Inhaled salbutamol induces leanness in well-trained healthy females but not males during a period of endurance training: a randomised controlled trial

Abstract

Introduction: Many athletes use short-acting inhaled β₂-agonists multiple times weekly during training sessions to prevent exercise-induced bronchoconstriction, but it is unclear if treatment impairs training outcomes. Herein, we investigated performance adaptations in well-trained females and males training with prior inhalation of salbutamol.

Methods: 19 females and 21 males with maximal oxygen uptake (V'_O2max) of 50.5±3.3 and 57.9±4.9 mL·min^-1·kg^-1, respectively, participated in this double-blinded, placebo-controlled, parallel-group study. We randomised participants to placebo or salbutamol inhalation (800-1600 µg·training day^-1) for 6 weeks of combined endurance (1× per week) and high-intensity interval training (2× per week). We assessed participants' body composition, V'_O2max and muscle contractile function, and collected vastus lateralis muscle biopsies.

Results: Salbutamol induced a sex-specific loss of whole-body fat mass (sex×treatment: p=0.048) where only salbutamol-treated females had a fat mass reduction compared to placebo (-0.8 kg at 6 weeks; 95% CI: -0.5 to -1.6; p=0.039). Furthermore, salbutamol-treated females exhibited a repartitioning effect, lowering fat mass while gaining lean mass (p=0.011), which was not apparent for males (p=0.303). Salbutamol negatively impacted V'_O2max in both sexes (treatment main effect: p=0.014) due to a blunted increase in V'_O2max during the initial 4 weeks of the intervention. Quadriceps contractile strength was impaired in salbutamol-treated females (-39 N·m; 95% CI: -61 to -17; p=0.002) compared to placebo at 6 weeks. Muscle electron transport chain complex I-V abundance increased with salbutamol (treatment main effect: p=0.035), while content of SERCAI, β₂-adrenoceptor and desmin remained unchanged.

Conclusion: Inhaled salbutamol appears to be an effective repartitioning agent in females but may impair aerobic and strength-related training outcomes.

FIGURE 1

Experimental overview. a) Study design, b) experimental trial days and c) training days. DXA: dual-energy X-ray absorptiometry; V′_O2max: maximal oxygen uptake; HR_max: maximal heart rate; HIT: high-intensity interval training.

FIGURE 2

Change in body composition during 6 weeks of exercise training with concurrent salbutamol inhalation in moderately trained males (n=21; left panels) and females (n=19; right panels). a) Whole-body fat mass, b) arm fat mass, c) leg fat mass and d) visceral adipose tissue mass. All values are changes relative to baseline. Symbols are means and shaded areas are 95% confidence intervals. p-values in bold denote statistical significance. ^#: between-group difference (p<0.05).

FIGURE 3

Relationship between change in fat mass and lean mass after 6 weeks of exercise training with concurrent salbutamol inhalation in moderately trained males (n=21; left panels) and females (n=19; right panels). Plots on outer edges of panels denote the distributions of data points on the respective axes and were created in R with base density function using Gaussian distribution. Symbols with bold border are means and error bars are 95% confidence intervals.

FIGURE 4

Changes in a) maximum oxygen uptake (V′_O2max) and b) incremental exercise performance during 6 weeks of exercise training with concurrent salbutamol inhalation in moderately trained males (n=21; left panels) and females (n=19; right panels). All values are changes relative to baseline. Symbols are means and shaded areas are 95% confidence intervals. p-values in bold denote statistical significance. ^#: between-group difference (p<0.05).

FIGURE 5

Change in a) maximal voluntary contraction torque and b) voluntary activation level during 6 weeks of exercise training with concurrent salbutamol inhalation in moderately trained males (n=21; left panels) and females (n=19; right panels). All values are changes relative to baseline. Symbols are means and shaded areas are 95% confidence intervals. p-values in bold denote statistical significance. ^#: between-group difference (p<0.05).

FIGURE 6

Change in muscle individual and mean muscle content of a) mitochondrial electron transport chain complexes, and b) SECAI, β₂-adrenoceptor and desmin content after 6 weeks of exercise training with concurrent salbutamol inhalation in moderately trained males (n=21; left panels) and females (n=19; right panels). Bars are means with 95% confidence intervals. B2AR: β₂-adrenoceptor. ^#: between-group difference (p<0.05).