Acute effects of single vs. combinatory inhaled β2-agonists Salbutamol and Formoterol on time trial performance, lung function, metabolic and endocrine variables

Abstract

Background: High prevalence rates of β2-agonists amongst 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 β2-agonists and its underlying molecular basis are scarce. Methods: To investigate single vs. combinatory effects of the nonprohibited short-acting β2-agonists salbutamol (SAL) and long-acting formoterol (FOR), 24 competitive endurance athletes (12f/12m) participated in a double-blinded balanced 4-way block cross-over trial to evaluate the potential performance-enhancement of SAL, FOR, and SAL+FOR compared to placebo (PLA). Measurements included skeletal muscle gene and protein expression of nuclear NR4A receptors, endocrine regulation, urinary and serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing as well as the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected Pre-, Post-, 3h Post-, and 24h Post TT. Results: Mean power output during TT was not different between study arms. Treatment effects regarding lung function, echocardiographic and metabolic variables were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Muscle and microarray analysis did not show any treatment effect on NR4A protein and NR4A1/NR4A3 gene expression, whereas a whole group treatment effect was calculated for NR4A2 and further target genes in energy metabolism with strongest effect by SAL+FOR. Noradrenaline, adrenaline, insulin-like growth factor, and transforming growth factor-β concentrations in blood were not affected by treatment or sex, whereas follicle-stimulating hormone (3h Post-Post TT), luteinizing hormone (3h Post-Pre TT), and insulin (Post-Pre TT) concentrations showed a treatment effect at different time points. Conclusion: We did not find an endurance performance-enhancing effect for SAL, FOR, or SAL+FOR within the permitted dosages compared to PLA. An acute effect on lung and cardiac function as well as endocrine and metabolic variables was observed without clinically relevant side effects and presumably without impact on endurance performance in healthy participants. However, the impact of chronically applied β2-agonists on performance in healthy athletes and sex-specific thresholds for daily β2-agonists’ doses have still to be determined.