Clin Physiol Funct Imaging (2012) 32, pp247–252 doi: 10.1111/j.1475-097X.2012.01126.

REVIEW ARTICLE

Exercise intensity and muscle hypertrophy in blood

flow–restricted limbs and non-restricted muscles: a brief
review
Takashi Abe, Jeremy P. Loenneke, Christopher A. Fahs, Lindy M. Rossow, Robert S. Thiebaud
and Michael G. Bemben
Department of Health and Exercise Science, University of Oklahoma, Norman, OK, USA

Summary

Correspondence Although evidence for high-intensity resistance training–induced muscle hypertro-

Takashi Abe, PhD, 1401 Asp Avenue, Room 15
HHC, Norman, OK 73019, USA
E-mail: t12abe@gmail.com
Accepted for publication
Received 09 December 2011;
accepted 10 February 2012
Key words
blood flow occlusion; low-intensity exercise;
resistance training
phy has accumulated over the last several decades, the basic concept of the train-
ing can be traced back to ancient Greece: Milo of Croton lifted a bull-calf daily
until it was fully grown, which would be known today as progressive overload.
Now, in the 21st century, different types of training are being tested and studied,
such as low-intensity exercise combined with arterial as well as venous blood
flow restriction (BFR) to/from the working muscles. Because BFR training
requires the use of a cuff that is placed at the proximal ends of the arms and/or
legs, the BFR is only applicable to limb muscles. Consequently, most previous
BFR training studies have focused on the physiological adaptations of BFR limb
muscles. Muscle adaptations in non-BFR muscles of the hip and trunk are lesser
known. Recent studies that have reported both limb and trunk muscle adaptations
following BFR exercise training suggest that low-intensity (20–30% of 1RM)
resistance training combined with BFR elicits muscle hypertrophy in both BFR
limb and non-BFR muscles. However, the combination of leg muscle BFR with
walk training elicits muscle hypertrophy only in the BFR leg muscles. In contrast
to resistance exercise with BFR, the exercise intensity may be too low during BFR
walk training to cause muscle hypertrophy in the non-BFR gluteus maximus and
other trunk muscles. Other mechanisms including hypoxia, local and systemic
growth factors and muscle cell swelling may also potentially affect the hypertro-
phic response of non-BFR muscles to BFR resistance exercise.

trunk muscle hypertrophy and strength gains as well as

Introduction
The concept for using high-intensity resistance training for
muscle hypertrophy can be traced back to ancient Greece (6th
century BC). Milo of Croton, who was a famous Olympian
wrestler, lifted a bull-calf daily until it was fully grown, which
today is known as ‘progressive overload’ (Tan, 1999). Com-
pared with low-intensity exercise, moderate- and high-inten-
sity (60–85% of one repetition maximum, 1 RM) resistance
exercise is a potent stimulus for increases in muscle protein
synthesis (MacDougall et al., 1995; Phillips et al., 1997) and
satellite cell activity (Hawke & Garry, 2001; Harridge, 2007)
and a decrease in proteolysis (Louis et al., 2007). Subse-
quently, high-intensity resistance training can induce limb and
© 2012 The Authors
Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine 32, 4, 247–252
improve insulin resistance and decreased risk for type-2 diabe-
tes (Campos et al., 2002; Dunstan et al., 2002). However, the
high intensity required to induce muscle adaptation with
traditional resistance exercise may not be practical for those
recovering from injury, those with chronic health conditions
and some elderly who may be unable to withstand the high
mechanical stresses placed upon the joints during heavy resis-
tance training.
Now, in the 21st century, different types of exercise are
being tested and studied, such as blood flow restriction (BFR)
during low-intensity resistance training (Shinohara et al.,
1998; Takarada et al., 2000b). It has been reported that an
exercise intensity as low as that associated with walking, when
247
248 Blood flow–non-restricted muscle hypertrophy, T. Abe et al.

combined with BFR, can lead to significant improvements in
thigh muscle cross-sectional area (CSA)/mass and knee joint
strength in young and elderly subjects (Abe et al., 2006a,
2010; Ozaki et al., 2011b). Unlike high-intensity resistance
training (Miyachi et al., 2004), walk training with BFR
improves muscle size as well as carotid arterial (Ozaki et al.,
2011a) and venous (Iida et al., 2011) compliance. Blood flow
–restricted exercise training may be a potentially useful
method for promoting muscle hypertrophy with a low risk of
cardiovascular or orthopaedic problems (Manini & Clark,
2009; Loenneke et al., 2011). This training, however, requires
the use of cuffs that are placed at the proximal ends of the
upper arms or the thighs. As the restriction of blood flow is
only applicable to limb muscles, most BFR training studies
have focused on the physiological adaptations of the blood
flow–restricted limb muscles. Recently, several studies
reported that BFR training induced limb as well as non-
restricted muscle adaptations. In this review, we summarize
the recent articles demonstrating the blood flow–restricted
limb and non-restricted muscle hypertrophic adaptations, and
discuss potential mechanisms.
Non-blood flow–restricted muscle hypertrophy
by BFR training
Type of exercise
To date, four studies have reported the changes in limb and
non-restricted muscle size following different exercise train-
ing combined with BFR (Table 1). Abe et al. (2005) investi-
gated the effects of low-intensity (20% of 1RM) squat and
leg curl exercise training with and without BFR on blood
flow–restricted thigh and non-restricted gluteus muscle vol-
umes in young men. They found that the quadriceps, biceps
femoris and gluteus maximus muscle volumes increased,
respectively, 7·7%, 10·1% and 9·1% for the BFR training
group. In contrast, there were no changes in muscle volumes
in the non-BFR training group (1·4%, 1·9% and 0·6%,
respectively). Triceps surae muscle volume, which was
another muscle group under BFR during training, did not
increase following BFR training (Table 1). Yasuda et al.
(2010) examined the muscle hypertrophic response to low-
intensity (30% of 1RM) bench press training with and with-
out BFR and found that triceps brachii and pectoralis major
muscle thickness increased 8% and 16%, respectively, in the
BFR training group, but not in non-BFR training group
( 1% and 2%, respectively). The same authors reported the
effects of 6 weeks of blood flow–restricted low-intensity
(30% of 1RM) bench press training on upper arm and chest
muscle cross-sectional areas (CSA) (Yasuda et al., 2011). They
found that triceps brachii and pectoralis major muscle CSA
increased 4·9% and 8·3%, respectively, following training.
Additionally, Sakamaki et al. (2011) reported that muscle vol-
ume of the thigh and lower leg increased by 3·8% and 3·2%,
respectively, in BFR walk group following training; however,
gluteus maximus muscle volume and lumber L4-L5 muscle
CSA did not change in the BFR walk group, although
iliopsoas muscle volume tended to increase (P = 0·07).
Therefore, previous results suggest that low-intensity (20–
30% of 1RM) resistance exercise training combined with BFR
elicits muscle hypertrophy in both blood flow–restricted limb
and non-blood flow–restricted muscles. However, the combi-
nation of leg muscle BFR with slow-walk training elicits
muscle hypertrophy only in the blood flow–restricted leg
muscles. This might be due to the exercise intensity being
too low during BFR walk training to cause muscle hypertro-
phy in the non-blood flow–restricted gluteus maximus and
other trunk muscles.

Table 1 Limb and trunk muscle adaptations following low-intensity BFR training.

Type Exercise Assessment technique

Author (year) Subjects of exercise intensity and parameter Muscle site %Change
3
Abe et al. (2005) YM Squat/leg curl 20% 1RM MRI (MV, cm ) Quadriceps 7·7
9 BFR Triceps suraea 1·2*
7 CON Gluteus maximus 9·1
Yasuda et al. (2010) YM Bench press 30% 1RM Ultrasound (MTH, cm) Triceps brachii 8
5 BFR Pectoralis major 16
5 CON
Yasuda et al. (2011) YM Bench Press 30% 1RM MRI (CSA, cm2) Triceps brachii 4·9
10 BFR Pectoralis major 8·3
10 CON
Sakamaki et al. (2011) YM Walking Slowb MRI (MV, cm3) Thigh 3·8
9 BFR Lower leg 3·2
8 CON Gluteus maximus 0·4*

YM, young men; BFR, blood flow restriction training group; CON, control training group; 1RM, one repetition maximum; MRI, magnetic reso-
nance imaging; MV, muscle volume; MTH, muscle thickness; CSA, muscle cross-sectional area.
aData from Abe et al. (2006b).
bTreadmill walking speed was 50 m min 1.
*Not statistically significant.
© 2012 The Authors
Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine 32, 4, 247–252

Exercise intensity
We examined the relationship between exercise intensity and
changes in limb and trunk muscle size (only use MRI-mea-
sured muscle size data) following different types of BFR train-
ing (Fig. 1). One problem with most previously reported
studies is the fact that exercise duration and frequency of the
training interventions are different (Abe et al., 2005; Sakamaki
et al., 2011; Yasuda et al., 2011). Therefore, in order to com-
pare different exercise protocols, the magnitude of hypertro-
phic potential (per cent increase in muscle size divided by the
number of total training sessions) was calculated. These stud-
ies also did not measure the exercise intensity for each indi-
vidual muscle; therefore, we estimated the exercise intensity
of lower body muscles during walking and during low-inten-
sity squat training using previously reported studies (Isear
et al., 1997; Masumoto et al., 2004; Sawai et al., 2006).
Because these studies reported electromyographic analyses of
individual lower body muscle activity during each exercise, as
well as during maximum voluntary isometric contraction
(MVIC), the exercise intensity for each muscle could then be
expressed as a per cent of MVIC.
Figure 1 illustrates that the muscle hypertrophic potential is
positively associated with exercise intensity during BFR train-
ing. Interestingly, exercise intensities of the quadriceps, ham-
strings and triceps surae muscles during walking probably
ranged between 10% and 20% of MVIC, yet both thigh and
lower leg muscle size increased significantly following train-
ing. In contrast, exercise intensity of the blood flow–restricted
triceps surae muscle during squat training may be <10% of
MVIC, while exercise intensity of non-restricted gluteus maxi-
mus during walking ranged between 10% and 20% of MVIC,
resulting in no significant changes in either muscle after
0·5
Change in muscle size (% per session)
0·4
SQ(GM)
0·3
0·2
Walk(TH)
Walk(LL)
0·1
SQ(TS)
Walk(GM)
0 tance exercise and low-intensity BFR resistance exercise. In the
0 10 20
Exercise intensity (% of MVIC)
Figure 1 Relationship between estimated exercise intensity for each
muscle and per cent change in muscle size following training. SQ,
squat/leg curl training; BP, bench press training; walk, walk training;
QF, quadriceps; GM, gluteus maximus; PM, pectoral major; TB, triceps
brachii; TS, triceps surae; TH, thigh; LL, calf. Open circles (○) indicate
no significant change. Closed circles (●) indicate significant increase
in muscle size (P<0·05).
© 2012 The Authors
Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine 32, 4, 247–252
Blood flow–non-restricted muscle hypertrophy, T. Abe et al. 249
training. These results suggest that a minimum exercise inten-
sity for muscle hypertrophy in the blood flow–restricted limb
muscles is approximately 10% MVIC and for non-restricted
trunk and hip muscles is 20% MVIC, although training
effects are also influenced by other factors besides exercise
intensity.
Relationship between blood flow–restricted limb
and non-restricted muscle hypertrophy
Surprisingly, very few studies reported trunk muscle hypertro-
phy following high-intensity resistance training or low-inten-
sity BFR training (Abe et al., 2000). In well-designed,
high-intensity resistance exercise studies that utilized bench
press and squat exercises, subjects typically perform the move-
ment until near exhaustion or completely exhausted, so that
both limb and trunk muscles are fully activated during each
exercise session. This increased muscle activation would stim-
ulate muscle protein metabolism and muscle hypertrophy for
both limb and trunk muscles. As a result, there is a significant
positive correlation between limb and trunk muscle hypertro-
phy (r = 0·70, P = 0·02) following high-intensity bench press
training (Yasuda et al., 2011); however, following low-inten-
sity BFR training, there is a moderate, non-significant positive
correlation (r = 0·54, P = 0·13) between limb and trunk mus-
cle hypertrophy (Yasuda et al., 2011).
Non-blood flow–restricted muscle hypertrophy:
potential mechanisms
Muscle protein metabolism
In blood flow–restricted vastus lateralis muscle, muscle protein
synthesis increased and mammalian target of rapamycin
(mTOR) signalling pathway was activated 3 h after an acute
BP(PM) bout of low-intensity BFR knee extension exercise in young
men (Fujita et al., 2007). Fry et al. (2010) demonstrated that
muscle protein synthesis increased by 56% in the BFR group,
while muscle protein synthesis did not increase in the control
SQ(QF)
group, who exercised without BFR. The same laboratory using
BP(TB)
the same technique reported that 70% 1-RM intensity knee
extension exercise without BFR increased vastus lateralis mus-
cle protein synthesis (48% at 2 h postexercise) through the
mTOR pathway in young men (Dreyer et al., 2006). Those
results indicated that increases in postexercise muscle protein
synthesis are probably similar between high-intensity resis-
30 40 exercised muscle with BFR, there was also a significant
increase in the phosphorylation of p70 ribosomal S6 kinase 1
(Fujita et al., 2007; Fry et al., 2010) and ribosomal protein S6
(Fry et al., 2010), suggesting enhanced mTOR complex 1
signalling following low-intensity exercise with BFR. The
mTOR complex 1 signalling is indicative of improved transla-
tion initiation, which obviously explains the increase in
muscle protein synthesis with BFR exercise. Although mTOR
250 Blood flow–non-restricted muscle hypertrophy, T. Abe et al.
complex 1 signalling appears to be an important regulator of
translation initiation, the BFR exercise–induced protein synthe-
sis may be activated by other regulators (e.g. mitogen-acti-
vated protein kinase, MAPK signalling pathway) (Fry et al.,
2010). Downregulation of proteolytic markers (forkhead box
O3, atrogin-1 and muscle RING-finger protein-1) has also
been reported 8 h postexercise in blood flow–restricted limb
muscle (Manini et al., 2011). However, there are no direct
reports demonstrating the changes in muscle protein metabo-
lism in non-restricted trunk and limb muscles (proximal of
the cuff) after an acute bout of BFR exercise, as similar
changes in protein metabolism would be needed for non-
restricted muscle hypertrophy.
Hypoxia
At rest and during BFR exercise, stroke volume decreases
because of venous blood pooling in the blood flow–restricted
limbs, while heart rate increases to maintain cardiac output
(Takano et al., 2005; Iida et al., 2007). Thus, circulating blood
to the non-restricted muscles is not reduced compared to
exercise performed at the same intensity without BFR. There-
fore, trunk muscles hypoxia would not be expected to occur
during BFR exercise even if the blood flow–restricted limb
muscles are hypoxic.
Muscle activation
During an acute low-intensity BFR resistance training session
(30% of 1RM and four sets of 75 reps), muscle activity
assessed using integrated electromyography is synergistically
increased in both the blood flow–restricted limb muscles and
the non-restricted trunk muscles (Yasuda et al., 2006). The
greater muscle activation in the trunk muscles may have
occurred to compensate for the deficit in force development
of the blood flow–restricted limb muscles during exercise.
Increased muscle activation associated with low external loads
(20–30% of 1RM) caused by the restriction of blood flow
appears to result in greater internal activation intensity on the
muscle relative to the external load (Yasuda et al., 2009). Dur-
ing slow walking with BFR, however, the level of muscle acti-
vation may be still low in the thigh and triceps surae muscle
because muscle fatigue does not occur in the knee extensor
muscles during BFR walking (Ogawa et al., 2012). Thus, mus-
cle activation of the gluteus maximus muscle may not be great
enough during BFR walking to induce muscle hypertrophy
(Fig. 1).
Growth factors
Acute change in anabolic hormones such as growth hormone
(GH) and testosterone are promoting factors for skeletal mus-
cle growth. In response to an acute bout of low-intensity BFR
exercise, plasma GH concentrations increased significantly
above resting levels (Takarada et al., 2000a; Reeves et al.,
Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine 32, 4, 247–252
2006). GH has been shown to be a positive regulator of
cellular differentiation in a variety of cells, including muscle
(Ewton & Florini, 1980). In animal and in vitro studies, GH
treatment is associated with increased muscle protein synthesis
rates and decreased muscle protein breakdown (Rooyackers &
Nair, 1997). Although GH concentrations increased after an
acute bout of BFR walk training session (Abe et al., 2006a),
non-restricted gluteus maximus and iliopsoas muscle volume
and lumber L4-L5 muscle CSA did not change following BFR
walk training (Sakamaki et al., 2011). Additionally, blood flow
–restricted triceps surae muscle volume did not increase fol-
lowing BFR squat/leg curl training, while thigh and gluteus
maximus muscle volumes increased after training (Abe et al.,
2005). These results indicate a lack of a consistent benefits
caused by acutely elevated GH for limb and trunk muscle
hypertrophy following BFR training.
There is recent evidence indicating that elevations of local-
ized hormones may play some role in the hypertrophic
response. Mechano growth factor (MGF) is locally increased
in response to both mechanical stimuli and cellular damage,
providing a potential mechanism for skeletal muscle hypertro-
phy (Goldspink et al., 2008). Interestingly, using an animal
model in which the insulin-like growth factor 1 receptor was
knocked out, animals were still able to undergo significant
muscle hypertrophy (Spangenburg et al., 2008). This finding
supports Hornberger et al. (2004) who have observed
increased activation of the mTOR pathway in response to
mechanical stimulation (passive stretch), independent of
locally activated growth factors. It is currently premature to
definitively state whether local growth factors (e.g. MGF) are
activated and play a role in limb and trunk muscle hypertro-
phy following BFR training.
Muscle swelling
Low-intensity resistance exercise with BFR leads to an acute
increase in muscle size in both blood flow–restricted limb and
non-restricted muscles. For instance, acute increases in muscle
size are found in both triceps brachii and pectoralis major
muscles following a single bout of BFR bench press exercise
(Yasuda et al., 2011). The magnitude of the acute changes is
higher in the chest than in the triceps, which is consistent
with the training-induced muscle hypertrophy observed in
both muscles. Acute changes in muscle size are also found in
blood flow–restricted quadriceps and triceps surae muscles,
but not non-restricted and non-active trunk muscles, during
and immediately after 30-min walking (Ogawa et al., 2012).
Furthermore, these acute changes in muscle size are higher
than what is observed from walking without BFR. Acute
increases in muscle size are correlated with a loss of plasma
volume (Abe, 2004), suggesting that increases in muscle size
after BFR exercise reflect primarily a fluid shift from the vas-
cular space into blood flow–restricted and non-restricted active
but not inactive muscles. Pilot biopsy data from our laboratory
suggest that low-intensity knee extension exercise with BFR
© 2012 The Authors
 Blood flow–non-restricted muscle hypertrophy, T. Abe et al. 251

results in decreased plasma volume and an acute increase in Conclusion

muscle fibre CSA (approximately 4% increase) of the restricted
Low-intensity (20–30% of 1RM) resistance exercise training
muscle. This demonstrates that at least part of the fluid shifts
combined with BFR elicits muscle hypertrophy in both blood
into the actual muscle cell increasing cell volume. Acute mus-
flow–restricted limb and non-blood flow–restricted muscles.
cle volume changes (cell swelling) are associated with reduced
However, the combination of leg muscle BFR with slow-walk
proteolysis (Berneis et al., 1999). A reduction in proteolysis,
training elicits muscle hypertrophy only in the blood flow–
secondary to BFR exercise–induced acute muscle volume
restricted leg muscles. The exercise intensity may be too low
changes, could contribute to a net increase in protein balance
during BFR walk training to cause muscle hypertrophy in the
and subsequently to an anabolic response of skeletal muscle.
non-blood flow–restricted gluteus maximus and other non-
Muscle volume changes after BFR resistance exercise may be
restricted muscles. Muscle activation is an important factor for
associated with the blood flow–restricted limb as well as with
BFR training–induced muscle hypertrophy, and the minimum
the non-restricted trunk/limb muscle hypertrophy. The mech-
exercise intensity for muscle hypertrophy may be about 10%
anisms behind the potential anabolic effect of muscle cell
of MVIC for the blood flow–restricted limb muscles and about
swelling are not well understood. However, a recent article
20% of MVIC for non-restricted trunk muscles.
hypothesized that BFR exercise–induced muscle cell swelling
is detected by an intrinsic volume sensor. The activation of
this volume sensor may lead to a G-protein-medicated activa- Acknowledgments
tion of a currently unidentified tyrosine kinase, which leads
No sources of funding were used to assist in the preparation
to an activation of mTOR and MAPK signalling pathway
of this review. The authors have no conflicts of interest.
(Loenneke et al., 2012).

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