The ergogenic effect of formoterol and terbutaline

Code: 20C20MH

The updated 2019 Global Initiative for Asthma (GINA) guidelines, now recommending inhaled corticosteroid (ICS) in combination with the long-acting beta2-agonist (LABA) formoterol as preferred controller step 1 & 2 for asthma-related symptoms in adults and adolescences. Therefore, the use of formoterol in combination with an ICS will surely increase among athletes, given the high prevalence of asthma and exercise-induced bronchoconstriction (EIB) in the athletic population. Given the potential performance enhancing effects of beta2-agonists, WADA has imposed a urine threshold for formoterol of 40 ng/ml with a maximum dose of 54 µg over 24 hours. However, inhalation of 54 µg formoterol has been shown to enhance muscle strength and sprint performance. Thus, it is necessary to re-evaluated the current maximum doses especially considering that more athletes will receive formoterol for treating asthma and EIB. Nonetheless, no studies have examined whether daily inhalation of formoterol in therapeutic doses exert anabolic actions or can cause potentil adverse in trained males and females. The project consists of two studies. Study I will investigate the chronic effect of inhaled formoterol on exercise performance and body composition in therapeutic doses in males and females. Study II will examine the pharmacokinetic profile of inhaled formoterol with or without budesonide and oral ingestion of formoterol in therapeutic doses in males and females.

Main findings

Use of the inhaled beta2-agonist formoterol is increasing among athletes due to updated asthma management guidelines. However, the acute and long-term effects of formoterol on exercise performance and muscle function in trained individuals remain inadequately explored. In a series of randomized placebo-controlled trials, we explored these effects in endurance-trained individuals. The first study investigated the effect of therapeutic doses of inhaled formoterol (24 μg twice daily for 6 weeks) versus placebo in 51 endurance-trained men and women. Participants were assessed for aerobic capacity, body composition, muscle mitochondrial function, and cardiac parameters. Results showed that formoterol increased lean body mass but significantly impaired maximal oxygen uptake (V̇O2max), incremental exercise performance, and muscle mitochondrial oxidative capacity. No changes were observed in cardiac function or blood volume.

The second study examined the acute effects of a high, one-off inhaled dose of formoterol (54 μg) versus placebo in 21 elite male cyclists. After administration, cyclists performed sprints and a 4-minute all-out cycling test. Formoterol led to a slight enhancement of sprint and short intense exercise performance. The third study compared the acute effect of inhaled formoterol (with and without budesonide) and oral formoterol versus placebo in 20 well-trained males and females. Only the combination of inhaled formoterol and budesonide produced a small improvement in sprint performance and time to peak twitch force, with no effect on isometric muscle strength or 4-minute time trial performance. Collectively, these studies indicate that while inhaled formoterol may acutely enhance sprint performance, chronic use at therapeutic doses can impair aerobic capacity in endurance athletes, likely through negative effects on muscle mitochondrial function. The combination with budesonide may offer minor sprint benefits, but further research is needed on long-term use in athletes.