Brad Pilon

This is a review of

the collection of
the available research regarding
inflammation and muscle growth.

It is by no means complete or

conclusive, but rather a theory

based on my personal
interpretation of the available
evidence.

Finally, it should be obvious, but

just in case This document
should not be mistaken for
medical advice.

 Latin: inflammare, to set on fire

Two main types Acute and
Chronic

biological response to harmful

stimuli

removes the injurious stimuli and

initiates the healing process

Without inflammation, wounds

and infections would never heal

However, long term inflammation

is associated with disease.

 Other than the obvious health

reasons (prevention of disease),

inflammation plays an important
role in regulating muscle growth.

As this presentation will show, the

Signal and Noise theory of

inflammations role in regulating
muscle growth attempts to explain
how many lifestyle factors can
prevent optimal muscle growth.

Simply put the Inflammation

Theory of Muscle growth is as

follows:

The Inflammation Theory of Muscle

growth

Above: The Acute Inflammation Response to periods of

Resistance Training in a person with no chronic
Inflammation. The Spikes are large enough to initiate
muscle growth.
Below: The Same Acute Inflammation Response to periods
of Resistance Training in a person WITH chronic
inflammation. The Spikes are hidden by the noise and
thus muscle growth is not initiated.

 Chronic inflammation is the

bodys response to the chronic

harmful stimuli, such as excess
body fat or other chronic
metabolic insults.

Low grade chronic inflammation is

characterized by a 2 to 3 fold
increase in the systemic
concentrations of cytokines such
as TNF-alpha, IL-6 and CRP.
(Peterson 2005)

In the case of

Obesity the extra fat

is the harmful stimuli that is
causing the inflammation; our
bodies cannot get rid of the fat
with the inflammation response
and thus will stay inflamed as long
as the extra fat is still present.

 Cytokines are small cell-signaling

protein molecules

The term "cytokine" has been used

to refer to the immunomodulating
agents, such as interleukins and
interferons.

3 Common types: TNF-Alpha, IL-6

and CRP

TNF-Alpha is proposed as the

main driver of chronic low grade

inflammation (Brandt, 2010)

IL-6 increases several fold post-

exercise after exhaustive exercise

(Levinger, 2009)

C-Reactive Protein - acute-phase

protein, elevated in inflammation

and illnesses such as cancer

 This type of

prolonged whole body

(systemic) inflammation is
associated with many disease
states including:
Rheumatoid arthritis,

hypertension, atherosclerosis,
Fatty liver
Asthma
Insulin resistance and diabetes
Cardiovascular disease
Alzheimer Disease
And even the aging process
itself.

(Arend 2001; Bruunsgaard 2003;

Sriwijitkamol 2006; Schlitt
2004; Finch CE, 2007)

 Chronic Inflammation is a process

that seems to be an underlying
mechanism in many forms of
cancer (Bharat 2009; Aggarwal
BB, 2006)

Surprisingly, this inflammation-

cancer link was suggested as far

back as the late 1800s when
German Pathologist Rudolf
Virchow stated:

Chronic irritation which is

manifested by a chronic
inflammation is a key promoter
of cancer.

 Chronic inflammation is widely

observed in obesity (Kershaw,
2004).

The obese commonly have many

elevated markers of inflammation

including:

IL-6,
TNF-Alpha,
CRP,
Insulin,
Blood glucose,
Leptin
IL-18
(Loffreda S 1998; Esposito K
2002).

 Waist circumference significantly

influences the inflammatory
response. (Rogowksi, 2010)

Adipose tissue has been shown to

produce 10-35% of IL-6 in a

resting individual, and this
production increases with
increasing adiposity (Mohamed-Ali
V, 1997)

Thus there is a link between

increasing levels of obesity, and

increasing levels of inflammation.

 Hyperglycemia induces IL-6

production from endothelial cells

and macrophages. (Hotamisligil,
2006)

High Sat Fat containing meals and

even large mixed meals have also

been associated with increased
markers of inflammation
(Zimmerman MB 2008; Blackburn
P, 2006; Van Dijk SJ, 2009).

This is an acute response however

it may become chronic if the
overeating is chronic.

 The bodies response to insult and

injury

(Think Bee sting)

It Involves the mobilization of

Cytokines and other immune

molecules to protect the body.

Role of

acute inflammation is to
remove the injurious stimuli and
damaged tissue and to initiate the
healing process

From the available

research we know that

muscular contraction is
the signal for workinduced muscle growth.

This has been shown in

research using:
Cross Sectional Area
Fractional Synthetic
Rate
Amino Acid Markers
Increases in Muscular
Strength
Increases in Muscular
Weight

 There is a known relationship

between inflammation and muscle

growth. (Toth MJ, 2005)

Acute localized inflammation as a

response to muscular
contractions seems to be
necessary for muscle growth
(Marimuthu 2010).

Muscles can synthesize cytokines

in response to contractions (Lang
CH, 2003; Frost RA, 2002;
Pedersen BK 2009; Bruunsgaard
H. 1997 )

High doses of

anti-inflammatory
medicines are able to blunt
muscle growth (Mikkelsen UR,
2009; Trappe TA 2001.)

 The inflammation response plays

a role in the degeneration and

regeneration process of muscle
and surrounding connective tissue
after exercise induced muscle
damage.

As a response to muscular

contractions the acute

inflammatory response initiates
the breakdown and removal of
damaged muscle tissue (Cannon
J, 1998)

The Cytokines Il-1B and TNF-A

and IL-6 are expressed in skeletal

muscle up to 5 days after exercise
(Cannon J, 1989; Fielding R 1993)

 IL-6 is released by muscle cells as

a response to muscular
contraction. (Hiscock 2004)

This increase can be up to 100

fold above resting levels.
(Pedersen, 2009)

IL-6 responds differently to

different workloads and intensities

of training.

The IL-6 increase associated with

training increases about 4 hours
after resistance training and
remains elevated for up to 24
hours, but this seems to be
training protocol dependent
(volume, intensity etc) (Phillips,
2010; MacIntyre, 2001; Louis E,
2007)

 Satellite cells are crucial for

skeletal muscle adaption to

exercise. (Serrano AL, 2008)

They contribute to hypertrophy by

providing new myonuclei and
repair damaged segments of
mature myofibers for successful
regeneration following injury or
exercise induced muscle damage.
(Grounds MD, 2002; Hawke TJ
2005, Hawke TJ 2001)

High level power-lifters can have

up to 100% more satellite cells
than untrained controls (Kadi F
1977; Eriksson A, 2005)

 A rapid and transient localization

of the IL-6 receptor and increased

IL-6 expression occurs in satellite
cells following contractions
(McKay 2009)

IL-6 has been shown to mediate

hypertrophic muscle growth both

in vitro and in vivo (Serrano AL,
2008)

Unaccustomed exercise can

increase IL-6 by up to 6 fold at 5

hours post exercise and 3 fold 8
days after exercise (Mikkelssen UR
2010)

Non-Steroidal Anti-inflammatory

Drugs can decrease satellite cell

response to exercise (Mackey AL,
2007; Mikkelsen UR 2009) and
exercise induced protein synthesis
(Trappe TA, 2002)

 The increase in Cytokines after

resistance exercise coincides with

the decrease in myostatin levels.
(Louis E, 2007)

The cytokine response to

resistance exercise and running

occur differently with running
causing a more pronged response,
especially at the 12-24 hour mark
(Louis E, 2007)

 Even a small increase in chronic

inflammation can increase the risk

of muscle strength loss and cause a
decrease in your ability to build
muscle.

Chronic inflammation has been

implicated as part of the cause of

the muscle loss that occurs with
aging (sarcopenia). (Toth, 2005;
Visser M, 2002)

Increased protein levels of

myostatin have been described in

patients with diseases characterized
by chronic low-grade inflammation
(Reardon, 2001)

Increased levels of

TNF-Alfa can
suppress the AKT/mTOR pathway
and increase muscle catabolism
(Lang CH, 2007; Garcia-Martinez
1993; Jansen, 2005)

Cytokines may antagonize the

anabolic effects of IGF-1 (Frost RA

2007; Juraniski CV 1995)

 Sepsis is an extreme whole body

inflammatory state that is able to

inhibit the synthesis of both
myofibrillar and sarcoplasmic
proteins preferentially in muscles
composed of fast twitch fibers.
(Vary, 1992; Lang 2007)

Sepsis is able to prevent leucine

from stimulating muscle protein

synthesis (Lang 2005)

In animal models when

inflammation is created mTOR

loses its ability to be stimulated
by muscle growth (Lang, 2010)

 Chronic Exhaustive Exercise

(Gleeson M, 2006)

Stress (Carpenter LL, 2010)

Aging (Bruunsgaard, 2003;
Ershler, 2000, 1994)

Lack of
2010)

Sleep (Mullington JM,

Overeating (Vozarova B, 2001;

Esposito K, 2002)

Obesity (Monterio R, 2010;

Rogowski O, 2010; Loffreda S,

1998)

Above: The Acute Inflammation Response to periods of

Resistance Training in a person with no chronic
Inflammation. The Spikes a large enough to initiate
muscle growth.
Below: The Same Acute Inflammation Response to periods
of Resistance Training in a person WITH chronic
inflammation. The Spikes are hidden by the noise and
thus muscle growth is not initiated.

 Research has shown that there is a

strong trend towards reduced post

absorptive muscle protein
synthesis associate with aging.

Evidence suggests that this is

related to increased circulating

levels of inflammatory cytokines
TNF-Alpha, IL-6 and CRP (Toth MJ,
2005)

High levels of

circulating IL-6 can

predict muscle atrophy in the
elderly (Ferrucci L 2002; Payette
H 2003; Roubenoff R, 2003)

 There are as many as 100 original

scientific reports concerning
exercise and cytokines (Suzuki K,
2002)

There is a strong relationship

between exhaustive exercise and

chronic low grade inflammation
(Suzuki K, 2003)

Marathon running may enhance

IL-6 levels as much as 100 times

over normal and increases total
leuckocyte count and neturophil
mobilization. (Suzuki K, 2003)

 Regular physical activity is reported

to decrease markers of
inflammation. (Smith JK, 1999,
McFarlin BK 2005, Stewart LK,
2005)

Baseline measurements of

circulating inflammatory markers do

not seem to differ greatly between
healthy trained and untrained adults
(Gleeson M, 2006, Pedersen 2000)

However long-term chronic training

may help reduce chronic low grade
inflammation (Ploeger HE, 2009)

Levels of

inflammatory markers
(IL-6) remained elevated longer into
the recovery period following and
acute bout of exercise in patients
with inflammatory diseases as
opposed to healthy controls (Ploeger
HE, 2009)

 Low intensity training can reduce

resting pro-inflammatory markers

(CRP, IL-6)

Moderate exercise can have some

anti-inflammatory benefits.

Strenuous or exhaustive exercise

can increase inflammation.

(Niclas BJ, 2008;Timmerman KL,

2008; Gleeseon M, 2006;
Mackinnon LT 2000)

 Weight Loss achieved through

different diet programs in

combination with or without
exercise resulted in decreases of
markers of low grade
inflammation by 7 to 48%. (Basu,
2006)

Short term fasting may have anti-

inflammatory benefits (Varaday K,

2009)

Calorie restriction is anti-

inflammatory (Morgan TE 2007,

Fontana L 2009)

Weight loss is effective at reducing

inflammatory markers, specifically

IL-6 and Leptin (Reed JL, 2010)

 Testosterone injections result in

profound declines in markers of

inflammation (Glitay EJ, 2008)

Testosterone is able to suppress

the expression IL-6, IL-1B and

TNF-Alpha (Hatakeyama H, 2002;
Dagostino P 1999; Li ZG, 1993)

Testosterone can also stimulate

the production of antiinflammatory IL-10 (liva SM,
2001)

 Overeating has been purported to

add in the muscle building
process in young, non-steroid
using athletes.

However this effect seems to

decrease with time, leading to

speculation that the slow build up
of inflammation eventually
reaches a point where muscle
growth is blunted.

This time course would depend on

the degree of overeating and

speed of fat gain in the individual.

 Low grade chronic inflammation

brought about by any combination

of overeating, obesity, stress, lack
of sleep, aging, and exhaustive
exercise may blunt muscle growth
signals form both exercise and
diet

Decreasing chronic inflammation

may allow for a return to proper
anabolic signaling.

However, it seems wiping out

inflammation completely also

prevents the acute local
inflammation needed for muscle
growth (as evidenced by high does
NSAID Studies)

 Utilizing the signal/noise theory of

the role of inflammation in muscle

growth it seems very plausible
that the best course of action for
long term muscle growth is the
opposite of what we have been
lead to believe.

Keep Calories low, body fat low,

get lots of sleep, and avoid
excessive use of exhaustive
exercise for optimal muscle
growth and long term health.

Train consistently, and match

strenuous exercise with periods of

light exercise.

 References available at:

Inflammationtheory.com/references