International  Journal  of
Environmental Research
and Public Health
Article
Interval Hypoxic Training Enhances Athletic
Performance and Does Not Adversely Aﬀect Immune
Function in Middle- and Long-Distance Runners
Won-Sang Jung 1
, Sung-Woo Kim 1
and Hun-Young Park 1,2,*
1
Physical Activity and Performance Institute, Konkuk University, 120 Neungdong-ro, Gwangjin-gu,
Seoul 05029, Korea; jws1197@konkuk.ac.kr (W.-S.J.); kswrha@konkuk.ac.kr (S.-W.K.)
2
Department of Sports Medicine and Science, Graduate School, Konkuk University, 120 Neungdong-ro,
Gwangjin-gu, Seoul 05029, Korea
*
Correspondence: parkhy1980@konkuk.ac.kr; Tel.: +(82)-2-2049-6035
Received: 12 February 2020; Accepted: 15 March 2020; Published: 16 March 2020


Abstract: This study evaluated the eﬀects of intermittent interval training in hypoxic conditions
for six weeks compared with normoxic conditions, on hemodynamic function, autonomic nervous
system (ANS) function, immune function, and athletic performance in middle- and long-distance
runners. Twenty athletes were divided into normoxic training (normoxic training group (NTG);
n = 10; residing and training at sea level) and hypoxic training (hypoxic training group (HTG);
n = 10; residing at sea level but training in 526-mmHg hypobaric hypoxia) groups. All dependent
variables were measured before, and after, training. The training frequency was 90 min, 3 d per
week for six weeks. Body composition showed no signiﬁcant diﬀerence between the two groups.
However, the HTG showed more signiﬁcantly improved athletic performance (e.g., maximal oxygen
uptake). The hemodynamic function (e.g., oxygen uptake, oxygen pulse, and cardiac output) during
submaximal exercise and ANS function (e.g., standard deviation and root mean square of successive
diﬀerences, high frequency, and low/high frequency) improved more in the HTG. Immune function
parameters were stable within the normal range before and after training in both groups. Therefore,
hypoxic training was more eﬀective in enhancing athletic performance, and improving hemodynamic
and ANS function; further, it did not adversely aﬀect immune function in competitive runners.
Keywords: interval hypoxic training; hemodynamic function; autonomic nervous system balance;
exercise performance; immune function; competitive middle- and long-distance runners
1. Introduction
Endurance exercise performance is related to various factors that can be altered by diverse
hypoxic training methods, including erythropoiesis, exercise economy, capillary density, hemodynamic
function, and acid-base response in the skeletal muscle [1,2]. Enhancing these factors, which are
related to endurance exercise performance, increases the eﬃciency of aerobic energy production and
consequently enhances maximum oxygen uptake (VO2max). It also enhances athletic performance by
improving time until fatigue and increasing exercise intensity [3–6]. In particular, endurance exercise
performance is reported to be the most aﬀected by hemodynamic function, which is an indicator of
oxygen transport and utilization ability [7].
Currently, altitude/hypoxic training is a common and popular practice for enhancing athletic
performance in normoxic conditions among various athletes [8]. The most typical altitude/hypoxic
training regimens proposed include living high-training high (LHTH), living high-training low (LHTL),
and living low-training high (LLTH) methods. The LHTH method involves living and training at
Int. J. Environ. Res. Public Health 2020, 17, 1934; doi:10.3390/ijerph17061934
www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2020, 17, 1934
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1500–4000 m in natural altitude environments, while the LHTL method involves living at or near sea
level but training under a natural or simulated altitude condition of 2000–3000 m [3,4,6]. The LLTH
method may be of particular interest to athletes because this training commonly involves shorter
hypoxic exposure (approximately two to ﬁve sessions per week of <3 h), lower cost, lesser eﬀort, and
lesser time than the LHTH and LHTL methods [1]. Further, the LLTH method, includes interval hypoxic
training (IHT), repeated sprint training in hypoxia, and resistance training in hypoxic conditions; it has
become an increasingly popular altitude/hypoxic practice, where athletes live at or near sea level but
train in 2000–4500 m simulated hypobaric or normobaric hypoxic conditions [9–11].
Among the various LLTH methods, IHT consists of repeated exposures to 5–7 min of steady or
progressive hypoxia, interrupted by equal periods of recovery; it can modify oxygen transport and
energy utilization and induce permanent modiﬁcations in cardiac function [12]. Short-term repeated
exposure to hypoxic conditions with high-intensity exercise enhances athletic performance via the
metabolic and oxygen utilizing capacity [11,13–15]. However, some studies have not supported the
enhancing eﬀect of high-intensity training in hypoxic conditions on athletic performance [16–19].
These conﬂicting results are attributed to the fact that the enhancement of athletic performance was
not veriﬁed on the basis of changes in hemodynamic function.
Heart rate (HR) variability (HRV) is a widely used marker reﬂecting cardiac modulation by
sympathetic and vagal components and autonomic nervous system (ANS) activity.
Dynamic
adjustments in cardiac and peripheral vascular control, including their regulation by the ANS,
occur in response to rapid changes in the HR [20,21]. Change in HRV with exercise training have often
been interpreted as increase in vagal activity or ANS balance function, which is related to athletic
performance [21]. Herzig et al. [22] reported that HRV markers of vagal activity are moderately
associated with athletic performance variables, such as 10-mi race time. Dong [23] explained that HRV
was becoming one of the most useful tools for tracking the time course of exercise training adaptation
of athletes and for setting the optimal exercise intensity that leads to enhanced athletic performance.
Therefore, it is essential to examine the eﬀectiveness of exercise training in hypoxic conditions with
changes in HRV, which is useful in enhancing the athletic performance.
Exercise in hypoxic conditions acts as a stressor to yield greater physiological and metabolic
functions than exercise in normoxic conditions, thereby causing changes in the neuroendocrine system
and aﬀecting immune function [24,25]. Further, exposure to hypoxic conditions stimulates the release
of epinephrine in the adrenal medulla, increases the sympathetic nervous system activity, and increases
the concentration of cortisol and adrenal cortical hormone in the blood [26,27]. The most representative
changes in immune function following exposure to hypoxic conditions include decreased CD4+ T cell
count; decreased T cell activation and proliferation; lymphocytosis; neutropenia; and inﬂammatory
upregulation of cytokines, such as interleukin (IL)-6, IL-1, C-reactive protein, and tumor necrosis
factor (TNF)-α [25,28–31]. As described above, exposure to hypoxic conditions results in a change
in immune function based on various changes in the physiological, metabolic, and neuroendocrine
systems. However, studies on changes in immune function following exercise training in hypoxic
conditions are scarce.
Considering that various hypoxic training regimens are commonly used to enhance athletic
performance in normoxic conditions based on hematological and non-hematological changes, it is
important to examine the eﬀects on immune function in terms of health and conditioning. Moreover,
the World Anti-Doping Agency is concerned that various hypoxic training regimens can have a
potentially negative eﬀect on health [32]. Thus, an essential task for elite athletes is to examine how
exercise training in hypoxic conditions aﬀects their immune function, and establish the eﬃcacy and
stability of hypoxic training.
Therefore, this study aimed to investigate the eﬀects of intermittent interval training on
hemodynamic function, ANS function, immune function, and athletic performance of competitive
middle- and long-distance runners in a hypoxic condition versus that in a normoxic condition.
We
hypothesized that intermittent interval training in a hypoxic condition would enhance
Int. J. Environ. Res. Public Health 2020, 17, 1934
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hemodynamic function, ANS function, and athletic performance more than in a normoxic condition,
and would not adversely aﬀect immune function in competitive middle- and long-distance runners.
2. Materials and Methods
2.1. Subjects
Subjects, whose characteristics are presented in Table 1, were men and were competitive,
moderately trained, middle- and long-distance runners (n = 20) registered with the Korea Association of
Athletics Federations. They were assigned equally to the normoxic (NTG) and hypoxic (HTG) training
group based on their body composition and athletic performance. We explained the experiment and
possible adverse eﬀects before the start of the study to participants and obtained their signed informed
consent to participate in this study. This study was approved by the institutional review board of
Konkuk University (7001355-2020002-HR-359) and was conducted in accordance with the provisions
of the Declaration of Helsinki.
Table 1. Characteristics of the athletes.
Variables
NTG
HTG
t-Value
p-Value
Number (n)
n = 10
n = 10
-
-
Environmental
condition (mmHg)
Sea level
(760 mmHg)
3000-m simulated altitude
(526 mmHg)
-
-
Age (year)
25.9 ± 1.2
26.3 ± 1.5
−0.499
0.624
Height (cm)
176.9 ± 7.6
178.2 ± 3.5
−0.514
0.616
Weight (kg)
70.8 ± 5.8
71.2 ± 6.3
−0.490
0.630
BMI (kg/m2)
23.1 ± 1.5
22.8 ± 0.9
−1.554
0.138
FFM (kg)
51.1 ± 4.4
52.1 ± 4.8
−0.490
0.630
Percent body fat (%)
17.5 ± 2.7
18.4 ± 1.8
−0.882
0.389
Values are expressed as means ± standard deviations. NTG = normoxic training group, HTG = hypoxic training
group, BMI = body mass index, FFM = free fat mass.
2.2. Study Design
The study design is shown in Figure 1. Twenty athletes were equally divided into the NTG (n = 10;
intermittent interval training in a normoxic condition; 760 mmHg) and HTG (n = 10; intermittent
interval training in a hypoxic condition; 526 mmHg; simulated altitude of 3000 m). All testing and
training were performed in a 9-m (width) × 7-m (length) × 3-m (height) chamber with a temperature
of 22 ± 1 ◦C and humidity of 50 ± 5% regulated by an environmental control chamber (NCTC-1, Nara
control, Seoul, Korea).
The present study comprised a 5-day pre-test period (i.e., 3 testing days and 1 rest day between
the testing days), 6-week training period under each environmental condition, and 5-day post-test
period. The post-test period began 3 d after the ﬁnal training session.
On the ﬁrst pre- and post-testing days, blood samples were collected between 8:00 and 10:00 a.m.
after 12 h of fasting for the analysis of blood variables related to immune function in the normoxic
condition. Thereafter, body composition and ANS function were measured. Subsequently, the VO2max
was measured to evaluate exercise performance in the afternoon. On the second pre- and post-testing
days, hemodynamic function parameters were measured during a 30-min bout of submaximal cycle
ergometer exercise. The exercise intensity was set at individual cycle ergometer exercise load values
corresponding to 80% maximal HR (HRmax) obtained during the pre-test period. On the third testing
day, a 3000-m time trial record was measured on an authorized track stadium at sea level.
Int. J. Environ. Res. Public Health 2020, 17, 1934
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Figure 1. Study design of the present study. 
All athletes performed the following in 90-min sessions: warm-up, interval training, and cool-
down. The training frequency was 90 min, 3 d per week for 6 weeks. Warm-up and cool-down were 
set at 50% HRmax for each participant for 5 min, which was then increased by 10% HRmax every 5 
min and performed for 15 min. The interval training sessions consisted of 10 repetitions of interval 
running exercise (5 min of exercise corresponding to 90–95% HRmax and 1 min of rest) on a treadmill. 
All exercise training sessions in the hypoxic conditions were supervised by directors, coaches, 
and the researchers. 
2.3. Blood Composition 
Body composition parameters, such as weight, free fat mass, and percentage body fat were 
analyzed using Inbody 770 (Inbody, Seoul, Republic of Korea). 
2.4. Hemodynamic Function 
Hemodynamic function was measured before and after training while the participants 
performed submaximal cycle ergometer exercise corresponding to 80% HRmax obtained during the 
pre-test period for 30 min at sea level [1,11]. The oxygen uptake (VO2) was measured using the K5 
auto metabolism analyzer (Cosmed, Rome, Italy) and a breathing valve in the form of a facemask. 
The HR, stroke volume index (SVi), and cardiac output index (COi) were assessed non-invasively 
using a thoracic bioelectrical impedance device (PhysioFlow PF-05, Paris, France). The oxygen pulse 
(O2 pulse) was calculated as VO2/HR. 
2.5. ANS Function 
ANS function was assessed by measuring HRV. After approximately 10 min of rest, four pads 
were placed on the wrists and ankles using an HRV meter (LAXTHA; CANS-3000, Daejeon, Republic 
of Korea), and participants’ HRV was measured in the resting condition. The following parameters 
were evaluated: standard deviation (SD) of successive differences (SDNN) and root mean square of 
successive differences (RMSSD) for the time domain methods and low frequency (LF) band, high 
frequency (HF) band, and LH/HF band ratio for the frequency domain methods [33]. 
 
Figure 1. Study design of the present study.
All athletes performed the following in 90-min sessions: Warm-up, interval training, and
cool-down. The training frequency was 90 min, 3 d per week for 6 weeks. Warm-up and cool-down
were set at 50% HRmax for each participant for 5 min, which was then increased by 10% HRmax every
5 min and performed for 15 min. The interval training sessions consisted of 10 repetitions of interval
running exercise (5 min of exercise corresponding to 90–95% HRmax and 1 min of rest) on a treadmill.
All exercise training sessions in the hypoxic conditions were supervised by directors, coaches,
and the researchers.
2.3. Blood Composition
Body composition parameters, such as weight, free fat mass, and percentage body fat were
analyzed using Inbody 770 (Inbody, Seoul, Korea).
2.4. Hemodynamic Function
Hemodynamic function was measured before and after training while the participants performed
submaximal cycle ergometer exercise corresponding to 80% HRmax obtained during the pre-test period
for 30 min at sea level [1,11]. The oxygen uptake (VO2) was measured using the K5 auto metabolism
analyzer (Cosmed, Rome, Italy) and a breathing valve in the form of a facemask. The HR, stroke
volume index (SVi), and cardiac output index (COi) were assessed non-invasively using a thoracic
bioelectrical impedance device (PhysioFlow PF-05, Paris, France). The oxygen pulse (O2 pulse) was
calculated as VO2/HR.
2.5. ANS Function
ANS function was assessed by measuring HRV. After approximately 10 min of rest, four pads were
placed on the wrists and ankles using an HRV meter (LAXTHA; CANS-3000, Daejeon, Korea), and
participants’ HRV was measured in the resting condition. The following parameters were evaluated:
Standard deviation (SD) of successive diﬀerences (SDNN) and root mean square of successive diﬀerences
Int. J. Environ. Res. Public Health 2020, 17, 1934
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(RMSSD) for the time domain methods and low frequency (LF) band, high frequency (HF) band, and
LH/HF band ratio for the frequency domain methods [33].
2.6. Immune Function
To assess immune function, white blood cell (WBC), eosinophil, neutrophil, basophil, natural killer
(NK) cell, B cell and T cell counts were measured before and after the intervention. Three milliliters of
blood were collected between 8:00 and 10:00 a.m. after 12 h of fasting. All blood samples were placed in
an anticoagulant heparin tube and centrifuged at 3500 rpm for 10 min, and the serum was collected and
rapidly frozen at −70 ◦C. Thereafter, the frozen or refrigerated serum was commissioned by the Clinical
Laboratory of Green Cross Medical Foundation and analyzed using the method described below.
In detail, WBC, neutrophil, eosinophil, and basophil counts were measured via ﬂow cytometry
using a cellpack kit (Sysmex, Kobe, Japan). NK cell, B cell, and T cell counts were analyzed using
FC500 (Beckman Counter, CA, USA) and measured via ﬂow cytometry using an NK cell kit (Beckman
Coulter, Paris, France), a CD19-PE kit (Beckman Coulter, Paris, France), and a CD3-PC5 kit (Beckman
Coulter, Paris, France), respectively.
2.7. Athletic Performance
To evaluate athletic performance, VO2max was measured before and after the intervention with
the modiﬁed BRUCE protocol for graded exercise testing on a treadmill (S25TX, SFET, Seoul, Korea)
using a K5 breath by breath auto metabolism analyzer (K5, Cosmed, Rome, Italy). The graded exercise
test was completed when the following three criteria were satisﬁed: (1) VO2 plateau: No further
increase in oxygen use per minute even with an increase in work performed, (2) HR within 10 beats
of the age-predicted HRmax: This is the basis for using participants’ HRmax as a surrogate for the
VO2max when designing personal training programs, and (3) plasma (blood) lactate concentrations of
>7 mmol/L.
The 3000-m time trial records were measured on a 400-m track at sea level in Seoul between 9:00
and 10:00 a.m. (temperature = 22–24 ◦C; humidity = 60–80%; wind = 0–10 km/h). To avoid the eﬀect of
racing strategies, all starts were staggered by at least 2 min.
2.8. Statistical Analysis
Means and SDs were calculated for each primary dependent variable. Normality of distribution of
all outcome variables was veriﬁed using the Sharpiro-Wilk test. The two-way analysis (time × group)
of variance with repeated measures of the “time” factor was used to analyze the eﬀects of the training
methods on each dependent variable. Partial eta-squared (η2) values were calculated as measures of
the eﬀect size. When a signiﬁcant interaction eﬀect was found, the Bonferroni post-hoc test was used to
identify within-group changes over time. Additionally, the paired t-test was used to compare between
the post- and pre-training values of the dependent variables in each group separately. A priori power
analysis was performed with G-power for the energy metabolic parameter (VO2 during 30-min of
submaximal exercise) based on previous research [1], indicating that a sample size of 14 participants
(7 subjects per group) would be required to provide 80% power at an α-level of 0.05. We anticipated a
dropout rate of >10% and aimed for a starting population of 20. All analyses were performed using
the Statistical Package for the Social Sciences version 24.0 (IBM Corp., Armonk, NY, USA). The level of
signiﬁcance was set at 0.05 (a priori).
3. Results
3.1. Body Composition
Data on the body composition in both groups before and after training are shown in Table 2.
No signiﬁcant interaction was observed in all body composition parameters, i.e., body composition
did not aﬀect the change in the other dependent variables.
Int. J. Environ. Res. Public Health 2020, 17, 1934
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Table 2. Changes in the body composition of the competitive runners before and after the tests.
Variables
NTG (n = 10)
p-Value
HTG (n = 10)
p-Value
p-Value (η2)
Pre
Post
Pre
Post
Group
Time
Interaction
Weight (kg)
70.8 ± 5.8
71.1 ± 5.8
0.146
71.2 ± 6.3
71.1 ± 7.3
0.945
0.555
(0.020)
0.233
(0.078)
0.269
(0.067)
BMI (kg/m2)
23.1 ± 1.5
23.1 ± 1.6
0.105
22.8 ± 0.9
22.6 ± 0.9
0.390
0.136
(0.119)
0.138
(0.118)
0.919
(0.001)
FFM (kg)
51.1 ± 4.4
50.6 ± 4.4
0.147
52.1 ± 4.8
52.1 ± 5.5
0.952
0.555
(0.020)
0.233
(0.078)
0.269
(0.067)
Percent body
fat (%)
17.5 ± 2.7
17.3 ± 2.9
0.274
18.4 ± 1.8
17.8 ± 2.0
0.275
0.477
(0.028)
0.144
(0.115)
0.549
(0.020)
Values are expressed as means ± standard deviations. NTG = normoxic training group, HTG = hypoxic training
group, BMI = body mass index, FFM = free fat mass.
3.2. Athletic Performance
Figure 2 depicts the pre- and post-training data on athletic performance in both groups. There was
a signiﬁcant interaction for the VO2max (η2 = 0.686, p < 0.001). The post-hoc analysis revealed
signiﬁcant enhancements in both groups (NTG: p < 0.01, HTG: p < 0.001), and the improvement in
VO2max was greater in the HTG than in the NTG (NTG: 1.5%, HTG: 6.3%). No signiﬁcant interaction
was observed for the 3000-m time trial records.
 
 
Table 2. Changes in the body composition of the competitive runners before and after the tests. 
Variables 
NTG (n = 10) 
p-Value 
HTG (n = 10) 
p-Value 
p-Value (ɳ2) 
Pre 
Post 
Pre 
Post 
Group 
Time 
Interaction 
Weight (kg) 
70.8 ± 5.8 71.1 ± 5.8 
0.146 
71.2 ± 6.3 71.1 ± 7.3 
0.945 
0.555 (0.020) 0.233 (0.078) 0.269 (0.067) 
BMI (kg/m2) 
23.1 ± 1.5 23.1 ± 1.6 
0.105 
22.8 ± 0.9 22.6 ± 0.9 
0.390 
0.136 (0.119) 0.138 (0.118) 0.919 (0.001) 
FFM (kg) 
51.1 ± 4.4 50.6 ± 4.4 
0.147 
52.1 ± 4.8 52.1 ± 5.5 
0.952 
0.555 (0.020) 0.233 (0.078) 0.269 (0.067) 
Percent body fat (%) 17.5 ± 2.7 17.3 ± 2.9 
0.274 
18.4 ± 1.8 17.8 ± 2.0 
0.275 
0.477 (0.028) 0.144 (0.115) 0.549 (0.020) 
Values are expressed as means ± standard deviations. NTG = normoxic training group, HTG = hypoxic 
training group, BMI = body mass index, FFM = free fat mass 
3.2. Athletic Performance 
Figure 2 depicts the pre- and post-training data on athletic performance in both groups. There 
was a significant interaction for the VO2max (η2 = 0.686, p < 0.001). The post-hoc analysis revealed 
significant enhancements in both groups (NTG: p < 0.01, HTG: p < 0.001), and the improvement in 
VO2max was greater in the HTG than in the NTG (NTG: 1.5%, HTG: 6.3%). No significant interaction 
was observed for the 3000-m time trial records. 
 
Figure 2. Athletic performance parameters before and after the 6-week exercise training. (A) Change 
in the VO2max after exercise training in each environmental condition. (B) Change in the 3-km time 
trial record after exercise training in each environmental condition. VO2max = maximum oxygen 
uptake, NTG = normoxic training group, HTG = hypoxic training group. * Significant difference 
between the pre- and post-tests, ** p < 0.01, *** p < 0.001. 
3.3. Hemodynamic Function 
As shown in Table 3, there was a significant interaction for the VO2 (η2 = 0.251, p < 0.05), O2 pulse 
(η2 = 0.588, p < 0.001), and COi (η2 = 0.575, p < 0.001). Compared with the NTG, the HTG showed a 
significant decrease in the VO2 (p < 0.001) and a significant increase in the COi (p < 0.001) during 
submaximal exercise for 30 min. The O2 pulse (NTG: p < 0.01, HTG: p < 0.01) during submaximal 
exercise for 30 min significantly increased in both groups, and the improvement in O2 pulse was 
greater in the HTG than in the NTG (NTG: 17.7%, HTG: 24.7%). No significant interaction was 
observed for the HR and SVi.
Figure 2. Athletic performance parameters before and after the 6-week exercise training. (A) Change in
the VO2max after exercise training in each environmental condition. (B) Change in the 3-km time trial
record after exercise training in each environmental condition. VO2max = maximum oxygen uptake,
NTG = normoxic training group, HTG = hypoxic training group. * Signiﬁcant diﬀerence between the
pre- and post-tests, ** p < 0.01, *** p < 0.001.
3.3. Hemodynamic Function
As shown in Table 3, there was a signiﬁcant interaction for the VO2 (η2 = 0.251, p < 0.05), O2 pulse
(η2 = 0.588, p < 0.001), and COi (η2 = 0.575, p < 0.001). Compared with the NTG, the HTG showed
a signiﬁcant decrease in the VO2 (p < 0.001) and a signiﬁcant increase in the COi (p < 0.001) during
submaximal exercise for 30 min. The O2 pulse (NTG: p < 0.01, HTG: p < 0.01) during submaximal
exercise for 30 min signiﬁcantly increased in both groups, and the improvement in O2 pulse was greater
in the HTG than in the NTG (NTG: 17.7%, HTG: 24.7%). No signiﬁcant interaction was observed for
the HR and SVi.
Int. J. Environ. Res. Public Health 2020, 17, 1934
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Table 3. Changes in hemodynamic function during submaximal cycle ergometer exercise for 30 min among the competitive runners before and after the tests.
Variables
NTG (n = 10)
p-Value
HTG (n = 10)
p-Value
p-Value (η 2)
Pre
Post
Pre
Post
Group
Time
Interaction
HR (beat/30 min)
5375.7 ± 431.4
4946.1 ± 287.8
0.003
5207.4 ± 308.7
4830.5 ± 267.6
0.001
0.296 (0.060)
0.000 (0.674) †††
0.694 (0.009)
VO2 (mL/30 min)
1355.6 ± 114.4
1322.9 ± 118.9
0.094
1194.1 ± 139.5
1118.1 ± 141.8
<0.001 ***
0.005 (0.364) ††
0.000 (0.678) †††
0.024 (0.251) †
O2 pulse (mL/beat/30 min)
553.5 ± 111.2
651.5 ± 49.2
0.004 **
551.4 ± 129.1
687.7± 35.9
0.007 **
0.614 (0.014)
0.418 (0.037)
0.000 (0.588) †††
SVi (mL/beat/30 min)
1691.5 ± 99.4
1660.7 ± 102.5
0.018
1520.4 ± 117.4
1518.2 ± 188.1
0.971
0.007 (0.342) ††
0.579 (0.017)
0.629 (0.013)
COi (L/30 min)
244.7 ± 20.8
253.7 ± 15.4
0.280
281.7 ± 22.1
227.2 ± 31.4
<0.001 ***
0.526 (0.023)
0.002 (0.411) ††
0.000 (0.575) †††
Values are expressed as means ± standard deviations. NTG = normoxic training group, HTG = hypoxic training group, HR = heart rate, VO2 = oxygen consumption, O2 pulse = oxygen
pulse, SVi = stroke volume index, COi = cardiac output index. Signiﬁcant interaction or main eﬀect: † p < 0.05, †† p < 0.01, ††† p < 0.001; Signiﬁcant diﬀerence between the pre- and
post-tests: ** p < 0.01, *** p < 0.001.
Int. J. Environ. Res. Public Health 2020, 17, 1934
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3.4. ANS Function
Table 4 depicts the pre- and post-training data on HRV in both groups. Signiﬁcant interaction was
seen for all HRV parameters, including SDNN (η2 = 0.732, p < 0.001), RMSSD (η2 = 0.777, p < 0.001), LF
band (η2 = 0.616, p < 0.001), HF band (η2 = 0.693, p < 0.001), and LF/HF band ratio (η2 = 0.420, p < 0.01).
In the post-hoc analysis, the NTG showed a signiﬁcant decrease in the average of all R wave to R wave
intervals (mean RR; p < 0.001), SDNN (p < 0.01), RMSSD (p < 0.001), LF band (p < 0.01), and HF band
(p < 0.001). In contrast, the HTG presented a signiﬁcant increase in the mean RR (p < 0.01), SDNN
(p < 0.01), RMSSD (p < 0.01), total power (p < 0.05), HF band (p < 0.01), and LF/HF band ratio (p < 0.01).
Table 4. Changes in ANS function among the competitive runners before and after the tests.
Variables
NTG (n = 10)
p-Value
HTG (n = 10)
p-Value
p-Value (η 2)
Pre
Post
Pre
Post
Group
Time
Interaction
SDNN (ms)
61.0 ± 4.5
50.1 ± 6.8
0.001 **
56.6 ± 14.4
66.9 ± 11.0
0.001 **
0.157 (0.108)
0.827 (0.003)
0.000 (0.732) †††
RMSSD (ms)
37.6 ± 7.7
23.7 ± 4.9
<0.001 ***
32.5 ± 10.4
44.8 ± 12.9
0.002 **
0.055 (0.190)
0.646 (0.012)
0.000 (0.777) †††
LF band (ms2)
7.1 ± 0.6
6.7 ± 0.4
0.001 **
7.0 ± 0.7
7.2 ± 0.6
0.052
0.399 (0.040)
0.013 (0.294) †
0.000 (0.616) †††
HF band (ms2)
6.5 ± 0.4
5.9 ± 0.3
<0.001 ***
6.0 ± 1.1
6.9 ± 1.0
0.003 **
0.455 (0.031)
0.353 (0.048)
0.000 (0.693) †††
LF/HF band ratio
1.2 ± 0.1
1.3 ± 0.2
0.207
1.5 ± 0.5
1.2 ± 0.3
0.008 **
0.447 (0.032)
0.012 (0.304) †
0.002 (0.420) ††
Values are expressed as mean ± standard deviation. ANS = autonomic nervous system, NTG = normoxic training
group, HTG = hypoxic training group, SDNN = standard deviation of the NN interval, RMSSD = root mean square
of successive diﬀerences, LF = low frequency, HF = high frequency. Signiﬁcant interaction or main eﬀect: † p < 0.05,
†† p < 0.01, ††† p < 0.001; Signiﬁcant diﬀerence between the pre- and post-tests: ** p < 0.01, *** p < 0.001.
3.5. Immune Function
As shown in Table 5, there was a signiﬁcant interaction for the WBC (η2 = 0.293, p < 0.05),
neutrophil (η2 = 0.416, p < 0.01), monocyte (η2 = 0.580, p < 0.001), and B cell (η2 = 0.258, p < 0.05) counts.
Compared with the NTG, the HTG showed a signiﬁcant increase in the WBC (p < 0.05) and neutrophil
(p < 0.01) counts and a signiﬁcant decrease in the monocyte count (p < 0.001). Conversely, the B
cell count signiﬁcantly decreased (p < 0.05) in the NTG compared to that in the HTG. No signiﬁcant
interaction was observed for the eosinophil, basophil, NK cell, and T cell counts.
Table 5. Changes in immune function among the competitive runners before and after the tests.
Variables
NTG (n = 10)
p-Value
HTG (n = 10)
p-Value
p-Value (η 2)
Pre
Post
Pre
Post
Group
Time
Interaction
WBC count (103/µL)
5.4 ± 0.5
5.6 ± 0.6
0.124
4.6 ± 0.8
6.4 ± 2.1
0.013 *
0.977 (0.000)
0.003 (0.387) ††
0.014 (0.293) †
Eosinophil count (%)
3.8 ± 1.5
3.7 ± 1.6
0.623
3.4 ± 1.3
3.1 ± 1.4
0.153
0.459 (0.031)
0.126 (0.125)
0.286 (0.063)
Neutrophil count (%)
48.5 ± 5.8
46.4 ± 4.8
0.312
44.6 ± 4.6
53.0 ± 11.1
0.004 **
0.635 (0.013)
0.047 (0.201) †
0.002 (0.416) ††
Basophil count (%)
1.3 ± 0.5
1.2 ± 0.6
0.434
0.8 ± 0.1
0.6 ± 0.1
<0.001
0.004 (0.385) ††
0.018 (0.273) †
0.343 (0.050)
Monocyte count (%)
9.2 ± 2.6
9.8 ± 2.0
0.141
9.1 ± 0.7
7.3 ± 0.7
<0.001 ***
0.090 (0.151)
0.023 (0.255) †
0.000 (0.580) †††
NK cell count (%)
22.0 ± 4.9
21.3 ± 4.9
0.603
19.6 ± 5.1
19.0 ± 5.6
0.622
0.280 (0.064)
0.467 (0.030)
0.988 (0.000)
B cell count (%)
14.6 ± 2.9
13.1 ± 3.8
0.048 *
16.7 ± 2.0
17.6 ± 1.6
0.229
0.008 (0.331) ††
0.548 (0.020)
0.022 (0.258) †
T cell count (%)
66.6 ± 8.0
65.9 ± 10.3
0.633
70.1 ± 6.9
71.1 ± 8.1
0.126
0.249 (0.073)
0.780 (0.004)
0.256 (0.071)
Values are expressed as means ± standard deviations. NTG = normoxic training group, HTG = hypoxic training
group, WBC = white blood cell, NK= natural killer. Signiﬁcant interaction or main eﬀect: † p < 0.05, †† p < 0.01, ††† p
< 0.001; Signiﬁcant diﬀerence between the pre- and post-tests: * p < 0.05, ** p < 0.01, *** p < 0.001.
4. Discussion
In the present study, we hypothesized that intermittent interval training in a hypoxic condition
(simulated 3000-m, 526-mmHg hypobaric hypoxia) versus that in a normoxic condition would enhance
athletic performance and improve hemodynamic function and ANS function and would not adversely
aﬀect immune function in competitive middle- and long-distance runners. Our ﬁndings were consistent
with these hypotheses.
4.1. Athletic Performance
Our study conﬁrmed that intermittent interval training in a hypoxic condition improved VO2max
more than that in a normoxic condition.
Int. J. Environ. Res. Public Health 2020, 17, 1934
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The oxygen transport capacity in systemic conditions is most often evaluated using VO2max [8].
Exercise training in a hypoxic condition may increase exercise performance by inducing various
biochemical and structural adaptive changes in the skeletal and cardiac muscles, which favor the
oxidative process and can enhance non-hematological parameters, such as exercise economy, acid-base
balance, and metabolic response during submaximal exercise, ultimately leading to improved oxygen
delivery and utilization capacity [1,8–11,13]. Among the various LLTH methods, IHT consists of
repeated exposures to 5–7 min of steady or progressive hypoxia, interrupted by equal periods of
recovery; it can modify oxygen transport and energy utilization and induce permanent modiﬁcations in
the cardiac function [12]. The short-term repeated exposure to hypoxic conditions, with high-intensity
exercise, enhances athletic performance via the metabolic and oxygen utilizing capacity [11,13–15].
However, research ﬁndings on IHT as an eﬀective hypoxic training method for enhancing athletic
performance at sea level are inconclusive [8]. In various previous studies, the diﬀerence in the
enhancement of athletic performance, via the IHT method, was attributed to the intensity of the exercise
performed in the hypoxic conditions [8,9,34]. There are also some diﬀerences in the type of exercise.
Park and Lim [8] evaluated the eﬀects of six weeks of hypoxic training on exercise performance in
moderately trained competitive swimmers and reported that a moderate intensity of continuous and
interval training in a hypoxic condition for six weeks resulted in an unclear change in the aerobic
and anaerobic performance compared to normoxic training. They also argued that the unclear
improvement after hypoxic training was attributed to the relatively low exercise intensity. Conversely,
Czuba et al. [14] evaluated the eﬀects of a three-week continuous hypoxic training with a relatively
high exercise intensity corresponding to 95% lactate threshold workload on athletic performance
in well-trained cyclists and reported a signiﬁcant increase in exercise performance (e.g., VO2max,
VO2 at the lactate threshold, maximal work load, and work load at the lactate threshold). Further,
Roels et al. [35] observed a signiﬁcant increase in the VO2max after seven weeks of high-intensity
IHT compared to that after normoxic training. Regarding the inconsistency of previous research
results, McLean et al. [34] suggested that the greater athletic performance (e.g., VO2max and time trial
records) with IHT was more likely achieved if exercise training in hypoxic conditions is performed
with high-intensity interval workouts. Our study also showed that intermittent interval training in
a hypoxic condition was eﬀective in enhancing athletic performance by increasing the VO2max of
competitive runners compared to training in a normoxic condition. We believe that these positive
results were attributable to IHT performed with high-intensity interval workouts.
4.2. Hemodynamic Function
Our study veriﬁed that intermittent interval training in a hypoxic condition improved VO2, O2
pulse, and COi during submaximal exercise more than that in a normoxic condition.
Hemodynamic function represents the dynamics of blood ﬂow in systemic conditions, and
the hemodynamic system continuously monitors and adjusts to the conditions in the body and its
environment. Further, athletic performance is highly related to hemodynamic function, which serves
as an indicator of oxygen transport and utilization capacity [13].
As mentioned earlier, various previous studies have reported that IHT eﬀectively enhanced
athletic performance by improving the metabolic responses (e.g., blood lactate level, glycolytic enzyme
and glucose transport, and acid-base balance regulation) and oxygen utilization capacity [1,11,14,15].
IHT may increase exercise performance by inducing various biochemical and structural adaptive
changes in the skeletal and cardiac muscles that favor the oxidative process and can enhance
non-hematological parameters, such as exercise economy, acid-base balance, and metabolic response
during submaximal exercise, ultimately leading to improved oxygen delivery and utilization
capacity [1,8–11,13]. However, there is a lack of studies demonstrating that IHT enhanced athletic
performance based on changes in hemodynamic function, which indicates oxygen delivery and
utilization capacity in systemic conditions.
Therefore, we examined the enhancement eﬀect of
intermittent interval training in the hypoxic condition on athletic performance in relation to
Int. J. Environ. Res. Public Health 2020, 17, 1934
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hemodynamic function and found that compared to training in a normoxic condition, intermittent
interval training in a hypoxic condition eﬀectively improved hemodynamic function by decreasing
the VO2 and COi and increasing the O2 pulse during submaximal cycle ergometer exercise for 30 min
among competitive runners.
In the present study, the signiﬁcantly improved hemodynamic function (signiﬁcant decrease in the
VO2 and COi and signiﬁcant increase in the O2 pulse) indicates enhanced exercise economy, which is
deﬁned as the amount of energy per unit distance [4,36–38]. Exercise economy and VO2max are widely
known as determinant factors of athletic performance [13,36–38]. IHT has been shown to enhance ATP
re-synthesis (per 1 mole O2) and decrease ATP levels at a given exercise intensity (e.g., speed and
workload) [36,38,39]. Exercise training enhances athletic performance by increasing the eﬃciency of
oxygen transport and utilization and increases energy availability, which consequently improves the
invigoration of the parasympathetic nervous system via the activation of β-adrenergic receptors in the
cardiac muscles and eﬃciently changes cardiac function by increasing venous return [13,39]. Thus,
the reduced COi and increased VO2 and O2 pulse during submaximal exercise in our study indicate
improvement in the function of the heart as a pump for delivering oxygen and oxygen utilization and
delivery to the muscle tissue [13,39]. Thus, the IHT in our study enhanced the VO2max and exercise
economy, which are two important factors of athletic performance; this enhancement was probably
aﬀected by improvements in hemodynamic function.
4.3. ANS Function
Our study proved that intermittent interval training in a hypoxic condition improved successive
diﬀerences (SDNN), root mean square of successive diﬀerences (RMSSD), high frequency (HF) band,
and LF/HF band ratio.
HRV is a widely used marker reﬂecting cardiac modulation by sympathetic and vagal components
and ANS activity; it is the most sensitive and reproducible marker among those obtained from tests
for measuring changes in the ANS [20,40,41]. Further, HRV is caused by the interaction between the
sympathetic and parasympathetic nervous system on the sinoatrial nodes. Therefore, the HRV test is
generally used in the ﬁeld of mental health examination and health science [20,40]. Clinical application
of HRV is mainly associated with the prediction of sudden cardiac infarction and assessment of
progression of cardiovascular and metabolic illness [23]. Recently, the sports science ﬁeld has been
using the HRV test for monitoring exercise training eﬀects and recovery [22,23,42].
Decreases and increases in the vagal-derived indices of HRV have been shown to indicate negative,
and positive adaptations, respectively, to exercise training [42]. In elite athletes, HRV changes are highly
related to the eﬃciency of exercise training, and positive adaptations, such as increased cardiovascular
ﬁtness after exercise training, have been reported to be associated with HRV [23,36,42]. Moreover,
some previous studies reported that athletic performance (e.g., VO2max) correlated with improvement
in HRV [23,43]. Therefore, our study examined the eﬀect of intermittent interval training on athletic
performance along HRV parameters in a hypoxic condition versus that in a normoxic condition.
We found that all HRV parameters (e.g., SDNN, RMSSD, LF band, HF band, and LF/HF band ratio)
showed a signiﬁcant interaction between the NTG and HTG; the SDNN, RMSSD, HF band, and LF/HF
band ratio indicated greater improvements in the HTG than in the NTG.
Among the HRV parameters, SDNN is an indicator of comprehensive HRV, has a high correlation
with the HF band, and mainly reﬂects parasympathetic nervous system activity [44]. The RMSSD is
an estimate of the short-term components of HRV, and the larger the value, the more physiologically
healthy and relaxed it is [44,45]. The HF band mainly reﬂects the activity of the vagal nerve supplying
the heart and is representative of parasympathetic nervous system activity [46]. Conversely, the LF
band correlates with stress and reﬂects the sympathetic nervous system activity [47]. As the LF band
increases, the overall HRV decreases and heart instability increases. The LF/HF band ratio reﬂects the
overall balance of the ANS. A higher LF/HF band ratio indicates that the sympathetic nervous system
is relatively activated or the parasympathetic nervous system activity is suppressed [21]. In the present
Int. J. Environ. Res. Public Health 2020, 17, 1934
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study, the HTG showed more signiﬁcant improvements in most HRV parameters (e.g., SDNN, RMSSD,
HF band, and LF/HF band ratio) than did the NTG; this positive HRV adaptation may have inﬂuenced
the enhancement of exercise performance. Further, our study showed that IHT could improve the
training and recovery quality, and yield more eﬃcient exercise training eﬀect by improving HRV.
4.4. Immune Function
Our study conﬁrmed that intermittent interval training in a hypoxic condition showed signiﬁcant
changes in WBC, neutrophil, monocyte, and B cell count, however, all parameters of immune function
were altered after the two-week IHT was clinically within the normal range.
As mentioned above, the IHT regimen in our study enhanced the athletic performance with
improvement in hemodynamic function and HRV; it is critical to examine the impact of the regimen on
immune function in terms of the health and conditioning of athletes. The World Anti-Doping Agency is
concerned that various hypoxic training regimens can have a potentially negative eﬀect on health [32].
Therefore, it is an imperative task for elite athletes to examine how exercise training in hypoxic
conditions aﬀects immune function and to establish the eﬃcacy and stability of hypoxic training.
Exercise in hypoxic conditions acts as a stressor to yield greater physiological and metabolic
function than that in normoxic conditions, causing changes in the neuroendocrine system and
consequently aﬀecting immune function [24,25]. Representative changes in the nervous and endocrine
systems by acute exposure to hypoxic conditions correspond to stimulating the release of epinephrine
in the adrenal medulla, increasing the sympathetic nervous system activity, and increasing the
concentration of cortisol and adrenal cortical hormones in the blood [26,27].
Changes in the
neuroendocrine system by exposure to hypoxic conditions induce changes in immune function,
such as decreased T cell count; decreased T cell activation and proliferation; increased neutrophil count;
and upregulation of inﬂammatory markers, including IL-6, IL-1, C-reactive protein, and TNF-α [28,48].
As described above, exposure to hypoxic conditions has been reported to result in a change in immune
function based on changes in the physiological, metabolic, and neuroendocrine systems. However,
studies on changes in immune function following exercise training in hypoxic conditions are scarce.
Although there are diﬀerences in the regimen of hypoxic training, Tiollier et al. [49] investigated
the impact of an 18-day LHTL training camp on secretory immunoglobulin A (sIgA) levels in 11 (six
female and ﬁve male) elite cross-country skiers. There was a downward trend in the sIgA levels, which
reached signiﬁcance in the LHTL group but not in the control group. Further, the salivary IgA levels
were still lower at baseline than those post-operatively. They strongly suggested a cumulative negative
eﬀect of physical exercise and hypoxia on the sIgA levels during LHTL training. Brugniaux et al. [50]
examined the eﬀect of LHTL training performed for 13–18 d through leukocyte count evaluation in
41 athletes from 3 federations (cross-country skiers, n = 11; swimmers, n = 18; runners, n = 12) and
found that the leukocyte count was not aﬀected, except at 3500 m. Park et al. [51] recently reported a
case study in which an LLTL regimen was used to evaluate the eﬀects of a 2-week hypoxic training on
immune function in Korean national cycling athletes with disabilities. They found that all immune
function parameters were in the normal range even after two weeks of hypoxic training.
In the present study, the HTG showed a more signiﬁcant increase in the WBC and neutrophil
counts and a signiﬁcant decrease in the monocyte count than did the NTG. Conversely, the B cell
count signiﬁcantly decreased in the NTG compared to that in the HTG. However, all immune function
parameters that were altered after the two-week IHT were clinically within the normal range. Thus, the
six-week IHT in this study did not negatively aﬀect the immune function of the competitive runners,
which is consistent with the results of a previous study [51].
5. Limitation of the Study
Some limitations of our study should be considered when interpreting our results. Although
the present study was designed systematically with equally controlled experiments, small sample
sizes were a limitation to check the eﬀects of an intermittent interval training in a hypoxic condition
Int. J. Environ. Res. Public Health 2020, 17, 1934
12 of 15
versus that in a normoxic condition on athletic performance, hemodynamic function, ANS function,
and immune function in middle- and long-distance competitive runners. Thus, larger samples are
warranted in future studies to access sports ﬁeld practice. Furthermore, the athlete’s dietary intake
and conditioning were not investigated.
6. Conclusions
Our study conﬁrmed that intermittent interval training in a hypoxic condition for six weeks would
enhance the athletic performance and improve hemodynamic and ANS function; further, it did not
adversely aﬀect the immune function of competitive runners compared to that of runners training in a
normoxic condition.
Author Contributions: Study conception and design, W.-S.J. and H.-Y.P.; statistical analysis, S.-W.K. and W.-S.J.;
investigation, W.-S.J., S.-W.K., and H.-Y.P.; data interpretation, W.-S.J., S.-W.K., and H.-Y.P.; writing-original draft
preparation, W.-S.J. and H.-Y.P.; writing-review and editing, W.-S.J., S.-W.K., and H.-Y.P.; supervision, W.-S.J.,
S.-W.K., and H.-Y.P. All authors have read and agreed to the published version of the manuscript.
Funding: This work was supported by the Ministry of Education of Korea and the National Research Foundation
of Korea (NRF-2019S1A5A8032648).
Acknowledgments: This study was supported by the Konkuk University Research Professor Program.
Conﬂicts of Interest: The authors declare no conﬂicts of interest.
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Interval Hypoxic Training Enhances Athletic Performance and Does Not Adversely Affect Immune Function in Middle- and Long-Distance Runners.
Jung, Won-Sang,Kim, Sung-Woo,Park, Hun-Young