Inhaled beta₂-adrenoceptor agonists (beta₂-agonists) are used extensively in the treatment of asthma and exercise-induced bronchoconstriction, which is highly prevalent among elite athletes. Consequently, elite athletes have a high use of beta₂-agonists. Because of rising suspicions of performance enhancing effects, restrictions toward the use of beta₂-agonists were introduced in the
early 1970’s and still remain today. While the scientific basis for the performance enhancing effects with acute high-dose inhaled beta₂-agonists is well-established, limited knowledge exists on the effects of chronic administration of beta₂-agonists within the limits of the current anti-doping regulations. Specifically, there is reason to believe that beta₂-agonists can increase lean mass and sprinting ability in humans, but at present this notion is largely based on data from rodents. In the present thesis, three randomized, double-blinded, placebo controlled intervention studies were conducted to evaluate the potential of beta₂-agonists to induce increases in lean mass in humans and to evaluate the effects on exercise performance.
In Study I, 26 moderately trained, healthy, male participants (maximal oxygen consumption (V̇ O_2max): ≈50 mL/min/kg bw) received either placebo (n=13) or oral salbutamol (n=13) daily and completed an 11-week resistance training intervention (3 sessions weekly). Before and after the intervention, we collected a muscle biopsy from m. vastus lateralis and evaluated 10-s maximal sprinting ability on a bike ergometer and isometric and dynamic maximal torque of the quadriceps muscle. In Study II, 67 moderately trained male participants (V̇O_2max: ≈50 mL/min/kg bw) received either placebo (n=29) or inhaled terbutaline (4 mg once daily; n=38) for 4 weeks. Participants were additionally allocated to one of three interventions, where they either a) maintained their habitual physical activity lifestyle (“no structured training; n=23), b) performed endurance training on indoor spinning bikes three times weekly (“endurance training”; n=21), or c) performed whole-body resistance training three times weekly (“resistance training”; n=23). Before and after the intervention, we assessed lean mass by dual-energy X-ray absorptiometry (DXA), V̇ O_2max, and 30-s maximal sprinting ability. In Study III, 61 well-trained, healthy participants (31 male, V̇ O_2max: ≈60 mL/min/kg/bw; 30 female, V̇ O_2max: ≈55 mL/min/kg bw) received either placebo (n=20), inhaled formoterol (24 μg twice daily; n=21), or inhaled terbutaline (2 mg twice daily; n=20) for 6 weeks. Participants did not complete a training intervention but maintained their own high volume of
training. Before and after the intervention, as well as every second week, we assessed lean mass by DXA scanning, quadriceps isometric maximal contraction torque, V̇ O_2max, and sprinting ability.
In Study I we observed that high-dose oral beta₂-agonist administration during an 11-week resistance training intervention increased muscle fiber cross sectional area more than placebo, and that this was preferentially related to increased hypertrophy of myosin heavy chain IIa fibers. However, there were
no improvements with salbutamol in isometric and dynamic muscle strength of the quadriceps muscle compared to placebo, and only mean power output was augmented with salbutamol during maximal sprinting whereas peak power output was unchanged. In Study II, we observed that anabolic effects are also achievable with high-dose inhalation of beta₂-agonist terbutaline in a dose that is permitted by current anti-doping regulations with a therapeutic use exemption. In addition, the anabolic effect of terbutaline was evident in the “resistance training” intervention – in line with the observations from Study I – but also in the “no structured training” intervention. However, in the “endurance training” intervention, the anabolic effect of terbutaline was blunted. Lastly, inhaled terbutaline had no effect on anaerobic sprinting ability. In Study III, we observed an anabolic effect of twice-daily beta₂-agonist inhalation of both formoterol and terbutaline, respectively, although less so than with the once-daily administration regimen of terbutaline employed in Study II. However, once again there were no apparent performance enhancements on muscle strength or anaerobic sprinting ability. Conversely, formoterol lowered V̇ O_2max and both formoterol and terbutaline decreased markers of aerobic exercise performance.
In conclusion, chronic beta₂-agonist administration in humans is anabolic and this effect is achievable with inhalation within doses permitted by the current anti-doping regulations. The effects of beta₂-agonists on lean mass appear related to a drug class effect as in the present thesis beta₂-agonists salbutamol, formoterol, and terbutaline all increased lean mass. Despite increasing lean mass, beta₂-agonists do not appear to improve muscle strength or anaerobic exercise performance in healthy individuals. On the contrary, chronic beta₂-agonist administration may in fact be detrimental to aerobic exercise performance. These results indicate that within the current anti-doping regulations, there is very limited potential to enhance exercise performance with chronic beta₂-agonist treatment.