Anabolic and lipolytic actions of beta₂‐agonists in humans and antidoping challenges

Abstract

Inhaled beta 2 -adrenoceptor agonists (beta 2 -agonists) are among the most used substances in competitive sports. The 2020 Prohibited List issued by the World Anti-Doping Agency restricts use of all selective and non-selective beta 2 -agonists in-and out-of competition with few exemptions. Formoterol, salbutamol, and salmeterol are allowed by inhalation within defined dosing limits. These restrictions are in place because supratherapeutic use of beta 2 -agonist has the potential to be anabolic and to enhance performance, as well as due to potential side effects. Despite substantial documentation that beta 2 -agonists exert anabolic and lipolytic actions, these actions are not widely recognized. Furthermore, a common misconception is that the inhaled route does not exert these effects. However, given the high relative systemic bioavailability via the inhaled route, inhalation at high doses can also exert anabolic and lipolytic actions. In this review, we highlight the anabolic and lipolytic actions beta 2agonists can exert, regardless of the type of beta 2 -agonist and the route of administration. The doses needed to provide such effects are also associated with adverse effects and would in most cases be detected in routine doping control. Notwithstanding, the beta 2 -agonist regulations are associated with some challenges and given their ability to induce muscle growth and to enhance performance, it is important to continue developing effective detection strategies to prevent potential misuse of beta 2 -agonists while allowing treatment of asthmatic subjects without causing adverse side effects or ergogenic actions. K E Y W O R D Sanabolic, beta agonists, doping, hypertrophy, muscle growth

Risk Associated with the Use of Selected Ingredients in Food Supplements

“…Clenbuterol is placed in the WADA list of doping agents in group S1 – Anabolic Agents [13] . There are known cases of detection of clenbuterol in professional athletes during anti‐doping control [231–235] …”

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

“…A continuously growing body of evidence exists that the aerobic performance does not appear to be acutely affected by the use of β 2 ‐agonists such as terbutaline 126–128 . Conversely, β 2 ‐agonists such as salbutamol and salmeterol can enhance anaerobic performance concerning disciplines such as, for example, sprint 129–131 but not necessarily when used at dosages permitted according to WADA's regulations 132 . These regulations include maximum permitted doses for formoterol, salbutamol, and salmeterol, 10 with corresponding urinary thresholds existing for formoterol and salbutamol, 133 while salmeterol is reported as AAF when exceeding 50% of the MRPL (i.e., 10 ng/ml).…”

Pharmacokinetics of salmeterol and its main metabolite α‐hydroxysalmeterol after acute and chronic dry powder inhalation in exercising endurance‐trained men: Implications for doping control

“…The need for dosing limits of beta 2 -agonists has become increasingly pertinent given the potential performance-enhancing effects when used at high doses. [4][5][6][7][8][9][10][11] For formoterol and salbutamol, [12][13][14][15][16][17][18][19][20] urine thresholds have been in place for years to control for supratherapeutic misuse exceeding the dosing limits. However, as data on urine pharmacokinetics of salmeterol are limited, [21][22][23] no urine threshold has been established for this beta 2 -agonist.…”

“…One such beta 2 ‐agonist is salmeterol, which is allowed by inhalation at therapeutic doses up to 200 μg daily. The need for dosing limits of beta 2 ‐agonists has become increasingly pertinent given the potential performance‐enhancing effects when used at high doses 4–11 . For formoterol and salbutamol, 12–20 urine thresholds have been in place for years to control for supratherapeutic misuse exceeding the dosing limits.…”