Lean Mass Gains, Cardiac Remodeling, and Muscle Oxidative Changes With High-Dose Salbutamol During Resistance Training: A Randomized Controlled Trial.

Misuse of beta2-agonists to promote leanness is increasingly reported among young men undertaking resistance training. However, preclinical models demonstrate adverse cardiac remodeling with high-dose beta2-agonist. We investigated effects of prolonged supratherapeutic treatment with salbutamol on body composition, cardiac morphology and function, and muscle oxidative phenotyping during resistance training. In a double-blind, randomized trial, 30 healthy, trained men (age 23 ± 2 years, mean ± SD) received oral salbutamol 16 mg/day (SAL) or placebo (PLA) during an 11-week, supervised full-body resistance training program (3 sessions/week). Assessments at baseline and follow-up included dual-energy X-ray absorptiometry, echocardiography, cardiac magnetic resonance imaging (CMR), cardiopulmonary exercise testing (CPET), and vastus lateralis biopsies. The primary outcome was change in lean mass. Twenty-six participants completed the study. Lean mass increased 1.8 kg more in SAL than PLA (95% CI 0.5-3.1; p < 0.01). CMR showed no between-group differences in cardiac structure or function, including left ventricular mass. Echocardiography showed increased posterior, septal, and relative wall thickness in SAL compared to PLA (p < 0.01). Time to exhaustion during CPET did not change in SAL but increased by 7% in PLA (p < 0.01). Muscle capillary density and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activity decreased in SAL (all p < 0.01), with no such changes in PLA. While supratherapeutic salbutamol augmented lean mass gains during resistance training, it concurrently impaired muscle oxidative capacity, attenuated cardiopulmonary fitness improvements, and showed echocardiographic signals consistent with increased wall thickness. These risk-benefit trade-offs inform illicit users of potential harms and support restrictions on supratherapeutic salbutamol in sports.