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Akinobu Nishimura is with the Department of Orthopaedic Surgery, Mie University Graduate School of
Medicine, Tsu City, Mie Prefecture, Japan. Masaaki Sugita is with the Department of Health and
Physical Education, Mie University Faculty of Education, Tsu City, Mie Prefecture, Japan. Ko Kato is
with the Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City,
Mie Prefecture, Japan. Aki Fukuda is with the Department of Orthopaedic Surgery, Suzuka Kaisei
Hospital, Suzuka, Japan. Akihiro Sudo is with the Department of Orthopaedic Surgery, Mie University
Graduate School of Medicine, Tsu City, Mie Prefecture, Japan, and Atsumasa Uchida is with the
Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City, Mie
Nishimura et al.
Resistance Training Under Hypoxic Conditions
Hypoxia Increases Muscle Hypertrophy
Induced by Resistance Training
Akinobu Nishimura, Masaaki Sugita, Ko Kato, Aki Fukuda,
Akihiro Sudo, and Atsumasa Uchida
Purpose: Recent studies have shown that low-intensity resistance training with
vascular occlusion (kaatsu training) induces muscle hypertrophy. A local hypoxic
environment facilitates muscle hypertrophy during kaatsu training. We postulated
that muscle hypertrophy can be more efficiently induced by placing the entire body
in a hypoxic environment to induce muscle hypoxia followed by resistance training.
Methods: Fourteen male university students were randomly assigned to hypoxia
(Hyp) and normoxia (Norm) groups (n = 7 per group). Each training session
proceeded at an exercise intensity of 70% of 1 repetition maximum (RM), and
comprised four sets of 10 repetitions of elbow extension and flexion. Students
exercised twice weekly for 6 wk and then muscle hypertrophy was assessed by
magnetic resonance imaging and muscle strength was evaluated based on 1RM.
Results: Muscle hypertrophy was significantly greater for the Hyp-Ex (exercised
flexor of the hypoxia group) than for the Hyp-N (nonexercised flexor of the hypoxia
group) or Norm-Ex flexor (P < .05, Bonferroni correction). Muscle hypertrophy
was significantly greater for the Hyp-Ex than the Hyp-N extensor. Muscle strength
was significantly increased early (by week 3) in the Hyp-Ex, but not in the
Norm-Ex group. Conclusion: This study suggests that resistance training under
hypoxic conditions improves muscle strength and induces muscle hypertrophy
faster than under normoxic conditions, thus representing a promising new training
Keywords: hypoxic conditions, resistance training, magnetic resonance imaging,
MRI, rating of perceived exertion, RPE, muscle hypertrophy
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Training under hypoxic conditions is believed to be generally useful for
improving aerobic performance by increasing erythropoietin and maximum oxygen
intake (VO2max).1 The altitude house,2 where air inside the house is aspirated to
increase the concentration of nitrogen and thus create a hypoxic state at low altitude, is
more convenient for training under hypoxic conditions than at high altitude. Training
under hypoxic conditions is currently under investigation using such facilities. On the
other hand, chronic exposure to high altitude leads to a reduction in muscle
cross-sectional area (CSA) and a decrease in the size of muscle fibers in humans.3
Hypoxia per se might be responsible for this atrophy, but malnutrition and reduced
activity levels are also possible causes of muscle loss.4–6 We assume that such muscle
loss has not been identified by studies using intermittent hypoxia in which subjects
exercise under hypoxic conditions but live in a normoxic environment between
The effects of resistance training under hypoxic conditions with recovery under
normoxia are mostly unknown. Takarada et al7 reported that low-intensity training
(30–50% 1-repetition maximum [1RM]) with vascular occlusion not only increases
electrophysiological activities during exercise, but also significantly increases the
CSA of the biceps brachii, brachialis and triceps brachii muscles after 16 weeks of
training. Their study showed that low-intensity resistance training with restricted
muscular venous blood flow causes muscle hypertrophy and strength gain, and they
described this process as kaatsu training. These findings suggest that restricted blood
circulation causes an intermittent hypoxic and acidic muscular environment, which
induces the recruitment of additional motor units and leads to increased muscle
hypertrophy. We postulated that muscle hypertrophy could be efficiently achieved by
resistance training under intermittent systemic hypoxia. Kaatsu training is useful for
resistance training of the extremities, but not for those of the trunk muscles because
tourniquets are required. If resistance training under hypoxic conditions leads to
hypertrophy, it would be very useful because all muscles including those of the trunk
We compared the induction of muscle hypertrophy by resistance training under
hypoxic and normoxic conditions using magnetic resonance imaging (MRI). Muscle
strength was also assessed based on 1RM (the maximum weight that can be lifted once
over the entire range of motion). Levels of exertion were compared between training
under hypoxic and normoxic conditions using the subjective rating of perceived
exertion (RPE) scale.
Materials and methods
Fourteen untrained male university students (age [mean ± standard deviation], 21.4 ±
1.1 y; height, 173.0 ± 5.4 cm; body mass, 65.9 ± 8.1 kg; body fat, 12.6 ± 3.7%)
provided written, informed consent to participate in the study after reviewing a
detailed explanation of its purposes and procedures. Body mass and percentage fat
were measured using a body composition analyzer (BC-118E, Tanita, Tokyo, Japan).
The students were randomly assigned to hypoxia (Hyp) and normoxia (Norm) groups
(n = 7 per group). Table 1 summarizes the physical characteristics of the participants.
Training intensity was established based on the maximum weight that could be lifted
over the entire range of motion (1RM) under normoxia. We referred to a published
protocol8 to determine 1RM from the 10RM test. Exercise intensity was set before the
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first training session and then revised 3 wk later. The participants continued with their
normal lives and were instructed not to start any new exercise during the course of the
study. The ethics review board of Mie University approved the study protocol.
\ insert Table 1 \
Constant Hypoxic Room
The constant hypoxic room (Alticube, USK, Nara, Japan) consists of a compressor, a
hypoxia generator with a polymer membrane and a hypoxic chamber covered with a
membrane separation-type vinyl tent to block air (width × length × height: 2900 ×
2000 × 2200 mm). Ambient air was compressed using the hypoxia generator and
hyperoxic air separated by the polymer membrane from hypoxic air was sent to the
hypoxic chamber to create a hypoxic environment. The oxygen concentration was
maintained at 16.0% (normal oxygen concentration, approx. 21%) during training and
room temperature was maintained at 27°C using an air conditioner for both groups.
Each participant stood holding a dumbbell in the nondominant hand and performed
standing French presses and arm curls. The Hyp and Norm groups sat inside the
hypoxic chamber under hypoxic condition or outside the chamber under normoxic
conditions, respectively, for 30 min before training. Both groups warmed up by
performing 10 repetitions each of standing French presses and arm curls at 30% 1RM
before the 30-min acclimation period. The exercise intensity during training was 70%
1RM for both standing French presses and arm curls. Each training session consisted
of four sets of 10 repetitions each, with a 1-min break between sets. If 10 repetitions
could not be finished, the set was ended at that point. A 3-min break was provided
between sets of both exercises. The Hyp group rested in the hypoxic chamber for 30
min after the end of each training session and then left the chamber for the next bout of
exercise. At 3 weeks after starting the training regime, muscle strength was measured
to adjust the intensity level of exercise as needed. The groups trained twice each week
for 6 consecutive weeks and all 14 participants completed the total of 12 sessions. The
dumbbell was raised or lowered at comparable rates within about 3 s (1 and 2 s for
concentric and eccentric movement). The mean numbers of standing French press
repetitions performed by the exercised upper arms of the Hyp (Hyp-Ex) and Norm
(Norm-Ex) groups were 36.2 ± 3.3 and 36.1 ± 2.9, and the mean numbers of arm curl
repetitions performed by the Hyp-Ex and Norm-Ex group were 35.6 ± 4.0 and 35.4 ±
3.2, respectively. The numbers of repetitions did not significantly differ between the
Hyp-Ex and Norm-Ex groups. Table 2 summarizes the exercise intensity and
repetitions actually applied by the two groups. The mean duration of each training
session was about 13 min.
\ insert Table 2 \
Magnetic Resonance Imaging
The cross-sectional areas of the Norm-Ex and Hyp-Ex groups, and of the
nonexercised arm of the Hyp (Hyp-N) group were measured using a 1.5-T super
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coiling system (Excel ART, Toshiba, Tokyo, Japan), of which the coil covered the
whole upper arm. The center of the upper arm was defined as the point equidistant
between the head of the humerus and the olecranon. Multislice sequences at 6-mm
intervals were obtained under the following conditions: 1.0 mm interception gap, 20 ×
20 cm field of view (FOV), spin echo T1-weighted pulse sequence, 500-ms repetition
time and 15-ms echo time. The scan matrix was 208 × 320. Scanning was immediately
initiated after supine participants relaxed while extending the arms to minimize
possible effects of a gravitational fluid shift. The entire sequence was completed
within 3–5 min. Images were captured along the long axis of the upper arm and the
range of acceptable slices was carefully determined. Of 11 slices, three images at the
center of the upper arm were selected to measure muscle CSA. Tissue outlines and the
CSA of muscles and other tissues were determined using Image J (version 1.37v)
software. The CSA value was the mean of three determinations. The standard
deviation of these three sets of measurements was 1.0%. The percent increase in CSA
relative to that before training was then calculated.
We determined muscle strength of each participant as 1RM from 10 RM tests8 at 1 wk
before, and at 3 and 6 wk after starting training. We referred to a published protocol8
to determine 1RM from the 10RM test (for example, 10 repetition maximum equals
75% 1RM). The intensity of subsequent training sessions was adjusted based on 1RM
measured 3 weeks after start of training.
We measured SpO2 at 10 min before, and at 0 and 30 min and 24 h after each training
session using a PULSOX-3i (Minolta, Osaka, Japan) placed on the index finger of the
dominant hand (nonexercise side). The SpO2 after 24 h was measured in both groups
under normoxic conditions.
Rating of Perceived Exertion
The level of perceived exertion was assessed after training using the Borg 6-20 RPE
scale.9 After each training session, the examiner showed the board with RPE scores to
the participant. The RPE scores of the participants were determined based on their
descriptions of difficulty in lifting the weight ranging from “very, very light” (6
points) to “very, very heavy” (20 points).
Unless otherwise stated, standard deviations were calculated for variables. The
statistical significance of differences among the degrees of change in the CSA of
Hyp-Ex, Hyp-N and Norm-Ex was determined using the one-way analysis of variance
(ANOVA). The statistical significance of differences among the CSA of Hyp-Ex,
Hyp-N, and Norm-Ex was determined using a two-way (group × time) ANOVA. The
statistical significance of differences between the muscle strength of Hyp-Ex and
Norm-Ex was determined using a two-way (group × time) repeated-measures
ANOVA. The significance of individual differences was evaluated using the
Bonferroni post hoc test. Differences between two variables within the same
individual were examined using Student’s paired t test. Differences in physical data,
characterization of exercise training, SpO2 and RPE between Hyp and Norm were
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examined using Student’s unpaired t test. A value of P < .05 with the Bonferroni
correction was regarded as significant for all statistical analyses.
Changes in CSA After Training
Table 3 shows the CSAs of all groups. The percentage increases of the elbow extensor
and flexor of the Hyp-Ex group were significantly larger (P < .05) compared with
before training (7.3 and 9.6%, respectively at week 6; Figure 1). In contrast, the CSA
values of the Norm-Ex and Hyp-N groups did not significantly increase.
\ insert Table 3 \
Muscle Strength (1RM)
Figure 2 shows the 1RM for all groups. This value significantly increased in both the
Hyp-Ex and Norm-Ex groups. Muscle strength following the standing French presses
and arm curls in the Hyp-Ex group increased by 71.1 and 61.6%, respectively, and in
the Norm-Ex group by 56.4 and 38.9%, respectively, with no significant differences
between the groups. Muscle strength significantly increased after 6 wk and between 3
and 6 wk of training in both groups, but at 3 wk of training only in the Hyp-Ex group.
\ insert Figure 1 thru 4 \
Figure 3 shows the effect of training under hypoxic and normoxic conditions on SpO2.
The SpO2 value of the Hyp group was significantly lower at 10 min before and at 0
and 30 min after training. At 24 h after training, no significant intergroup differences
were apparent, because SpO2 was measured in both groups under normoxic
Rating of Perceived Exertion
Figure 4 shows that the RPE did not significantly differ after either the standing
French presses or arm curls.
Compared with normoxic conditions, resistance training under hypoxic conditions
induced more muscle hypertrophy without differences in RPE during training. Muscle
strength (defined as 1RM) was significantly increased at week 6 for both groups, but
only for the Hyp-Ex group at week 3, suggesting that exposure to hypoxia accelerates
increases in muscle strength. Muscle hypertrophy was not significant in the Hyp-N
group (non-exercised-arm under hypoxic conditions), indicating that hypoxia alone is
insufficient to increase muscle strength (1RM) or induce muscle hypertrophy and that
it must be combined with exercise to achieve these results.
The time course of gains in muscle strength is affected by neural factors and by
muscle hypertrophy.10 We found here that 1RM had significantly increased in the
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Hyp-Ex group by week 3, whereas 6 wk were required to elicit an increase in CSA.
We also found a significant increase in 1RM of the Hyp-Ex group by week 6, although
CSA in this group did not increased significantly until that time. Dissociation between
increases in 1RM and in CSA would be expected since neuromuscular adaptations
occur before hypertrophy.11–13 The role of neural factors is particularly critical during
the early phase of strength training. Although protein synthesis is noticeable after a
single strength training session,14 overt changes in muscle hypertrophy are not evident
until 8 wk of exercise training in beginners.13,15–17 This delay, which is concurrent with
a substantial gain in muscle strength, has led some to suggest that neural factors are
important.12 Surface electromyography (SEMG) findings have revealed that strength
gains during the early phase of a training regimen without noticeable muscle
hypertrophy are associated with an increase in the amplitude of SEMG activity. This
has been interpreted as an increase in neural drive, which denotes the magnitude of
efferent neural output from the CNS to active muscle fibers. Moritani et al12 concluded
that increases in the amplitude of the SEMG signal appear well before muscle
hypertrophy, and thus neural factors account for the larger proportion of the initial
increase in strength. The present study found that 1RM significantly increased only in
the Hyp-Ex group after 3 wk. Although neural factors were involved in both groups,
the effect of early muscle hypertrophy might have increased muscle strength after 3
wk in the Hyp-Ex group.
Takarada et al7 reported that vascular occlusion combined with low-intensity
resistance training (Kaatsu training) effectively increases cross-sectional area and
muscle strength. Abe et al18 reported that muscle hypertrophy and muscle strength
could be increased by walking slowly while restricting blood flow. They also reported
that the combination of vascular occlusion and resistance training achieves muscle
hypertrophy because of hypoxia. They suggested that restricted blood circulation
causes a hypoxic and acidic muscular environment, which leads to greater muscle
hypertrophy. We believe that this mechanism functioned in the present study. The
effects of exercise training regimens under hypoxia are likely mediated by moderate
production of reactive oxygen species (ROS) promoting tissue growth,7 growth
hormone secretion stimulated by the intramuscular accumulation of metabolic
subproducts, such as lactate,19 testosterone secretion in Leydig cells20 and additional
recruitment of type ІІ fibers.7 These studies suggest that the ability of resistance
exercise to elicit muscle hypertrophy involves not only mechanical stress but also
metabolic, hormonal and neuronal factors. However, the precise mechanism of
muscle hypertrophy in resistance training under hypoxia (hypoxic training) requires
further studies for clarification.
Narici et al3 reported that subjects exposed to chronic hypoxia show less muscle
hypertrophy than the same subjects exposed to normoxia and Mizuno et al21 also
reported that general chronic exposure to hypoxia leads to muscle atrophy rather than
hypertrophy. However, these studies had a different design from our study in that the
conditions comprised chronic hypoxia, whereas our conditions consisted of training
under hypoxia with recovery under normoxia. Some authors4–6 have reported that
chronic hypoxia leads to malnutrition and reduced activity levels; thus, chronic
hypoxia is considered a possible cause of muscle loss. Friedmann et al22 reported that
strength training under hypoxia with recovery under normoxia could not promote
muscle hypertrophy. However, their study conditions comprised low-resistance (30%
1RM)/high repetition whereas ours comprised moderate resistance (70% 1RM)/low
repetition. Considering these findings, hypoxic training cannot lead to muscle
Page 7 of 15
hypertrophy simply by low resistance training such as kaatsu training. The induction
of muscle hypertrophy under hypoxia requires high resistance training.
This study suggests that exercise combined with exposure to hypoxia effectively
induces muscle hypertrophy and increases muscle strength. However, with kaatsu
training, tourniquets can only be placed on the extremities, whereas training under
hypoxic conditions can exercise all muscles, including those of the trunk. Thus, more
balanced muscle training programs can be designed, as this method is applicable to the
One limitation of this study is that it was not blinded (the Norm group trained
outside the chamber, so the subjects knew the group [Hyp or Norm] to which they had
been assigned), so some biases may affect the results. Another is that we used only
one O2 level (16%), so how the level of O2 affects muscle hypertrophy is unclear.
Further studies (several levels of hypoxia) are required to determine a dose-response
Because hypoxia leads to hypoxic pulmonary hypertension,23,24 adaptation must
be carefully controlled. Although further investigation is needed, high resistance
training under hypoxia appears to offer a practical and effective method of increasing
strength and inducing muscle hypertrophy.
Compared with normoxic conditions, resistance training under hypoxic conditions
efficiently improves muscle strength and rapidly induces muscle hypertrophy without
an obvious increase in the rate of perceived exertion (RPE) since it occurred at 6 rather
than at 8 wk in this group of beginners. While further studies are currently
investigating whether harmful effects can be induced during training, resistance
training under hypoxic conditions might be a novel method of increasing strength and
We are grateful to Takafumi Kawai and Tsubasa Sakurai for exceptional technical assistance, to
Tomomi Yamada for statistical analysis, and to the radiological technologists of Suzuka Kaisei
Hospital for the MRI measurements. This study was sponsored by grants from the Ministry of
Education, Culture, Sports, Science and Technology (Japan).
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Figure 1 — Degree of change in cross-sectional area (CSA) of extensors (top) and flexors
(bottom) after 6 wk of training. *Significant differences between groups (P < .05). Hyp-Ex,
exercised arm of hypoxia group; Hyp-N, nonexercised arm of hypoxia group; Norm-Ex,
exercised arm of normoxia group.
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Figure 2 — Degree of change in muscle strength (1 repetition maximum [RM]) of the extensors (top)
and flexor (bottom) after 6 wk of training. The Hyp-Ex and Norm-Ex groups did not significantly differ.
Significant differences from pretraining values, *P < .05 and **P < .01, respectively; significant
differences from 3-wk values, #P < .05 and ##P < .01, respectively. Hyp-Ex, exercised arm of hypoxia
group; Norm-Ex, exercised arm of normoxia group.
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Figure 3 — Mean SpO2 for hypoxia (Hyp) and normoxia (Norm) groups. All values of SpO2 were
measured at 24 h after training under normoxic conditions. *Significant differences between groups (P <
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Figure 4 — Changes in rating of perceived exertion (RPE) after each set of standing French presses
(top) and arm curls (bottom). Intergroup differences are not significantly different at any time point.
Hyp, hypoxia group; Norm, normoxia group.
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Table 1 Physical data of hypoxia (Hyp) and normoxia (Norm)
groups before and after 6 wk of training
Hyp (n = 7) Norm (n = 7)
Pretraining Posttraining Pretraining Posttraining
Age (y) 22.7 ± 2.7 — 21.6 ± 1.6 —
Height (cm) 174.6 ± 5.0 — 171.4 ± 5.2 —
Body mass (kg) 66.8 ± 6.0 66.9 ± 6.8 65.0 ± 8.1 65.1 ± 8.1
Body fat (%) 12.3 ± 3.0 13.2 ± 0.7 12.8 ± 4.5 12.7 ± 4.3
Note. Body mass and percentage fat were measured using a body composition analyzer (BC-118E,
Tanita, Tokyo, Japan). The Hyp and Norm groups did not significantly differ.
Table 2 Characterization of exercise training
French press Intensity % 1RM (%) 0–3 wk 70.7 ± 2.1 70.6 ± 1.7
4–6 wk 69.6 ± 1.4 71.0 ± 1.5
Repetitions 36.2 ± 3.3 36.1 ± 2.9
Arm curl Intensity % 1RM (%) 0–3 wk 70.3 ± 0.8 69.5 ± 1.3
4–6 wk 70.1 ± 0.7 69.7 ± 0.5
Repetitions 35.6 ± 4.0 35.4 ± 3.2
Note. The Hyp-Ex and Norm-Ex groups did not significantly differ. RM, repetition maximum;
Hyp-Ex, exercised arm of hypoxia group; Norm-Ex, exercised arm of normoxia group.
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Table 3 Cross-sectional areas (CSA) of elbow extensor and
flexor before and after 6 weeks of training
Extensors (cm2) Flexors (cm2)
Pretraining Posttraining ΔChange Pretraining Posttraining ΔChange
Hyp-Ex 25.6 ± 2.6 27.5 ± 3.9* 1.9 ± 1.1 12.9 ± 1.1 14.2 ± 1.5* 1.3 ± 0.9
Hyp-N 26.3 ± 3.1 26.2 ± 3.2 –0.1 ± 0.2 13.2 ± 1.5 13.1 ± 1.7 0.0 ± 0.3
Norm-Ex 25.8 ± 4.4 25.9 ± 4.4 0.3 ± 0.6 12.3 ± 1.9 12.5 ± 1.9 0.3 ± 0.3
Note. The Hyp-Ex, Hyp-N and Norm-Ex groups did not significantly differ. *P < .05, significant
differences from pretraining values. RM, repetition maximum; Hyp-Ex, exercised arm of hypoxia
group; Hyp-N, nonexercised arm of hypoxia group; Norm-Ex, exercised arm of normoxia group.