J Physiol 594.
24 (2016) pp 71697170
JOURNAL CLUB
The physiology of interval
training: a new target to HIIT
Andrea Nicolo` and Michele Girardi
Department of Movement, Human and
Health Sciences, University of Rome Foro
Italico, Piazza Lauro De Bosis 6, Rome
00135, Italy
Email: andrea.nicolo@uniroma4.it
Given the enormous health benefits
of exercise, there is a large body of
research aimed at identifying the optimal
type and dose of training to maximise
physiological and performance adaptations.
The Journal of Physiology
Among a variety of training modalities,
high-intensity interval training (HIIT) is
recognized as a time-efficient training
strategy to induce similar or even super-
ior adaptations compared to traditional
moderate-intensity continuous training
according to a number of physiological,
performance and health-related markers
(Gibala et al. 2012).
A strong interest in HIIT has been
stimulated by the evidence that three
sessions per week of low-volume Wingate-
based HIIT (i.e. repeated bouts of 30-s
all-out cycling efforts interspersed with
4/4.5 min of recovery) induce similar
performance adaptions to those obtained
with an almost 10 times greater weekly
training volume performed in the
traditional continuous training mode
(Gibala et al. 2012). Moreover, in the
Wingate-based HIIT studies reviewed
by Gibala et al. (2012), the overall time
commitment for HIIT was about 3 times
shorter than that of traditional continuous
training. This is of great importance
considering that lack of time is commonly
cited as one of the main barriers to
exercise adherence (Gibala et al. 2012).
Interestingly, despite the sprint nature
of Wingate-based HIIT, endurance-like
adaptations were documented after a few
weeks (26) of training with this HIIT
format. These include increased muscle
oxidative capacity and glucose transport
capacity and therefore improved insulin
sensitivity and glycaemic control, along
with cardiovascular adaptations (Gibala
et al. 2012). The remarkably similar
changes observed after HIIT and traditional
endurance training suggest that metabolic

C 2016 The Authors. The Journal of Physiology 
C 2016 The Physiological Society
7169
adaptations to HIIT could be mediated in
part through signalling pathways normally
associated with endurance training. This is
supported by the well-documented increase
in the peroxisome proliferator-activated
receptor- coactivator 1 (PGC-1; i.e. The authors used a single-leg cycling
the master regulator of mitochondrial
biogenesis in muscle) after HIIT (Gibala
et al. 2012). The increase in PGC-1
further highlights the potential widespread
health benefits of HIIT, given the positive
effects that an increase in PGC-1 has
on oxidative capacity, glucose uptake,
anti-oxidant defence and resistance to
age-related sarcopenia (Gibala et al. 2012).
However, the Wingate-based HIIT is an
extremely demanding exercise format and
may not be safe, well-tolerated or appealing
for some individuals (Gibala et al. 2012).
Less extreme and more practical HIIT
formats have been extensively used
and commonly compared to traditional
continuous training on a matched-work
basis or isocaloric basis. When using this
method of comparison, the superiority of
HIIT over continuous training is even
more evident in promoting health benefits
in both healthy individuals and diseased
populations (Gibala et al. 2012; Weston et al.
2014). A meta-analysis comparing HIIT and
continuous training in patients with cardio-
metabolic disease found an almost doubled
increase in cardiorespiratory fitness (as
measured by V O2 peak ) after HIIT compared
to continuous training (Weston et al. 2014).
This should translate into a greater decrease
in risks of morbidity and all-cause mortality.
Other health-related adaptations occurred
significantly more in HIIT compared
to continuous training, such as reduced
blood pressure, improved insulin sensitivity,
increased nitric oxide availability, improved
lipid metabolism and increased PGC-1
(Weston et al. 2014). Despite the strong
efficacy of HIIT, methodological limitations
are commonly reported in HIIT studies
(Weston et al. 2014). Among these, it
is worth mentioning the possibility of
committing a type II statistical error, given
the fact that the length of training is
often relatively short, the sample size is
usually small and a between-subject design
is typically used.
A recent study published in The Journal
of Physiology by a group of leading
scientists in the physiology of HIIT
provided an elegant experimental design
to further our understanding of the effect
of HIIT on skeletal muscle mitochondrial
adaptations as compared to matched-work
continuous training (MacInnis et al. 2016).
within-subject parallel-group design, i.e.
one leg was trained with HIIT and the
other with moderate-intensity continuous
training (MICT). Specifically, each leg was
randomly assigned to complete six sessions
of work- and duration-matched HIIT (4
(5 min at 65% of peak power and 2.5 min
at 20% of peak power)) or MICT (30 min
at 50% of peak power) over 2 weeks.
The HIIT and MICT sessions for the two
different legs were performed 10 min apart
on the same day, and in alternating order
across the six training sessions. Ten healthy
young men were included in the study.
Methodologically, this experimental design
allowed for control of individual variability
in training responsiveness, increase in
statistical power and elimination of the
need for washout periods. This is a very
important methodological improvement
made in order to limit the occurrence
of a type II error in HIIT longitudinal
studies. Physiologically, single-leg cycling
may induce greater adaptations than those
induced by double-leg cycling, possibly
in view of the increased relative exercise
intensity (MacInnis et al. 2016). This makes
single-leg cycling an appealing exercise
modality when investigating skeletal muscle
adaptations following short-term training
programmes. Of course, the applicability
of the single-leg cycling within-subject
parallel-group design is limited to the
investigation of physiological adaptations
(e.g. mitochondrial adaptations) that show
no evidence of transfer from the trained leg
to the non-trained leg.
MacInnis et al. (2016) found that HIIT
induces greater increases in mitochondrial
content biomarkers in human skeletal
muscle compared to MICT. Specifically,
citrate synthase maximal activity and
mass-specific oxidative phosphorylation
capacities (complex I, and complexes I and
II) were greater in HIIT relative to MICT,
while whole-muscle cytochrome c oxidase
subunit IV protein content increased
similarly between training modalities.
Conversely, no change in mitochondrial
function (i.e. mitochondria-specific oxygen
DOI: 10.1113/JP273466
7170
flux) was found in either leg. Unlike
previous double-leg cycling HIIT studies,
V O2 peak did not increase in either of the
exercise modalities, possibly due to the
lower cardiorespiratory stimulus associated
with single-leg cycling. These findings
led the authors to conclude that HIIT
induces superior mitochondrial adaptations
compared to MICT despite equal total
work and session duration, probably
because of the higher intensity and/or the
different pattern of contractions (MacInnis
et al. 2016). However, ratings of perceived
exertion, dyspnoea, heart rate and blood
lactate were substantially higher during
the HIIT sessions compared to continuous
sessions (MacInnis et al. 2016). Taken
together, these responses may indicate
that the overall effort, and thus relative
exercise intensity, was higher during HIIT.
Despite the benefits derived from adopting
the above-described experimental design,
the potential difference in overall effort
between the two training regimens may
introduce a confounding factor potentially
raising doubts about the superiority of
HIIT vs. continuous training. This is a
common limitation of the matched-work
approach, which results in HIIT being
more demanding than continuous training
(Nicolo` et al. 2014). Indeed, when the
session duration is the same, the practice
of matching total work implies that HIIT
and continuous training are equalized by
absolute exercise intensity (same average
workload) instead of relative exercise
intensity (similar overall effort, stress
and exercise demand). Although exercise
is often prescribed according to relative
exercise intensity, the adaptations induced
by HIIT or continuous training are rarely
investigated by balancing the different
exercise modalities for the same relative
exercise intensity. The comparison of HIIT
with matched-work continuous training
Journal Club
is further complicated by the fact that
the difference in effort between HIIT and
continuous training is influenced by the
specific format of HIIT. For instance, this
difference increases with the decrease in the
work-to-rest duration ratio (Nicolo` et al.
2014).
Since a considerable number of studies
comparing HIIT with continuous training
used the matched-work approach (Gibala
et al. 2012; Weston et al. 2014), the super-
iority of HIIT over continuous training may
have been biased at least to some extent by
the extensive adoption of this method of
comparison (Nicolo` et al. 2014). In order
to overcome some of the limitations of
balancing HIIT and continuous exercise
for total work, the use of a method of
comparison that guarantees the same over-
all effort across different exercise modalities
has been proposed (Nicolo` et al. 2014).
Nevertheless, the matched-work approach
is still one of the methods of comparisons
prevalently used to evaluate the efficacy
of HIIT vs. continuous training, as the
study by MacInnis et al. (2016) testifies.
What may appear a purely methodological
issue is in fact of fundamental physio-
logical and practical relevance. Suffice to
consider that one of the main barriers to
regular physical activity is the physical effort
required (Marcora, 2016). Accordingly,
moderate-intensity exercise may be pre-
ferable to vigorous exercise for some
individuals as the latter requires more effort
and is unpleasant (Marcora, 2016). On the
other hand, vigorous exercise has a clear
advantage over moderate-intensity exercise
in inducing health-related adaptations.
Therefore, training modalities that reduce
effort while maintaining the physio-
logical stimulus for adaptations should be
recommended from an exercise-adherence
perspective. With this in mind, the burning
question that exercise physiologists still need

C 2016 The Authors. The Journal of Physiology 
J Physiol 594.24
to answer convincingly is the following: is
there an HIIT format that induces superior
physiological and performance adaptations
compared to other exercise modalities when
the overall effort required by different
training regimens is the same?
References
Gibala MJ, Little JP, MacDonald MJ & Hawley
JA (2012). Physiological adaptations to
low-volume, high-intensity interval training
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10771084.
MacInnis MJ, Zacharewicz E, Martin BJ,
Haikalis ME, Skelly LE, Tarnopolsky MA,
Murphy RM & Gibala MJ (2016). Superior
mitochondrial adaptations in human skeletal
muscle after interval compared to continuous
single-leg cycling matched for total work.
J Physiol DOI: 10.1113/JP272570.
Marcora S (2016). Can doping be a good thing?
Using psychoactive drugs to facilitate physical
activity behaviour. Sports Med 46, 15.
Nicolo` A, Bazzucchi I, Haxhi J, Felici F &
Sacchetti M (2014). Comparing continuous
and intermittent exercise: an isoeffort and
isotime approach. PLoS One 9, e94990.
Weston KS, Wislff U & Coombes JS (2014).
High-intensity interval training in patients
with lifestyle-induced cardiometabolic
disease: a systematic review and
meta-analysis. Br J Sports Med 48, 12271234.
Additional information
Competing interests
None declared.
Acknowledgements
The authors apologise for not citing all relevant
articles due to reference limitations imposed by
the Journal Club format.
C 2016 The Physiological Society