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100:1238-1248, 2006. doi:10.1152/japplphysiol.00742.2005 Journal of Applied Physiology
Véronique Billat, Bertrand Mettauer, Ruddy Richard and Jean Lonsdorfer
Lonsdorfer-Wolf, Bernard Geny, Eliane Lampert, Martin Flück, Hans Hoppeler,
Stéphane P. Dufour, Elodie Ponsot, Joffrey Zoll, Stéphane Doutreleau, Evelyne
capacity
runners. I. Improvement in aerobic performance
Exercise training in normobaric hypoxia in endurance
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Exercise training in normobaric hypoxia in endurance runners.
I. Improvement in aerobic performance capacity
Ste´phane P. Dufour,
1
Elodie Ponsot,
1
Joffrey Zoll,
2
Ste´phane Doutreleau,
1
Evelyne Lonsdorfer-Wolf,
1
Bernard Geny,
1
Eliane Lampert,
1
Martin Flu¨ck,
2
Hans Hoppeler,
2
Ve´ronique Billat,
3
Bertrand Mettauer,
1,4
Ruddy Richard,
1
and Jean Lonsdorfer
1
1
De´partement de Physiologie et des Explorations Fonctionnelles, Hoˆpital Civil, and Faculte´deMe´dicine, Institut de
Physiologie, Unite´ Propre de Recherche de l’Enseignement Supe´rieur E
´
quipe d’Accueil 3072, Strasbourg, France;
2
Institute of Anatomy, University of Bern, Bern, Switzerland;
3
Laboratoire d’Etudes Physiologiques a` l’Exercice,
De´partement des Sciences du Sport et de l’Exercice, E
´
quipe d’Accueil 3872, Universite´ d’Evry Val d’Essonne,
Evry, France; and
4
Service de Cardiologie, Hoˆpitaux Civils de Colmar, Colmar, France
Submitted 22 June 2005; accepted in final form 27 July 2005
Dufour, Ste´phane P., Elodie Ponsot, Joffrey Zoll, Ste´phane
Doutreleau, Evelyne Lonsdorfer-Wolf, Bernard Geny, Eliane
Lampert, Martin Fluck, Hans Hoppeler, Ve´ronique Billat, Ber-
trand Mettauer, Ruddy Richard, and Jean Lonsdorfer. Exercise
training in normobaric hypoxia in endurance runners. I. Improvement
in aerobic performance capacity. J Appl Physiol 100: 1238–1248,
2006; doi:10.1152/japplphysiol.00742.2005.—This study investigates
whether a 6-wk intermittent hypoxia training (IHT), designed to avoid
reductions in training loads and intensities, improves the endurance
performance capacity of competitive distance runners. Eighteen ath-
letes were randomly assigned to train in normoxia [Nor group; n ⫽ 9;
maximal oxygen uptake (V
˙
O
2 max
) ⫽ 61.5 ⫾ 1.1 ml䡠 kg
⫺1
䡠 min
⫺1
]or
intermittently in hypoxia (Hyp group; n ⫽ 9; V
˙
O
2 max
⫽ 64.2 ⫾ 1.2
ml䡠 kg
⫺1
䡠 min
⫺1
). Into their usual normoxic training schedule, athletes
included two weekly high-intensity (second ventilatory threshold) and
moderate-duration (24 – 40 min) training sessions, performed either in
normoxia [inspired O
2
fraction (FI
O
2
) ⫽ 20.9%] or in normobaric
hypoxia (F
I
O
2
⫽ 14.5%). Before and after training, all athletes realized
1) a normoxic and hypoxic incremental test to determine V
˙
O
2 max
and
ventilatory thresholds (first and second ventilatory threshold), and 2)
an all-out test at the pretraining minimal velocity eliciting V
˙
O
2 max
to
determine their time to exhaustion (T
lim
) and the parameters of O
2
uptake (V
˙
O
2
) kinetics. Only the Hyp group significantly improved
V
˙
O
2 max
(⫹5% at both FI
O
2
, P ⬍ 0.05), without changes in blood
O
2
-carrying capacity. Moreover, T
lim
lengthened in the Hyp group
only (⫹35%, P ⬍ 0.001), without significant modifications of V
˙
O
2
kinetics. Despite similar training load, the Nor group displayed no
such improvements, with unchanged V
˙
O
2 max
(⫹1%, nonsignificant),
T
lim
(⫹10%, nonsignificant), and V
˙
O
2
kinetics. In addition, T
lim
improvements in the Hyp group were not correlated with concomitant
modifications of other parameters, including V
˙
O
2 max
or V
˙
O
2
kinetics.
The present IHT model, involving specific high-intensity and moder-
ate-duration hypoxic sessions, may potentialize the metabolic stimuli
of training in already trained athletes and elicit peripheral muscle
adaptations, resulting in increased endurance performance capacity.
maximal oxygen uptake; time to exhaustion; competitive endurance
runners
AT SEA LEVEL, IT IS WELL KNOWN that the training-induced
improvements in endurance performance progressively level
off as the aerobic fitness progresses. Therefore, the use of the
metabolic stimulus provided by living (i.e., living high-training
low) or training at altitude (i.e., living low-training high) has
gained popularity in athletes to further enhance endurance
performance. In this context, methods that impose short-term
altitude exposure while exercising have progressively emerged
to cope with the growing evidence that long-term altitude
exposure possesses several detrimental effects, including a
limited aerobic power, reducing both the metabolic and me-
chanical components of the total training load (24). To concil-
iate altitude training with a maintained training load, it has
recently been proposed to use altitude in several but not all
training sessions, included into a training program otherwise
performed in normoxia [intermittent hypoxia training (IHT)]
(38, 44 – 46).
To date, these training programs have provided conflicting
results in endurance athletes (38, 44, 46), which could be due
to the various combinations of duration and intensity of the
hypoxic training sessions employed (32). Accordingly, im-
provement of performance in competitive swimmers has not
been observed after an IHT program, including very short
high-intensity (30 – 60 s) hypoxic sessions (44), whereas longer
periods of high-intensity hypoxic exercise (70 s to 3 min)
improved maximal power output at sea level in professional
cyclists (39). In addition, significant maximum oxygen uptake
(V
˙
O
2 max
) improvement at sea level has been reported in trained
subjects after hypoxic exercise bouts of 2- to 12-min duration
(38). Recent evidence also demonstrated no beneficial effects
of IHT programs, when the hypoxic exercise intensity is set
below 80% of normoxic V
˙
O
2 max
(44, 46). Collectively, these
findings point to a pivotal role for a minimal hypoxic exercise
duration and intensity in IHT models, especially in trained
athletes. Based on these observations, we assumed that two
successive hypoxic training bouts, of 12–20 min, performed at
the second ventilatory threshold (VT
2
)(⬃80% of normoxic
V
˙
O
2 max
) are likely to comply with the above information.
Moreover, integrated within the usual normoxic training of
competitive runners, the intermittent nature of such specific
hypoxic sessions would allow maintaining high levels of total
training load and may elicit significant improvement of endur-
ance performance capacity.
Characterization of the endurance performance capacity in
athletes involves incremental exercise testing, allowing for the
determination of the ventilatory thresholds [first ventilatory
Address for reprint requests and other correspondence: J. Lonsdorfer,
Hoˆpital de la Robertsau, 83 rue Himmerich, BP 426, 67091 Strasbourg Cedex,
France (e-mail: jeanlonsdorfer@hotmail.fr).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
J Appl Physiol 100: 1238 –1248, 2006;
doi:10.1152/japplphysiol.00742.2005.
8750-7587/06 $8.00 Copyright
©
2006 the American Physiological Society http://www. jap.org1238
on March 22, 2006 jap.physiology.orgDownloaded from
threshold (VT
1
) and VT
2
], V
˙
O
2 max
, as well as their associated
minimal running velocities (vVT
1
, vVT
2
, and vV
˙
O
2 max
). Ad
-
ditionally, since vV
˙
O
2 max
falls among the significant predictors
of endurance performance (4, 5), the time to exhaustion at
vV
˙
O
2 max
(T
lim
) is thought to constitute an important determi
-
nant of the endurance performance capacity. Despite its ath-
letic relevance, the effect of IHT program on T
lim
in endurance
athletes remains unknown. Since the maximal rate (i.e.,
V
˙
O
2 max
or vV
˙
O
2 max
) (6, 23) and/or kinetic changes in the O
2
flux adjustment (13) are expected to contribute to T
lim
perfor
-
mance, the possible influence of IHT on both of these respec-
tive properties of aerobic metabolism is also not elucidated.
Therefore, the purpose of this study was to test the hypoth-
eses that an original IHT model, including two weekly mod-
erate-duration (24 – 40 min) and high-intensity (VT
2
) hypoxic
sessions within the usual normoxic training of already trained
athletes, 1) improves running velocities at sea level due to
amelioration of aerobic energy provision, including V
˙
O
2 max
;
and 2) lengthens T
lim
at sea level with concomittant adaptations
of aerobic metabolism properties, mainly V
˙
O
2 max
and/or oxy
-
gen uptake (V
˙
O
2
) kinetics.
METHODS
Subjects
Eighteen highly trained male distance runners were recruited from
local athletic teams and completed the study before the beginning of
their competitive season. Their main physical and physiological char-
acteristics are shown in Table 1. After all the potential risks were
explained, the athletes gave a voluntary written consent to participate
to the protocol, approved by our hospital and national review boards.
In the weeks before and during the study, the subjects lived under the
altitude of 300 m and were engaged in a regular training schedule
comprising five training sessions per week, including two weekly
training sessions performed specifically at VT
2
(49). Their respective
individual training schedule remained unaltered during the experi-
mental period. All were highly motivated to participate in the study,
familiar with treadmill running, and with current 10,000 m or equiv-
alent personal-best times of ⬍35:00 (min:s).
Experimental Design
As shown in Fig. 1, the study was organized in four successive
phases: a basal medical examination, the pretraining treadmill perfor-
mance evaluation, the training process, and the posttraining treadmill
performance evaluation.
Basal medical examination. Two weeks before the beginning of the
training period, each subject came to the laboratory for anthropomet-
ric measurements, physical examination, resting electrocardiography,
and echocardiography recordings. To verify their exercise and hyp-
oxic tolerance under careful cardiac monitoring, all athletes also
performed maximal graded cycle tests in normoxia and hypoxia.
These tests did not reveal any abnormality that could prevent the
subjects from being included in the experimental protocol.
Pre- and posttraining treadmill performance evaluation. In the
week before and after the training intervention, all of the subjects
performed three exercise tests on a motorized treadmill (Gymrol 2500
SP, Tecmachine), which were separated by at least 24 h of rest: 1)a
treadmill incremental exercise test (IET) to exhaustion in Nor [IET
N
;
inspired O
2
fraction (FI
O
2
) ⫽ 20.9%]; 2) a treadmill IET to exhaustion
in Hyp (IET
H
;FI
O
2
⫽ 14.5%, equivalent to an altitude of 3,000 m);
and 3) a normoxic all-out test at pretraining vV
˙
O
2 max
. For a given
subject, all tests were performed at the same time of day in a
climate-controlled environment (21–23°C).
Training program. During the 6 wk of the study, both groups
continued their usual training program (5 sessions/week), including
their two weekly sessions at VT
2
that were performed in the labora
-
tory. All of the laboratory training sessions were performed under
careful supervision of an experimented physician. For the group who
trained in normoxia (Nor group), VT
2
was determined during the
IET
N
, and for the group who trained in hypoxia (Hyp group), VT
2
was
determined during the IET
H
. Each VT
2
session began with a 10-min
warm-up at 60% V
˙
O
2 max
(⬍VT
1
), followed by two periods at VT
2
(time run at VT
2
specified in Fig. 1), separated by 5-min recovery at
60% V
˙
O
2 max
. For the Hyp group, the subjects trained under hypoxic
conditions only during the running periods at VT
2
by breathing
through face masks connected to a mixing chamber via appropriate
tubing. Warm-up and recoveries were performed under normoxia. The
training load during the laboratory sessions was organized into two
3-wk periods in which the exercise duration at VT
2
increased pro
-
gressively (Fig. 1). At the 4th wk, the training velocity was readjusted
to maintain an exercise heart rate (HR) corresponding to the one
achieved at the first training session. Throughout the study, each
athlete underwent a total of 12 controlled laboratory training sessions.
No athletes withdrew from the study before the achievement of the
posttraining treadmill performance evaluation, and none complained
of health complications throughout the study.
Procedures
Altitude simulation. Normobaric hypoxic conditions corresponding
to an altitude of 3,000 m (F
I
O
2
⫽ 14.5%) were simulated by diluting
ambient air with nitrogen via a mixing chamber, with the dilution
being constantly controlled by a P
O
2
probe (Alti-Trainer
200
, Sport and
Medical Technology). This device allows the inspired P
O
2
to be set at
a predetermined value to simulate altitude. The precision of the P
O
2
is
of ⫾0.82 Torr. The respiratory effort induced by the device at 6 l/s
was negligible (⬍0.01 W).
Treadmill tests. The IET
N
or the IET
H
were performed in random
order on a motorized treadmill with 0% slope, to determine VT
1
,VT
2
,
V
˙
O
2 max
, the associated velocities, and the running economy (RE) in
both conditions of oxygen availability. During each IET, the initial
running speed was set at 10 km/h and increased by 1 km/h every
2-min until volitional exhaustion. Each subject was encouraged to
give a maximum effort. Arterialized blood samples were obtained
from the earlobe at rest, at exhaustion, as well as at the first and third
minute of recovery to determine total blood lactate concentration
([La]).
Table 1. Anthropometric data and performance
capacity of the subjects
Hypoxic Group Normoxic Group P Value
Number of subjects 9 9 NS
Body weight, kg 70.6⫾2.2 71.3⫾2.2 NS
Height, cm 180⫾1 180⫾2NS
Age, yr 30.3⫾6.3 30.3⫾6.1 NS
Body fat, % 11.8⫾0.8 12.1⫾1.2 NS
[Hb], g/l 15.3⫾0.2 15.3⫾0.3 NS
Hct, % 45.1⫾0.8 46.0⫾1.2 NS
V
˙
O
2 max
,ml䡠kg
⫺1
䡠min
⫺1
64.2⫾1.2 61.5⫾1.1 NS
vV
˙
O
2 max
, km/h
19.6⫾0.2 19.0⫾0.4 NS
VT
2
,%V
˙
O
2 max
89.7⫾1.5 88.7⫾1.2 NS
Values are means ⫾ SE. Hypoxic and normoxic groups are groups that
included only two training sessions at the velocity corresponding to the second
ventilatory threshold (VT
2
) in their usual weekly training schedule and per
-
formed under hypoxic or normoxic condition, respectively. %Body fat is the
percentage of body fat determined according to Durnin and Womersley (16).
[Hb], hemoglobin concentration; Hct, hematocrit; V
˙
O
2 max
, maximal oxygen
uptake determined in the normoxic incremental test; vV
˙
O
2 max
, the lowest
running speed associated with V
˙
O
2 max
in the normoxic incremental exercise
test. VT
2
was determined during the normoxic incremental test. NS, no
significant difference between hypoxic and normoxic groups.
1239INTERMITTENT HYPOXIA TRAINING AND AEROBIC CAPACITY
J Appl Physiol • VOL 100 • APRIL 2006 • www.jap.org
on March 22, 2006 jap.physiology.orgDownloaded from
The all-out running test was performed in normoxia at pretraining
vV
˙
O
2 max
, i.e., the same absolute running speed before and after
training. The test began by 10-min warm-up at 60% of the subject’s
vV
˙
O
2 max
(lower than vVT
1
in all subjects). The subjects were then
connected to the test equipments during a 5-min period of rest and
immediately asked to run at their individual vV
˙
O
2 max
for as long as
possible. The transition from rest to vV
˙
O
2 max
occurs within a 20-s
delay (range 17–23 s), necessary for the treadmill to reach the desired
speed. No information about the time elapsed was provided to the
athletes. During this test, arterialized blood samples were obtained
from the earlobe at rest, at exhaustion, as well as at the 1st and 3rd min
of recovery to determine total blood [La].
HR monitoring. During all of the running tests, as well as during
the controlled training sessions, HR was continuously monitored by
telemetry (Polar Vantage, Kempeley, Finland).
Gas exchange measurements. During all tests, inspiratory (V
˙
I) and
expiratory minute ventilation (V
˙
E), V
˙
O
2
, and carbon dioxide output
(V
˙
CO
2
) were measured breath by breath with an open-circuit meta
-
bolic cart with rapid O
2
and CO
2
analyzers (Sensor Medics MSE,
Yorba Linda, CA). Before each individual exercise test, the pneumo-
tachograph was calibrated with several strokes given by a 3-liter
calibration syringe. The gas analyzers were calibrated by using ref-
erence gases with known O
2
and CO
2
concentrations (12% O
2
,5%
CO
2
). FI
O
2
and fraction of O
2
in the expired air (FE
O
2
) were analyzed
continuously for each breath. Therefore, V
˙
O
2
was calculated in nor
-
moxia and hypoxia by the following formula, where all parameters are
expressed in
STPD conditions: V
˙
O
2
⫽ V
˙
I ⫻ FI
O
2
⫺ V
˙
E ⫻ FE
O
2
.
During the IET, each athlete was encouraged to give a maximal
effort. Peak treadmill velocity was defined as the last achieved
running speed sustained for at least 30 s. V
˙
O
2 max
was always defined
as the highest 30-s averaged V
˙
O
2
value. As previously described by
Billat and Koralsztein (4), vV
˙
O
2 max
was defined as the minimal
velocity at which V
˙
O
2 max
occurred. In detail, if V
˙
O
2 max
was reached
during the last stage, which was maintained ⬎90 s, that particular
velocity was taken as vV
˙
O
2 max
. If that velocity eliciting V
˙
O
2 max
was
sustained ⬍60 s, then vV
˙
O
2 max
was taken as the velocity at the
previous stage. If that velocity eliciting V
˙
O
2 max
was maintained
between 60 and 90 s, then vV
˙
O
2 max
was considered to be equal to the
velocity during the previous stage plus the half velocity increase
between the last two stages, i.e., (1 km/h)/2 ⫽ 0.5 km/h (29).
Ventilatory thresholds were assessed by using established criteria (3,
49). VT
1
corresponds to the break point in the plot of V
˙
CO
2
as a
function of V
˙
O
2
. At that point, the ventilatory equivalent for O
2
(V
˙
E/V
˙
O
2
) increases without an increase in the ventilatory equivalent
for CO
2
(V
˙
E/V
˙
CO
2
). VT
2
was located between VT
1
and V
˙
O
2 max
, when
V
˙
E/V
˙
CO
2
starts to increase while V
˙
E/V
˙
O
2
continues to increase. The
oxygen pulse (O
2
p) was calculated as the ratio between V
˙
O
2
and HR,
also representing stroke volume times arteriovenous oxygen differ-
ence [⌬(a-v)O
2
] (30). RE was defined as the rate of V
˙
O
2
for a given
submaximal work rate (9). Therefore, RE corresponds to the 1-min
average of the V
˙
O
2
values recorded at the end of the 12 km/h stage
during each IET. This speed was lower than VT
1
for all of the subjects
in both environmental conditions and allows an estimation of RE for
an exercise intensity expected to be mainly aerobic. To provide
additional insights in the effect of IHT on RE, we also determined RE
at 18 km/h in IET
N
and at 15 km/h in IET
H
. These running speeds
amounted to ⬃92 and 90% of the respective normoxic and hypoxic
vV
˙
O
2 max
, corresponding to recommended speed for RE determination
in athletes (10).
Blood O
2
-carrying capacity and lactate. On the first day of the
treadmill performance evaluation before and after training, blood was
drawn from an antecubital vein in each group to immediately measure
Fig. 1. Study design with the 4 phases of the experimental protocol. , Incremental running tests; , all-out running tests in normoxia. Normoxia:
inspired O
2
fraction (FI
O
2
) ⫽ 20.9%. Hypoxia: FI
O
2
⫽ 14.5%. Phases 1, 2, 3, and 4 are the respective experimental phases (see text for details). vVT
2
, running
velocity corresponding to the second ventilatory threshold.
1240 INTERMITTENT HYPOXIA TRAINING AND AEROBIC CAPACITY
J Appl Physiol • VOL 100 • APRIL 2006 • www.jap.org
on March 22, 2006 jap.physiology.orgDownloaded from
hematocrit (Hct) and hemoglobin concentration. Earlobe blood sam-
ples obtained during all running tests were also immediately analyzed
for total blood [La] by an enzymatic method.
Oxygen saturation. During each exercise test, hemoglobin satura-
tion was monitored continuously by earlobe pulse oximetry (Oxy-
pleth, Novametrix-Medical System).
V
˙
O
2
Kinetics
Data modelization. To describe the V
˙
O
2
kinetics [V
˙
O
2
(t)] during the
all-out test, we used a mathematical model with two exponential
functions (2):
V
˙
O
2
共t兲 ⫽ V
˙
O
2b
⫹ A
1
兵1 ⫺ e
⫺关共t⫺td
1
兲/
1
兴
其U
1
关Phase 2 共fast component兲兴
⫹ A
2
兵1 ⫺ e
⫺关共t⫺td
2
兲/
2
兴
其U
2
关Phase 3 共slow component兲兴
(1)
where U
1
⫽ 0 for t ⬍ td
1
and U
1
⫽ 1 for t ⱖ td
1
;U
2
⫽ 0 for t ⬍ td
2
and U
2
⫽ 1 for t ⱖ td
2
;V
˙
O
2b
is the rate of V
˙
O
2
at rest before the start
of the all-out test; A
1
and A
2
are the asymptotic amplitudes for the first
and second exponential terms, respectively;
1
and
2
are the time
constants and represent the time to reach 63% of the total amplitude
of the respective fast and slow V
˙
O
2
components; td
1
and td
2
represent
the time delays for the fast and the slow components, respectively. As
the initial cardiodynamic phase of the V
˙
O
2
adjustment to a rest-to-
exercise transition does not influence the fast component of V
˙
O
2
(36)
and because we focused on the fast and slow components of the V
˙
O
2
response, the cardiodynamic phase was excluded from analysis by
removing the data from the first 20 s of the all-out test. The parameters
of the model were determined with an iterative procedure that mini-
mizes the sum of the mean squares of the differences between the
model V
˙
O
2
estimates and the corresponding V
˙
O
2
measurements. To
exclude aberrant breaths from analysis, breath-by-breath V
˙
O
2
values
that were greater than three standard deviations from the modeled V
˙
O
2
were removed and assumed to represent events unrelated to the
physiological response of interest (31, 39). These values represented
⬍1% of the total data.
Slow component of V
˙
O
2
kinetics. Because the asymptotic value of
the second exponential term is not necessarily reached at the subject’s
exhaustion, the amplitude of the slow component was computed as
A⬘
2
(7):
A⬘
2
⫽ A
2
关1 ⫺ e
⫺共T
lim
⫺td
2
兲/
2
兲](2)
where T
lim
is the time at the end of the all-out exercise test. Moreover,
to compare the amplitude of the V
˙
O
2
slow component at consistent
time before and after training, we also calculated the amplitude of the
V
˙
O
2
slow component achieved posttraining when the subjects attained
their pretraining T
lim
value (A⬘
2
old).
O
2
deficit calculation. According to Whipp and Ozyener (51), the
fast component of the V
˙
O
2
kinetics represents an “expected V
˙
O
2
,”
whereas the slow component is the manifestation of an “excess V
˙
O
2
”
occurring later during exercise (i.e., after td
2
). Consequently, the
oxygen deficit (O
2
def) is estimated from the area between the fast-
component response curve and the fast-component asymptote (13):
O
2
def ⫽ 共td
1
⫻ A
1
兲 ⫹ 共
1
⫻ A
1
兲 (3)
where O
2
def is in milliliters, td
1
and
1
are in seconds, and A
1
is in
milliliters per second.
Computation of the time sustained at pretraining V
˙
O
2 max
. Besides
T
lim
, which could be considered as a mechanical parameter of endur
-
ance performance (reflecting the total mechanical work performed at
vV
˙
O
2 max
), we also calculated a metabolic correlate (Eq. 4), from the
time sustained while the athlete ran at ⬎95% of pretraining V
˙
O
2 max
(T
lim
@V
˙
O
2 max
). This percentage was chosen to account for a 5%
random error in the determination of V
˙
O
2 max
(33) and also because all
athletes did not necessarily reach 100% V
˙
O
2 max
in T
lim
testing (13).
T
lim
@V
˙
O
2max
共s兲 ⫽ T
lim
⫺ TA V
˙
O
2max
(4)
where T
lim
is the time to exhaustion while the athletes ran at the
pretraining minimal velocity associated with V
˙
O
2 max
(s), and the time
to attain V
˙
O
2 max
(TA V
˙
O
2 max
) corresponds to the time necessary to
reach 95% of pretraining V
˙
O
2 max
(s). Depending on whether the V
˙
O
2
kinetics were better described by a mono- or a double-exponential
model, TA V
˙
O
2 max
was computed from the equations below.
1) For the monoexponential model (fast component in Eq. 1)
TA V
˙
O
2max
⫽ td
1
⫺
1
⫻ 兵ln关1 ⫺ 共0.95 ⫻ V
˙
O
2max
⫺ V
˙
O
2b
兲/A
1
兴其
2) For the double-exponential model (fast ⫹ slow component in Eq. 1)
TA V
˙
O
2max
⫽ td
2
⫺
1
⫻ 兵ln关1 ⫺ 共0.95 ⫻ V
˙
O
2max
⫺ V
˙
O
2b
⫺ A
1
兲/A
2
兴其
Evaluation of Training
All athletes were asked to report their individual training schedule
into detailed training logs, including duration, distance, and intensity
of each training sessions. Laboratory as well as field work bouts were
taken into account to provide both quantitative and qualitative char-
acterization of the overall training load. Duration and intensity of the
training sessions performed out of the laboratory were assessed based
on the running velocity spread out in four intensity zones: low
(⬍vVT
1
), moderate (vVT
1
⫺ vVT
2
), heavy (vVT
2
⫺ vV
˙
O
2 max
), and
severe intensity (⬎vV
˙
O
2 max
).
Statistics
Whether a mono- or biexponential model better described the V
˙
O
2
kinetics during the all-out tests was determined using a Fisher test. We
used the bootstrap method to obtain an estimation of the accuracy of
the parameters describing the V
˙
O
2
kinetics (7, 8, 17). This method,
creating 1,000 different samples of the same size than the original data
set, allows the determination of a coefficient of variation for each
mathematical parameter on an individual basis.
Data were first tested for distribution normality and variance
homogeneity. Subsequently, the differences between groups before
the training period were analyzed with the Mann-Whitney procedure.
To test for both treatment (Hyp vs. Nor) and time (before vs. after)
effects on each of the measurements during the training period, we
used a two-way ANOVA for repeated measures. When significant
modifications were found, the Student-Newman-Keuls post hoc pro-
cedure was performed to localize the difference. Pearson linear
regression analysis was used to determine any potential linear rela-
tionship between variables. All statistical analyses were performed
with the SigmaStat 3.0 software (SPSS, Chicago, IL), and the level of
significance was chosen for P ⬍ 0.05. Values are means ⫾ SE.
RESULTS
The anthropometric and treadmill performance characteris-
tics of the athletes are shown in Table 1. No significant
differences were reported between the two experimental
groups before the training period. Moreover, in both groups,
the training period did not modify anthropometric and blood
parameters, including body mass [Hyp after: 70.5 ⫾ 2.2 kg,
nonsignificant (NS); Nor after: 71.3 ⫾ 2.2 kg, NS], hemoglo-
bin (Hyp after: 15.8 ⫾ 0.5 g/dl, NS; Nor after: 15.7 ⫾ 0.5 g/dl,
NS), and Hct (Hyp after: 46.4 ⫾ 1.5%, NS; Nor after: 46.9 ⫾
1.2%, NS).
Training Load
Laboratory training sessions. At the beginning of the study
and according to the training environment, the Hyp group
trained at a significantly lower running speed (Table 2). These
different running speeds corresponded to the same exercise
HR, whether expressed in absolute (Hyp: 166 ⫾ 3 vs. Nor:
172 ⫾ 3 beats/min; NS) or in relative value (Hyp: 96 ⫾ 1 vs.
1241INTERMITTENT HYPOXIA TRAINING AND AEROBIC CAPACITY
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Nor: 94 ⫾ 1%; NS). During the first VT
2
training session in the
Hyp group, blood oxygen saturation stabilized at a value of
80 ⫾ 1%. At the 4th wk, the running speed of the VT
2
bouts
was increased by 0.4 ⫾ 0.1 km/h for the Hyp group, but not
modified for the Nor group. As a result, HR values remained
unaltered throughout the 6-wk intervention in both groups as it
was the case for blood oxygen saturation in the Hyp group. For
the Hyp group, the total duration of hypoxic exposure
amounted to 384 min (i.e., week 1 ⫹ week 2 ⫹...⫹ week 6)
and was well tolerated.
Total training load. The total training load (i.e., field and
laboratory training sessions) was comparable in both groups.
During the 6-wk training, Hyp and Nor groups performed,
respectively, 33.0 ⫾ 0.6 and 31.2 ⫾ 1.7 training sessions,
leading to no difference in total training time and total training
distance (Hyp: 2,013 ⫾ 114 min and 478 ⫾ 27 km vs. Nor:
2,095 ⫾ 158 min and 498 ⫾ 40 km). Consequently, the
averaged running speed over the 6-wk training intervention
was similar in both groups (Hyp: 14.3 ⫾ 0.2 vs. Nor: 14.2 ⫾
0.2 km/h). No significant differences appeared either in total
time or in total distance run in the respective intensity zones
(Table 2).
Exercise Capacity in Hypoxia
IET. Table 3 and Fig. 2A report the effects of the 6-wk
training on results of the IET
H
. Only the Hyp group signifi
-
cantly improved submaximal and maximal running velocities
(Table 3) under hypoxia. Indeed, vVT
1
, vVT
2
, and vV
˙
O
2 max
increased, respectively, by ⫹7, ⫹8, and ⫹5% after IHT. The
V
˙
O
2
associated with these velocities improved in the same
proportions by ⫹7, ⫹7, and ⫹5%, respectively (Fig. 2A), but
RE did not change. The maximum O
2
p(O
2
p
max
) improved
(⫹5%) only in the Hyp group after IHT (Table 3). Conversely,
the Nor group demonstrated no improvement of all of these
parameters under hypoxic conditions.
Exercise Capacity in Normoxia
IET. vV
˙
O
2 max
improved significantly by ⫹4 and ⫹3% and
vVT
2
increased significantly by ⫹5 and ⫹3% in the Hyp and
Nor groups, respectively (P ⬍ 0.05), under normoxic condi-
tions (Table 3). However, only the Hyp group significantly
enhanced V
˙
O
2 max
as well as V
˙
O
2
at VT
2
by ⫹5 and ⫹7%,
respectively (P ⬍ 0.05), with no modification of the RE (Fig.
Table 2. Training load characteristics
Hypoxic
Group
Normoxic
Group P Value
Laboratory controlled sessions
First 3 wk
Running speed at VT
2
, km/h
15.0⫾0.2 16.7⫾0.3 ⬍0.01
Running speed absolute, % 77⫾188⫾1 ⬍0.01
Running speed relative, % 89⫾288⫾1NS
Last 3 wk
Running speed at VT
2
, km/h
15.4⫾0.2 16.7⫾0.3 ⬍0.01
Running speed absolute, % 76⫾186⫾1 ⬍0.01
Running speed relative, % 87⫾186⫾1NS
Total training, % of total training time
Low 72.7⫾1.8 68.7⫾4.2 NS
Moderate 4.9⫾1.4 9.7⫾1.9 NS
Heavy 21.0⫾1.0 21.4⫾2.8 NS
Severe 1.3⫾0.5 0.3⫾0.1 NS
Values are means ⫾ SE. The running velocity of the controlled training
sessions was readjusted after 3 wk of training, according to heart rate changes
(See
METHODS). Running speed absolute is running velocity expressed as a
percentage of the pre- (first 3 wk) or posttraining (last 3 wk) velocity
associated with V
˙
O
2 max
under normoxic conditions. Running speed relative is
running velocity expressed as a percentage of the pre- (first 3 wk) or
posttraining (last 3 wk) velocity associated with V
˙
O
2max
in the group-specific
environment. Intensity zones are as follow: Low ⬍ velocity associated with the
first ventilatory threshold ⬍ Moderate ⬍ velocity associated with the second
ventilatory threshold ⬍ Heavy ⬍ velocity associated with maximal oxygen
uptake ⬍ Severe. P value, level of significance for the difference between
groups.
Table 3. Running velocities, running economy, and selected
maximal physiological parameters measured in normoxic
and hypoxic incremental tests before and after
the 6-wk training period
Hypoxic Group Normoxic Group
Pre Post Pre Post
Running velocities
V
peak
, km/h
Normoxia 20.5⫾0.2 20.9⫾0.2* 19.8⫾0.4 20.2⫾0.4*
Hypoxia 17.7⫾0.3 18.4⫾0.2
†
17.2⫾0.4 17.6⫾0.4
vV
˙
O
2max
, km/h
Normoxia 19.6⫾0.2 20.3⫾0.2
†
19.0⫾0.4 19.6⫾0.3*
Hypoxia 17.0⫾0.4 17.8⫾0.3
†
16.3⫾0.3 16.7⫾0.4
vVT
2
, km/h
Normoxia 18.0⫾0.2 18.9⫾0.1
†
17.2⫾0.4 17.8⫾0.4*
Hypoxia 15.4⫾0.2 16.6⫾0.2
†
15.1⫾0.3 15.6⫾0.4
vVT
1
, km/h
Normoxia 15.3⫾0.2 15.6⫾0.2 14.4⫾0.4 15.0⫾0.4*
Hypoxia 13.1⫾0.2 14.0⫾0.2
†
12.9⫾0.3 13.2⫾0.4
Running economy, ml O
2
䡠min
⫺1
䡠kg
⫺1
Normoxia at 12 km/h 38.2⫾1.9 36.9⫾0.8 36.9⫾1.2 36.1⫾1.0
Hypoxia at 12 km/h 39.3⫾1.1 38.6⫾1.6 39.9⫾1.3 38.7⫾1.3
Normoxia at 18 km/h 57.9⫾1.6 57.8⫾1.4 57.2⫾1.8 55.6⫾1.1
Hypoxia at 15 km/h 50.2⫾1.3 50.6⫾2.1 51.4⫾1.8 49.8⫾1.2
Maximal physiological parameters
O
2
p
max
,ml䡠 beats
⫺1
䡠
min
⫺1
Normoxia 24.7⫾0.8 26.2⫾1.0* 23.8⫾0.6 23.9⫾0.9
Hypoxia 23.5⫾1.0 24.8⫾1.2* 22.6⫾0.8 22.5⫾0.5
HR
max
, beats/min
Normoxia 183⫾2 182⫾4 184⫾4 185⫾3
Hypoxia 170⫾3 172⫾3 174⫾4 174⫾3
V
˙
E
max
, l/min
Normoxia 157⫾7 162⫾8 147⫾7 144⫾5
Hypoxia 134⫾7 137⫾8 142⫾5 132⫾7
[La]
max
, mmol/l
Normoxia 6.9⫾0.8 6.5⫾0.5 7.3⫾0.5 7.9⫾0.7
Hypoxia 6.7⫾0.9 6.6⫾0.7 8.6⫾0.7 7.7⫾0.7
RER
max
Normoxia 1.05⫾0.02 1.05⫾0.02 1.04⫾ 0.03 1.04⫾0.03
Hypoxia 1.04⫾0.02 1.07⫾0.04 1.06⫾0.01 1.06⫾0.03
V
˙
O
2
leveling off
(yes/no), no.
Normoxia 7/2 6/3 6/3 8/1
Hypoxia 6/3 6/3 7/2 6/3
Values are means ⫾ SE. Pre and Post, before and after the 6-wk training
period; V
peak
, vV
˙
O
2 max
, vVT
2
, vVT
1
: running velocities achieved during the
incremental exercise test at exhaustion, at V
˙
O
2max
, and at the second and first
ventilatory threshold, respectively; O
2
p
max
,HR
max
,V
˙
E
max
, [La]
max
, and
RER
max
: maximal values for oxygen pulse, heart rate, ventilation, blood
lactate, and respiratory exchange ratio, respectively; V
˙
O
2
leveling off, number
of subjects who have/have not reached a V
˙
O
2
plateau at the end of the
incremental test. Significant differences between Pre and Post values: *P ⬍
0.05,
†P ⬍ 0.01.
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2B). Again, O
2
p
max
increased (⫹6%) only in the Hyp group
after IHT (Table 3). The Nor group disclosed no significant
changes, neither for exercise V
˙
O
2
nor for RE.
All-out exercise test. The all-out exercise tests were per-
formed in normoxia at the same absolute running velocity
before and after training, i.e., pretraining vV
˙
O
2 max
. After train
-
ing, this speed amounted to 96 and 97% of the posttraining
vV
˙
O
2 max
for the Hyp and Nor group, respectively, therefore
corresponding to the same relative running speed in both
groups. As shown in Fig. 3, training significantly enhanced
T
lim
in the Hyp but not in the Nor group (⫹35 vs. ⫹10%, P ⬍
0.05). Similar changes in the time sustained at pretraining
vV
˙
O
2 max
were obtained when the transition period required for
treadmill speed stabilization was subtracted from T
lim
(⫹35 vs.
⫹10%, P ⬍ 0.05). Concomitantly, the end-exercise V
˙
O
2
achieved during the all-out test increased in the Hyp group only
(⫹6%, P ⬍ 0.05), whereas the maximal [La] values remained
unchanged after training (Table 4).
The kinetics of V
˙
O
2
response of a typical subject from the
Hyp and Nor group are shown in Fig. 4. Training did not
modify parameters of the fast component of V
˙
O
2
kinetics
(Table 4) and O
2
def remained unchanged (Hyp group: before
3,319 ⫾ 266 vs. after 3,372 ⫾ 469 ml O
2
, NS; Nor group:
before 2,793 ⫾ 239 vs. after 2,563 ⫾ 169 ml O
2
, NS). A slow
Fig. 2. Percent change in maximal oxygen uptake (V
˙
O
2 max
) in hypoxia (A) and in normoxia (B) for each individual subject of the hypoxia group (Hyp; left) and
normoxia group (Nor; middle), before and after the training program. Horizontal solid lines with vertical bars represent group changes. Horizontal dashed lines
are the zero level. Right: absolute mean changes for all subjects from the Hyp and Nor groups. Hyp and Nor represent the groups of subjects that performed the
laboratory-controlled training sessions under hypoxic or normoxic conditions, respectively. All values are presented as means ⫾ SE. Significant differences
before vs. after training, *P ⬍ 0.05.
Fig. 3. Percent change in time to exhaustion for each individual subject before and after the training program in the Hyp (A) and Nor (B) groups. Horizontal
solid lines with vertical bars represent group changes. Horizontal dashed lines are the zero level. C: absolute mean changes for all subjects from the Hyp and
Nor groups. Values are presented as means ⫾ SE. Hyp and Nor represent the group of subjects who performed the laboratory-controlled training sessions under
hypoxic or normoxic conditions, respectively. T
lim
, running time to exhaustion at the pretraining minimal velocity associated with V
˙
O
2 max
. Significant differences
before vs. after training, *P ⬍ 0.05.
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component of V
˙
O
2
kinetics was consistently observed in only
five subjects in the Hyp and six subjects in the Nor group,
respectively. Its computed amplitude (A⬘
2
) did not change after
training, even when expressed at similar exercise time after vs.
before training (A⬘
2
old). Neither V
˙
O
2
kinetics alterations nor
IET
N
-derived factors significantly correlated with the observed
modifications in T
lim
, either in absolute or in delta (after vs.
before) values. There was no difference between groups in TA
V
˙
O
2 max
or in T
lim
at V
˙
O
2 max
before training (Table 4). How
-
ever, T
lim
at V
˙
O
2 max
significantly improved by 2.5 times only
in the Hyp group after IHT, without modification of TA
V
˙
O
2 max
.
DISCUSSION
Major Findings
This study demonstrates that, when the hypoxic sessions of
an IHT program features moderate duration (24 – 40 min) and
high intensity (VT
2
), significant improvements of V
˙
O
2 max
are
obtained in already trained athletes, not only at altitude but also
at sea level. Despite similar total training load (i.e., absolute
and relative values), no such amelioration in the maximal rate
of O
2
fluxes was observed in a control group exercising under
permanent normoxia. The second finding of this work is that
the present IHT program significantly lengthened T
lim
, specif
-
ically in the Hyp group, without significant changes in V
˙
O
2
kinetics. These results suggest that IHT did not change the
control of O
2
flux adjustment to high-intensity exercise in
competitive runners. Moreover, T
lim
improvement in the Hyp
group was correlated neither with V
˙
O
2 max
nor with ventilatory
thresholds changes.
Maximal Aerobic Capacity and Ventilatory Thresholds
In hypoxia. This study demonstrates that the present IHT
program elicits significant improvements of maximal and sub-
maximal running velocities under hypoxia (vV
˙
O
2 max
, vVT
2
,
Table 4. Training effects on the time until exhaustion and the parameters of the V
˙
O
2
kinetics
Hypoxic Group Normoxic Group
Pre Post Pre Post
Values
CV mean,
% Values
CV mean,
% Values
CV mean,
% Values
CV mean,
%
td
1
,s
18.0 ⫾ 1.7 13.9 22.6 ⫾ 2.6 20.5 19.3 ⫾ 2.2 23.0 16.2 ⫾ 1.4 19.8
1
,s
31.0 ⫾ 4.4 19.8 32.3 ⫾ 2.5 22.4 29.7 ⫾ 2.1 20.4 26.9 ⫾ 2.1 24.3
A
1
, ml/min
3,605 ⫾ 159 2.0 3,825 ⫾ 202 3.3 3,680 ⫾ 138 2.3 3,565 ⫾ 107 3.0
td
2
,s
136.1 ⫾ 15.3 (n ⫽ 5) 16.9 207.8 ⫾ 29.1 (n ⫽ 5) 28.7 179.1 ⫾ 13.7 (n ⫽ 6) 20.6 140.1 ⫾ 21.1 (n ⫽ 6) 21.2
2
,s
157.3 ⫾ 38.1 (n ⫽ 5) 25.4 148.8 ⫾ 49.3 (n ⫽ 5) 44.5 163.4 ⫾ 39.7 (n ⫽ 6) 17.4 108.6 ⫾ 38.2 (n ⫽ 6) 29.3
A⬘
2
, ml/min
475 ⫾ 101 (n ⫽ 5) 39.4 532 ⫾ 92 (n ⫽ 5) 30.2 269 ⫾ 65 (n ⫽ 6) 41.1 371 ⫾ 89 (n ⫽ 6) 35.7
A⬘
2
old, ml/min
475 ⫾ 92 (n ⫽ 5) 333 ⫾ 74 (n ⫽ 5)
TA V
˙
O
2 max
,s
344 ⫾ 66 207 ⫾ 34 187 ⫾ 32 264 ⫾ 61
T
lim
@V
˙
O
2 max
,s
228 ⫾ 47 577 ⫾ 75* 319 ⫾ 46 281 ⫾ 73
EE V
˙
O
2
,
ml䡠 kg
⫺1
䡠min
⫺1
62.7 ⫾ 1.3 66.8 ⫾ 1.5* 62.0 ⫾ 0.4 61.6 ⫾ 1.1
EE HR, beats/min 176 ⫾ 3 179 ⫾ 3 177 ⫾ 3 178 ⫾ 4
EE [La], mmol/l 7.7 ⫾ 0.6 7.2 ⫾ 0.7 9.5 ⫾ 0.8 9 ⫾ 1.1
Values are means ⫾ SE. CV mean coefficient of variation estimated by the bootstrap method; A
1
and A⬘
2
, amplitude terms for V
˙
O
2
;td
1
and td
2
, time delays
to onset of each component;
1
and
2
, time constants of each component; A⬘
2
old, amplitude of the posttraining slow component obtained when the subject
reached his pretraining T
lim
(only 5 and 6 subjects demonstrated a slow component of the V
˙
O
2
kinetics in the hypoxia and normoxia groups, respectively); EE
V
˙
O
2
, end-exercise oxygen uptake; TA V
˙
O
2max
, time to reach pretraining V
˙
O
2max
;T
lim
at V
˙
O
2max
, time sustained at pretraining V
˙
O
2max
; EE HR and EE [La],
end-exercise values for heart rate and blood lactate, respectively. Significant differences between Pre vs. Post values, *P ⬍ 0.05.
Fig. 4. Kinetics of the oxygen uptake (V
˙
O
2
) response of one representative
individual from the Hyp group (A) and Nor group (B) during the all-out run at
the pretraining minimal velocity associated with V
˙
O
2 max
, before (■) and after
(
䊐) the 6 wk of intermittent hypoxia training program. Note that T
lim
changes
appeared, despite no modification in the kinetics of the V
˙
O
2
response in both
subjects.
1244 INTERMITTENT HYPOXIA TRAINING AND AEROBIC CAPACITY
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and vVT
1
). Accordingly, all of the athletes of the Hyp group
required an increase of the training velocity under hypoxia
(⫹0.4 km/h) to maintain the initial HR values throughout the
6-wk IHT program. Since no RE changes resulted from the
training period, the improvements observed in running speeds
are mainly due to significant increases in the associated O
2
flux
rates in the Hyp group only (V
˙
O
2 max
and V
˙
O
2
at the ventilatory
thresholds). These findings expand the observations reported
by Terrados et al. (43) in professional cyclists, demonstrating
a specific increase of exercise capacity under hypoxia after
altitude training only. Moreover, the present data also ex-
tend to already trained athletes the results obtained in
untrained subjects, in which some consensus has been reach
about the beneficial effect of hypoxic training on V
˙
O
2 max
at
altitude (21, 47).
At sea level. The effects of IHT on the aerobic performance
capacity at sea level remains highly debated, especially in
trained subjects (32). Despite both groups improving their
running velocities at sea level (vV
˙
O
2 max
and vVT
2
) in quite
near proportions, the underlying physiological adaptations may
well have been different. vV
˙
O
2 max
and vVT
2
increased in the
Nor group, through concomitant changes of V
˙
O
2
and RE values
(although not statistically significant). Conversely, one impor-
tant result of this study is that the running speed improvements
of the Hyp group were associated with increases in V
˙
O
2 max
and
V
˙
O
2
at VT
2
, with no RE alterations. These findings suggest that
a normoxic training effect was present in the Nor group over
the 6-wk period and that this effect was further potentialized by
IHT in the Hyp group, through an additional effect of IHT vs.
normoxic training on aerobic power. This amelioration of
aerobic power in the Hyp group is further exemplified by the
increased V
˙
O
2
at exhaustion during the all-out test. According
to the specific intensity and duration of the present hypoxic
training sessions, our results are in agreement with previous
observations (38, 44, 46). Studies reporting no improvement in
V
˙
O
2 max
after IHT either used lower hypoxic exercise intensity
(at VT
1
) (46) or shorter hypoxic exercise bouts (0.5–1 min)
(44). On the other hand, similar increase in V
˙
O
2 max
has been
recently reported with an IHT model, including longer periods
of hypoxic exercise (2–12 min) (38). A specific oxygen-
sensing transcription factor, the hypoxia-inducible factor-1␣
(HIF-1␣), is expected to play a pivotal role for the functional
adaptations to hypoxic training (1, 11, 47). Of note, the
duration and intensity of the hypoxic exercise bouts included in
the present IHT model are in good agreement with the prop-
erties of HIF-1␣ expression at the cellular level in humans. Not
only does the half-time of the HIF-1␣ response to hypoxia fall
in the range of 12–13 min (25), but also the magnitude of this
response varies exponentially with the degree of Hyp in the
physiological range (26). These observations further reinforce
the necessity to combine a minimum duration and intensity of
hypoxic exercise in IHT programs, to reduce oxygen pressure
in the active muscle (37) and achieve a substantial HIF-1␣
response, resulting in peripheral muscle adaptations. Conse-
quently, present and previous results suggest that the combi-
nation of sufficient hypoxic exercise intensity and duration
within IHT programs is of paramount importance to obtain
significant performance ameliorations in already trained ath-
letes. An additional advantage of the hypoxic sessions in the
present IHT design (i.e., 19% of the total training time in the
present study) is the possibility to maintain the usual training
load, which could also participate in the V
˙
O
2 max
improvement
that we observed.
Some of our findings let us consider that peripheral adapta-
tions might have been involved. We observed that O
2
p
max
improved in the Hyp group only after IHT. Because O
2
p
represents the product of stroke volume with ⌬(a-v)O
2
, and
because invasive experiments have shown that O
2
p
max
is
largely determined by ⌬(a-v)O
2
(35, 42), O
2
p
max
is likely to
have increased via an ⌬(a-v)O
2
-mediated mechanism after
IHT, suggesting an enhanced tissue O
2
extraction. Because our
study was not designed to investigate O
2
extraction, further
studies are needed to verify this hypothesis. Nevertheless,
several muscle changes have already been observed after
hypoxic training programs in endurance-trained subjects, such
as larger deoxygenation in active muscles (28) and, although
not reaching significance, a 36% increase in capillary density
(43), supporting the concept of an improved O
2
extraction after
IHT. Moreover, modelization studies have suggested that ex-
ercising in Hyp may increase the relative contribution of
peripheral factors (i.e., muscle perfusion, peripheral diffusion,
and mitochondrial capacity) to O
2
delivery and utilization (14,
15, 19, 48). We believe that the intensity and duration of the
hypoxic exercise bouts included in the present IHT program
are sufficient to induce the signaling cascade initiated by
HIF-1␣, leading to molecular and tissue changes within the
exercising skeletal muscles of our Hyp subjects (34). The
results disclosed in the two companion papers of our study,
appearing in the present issue, also support this concept, at
least in part. Conversely, as far as O
2
transport is concerned,
we observed that hemoglobin and Hct were similar in both
groups, before vs. after training, in agreement with previous
reports (22, 28, 34, 38, 43). Together with the unchanged
maximum HR (HR
max
), these results suggest that O
2
delivery
capacity is unlikely to represent a major cause of the V
˙
O
2 max
improvement of the Hyp group after IHT.
T
lim
at vV
˙
O
2 max
and Oxygen Kinetics
A major finding of the present study is that T
lim
is specifi
-
cally improved after IHT (⫹35%) but unchanged after nor-
moxic training. Due to the exponential shape of the running
velocity/time-to-fatigue relationship, our observed 3.7-min
lengthening of T
lim
suggests that larger improvements of en
-
durance time at lower velocities may have occurred. Thus this
observation can be considered as a hallmark of an enhanced
performance capacity in middle and long-distance running
events. Consequently, T
lim
lengthening in the present study
extends previous findings, demonstrating that 3 wk of IHT
dramatically delayed fatigue during a submaximal constant-
load test in elite triathletes (45).
To date, the mechanisms leading to T
lim
improvement re
-
main poorly understood. It has been proposed that normoxic
training may lengthen the endurance time at a given absolute
running velocity, due to increases of vV
˙
O
2 max
and/or submaxi
-
mal running velocity (velocity at the lactate threshold), reduc-
ing the relative running speed the subjects have to sustain (i.e.,
expressed in percentage of the posttraining vV
˙
O
2 max
) (12, 23).
In the present study, we did not find any correlation between
T
lim
changes and alterations of maximal (V
˙
O
2 max
) and sub
-
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maximal (ventilatory thresholds) V
˙
O
2
nor with their associated
velocities (vV
˙
O
2 max
, vVT
2
, and vVT
1
). Therefore, it is unlikely
that changes in O
2
fluxes (i.e., V
˙
O
2 max
) and/or running veloc
-
ities (i.e., vV
˙
O
2 max
) are the major causes of the T
lim
improve
-
ment that we observed. However, as V
˙
O
2 max
and ventilatory
thresholds improved concomitantly with T
lim
in the Hyp group,
we cannot rule out the possible relevance of these changes, and
this point warrants further investigations.
Alternatively, V
˙
O
2
kinetics have also been proposed as a
determinant of T
lim
that may be improved after normoxic
training. To the best of our knowledge, the effect of hypoxic
training on V
˙
O
2
kinetics has never been reported, especially in
already trained athletes. A speeding of V
˙
O
2
adjustment has
been proposed as a potential contributor of the delayed fatigue
after high-intensity training at sea level (13). These changes are
expected to reduce the reliance toward anaerobic metabolisms
for energy provision, which have been reported to amount to
⬃15% of energy expenditure during such T
lim
testing (18).
Nevertheless, we failed to observe such a mechanism, as
illustrated by an unchanged fast component of V
˙
O
2
kinetics,
leading to unaltered O
2
def in both experimental groups. Addi
-
tionally, sea level training was often demonstrated to reduce
the amplitude of the V
˙
O
2
slow component, thereby contributing
to improve exercise tolerance and delay fatigue (20). Again, we
recorded no alterations in the V
˙
O
2
slow component, even when
expressed at consistent exercise time before vs. after IHT
(A⬘
2
old). Taken together, the unchanged fast and slow compo
-
nents of V
˙
O
2
kinetics suggest that the dynamic control of O
2
fluxes is not a likely contributor to T
lim
changes after IHT in
already trained athletes. Therefore, neither the rates of O
2
fluxes nor V
˙
O
2
kinetics significantly account for the T
lim
lengthening that we observed, suggesting that IHT may im-
prove T
lim
by specific, hypoxic-related adaptations.
A 2.5 times longer T
lim
at V
˙
O
2 max
was observed in the Hyp
group after IHT, indicating an improved capacity to sustain
high levels of O
2
fluxes close to or above pretraining V
˙
O
2 max
,
before exhaustion occurs. This observation appears, despite
unchanged [La] values recorded at exhaustion during the all-
out test after vs. before IHT. Collectively, these findings
suggest either a slower rate of blood lactate accumulation
and/or a better tolerance of high levels of blood lactate after
IHT. This might be associated with a concomitant amelioration
of metabolite exchange and/or removal, contributing to en-
hance cellular homeostasis, thereby delaying the time at which
fatigue occurs. This idea has already been suggested by a
previous study, demonstrating that T
lim
is related to the capac
-
ity of lactate exchange and removal. Due to its coupled trans-
port with H
⫹
(27), an improved lactate exchange and removal
could have contributed to slow down the progressive lowering
of muscle pH while running at pretraining vV
˙
O
2 max
. Although
purely speculative in the present study, additional supports for
the peripheral hypothesis underlying the improvement of en-
durance performance capacity after IHT are presented in the
two following papers appearing in this issue. The second
companion paper of the present study suggests that IHT in-
duces qualitative mitochondrial changes leading to an en-
hanced channeling of energy within the muscle cell, whereas
the third companion paper shows that IHT training induces
transcriptional changes, potentially mediated by HIF-1␣, lead-
ing to enhanced metabolite exchanges and improved aerobic
metabolism within the skeletal muscle cell.
Limitations of the Study
A limitation of the present study is related to the IHT design
and management of training intensities. First, we speculated
that VT
2
might be more effective in IHT designs than lower
(i.e., VT
1
) or higher (i.e., vV
˙
O
2 max
) training intensities, be
-
cause of the achievement of a unique combination of intensity
and duration of the hypoxic training stimulus. Moreover, this
protocol was chosen as it allowed the usual training load of
athletes to be unaltered (Table 2). Nevertheless, we did not test
this hypothesis in the present study by including additional
experimental groups training at either lower or higher intensity
during the hypoxic sessions. Therefore, it remains to be deter-
mined whether different hypoxic training intensities and dura-
tions elicit similar beneficial effects on endurance performance
capacity in already trained athletes. Especially including a
group trained at, or close to, VT
1
, would have been helpful and
remains to be done.
Second, only the Hyp group required its laboratory running
speed to be increased at the end of week 3 to maintain the initial
HR level, raising the question as to whether the Hyp group may
have trained harder than the Nor group. We believed that this
possibility is not supported by the unchanged VT
2
at the end
vs. the beginning of training, when expressed in percentage of
posttraining vV
˙
O
2 max
, indicating that both groups trained at the
same relative intensity during the laboratory sessions (Table 3).
Nevertheless, a different time course of training speed and
vV
˙
O
2 max
improvements may have led to a transient increase
(i.e., weeks 4 and 5) in relative training intensity, thereby
potentially acting as a confounding factor in our results. We
believe that this possibility should have been counterbalanced
by the transient lower relative intensity that could be expected
in the Hyp group just before training speed adjustments (i.e.,
weeks 2 and 3). Therefore, differences in relative training
intensity, if present, may have probably played a minor role in
the present study. Nevertheless, future studies need to incor-
porate serial V
˙
O
2 max
testing to completely eliminate this pos
-
sibility.
On the same token, an additional T
lim
test performed at the
new vV
˙
O
2 max
after training (same relative intensity before vs.
after training) could have been helpful to clarify the role of
V
˙
O
2 max
and vV
˙
O
2 max
in the improvement of T
lim
that we
observed in the Hyp group (⫹35%). However, since both
groups improved vV
˙
O
2 max
in quite near proportions, the post
-
training T
lim
was performed at a similar relative intensity in
both groups (96 vs. 97% of the posttraining vV
˙
O
2 max
in the
Hyp and Nor group, respectively). Therefore, although not
performed at 100% of posttraining vV
˙
O
2 max
, the changes in
relative testing intensity are unlikely to account for the T
lim
improvements that we observed.
On a methodological standpoint, it can be argued from our
relatively low maximum respiratory exchange ratio and max-
imum [La] values (Table 3) that V
˙
O
2 max
might have been
underestimated. Nevertheless, 67–89% of the subjects reached
a true V
˙
O
2
plateau (i.e., always at least 6 of 9 subjects in each
test), and the HR
max
were close to (97%) the theoretical HR
max
.
Moreover, V
˙
O
2 max
as well as HR
max
were significantly higher
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on the treadmill than the ones previously obtained on the cycle
ergometer at the time of subjects’ basal medical examination.
Conversely, these parameters were similar between IET and
T
lim
testing. Therefore, we believe that true V
˙
O
2 max
has been at
least closely approached. On the other hand, our RE values
were estimated at moderate mainly aerobic (12 km/h) and high
(18 and 15 km/h in normoxia and hypoxia, respectively)
running speeds, yielding results consistent with previous re-
ports (40, 41, 50). Nevertheless, since they were not measured
at steady state during constant load exercise, these RE values
must be interpreted with caution, until appropriate RE testing is
done by further investigations.
In conclusion, the present study investigates the effects of a
carefully calibrated IHT program, designed to avoid reduction
in training load, by including high-intensity (VT
2
) and moder
-
ate-duration (24 – 40 min) hypoxic sessions, into the usual
normoxic training of already trained athletes. Such an IHT
model provides an original framework, in which the metabolic
stimulus is enhanced through hypoxic sessions, without alter-
ing the mechanical component of the usual training load.
Significant improvements of several indexes of aerobic perfor-
mance capacity were observed not only at altitude but also at
sea level, including V
˙
O
2 max
and T
lim
. Additionally, IHT did not
significantly modify V
˙
O
2
kinetics such that T
lim
lengthening
was correlated neither with changes in the rate of V
˙
O
2
adjust
-
ment nor with V
˙
O
2 max
and ventilatory thresholds. Collectively,
these findings suggest that the enhanced endurance perfor-
mance capacity obtained with IHT might be due to specific
muscle adaptations to hypoxic training. This hypothesis is
further explored in the two following companion papers of our
study appearing in the present issue.
ACKNOWLEDGMENTS
The authors thank all of the athletes for enthusiastic participation; the whole
laboratory staff from the De´partement de Physiologie et des Explorations
Fonctionnelles and the Equipe d’Accueil 3072 for daily technical support; M.
Franc¸ois Piquard for statistical advices; and Vale´rie Bougault and Fre´de´ric
Daussin for contribution during the training sessions. The help of M. Fabio
Borrani was greatly appreciated for the application of the bootstrap method to
the statistical treatment of the V
˙
O
2
kinetics.
GRANTS
This project was supported by grants from the International Olympic
Committee and the Ministe`re Franc¸ais de la Jeunesse et des Sports. The
scientific and sport coordination were, respectively, assumed by Prof. Jean-
Paul Richalet and M. Laurent Schmitt, to whom we express our sincere
gratitude.
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