence on human metabolism, changing several parameters in many tissues, organs, and bio‐fluids; (2) metabolomics has been demonstrated to be a very accurate tool to depict the metabolic status of several organisms, tissues, and for several human diseases, including hormone deficiencies; (3) metabolomics has been demonstrated to be able to distinguish hormone‐treated animals from controls in many species, without the need for a priori knowledge of the metabolism for the specific substance. The literature shows that metabolomics could be an appropriate tool to detect hormone abuse, keeping in mind the strength and the limitation of such an approach.

Applying metabolomics to detect growth hormone administration in athletes: Proof of concept

“…If the validation studies demonstrate a high specificity of the biomarkers for the recGH, metabolomics could be used in a similar manner to the athlete biological passport, to build a metabolomics passport. If the results are rather unspecific, it could be a valuable (and costless) preliminary screening to target “suspect” athletes with more specific tests 20 …”

“…Growth hormone is known to affect metabolism: it is well known for its catabolic effects on lipids, 14,15 the anabolic effects on bones and muscles, 16 but also for several indirect effects on energy metabolism, carbohydrate metabolism, 17 amino‐acid release, and protein turnover 18,19 . Therefore, it can be assumed that metabolomics might be able to spot athletes who have administered recGH from their clean counterparts 20 …”

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

“…The athlete biological passport (ABP) with its steroidal module composed of concentrations and selected ratios of T, EpiT, A, E, 5α‐androstane‐3α,17β‐diol (5αAdiol), and 5β‐androstane‐3α,17β‐diol (5βAdiol) has been shown to be of particular value in identifying atypical alterations in an individual's urinary steroid profile 65 . The ABP's advantage over population‐based reference ranges has been the superior sensitivity of the longitudinal and individual monitoring of the steroid profile especially towards T and T prohormone misuse, enabled by the fact that each athlete is provided with specific and adapted reference ranges 66 .…”

“…Expanding test methods for the detection of GH misuse in sports by means of additional, complementary biomarkers has been desirable but also particularly complex 65 . Employing plasma and urine samples collected from the same microdose administration study as reported by Marchand et al ( vide supra ), 117 Narduzzi et al conducted metabolomics studies yielding a set of 29 features identified at high confidence level that contributed to the identification of three altered metabolic pathways due to the GH administration 122 .…”

Hyphenated high-resolution mass spectrometry—the “all-in-one” device in analytical toxicology?

“…There are two main application fields, one focusing on the change of the endogenous compounds under the influence of drug administration [62,[64][65][66][67][68][69] or sample manipulation [65,[70][71][72][73][74] and one on the use of metabolomics techniques for investigating the metabolism of new drugs, namely of NPS [60,61,75]. Metabolomics could also play a role in doping control, e.g., for detecting hormone abuse considering that hormones have a strong influence on human endogenous metabolism changing several endogenous parameters [76].…”