Mario Thevis's research while affiliated with Deutsche Sporthochschule Köln and other places

Publications (552)

Poster
Depression is a common disorder with a worldwide prevalence of 3.8 %, according to the World Health Organization (WHO). Little is known about the risk factors for the development of depression. However, it seems clear that it is multifactorial and requires a complex interaction of social, psychological, and biological factors. A possible influence...
Article
In 2020, the confirmation of the non-endogenous origin of several pseudo-endogenous steroids by means of isotope ratio mass spectrometry (IRMS) was recommended by the World Anti-Doping Agency (WADA), in addition to previously established target analytes for IRMS in sports drug testing. To date, however, IRMS-based methods validated in accordance wi...
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Bioactive peptides with a molecular mass between 2 and 10 kDa represent an important class of substances banned in elite sports, which has been recognized with an increasing number and variety of substances by anti-doping organizations. Also, the annually renewed list of prohibited substances of the World Anti-Doping Agency (WADA) explicitly mentio...
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Situations of both, intentional as well as inadvertent or accidental doping, necessitate consideration in today’s doping controls, especially in the light of the substantial consequences that athletes are facing in case of so‐called adverse analytical findings. The aim of this study was to investigate, whether a transdermal uptake of doping substan...
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For decades, blood testing has been an integral part of routine doping controls. The breadth of information contained in blood samples has become considerably more accessible for anti-doping purposes over the last 10 years through technological advancements regarding analytical instrumentation as well as enhanced sample collection systems. Particul...
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Background The development of analytical approaches to help reduce the risk of growth hormone (GH) doping is important to fair competition and the health of athletes. However, the reliable detection of GH use remains challenging. The identification of novel biomarkers of GH administration could lead to a better understanding of the physiological re...
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RAD140 is a selective androgen receptor modulator which has been abused in sporting competitions. Its use is prohibited by the World Anti-Doping Agency (WADA) for athletes at all times. In addition to its illicit use, adverse analytical findings of RAD140 in doping control samples might result from other scenarios, e.g., the ingestion of contaminat...
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RATIONALE The synthetic β-adrenoreceptor agonist zilpaterol is legitimately used as an animal feed supplement in selected countries due to its known effects on lipolysis and protein biosynthesis. These pharmacological characteristics of zilpaterol have contributed to its classification as doping agent in sport by the World Anti-Doping Agency. Howev...
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Dried blood spot (DBS) testing allows fast, easy, and minimally invasive collection of microvolumes of blood. In an anti‐doping context, DBS testing has particular relevance for substances prohibited in‐competition only such as ephedrine, which is currently detected by urine analysis, since DBS can add information about the blood drug concentration...
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Rationale: The anabolic steroid 5α-androst-2-en-17-one (2EN) is sold as a prohormone and has been investigated regarding its potential as steroidal aromatase inhibitor. The administration of 2EN was detected in a doping control sample in 2015, and investigations into its metabolism allowed for the identification and characterization of three urina...
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Aim: To compare endocrine and metabolic counterregulation to postprandial hypoglycemia in patients with postbariatric hypoglycemia (PBH) after gastric bypass (GB) vs. surgical and non-surgical controls. Methods: Thirty-two adults (age 42.9±12.8 years, 13% male, BMI 28.2±4.3kg/m2) of 4 matched groups (PBH patients, GB, sleeve gastrectomy [SG] and no...
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Consumption of hemp products is continuously growing, with an expanding scope of applications. Suppliers operate through different distribution channels but the Internet is a major retail platform. Hemp products are prepared from cannabis plants and, therefore, might contain a variety of different natural cannabinoids. According to the regulations...
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Analytics employed in modern doping controls are designed to cover an extensive range of rather diverse classes of substances, all of which are banned in sport according to the list of prohibited substances and methods of doping, resulting from their potential to be performance-enhancing and/or harmful to health. Many of these bioactive substances...
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The anti-estrogen clomiphene is prohibited in sports at all times. Yet, adverse analytical findings (AAFs) have increased since 2011. This is possibly due to improved analytical sensitivity, but also contamination of food of animal origin needs to be taken into consideration as a potential source of drug exposure. For instance, studies with laying...
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Studying the metabolism of prohibited substances is an essential element in anti-doping research in order to facilitate and improve detectability. Whilst pharmacokinetic studies on healthy volunteers are valuable, they are often difficult, not least due to safety reasons and ethical constraints, especially concerning peptidic substances, which must...
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Rationale: Anti-SARS-CoV-2 antibody responses elicited by infection or vaccination vary among individuals and over time. Their knowledge is of particular importance in, amongst others, elite sport. Can dried blood spots serve as a minimally-invasive, low-cost, decentralized tool to monitor the quantitative antibody response and thus represent an al...
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RATIONALE Exhaled Breath (EB) was found to be a promising matrix in the field of sports drug testing due to the non-invasive and non-intrusive sampling procedure, but significant interindividual variations regarding detected drug concentrations have been observed in previous studies. In order to investigate whether the detectability of doping agent...
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Purpose Synthetic cannabinoids (SCs), highly metabolized substances, are rarely found unmodified in urine samples. Urine screening relies on SC metabolite detection, requiring metabolism knowledge. Metabolism data can be acquired via in vitro assays, e.g., human hepatocytes, pooled human liver microsomes (pHLM), cytochrome P450 isoforms and a funga...
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An increasing number of adverse analytical findings (AAFs) in routine doping controls has been suspected and debated to presumably result from intimate contact with bodily fluids (including ejaculate), potentially facilitating the transfer of prohibited substances. More precisely, the possibility of prohibited drugs being present in ejaculate and i...
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Immunopurification of doping control samples is a mandatory necessity in EPO analysis during a Confirmation Procedure; moreover, it has become common practice to also immunopurify samples for the Initial Testing Procedure. Typically used materials (e.g. Stemcell purification plate, MAIIA purification kit) rely on anti-EPO antibodies for purificatio...
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For decades, anabolic androgenic agents have represented the substance class most frequently observed in doping control samples. They comprise synthetic and pseudoendogenous anabolic androgenic steroids and other, mostly non-steroidal compounds with (presumed) positive effects on muscle mass and function. While exogenous substances can easily be de...
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LGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated...
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Context Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. Objective Test the hypothesis that longitudinal profiling of hGH biom...
Chapter
The Prohibited List of the World Anti-Doping Agency (WADA) defines the analytical framework for the anti-doping laboratories by introducing the substances and methods banned in sport context and which shall be incorporated into the analytical test menus in order to comply with the accreditation requirements and to ensure globally harmonized perform...
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Most core areas of anti‐doping research exploit and rely on analytical chemistry, applied to studies aiming at further improving the test methods’ analytical sensitivity, the assays’ comprehensiveness, the interpretation of metabolic profiles and patterns, but also at facilitating the differentiation of natural/endogenous substances from structural...
Article
The misuse of 2‐phenylethylamine (PEA) in sporting competitions is prohibited by the World Anti‐Doping Agency (WADA). As it is endogenously produced, a method is required to differentiate between naturally elevated levels of PEA and the illicit administration of the drug. In 2015, a sulfo‐conjugated metabolite (2‐(2‐hydroxyphenyl)acetamide sulfate...
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Various substances classified by the World Anti-Doping Agency (WADA) as prohibited in sports feature one or more chiral centers. Amongst those, few analytes exist that are so-called threshold substances, for which also enantiomerically pure drugs are available. The commonly employed non-chiral analysis of these compounds does not allow for differen...
Article
Probing for evidence of the administration of prohibited therapeutics, drugs and/or drug candidates as well as the use of methods of doping in doping control samples is a central assignment of anti-doping laboratories. In order to accomplish the desired analytical sensitivity, retrospectivity, and comprehensiveness, a considerable portion of anti-d...
Article
The hunger hormone ghrelin (G) is classified as prohibited substance in professional sport by the World Anti‐Doping Agency (WADA), due to its known growth hormone releasing properties. The endogenous bioactive peptide consists of 28 amino acids with a caprylic acid attached to serine at position 3. Within this study it was aimed to develop methods...
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The testing strategy for the detection of testosterone (T) or T‐prohormones is based on the longitudinal evaluation of urinary steroid concentrations accompanied by subsequent isotope ratio mass spectrometry (IRMS)‐based confirmation of samples showing atypical concentrations or concentration ratios. In recent years, the IRMS methodology focussed m...
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Similar to the general population, elite athletes are exposed to a complex set of environmental factors including chemicals, radiation, but also biological and physical stressors, which constitute an exposome that is, unlike for the general population, subjected to specific scrutiny for athletes due to applicable anti‐doping regulations and associa...
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A fundamental challenge in preventive doping research is the study of metabolic pathways of substances banned in sport. However, the pharmacological predictions obtained by conventional in vitro or in vivo animal studies are occasionally of limited transferability to humans according to an inability of in vitro models to mimic higher‐order system p...
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Lately, the veterinary drug Emidonol® has been discussed as a possible scenario for inadvertent doping in sports. Emidonol® is approved for use in livestock breeding, exhibiting antihypoxic and weak sedative effects. The veterinary drug rapidly dissociates into meldonium, a substance prohibited in sports, and is excreted largely in its unchanged fo...
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Rationale: Chlorphenesin is an approved biocide frequently used in cosmetics, and its carbamate ester is an approved skeletal muscle relaxant in certain countries for the treatment of discomfort related to skeletal muscle trauma and inflammation. A major urinary metabolite is 4-chlorophenoxy acetic acid (4-CPA), also known as para-chlorophenoxyace...
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Little information on the human metabolism and urinary elimination of hydrafinil (9‐fluorenol) exists. In order to support preventive anti‐doping activities concerning compounds such as hydrafinil, a pilot elimination study was conducted with three healthy male volunteers receiving a single oral dose of 50 mg of hydrafinil. Urine samples were colle...
Article
The selective oestrogen receptor modulator (SERM) clomiphene is therapeutically used to induce ovulation. While prohibited as a doping agent in sports, it is frequently detected in sports drug testing urine samples. Few reports exist on clomiphene’s (illicit) use in the farming industry to increase the egg production rate of laying hens, which crea...
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In order to detect the misuse of testosterone (T) or boldenone (Bo) in doping control analysis, the confirmation of atypical findings employing the determination of carbon isotope ratios (CIR) is mandatory for issuing adverse analytical findings. Elevated concentrations of T (or elevated T/epitestosterone ratios) may result from confounding factors...
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In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). F...
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In order to detect the misuse of testosterone (T), urinary steroid concentrations and concentration ratios are quantified and monitored in a longitudinal manner to enable the identification of samples exhibiting atypical test results. These suspicious samples are then forwarded to isotope ratio mass spectrometry (IRMS)–based methods for confirmatio...
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The exogenous anabolic‐androgenic steroid (AAS) stanozolol stays one of the most detected substances in professional sports. Its detection is a fundamental part of doping analysis and the analysis of this steroid has been intensively investigated for a long time. This contribution to the detection of stanozolol doping describes for the first time t...
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The human microsomal cytochrome P450 enzyme CYP46A1 plays a crucial role in cholesterol elimination from the brain. It performs a 24-hydroxylation of cholesterol and is of outstanding significance for memory and cognition. This study demonstrates the catalytic activity of human CYP46A1 towards an anabolic androgenic steroid, oral turinabol (dehydro...
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For decades, the class of anabolic androgenic steroids has represented the most frequently detected doping agents in athletes’ urine samples. Roughly 50% of all adverse analytical findings per year can be attributed to anabolic androgenic steroids, of which about 2/3 are synthetic exogenous steroids, where a qualitative analytical approach is suffi...
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The increasing importance to determine bioactive peptide hormones such as insulin, its synthetic analogs, and C-peptide in urine samples represents an analytical challenge. The physiological concentrations of insulin in urine are commonly found at sub-ng/mL levels and thus represent a complex analytical task. C-peptide concentrations, on the other...
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Objective To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS). Methods Sixty-nine pwMS (...
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Serological test methods to detect anti‐SARS‐CoV‐2 antibodies represent a major measure to manage the pandemic caused by the coronavirus disease 2019 (COVID‐19). In this communication, test results obtained from minimal‐invasively collected dried blood spot (DBS) specimens, which can be sampled ‘at home’ without the need of medically trained person...
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Isopropylnorsynephrine (isopropyloctopamine, deterenol, 4‐(1‐hydroxy‐2‐(isopropylamino)ethyl)phenol), a beta‐selective and direct‐acting adrenergic agonist, has been reported in the past as declared as well as non‐declared ingredient of dietary supplements. The proven biological activity and the structural similarity of isopropylnorsynephrine to su...
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Capillary blood sampled as dried blood spot (DBS) has shown substantial potential as test matrix in sports drug testing in various different settings, enabling the analysis of numerous different drugs and/or their respective metabolites. In addition to established beneficial aspects of DBS specimens in general (such as e.g. the minimally invasive a...
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Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-...
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Analytical methods to determine the potential misuse of the ghrelin mimetics capromorelin (CP-424,391), macimorelin (macrilen, EP-01572), and tabimorelin (NN703) in sports were developed. Therefore, different extraction strategies, i.e. solid-phase extraction, protein precipitation, as well as a 'dilute-and-inject' approach, from urine and EDTA-pla...
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Erythropoietin (EPO) is a hormone, which stimulates the production of red blood cells. Due to its performance enhancing effect, it is prohibited by the World Anti‐Doping Agency (WADA). In order to reduce the detection window of EPO‐doping, athletes have been applying low doses of recombinant EPO (e.g. < 10 IU/kg body weight, daily or every second d...
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The kynurenine (KYN) pathway gains growing research interest concerning the genesis, progression and therapy of solid tumors. Previous studies showed exercise-induced effects on metabolite levels along the KYN pathway. Modulations of the KYN pathway might be involved in the positive impact of exercise on prostate cancer progression and mortality. T...
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The steroid profile, that is, the urinary concentrations and concentration ratios of selected steroids, is used in sports drug testing to detect the misuse of endogenous steroids such as testosterone. Since several years, not only population‐based thresholds are applied but also the steroid profile is monitored via the Athlete Biological Passport w...
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The discovery of the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system as a programmable, RNA-guided endonuclease has revolutionized the utilization of gene technology. Because it enables the precise modification of any desired DNA sequence and surpasses all hitherto existing alternatives for gene editi...
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Due to the current demands in the fight against manipulation of blood and blood components, commonly referred to as “blood doping” in sports drug testing, specific and sensitive detection methods enabling the detection of prohibited substances and methods of doping are required. Similar to illicit blood transfusions, erythropoiesis stimulating agen...
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The consumption of the offal of noncastrated pigs can lead to the excretion of 19‐norandrosterone (NorA) in urine of humans. In doping control, GC/C/IRMS is the method of choice to differentiate between an endogenous or exogenous origin of urinary NorA. In some cases, after the consumption of wild boar offal, the δ¹³C values of urinary NorA fulfill...
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Analytical chemistry‐based research in sports drug testing has been a dynamic endeavor for several decades, with technology‐driven innovations continuously contributing to significant improvements in various regards including analytical sensitivity, comprehensiveness of target analytes, differentiation of natural/endogenous substances from structur...
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According to the World Anti‐Doping Agency (WADA) regulations, cannabinoids use is prohibited in competition except for cannabidiol (CBD) use. For an adverse analytical finding (AAF) in doping control, cannabinoid misuse is based on identification of the pharmacologically inactive metabolite 11‐nor‐delta‐9‐carboxy‐tetrahydrocannabinol‐9‐carboxylic a...
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The possibility of nutritional supplement contamination with minute amounts of the selective androgen receptor modulator (SARM) ostarine has become a major concern for athletes and result managing authorities. In case of an adverse analytical finding (AAF), affected athletes need to provide conclusive information, demonstrating that the test result...
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Cytokines of the transforming growth factor beta (TGF‐β) superfamily such as myostatin and activin A are considered as key regulators of skeletal muscle mass. In vivo, their activity is controlled by different binding proteins such as follistatin (FST), whose interaction with the circulating growth factors prevents activation of the activin type II...
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RATIONALE Exhaled breath (EB) has been demonstrated to be a promising alternative matrix in sports drug testing due to its non‐invasive and non‐intrusive nature compared with urine and blood collection protocols. In this study, a pilot‐test system was employed to create drug‐containing aerosols simulating EB in support of the analytical characteriz...
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In this proof‐of‐concept study, paper spray mass spectrometry was investigated as a high‐throughput and fully automated technique for the initial testing of particularly polar compounds that are prohibited in sports. The technique allows the ionization of analytes from complex sample matrices such as blood and urine when spotted onto a paper strip....
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Early 2020, racehorse doping cases revolved around the hypoxia‐inducible factor (HIF) activator IOX‐2. While the composition of IOX‐2 was known and monitored also in human doping controls since several years, the testing capability of routine sports drug testing methods was revisited concerning this newly surfaced doping agent. IOX‐2 and the analyt...
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A narrative review with an overall aim of indicating the current state of knowledge and the relevance concerning food and supplement contamination and/or adulteration with doping agents and the respective implications for sports drug testing is presented. The identification of a doping agent (or its metabolite) in sports drug testing samples consti...
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Clenbuterol is a β2‐agonist prescribed for asthmatic patients in some countries. Based on its anabolic and lipolytic effects observed in studies on rodents and in livestock destined for food production, clenbuterol is abused by bodybuilders and athletes seeking leanness. Urinary clenbuterol analysis is part of routine doping analysis. However, the...
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PurposeDue to distinct immuno- and neuro-modulatory properties, growing research interest focuses on exercise-induced alterations of the kynurenine (KYN) pathway in healthy and clinical populations. To date, knowledge about the impact of different acute strength exercise modalities on the KYN pathway is scarce. Therefore, we investigated the acute...
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Trenbolone is a synthetic anabolic-androgenic steroid, which has been misused for performance enhancement in sports. The detection of trenbolone doping in routine sports drug testing programs is complex as methods utilizing gas chromatography/mass spectrometry are complicated by unspecific derivatization products and artifacts, and liquid chromatog...