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Effects of Inhaled β2-AR Agonists in Athletes According to the WADA 2025 List: New Insights From a Systematic Review
Luigino Calzetta1, Elena Pistocchini2, Gian Marco Manzetti2
1Unit of Respiratory Clinical Pharmacology, Department of Clinical Science and Translational Medicine, University of Rome "Tor Vergata", Rome, Italy.
Abstract:
This systematic review and meta-analysis (CRD420251006746) investigated the impact of inhaled β2-adrenoceptor (AR) agonists (IBA) with exemption according to the World Anti-Doping Agency (WADA) 2025 list on athletic performance, respiratory, and cardiovascular outcomes. A key subgroup analysis focused on IBA administered within WADA 2025 permitted dose intervals. Findings indicate that IBA significantly improved sprint time by 0.30 s (95% CI 0.52-0.07) overall, and by 0.27 s (95% CI 0.50-0.05) in healthy subjects, with long-acting β2-AR agonists yielding a 0.49 s (95% CI 0.81-0.17) improvement. These sprint time enhancements persisted even at WADA-permitted doses. Blood lactate levels significantly increased by 0.67 mmol/L (95% CI 0.19-1.14) overall and by 0.65 mmol/L (95% CI 0.17-1.14) in healthy subjects, though this effect was not significant at WADA-permitted doses. IBA significantly improved forced expiratory volume in 1 s by 0.19 L (95% CI 0.14-0.23) and forced expiratory flow between 25% and 75% by 0.40 L/s (95% CI 0.24-0.56), with lung function improvements confirmed at WADA-permitted doses. Heart rate significantly increased by 1.40 bpm (95% CI 0.32-2.48). IBA did not influence aerobic performance. When administered within WADA 2025 permitted doses, IBA can provide small but relevant gains in anaerobic performance in healthy individuals, while simultaneously offering therapeutic bronchodilation for athletes with asthma or exercise-induced bronchoconstriction. Dose restrictions are critical to minimize the risk of performance enhancement that exceeds therapeutic intent and to mitigate adverse effects. Further research is pivotal to ensure that anti-doping policies align with health standards and ethical considerations for all athletes.
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