Mechanisms of Muscle Hypertrophy and its relation to Resistance Training Protocols: A

Systematic Review
Kin 4400
Dr. Kerry Ritchie
Salima Hassam
0805707
April 8th 2016

Table of Contents
1. Abstract
2. Introduction
2.1. Background information
2.2. Rationale
3. Methods
3.1. Eligibility Criteria
3.2. Information Sources
3.3. Study Selection
3.4. Risk of Bias
3.5. Methodology Flow Chart
4. Results
4.1. Study Selection
4.2. Study Characteristics : Data Table
4.3. Summary of results
4.4. Relationships to other studies under review
5. Discussion
5.1. Summary of Evidence
5.2. Limitations
6. Conclusion

1.Abstract
Background
Muscular size has positive implications for sport performance and overall health. The primary
mechanisms involved in muscular hypertrophy include mechanical loading, and metabolic stress.
Research is not consistent on the best approach to achieve muscle hypertrophy and the
combination of these mechanisms. Therefore the purpose of this review is to examine the
mechanisms of muscular hypertrophy and its application to resistance training.
Methods
Studies were identified through databases PubMed, Cinahl, SPORTdiscus, and through reference
lists up to March 31st 2016. Criteria for inclusion was a) published in last 10 years b) Human trial
c) clinical trials d) Published in English e) Had an outcome measure of muscle thickness. No
restrictions were placed on age, gender, or training status.
Results
20 studies fulfilled the criteria. All studies showed improved muscle CSA with resistance
training, with 4 showing specific increases to muscle CSA with mechanical tension, 3 with no
difference between the two mechanisms, and 2 showing benefits to metabolic stress. Sample
sizes were typically small with untrained subjects.
Conclusions
Current research suggests that. Training procedures should aim to create a significant amount of
metabolic stress, while maintaining moderate muscle tension. The rep range shown to be most
1

optimal is 6-12 with a moderate 60-90 second rest time with typically no less than 65% 1 RM.
Further research with less methodological limitations such as larger sample sizes and trained
individuals is recommended
Key Words:
Metabolic Stress, Mechanical Tension, Muscle Hypertrophy, Muscular Hypertrophy, Resistance
Training.

2.Introduction
Skeletal Muscle Hypertrophy is an increase in muscle size due to net protein synthesis
being greater than net protein breakdown (Schoenfield et al. 2014). Muscle cross sectional area is
increased due to a larger diameter being created. When there is substantial stimulus there are
perturbations in extracellular matrix and fibers which leads to a chain of events resulting in an
increase in the size and number of contractile proteins called actin and myosin, as well as
sarcomeres being laid down.(Buitrego et al.2013; Campus et al 2002;Schoenfield 2010; Toigo et
al. 2006). This leads to individual fiber growth and increase in muscle.
This is an important area of research as an increase in muscular size has positive
implications for sport performance and overall health. Low levels of muscle mass are strongly
correlated with a loss of functional independence and mobility (Janssen et al. 2002). This can be
an important aspect for the elderly population as hypertrophy increases muscle mass. A strong
correlation is seen between muscle strength and muscle cross sectional area, which is why
hypertrophy is an important target with various sports involving strength and power such as
rugby and football (Maughan 1983). Hypertrophy is necessary for bodybuilding, as competitors
2

are judged on the amount and the quality of their muscle mass and development (Schoenfield
2010). It is also important for powerlifting, where both fat-free mass and muscle cross sectional
area are found to be good predictors of powerlifting ability (Brechue et al. 2002; Kraemer 2004;
Schoenfeld 2010).

The primary mechanisms involved in muscular hypertrophy include mechanical loading,

and metabolic stress (Mangine et al. 2015; McCall et al.2004; Pearson and Hussain 2014).
Mechanical tension involves high intensity loading, with long rest periods. Mechanical
tension is induced by force generated and stretch which has an additive effect and increases
muscle mass due to increasing protein synthetic rate. Mechanical loading can be active (high
force production with muscle activation or passive (occurs during stretch((McMahon et al.
2014). (Jones et al.1987; Hornberger et al. 2006; Shinohara et al 1988). Mechanical tension is
thought to directly stimulate mTOR. (Bamman et al. 2001) and is considered to be a primary
input as an increased force development is essential in order to gain an adaptive hypertrophic
response (Goldberg et al. 1975).
Metabolic stress results from exercise relying primarily on anaerobic glycolysis or for
exercise performed under ischemic conditions and mainly results from accumulation of
metabolites such as lactate, hydrogen ions and muscle hypoxia. Metabolic Stress exercise
typically involves low intensity, higher rap ranges, and moderate rest intervals. (Suga et al
2009;Tesch et al.1986;Toigo et al 2006).
The concentrations of hormones such as testosterone, growth hormones, and insulin-like
growth factor-1, can show increases with resistance training which are not necessarily always
3

related to muscle increases in cross sectional area. (Goto 2004; Hornberger et al. 2006; Kraemer
et al 1991; McCall et al.1995; Raastad et al. 2000).

Research is not consistent on the best approach to achieve muscle hypertrophy and the
combination of these mechanisms. (Schoenfeld et al, 2014).Therefore the purpose of this review
is to examine the mechanisms of muscular hypertrophy and its application to resistance training.
This paper will focus on comparisons between mechanical stress, metabolic stress by looking at
clinical trials in humans with resistance training protocols with measures of muscle thickness and
various hormones. This information will then be applied to the prescription of resistance training
variables in order to optimize muscular hypertrophy.

2. Methods
3.1 Eligibility Criteria
Primary research articles published by or accepted by peer reviewed research journals
were included. Review articles, animal studies, articles not in past 10 years were excluded. No
restrictions were placed on age, gender, or training level. Studies needed to use resistance
training protocols and measure muscle cross sectional area.
3.2 Information Sources
Potential studies were identified through searching databases PubMed, SPORTdiscus,
and Cinahl. The last completed search was on March 21st 2016. Common search terms used
included metabolic stress or Metabolic stress, Mechanical tension or Metabolic tension,
4

muscle damage or Muscle damage, Muscular Hypertrophy or Muscular Hypertrophy, Search

Metabolic stress or Metabolic stress and muscular hypertrophy OR Muscular hypertrophy,
Search Muscle Damage or muscle damage and muscular hypertrophy OR Muscular
hypertrophy, and Search Mechanical tension or Mechanical Tension and muscular
hypertrophy OR Muscular Hypertrophy. The Language was limited to English. The date was
limited from 2006-2016. Participants were limited to humans. Limit was set to clinical trials
only. Articles were limited to full text only. Reference lists were checked for additional sources.
3.3 Study Selection
All studies looking at mechanisms of hypertrophy and resistance training meeting the
eligibility criteria listed above were considered. Studies were first screened by title or abstract,
and then the manuscript was reviewed if the study characteristics satisfied the eligibility criteria
and the purpose of the review.
3.4Risk of Bias
Out of 20 articles 13 trials were randomized. There was no blinding in the studies.
Treatment compliance was reported in the studies. Sample size was typically small with 12 of the
studies have less than 20 participants.

3.5 Prisma Flow Chart

4. Results
4.1 Study Selection
Following article screening 20 articles were selected for review including 460 individuals
(404males, 54 females). All major study characteristics are summarized in the data extraction
table below. 8 studies were randomized control trials, 8 were crossover studies, and 4 were
intervention clinical trials.

4.2 Study Characteristics

Study

Study Design

(Buitrag

Crossover Trial

Populatio
n
Trained

Intervention
Completed four

Duration of
Intervention
3 week period

Control
Crossover

Outcome
Measures
Lactate

Results

Study
Limitations
Only 1 set

Lactate

o et al.
2013)

(Buresh
and
Berg
and
French
2009)

Males
(n=10)

Randomized
Trial

Untrained
males
(n=12)
Age 19-27

protocols of bench
press to exhaustion
on four different
day (randomized
order):
1 set to failure
55% 1RM
Strength
55% 1RM fast
velocity
70%1RM
Hypertrophy
85%1RM max
strength
4X week resistance
training protocol

EPOC (VO2
measured during
and after)

10 weeks

No Control

Testosterone
Growth Hormone

Volume Equated (10

RM, 22 sets session
1/3,
18 sets session
2/4) :

Arm Cross
Sectional Area
Thigh Muscle
Cross Sectional
Area

Short Rest: 1
minute rest between
sets (N=6)

significantly
higher after
all protocols
EPOC not
higher in
hypertrophy
protocol

Lean Body Mass

Long Rest =2.5

minute rest between
sets (N=6 )

SR > LR
Hormonal
response:
week 1 (p
<0.05) No
difference in
hormones by
week 5-10.
Arm CSA
increased
more with LR
(12.3 6 7.2%)
than with SR
(5.1 6 2.9%, p
, 0.05)
Sig Increases
for SR and
LR for thigh
muscle CSA
Sig Increases
for SR in
LBM.

(Cadore
et al.
2014)

Randomized
Control Trial

Males and
Females
(n=22)
M=8
W = 14

2X week (start at 2
sets 10 reps,
progress to 5 sets 10
reps)
Concentric training
(CON, n =11, 7 W,
4 M)
Eccentric training
(ECC,n=11, 7W,4
M)

6 weeks

Right Leg
Training
leg, Left leg
control

Vastus Lateralis
Muscle Thickness
(biopsy)

CON and
ECC showed
Vastus
lateralis
muscle
thickness (P
<0.05)

completed
low volume
chronic
training
adaptations
cannot be
concluded

Training
sessions
unsupervise
d
small
sample
size
limited
statistical
power
-SR were
stronger at
baseline
than LR
-Untrained
subjects
-Age of SR
group
significantly
different
than LR
group at
baseline (SR
older)
-no control
for caloric
intake
-Only
Vastus
lateralis
assessed
-Eccentric
workload
was greater
than
Concentric
-low volume
used
-short

(de
Souza
et al.
2010)

Randomized
Control Trial

Recreatio
nally
Trained
Males
(N=20)

Constant rest
interval group: first
2 weeks = 3 sets of
10-12, 2 min rest
6 weeks: 4 sets 810, 2 min rest

8 weeks

Constant
interval
group was
control

Muscle CSA: arm

and thigh

No significant
difference
between
Muscle CSA
between
groups, both
increased
significantly

12 weeks

No Control

Muscle Biopsy
Vastus Lateralis
Muscle CSA

Mean CSA
improved in
both LL and
HL (P <0.05)
CSA
improvements
significantly
greater in HL
than LL (P
<0.05)
No changes in
hormones
except IGF-1
elevation 5
min after
exercise.

Decreased Rest
interval Group:
First two weeks 3
sets of 10 -12, 2
min rest,
6 weeks: 4 sets 810, 30 seconds rest

(Holm
et al.
2008)

Cross over Trial

Untrained
Men.
(N=11)
Age =
25+- 1
year

3X week
Unilateral
Resistance training
Volume Equated
Knee Extensions
10 sets each leg

Growth Hormone
IGF-1

Trained one leg at

70% 1 RM (heavy
load) 10 RMper set
Other leg at 15.5%
1 RM (Light load)
36 RM per set

(Kurobe
et al.
2015)

(Mangi
ne et al.
2015)

Randomized
Control Trial

Randomized
Trial

Testosterone

Untrained
Men
(N=13)
Age = 23
+- 1 year

3X a week -3 sets 1
minute intervals
elbow extension-10
RM
Hypoxic Group (H)
=
(N = 6)
Normoxic Group
(NO) =(N=7)

8 weeks

Trained
Men (n=
28)

High Volume:
(n=14)
4 sets 10-12 Reps
-70% 1 RM 1 min
rest
High Intensity:
(n=15)
4 sets * 3-5 reps

8 weeks

Left Arm
Control
Right Arm
trained

Blood Lactate
Growth Hormone
Muscle CSA
(ultrasound)

No Control

Muscle CSA
(vastus lateralis,
rectus femoris,
pectoralis major,
triceps) via
ultrasound
Growth Hormone

intervention
time
Short
training
period, long
term effects
cant be
applied.
Lower
Training
volume in
DI group in
weeks 6-8.
Medial
Muscle
CSA used to
assess
changes
-untrained
subjects
-very low
1RM for
light load
-Trained
only one
muscle
contralateral
cross
training
effects
possible

GH
Concentration
greater in H
group than
NO group (P
<0.05)
Muscle CSA
greater in
triceps Brachii
in H

-Untrained
subjects
-Low
Volume
Protocol

Increase in
muscle CSA >
in arm of high
intensity vs
high volume
Growth
hormone
greater in

-short term
study

90% 1RM -3
minute rest

(Mata et
al.
2011)

Randomized
Control Trial

Untrained
men
(N=49)

Training Group
(n=40)
Control Group (n
=9)
24 sessions 2X
week- 72 hr
between sessions

12 weeks

Control
group did 2
sessions per
week with 4
sets 12-15
reps

Muscle Thickness
Biceps Brachii
and Triceps
Brachii

4 weeks

Control
Subjects
rest do no
protocol

Vastus Medialis
and Biceps
Femoris
measured.
Cortisol
Testosterone
Muscle Activity
Rate of Force
Development

10 weeks

30% 1RM
was used in
previous
study and
acted as
control

Muscle Cross
Sectional Area
Vastus lateralis
(biopsy)
mTOR

Training group did

4 sets 12-15 reps
session 1, 3 sets 810 reps session 2, 2
sets 3-5 reps session
three, with
increasing intensity
per session,
progressing to 2 sets
3-5 reps per rest of
session.

(McCau
lley et
al.2009)

(Mitche
ll et al.
2012)

Crossover Trial

Randomized
Control Trial

Trained
Males (2
years) n =
10

Untrained
Men(N=1
8)
Age =( 21
+- 0.8)

4 back squat
protocols with one
week in between
Volume Equated
Hypertrophy: 4 sets
of 10 squats @ 75%
1RM (90 sec rest)
Strength :11 sets of
3 squats @ 90%
1RM (5 min rest)
Power: 8 sets of 6
jump squats @
maximum power
load (3 minute rest)
1RM squat protocol
Control : subject
quietly rests
Randomly assigned
to 2 of 3 training
conditions with
different intensity. 1
training protocol
per leg.
3X a week
1 set of knee

week 3 in
high volume
group
signifcantly
no differences
after this
Strength
training
created
uniform
increases in
hypertrophy
of triceps, and
had
significant
hypertrophy
of bicep
muscle, with
more in
certain areas
of bicep than
others (P
<0.05).
Strength
training
shown to
increase
hypertrophy
Greater
muscle
activity in H
protocol
compared to
S.
Significant
changes in
hormone
concentrations
in H type
protocol (P
<0.05)

-Significant
increase in
muscle CSA
in all 3
conditions (P
= <0.0001)
-No statistical
significant

-untrained
subjects
-low volume
per week
with varied
rep schemes
-not even
number of
people in
control
group

-More than
one session
could be
necessary to
see chronic
adaptations
to hormone
responses
this is short
term
-muscle
activity
measured
not CSA

-Mixed
design did
not permit
for within
subject
comparisons
could only
do between-

extension
performed to failure
at 80% of 1RM
(80%-1);
3 sets of knee
extension to fatigue
at 80% of 1RM
(80%);
3 sets to fatigue
with 30% of 1RM
(30%).

(Mitche
ll et al.
2013)

Crossover Trial

Untrained
males(N=
23)
Age 24 +3 years

4 sessions per week

(2 upper body, 2
lower body)
4 blocks of 4 weeks
each
Block 1 = 3 sets, 12
reps, 60 sec rest
2 = 3 sets, 10 reps
90 seconds rest
3= 4 sets 8 reps,100
second rest
4= 4 sets, 6 reps =
120 seconds rest

16 weeks

No Control

Muscle Biopsies
-Muscle CSA
Hormone Levels:
GH
Testosterone
IGF-1
(15,30,60 min
post exercise)

(Nornbr
and et
al,
2008)

Randomized
Trial

Untrained
males(N=
15)

Four sets-7 RM
unlitateral
concentric-eccentric
knee extensions 23x weekly for 12
sessions total.
Weight Stack (n=8)
Fly Wheel
Eccentric Overload

5 weeks

No control

-Volume of
Quadriceps (MRI)

(Age = 39
+-9.1
years)

difference in
degree of
quadriceps
hypertrophy
between 80%1 and 80%-3
condition
however80%3 and 30%-3
showed
double the
average
hypertrophy
of 80%-1.
-80%-3
condition and
30%-3
condition
showed
equivalent
hypertrophy
Significant
increases in
mTOR in all
conditions

condition
comparisons
Participatio
n in one
condition
could affect
other
condition.
-larger
sample size
could be
needed to
show
statistical
significance

Significant
Increase in
muscle cross
sectional area
(P = <0.005)
no
relationship
between the
training
exerciseinduced
changes in
free
testosterone,
GH, or IGF-1
concentration
and muscle
fiber
hypertrophy
Significant
changes in
volume in all
four
quadriceps
muscles with
ECC but just
rectus femoris
with CON

Subjects self
reported
their food
-results of
one block
could
possibly
affect the
other

10

Training
was done
either twice
or 3 times a
week Not
a constant
frequency.
difference in
frequency

(n=7)

exercise
weight stack.

could
impact
hypertrophy.
-range of
motion
during
exercise was
not
controlled
for

(Ogasa
wara et
al.
2013)

Crossover Trial

(N=9)
Untrained
Males

High-Load
Resistance Exercise
(75%-1RM for 10
reps, 3 sets 3x week
to fatigue 3minute
rest) (n=9)
12 month
detraining.
Low-Load
Resistance Exercise
(30% 1 RM, 4 sets
3x/week, to fatigue
-3 minute rest)

6 weeks per
each protocol,
12 months in
between

No control

Muscle Cross
Sectional Area of
triceps and pec
major

Significant
increase in
muscle CSA
in both HL
RE and LL
RE, and
similar
between LL
RE and HL
RE.

Detraining
for a year
the
participants
still had an
elevated
strength
level.
-research
completed
in upper
body,
currently
understudie
d.

(Peterso
n et al.
2010)

Randomized
Control Trial

(n=83)
(n =43
males,
n=40
females;
age =
25.12 +5.5 years)

Unilateral arm
resistance exercise
9 sets of bicep curls
-volume and
intensity equated.
Week 1-4:
3 sets -12 reps-to
failure

12 weeks

Control =
Other Arm

Muscle Volume
(MRI upper arm)

Volume load
was
independently
associated
with
hypertrophy
only among
females
Males had
greater
increases in
hypertrophy.

6 months

Control
Group
=bodyweigh
t training 1
hour 3x

Muscle Thickness
(elbow flexors
and extensors)

Greater
muscle
thickness in
both 3 set
group and 5

Training
frequency
was same
for all
subjects but
relative rest
per given
work
volume was
not
Short time
frame of
study
Unilateral
protocol
reduces
external
validity
compared to
full body
protocols
Muscle
thickness
was only
evaluated at
one point of

Week 5-9
3 sets 8 reps-failure
Week 10-12
3 sets 6 reps failure

(Radaell
i et
al.2015)

Randomized
Control Trial

(n=48)
Untrained
Males

3x per week, 9
exercises, 8-12 RM,
90s-120 s rest
varying in sets per
exercise.

11

1 set group: (n=12)

3 set group: (n=13)
5 set group: (n=12)
Control: (n=10)

week

(Schoen
feld et
al. 2014
b)

Randomized
Trial

(n=17)
Untrained
Males
Age: 2031

Hypertrophy
Group : 3 exercises
per session: 3 sets
10 RM 90s rest
(n=9)
Strength Group: 3
exercises per
session: 7 sets 3
RM 3 minute rest.
(n=8)
3 sessions per week
non consecutive
days Volume
Matched & to
failure

8 weeks

Pair
Matched

Ultrasound:
Muscle Thickness
of Biceps Brachii

(Schoen
feld et
al. 2014
a)

Crossover

Trained
men(n=10
)

High Load (HL):

75% 1 RM to
muscular failure on
Leg press
Low-Load (LL)
30% 1 RM to
muscular failure on
Leg Press
(separation of 15
minutes between
two types of
exercises)

1 session

Counterbala
nced Design

EMG activity
Vastus Lateralis,
Vastus Medialists,
Biceps Femoris

set group, no
significant
increase in 1
set group, and
5 set group
was
significantly
greater than 3
set group.
Significant
increases
occurred from
pre- to
posttesting for
both HT and
ST
No
differences in
the magnitude
of
hypertrophic
changes were
noted between
groups.

Greater EMG
activity seen
in HL set
compared to
LL set.
training with a
load

the muscle
group.

Short time
frame of 8
weeks
Did not test
mid
protocol
cannot
determine if
there was
greater
hypertophic
gains
immediately
or
throughout
intervention
Specific to
biceps dont
know
applicability
to other
muscle
groups.
Didnt
measure
muscle
cross
sectional
area or have
more
sessions of
training to
see
changes/acti
vity
Activity
measure is
not same as
muscle CSA
Protocol
completed
15 minutes
apart
possible

12

influence of
Fatigue
Limitation
of

(Tanimo
to et al.
2008)

(Wilbor
n et
al.2009)

(Wilson
et al.
2013)

Randomized
Control Trial

Crossover Trial

Cross over Trial

Untrained
Men
(n=36)

Untrained
men
(n=13)
Age =
(21.5+2.9)

Trained
Males
(n=12)

2x a week- Full
body 5 exercises
8 RM max. 4 sets
-1 warm up, 60
second rest
completed to
exhaustion. 3
minutes between
exercise.
Low intensity
training:
(n=12): 55-60% 1
RM, 3 second CON,
3 second ecc, no
relaxation
High intensity
training: 80-90%
1RM, 1 second con,
1 second ecc, 1
second per relaxing
4 sets of 18-20 reps
-60-65% -1Rm
4 sets 8-10 reps, 8085% -1RM

Completed
30,15,15,30 rep
scheme -30% RM
leg press with
occlusion and with

13 weeks

Sedentary
control
group

Muscle Thickness
(Subscap,
Arm,Posterior
Thigh, Anterior
Thigh)

LST increased
thickness
comparable to
HST thickness
and both were
significant(P<
0.05)

2 bouts of
exercise
separated by 2
weeks

Participants
acted as
own control
during cross
over design

Biopsies of Vastus
lateralis
MHC (1, 11a,11x)
IGF-1

No difference
in factors
between
intensities,
significant
increases in
factors with
both.

2 week

Control had
occlusion
cuffs with
zero
pressure

Muscle Thickness
(ultrasound)
Soreness
Muscle Swelling

Blood flow
restriction
increased
muscle
activation and

13

EMG
measures
surface
activity
So can
possibly
underestima
te motor
unit activity
Untrained
Subjects

-untrained
subjects
completing
only 1 trial
per each
exercise
may not be
accurate
representati
on, of
hormone/fac
tors in
trained
population.
Increase in
muscle
thickness/s
welling may
be due to

no occlusion
(control) for 5
sessions with no
more than 72 h rest
in between.

thickness
without
damage
(P<0.05)

venous
pooling
Measures
were taken
post
exercise
cannot
account for
changes
during.

4.3 Synthesis of results:

Cross Sectional- High load vs. Low Load
(Schoenfeld et al. 2014 a) compared a high load leg press at 75% 1 RM to muscular
failure to a 30% 1 RM Leg press with 15 minutes in between with trained males and reported
greater activity with high load compared to low(P= <0.005). One protocol could affect protocol
of other; not completed on separate training days. On two separate occasions two weeks apart
Wilborn et al. (2009) had untrained participants complete 4 sets of 18-20 reps 60-65% 1 RM or
4 sets 8-10 reps 80-85% 1 RM, and found no differences on muscle cross sectional area between
the groups. Untrained subjects were not given training sessions before this training time therefore
results may be confounded.
Hypoxia Condition (Increased Metabolic Stress)
Kurobe et al. (2011) completed a trial with untrained men completing either a 3 week- 3
sets 1 minute rest interval elbow extensions 10 RM in hypoxic conditions (n=6) or normoxic
(n=7) conditions. Muscle CSA was greater in the hypoxic condition. Left arm control right arm
was trained, unilateral training protocol may not be applied to entire body.

14

Metabolic Stress & High Volume

Radell et al (2015) completed a randomized control trial with untrained males (n=48)
completing 9 exercises per 3 sessions for week for 6 months, either completing 1 set (n=12), 3
sets (n=12), 5 sets (n=10) and found significant muscle cross sectional area in the 3 set and 5 set
group, with the 5 set being significantly higher than the three set group. (P=<0.005). Muscle
thickness was only evaluated at one point in the arm.

Long Rest vs Short Rest:

Buresh and Berg et al. (2009) had untrained males (n=12) completing 10 weeks of a 4
times a week resistance training protocol that was volume equated with long rest and short rest
periods. The Long rest period (n=6) group had 2.5 minute rest between sets with 22 sets per
session completed to 10 RM while the short rest period group (n=6) had a 1 minute rest minute
interval. The short rest period showed increased muscle CSA compared to the long rest group in
the arm, and significant increases in both groups with quadriceps muscle CSA. Short rest group
had greater strength at baseline and were significantly older at baseline. Training protocols were
unsupervised. Buresh and Berg et al. (2009) showed shorter rest periods had a significant
increase in muscle CSA.

Females and males differences

Peterson et al. (2010) Showed that volume load was independently correlated with
hypertrophy among females (n=43) which was not shown in males to males (n=40) when
15

completing 3 sets of unilateral bicep curls for 3 weeks, however males showed greater significant
hypertrophy. Unilateral protocol reduces external validity to full body, short time frame of study;
rest periods were not constant between groups. Cadore et al. (2014) found no differences
between untrained males (n=8) and untrained females (n= 14) both showed increases in vastus
lateralis muscle thickness when completing a 6 week protocol doing concentric and eccentric
exercises. Not an even amount of males and females considered, and this is a small sample size.

Eccentric vs. Concentric

Nornbrand et al. (2008) looked untrained males (n=15) completing 4 sets of unilateral
concentric or eccentric overload training for 5 weeks- 3 sessions per week for 4 sets of 7RM.
Eccentric exercise showed greater significant increases in muscle CSA than concentric. Training
was completed either twice or three times a week- increased frequency may confound results &
range of motion during knee extension was not controlled for and this was a short time period.
Cadore et al. (2014) showed significant increases with both concentric and eccentric exercise
training for 6 weeks with a 5 set 10 rep protocol. Only right leg completed the exercise left leg
was control unilateral training may not apply for entire body.

High Intensity vs. Low Intensity

Holm et al. (2008) completed 12 weeks of 3 times a week unilateral resistance training
knee extensions in a cross over trial with 10 sets per leg with untrained men (n=11). Trained one
leg at 70% 1 RM (heavy load) - 10 RM per set and the other leg at 15.5% 1 RM (Light load)

16

36 RM per set. Muscle CSA improved in both high load and low load significantly, with the high
load having significantly greater increases in muscle CSA. A very low 1 RM was used for light
load, there was no control, and a contralateral cross training effect is possible.
Mangine et al. (2015) completed a high volume (n=14,4 sets 10-12 reps- 70% 1 RM -1
minute rest interval) protocol or a high intensity (n=14, 4 sets* 3-5 reps 90% 1 RM-3 minute
rest) protocol for 8 weeks on trained men (n=28). Muscle CSA was greater in the high intensity
group and was significant in both groups. This was a short term study.
Mata et al. (2011) completed a 12 week resistance training protocol with the training
group (n=40) completing 4 sets 12-15 reps session 1, 3 sets 8-10 reps session 2, 2 sets 3-5 reps
session three, with increasing intensity per session, progressing to 2 sets 3-5 reps per rest of
session and the control group completing 4 sets 12-15 reps per session (n=9). There was a
significant effect on the strength training on muscle cross sectional area. The subjects were
untrained, the intensity was not consistent throughout the protocol, the training group had much
greater subjects than the control.
McCaulley et al. (2009) looked at trained males (n=12) and completed 4 back squat
protocols with one week between each -a volume equated cross over trial. There was a
Hypertrophy protocol involving 4 sets of 10 squats -75% 1RM (90 sec rest), strength protocol:
11 sets of 3 squats -90% 1RM (5 min rest), power protocol (squat jumps 8 sets of 6), and
control. Greater muscle was shown activity in hypertrophy protocol. More than one week could
be needed to see chronic adaptations to different protocols.
Mitchell et al. (2012) completed 2 training protocols one on each leg on untrained men
(n=8) for 10 weeks. There were 3 protocols and each men got 3. 3 times a week (randomly
17

assigned) either 1 set of knee extension was performed to failure at 80% of 1RM (80%-1) or/and
3 sets of knee extension to fatigue at 80% of 1RM (80%) or/and3 sets to fatigue with 30% of
1RM (30%).Muscle Cross sectional area of the vastus lateralis showed significant increases in all
conditions, with both the 80% - 3 set protocol and 30% protocol showing significantly greater
muscle CSA than the 1 set protocol and no difference from each other. There was a small sample
size, mixed design did not allow for within subject comparison, and participation in one
condition could affect the other condition.
Mitchell et al (2013) looked at untrained males (n=23) completing 16 weeks of four
blocks of resistance training two upper body and two lower body sessions per week. Block
1included 3 sets, 12 reps, 60 sec rest, block included 3 sets, 10 reps 90 seconds rest, black 3
included 4 sets 8 reps,100 second rest and block 4 included 4 sets, 6 reps = 120 seconds rest.
There were significant increases in muscle hypertrophy in all conditions.
Ogasawara et al (2013) completed a High-Load Resistance Exercise (75%-1RM for 10
reps, 3 sets 3x week to fatigue 3minute rest) (n=9)) 12 months of detraining and then a LowLoad Resistance Exercise protocol (30% 1 RM, 4 sets 3x/week, to fatigue -3 minute rest). Each
protocol was completed for 6 weeks. There was significant muscle cross sectional area in both
and no difference between the 2. Detrained subjects still had elevated strength a year later. Short
protocol completed.
Schoenfeld et al (2014 b) looked at a hypertrophy group (n=9, untrained): 3 sets 10 RM90 seconds rest or strength group completing 7 sets (3RM)-3 minute rest. (n=8). 3 sessions were
completed per week to failure and volume and intensity were matched. Muscle CSA was
significant for both groups, and no advantage was seen in hypertrophy group. Did not test muscle

18

CSA mid protocol just post, short study time frame of 8 weeks. Measure was specific to the
biceps, application to full body not fully applicable.
Tanimoto et al. (2008) completed a high intensity or low intensity full body twice a week
protocol for 12 weeks, with no differences in muscle CSA found between groups, and both being
significant. Low intensity training (n=12) involved 55-60% 1 RM, 3 second CON, 3 second ecc,
no relaxation, and high intensity training: 80-90% 1RM, 1 second con, 1 second ecc, 1 second
per relaxing.

4.4 Relationship to other studies under review:

High load showed greater activity in one study (Schoenfeld et al 2014 a), no difference
between high and low load showed in other study (Wilborn et al.2009). Hypoxia induced
metabolic stress showed significantly increased muscle CSA in one study. (Kurobe et al.2011).
High volume was able to induce significant metabolic stress and cross sectional area in one
study, with no comparison to mechanical tension. Radell et al (2015).Peterson et al. (2010) found
sex differences between males and females with high volume significantly increasing muscle
CSA in females, and greater muscle CSA seen in males, while Cadore et al. (2014) found no sex
differences with males and females in muscle CSA with concentric and eccentric exercise
protocols. Greater mechanical stress induced by eccentric tension showed significant increases in
muscle cross sectional area compared to concentric in one study, and not in another protocol.
(Cadore et al. 2014; Nornbrand et al. 2008). High intensity vs. low intensity protocols resulted in
4 studies with greater mechanical tension being more effective (Holm et al. 2008; McCaulley et
19

al. 2009; Mangine et al.2015; Mata et al. 2011), 2 studies with metabolic stress being more
effective (Mitchell et al. 2012; Tanimoto et al 2008), and 3 studies showing equal effects of
protocols (Mitchell et al. 2013; Ogasawara et al. 2013;Schoenfeld et al.2014 b).

5. Discussion
5.1 Summary of Evidence
All protocols showed both metabolic stress and mechanical tension resulted in significant
muscle hypertrophy and increases in cross sectional area. No study showed neither protocol did
not increase muscle cross sectional area. It was identified specifically in two protocols that
metabolic stress was more effective (Mitchell et al. 2012; Tanimoto et al 2008), 4 protocols that
mechanical tension was more effective (Holm et al. 2008; McCaulley et al. 2009; Mangine et
al.2015; Mata et al. 2011), and 3 protocols that there was no difference(Mitchell et al.
2013;Ogasawara et al. 2013;Schoenfeld et al.2014 b).
Hypertrophic advantages seen with metabolic stress programming could possibly be due
to greater volume loads rather than the protocol itself. However these protocols are also faster to
complete, than higher mechanical tension longer rest protocols. (Mangine et al 2015;Schoenfeld
et al. 2014b). When matched with high volume power lifting protocol could possibly have an
increased risk of injury due to high intensity and high volume combination. For example two
drop outs were seen due to injury in a high volume high intensity power lifting protocol.
(Schoenfeld et al 2014). Mechanical tension and metabolic stress can occur together so it can be
difficult to separate effects from each other. There may be a dose response with metabolic stress,
mechanical tension and hypertrophy where once certain intensity is reached there is no additive
20

effect, and no increased benefit of both. Volume and Intensity play a role in how much of each
mechanism is required. (Crewther et al. 2006; Kraemer et al. 1990; Mangine et al. 2015;
Mccaulley et al. 2009;Mithcell et al. 2012;Schoenfeld et al. 2014;Tanimoto et al. 2008)

Volume and Intensity are the most important variables to change in regards to metabolic
stress and mechanical tension. Volume is calculated as sets*reps*load, while intensity is a
percentage of 1 rep max. Typically metabolic stress programs have greater volume and lower
intensity, while mechanical tension programs have higher intensity and lower volume. There
appears to be a dose effect with volume increases result in increased hypertrophy until a certain
amount. Volume should be fairly high and total workload is important to stimulus. With intensity
it appears that the lower the intensity the greater the dependency on going to fatigue or failure in
order to achieve hypertrophic benefits. However it is important that going to failure is
periodized. Rest intervals of 30 seconds or less reduce performance in subsequent sets, and rest
intervals over 2 minutes have shown to allow too little metabolic stress. A rest interval for 60-90
seconds is shown to be effective for increasing muscle size. (Cadore et al.2014;Crewther et al.
2006; Kraemer et al. 1990; Mangine et al. 2010; Mccaulley et al. 2009;Mithcell et al. 2012;
Schoenfeld et al 2010;Schoenfeld et al. 2014;Tanimoto et al. 2008)

5.2 Limitations
Age

21

Decreased hypertrophic responses are seen with elderly and older people therefore
interventions done in young or middle age subjects may require different variables looked at, or
may not be effective with elderly. Applications of mechanisms with elderly would require more
studies completed with older subjects. (Mayer et al. 2011; Welle et al. 1996)
Genetics
Genetics may contribute significantly to muscle hypertrophy which may affect responses
to hypertrophy interventions and mechanisms. Genetics can contribute to responders and non
responders of hypertrophy. (Bamman et al. 2007; Hubal et al. 2005) Some individuals may
naturally show greater degrees of hypertrophy in development which continues, and genetic
factors can play a part in individual variability seen with hypertrophy seen even with an identical
protocol for all participants. (Puthucheary et al. 2011)
Individual Variation:
Individual Variation is seen with hypertrophy responders and non responders to certain
methods. It is difficult to prescribe one mechanism or protocol that will work with every single
person. (Martel et al. 2006; Prince et al. 1976)
Untrained Subjects
Most studies completed were on untrained subjects. Untrained subjects at first typically show
strength gains and virtually no hypertrophy due to adaptations being mostly neural. After this
untrained subjects typically respond to a multitude of stimuli, therefore some interventions may
work in untrained may not work in trained. Trained subjects typically require a greater stimulus
to create muscle size. This indicates difficulties in applying results from studies in untrained

22

subjects to trained populations. With the few studies that used trained subjects details about their
training programs beforehand are a limitation, as a change in program will typically lead to
results, so if the trained subjects intervention was similar vs different than their usual training
program it may influence results. (Ahtiainen et al. 2003; Mulligan et al. 1996; Sinha-Hikim et al.
2002)
Bodybuilder/Powerlifter Steroid Use
Typically bodybuilders and power lifters use steroids to further enhance their sports
(Schoenfeld et al. 2014). This affects their hormone level and improves their recovery with
resistance training, allowing for higher volumes to be used. Thus the protocols used in studies
may not directly apply to their training and hormone levels may make more significant
differences in bodybuilders with training that are not seen as much with trained/untrained
subjects. (Mangine et al.2015; Schoenfield et al. 2014b).
Study Length:
Studies used in this review were typically short term studies, some being cross sectional
at 1 time point. 10 of the 20 reviewed studies were completed in less than 10 weeks. Therefore it
is not known if results shown can be applied chronically in some cases. Shorter length studies
either may not be long enough to show hypertrophic improvements or the ones that show
improvements may be due to exposure of new stimuli and may not last. Hypertrophic effects
typically take a longer time to occur (4 vs. 8 vs. 12 vs. 16week studies). (Raudenbush et al 2001)
Measurements

23

Measures focused on this review were measurements of muscle thickness and size via
muscle cross sectional area. An issue with this may be the location of the muscle CSA
measurement taken on the body done by biopsies, MRI, and/or ultrasounds. For example some
full body protocols only measured the biceps or quadriceps. So applications from just these
smaller groups or isolated locations may not apply to the full body. Placement of the measure can
also be important for example Schoenfeld et al. (2014) took the biopsy of the midpoint in the
bicep, where it has been shown that distal and proximal may be more applicable. There is also an
unknown direct role of all endocrine responses/hormones to hypertrophy. (Durand 2003; Goto
2004)
Gender Differences
There are different hormone levels as well as physiological differences between males
and females. Most studies looked at have been with male participants only. The study that
included female participants showed a difference between females and males. Results of all
protocols from all male participants may not be completely applicable to females. (Mayer et al.
2011; Peterson et al.2010)
Resistance Variable Limitations
Volume & Intensity
It is expected that there will be variation in volume and intensity in order to manipulate
mechanical or metabolic stress so differences were expected between these protocols. However
metabolic stress and mechanical tension studies themselves greatly vary in these variables from
each other and there is no standard amount of volume or intensity in these studies between
protocols. It is difficult to standardize therefore, and when comparing metabolic stress to
24

mechanical tension it may be difficult to identify the exact metabolic/mechanical tension that is
effective. (Mangine et al. 2015; Mitchell et al. 2012; Schoenfeld et al. 2014;Tanimoto et al 2008)
Exercise Selection
There were a variety of exercises selected in different study protocols- some looked at
isolation exercises vs., some did fully body protocols. Comparing results it is important to note
that different exercises, amount of exercises, and routines may affect comparisons to other
programs. (Kraemer and Ratamess 2004; Schoenfeld et al. 2014)
Sample Size
Most study protocols had small sample sizes, this limits statistical power and effects may
not be as applicable to the population level for general recommendations.

Articles analyzed
Articles analyzed through pubmed, CINAHL, and SPORTsdiscus were of limited
quantity after search terms were put through, and many other references were gathered through
additional sources/reference lists. In future research on this topic it may be possible that many
articles look at metabolic or mechanical tension however do not have it in their title/abstract so a
different screening method can be considered.
Conclusion
Current research suggests that combinations of both mechanical and metabolic stress are
essential factors for hypertrophy. Training procedures should aim to create a significant amount

25

of metabolic stress, while maintaining moderate muscle tension. The rep range shown to be most
optimal is 6-12 with a moderate 60-90 second rest time with typically no less than 65% 1 RM
(moderate mechanical and moderate metabolic stress intensity). (Crewther et al. 2006; Kraemer
et al. 1990; Mangine et al. 2010; Mccaulley et al. 2009;Mithcell et al. 2012;Schoenfeld et al.
2014;Tanimoto et al. 2008). There appears to be a dose response with mechanical tension and
metabolic stress which has not been yet exactly defined and could be something to be further
looked into. Future research should aim to look at longer term studies in order to see chronic
adaptations, use trained participants, include both males and females, look at aged populations,
and account for previous training protocols in trained participants.

26

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