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European Journal of AppliedPhysiology ISSN 1439-6319Volume 113Number 2 Eur J Appl Physiol (2013) 113:411-418DOI 10.1007/s00421-012-2447-0

Acute supra-therapeutic oral terbutalineadministration has no ergogenic effect innon-asthmatic athletes

Anthony M. J. Sanchez, Fabio Borrani,Marie Amélie Le Fur, Anais Le Mieux,Virgile Lecoultre, Guillaume Py,Christophe Gernigon, et al.

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ORIGINAL ARTICLE

Acute supra-therapeutic oral terbutaline administrationhas no ergogenic effect in non-asthmatic athletes

Anthony M. J. Sanchez • Fabio Borrani • Marie Amelie Le Fur •

Anais Le Mieux • Virgile Lecoultre • Guillaume Py •

Christophe Gernigon • Katia Collomp • Robin Candau

Received: 29 February 2012 / Accepted: 16 June 2012 / Published online: 6 July 2012

� Springer-Verlag 2012

Abstract This study aimed to investigate the effects on a

possible improvement in aerobic and anaerobic performance

of oral terbutaline (TER) at a supra-therapeutic dose in 7

healthy competitive male athletes. On day 1, ventilatory

threshold, maximum oxygen uptake ð _VO2 maxÞ and corre-

sponding power output were measured and used to determine

the exercise load on days 2 and 3. On days 2 and 3, 8 mg of

TER or placebo were orally administered in a double-blind

process to athletes who rested for 3 h, and then performed a

battery of tests including a force–velocity exercise test, run-

ning sprint and a maximal endurance cycling test at D50 %

(50 % between VT and _VO2 max). Lactatemia, anaerobic

parameters and endurance performance ( _VO2; _VE and time

until exhaustion) were raised during the corresponding tests.

We found that TER administration did not improve any of the

parameters of aerobic performance (p [ 0.05). In addition,

no change in _VO2 kinetic parameters was found with TER

compared to placebo (p [ 0.05). Moreover, no enhancement

of the force–velocity relationship was observed during sprint

exercises after TER intake (p [ 0.05) and, on the contrary,

maximal strength decreased significantly after TER intake

(p \ 0.05) but maximal power remained unchanged

(p [ 0.05). In conclusion, oral acute administration of TER at

a supra-therapeutic dose seems to be without any relevant

ergogenic effect on anaerobic and aerobic performances in

healthy athletes. However, all participants experienced

adverse side effects such as tremors.

Keywords b2-Agonist � Doping � Force–velocity

relationship � Endurance performance � Anaerobic

performance � Healthy athletes

Introduction

The prevalence of asthma is higher in athletes than in the

general population. b2-adrenergic agonists (b2-agonists)

are the most commonly prescribed medication for

bronchospasm and exercise-induced asthma, affectingCommunicated by Fabio Fischetti.

A. M. J. Sanchez (&) � M. A. Le Fur � A. Le Mieux �G. Py � R. Candau

Faculte des Sciences du Sport, Universite Montpellier

Sud-de-France, 700 avenue du Pic Saint Loup,

34060 Montpellier, France

e-mail: anthony.sanchez@univ-montp1.fr;

anthony.mj.sanchez@gmail.com

A. M. J. Sanchez � M. A. Le Fur � A. Le Mieux � G. Py �R. Candau

INRA, UMR866-Dynamique Musculaire Et Metabolisme,

2 Place Viala, 34060 Montpellier, France

F. Borrani

Department of Sport and Exercise Science,

University of Auckland, Auckland, New Zealand

V. Lecoultre

Department of Physiology, University of Lausanne,

Lausanne, Switzerland

C. Gernigon

Faculty of Sport and Physical Education Sciences, Southern

France University of Montpellier, Laboratory Epsylon,

Montpellier, France

K. Collomp

Laboratoire CIAMS, Universite Paris Sud-Universite Orleans,

Orleans cedex, France

K. Collomp

Departement des Analyses, AFLD, Paris, France

123

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DOI 10.1007/s00421-012-2447-0

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&10–20 % of all athletes (Weiler et al. 1998). b2-agonists

such as salbutamol, fenoterol and terbutaline (TER) have

pharmacological effects on smooth and skeletal muscles

(Tashkin 1995). Consequently, b2-agonists have been

prohibited by the World Anti-Doping Agency’s (WADA)

prohibited list. In 2010, all b2-agonists were prohibited

except salbutamol and salmeterol which were authorized

only by inhalation, and for which a declaration of use was

no longer required from January 2011. In January 2012, the

list prohibited the administration of all b2 agonists with the

exception of salbutamol (maximum 1,600 lg over 24 h),

salmeterol and also formoterol (maximum 36 lg over

24 h) when taken by inhalation. The issue of b2-agonists

will continue to be a focus of WADA’s research activity in

order to ensure that the administration of large doses, or by

systemic routes, of these substances is prevented and pro-

hibited, but that the appropriate care and treatment of

asthmatic athletes is facilitated.

The potential ergogenic effects of b2-agonists in athletes

have been the subject of controversy for decades. Systemic

administration of salbutamol is prohibited by the WADA

because of possible positive effects on the user’s perfor-

mance. Experiments performed in animal models using

chronic b2-agonists intakes at doses 10- to 20-fold higher

than therapeutic doses showed a muscle anabolic effect

(Mounier et al. 2007; Douillard et al. 2011, 2012; Ryall and

Lynch 2008; Tonge et al. 2010). But several toxicological

effects such as alterations of trabecular bone or an

increased heart weight associated with inflammation, focal

myocardial necrosis and fibrosis were also described

(Weiler et al. 1998; Bonnet et al. 2005, 2007).

Although many groups have studied the performance

effects of b2-agonists, few studies have revealed an

increase in endurance performance. Several years ago, it

was found that oral and inhaled administration of salbuta-

mol may improve the time until exhaustion during a con-

stant work test or the final sprint during an endurance

exercise (Collomp et al. 2000; van Baak et al. 2004; Bedi

et al. 1988). However, this ergogenic effect has not been

identified for any b2-agonist other than salbutamol with

inhaled administration (Kindermann 2007). Moreover, no

study has evaluated the effects of oral TER administration

on endurance performance.

Concerning anaerobic performance, an increase in the

maximal power output was found with acute and chronic oral

salbutamol treatments (Sanchez et al. 2012) and with

administration by inhalation (Signorile et al. 1992).

Depending on the muscle group considered, this increase

ranges from about 5–13 % (Collomp et al. 2005; Le Panse

et al. 2005, 2006). Interestingly, during leg extension exer-

cise, increase in peak torque was preferentially obtained for

low speeds of shortening (van Baak et al. 2000). This element

suggests that b2-agonists would have more significant effects

on high-load exercise on cyclo-ergocycle, which requires

low speeds of shortening, than on running sprint which

requires high speeds of shortening. Otherwise, the appear-

ance of acute deleterious effects such as tachycardia and

muscular tremors when participants use b2-agonists is fre-

quently observed (van Baak et al. 2000; Ryall and Lynch

2008). van Baak et al. (2000) concluded that oral salbutamol

appears to be an effective ergogenic aid, but only in non-

asthmatic individuals not experiencing adverse side effects.

Interestingly, TER seems to involve fewer side effects than

the other b2-agonists (Whitsett et al. 1981).

TER is a fast-acting b2-agonist available for both inha-

lation and per os therapeutic administration [used at 0.5 and

5 mg, respectively (Vidal 2011)]. TER combines a rapid

onset of action with a long duration of 12 h and represents a

valuable addition to the treatment of asthmatic patients,

especially those with ongoing symptoms. Due to the rapid

onset and long duration of its action and its fewer side effects

compared to other b2-agonists, this drug may be of benefit to

asthmatic athletes performing in endurance sports both for

the prevention of exercise-induced asthma and as a regular

treatment of chronic asthma in athletes. The problem lies in

the potential benefit of the drug in non-asthmatic athletes. A

threshold has been attributed to salbutamol and salmeterol

urinary concentration but not to TER. It is thus important to

consider the potential effects of this drug on performance.

Indeed, the potential ergogenic effects of TER must be

explored in order to encourage studies on the definition of a

urinary threshold. Larsson et al. (1997) have already found

that inhalation of TER at therapeutic doses that yield sig-

nificant bronchodilatation does not influence physical per-

formance at low temperatures in healthy athletes. But, to our

knowledge, no study has investigated the potential ergogenic

effects of oral TER administration at supra-therapeutic doses

in non-asthmatic competitive athletes. Thus, the aim of this

study was to determine whether an acute supra-therapeutic

TER administration (8 mg) improves aerobic and anaerobic

performance in healthy athletes.

Methods

Subjects

Seven well-trained male competitive athletes (mean ± SD;

age 29 ± 6 years; height 180 ± 5 cm; body mass 74 ± 8;

body mass index 22.8 ± 3.2 kg m-2) volunteered to par-

ticipate in this study after being informed of the nature of,

and the possible disadvantages associated with, the

experiment. These subjects engaged in recreational sports

an average of 10 h/week. The study procedures complied

with the Declaration of Helsinki on human experimentation

and were approved by the local human ethics committee.

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Each participant gave written informed consent before

beginning the tests. The subjects were asked to maintain

their dietary habits throughout the study period, but to

abstain from alcohol and caffeine for a minimum of 24 h

before each laboratory visit to avoid interactions. Partici-

pants were screened with a medical history and physical

examination to exclude those with a history of broncho-

spasm or atopy. Other exclusion criteria were respiratory

tract infection during the previous month, regular tobacco

use, regular use of any medical drug, and recognized

asthma or allergy during the 5 years preceding the study.

Moreover, pulmonary function was tested before the

experiment to ensure that the subjects did not have asthma

or exercise-induced bronchospasm. The highest forced

expiratory volume during 1 s (FEV1) was recorded at rest

in a standing position and after the incremental maximal

test of the preliminary session. None of the subjects

showed a post-exercise fall in FEV1 [10 %.

Drug

In accordance with a double-blind, equilibrated random-

ized crossover study, either 8 mg TER (Bricanyl, UK) or

placebo (sweetener) was administered to each subject 3 h

before the tests. The therapeutic dose in pregnancy is 5 mg

(Vidal 2011; Le Fur et al. 2012). Placebo and TER were

packaged in identical capsules. An independent researcher

was involved and he was the only one to know the order of

the processing. The experimenters questioned the subjects

immediately after the two trials, as to their knowledge of

which of the two treatments they had received first, and

whether they were able to report any difference. The sub-

jects and the experimenters were informed about admin-

istration of the processing only after analysis of the results.

Tests

There were three study days in total. On day 1, all partic-

ipants performed a primary incremental test on a cycl-

oergometer (Monarck 818E, Stockholm, Suede), with no

drug intake, to establish a performance baseline for each

participant and to verify that they satisfied the inclusion

criteria. The power output associated with maximal oxygen

consumption ð _VO2 maxÞ was defined as the minimal work-

load at which ð _VO2 maxÞ occurred. All participants gave

maximum effort and were encouraged to do so.

Participants were then randomized to one of the two

treatment sequences: TER or placebo. Three hours after

treatment, they performed a battery of tests (Fig. 1) starting

with postural sway measures. Immediately after this test,

the participants performed 5 9 4 s cycling sprints inter-

spersed with 3 min of passive recovery, which constituted

the force–velocity exercise test. The parameters measured

were the force–velocity relationship, maximal velocity

ðvmaxÞ, maximal force ðFmaxÞ; maximal power output

ðPmaxÞ; optimal velocity ðvoptÞ and optimal force ðFoptÞ.After 5 min of passive recovery, participants performed a

70-m running sprint during which performance was

measured using a radar (Stalker professional sports

radar, Applied concept, Texas) enabling evaluation of the

instantaneous speeds. The parameters measured were

the maximal velocity ðvmaxÞ mean velocity ðvmeanÞ and the

initial acceleration. The acceleration phase was obtained by

fitting the speed–time curve from the standing start to the

maximal velocity to the following exponential equation

(Chelly and Denis 2001):

vðtÞ ¼ vmaxð1� e�t=sÞ;

where vmax is the maximal velocity, s is the time constant

of the acceleration phase.

The initial acceleration of each sprint was calculated as

the ratio vmax=s.

After 5 min of passive recovery, participants performed

a constant work cycling exercise at D50 % [50 % between

the ventilatory threshold (VT) and _VO2 max] until exhaus-

tion. Aerobic performance was evaluated with _VO2peak;

peak ventilation ð _VEpeakÞ and time until exhaustion.

Finally, the participants completed the Affect Grid.

Force–velocity exercise test

As recommended by Arsac et al. (1996), the subjects were

familiarized with the friction-loaded cycle ergometer by

5 min of submaximal cycling (100–150 W) and sprints of

2–4 s against friction loads of 0.20–1 N kg-1 body mass.

Wash out period

5min 5min

TreatmentPlacebo or8 mg TER

F-v relationship test5 x 4 s repetitions

Running sprint70m

Endurance cycling testTime to exhaustion at Δ50%

3h

Postural sway Affect Grid

Day 1

Incrementaltest

Day 2 or 3

1 week

Fig. 1 Sequence of the

experimental protocol

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After stretching and 5 min of rest, the subjects were asked

to perform five sprints separated by at least 3 min of rest.

Frictional loads of 0.2, 0.6 and 1.0 N kg-1 body mass were

applied to the friction belt in randomized order. The saddle

height and toe clips were adjusted for each subject. The

saddle height was measured and used for the whole tests.

At a signal given by the experimenter, the subjects were

asked to pedal as fast as possible until told to stop at the

signal given 4 s after the start. During the effort, each

subject was vigorously encouraged. The goal of this task

was to create the greatest acceleration of the flywheel, so

the subjects were required to produce the highest explosive

force possible on the pedal.

A standard friction-loaded cycle ergometer (model

918E, Monark-Crescent AB, Stockholm, Sweden) was

used, equipped with a strain gauge (interface MFG type,

Scottsdale, AZ, USA) and an incremental encoder (Engs-

tler type RIS IP50, 100 digits/turn of wheel, Aldingen,

Germany) fixed on a wheel (for details see Arsac et al.

1996). The strain gauge measured the friction force applied

by the belt that surrounds the flywheel. It was calibrated

with a known mass (9.78 kg) hung on the friction belt and

in an unloaded condition to give a 0 value. The strain gauge

was checked after 10 min of switching on the system to

avoid possible effects of temperature shift. The strain

gauge’s non-linearity was no more than 0.3 %. The

incremental encoder measured the displacement with a

precision of 12,060.6 points per pedal revolution or 2,010.1

points m-1.

Flywheel inertia varies among ergometers, even for a

specific model. Therefore, to ensure accurate measurement

of the inertia, the method proposed by Lakomy et al.

(Lakomy 1986) was used. Briefly, the inertia of the ergo-

cycle was simply determined from the linear relationship

between the free decelerations of the flywheel and the

corresponding friction loads. The following equation was

obtained to assess the force exerted by the subject when he

accelerated the flywheel (Finertia):

Finertia ¼ 0:1322a� 0:0453;

where the inertia force is expressed in N and a is the

acceleration of the flywheel expressed in rpm s-1.

Force and displacement signals were sampled at 200 Hz

and stored on a PC via an interface (Electronic, Informa-

tique du Pilat, Jonzieux, France). For further calculations,

instantaneous force and displacement data were low-pass

filtered (Butterworth 4th order with no phase lag) with a

cut-off frequency of 10 Hz. The velocity and acceleration

of the flywheel were obtained by 1st and 2nd order digital

derivations of the displacement signal, respectively. The

total external force (F) was the sum of the inertia force and

the friction force (Ffriction):

F ¼ Finertia þ Ffriction:

F and velocity data were averaged for each pedal

downstroke (i.e. 1/2 revolution), which was limited

between two minimal values of instantaneous velocity

corresponding to the top and bottom dead centers of a

crank revolution.

Blood analysis

Blood lactate concentrations were measured 1 min after the

end of the force–velocity exercise test. Capillary blood

samples were collected from the fingertip and analyzed

using the Lactate Pro analyzer (LT-1710, Arkray, Japan).

_VO2 kinetics

Breath-by-breath ventilation and gas exchange were con-

tinuously measured using a calibrated automated gas-

analysis system (VMAX29, Sensormedics).

Data were fitted with a classical serial model including

two components as described previously (e.g. Borrani et al.

2003):

_VO2ðtÞ ¼ _VO2i

þ A1½1� e� ðt�TD1Þ=s1f g�Phase 1 (primary component)

þ A2½1� e� t�TD2ð Þ=s2f g�UPhase 2 (slow component)

where U ¼ 0 for t\TD2 and U ¼ 1 for t� TD2; _VO2i is the

oxygen consumption at rest, A1 and A2 are the asymptotic

amplitudes for the primary and second exponential,

respectively, s1 and s2 are the times constant of each

exponential and TD1 and TD2 represents the time delay to

onset of the primary and the slow component, respectively.

The initial component (cardiodynamic phase) was not

modeled since the focus was on the SC kinetic. The pri-

mary component phase is not distorted by any early car-

diodynamic influence (Paterson and Whipp 1991; Whipp

et al. 1982). As a consequence, the first 20 s were removed

from analysis to ensure that the early initial component did

not influence the result (Whipp et al. 1982).

The magnitude of SC was assigned the value ðA02Þ:

A02 ¼ A2½1� e� ðte�TD2Þ=s2f g�;

where te is the time at the end of exercise.

VT was determined as the power output corresponding

to the point where a systematic increase in the ventilatory

equivalent for O2_VE�

_VO2

� �occurred without an increase

in the ventilatory equivalent for CO2_VE�

_VCO2

� �.

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Postural sway measures and Affect Grid

Before exercises, participants had to stand on a force

platform (Medicapteurs, France). Center of pressure (COP)

displacement data were recorded during 51.2 s at a sample

frequency of 40 Hz. The variability (standard deviation) of

COP time series and their power spectra were computed in

both anteriorposterior (AP) and mediolateral (ML) direc-

tions (Prieto et al. 1996). Immediately after the constant

work cycling exercise, participants completed the Affect

Grid that measures the dimensions of pleasure-displeasure

(from 1 = unpleasant feelings to 9 = pleasant feelings)

and arousal-sleepiness (from 1 = sleepiness to 9 = high

arousal) (Russell 1989).

Statistical analysis

Data are presented as mean values ± standard deviation

(SD). When the normality of distribution was satisfied, a

student-paired test was used to test differences between

placebo and TER treatments. When normality of distribu-

tion was not satisfied, data were evaluated by a paired

Wilcoxon test. The parameters of _VO2 kinetics models

were determined using an iterative procedure by mini-

mizing the sum of the residual mean squares of the dif-

ferences between the _VO2 model and the _VO2 measured.

Statistical significance was accepted at the 0.05 level.

Results

When questioned after the two trials, as to their knowledge

of which of the two treatments they had received, all

subjects were able to identify the TER treatment although

the double-blind protocol was effectively completed. All

participants reported adverse effects such as tremors,

starting 1 h after the 8 mg TER administration, with an

increased magnitude during the following 2 h, just before

performing the exercises.

Incremental test

The mean value for _VO2 max was 57 ± 3 ml min-1 kg-1.

The mechanical power corresponding to _VO2 max was

351 ± 57 W and Delta T50 was 241 ± 36 W.

Force–velocity exercise test

No improvement was found in the force–velocity rela-

tionship after TER intake (p [ 0.05). TER was not found

to improve maximal velocity (p [ 0.05) but a significant

decrease of peak force was obtained with TER (p \ 0.05),

without altering the peak power (p [ 0.05). No difference

was found for optimal force and optimal velocity

(p [ 0.05). These results are detailed in Table 1.

Blood lactate

Blood lactate concentrations 1 min after the force–velocity

exercise test were no different between placebo and TER

(p [ 0.05). The values were 7.8 (2.1) and 6.1 (2.1) mM,

respectively.

Running test

During the running test, no difference on mean speed,

maximal speed and initial acceleration was found between

placebo and TER (p [ 0.05) (Table 2).

Endurance test

Table 3 presents kinetic parameters for the curve fitting of_VO2 response during the endurance test. TER was not

found to improve aerobic performance with regard to the

collected variables. Indeed, no significant differences in_VO2peak; _VEpeak and in cycling time until exhaustion at a

power output corresponding to Delta T50 were found

between TER and placebo (p [ 0.05). No significant dif-

ference was found between placebo and TER treatment on

Table 1 Force-velocity test on ergocycle under placebo and 8 mg

TER conditions in the 7 male study participants

Variable Placebo Terbutaline Significance

vmax (rpm) 183 (8) 190 (17) NS

Fmax (N) 245.4 (36.9) 231.1 (38.2) p \ 0.05

Pmax (W kg-1) 25.8 (3.3) 24.7 (2.3) NS

vopt (rpm) 100.1 (7.2) 101.8 (8.9) NS

Fopt (N) 150.2 (34.2) 141.9 (31.1) NS

Results are given as mean values with standard deviation in paren-

theses (SD)

NS not significant, vmax maximal velocity, Fmax maximal force, Pmax

maximal power output, vopt optimal velocity, Fopt optimal force

Table 2 Running sprint performance under placebo and 8 mg TER

conditions in the 7 male study participants

Variable Placebo Terbutaline Significance

vmax (m s-1) 8.6 (0.4) 8.4 (0.5) NS

vmean (m s-1) 6.2 (1.3) 6.3 (1.1) NS

vmax=s (m s-2) 5.1 (1.7) 5.0 (0.6) NS

Results are given as mean values with standard deviation in paren-

theses (SD)

NS not significant, vmax vmean maximal velocity, mean velocity, vmax=sinitial acceleration

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the magnitude of the primary and the slow component of_VO2 (p [ 0.05). TER was not found to induce any sig-

nificant difference on the time constant of the slow com-

ponent. No difference was noted on the time delay of the

slow component between placebo and TER (p [ 0.05).

Postural sway measures and Affect Grid

A significant increase in variability of the COP position

in ML direction was found under TER compared to

placebo (p \ 0.05). The values were 2.60 ± 0.88 and

2.01 ± 0.64 mm for TER and placebo, respectively.

Moreover, the analysis of the power spectra of the ML

COP signals showed a significant increase (p \ 0.05) of

the spectral power under TER for the highest range of

observed frequencies (from 0.5 to 1 Hz). After the constant

work cycling exercise, a significant decrease in arousal as

measured with the Affect Grid was observed under TER

compared to placebo (p \ 0.05). The values were

6.14 ± 1.2 and 7.43 ± 1.72 a.u. for TER and placebo,

respectively.

Discussion

The present work is the first to study the effects of oral

systemic TER per os administration on performance in

healthy athletes. In this study, we provide new insight

concerning the implication of b2-agonists in athlete

performance.

Interestingly, we found no improvement on anaerobic

and aerobic performances after a single oral administration

of TER at a supra-therapeutic dose. One could argue that

the relatively small number of participants (7) in the

present study may explain the lack of significant ergogenic

effect of TER. However, instead of a positive effect, a

slight but significant decrease was observed in maximal

force under TER condition compared to placebo indicating

a weak probability of detecting a positive effect of TER

with a larger number of participants, i.e. a greater statistical

power. Based on the study by van Baak and coworkers (van

Baak et al. 2000), we hypothesized a specific enhancement

in power output at low levels of shortening velocity under

TER treatment. Our hypothesis was rejected since TER has

no specific ergogenic effect in our experimental conditions.

Furthermore, the absence of an ergogenic effect on

anaerobic performance is in accordance with the recent

study by Crivelli and colleagues who found that oral acute

administration of salbutamol (6 mg) is without any rele-

vant ergogenic effect on muscle contractility and fatiga-

bility in non-asthmatic recreational male athletes (Crivelli

et al. 2011). However, there is some controversy. Acute

oral administration of 4–6 mg salbutamol is also known to

increase anaerobic performance, with an increase in max-

imal power output of about 5–13 % (Collomp et al. 2005;

Le Panse et al. 2005, 2006; Sanchez et al. 2012). This

apparent controversy may be linked to the molecule used

and the dose administered, inducing, or not inducing,

adverse side effects.

As for anaerobic exercise, no improvement in aerobic

performance was found in our study. Endurance perfor-

mance was measured through running time until exhaus-

tion during a cycling test performed at heavy intensity

(Delta T50) and maximal aerobic power through _VO2peak.

A lack of TER effect on endurance time was observed.

This result is confirmed by the lack of change in oxygen

uptake and the cardio-respiratory variables between the

two experimental conditions. Moreover, we did not find

any relevant effect of TER in the magnitude of the slow

component of _VO2. Since the latter is closely related to the

progressive development of fatigue that is evident during

heavy and severe exercises (Burnley and Jones 2008), our

result is in accordance with the absence of TER effect on

fatigue resistance during aerobic performance.

It is important to note that all of the participants com-

plained about the same adverse side effects in the hours

following TER administration, i.e. during the exercise tri-

als. The significant decrease in arousal under TER is

consistent with these reactions and might be related to the

yawns that were observed under TER before exercises. Pre-

competitive stress implying catecholamine secretion and

b2-agonist stimulation is known to induce yawning and a

Table 3 Results of testing procedure parameters estimated for

biexponential curve fitting of individual _VO2 response during the

endurance exercise on two different days with placebo and TER 8 mg

taken before exercise in the 7 male study participants

Variable Placebo Terbutaline Significance

Peak O2 uptake

(ml kg-1 min-1)

51.7 (3.3) 53.3 (3.8) NS

Peak ventilation

(l min-1)

114.1 (13.3) 109.3 (20.2) NS

Time until exhaustion (s) 714 (392) 845 (736) NS

A1 (ml min-1) 2.52 (0.40) 2.52 (0.57) NS

s1 (s) 15.6 (4.3) 21.2 (11.9) NS

TD1 (s) 18.4 (4.6) 13.1 (9.4) NS

A2 (ml min-1) 0.76 (0.30) 0.67 (0.19) NS

s2 (s) 158.5 (70.2) 171.8 (89.4) NS

TD2 (s) 86.1 (30.9) 109.5 (49.7) NS

Results are given as mean values with standard deviation in paren-

theses (SD)

NS not significant, A1 amplitude, TD1 time delay and time constant

(s1) of the primary phase of oxygen uptake, A2 amplitude, TD1 time

delay and time constant (s2) of the slow component of oxygen uptake

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state of febrility. Moreover, the analysis of postural control

may provide further insight into TER side effects. The

increase in variability of the center of pressure and power

spectrum in ML direction under TER may be related to

tremor, the most characteristic adverse effect following

administration of b2-adrenergic agonists (Cazzola and

Matera 2012). It can therefore be hypothesized that these

marked adverse effects may prevent a possible ergogenic

effect of TER. Indeed, van Baak et al. (2000) reported that

oral salbutamol intake appears to be an effective ergogenic

aid, only in non-asthmatic individuals not experiencing

adverse side effects.

Otherwise, participants in the present study took this

drug for the first time. Taking these substances repeatedly

can involve a reduction in b2-receptor contents and side

effect manifestations (Sato et al. 2010). Anabolic effects

have been reported in animals with chronic salbutamol

treatment. These observations have not been reported for

humans in scientific literature but it is well known that

bodybuilders frequently use clenbuterol at high doses

because of their anabolic and lipolytic properties (e.g.

http://www.musclesprod.com/steroid-profiles/axiolabs/clen

butaplex/). The apparent discrepancy between studies with

respect to ergogenic effects may be due primarily to the

nature and the mode of intake and more particularly the

distribution of b2-agonists in the organism. All the studies

that found no ergogenic effect of salbutamol on force pro-

duction used inhalation administration; in contrast, studies

that noted an ergogenic effect used oral administration.

Inhalation is associated with a more marked local effect on

pulmonary b2-adrenoceptors than on peripheral skeletal

muscle adrenoceptors. To the best of our knowledge, no

study has evaluated the anabolic effects of oral TER at high

doses. Thus, taking all these factors into account, we cannot

exclude a potential effect on anaerobic performance with a

chronic treatment of TER, especially at therapeutic doses.

Conclusions

In conclusion, acute supra-therapeutic dose of TER seems

to be without any relevant ergogenic effect on anaerobic

and aerobic performances in healthy athletes. The absence

of an ergogenic effect for an amount of 8 mg is concom-

itant with the occurrence of marked adverse side effects

and does not exclude a potential ergogenic effect of a lower

dose, where the deleterious effects could be reduced. Nor

does it exclude potential effects of short-term treatment. In

the anti-doping fight, these elements must be highlighted in

preventive action.

Acknowledgments We give special thanks to the participants for

their great effort, compliance and enthusiasm when participating in

the study. We would like to thank Drs Sofiane Ramdani and Benoit

Seigle for their analysis and helpful discussions related to postural

sway data. This work was supported by the World Anti-Doping

Agency and by a fellowship from the Ministere de la Recherche et de

la Technologie (to AMJS).

Conflict of interest The authors declare no conflict of interest.

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