The effects of nightly normobaric hypoxia and high

intensity training under intermittent normobaric

hypoxia on running economy and hemoglobin mass
Mituso Neya, Taisuke Enoki, Yasuko Kumai, Takayuki Sugoh and Takashi
Kawahara
J Appl Physiol 103:828-834, 2007. First published 7 June 2007; doi:10.1152/japplphysiol.00265.2007

You might find this additional info useful...

This article cites 51 articles, 23 of which can be accessed free at:

http://jap.physiology.org/content/103/3/828.full.html#ref-list-1

This article has been cited by 1 other HighWire hosted articles

The effect of intermittent hypobaric hypoxic exposure and sea level training on
submaximal economy in well-trained swimmers and runners
Martin J. Truijens, Ferran A. Rodríguez, Nathan E. Townsend, James Stray-Gundersen,
Christopher J. Gore and Benjamin D. Levine
J Appl Physiol, February, 1 2008; 104 (2): 328-337.
[Abstract] [Full Text] [PDF]

Downloaded from jap.physiology.org on March 16, 2011

Updated information and services including high resolution figures, can be found at:
http://jap.physiology.org/content/103/3/828.full.html

Additional material and information about Journal of Applied Physiology can be found at:
http://www.the-aps.org/publications/jappl

This infomation is current as of March 16, 2011.

Journal of Applied Physiology publishes original papers that deal with diverse areas of research in applied physiology, especially
those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a year (monthly) by the American
Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2007 by the American Physiological Society.
ISSN: 0363-6143, ESSN: 1522-1563. Visit our website at http://www.the-aps.org/.
J Appl Physiol 103: 828–834, 2007.
First published June 7, 2007; doi:10.1152/japplphysiol.00265.2007.
The effects of nightly normobaric hypoxia and high intensity training under
intermittent normobaric hypoxia on running economy and hemoglobin mass
Mituso Neya,1 Taisuke Enoki,2 Yasuko Kumai,2 Takayuki Sugoh,2 and Takashi Kawahara2
1
The Graduate School of Arts and Sciences, The University of Tokyo; and 2Japan Institute of Sports Sciences, Tokyo, Japan
Submitted 6 March 2007; accepted in final form 22 May 2007
Neya M, Enoki T, Kumai Y, Sugoh T, Kawahara T. The effects
of nightly normobaric hypoxia and high intensity training under
intermittent normobaric hypoxia on running economy and hemoglo-
bin mass. J Appl Physiol 103: 828–834, 2007. First published June 7,
2007; doi:10.1152/japplphysiol.00265.2007.—We investigated the ef-
fects of nightly intermittent exposure to hypoxia and of training
during intermittent hypoxia on both erythropoiesis and running econ-
omy (RE), which is indicated by the oxygen cost during running
at submaximal speeds. Twenty-five college long- and middle-
distance runners [maximal oxygen uptake (V̇O2max) 60.3 ⫾ 4.7
ml 䡠 kg⫺1 䡠 min⫺1] were randomly assigned to one of three groups:
hypoxic residential group (HypR, 11 h/night at 3,000 m simulated
altitude), hypoxic training group (HypT), or control group (Con), for
an intervention of 29 nights. All subjects trained in Tokyo (altitude of
60 m) but HypT had additional high-intensity treadmill running for 30
min at 3,000 m simulated altitude on 12 days during the night
intervention. V̇O2 was measured at standing rest during four submaxi-
mal speeds (12, 14, 16, and 18 km/h) and during a maximal stage to
volitional exhaustion on a treadmill. Total hemoglobin mass (THb)
was measured by carbon monoxide rebreathing. There were no sig-
nificant changes in V̇O2max, THb, and the time to exhaustion in all
three groups after the intervention. Nevertheless, HypR showed ⬃5%
improvement of RE in normoxia (P ⬍ 0.01) after the intervention,
reflected by reduced V̇O2 at 18 km/h and the decreased regression
slope fitted to V̇O2 measured during rest position and the four
submaximal speeds (P ⬍ 0.05), whereas no significant corresponding
changes were found in HypT and Con. We concluded that our dose of
intermittent hypoxia (3,000 m for ⬃11 h/night for 29 nights) was
insufficient to enhance erythropoiesis or V̇O2max, but improved the RE
at race speed of college runners.
running economy; oxygen uptake; intermittent hypoxia
TO ENHANCE AEROBIC PERFORMANCE at sea level, many endurance
athletes include altitude or other hypoxic training in their
seasonal schedule. The major purpose of altitude training has
traditionally been to increase red blood cells, total hemoglobin
mass (THb), and subsequent aerobic performance (8, 25). The
effect of this training on sea level performance has been
documented by many studies, and among these the “living
high, training low” (LHTL) approach has also been shown to
increase THb and maximal oxygen uptake (V̇O2max) compared
with a control group (24). To overcome the geographical
restriction in many countries, which do not have appropriate
topography for this approach, normobaric hypoxia has been
employed to provide a simulated altitude environment near sea
level (22, 32).
LHTL has been reported to provide the athletes with an
acclimatization response that includes increases in THb,
Address for reprint requests and other correspondence: M. Neya, The
Graduate School of Arts and Sciences, The Univ. of Tokyo, 3-8-1 Komaba
Meguro-ku Tokyo, 153-8902, Tokyo, Japan (e-mail: neya@idaten.c.u-tokyo.
ac.jp).
828 8750-7587/07 $8.00 Copyright © 2007 the American Physiological Society
V̇O2max, and aerobic performance, while maintaining a similar
level of training intensity as at sea level (24, 25, 34, 43).
However, some studies using nightly normobaric hypoxia
reported no increases in THb and V̇O2max (1, 11, 41). The
extent to which LHTL mediates an increase in red blood cells
has recently been the subject of vigorous debate (10, 26),
although it has recently been argued that the minimum effec-
tive dose of hypoxia to attain a hematological acclimatization
effect is ⬎12 h/day for at least 3 wk at an altitude or simulated
altitude of 2,100 –2,500 m (40). Therefore it is still relevant to
Downloaded from jap.physiology.org on March 16, 2011
further investigate the effects of LHTL on sea level perfor-
mance in respect of hematological acclimatization.
In addition to a continuous increase in THb, altitude accli-
matization affects oxygen delivery and use during submaximal
exercise, which may result in the reduction of oxygen uptake of
the whole body or working muscles at submaximal intensities
(4, 15, 51). The most plausible mechanism that affects lowered
oxygen uptake is the transition of fuel supply from fat oxida-
tion toward greater glycolysis because the oxidation of glyco-
gen yields ⬃11% more ATP per mole of O2 compared with the
oxidation of fats (15, 16, 41). In favor of these mechanisms,
some recent studies documented decreased oxygen consump-
tion at submaximal intensities indicating improvement of
athletes’ running economy (RE; 19, 41). The net energy cost at
submaximal intensities or RE has been reported as a more
predictive parameter of aerobic performance than V̇O2max (6, 7,
31). Therefore, an improvement of these parameters induced
by altitude or hypoxic training would be advantageous for
aerobic athletes. However, a number of the studies that dem-
onstrate changes in substrate use after altitude acclimatization
have been conducted by using higher altitudes for longer
periods than athletes typically adopt (4, 15, 51). Therefore
further careful investigation about the efficacy of “living sim-
ulated high and training at sea level” in terms of increase in
THb and improvement of O2 utilization for the enhancement of
athletic performance is warranted.
As an alternative to LHTL, training with intermittent expo-
sure to hypoxia has been investigated for its efficacy on
improvement of athletic performance (29, 38, 39, 44). This
mode is equivalent to “living low, training high” (LLTH). Brief
periods of hypoxia are appealing to athletes whose normal
training regimen does not make it practical to spend as long as
12 h/day or more (40) inside a hypoxic chamber to improve
their performance. Therefore, training with intermittent expo-
sure to hypoxia may be a viable alternative for athletes seeking
to enhance their performance (17, 37), but the evidence for any
benefit is inconclusive.
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.
http://www. jap.org
 INTERMITTENT HYPOXIA AND SUBMAXIMAL EXERCISE
The purpose of this study was twofold; first to evaluate the
effectiveness of LHTL and second to evaluate the performance
benefits of training in hypoxia (LLTH). Specifically, we hy-
pothesized that 30 days intermittent nightly exposure to simu-
lated altitude (3,000 m) would increase both THb and improve
RE. We also hypothesized that LLTH (for 30 min, 3 times/wk
for 4 wk at 3,000 m) would improve athletic performance
reflected by improvement of RE without altering THb, since
the duration of hypoxia is insufficient to induce a sustained
increase in serum erythropoietin even at 5,450 m (21).
METHODS
Subjects. Twenty-five, male, college long- and middle-distance
runners (mean ⫾ SD age 21 ⫾ 2 yr, body mass 58.4 ⫾ 6.0 kg, V̇O2max
60.3 ⫾ 4.7 ml 䡠 min⫺1 䡠 kg⫺1) participated in this study, which was
approved by Japan Institute of Sports Sciences Ethics Committee. The
subjects gave their written consent to participate in this study. All
the subjects had more than 3 years training history as long- or
middle-distance race runners. Their 5,000 m best time during the 3 mo
before the intervention ranged from 17:52 to 14:57 and the average
was 15:57 (min:s).
This cohort was divided into three groups: hypoxic residential
group (HypR), hypoxic training group (HypT), and control group
(Con). Ten subjects were assigned to HypR and they spent 10 –12
h/night for 29 consecutive nights in a dormitory accommodation that
was controlled to normobaric hypoxia by enrichment with nitrogen
equivalent to 3,000 m above sea level [fraction of inspired oxygen
(FIO2) ⫽ 0.144] and they trained at sea level (Tokyo, Japan; 60 m
altitude) during the intervention. Nine subjects were assigned to HypT
and they slept in their own homes in Tokyo. They trained at sea level
(same environment as the HypR group) but had an additional 30 min
treadmill running training in normobaric hypoxia for 12 days of the
31-day intervention. Six subjects were assigned to Con, they slept in
their own homes in Tokyo and trained at sea level throughout the
intervention. The subjects’ sea level training distance, time, and
intensity were recorded and controlled to be similar among the three
groups, although the hypoxic treadmill training of the HypT group
was excluded from this calculation. The physical characteristics and
training volume are shown in Table 1.
Study design. The study intervention was 31 days (day 0 to day 30).
HypR slept at the accommodation controlled to normobaric normoxia
on the first night and in normobaric hypoxia for the remaining 29
nights. During the preliminary period, which was set 2 wk before the
study intervention, all subjects completed each of the V̇O2max and THb
measurement tests twice. The THb and V̇O2max test were conducted
once after the intervention. The outline of the study design is shown
in Fig. 1.
Treadmill testing for V̇O2max and running economy. V̇O2 was
measured during submaximal and maximal treadmill running. The
subjects ran at four submaximal speeds (12, 14, 16, and 18 km/h) each
of 4-min duration following 5-min standing resting on the treadmill.
Between each submaximal speed, there was a 1-min break to collect
a fingertip blood capillary sample for blood lactate concentration
Table 1. Subject characteristics, VO2max, THb, and runnning distance
Con
Pre Post
Age, yr 20.9⫾1.5
Body mass, kg 60.0⫾5.7 60.5⫾5.3
Running distance, km 244.6⫾82.7
Values are means ⫾ SD. Running distance means total of accumulated running distance during 31-day intervention. THb, total hemoglobin; Con, control;
HypT, hypoxic training group; HypR, residential group.
J Appl Physiol • VOL
829
(BLa). V̇O2, minute ventilation (V̇E), volume of carbon dioxide pro-
duced (V̇CO2), respiratory exchange ratio (RER), and heart rate (HR)
were measured during both submaximal and maximal running. One
minute after the fourth submaximal run, the subjects ran to volitional
exhaustion commencing at 18 km/h. The speed was increased by 1
km/h each minute up to 20 km/h, and thereafter the treadmill gradient
increased by 1% each minute until exhaustion. The time to exhaustion
(TTE) during the V̇O2max stage was used as the marker for perfor-
mance. HR was measured by telemetry electrocardiograph (WEP-
4202, Nihon Kohden) and BLa was measured by Biosen 1,000 (NSI).
Respiratory gas analysis. Respiratory gas samples were collected
in Douglas bags for 1 min during the last 2 min of each submaximal
stage and every 30 or 60 s of the maximal stage. The volume of
expired air was measured with a dry gas volume meter (10 liter,
custom built, Arco System) after 500 ml of the sample was analyzed
for fractions with mass spectroscopy (ARCO-2000, Arco System),
which was calibrated by three precision gas mixtures before each test.
The custom-designed software was employed to compute V̇O2, V̇CO2,
V̇E, and RER using standard algorithms. The highest 1-min V̇O2
during the last stage was regarded as V̇O2max of that test. The higher
value of V̇O2max in two preintervention tests was regarded as prein-
Downloaded from jap.physiology.org on March 16, 2011
tervention V̇O2max. The typical error of measurement (TEM) for the
two preintervention V̇O2max tests was 1.4 ml 䡠 kg⫺1 䡠 min⫺1 [95%
confidence interval (CI) ⫺2.2 to 1.0 ml 䡠 kg⫺1 䡠 min⫺1] or 2.3% for
mean V̇O2max.
THb measurement. Before and after the intervention, THb was
measured by carbon monoxide (CO) rebreathing method introduced
by Burge and Skiner (5) and modified by Saunders et al. (41). The
subjects were dosed with 99.95% CO twice and rebreathed each dose
for 10 min each (20 ml for initial dose and 1.50 ml/kg body mass for
second dose). Two milliliter blood samples were collected from an
antecubital vein to measure the percent of carboxyhemoglobin
(%HbCO). The average of %HbCO from eight replicates conducted
on each blood sample measured by an ABL OSM3 (Radiometer,
Copenhagen, Denmark) for both CO doses was obtained, and the
difference of %HbCO between primary and second doses was used to
calculate THb (5). The typical error of measurement for duplicate
THb measurements conducted during the preliminary period was 0.48
g/kg (95% CI was ⫺1.06 to 0.31 g/kg) or 3.3% of the mean THb. The
mean value of THb conducted twice during the preliminary period
was regarded as THb value of preintervention.
Hypoxic environment for HypR and HypT. In this study, we used
the two types of hypoxic environment for the two groups. They were
hypoxic accommodation and a training room. The hypoxic environ-
ment for both of them was created by filtering compressed air through
high-polymer membrane, controlled to yield an FIO2 of 0.144. The
volume flow through both the accommodation and training room was
sufficient to limit ĊO2 concentration to below 1,000 ppm. Each HypR
subject was accommodated in a single hypoxic room (⬃50 m3) with
bed and bathroom. HypT used the hypoxic training room (⬃100 m3)
equipped with the treadmill for running training.
Treadmill training for HypT. The HypT group conducted twelve
30-min treadmill running training sessions under normobaric hypoxia
(FIO2 ⫽ 0.144) in addition to their ordinary sea level training for the
HypT HypR
Pre Post Pre Post
20.0⫾2.3 21.1⫾1.3
60.4⫾4.4 61.1⫾4.8 55.3⫾4.0 55.4⫾4.4
267.8⫾161.3 248.4⫾83.6
103 • SEPTEMBER 2007 • www.jap.org
830 INTERMITTENT HYPOXIA AND SUBMAXIMAL EXERCISE
Fig. 1. The outline of the study. CON, control; HypT,
hypoxic training group; HypR, residential training group;
FIO2, fraction of inspired oxygen; THb, total hemoglobin
mass.
entire 31 days during the study intervention. The hypoxic training
sessions were conducted ⬃3 or 4 days apart at an intensity of 80 –90%
of maximal heart rate (HRmax) attained during the V̇O2max test at sea
level before the intervention. The subjects started at the speed equiv-
alent to their individual 80%HRmax for the first 10 min and gradually
increased the speed during the next 20 min to yield a heart rate of
up ⬃90%HRmax as assessed by telemetry (Heart rate monitor NV,
Polar). The standardized warm-up and cool-down before and after
each training session was conducted in normoxia.
Statistical analysis. A two-way analysis of variance with repeated
measures with groups (HypR, HypT, and Con) and the intervention
(pre- and postintervention) was used to test for interaction and main
effects. When interactions or main effects reached significance, the
Tukey’s post hoc test was used to identify significant differences. All
values were expressed as means ⫾ SD and significance was set at P ⬍
0.05. The statistical software package SPSS for Doctors (Nankodo,
Japan) was used for all analyses.
RESULTS
Hypoxic exposure. The HypR group accumulated a total of
316 h in hypoxia and their average time of nightly exposure to
normobaric hypoxia of HypR was 10:54 ⫾ 0:24 (h:min). The
HypT group accumulated a total of 6 h in hypoxia.
V̇O2max, THb, and time to exhaustion. There were no signif-
icant differences among the three groups at baseline in terms of
their physical characteristics, running distance, and THb. How-
Table 2. Statistical variables of relative VO2max and THb
Variable Significance
THb, main effect (time) F ⫽ 0.35
P ⫽ 0.56
THb, main effect (group) F ⫽ 2.49
P ⫽ 0.10
THb, interaction (time⫻group) F ⫽ 0.11
P ⫽ 0.89
V̇O2max, main effect (time) F ⫽ 3.29
P ⫽ 0.08
V̇O2max, main effect (group) F ⫽ 0.90
P ⫽ 0.42
V̇O2max, interaction (time⫻group) F ⫽ 0.78
P ⫽ 0.47
J Appl Physiol • VOL
Downloaded from jap.physiology.org on March 16, 2011
ever, because the Con had a higher absolute body mass,
relative values of V̇O2 and THb were used to evaluate the
differences among the groups. There were no significant
changes in V̇O2max and THb within or between groups during
the intervention. V̇O2max tended to decrease in both the Con and
HypR groups (by ⫺5.0 and ⫺4.2%, respectively), but not in
the HypT group (⫺0.3%). The mean THb remained within 1%
of the Pre value for all three groups. The results of THb and
V̇O2max between pre- and postintervention with F and P values
were shown in Table 2 and the changes in these variables of
each subject are shown in Figs. 2 (relative THb) and 3 (relative
V̇O2max).
TTE was also unchanged between pre- vs. postintervention
in all three groups [interaction (groups⫻time), F ⫽ 1.48, P ⫽
0.25; group main effect, F ⫽ 2.88, P ⫽ 0.11] but HypT only
showed a tendency to improve TTE after the intervention (pre
vs. post in each group, HypT, 220 ⫾ 90 vs. 257 ⫾ 66 s, P ⫽
0.07; HypR, 261 ⫾ 49 vs. 279 ⫾ 60 s, P ⫽ 0.17; Con, 300 ⫾
37 vs. 294 ⫾ 68 s, P ⫽ 0.78).
Running economy. At the four submaximal running speeds,
V̇O2 of HypR tended to be reduced at postintervention com-
pared with preintervention values at lower speeds (P ⫽ 0.06 at
12 km/h and P ⫽ 0.05 at 14 km/h) and was ⬃5% reduced at 18
km/h (P ⬍ 0.01). However, there was no significant change
in submaximal V̇O2 at all four speeds for the HypT and Con
groups between pre- and postinterventions (Table 3). The
changes of V̇E, RER, HR, and BLa at submaximal speeds
were shown in Table 3. The RER of HypT tended to be
higher at postintervention than preintervention (P ⬍ 0.05 at
12 km/h, P ⫽ 0.06 at 16 km/h and P ⫽ 0.05 at 18 km/h). No
other significant changes were detected among theses vari-
ables.
The regression data for the three groups were fitted through
the measured V̇O2 at rest (standing on the treadmill for 5 min)
and four running speeds (Fig. 4). There was a significant
decrease (P ⫽ 0.04) in the slopes of V̇O2 and running speed
between pre- and postintervention for HypR, but no significant
changes were found in the other two groups (P ⫽ 0.58 for
HypT and P ⫽ 0.64 for Con).
103 • SEPTEMBER 2007 • www.jap.org
 INTERMITTENT HYPOXIA AND SUBMAXIMAL EXERCISE 831
change in their THb (1.8% decrease) compared with a control
group (0.9% decrease). Other studies using LHTL also re-
ported no change in THb (11, 41). It appears that our study did
not have a sufficient hypoxic dose (number of hours per day or
a sufficient number of days) to increase THb, because the
altitude (3,000 m) is well above that required to stimulate
increased erythropoiesis (49) and was 500 m above that used
by Levine et al. (23).
The other major finding of this study was that this nightly
intermittent exposure to hypoxia improved running economy,
which was reflected at reduced whole body submaximal V̇O2
and a reduced slope between V̇O2 vs. running speed on a
treadmill. In particular, HypR showed a significant reduction in
submaximal V̇O2 at 18 km/h, which is close to race speed of
college athletes for a 5,000 m race. Therefore the improvement
of RE at 18 km/h was practically worthwhile for these subjects.

Downloaded from jap.physiology.org on March 16, 2011

Fig. 2. Changes in relative THb between pre- and postintervention. Individual
dashed lines, results of each subject; thick line, means ⫾ SD.

DISCUSSION

The main finding of this study was that 29 nights of sleeping

in normobaric hypoxia ⬃11 h/night at 3,000 m in long- and
middle-distance college runners (HypR) did not increase THb
or V̇O2max. Our results contrast with those of Levine and
Stray-Gundersen (23) in which the subjects slept and lived at
2,500 m altitude for 28 days for ⬃20 –22 h/day and the LHTL
group increased red blood cell volume (by 5.3%) and V̇O2max Fig. 3. Changes in relative maximal oxygen uptake (V̇O2max) between pre- and
(3.9%). On the other hand, Ashenden et al. (1) had subjects postintervention. Individual dashed lines, results of each subject; thick line,
spend 23 nights at 3,000 m (⬃9 h/night) and observed no means ⫾ SD.

J Appl Physiol • VOL 103 • SEPTEMBER 2007 • www.jap.org

832 INTERMITTENT HYPOXIA AND SUBMAXIMAL EXERCISE

Table 3. Changes in oxygen uptake, ventilation, RER, heart rate, and blood lactate concentration at submaximal running
12 14 16 18

Running Speed, km/h Pre Post Pre Post Pre Post Pre Post

V̇O2,
ml 䡠 kg⫺1 䡠 min⫺1
HypR 37.3⫾3.3 36.1⫾5.1 44.7⫾5.1 42.5⫾3.0 52.0⫾4.3 49.4⫾2.7 58.7⫾4.7 55.6⫾2.7†
HypT 34.9⫾4.5 36.3⫾2.0 41.8⫾2.7 42.2⫾2.4 48.1⫾3.3 48.7⫾2.7 54.4⫾3.0 53.9⫾4.0
Con 34.5⫾5.2 34.8⫾1.4 42.2⫾4.9 41.4⫾2.6 49.0⫾5.4 47.9⫾1.8 52.6⫾7.9 51.3⫾2.3
VE, l/min
HypR 44.0⫾3.3 44.1⫾3.3 55.7⫾6.9 54.4⫾4.4 69.7⫾8.3 68.0⫾5.9 89.3⫾13.2 85.1⫾10.3
HypT 43.0⫾4.6 48.4⫾5.0 54.8⫾6.7 59.6⫾7.0 68.1⫾8.1 74.2⫾9.7 89.3⫾13.2 92.7⫾11.8
Con 43.1⫾9.0 43.5⫾6.3 54.6⫾6.6 54.0⫾8.7 68.2⫾7.4 66.5⫾12.8 81.1⫾8.2 80.5⫾16.7
RER
HypR 0.92⫾0.07 0.91⫾0.05 0.98⫾0.03 1.00⫾0.03 1.03⫾0.03 1.05⫾0.04 1.12⫾0.05 1.13⫾0.05
HypT 0.87⫾0.02 0.92⫾0.04* 0.98⫾0.04 1.00⫾0.03 1.04⫾0.05 1.07⫾0.04 1.13⫾0.04 1.15⫾0.04
Con 0.87⫾0.04 0.86⫾0.05 0.96⫾0.04 0.95⫾0.04 1.03⫾0.06 1.01⫾0.04 1.09⫾0.08 1.10⫾0.07
HR, beats/min
HypR 133⫾10 130⫾9 153⫾12 148⫾9 170⫾11 166⫾11 183⫾10 180⫾10
HypT 139⫾15 138⫾12 158⫾14 153⫾12 173⫾11 168⫾10 185⫾8 181⫾9
Con 136⫾11 129⫾13 152⫾12 147⫾15 168⫾7 164⫾12 178⫾3 175⫾4
BLa, mM

Downloaded from jap.physiology.org on March 16, 2011

HypR 1.9⫾0.7 2.5⫾0.5 2.1⫾1.1 2.1⫾1.1 3.3⫾1.6 3.3⫾1.4 6.2⫾3.2 6.1⫾2.4
HypT 2.5⫾0.5 2.2⫾0.6 2.1⫾1.1 2.3⫾0.9 3.3⫾1.5 3.6⫾1.2 6.0⫾2.3 6.6⫾2.1
Con 1.9⫾0.4 1.3⫾0.3 2.3⫾0.9 1.4⫾0.3 3.4⫾1.3 2.5⫾0.4 6.0⫾2.5 4.9⫾1.7
Values are means ⫾ SD. V̇O2, oxygen uptake; V̇E, minute ventilation; RER, respiratory exchnge ratio; HR, heart rate; BLa, blood lactate concentration.
*⬍ 0.05 and †⬍ 0.01, differences between pre- and postintervention.

Improved RE in HypR. The net exercise cost at submaximal
workloads has been reported to be more related to endurance
athletic performance than V̇O2max (6, 7, 31) in a range of
locomotions, including swimming (45), cross-country skiing
(30), and running (41). Our results showed that V̇O2 during
5-min standing rest was not changed between pre- and postin-
tervention in all three groups. However, the slope between V̇O2
and running speed was reduced only in HypR, which suggests
that the LHTL intervention caused the decrease in the net
energy requirement during the submaximal exercise. Submaxi-
mal V̇O2 is a function of both central factors (such as cardiac
output and oxygen carrying capacity) and peripheral factors
(such as oxygen use by the working muscle; Refs. 11, 41). The
unchanged HR and THb in this study indicate that this LHTL
intervention method did not affect “the central” factors. By
implication, the reduced slope between V̇O2 vs. running speed
postintervention may be due to the change of “peripheral”
function of working muscle (15). Our results contribute to the
growing body of evidence that natural or simulated altitude
reduces V̇O2 in normoxia at submaximal intensities (11, 15, 16,
18 –20, 28, 41, 42). In comparison, a large number of studies
also reported that submaximal V̇O2 after altitude is unchanged
(12, 23, 27, 33, 50). The reasons for the discrepancy between
investigators are unclear, but great care was taken with our
measurement of V̇O2 as illustrated by our low typical error for
submaximal (TEM ⫽ 1.0 ml䡠kg⫺1 䡠min⫺1 with 95%CI; ⫺0.8 to
1.4 ml䡠kg⫺1 䡠min⫺1) and maximal (TEM ⫽ 1.4 ml䡠kg⫺1 䡠min⫺1
with 95%CI; ⫺2.2 to 1.0 ml䡠kg⫺1 䡠min⫺1) V̇O2.
The mechanisms of improved RE. With regards to mecha-
nisms of reduced submaximal V̇O2 in HypR, a decreased cost
of V̇E (15) and greater dependence on carbohydrate use to
generate ATP after acclimatization to hypoxia are major can-
didates to explain improved RE (3, 11, 15). In our results, the
former mechanism can be excluded due to no change in
submaximal V̇E (nor HR). On the other hand, numerous studies
J Appl Physiol • VOL
(3, 11, 15, 35, 36) reported that hypoxic acclimatization in-
creases dependence on glucose metabolism instead of fatty
acids to generate ATP, where the former are 10% energetically
more efficient. However, our results did not show a significant
increase in RER after LHTL, which has been reported previ-
ously by Gore et al. (11).
In addition to these possibilities to explain improved RE,
reduced ATP consumption needs at muscle level after altitude
exposure have been reported (13, 14). This change was typi-
cally indicated by downregulation of muscle Na⫹-K⫹-ATPase
content. Aughey et al. (2) concluded that 23 nights intermittent
exposure to 3,000 m simulated altitude was not sufficient for
downregulation of muscle Na⫹-K⫹-ATPase to influence mus-
cle performance. Our magnitude of hypoxia and duration were
very similar to their study and therefore we can speculate that
downregulation of muscle Na⫹-K⫹-ATPase content was un-
likely to have influenced the improved RE that we measured.
But it is possible that hypoxic exposure resulted in tighter
coupling of muscular intracellular bioenergetics, which im-
proved mitochondrial efficiency.
No effects of high-intensity training in hypoxia on perfor-
mance of HypT. Controlled investigations have not been able to
elucidate conclusive evidence about intermittent hypoxic train-
ing (IHT) with regard to the improvement of athletic perfor-
mance (9, 39, 46 – 48), although pooling the results is prob-
lematic because there has been a very wide range of duration,
frequency, intensity of the training, as well as the level of
hypoxia and training models. The study of Dufour et al. (9) is
closest to our study with respect of the level of hypoxia,
training model, and intensity. Their subjects were distance
runners and trained on treadmill at ⬃80% of V̇O2max of nor-
moxia for ⬃40 min a session and 2 days/wk for 6 wk in
normobaric hypoxia simulated to 3,000 m altitude. In contrast
to our results, they reported increased V̇O2max and increased
time to exhaustion during the incremental maximal test. Other
103 • SEPTEMBER 2007 • www.jap.org
 INTERMITTENT HYPOXIA AND SUBMAXIMAL EXERCISE
Fig. 4. The regression slopes between relative V̇O2 vs. running speed. Solid
lines, preintervention; dashed lines: postintervention. NS, not significant.
studies that have conducted high-intensity training in hypoxia
have also succeeded to induce effective results using IHT with
trained subjects (39, 46 – 48). The effective studies accumu-
lated a longer total exposure to hypoxia than we used; their
subjects were exposed to hypoxia of 2,500 – 4,000 m simulated
altitude for a total of 480 – 800 min, whereas our subjects
accrued 360 min at 3,000 m simulated altitude. Consequently,
it is speculated that the integral function of the total time and
the level of exposure to hypoxia influences the dividing line
between success and failure to induce beneficial effects of IHT
on sea level performance. Failure to detect any improvement of
sea level run time to exhaustion in our HypT group may be a
consequence of either an insufficient level of hypoxia and/or
the accumulated time of exposure.
Conclusion. The results of this study showed that sleeping at
normobaric hypoxia simulated altitude (3,000 m for 12 h/night
for 29 nights) resulted in no significant increase in THb or
V̇O2max but a ⬃5% improvement in RE of college long- and
middle- distance runners. On the other hand, living and training
J Appl Physiol • VOL 103 • SEPTEMBER 2007 •
833
at sea level with or without 60 min of intermittent exposure to
hypoxia (3,000 m) had no significant effects on THb, V̇O2max,
or RE. Overall, our chosen dose of LHTL improved RE at race
running speed for college level long- and middle-distance
runners, but whether international caliber runners also can
acquire improved RE at race pace after LHTL requires further
research.
ACKNOWLEDGMENTS
This study was a part of the research project of Japan Institute of Sport
Sciences for enhancement of athletic performance using hypoxia.
REFERENCES
1. Ashenden MJ, Gore CJ, Dobson GP, Hahn AG. “Live high, train low”
does not change the total haemoglobin mass of male endurance athletes
sleeping at a simulated altitude of 3000 m for 23 nights. Eur J Appl
Physiol 80: 479 – 484, 1999.
2. Aughey RJ, Gore CJ, Hahn AG, Garnham AP, Clark SA, Petersen
AC, Roberts AD, McKenna MJ. Chronic intermittent hypoxia and
incremental cycling exercise independently depress muscle in vitro max-
imal Na⫹-K⫹-ATPase activity in well-trained athletes. J Appl Physiol 98:
Downloaded from jap.physiology.org on March 16, 2011
186 –192, 2005.
3. Brooks GA, Butterfield GE, Wolfe RR, Groves BM, Mazzeo RS,
Sutton JR, Wolfel EE, Reeves JT. Increased dependence on blood
glucose after acclimatization to 4,300 m. J Appl Physiol 70: 919 –927,
1991.
4. Brooks GA, Wolfel EE, Groves BM, Bender PR, Butterfield GE,
Cymerman A, Mazzeo RS, Sutton JR, Wolfe RR, Reeves JT. Muscle
accounts for glucose disposal but not blood lactate appearance during
exercise after acclimatization to 4,300 m. J Appl Physiol 72: 2435–2445,
1992.
5. Burge CM, Skinner SL. Determination of hemoglobin mass and blood
volume with CO: evaluation and application of a method. J Appl Physiol
79: 623– 631, 1995.
6. Conley DL, Krahenbuhl GS. Running economy and distance running
performance of highly trained athletes. Med Sci Sports Exerc 12: 357–360,
1980.
7. Costill DL, Thomason H, Roberts E. Fractional utilization of the aerobic
capacity during distance running. Med Sci Sports 5: 248 –252, 1973.
8. Dick FW. Training at altitude in practice. Int J Sports Med 13, Suppl 1:
S203–206, 1992.
9. Dufour SP, Ponsot E, Zoll J, Doutreleau S, Lonsdorfer-Wolf E, Geny
B, Lampert E, Fluck M, Hoppeler H, Billat V, Mettauer B, Richard R,
Lonsdorfer J. Exercise training in normobaric hypoxia in endurance
runners. I. Improvement in aerobic performance capacity. J Appl Physiol
100: 1238 –1248, 2006.
10. Gore CJ, Hopkins WG. Counterpoint: Positive effects of intermittent
hypoxia (live high:train low) on exercise performance are not mediated
primarily by augmented red cell volume. J Appl Physiol 99: 2055–2058,
2005.
11. Gore CJ, Hahn AG, Aughey RJ, Martin DT, Ashenden MJ, Clark SA,
Garnham AP, Roberts AD, Slater GJ, McKenna MJ. Live high:train
low increases muscle buffer capacity and submaximal cycling efficiency.
Acta Physiol Scand 173: 275–286, 2001.
12. Grassi B, Marzorati M, Kayser B, Bordini M, Colombini A, Conti M,
Marconi C, Cerretelli P. Peak blood lactate and blood lactate vs.
workload during acclimatization to 5,050 m and in deacclimatization.
J Appl Physiol 80: 685– 692, 1996.
13. Green H, MacDougall J, Tarnopolsky M, Melissa NL. Downregulation
of Na⫹-K⫹-ATPase pumps in skeletal muscle with training in normobaric
hypoxia. J Appl Physiol 86: 1745–1748, 1999.
14. Green H, Roy B, Grant S, Burnett M, Tupling R, Otto C, Pipe A,
McKenzie D. Downregulation in muscle Na⫹-K⫹-ATPase following a
21-day expedition to 6,194 m. J Appl Physiol 88: 634 – 640, 2000.
15. Green HJ, Roy B, Grant S, Hughson R, Burnett M, Otto C, Pipe A,
McKenzie D, Johnson M. Increases in submaximal cycling efficiency
mediated by altitude acclimatization. J Appl Physiol 89: 1189 –1197, 2000.
16. Hochachka PW, Stanley C, Matheson GO, McKenzie DC, Allen PS,
Parkhouse WS. Metabolic and work efficiencies during exercise in
Andean natives. J Appl Physiol 70: 1720 –1730, 1991.
17. Julian CG, Gore CJ, Wilber RL, Daniels JT, Fredericson M, Stray-
Gundersen J, Hahn AG, Parisotto R, Levine BD. Intermittent normo-
www.jap.org
834 INTERMITTENT HYPOXIA AND SUBMAXIMAL EXERCISE
baric hypoxia does not alter performance or erythropoietic markers in
highly trained distance runners. J Appl Physiol 96: 1800 –1807, 2004.
18. Kacin A, Golja P, Eiken O, Tipton MJ, Mekjavic IB. The influence of
acute and 23 days of intermittent hypoxic exposures on the exercise-
induced forehead sweating response. Eur J Appl Physiol 99: 557–566,
2007.
19. Katayama K, Matsuo H, Ishida K, Mori S, Miyamura M. Intermittent
hypoxia improves endurance performance and submaximal exercise effi-
ciency. High Alt Med Biol 4: 291–304, 2003.
20. Katayama K, Sato K, Matsuo H, Ishida K, Iwasaki K, Miyamura M.
Effect of intermittent hypoxia on oxygen uptake during submaximal
exercise in endurance athletes. Eur J Appl Physiol 92: 75– 83, 2004.
21. Knaupp W, Khilnani S, Sherwood J, Scharf S, Steinberg H. Erythro-
poietin response to acute normobaric hypoxia in humans. J Appl Physiol
73: 837– 840, 1992.
22. Koistinen PO, Rusko H, Irjala K, Rajamaki A, Penttinen K, Sar-
paranta VP, Karpakka J, Leppaluoto J. EPO, red cells, and serum
transferrin receptor in continuous and intermittent hypoxia. Med Sci Sports
Exerc 32: 800 – 804, 2000.
23. Levine BD, Stray-Gundersen J. “Living high-training low”: effect of
moderate-altitude acclimatization with low-altitude training on perfor-
mance. J Appl Physiol 83: 102–112, 1997.
24. Levine BD, Stray-Gundersen J. “Living high-training low”: effect of
moderate-altitude acclimatization with low-altitude training on perfor-
mance. J Appl Physiol 83: 102–112, 1997.
25. Levine BD, Stray-Gundersen J. The effects of altitude training are
mediated primarily by acclimatization, rather than by hypoxic exercise.
Adv Exp Med Biol 502: 75– 88, 2001.
26. Levine BD, Stray-Gundersen J. Point: Positive effects of intermittent
hypoxia (live high:train low) on exercise performance are mediated
primarily by augmented red cell volume. J Appl Physiol 99: 2053–2055,
2005.
27. Lundby C, Calbet JAL, Sandar M, van Hall G, Mazzeo RS, Stray-
Gundersen J, Stager JM, Chapman RF, Saltin B, Levine BD. Exercise
economy does not change after acclimatization to moderate to very high
altitude. Scand J Med Sci Sports 17: 281–291, 2007.
28. MacDonald MJ, Green HJ, Naylor HL, Otto C, Hughson RL. Reduced
oxygen uptake during steady state exercise after 21-day mountain climb-
ing expedition to 6,194 m. Can J Appl Physiol 26: 143–156, 2001.
29. Meeuwsen T, Hendriksen IJ, Holewijn M. Training-induced increases
in sea-level performance are enhanced by acute intermittent hypobaric
hypoxia. Eur J Appl Physiol 84: 283–290, 2001.
30. Millet GP, Boissiere D, Candau R. Energy cost of different skating
techniques in cross-country skiing. J Sports Sci 21: 3–11, 2003.
31. Morgan DW, Martin PE, Krahenbuhl GS. Factors affecting running
economy. Sports Med 7: 310 –330, 1989.
32. Nummela A, Rusko H. Acclimatization to altitude and normoxic training
improve 400-m running performance at sea level. J Sports Sci 18:
411– 419, 2000.
33. Piehl Aulin K, Svedenhag J, Wide L, Berglund B, Saltin B. Short-term
intermittent normobaric hypoxia— haematological, physiological and
mental effects. Scand J Med Sci Sports 8: 132–137, 1998.
34. Robach P, Schmitt L, Brugniaux JV, Nicolet G, Duvallet A, Fouillot
JP, Moutereau S, Lasne F, Pialoux V, Olsen NV, Richalet JP. Living
high-training low: effect on erythropoiesis and maximal aerobic perfor-
mance in elite Nordic skiers. Eur J Appl Physiol 97: 695–705, 2006.
J Appl Physiol • VOL 103 • SEPTEMBER 2007 •
35. Roberts AC, Butterfield GE, Cymerman A, Reeves JT, Wolfel EE,
Brooks GA. Acclimatization to 4,300-m altitude decreases reliance on fat
as a substrate. J Appl Physiol 81: 1762–1771, 1996.
36. Roberts AC, Reeves JT, Butterfield GE, Mazzeo RS, Sutton JR,
Wolfel EE, Brooks GA. Altitude and beta-blockade augment glucose
utilization during submaximal exercise. J Appl Physiol 80: 605– 615,
1996.
37. Rodriguez FA, Truijens MJ, Townsend NE, Martini ER, Stray-
Gundersen J, Gore CJ, Levine BD. Effects of four weeks of intermittent
hypobaric hypoxia on sea level running and swimming performance. Med
Sci Sports Exerc 36: S338, 2004.
38. Rodriguez FA, Casas H, Casas M, Pages T, Rama R, Ricart A,
Ventura JL, Ibanez J, Viscor G. Intermittent hypobaric hypoxia stimu-
lates erythropoiesis and improves aerobic capacity. Med Sci Sports Exerc
31: 264 –268, 1999.
39. Roels B, Millet GP, Marcoux CJ, Coste O, Bentley DJ, Candau RB.
Effects of hypoxic interval training on cycling performance. Med Sci
Sports Exerc 37: 138 –146, 2005.
40. Rusko HK, Tikkanen HO, Peltonen JE. Altitude and endurance training.
J Sports Sci 22: 928 –945, 2004.
41. Saunders PU, Telford RD, Pyne DB, Cunningham RB, Gore CJ, Hahn
AG, Hawley JA. Improved running economy in elite runners after 20 days
of simulated moderate-altitude exposure. J Appl Physiol 96: 931–937,
2004.
Downloaded from jap.physiology.org on March 16, 2011
42. Schmitt L, Millet G, Robach P, Nicolet G, Brugniaux JV, Fouillot JP,
Richalet JP. Influence of “living high-training low” on aerobic perfor-
mance and economy of work in elite athletes. Eur J Appl Physiol 97:
627– 636, 2006.
43. Stray-Gundersen J, Chapman RF, Levine BD. “Living high-training
low” altitude training improves sea level performance in male and female
elite runners. J Appl Physiol 91: 1113–1120, 2001.
44. Terrados N, Melichna J, Sylven C, Jansson E, Kaijser L. Effects of
training at simulated altitude on performance and muscle metabolic
capacity in competitive road cyclists. Eur J Appl Physiol Occup Physiol
57: 203–209, 1988.
45. Toussaint HM, Hollander AP. Energetics of competitive swimming.
Implications for training programmes. Sports Med 18: 384 – 405, 1994.
46. Truijens MJ, Toussaint HM, Dow J, Levine BD. Effect of high-intensity
hypoxic training on sea-level swimming performances. J Appl Physiol 94:
733–743, 2003.
47. Vallier JM, Chateau P, Guezennec CY. Effects of physical training in a
hypobaric chamber on the physical performance of competitive triathletes.
Eur J Appl Physiol Occup Physiol 73: 471– 478, 1996.
48. Ventura N, Hoppeler H, Seiler R, Binggeli A, Mullis P, Vogt M. The
response of trained athletes to six weeks of endurance training in hypoxia
or normoxia. Int J Sports Med 24: 166 –172, 2003.
49. Weil JV, Jamieson G, Brown DW, Grover RF. The red cell mass-
arterial oxygen relationship in normal man. Application to patients with
chronic obstructive airway disease. J Clin Invest 47: 1627–1639, 1968.
50. Wolfel EE, Groves BM, Brooks GA, Butterfield GE, Mazzeo RS,
Moore LG, Sutton JR, Bender PR, Dahms TE, McCullough RE.
Oxygen transport during steady-state submaximal exercise in chronic
hypoxia. J Appl Physiol 70: 1129 –1136, 1991.
51. Young AJ, Evans WJ, Cymerman A, Pandolf KB, Knapik JJ, Maher
JT. Sparing effect of chronic high-altitude exposure on muscle glycogen
utilization. J Appl Physiol 52: 857– 862, 1982.
www.jap.org