Sarcoplasmic Hypertrophy

Myth or Reality?
Haun et al., bioRxiv, April 2, 2019

James Krieger, M.S.

 Sarcoplasmic Hypertrophy
Haun et al., bioRxiv, April 2, 2019

• General consensus is that

muscle hypertrophy occurs
via accretion of myofibrillar
proteins at the cellular level
• Some studies challenge this
consensus
– Some studies show
decreases in myofibrillar area
despite increases in overall
muscle size
 Sarcoplasmic Hypertrophy
Haun et al., bioRxiv, April 2, 2019

• Evidence suggests that

muscle fiber growth may
also occur via sarcoplasmic
expansion
– Intracellular fluid
– Sarcoplasmic proteins
– Glycogen
 Sarcoplasmic Hypertrophy
Haun et al., bioRxiv, April 2, 2019

• How does high volume

training impact the
sarcoplasmic space?
 Sarcoplasmic Hypertrophy: Methods
Haun et al., bioRxiv, April 2, 2019

• 31 trained males engaged in 6-week high volume resistance

training program
– 3 days per week
– Squat, bench, SDL, under grip pulldown
– Exercises progressed from 10 sets per week to 32 sets per
week
– Sets of 10 at 60% 1-RM
• A subset of 15 subjects who experienced an increase in muscle
fiber cross-sectional area (fCSA, a measure of muscle fiber size)
were selected for this study
 Sarcoplasmic Hypertrophy: Methods
Haun et al., bioRxiv, April 2, 2019

• Measurements at pre-, 3 weeks, and 6 weeks

– Muscle fCSA
– Muscle glycogen (a carbohydrate stored in muscles)
– Muscle fluid content
– Sarcoplasmic protein concentration
– Myofibrillar protein concentrations (actin and myosin)
– Actin content per fiber
– Muscle citrate synthase activity (a marker of mitochondrial density)
– Muscle 20S proteasome activity and poly-ubiquinated protein levels
• Surrogate markers of protein breakdown
– Enzymes involved in glycolysis (breakdown of muscle glycogen for fuel) and ATP
generation (ATP is the molecular source of energy for your cells)
– Blood creatine kinase (an indirect marker of muscle breakdown)
• Subset of subjects were measured again at week 7 after no training
 Sarcoplasmic Hypertrophy: Results
Haun et al., bioRxiv, April 2, 2019

• From weeks 1 to 6:
– No significant changes in:
• Glycogen
• Fluid content
• Sarcoplasmic protein concentration, although it did increase numerically
• Actin content per fiber, although it did increase numerically

Muscle Glycogen (nmol/nmg Fluid Content (% weight) Sarcoplasmic Protein (ug/mg

wet weight) 76.5 76.2 dry weight)
8 76 250
196 194
5.77 75.5 200
6 74.8 159
75 150
4 3.5 74.5 74.2
2.5 100
74
2 50
73.5
0 73 0
Pre Week 3 Week 6 Pre Week 3 Week 6 Pre Week 3 Week 6
 Sarcoplasmic Hypertrophy: Results
Haun et al., bioRxiv, April 2, 2019

– Significant decreases in:

• Citrate synthase (24%), indicating
lower mitochondrial density
• Myofibrillar protein concentrations
(~30%)
• Actin content per fiber after
removal of an outlier
Citrate Synthase activity Myosin protein content Actin protein content (AU/mg
(mM/min/mg protein) (AU/mg dry muscle) dry muscle)
0.4 80 80
0.29 64.7 61.2
0.3 60 60
0.21 0.22 48.9 44.5 47.3 43
0.2 40 40
0.1 20 20
0 0 0
Pre Week 3 Week 6 Pre Week 3 Week 6 Pre Week 3 Week 6
 Sarcoplasmic Hypertrophy: Results
Haun et al., bioRxiv, April 2, 2019

• Tight relationship between fCSA and fiber actin content at week 0 and
3 (R2 = 0.82 to 0.87), but no significant relationship at week 6 (R2 =
0.16)
– This suggests there was a disproportionate increase in fCSA
relative to the actin content of the fiber (i.e., a dilution of fiber
actin content)
 Sarcoplasmic Hypertrophy: Results
Haun et al., bioRxiv, April 2, 2019

• No significant changes over 6 weeks in 20S proteasome activity, ubiquinated protein,

or creatine kinase
– Suggests there was little or no muscle damage
• Significant upregulation of enzymes associated with glycolysis and ATP generation

20S proteasome activity Ubiquinated protein (AU/15 ug

(RFU/40 ug input protein) input protein)
85 83 7.5 7.3
7.16
80
7
75 71
70 6.52
70
6.5
65
60 6
Pre Week 3 Week 6 Pre Week 3 Week 6
 Sarcoplasmic Hypertrophy: Results
Haun et al., bioRxiv, April 2, 2019

• 8-day detraining response Actin (AU/mg dry muscle)

– No significant change in fCSA 60

50.1
50
– Sarcoplasmic protein remained 40 33.7
25.8
elevated 30
20
– Myofibrillar protein concentration 10
trended downward 0
Pre Week 6 Week 7

fCSA at 10x (um^2) Sarcoplasmic protein (ug/mg Myosin (AU/mg dry muscle)
dry weight) 60
5000 4381 50.7
4095 300
4000 3605 242 50
250
40 33.7
3000 200 166 26.7
146 30
2000 150
100 20
1000 50 10
0 0 0
Pre Week 6 Week 7 Pre Week 6 Week 7 Pre Week 6 Week 7
 Sarcoplasmic Hypertrophy: Results
Haun et al., bioRxiv, April 2, 2019

Muscle glycogen (nmol/mg dry

• 8-day detraining response
weight)
– Citrate synthase activity remained lower 5.87
5.9
– Muscle fluid content trended downward, even though it did not increase in
the 6 weeks of training 5.8
– No significant changes in glycogen or markers of muscle breakdown 5.7
5.6 5.6
Muscle fluid content (% 5.6
Citrate synthase activity
weight) 5.5
(mM/min/mg protein)
80 5.4
0.4 78.2
0.3 78 Pre Week 6 Week 7
0.3 0.24
0.23 76 74.7 Muscle glycogen (nmol/mg dry
0.2 73.8 weight)
74
5.9 5.87
0.1 72
5.8
70
0
Pre Week 6 Week 7 5.7
Pre Week 6 Week 7 5.6 5.6
5.6
5.5
5.4
Pre Week 6 Week 7
 Sarcoplasmic Hypertrophy: Discussion &
Implications
Haun et al., bioRxiv, April 2, 2019

• This study showed 6 weeks of high volume

training to cause a decrease in myofibrillar
protein concentration despite increases in
muscle fiber size
– The decrease in concentration was not due to less
fibers, but rather a dilution of existing fibers
• There was also a dilution of mitochondrial content
• Markers of muscle protein breakdown were not changed
– Sarcoplasmic proteins tended to increase
 Sarcoplasmic Hypertrophy: Discussion &
Implications
Haun et al., bioRxiv, April 2, 2019

• The results suggest that the observed

hypertrophy was primarily due to sarcoplasmic
expansion
• This expansion seemed to persist for up to 8
days after the last training session
 Sarcoplasmic Hypertrophy: Why Might It
Occur?
Haun et al., bioRxiv, April 2, 2019

• High volume training may promote sarcoplasmic

expansion to create enough space for cells to
eventually expand the amount of myofibrillar
proteins
• The increase in enzymes involved in ATP
generation may help satisfy the high energy
demands of adding more myofibrillar proteins
– Adding new myofibrillar protein is an energy-costly
process and requires a lot of ATP
 Sarcoplasmic Hypertrophy: Bodybuilders &
Specific Tension
Haun et al., bioRxiv, April 2, 2019

• Sarcoplasmic hypertrophy may explain why

bodybuilders have lower specific tension in
individual muscle fibers (maximum force
produced by a fiber normalized to its size)
compared to powerlifters or controls
Sarcoplasmic Hypertrophy: High Load vs. Low
Load Training
Haun et al., bioRxiv, April 2, 2019

• While low load training has been shown to stimulate similar hypertrophy to high load training,
these conclusions are based on measurements of muscle size (like muscle thickness) that do not
account for whether the hypertrophy is due to an increase in myofibrillar proteins, sarcoplasmic
proteins, or connective tissue
– Evidence for a difference
• High load training causes greater increases in 1-RM than low load training, perhaps due
to proportional increases in myofibrillar proteins and fCSA
– No research has compared myofibrillar protein accretion between high load and
low load training
• While this is related more to set volume rather than training load, some research has
shown similar strength gains but different hypertrophy with different training volumes
– Evidence against a difference
• Changes in isometric force production tend to be similar between high load and low
load training
• Low load training causes significantly greater increases in myofibrillar protein synthesis
compared to high load training
 Sarcoplasmic Hypertrophy: Limitations
Haun et al., bioRxiv, April 2, 2019

• Muscle biopsies were taken 24 hours after last

training bout
– It is possible that some muscle damage or edema
may have influenced results
• Evidence against edema:
– Fluid levels remained the same over 6 weeks
– Other studies have shown that higher volume training promotes
sarcoplasmic hypertrophy
 Sarcoplasmic Hypertrophy: Limitations
Haun et al., bioRxiv, April 2, 2019

• Small sample size

• No low volume comparison group
• Low fCSA responders were not analyzed to the
same degree relative to the high responders,
although there was a tendency for the same
things to happen in that group
– Increase in sarcoplasmic proteins
– Decrease in myofibrillar protein concentration
 Sarcoplasmic Hypertrophy:
Conclusions/Application
Haun et al., bioRxiv, April 2, 2019

• High volume training may cause sarcoplasmic

hypertrophy over the short-term
– This effect persists for up to 8 days after training
– This may act to prepare a muscle for increases in
myofibrillar protein concentrations
• While speculative, this lends credence to the idea of
cycling training volume over time
– High volume cycle: Sarcoplasmic hypertrophy/prep for
myofibrillar expansion
– Low volume cycle: Myofibrillar expansion/recovery