![Training effect in fat mass measured at baseline, before 18 sessions (T2) and a week (T3) and 4 weeks (T4) after intervention in each group [(A) SitN: sprint interval training normoxia; SitH: sprint interval training hypoxia; (B) AitN: aerobic interval training normoxia; AitH: aerobic interval training hypoxia]. *Significant difference respect to baseline (P < 0.05). #Significant difference between group in T3 (P < 0.05); &Significant difference between group in T4 (P < 0.05).](https://www.researchgate.net/publication/322978058/figure/fig3/AS:11431281255817670@1719438536485/Training-effect-in-fat-mass-measured-at-baseline-before-18-sessions-T2-and-a-week-T3_Q320.jpg)
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ORIGINAL RESEARCH
published: 07 February 2018
doi: 10.3389/fphys.2018.00060
Frontiers in Physiology | www.frontiersin.org 1February 2018 | Volume 9 | Article 60
Edited by:
Olivier Girard,
Qatar Orthopaedic and Sports
Medicine Hospital, Qatar
Reviewed by:
Tadej Debevec,
Faculty of Sport, University of
Ljubljana, Slovenia
Kazushige Goto,
Ritsumeikan University, Japan
*Correspondence:
Alba Camacho-Cardenosa
albacc@unex.es
Specialty section:
This article was submitted to
Exercise Physiology,
a section of the journal
Frontiers in Physiology
Received: 22 September 2017
Accepted: 18 January 2018
Published: 07 February 2018
Citation:
Camacho-Cardenosa A,
Camacho-Cardenosa M,
Burtscher M, Martínez-Guardado I,
Timon R, Brazo-Sayavera J and
Olcina G (2018) High-Intensity Interval
Training in Normobaric Hypoxia Leads
to Greater Body Fat Loss in
Overweight/Obese Women than
High-Intensity Interval Training in
Normoxia. Front. Physiol. 9:60.
doi: 10.3389/fphys.2018.00060
High-Intensity Interval Training in
Normobaric Hypoxia Leads to
Greater Body Fat Loss in
Overweight/Obese Women than
High-Intensity Interval Training in
Normoxia
Alba Camacho-Cardenosa 1
*, Marta Camacho-Cardenosa 1, Martin Burtscher 2,
Ismael Martínez-Guardado 1, Rafael Timon 1, Javier Brazo-Sayavera 3and
Guillermo Olcina 1
1Faculty of Sport Sciences, University of Extremadura, Cáceres, Spain, 2Medical Section, Department of Sport Science,
University of Innsbruck, Innsbruck, Austria, 3Instituto Superior de Educación Física, Universidad de la República, Montevideo,
Uruguay
A moderate hypoxic stimulus is considered a promising therapeutic modality for
several pathological states including obesity. There is scientific evidence suggesting
that when hypoxia and physical activity are combined, they could provide benefits for
the obese population. The aim of the present study was to investigate if exposure
to hypoxia combined with two different protocols of high-intensity interval exercise in
overweight/obese women was more effective compared with exercise in normoxia. Study
participants included 82 overweight/obese women, who started a 12 week program of
36 sessions, and were randomly divided into four groups: (1) aerobic interval training in
hypoxia (AitH; FiO2=17.2%; n=13), (2) aerobic interval training in normoxia (AitN;
n=15), (3) sprint interval training in hypoxia (SitH; n=15), and (4) sprint interval
training in normoxia (SitN; n=18). Body mass, body mass index, percentage of total fat
mass, muscle mass, basal metabolic rate, fat, and carbohydrate oxidation, and fat and
carbohydrate energy were assessed. Outcomes were measured at baseline (T1), after
18 training sessions (T2), 7 days after the last session (T3), and 4 weeks after the last
session (T4). The fat mass in the SitH group was significantly reduced compared with
the SitN group from T1 to T3 (p<0.05) and from T1 to T4 (p<0.05) and muscle mass
increased significantly from T1 to T4 (p<0.05). Fat mass in the AitH group decreased
significantly (p<0.01) and muscle mass increased (p=0.022) compared with the AitN
group from T1 to T4. All training groups showed a reduction in the percentage of fat
mass, with a statistically significant reduction in the hypoxia groups (p<0.05). Muscle
mass increased significantly in the hypoxia groups (p<0.05), especially at T4. While fat
oxidation tended to increase and oxidation of carbohydrates tended to decrease in both
Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
hypoxia groups, the tendency was reversed in the normoxia groups. Thus, high-intensity
interval training under normobaric intermittent hypoxia for 12 weeks in overweight/obese
women seems to be promising for reducing body fat content with a concomitant increase
in muscle mass.
Keywords: normobaric hypoxia, body mass loss, obese, exercise, high-intensity
INTRODUCTION
According to the World Health Organization (WHO, 2006),
overweight and obesity are defined as abnormal or excessive fat
accumulation that may impair health. Although there is a global
obesity pandemic, the prevalence of being overweight and obesity
among men and women is different, and overall, more women are
obese than men (Kanter and Caballero, 2012). Being overweight
and obesity are major public health concerns as they are key risk
factors for a number of chronic diseases (Malnick and Knobler,
2006); thus, effective fat loss strategies are required (Jakicic et al.,
2001). In this sense, increasing the level of physical activity is
likely a crucial intervention for efficient prevention and treatment
of obesity (Girard et al., 2017). During the last few decades,
it has been well-established that exercise is a good strategy for
maintaining weight loss (Bouchard et al., 1993). However, current
weight management exercise strategies are ineffective in the long-
term because after 6 months they often produce a plateau in
body mass or even a recovery of lost body mass (Urdampilleta
et al., 2012). This outcome is facilitated by the fact that adherence
to physical activity often declines over time (Urdampilleta
et al., 2012). Countless studies have shown that lack of time,
motivation, and adherence are the most commonly cited reasons
for not exercising (Smith-Ryan et al., 2016). On other hand,
obese patients would have to exercise relatively more than lean
individuals to increase exercise intensity and comply with the
World Health Organization (WHO) recommended guidelines
(Girard et al., 2017). Thus, the increased mechanical demand
during exercise for obese populations may be deleterious on
lower limb joints and limit the functional capabilities compared
to healthy and normal weight populations (Wearing et al., 2006).
Altogether, these impediments provoke non-adherence by obese
patients to current exercise recommendations.
In this context, moderate hypoxia is presently considered a
favourable treatment option for some diseases such as obesity
(Urdampilleta et al., 2012; Kayser and Verges, 2013; Millet
et al., 2016; Camacho-Cardenosa et al., 2017). Recently, it was
reported that hypoxia exposure may lead to considerable (3%)
body mass loss and improve other health conditions, including
some cardiorespiratory parameters (Netzer et al., 2008; Kayser
and Verges, 2013; Kong et al., 2016), likely due to a decrease
in food intake (hypoxia-induced appetite reduction) (Westerterp
and Kayser, 2006) and increased energy expenditure (Kayser and
Verges, 2013). A likely explanation for higher fat loss with this
novel therapy is the enhanced lipid metabolism, which might be
due to the intermittent hypoxic conditions (Wiesner et al., 2010;
Workman and Basset, 2012). These changes may be modulated
via hypoxia-inducible factor 1α(HIF-1α), which is not activated
to the same extent by passive hypoxic exposure (during rest) or
by active hypoxic exposure (during exercise) (Millet et al., 2016).
There is scientific evidence suggesting that a lower degradation of
HIF-1αresults when hypoxia and physical activity are combined
(Urdampilleta et al., 2012). It seems likely that the main
underlying mechanism is the larger hypoxemia resulting from the
combination of muscle deoxygenation (exercise) and systemic
desaturation (hypoxia) (Millet et al., 2016). Recent findings show
that the recovery time characteristics in intermittent hypoxia
exercise programs may contribute to the rapid body mass loss
(Kelly and Basset, 2017). In this sense, the amount of depleted
glycogen is correlated with lipid oxidation post-exercise. Thus,
exercise strategies that require a large amount of endogenous
glucose may be an effective strategy to increase lipid oxidation
post-exercise and improve body fat mass (Kelly and Basset,
2017). Trombold et al. (2013) showed that high intensity exercise
(2 min at 25% and 2 min at 90% of VO2max) was more
effective than moderate intensity exercise (50% of VO2max for
60 min) in increasing lipid oxidation post-exercise, which was
related to the increased muscle glycogen consumption during
the vigorous effort. High-intensity intermittent training (HIIT)
refers to intermittent exercise that involves alternating brief (6 s
to 4 min), high-intensity anaerobic exercise (85–250% VO2max)
separated by brief, but slightly longer bouts (10 s to 5 min) of
low-intensity aerobic (20 to 40% VO2max) rest (Batacan et al.,
2017). Supramaximal interval training (SIT), which involves 30 s
of “all out” supramaximal sprints, or aerobic interval training
(AIT), which requires longer (3–4 min) lower intensity intervals
(Smith-Ryan et al., 2015), are two distinct types of HIIT used to
reduce cardiometabolic disease risk (Kessler et al., 2012). Further
research in this area is required to validate these findings and
differentiate the effect of hypoxia at different intensities (Hobbins
et al., 2017). In addition to the possible benefits mentioned
previously, a recent study reported that vigorous exercise could
be effective for improving muscle mass, showing an additional
benefit with respect to other studies that used moderate-intensity
exercise (Oh et al., 2017). This could be especially important
in obese patients where reduced muscle mass (sarcopenia) is
common (Gallagher and DeLegge, 2011). Muscles have increased
fat infiltration, which stimulates muscle catabolism by expression
of proinflammatory cytokines rather than exercise-inducible
myokines (Walsh, 2009).
On the other hand, the benefits result in HIF activation
may be gender-dependent. In normoxic conditions, previous
studies have demonstrated gender specific differences in the
metabolic response to submaximal endurance exercise: higher
fat utilisation during endurance exercises was apparent in
females compared with males (Carter et al., 2001). In hypoxic
conditions, previous studies have suggested that oestrogen could
downregulate HIF activity. HIF may induce a shift in metabolism
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
in favour of glucose utilisation, which is higher in men compared
with women, who exhibit a greater reliance on fatty acids
for metabolism (Palmer and Clegg, 2014). Thus, it should be
considered that gender may affect the results of this type of
exercise strategy.
Given that current exercise strategies do not meet the
needs of the overweight/obese, clinically validated and specific
alternatives are required. Based on the above, we reasoned that
the combination of hypoxia and high-intensity exercise may
result in synergistic effects on body composition and metabolism
and thus, would be an appropriate and time-metabolic effective
form of exercise training for overweight/obese women. Thus, the
aim of the present study was to investigate if exposure to hypoxia
combined with two different protocols of high-intensity interval
exercise in overweigh/obese women would be more effective
when compared with exercising in normoxia. We hypothesised
that the addition of a hypoxic stimulus to high-intensity exercise
would be more effective in reducing body fat than the same
protocol performed in normoxic conditions.
MATERIALS AND METHODS
Participants
Participants were recruited through advertising in the
community and the researchers’ host institution, and personal
contact. Inclusion criteria were assessed during a screening
visit. Inclusion criteria were: BMI (body mass index) >25 kg/m2
(overweight or obese for adults according to WHO) or percentage
fat mass (% fat) >29.9% [elevated risk of cardiovascular disease
(ACSM, 2014)], absence of other associated diseases, pre-
menopausal, sedentary (<2 bouts of exercise lasting a minimum
of 30 min per bout per week), and have not been above 1,500 m
during the last 3 months. The exclusion criteria were diseases not
compatible with study exercise: myocardial infarction or stoke
within 6 months before the start of the study, unstable angina
pectoris, malignant hypertension, or chronic kidney disease.
In total, 112 female volunteers were informed about the study
procedures and, after verifying inclusion and exclusion criteria
through an exam, the volunteers were asked to sign a declaration
that they voluntarily consented to participate in this research.
The eligible volunteers (n=82; body mass: 78.12 ±14.70 kg;
BMI: 28.98 ±5.19; % fat: 38.63 ±5.78) started interval training
treatment under normoxic or hypoxic conditions. Due to health
problems (not related to the study protocol), occupational factors
and other personal problems, 23 participants dropped out during
the intervention period (see Figure 1).
The study was performed in line with the ethical standards
of the Declaration of Helsinki. The Bioethical and Biosecurity
Commission of the University of Extremadura approved the
study protocol.
Procedures
The study was designed as a randomised double-blind control
study. There were separate intervention and assessment teams.
The volunteers were randomly divided into four groups: (1)
aerobic interval training in hypoxia (AitH; n=13), in which
aerobic interval training under normobaric hypoxic conditions
was performed, (2) aerobic interval training in normoxia
(AitN; n=15) in which aerobic interval training under
normoxic conditions was performed, (3) supramaximal interval
training in hypoxia (SitH; n=15) in which sprint interval
training under normobaric hypoxic conditions was performed,
and (4) supramaximal interval training in normoxia (SitN;
n=18) in which sprint interval training under normoxic
conditions was performed. For 12 weeks, the volunteers
completed an intervention supervised by an experienced member
of the research group. Approximately 2 weeks prior to
baseline measurements, participants reported to the laboratory
for familiarisation with experimental trials and fitness and
psychological testing. A general questionnaire was completed
to collect medical and personal data before entering the study.
All participants were assessed at four time points by a group
of researchers who were blinded to the treatment assigned.
Outcomes were evaluated at baseline (T1), after 18 training
sessions (T2), in the 7 days after the last session (T3), and 4
weeks after the last session (T4). All time points for evaluations
consisted of the same measurements.
Exercise
All participants started the training protocol 1 week following
baseline. During the 20-week study period, 36 sessions were
completed within 12 weeks, 3 days per week. Sessions were
scheduled with at least 1 day of rest between for optimal recovery
(Mondays, Wednesdays, and Fridays) and participants were
requested to train at the same time throughout the 36 sessions.
At each session, an exercise physiologist recorded adherence,
exercise workloads, and physiological responses in a daily
training log. SpO2was controlled regularly via pulse-oximeter
(Konica Minolta, Japan). Heart rate (HR) was monitored during
each session with a HR monitor (Team System, Polar Electro Oy).
Participants rated their perceived exertion (0–10 scale) at the end
of each training session (Borg, 1982).
HIIT
Participants performed two different HIIT protocols 3 days
per weeks on a cycle ergometer (Ergoselect series 100/200,
Ergoline GmbH, Bitz, Germany). The two exercise protocols were
designed to maintain a progressive overall work over the 12 weeks
of study. During the 1st and 2nd weeks, subjects finished three
high-intensity intervals, four intervals between the 3rd and 5th
weeks, five intervals between the 6th and 8th weeks, and six
intervals during the last 9th and 12th weeks.
A 10 min warm-up and 3 min cool-down at 25% maximal
workload (Wmax) were completed by the participants (Heydari
et al., 2012; Keating et al., 2014; Lanzi et al., 2015). In the
exercise protocol, the AitH and AitN groups performed 3 min of
high intensity exercise [90% Wmax followed by 3 min of active
recovery (55–65% Wmax)]. The SitH and SitN groups underwent
30 s of all-out (130% Wmax) followed by 3 min of active recovery
at 55–65% Wmax (Wood et al., 2015). Maximal average exercise
time per session was 41.5 min in the Ait groups and 29.62 min
in the Sit groups. The exercise prescriptions are summarised in
Figure 2.
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
FIGURE 1 | Flow of participants through each stage of the trial. AitH: Aerobic interval training Hypoxia group; AitN: Aerobic interval training Normoxia group; SitH:
Sprint interval training Hypoxia group; SitN: Sprint interval training Normoxia group.
To assess Wmax, all participants performed a maximal ramp
incremental test to exhaustion (FATmax) (Lanzi et al., 2014,
2015) on the same cycle ergometer (Ergoselect series 100/200,
Ergoline GmbH, Bitz, Germany) as the training.
Hypoxic Stimulus
All training sessions were performed in two normobaric hypoxia
chambers (CAT 310, Lousiville, Colorado, USA) built in the
laboratory (24◦C and 40% relative humidity). The AitH and SitH
groups exercised at an inspired fraction of oxygen (FiO2) of 17.2
±0.3% corresponding to approximately 2,500 m while the AitN
and SitN groups exercised at FiO2of 20.9% corresponding to
sea level in the laboratory. Oxygen content within the chamber
could be reduced by insufflating nitrogen, which was produced
from chamber air through a molecular sieve. FiO2was controlled
regularly with an electronic device (HANDI+, Maxtec, Salt
Lake City, Utah, USA). Blinding of the subjects was done by
covering any displays in the hypoxic rooms and running the
ventilation system at the same power with closed windows. The
blinding success was assessed by interviewing the subjects after
the intervention.
Outcome Measures
In the four time points, assessments took place in one session.
Participants attended the research laboratory after a minimum
8-h overnight fast, for basal metabolic rate (BMR), and
anthropometric measurements.
Medical History and Lifestyle Questionnaires
Subjects in both groups were instructed to maintain their usual
eating habits and physical activities during the study period.
On their first and last visit to the laboratory, subjects provided
the International Physical Activity Questionnaire (IPAQ) (Craig
et al., 2003) and a 7-day diet inventory, which was analysed
using the diet software Nutriber (Nutriber v1.1.1.r5, Funiber,
Barcelona, Spain).
Basal Metabolic Rate
Following a minimum 8 h overnight fast, participants visited the
laboratory in the morning and rested. Participants were also
required to avoid strenuous activity for the previous 48 h. First,
subjects rested quietly in a comfortable position in a quiet neutral
environment. The mixing chamber pump was turned on and the
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
FIGURE 2 | Schematic representation of the four exercise prescriptions allocated at randomisation. AitH: Aerobic interval training Hypoxia group; AitN: Aerobic interval
training Normoxia group; SitH: Sprint interval training Hypoxia group; SitN: Sprint interval training Normoxia group; Wmax: maximal work-load; FiO2: inspired fraction
of oxygen.
plastic canopy was placed over the reclined subject’s head and
neck. One minute of data were allowed to expire before initiating
formal data collection to allow for acclimation to the gas analyser
(Metalyzer 3b, CORTEX Biophysik GmbH, Leipzig, Germany).
Appropriate calibrations of the O2and CO2sensors and the
volume transducer were performed before each measurement.
The metabolic rate was truncated by 10-min out of 20-min data
collection. The procedure discarded the first and last 5 min to
nullify any metabolic rate fluctuation due to familiarisation with
the facemask and the expected termination of data collection.
Data points were collected every 5 s and steady-state was defined
as the 10 min during which the volume of oxygen consumed,
ventilation (VE), and respiratory quotient (RQ) did not vary
0.10% (Horner et al., 2001). BMR was calculated using Weir
equations (Haugen et al., 2007):
BMR(kcal/day) =(3.9×VO2(L/min)) +(1.1×CO2(L/min))
×1440.
Fat oxidation (FAToxi), carbohydrate oxidation (CHOoxi),
energy fat (FATene), and energy carbohydrate (CHOene) were
calculated using stoichiometric equations (Weir, 1949) and
appropriate energy equivalents, with the assumption that the
urinary nitrogen excretion rate will be negligible (Brandou et al.,
2005):
FAToxi(g/min) =[(1.67×VC O2)−(1.67×VC CO2)]
CHOoxi(g/min) =[(4.55×VC CO2)−(3.21×VC O2)]
FATene =[(1.67×VC O2)−(1.67×VC CO2)]×9
CHOene =[(4.55×VC CO2)−(3.21×VC O2)]×4
Anthropometric Measures and Body Composition
Anthropometric data comprised body mass and height measures
to the nearest 0.1 kg and 0.5 cm, respectively. Body composition
was determined by bioelectrical impedance analysis using a
standardised body composition analyser (Tanita B C 418 MA,
Tanita Corp., Tokyo, Japan) and included estimation of body fat
percentage (% fat), muscle mass, and BMI (coefficient variation =
1.1% for body fat). Subjects maintained a standing position, with
feet side-by-side on the scale and were barefoot. They wore sport
clothes without metal objects.
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
Maximal Exercise Test
A maximal incremental test (FATmax) on a cycle ergometer
(Ergoselect series 100/200, Ergoline GmbH) with gas analyser
(Metalyzer 3b, CORTEX Biophysik GmbH) was performed. After
a 5-min warm-up at 50 W and 1 min of rest were allowed to expire
before initiating formal data collection to allow for acclimation
to the apparatus, the test was initiated. Subjects started cycling
at 30 W and the work rate was increased 15 W every 3 min
until exhaustion. HR was recorded continuously during the test
using a cardio belt (Polar H7 HR, Polar Electro Oy, Kempele,
Finland) integrated with the gas analyser software (MetaSoft
Studio, CORTEX systems, Leipzig, Germany). The measurement
finished when at least three of the following four criteria were
met (Wood et al., 2010): (1) a plateauing of VO2(defined as
an increase of no more than 2 mL·kg−1·min−1with an increase
in workload) during the latter stages of the exercise test, (2)
an HR <90% of the age predicted maximum (220–age), (3) a
RER >1.1, and (4) an inability to maintain the minimal required
pedalling frequency (i.e., 60 rpm) despite maximum effort and
verbal encouragement. Thus, the peak power was defined as
maximal power achieved during the last 3-min step completed
during the incremental test.
Statistical Analysis
Statistical analyses were performed using the statistical package
SPSS v.20 for MAC (IBM, New York, USA). Data are presented
as the mean ±standard deviation (SD). Standard statistical
methods were used for the calculation of the mean and
SDs. Kolmogorov–Smirnov tests were conducted to show the
distribution of the studied variables and Levene’s test was used
for homogeneity of variance. Treatment effects were obtained
for every variable as absolute change (T2/T3/T4 mean minus
T1 mean). All data were normally distributed; a two-way
repeated measures analysis of variance (ANOVA) was performed
accounting for time and the interaction term between group and
time. If a global difference over time appeared, a Bonferroni
post-hoc analysis was used to identify where changes occurred.
The p<0.05 criterion was used for establishing statistical
significance.
RESULTS
Demographic and physiological baseline characteristics for both
treatment groups are provided in Table 1. No initial difference in
body composition parameters was found via ANOVA. Because of
the neutral training place, subjects could not discriminate if they
were in hypoxia or normoxia. Blinding was successful as more
than 60% of subjects did not guess their conditions correctly.
There were no serious health problems reported by the subjects.
Oxygen saturation during the training session was lower (p<
0.01) and RPE was higher (p>0.05) for the hypoxia groups. HR
and training power during training sessions were not significantly
different between groups (Table 2).
Energy intake and estimated physical activity level prior to
and after the intervention are presented in Table 3. No significant
difference was noted before and after the intervention.
Body Composition Parameters
Body mass, BMI, percentage of fat mass, and muscle mass
changed across T1, T2, T3, and T4. There were no significant
differences in body mass and BMI in the within-subjects or in the
within-groups analysis in the normoxia groups. Hypoxia groups
showed significant differences in body mass and BMI variations.
The AitH group showed significantly increased body weight (p
<0.001) and BMI (p<0.001) from T1 to T3 and T4. The SitH
group showed slight reductions in body weight and BMI in the
same time comparison.
There were statistically significant differences between groups
in the percentage of fat mass (Figure 3) and muscle mass
(Figure 4). The reduction of fat mass in the SitH group was
statistically significant when compared with the SitN group from
T1 to T3 (p<0.05) and from T1 to T4 (p<0.05). Fat mass
in the AitH group showed a statistically significant decrease (p
<0.01) that was higher than the AitN group from T1 to T4.
There were statistically significant differences in the percentage
of change in muscle mass between hypoxia and normoxia groups
from T1 to T4. All training groups showed a reduction in the
percentage of fat mass, which was statistically significant in the
hypoxia groups (Figure 2,p<0.05). Muscle mass presented a
TABLE 1 | Baseline characteristics of the sample.
AitN
(n=13)
AitH
(n=13)
SitN
(n=15)
SitH
(n=18)
P-value
Mean ±SD Mean ±SD Mean ±SD Mean ±SD
Age, years 43.14 ±7.67 44.43 ±7.18b40.05 ±8.66 37.40 ±10.25a0.038
Height, m 1.64 ±0.06 1.63 ±0.06 1.65 ±0.07 1.63 ±0.05 NS
Body mass, kg 80.41 ±16.27 80.10 ±18.88 77.94 ±11.31 73.73 ±11.11 NS
BMI, kg·m229.59 ±5.25 30.03 ±6.37 28.74 ±4.77 27.71 ±4.55 NS
Fat mass, % 38.89 ±6.25 40.17 ±7.20 37.73 ±5.28 37.65 ±3.93 NS
BMI: body mass index; AitH: Aerobic interval training Hypoxia group; AitN: Aerobic interval training Normoxia group; SitH: Sprint interval training Hypoxia group; SitN: Sprint interval
training Normoxia group. P-values of analysis of variance to compare differences between groups at baseline.
aIndicates differences with respect to AitH (post hoc t-test with Bonferroni correction).
bIndicates differences with respect to SitH (post hoc t-test with Bonferroni correction).Values in bold are significant.
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
TABLE 2 | Average training control variables during the program.
AitN
(n=13)
AitH
(n=13)
SitN
(n=15)
SitH
(n=18)
P-value
Mean ±SD Mean ±SD Mean ±SD Mean ±SD
Pmax, watts 88.59 ±18.38 89.76 ±18.47 89.30 ±27.73 86.31 ±19.57 NS
HRave, bmp 131.6 ±11.99 138.90 ±10.49 133.76 ±12.64 139.86 ±11.54 NS
HR max, % 81.91 ±12.97 86.25 ±6.32 86.77 ±6.68 85.46 ±7.53 NS
SO2, % 95.20 ±3.19b88.86 ±2.61a95.14 ±2.83d88.66 ±1.75cp<0.001
RPE, Borg scale 4.29 ±1.60b5.42 ±1.32a4.04 ±1.26 4.83 ±1.31 p<0.01
Pmax: maximal power; HRave; average heart rate during total training session; HR max: maximal heart rate during main part training session; SO2: oxygen saturation during training
session; RPE: Rated Perceived Exertion; EE: energy expenditure; AitH: Aerobic interval training Hypoxia group; AitN: Aerobic interval training Normoxia group; SitH: Sprint interval training
Hypoxia group; SitN: Sprint interval training Normoxia group. P-values of analysis of variance to compare differences between groups at baseline.
aIndicates differences with respect to AitN (post-hoc t-test with Bonferroni correction).
bIndicates differences with respect to AitH (post-hoc t-test with Bonferroni correction).
cIndicates differences with respect to SitN (post-hoc t-test with Bonferroni correction).
dIndicates differences with respect to SitH (post-hoc t-test with Bonferroni correction).
Values in bold are significant.
TABLE 3 | Energy intake and physical activity prior to the intervention (Pre) and after the intervention (Post).
AitN
(n=13)
AitH
(n=13)
SitN
(n=15)
SitH
(n=18)
Mean ±SD Mean ±SD Mean ±SD Mean ±SD
Energy intake, kcal·day−1Pre 1488.24 ±539.37 1955.55 ±1647.71 1377.66 ±612.67 1966.20 ±1141.43
Post 1456.69 ±389.07 1608.07 ±962.85 1311.56 ±476.82 2283.50 ±1496.75
Physical activity, mets·day Pre 6081.23 ±1452.77 6158.72 ±598.31 6722.62 ±1355.74 6711.84 ±1543.01
Post 6029.96 ±1457.48 6404.20 ±1179.68 6985.14 ±605.62 6779.83 ±2642.24
AitH: Aerobic interval training Hypoxia group; AitN: Aerobic interval training Normoxia group; SitH: Sprint interval training Hypoxia group; SitN: Sprint interval training Normoxia group.
statistically significant increase in the hypoxia groups (Figure 3,
p<0.05), especially at T4.
Basal Energy Expenditure and Substrate
Utilisation
Effects of different trainings on RQ, BMR, energy and fat
oxidation, and energy and carbohydrate oxidation are presented
in Table 4. There were significant differences in BMR between
the AitN and AitH groups when T1 was compared with T2
and T4 (p<0.05). Basal metabolic rate tended to decrease in
normoxia groups, especially in the AitN group from T1 to T4,
which showed a decrease of 13.17%, but these changes were
not statistically significant. There was a statistically significant
increase (p<0.05) in BMR in the AitH group at T4 by 8.03%.
The statistical analysis revealed that RQ tended to increase in
both normoxia groups and decrease in both hypoxia groups after
completion of the training protocols, although there were no
significant changes within-subjects or between groups.
Significant differences were found in the percentage of change
of fat oxidation and energy from fat (p<0.001) and in the
oxidation of carbohydrates and energy from carbohydrates (p<
0.001) between the AitH and AitN groups. While fat oxidation
tended to increase and oxidation of carbohydrates tended to
decrease in both hypoxia groups, this tendency was reversed
in normoxia groups (Figure 5). However, the changes were
statistically significant (p<0.001) only in the AitN group,
where fat oxidation decreased by 36.96% and oxidation of
carbohydrates increased by 13.43% after training. Consequently,
energy from fat and carbohydrates changed proportionally (p<
0.001 in the AitN group).
DISCUSSION
To the best of our knowledge, this paper represents the first
four-group randomised controlled work investigating the effects
of simulated hypoxia combined with HIIT on human body
composition. The main findings confirm the hypothesis that
a 12-week program of HIIT in hypoxia reduces fat mass and
increases muscle mass to a greater extent in overweight/obese
women than exercising in normoxia. The greatest effects
were apparent immediately after completion of the training
program. The increase in fat oxidation and the decrease in
carbohydrate oxidation in the hypoxia groups could explain these
results.
White adipose tissue is known to present a hypoxic state in
obese subjects. Although this chronic state may favour other
diseases, intermittent hypoxia has been suggested as a treatment
option for being overweight and obesity (Heinonen et al., 2016).
Reductions in body weight observed at high altitudes (also
termed “altitude anorexia”) seem to be a consequence of blunted
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
FIGURE 3 | Training effect in fat mass measured at baseline, before 18
sessions (T2) and a week (T3) and 4 weeks (T4) after intervention in each
group [(A) SitN: sprint interval training normoxia; SitH: sprint interval training
hypoxia; (B) AitN: aerobic interval training normoxia; AitH: aerobic interval
training hypoxia]. *Significant difference respect to baseline (P<0.05).
#Significant difference between group in T3 (P<0.05); &Significant
difference between group in T4 (P<0.05).
appetite resulting in decreased energy intake (Benso et al., 2007).
Hypoxia alters the function of the nervous system and hormonal
levels, which lead to a disturbance of the energy balance explained
by a reduction in nutritional and intestinal energy uptake, and
increased energy expenditure (Kayser and Verges, 2013). During
periods of hypoxia, the activation of HIF could cause a shift
in metabolism away from the glycolytic pathway (Wheaton and
Chandel, 2011). These 2 sentences are not really understandable
to me; away from glycolysis of favouring glycolysis? Please check
carefully.
Since glycolysis only produces two adenosine triphosphate
(ATP) molecules for every mole of glucose, upregulation of HIF
leads to a greater dependency of glucose uptake to generate
adequate amounts of ATP (Wheaton and Chandel, 2011).
However, this change in metabolism is inefficient since only two
ATPs are formed for each mole of glucose metabolised and six
ATPs are used for every two molecules of lactate converted to
FIGURE 4 | Training effect in muscle mass measured at baseline, before 18
sessions (T2) and a week (T3) and 4 weeks (T4) after intervention in each
group [(A) SitN: sprint interval training normoxia; SitH: sprint interval training
hypoxia; (B) AitN: aerobic interval training normoxia; AitH: aerobic interval
training hypoxia). *Significant difference respect to baseline (P<0.05).
&Significant difference between group in T4 (P<0.05).
glucose. This energy wasting may play a role in the increase in
BMR, which occurs at high altitude (Palmer and Clegg, 2014).
Although studies investigating training under hypoxic
conditions on clinical pathologies are rare (Wiesner et al., 2010),
some studies have been conducted to test the effects of activities
in hypoxia as a treatment for weight loss and improvements in
body composition in overweight/obese subjects (Netzer et al.,
2008; Wiesner et al., 2010; Gatterer et al., 2015; Kong et al.,
2016). In these studies, hypoxic exposure (FiO2=12–15%)
was combined with cardiovascular exercise programs (running,
cycling, or stepping) of moderate intensity (55–65% VO2
max/60–70% HR max; 60–90 min). Kong et al. (2016) added
strength training (40–50% of 1 RM, 3 sets of 15 repetitions,
interspersed with 2–3 min rest periods). Overall, published
findings, at present, show changes in responses of body weight
and BMI following moderate-intensity and cardio-based exercise
programs in hypoxia (Netzer et al., 2008; Wiesner et al., 2010).
In addition, a higher decrease in fat mass has been shown in
obese patients who exercised under hypoxic conditions, but
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
TABLE 4 | Changes on resting energy expenditure and substrate utilization over 12-weeks intervention period.
T1
(A)
T2
(B)
1
(A-B)
T3
(C)
1
(A-C)
T4
(D)
1
(A-D)
ANOVA,
p-values
Mean ±SD Mean ±SD % Mean ±SD % Mean ±SD % Time Time x group
RQ AitN 0.98 ±0.09 0.93 ±0.10 −5.10 0.99 ±0.06 1.02 0.99 ±0.09 1.02 NS NS
AitH 0.97 ±0.09 0.97 ±0.08 0.00 0.95 ±0.06 −2.06 0.95 ±0.07 −2.06 NS
SitN 0.97 ±0.08 0.95 ±0.09 −2.06 1.01 ±0.07 4.12 0.98 ±0.08 1.03 NS NS
SitH 1.01 ±0.09 1.02 ±0.07 0.99 0.97 ±0.08 −3.96 0.96 ±0.09 −4.95 NS
BMR, kcal/day AitN 1676 ±252 1589 ±278α−5.19 1677 ±293 0.06 1455 ±320α−13.17 NS P<0.01
AitH 1588 ±320 1690 ±305α6.46 1530 ±347 −3.63 1715 ±404α8.03 NS
SitN 1692 ±307 1593 ±240 −5.82 1702 ±243 0.58 1534 ±184 −9.33 NS
SitH 1761 ±288 1699 ±390 −3.54 1707 ±343 −3.09 1710 ±362 −2.94 NS
Energy Fat (kcal/min) AitN 0.46 ±0.26 0.59 ±0.26 28.26 0.33 ±0.22*α−28.26 0.29 ±0.12α−36.96 0.000 p<0.001
AitH 0.43 ±0.18 0.43 ±0.26 0.00 0.46 ±0.19α6.98 0.57 ±0.25α32.56 NS
SitN 0.48 ±0.25 0.39 ±0.47 −18.75 0.29 ±0.19 −39.58 0.38 ±0.19 −20.83 NS NS
SitH 0.37 ±0.19 0.38 ±0.19 2.70 0.45 ±0.24 21.62 0.55 ±0.25 48.65 NS
FAToxi (g/min) AitN 0.052 ±0.03 0.064 ±0.03α40.30 0.036 ±0.02*α−30.75 0.031 ±0.01α−21.72 0.000 p<0.001
AitH 0.047 ±0.02 0.048 ±0.03α2.13 0.051 ±0.02α8.51 0.063 ±0.03α34.04 NS
SitN 0.054 ±0.03 0.043 ±0.05 −20.37 0.033 ±0.02 −38.89 0.043 ±0.02 −20.37 NS NS
SitH 0.040 ±0.02 0.042 ±0.02 5.00 0.050 ±0.03 25.00 0.062 ±0.03 55.00 NS
Energy CHO (kcal/min) AitN 0.73 ±0.25 0.51 ±0.26α−30.14 0.87 ±0.17* 19.18 0.76 ±0.32 4.11 0.000 p<0.001
AitH 0.70 ±0.22 0.79 ±0.34α12.86 0.62 ±0.24 −11.43 0.63 ±0.30 −10.00 NS
SitN 0.71 ±0.28 0.75 ±0.57 5.63 0.94 ±0.29 32.39 0.70 ±0.18 −1.41 NS NS
SitH 0.89 ±0.28 0.83 ±0.28 −6.74 0.76 ±0.33 −14.61 0.65 ±0.32 −26.97 NS
CHOoxi (g/min) AitN 0.183 ±0.06 0.128 ±0.06 −30.05 0.219 ±0.04* 19.67 0.188 ±0.08 2.73 0.000 p<0.001
AitH 0.174 ±0.05 0.191 ±0.09 9.77 0.155 ±0.06 −10.92 0.157 ±0.08 −9.77 NS
SitN 0.178 ±0.07 0.185 ±0.14α3.93 0.235 ±0.07 32.02 0.177 ±0.05α−0.56 NS NS
SitH 0.223 ±0.07 0.207 ±0.07α−7.17 0.190 ±0.08 −14.80 0.161 ±0.08α−27.80 NS
RQ: respiratory quotient; BMR: basal metabolic rate; FAToxi: fat oxidation; CHOoxi: carbohydrates oxidation AitH: Aerobic inter val training Hypoxia group; AitN: Aerobic interval training
Normoxia group; SitH: Sprint interval training Hypoxia group; SitN: Sprint interval training Normoxia group.
1, T2/T3/T4 minus T1 absolute change.
*Indicates differences with respect to baseline (post hoc t-test with Bonferroni correction).
α: Indicates differences AitN respect to AitH.
Values in bold are statistically significant.
lean body mass did not change. However, the effectiveness of
such low-intensity interventions remains questionable, mainly
over a longer period. The results of Gatterer et al. (2015)
did not demonstrate improvements in body weight between
hypoxic and normoxic exposure over a period of 8 months.
A reduced workload of participants carrying out moderate-
intensity continuous exercise in hypoxia and adaptations to the
same stimulus could explain the findings of the present study
(Wiesner et al., 2010; Morishima et al., 2014). In contrast, the
present research found additive effects of hypoxia combined
with higher exercise intensity. A greater decrease in fat mass
and an increase in muscle mass were shown in the hypoxia
group compared with the normoxia group even 4 weeks after
finishing the training program. Briefly, the present findings
indicated a greater long-term effect of combined HIIT with
normobaric hypoxia exposure compared with the same protocol
in normoxia. The metabolic efficient characteristics of the
high-intensity intermittent protocols had a marked advantage in
the development of a habitual strategic exercise for combatting
obesity (Zhang et al., 2017), which also seems to be more
suitable in the hustle and bustle of modern life (Gibala et al.,
2012). The impact of HIIT in normoxia on body composition
is controversial. Some evidence suggests that it could be an
effective strategy for the management of body fat levels in
overweight/obese adults (Heydari et al., 2012; Sijie et al., 2012;
Gillen et al., 2013; Fisher et al., 2015; Lanzi et al., 2015; Martins
et al., 2016; Zhang et al., 2017), but others have not found
differences (Whyte et al., 2010; Keating et al., 2014; Smith-Ryan
et al., 2015, 2016; Kong et al., 2016). Based on a recent systematic
review (Batacan et al., 2017), long-term HIIT protocols reduce
the fat percentage in overweight/obese populations. Therefore,
at least three times a week for more than 12 weeks of HIIT
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
FIGURE 5 | Training effect in percentage of change of fat (A) and
carbohydrates oxidation (B) between baseline and before 18 sessions (T2),
baseline and before week (T3) and baseline and before 4 weeks (T4) after
intervention in each group (AitN: aerobic interval training normoxia; AitH:
aerobic interval training hypoxia; SitN: sprint interval training normoxia; SitH:
sprint interval training hypoxia).
in normoxic conditions should be performed as part of an
exercise program to promote significant fat reductions in
overweight/obese populations. In the present study, all training
groups showed reductions in percentage of fat mass, but these
were only statistically significant in the hypoxia groups, with
larger differences in the hypoxia groups compared with the
normoxia groups.
The beneficial effects of combined intermittent hypoxia with
HIIT on greater reduction of body fat could be attributed to
the increased post-exercise lipid oxidation (Kendzerska et al.,
2016). During exercise in hypoxia, a greater dependence on
carbohydrate substrates (Kelly and Basset, 2017) and a shift
away from fat oxidation (Horscroft and Murray, 2014) are
commonly observed. This oxygen debt (due to a contribution
from non-oxidative mechanisms) will be repaid during recovery
from exercise. Thus, depleting glycogen during active hypoxia
exposure has been shown to increase resting FAToxi after an
exercise period. In this moment, muscle glycogen replenishment
is vital and thus, plasma and intramuscular triglycerides are
likely to be essential fuel sources for oxidative energy production
(Kimber et al., 2003). A recent study (Kelly and Basset, 2017) has
shown that substrate oxidation during the post-exercise recovery
period has been altered, displaying an increased contribution
from FAToxi and a suppressed CHOoxi. Similarly, in the
present study, fat oxidation tended to increase and oxidation
of carbohydrates tended to decrease in both hypoxia groups.
In the normoxia groups, there was an inverse tendency, with
a statistically significant difference between the AitH and AitN
groups sin substrate oxidation.
Sarcopenia is common in obese patients (Gallagher and
DeLegge, 2011). In the present study, vigorous exercise showed a
significant improvement in muscle mass, which may have caused
the body weight gain, in overweight/obese sedentary women
in both hypoxia groups. Previous evidence has shown that
chronic hypoxia generally leads to negative regulation of protein
metabolism and a loss of muscle mass. Conversely, acute hypoxia
seems to exert a positive effect on protein balance in humans
when combined with exercise (Nishimura et al., 2010). An acidic
environment produced by the accumulation of metabolic waste
products (such as lactate) due to anaerobic metabolism, could
stimulate the production of growth hormone (Takarada et al.,
2000). In this sense, although endurance exercise is generally
recognised to cause significant adaptations in skeletal muscle
capillarisation (Kon et al., 2015), high-intensity interval training
under hypoxic conditions may elicit synergistic effects, producing
structural muscle adaptations by stimulating glucose-dependent
metabolic pathways and consequently an acidic environment
(Vogt et al., 2001).
To the best of our knowledge, there are no studies suggesting
why hypoxia may have a beneficial effect on muscle mass.
Further investigations are needed to determine the molecular
mechanisms that regulate skeletal muscle mass during/after
intermittent hypoxia combined with endurance exercise.
In addition, exercise strategies such as those carried out
in this study may be especially beneficial for individuals who
are unable to maintain adequate workloads for compliance
with exercise prescriptions. Due to disproportionately heavier
limbs, obese patients need to increase the mechanical demand
during exercise to enhance exercise intensity and to meet
the current physical activity guidelines (Girard et al., 2017).
This increased mechanical demand during exercise in obese
populations may be deleterious and can cause pain in lower
limb joints (even leading to musculoskeletal pathologies) (Girard
et al., 2017). In this sense, the implementation of high intensity
exercise could lead to difficulties in maintaining the prescribed
work in untrained obese populations. This is where a hypoxic
stimulus could be especially beneficial, as it would increase the
metabolic stress (relative workload) without intensifying the
mechanical stress. Exposure to hypoxia at heights exceeding
2,000 m cause reductions in SpO2. To maintain delivery of O2
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Camacho-Cardenosa et al. High-Intensity Hypoxia Fat Loss Obese
during hypoxic exercise, breathing frequency (Bf), VE, HR, and
CHOoxi are all elevated above similar workloads performed
at sea level (Peronnet et al., 2006; Mazzeo, 2008). Therefore,
hypoxic conditions during endurance training programs could be
considered as an additional metabolic stress that the body must
overcome to achieve an adequate energy supply (Kelly and Basset,
2017). Briefly, including a hypoxic stimulus during endurance
training protocols may be beneficial to overweight/obese patients
who have problems achieving the workloads required to obtain
cardiovascular and metabolic health benefits (Kelly and Basset,
2017). With respect to the type of exercise, the level of impact
produced by the activity could influence joints, such as the knee
(Arokoski et al., 2000). Therefore, low impact activities, such
as walking or cycling, have been recognised as applying lower
loads on the tibiofemoral surfaces of the knee joint, thereby
decreasing the risk of injury (Vannini et al., 2016). In addition,
repeated-sprint ability (RSA) cycling was found to induce larger
decrements in muscle contractile properties in the knee joint
as well as higher levels of low-frequency fatigue compared with
running (Rampinini et al., 2016). For this reason, the use of these
types of exercises is recommended in this population.
Our study has some limitations. Information on food
intake and physical activity patterns were only registered twice
during the intervention protocol. Even though participants were
informed not to change their normal physical activity and
eating habits and non-significant differences were found between
records, some favourable behavioural alterations might have
occurred outside the study procedure. However, maintaining
the subjects on their normal food habits seems to be the most
logical choice, and their effect should be low and not influence
current conclusions. Based on previous studies, protocols with
30-s high-intensity intervals may be more enjoyable than longer
protocols (Martinez et al., 2015). One important aspect may be
related to the individual’s ability or competency to successfully
complete the training. In fact, the positive feedback to complete
a task increases enjoyment (Hu et al., 2007) and, in this way,
the adherence to exercise. On the other hand, the mechanical
load in hypoxic conditions may be reduced and thus, the
lower physical stress may actually decrease negative feelings and
increase enjoyment for the exercise over time (Girard et al., 2017).
Therefore, the larger variation of energy intake and physical
activity in SitH group could at least partly be due more distinct
differences in the adherence to high-intensity exercise in hypoxia.
Anyway, despite the large variation of both variables, especially
in SitH group, no significant differences were observed in any
group. Even though the dropout rate of study (28.05%) was lower
than previous studies (Miller et al., 2014; Gatterer et al., 2015),
the loss of sample might have led to a selection bias toward those
already more motivated and prepared to carry on and those who
could have gained more from the program because of a higher
rate of obesity. However, we do not believe that this alters the
outcome of the research.
We conclude that HIIT under normobaric intermittent
hypoxia for 12 weeks is promising for reducing body fat content
with a concomitant increase in muscle mass. The reduction
in the risk for orthopaedic injury and time and metabolic
efficiency, which was enhanced by hypoxia in the SIT and AIT-
HIIT programs, may be particularly feasible for overweight/obese
patients for whom exercise capacity is limited by orthopaedic
conditions. However, further studies are needed to validate these
findings and to determine the most appropriate dose of hypoxia
and high-intensity exercise for this population.
AUTHOR CONTRIBUTIONS
AC-C: Designed the research study, conducted the experiments,
and wrote the manuscript; MC-C: Acquired and analyse the
data, and wrote the manuscript; MB: Analysed the data, and
wrote the manuscript; IM-G: Conducted the experiments, and
acquired the data; RT: Designed the research study, and acquired
the data; JB-S: Designed the research study, acquired the
data, and wrote the manuscript; GO: Designed the research
study, analysed the data, and wrote the final version of the
manuscript.
ACKNOWLEDGMENTS
This research was funded by Junta of Extremadura: GAEDAF
Research Group (GR15020) and Ministerio de Educación,
Cultura y Deporte (FPU15/00450).
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Conflict of Interest Statement: The authors declare that the research was
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