Brad Pilon

This is a review of

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

It is by no means complete or

 Latin: inflammare, to set on fire Two main types Acute and

Chronic stimuli

biological response to harmful removes the injurious stimuli and

initiates the healing process

Without inflammation, wounds

and infections would never heal is associated with disease.

However, long term inflammation

 Other than the obvious health

reasons (prevention of disease), inflammation plays an important role in regulating muscle growth. Signal and Noise theory of inflammations role in regulating muscle growth attempts to explain how many lifestyle factors can prevent optimal muscle growth. Theory of Muscle growth is as follows:

As this presentation will show, the

Simply put the Inflammation

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

Low grade chronic inflammation is

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. and CRP

3 Common types: TNF-Alpha, IL-6 TNF-Alpha is proposed as the

main driver of chronic low grade inflammation (Brandt, 2010) exercise after exhaustive exercise (Levinger, 2009) protein, elevated in inflammation and illnesses such as cancer

IL-6 increases several fold post-

C-Reactive Protein - acute-phase

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

elevated markers of inflammation including:

 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) increasing levels of obesity, and increasing levels of inflammation.

Thus there is a link between

 Hyperglycemia induces IL-6

production from endothelial cells and macrophages. (Hotamisligil, 2006) even large mixed meals have also been associated with increased markers of inflammation (Zimmerman MB 2008; Blackburn P 2006; Van Dijk SJ, 2009). , it may become chronic if the overeating is chronic.

High Sat Fat containing meals and

This is an acute response however

 The bodies response to insult and

injury (Think Bee sting)

It Involves the mobilization of Role of

Cytokines and other immune molecules to protect the body. 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. research using: Cross Sectional Area Fractional Synthetic Rate Amino Acid Markers Increases in Muscular Strength Increases in Muscular Weight

This has been shown in

 There is a known relationship

between inflammation and muscle growth. (Toth MJ, 2005) response to muscular contractions seems to be necessary for muscle growth (Marimuthu 2010).

Acute localized inflammation as a

Muscles can synthesize cytokines

in response to contractions (Lang CH, 2003; Frost RA, 2002; Pedersen BK 2009; Bruunsgaard H. 1997 ) anti-inflammatory medicines are able to blunt muscle growth (Mikkelsen UR, 2009; Trappe TA 2001.)

High doses of

 The inflammation response plays

a role in the degeneration and regeneration process of muscle and surrounding connective tissue after exercise induced muscle damage. contractions the acute inflammatory response initiates the breakdown and removal of damaged muscle tissue (Cannon J, 1998) and IL-6 are expressed in skeletal muscle up to 5 days after exercise (Cannon J, 1989; Fielding R 1993)

As a response to muscular

The Cytokines Il-1B and TNF-A

 IL-6 is released by muscle cells as

a response to muscular contraction. (Hiscock 2004) fold above resting levels. (Pedersen, 2009)

This increase can be up to 100 IL-6 responds differently to

different workloads and intensities of training. 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)

The IL-6 increase associated with

 Satellite cells are crucial for

skeletal muscle adaption to exercise. (Serrano AL, 2008) 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) up to 100% more satellite cells than untrained controls (Kadi F 1977; Eriksson A, 2005)

They contribute to hypertrophy by

High level power-lifters can have

 A rapid and transient localization

of the IL-6 receptor and increased IL-6 expression occurs in satellite cells following contractions (McKay 2009) hypertrophic muscle growth both in vitro and in vivo (Serrano AL, 2008) increase IL-6 by up to 6 fold at 5 hours post exercise and 3 fold 8 days after exercise (Mikkelssen UR 2010) Drugs can decrease satellite cell response to exercise (Mackey AL, 2007; Mikkelsen UR 2009) and exercise induced protein synthesis (Trappe TA, 2002)

IL-6 has been shown to mediate

Unaccustomed exercise can

Non-Steroidal Anti-inflammatory

 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. implicated as part of the cause of the muscle loss that occurs with aging (sarcopenia). (Toth, 2005; Visser M, 2002) myostatin have been described in patients with diseases characterized by chronic low-grade inflammation (Reardon, 2001) TNF-Alfa can suppress the AKT/mTOR pathway and increase muscle catabolism (Lang CH, 2007; Garcia-Martinez 1993; Jansen, 2005) anabolic effects of IGF-1 (Frost RA 2007; Juraniski CV 1995)

Chronic inflammation has been

Increased protein levels of

Increased levels of

Cytokines may antagonize the

 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) from stimulating muscle protein synthesis (Lang 2005) inflammation is created mTOR loses its ability to be stimulated by muscle growth (Lang, 2010)

Sepsis is able to prevent leucine In animal models when

 Chronic Exhaustive Exercise

(Gleeson M, 2006)

Stress (Carpenter LL, 2010) Aging (Bruunsgaard, 2003;

Ershler, 2000, 1994) 2010)

Lack of

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. related to increased circulating levels of inflammatory cytokines TNF-Alpha, IL-6 and CRP (Toth MJ, 2005) circulating IL-6 can predict muscle atrophy in the elderly (Ferrucci L 2002; Payette H 2003; Roubenoff R, 2003)

Evidence suggests that this is

High levels of

 There are as many as 100 original

scientific reports concerning exercise and cytokines (Suzuki K, 2002) between exhaustive exercise and chronic low grade inflammation (Suzuki K, 2003) IL-6 levels as much as 100 times over normal and increases total leuckocyte count and neturophil mobilization. (Suzuki K, 2003)

There is a strong relationship

Marathon running may enhance

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

However long-term chronic training 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) , anti-inflammatory benefits.

Moderate exercise can have some 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) inflammatory benefits (Varaday K, 2009) inflammatory (Morgan TE 2007, Fontana L 2009) inflammatory markers, specifically IL-6 and Leptin (Reed JL, 2010)

Short term fasting may have anti Calorie restriction is anti-

Weight loss is effective at reducing

 Testosterone injections result in

profound declines in markers of inflammation (Glitay EJ, 2008) the expression IL-6, IL-1B and TNF-Alpha (Hatakeyama H, 2002; Dagostino P 1999; Li ZG, 1993) the production of antiinflammatory IL-10 (liva SM, 2001)

Testosterone is able to suppress

Testosterone can also stimulate

 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. the degree of overeating and speed of fat gain in the individual.

This time course would depend on

 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 may allow for a return to proper anabolic signaling.

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

Keep Calories low, body fat low,

Train consistently, and match

strenuous exercise with periods of light exercise.

 References available at:

Inflammationtheory.com/references