Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables.

Anti-doping Beta 2 agonists Detection methods Muscle metabolism Performance-enhancing methods Sex-specific thresholds

Journal

Sports medicine - open
ISSN: 2199-1170
Titre abrégé: Sports Med Open
Pays: Switzerland
ID NLM: 101662568

Informations de publication

Date de publication:
28 Aug 2023
Historique:
received: 12 03 2023
accepted: 17 08 2023
medline: 29 8 2023
pubmed: 29 8 2023
entrez: 28 8 2023
Statut: epublish

Résumé

High prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce. In total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT. Mean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post-Post-TT), luteinizing hormone (3 h Post-Pre-TT) and insulin (Post-Pre-TT) concentrations showed a treatment effect (all p < 0.05). No endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined. Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

Sections du résumé

BACKGROUND BACKGROUND
High prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.
METHODS METHODS
In total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.
RESULTS RESULTS
Mean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post-Post-TT), luteinizing hormone (3 h Post-Pre-TT) and insulin (Post-Pre-TT) concentrations showed a treatment effect (all p < 0.05).
CONCLUSIONS CONCLUSIONS
No endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.
TRIAL REGISTRATION BACKGROUND
Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

Identifiants

pubmed: 37640958
doi: 10.1186/s40798-023-00630-3
pii: 10.1186/s40798-023-00630-3
pmc: PMC10462601
doi:

Banques de données

DRKS
['DRKS00010574']

Types de publication

Journal Article

Langues

eng

Pagination

79

Subventions

Organisme : World Anti-Doping Agency
ID : 15C13MZ

Informations de copyright

© 2023. Springer Nature Switzerland AG.

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Auteurs

Daniel A Bizjak (DA)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany. daniel.bizjak@uniklinik-ulm.de.

Dorle Nussbaumer (D)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Kay Winkert (K)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Gunnar Treff (G)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.
Institute of Sports Medicine, Paracelsus Medical University Salzburg, 5020, Salzburg, Austria.

Kensuke Takabajashi (K)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Lennart Mentz (L)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Franziska Schober (F)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Jasmine-Lèonike Buhl (JL)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Lucas John (L)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Jens Dreyhaupt (J)

Institute of Epidemiology and Medical Biometry, Ulm University, 89075, Ulm, Germany.

Luise Steeb (L)

Institute of Epidemiology and Medical Biometry, Ulm University, 89075, Ulm, Germany.

Lukas C Harps (LC)

Pharmaceutical Analysis and Metabolism, Institute of Pharmacy, Freie Universität Berlin, 14195, Berlin, Germany.

Maria K Parr (MK)

Pharmaceutical Analysis and Metabolism, Institute of Pharmacy, Freie Universität Berlin, 14195, Berlin, Germany.

Patrick Diel (P)

Institute of Cardiovascular Research and Sports Medicine, Molecular and Cellular Sports Medicine, German Sport University Cologne, 50933, Cologne, Germany.

Martina Zügel (M)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Jürgen M Steinacker (JM)

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Classifications MeSH