Tuesday, May 22, 2018

β2-Agonists Build Muscle: Low Dose Terbutaline Adds 1kg (DXA) in 4 Weeks - With and Without Resistance Training

Who would have thought that? Asthma-sprays probably beat the crap out of good old clenbuterol tabs when it comes to building muscle - even if you don't train!
Have you ever wondered why so many poor athletes suffer from asthma? Well, if you read my old article about the effects of clenbuterol on myostatin it may long have dawned on you that this could be due to the muscle-building effects of β2-agonists - doping on prescription, so to say.

A couple of days ago, a group of Danish researchers confirmed your suspicions. They'd investigated if inhaled beta2‐agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men.
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In the corresponding 4-week RCT, sixty‐seven participants completed subjects received what was not even a "therapeutic" dosage (daily terbutaline, 8×0.5 mg) or placebo treatment without concurrent training (habitual; n=23), with resistance (n=23) or endurance (n=21) training three times weekly (Jessen 2018).
  • Participants in the endurance training group performed a high-intensity training program three times weekly on indoor spinning bikes. All training sessions were supervised by an instructor and consisted of 10 min warm-up followed by three blocks of exercise at ~85% of maximum heart rate for 10 min with 30 s of all-out sprinting at the end of each 10-min block.
  • Participants in the resistance training group performed a full-body programme three times weekly. All training sessions were supervised by an instructor and consisted of eight exercises until failure. Resistance was adjusted continually so failure occurred at ~10-12 repetitions.

    The training program was progressive, as each exercise consisted of two sets in the first week, three sets in the second and third week, and four sets in the fourth week. The training program consisted of leg press, bench press, knee extensions, military press, lunges, lat pulldowns, laying leg curl, and low row. Each set was separated by two minutes recovery.
  • Participants in the habitual group did not perform any specific training, but were habitually active in some cases, such as bicycle transportation to and from work, soccer matches, or light running. All participants were physically active less than 4 h weekly.
Before and after the interventions, participant's body composition was determined by dual‐energy X‐ray absorptiometry, and resting metabolic rate and substrate oxidation by indirect calorimetry.
Serum concentrations of terbutaline after oral administration of 10 mg and inhaled administration of 4 mg in 12 healthy trained men (Dyreborg 2016).
Inhalation may be the preferable method (compared to oral): As Jessen et al. point out, their study is the first of the handful of studies in which beta2-agonists have been shown to be potent anabolic agents in humans that used inhaled vs. orally ingested beta2-agonists - and that despite the fact that inhaled product have a higher systemic bioavailability as compared to oral ingestion(Dyreborg 2016).

Wrt both doping and side effects, it is also worth remembering that the study at hand proves that the dosage one needs to see (at least in the short term) significant results "was more than four times lower than the oral doses administered by Hostrup et al." (Jessen 2018)
The results in Figure 1 speak for themselves: While 'doing cardio' stopped the muscle gains in its tracks, both the resistance training and the sedentary groups gained ~1kg of lean body mass. In that, the scientists found no effects on metabolic rate, fat oxidation or body fat -- "[t]his was unexpected, as oral treatment with terbutaline has been shown to reduce fat mass16, and other beta2-agonists did increase fat oxidation acutely" (Jessen 2018).
Figure 1: Changes in lean mass (kg, left) and body fat percentage (right) after 4 weeks on only "near‐therapeutic" dosages of the beta-2-agonist terbutaline (8×0.5 mg) | DXA data (Jessen. 2018).
Overall impressive results, but still... we should not forget that we are talking about young healthy men with 2-5 h physical activity per week, and an average maximal oxygen consumption (VO2max) of 40-60 ml/min/kg - that's not exactly what you'd see in pro-athletes... accordingly, future studies won't just have to test the effects of higher dosages of terbutaline, but also if "real" athletes benefit to a similar extent. I guess, in this context, it is worth highlighting, again, that ...
"[...] the dose administered in the present study is higher than that normally prescribed to asthmatics, the dose is within the limit of what many elite athletes may use in association with training sessions as prophylactic treatment" (Jessen 2018).
Accordingly, the authors of the study at hand are right to point out that "present study should be a point of caution for clinicians who are treating elite athletes as terbutaline inhalation in doses of 4 mg, and presumably above, may potentiate training adaptations to resistance training" (Jessen 2018) - I guess none of the athletes would mind, though?!
If you look at the individual gainz, resistance training does no longer seem so useless as the non-significant inter-group difference in gains would suggest - does it (Jessen 2018)?
Mechanism = myostatin inhibition!? As I've discussed in the previously cited article about the anti-myostatin effects of clenbuterol beta-2-agonists may work by loosening the muscle-building brakes. Whether that was the case for terbutaline in the study at hand cannot be said in the absence of corresponding bio-assays. This, as well as possible desensitization effects, will have to be investigated in future studies.

Against that background, it is not really surprising that they work their performance-enhancing magic only in strength athletes, in endurance athletes, where they are commonly abused, they even seem to impair the intended training effects (Hostrup 2018) | Comment on Facebook!
  • Dyreborg, Anders, et al. "Pharmacokinetics of oral and inhaled terbutaline after exercise in trained men." Frontiers in pharmacology 7 (2016): 150.
  • Jessen, S. , Onslev, J. , Lemminger, A. , Backer, V. , Bangsbo, J. and Hostrup, M. (2018), "Hypertrophic effect of inhaled beta2‐agonist with and without concurrent exercise training: a randomized controlled trial." Scand J Med Sci Sports. Accepted Author Manuscript. doi:10.1111/sms.13221
  • Hostrup, Morten, et al. "Chronic β2‐adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men." The Journal of physiology 596.2 (2018): 231-252.