Doug and said:

“I am not sure what to make of the study from the article about it. With 36 subjects total, it is unlikely to have enough statistical power to reach any conclusions. Their conclusion seems counter-intuitive to me. I will try to get the full text article to review.

Doug McGuff”

Doug,

I read the full text of the study when it was first published some time ago, although I can’t seem to find it at the moment (I have 3000+ studies on my hard drive). Strictly from my recollection, I was skeptical of the results immediately. Not only was it contradictory to almost all of the previously published data, but the delta between the control group and treatments groups were huge (60% greater CSA increase in the treatment groups). I’m not sure we would see such a difference with anabolic steroids and untrained subjects over that short of a time period.

My initial thoughts were that had it been so effective at protein accumulation, we would have seen athletes using these substances over anabolic steroids for years now. If such a simple over-the-counter compound produced such a remarked change in hypertrophic responses, it would be nearly impossible that the cat would not have gotten out of the bag.

Other studies show direct contrast to the result of this study. See the following:

“Inflammation that occurs after injury actually further degrades the tissue, but prevention of the inflammation leads to a long-term loss in muscle function.”

J Sci Med Sport 1999 Oct;2(3):253-65 Mechanisms of muscle injury after eccentric contraction. Lieber RL, Friden J.

Am J Physiol Regul Integr Comp Physiol 2002 Jan;282(1):R323-9
Adaptation to lengthening contractions is independent of voluntary muscle recruitment but relies on inflammation. Lapointe BM, Fremont P, Cote CH.

“The so-called cellular and connective tissue hypotheses state that adaptation proceeds from successful muscle repair and/or reorganization of several contractile and structural components such as the sarcomeres, the extracellular matrix, and the cytoskeleton, making the muscle less vulnerable to EIMD. The repair process is presumably partially dependent on the inflammatory response triggered by the initial mechanical damage. Generally, inflammation serves to remove damaged muscle tissue by recruiting neutrophils and macrophages, but it is also likely important for the processes governing muscle repair and/or reorganization after trauma. Neutrophils and ED1+ macrophages are the leukocytes recruited after most trauma in rats. However, in recent work from our laboratory, we showed that, in rats, neutrophil recruitment does not occur in EIMD. The resident ED2+ macrophages are believed to promote and assist the regeneration phase by influencing satellite cell proliferation and differentiation. Macrophages could also influence fibroblasts found in skeletal muscle as they can modulate their proliferation and rate of collagen synthesis. Interestingly, it was shown that macrophages can produce type I collagen. This fits elegantly with the proposal that synthesis of extracellular matrix and collagen in skeletal muscle can be part of the adaptive mechanism leading to a better resistance to lengthening contractions and somehow supports the idea that the inflammatory response is an interesting candidate that could be closely linked to the repeated bout effect.”

“The fact that diclofenac administration after the first bout resulted in a diminished concentration of both macrophage subpopulations probably led to an incomplete or slower removal of necrotic fibers by ED1+ macrophages, which could have significantly impaired and/or prolonged the repair phase necessary for the adaptive response. This lengthened time devoted to the repair and/or adaptive process would explain why ED2+ macrophage concentration was still elevated 14 days after the first bout in the treated groups. The postulated altered repair probably led to an incomplete or inadequate muscle adaptation compared with the untreated group based on the observation that muscles from the two treated groups were damaged by a second bout of lengthening contractions and that both subpopulations of macrophages increased again. Hence, our results support the idea that diclofenac treatment may interfere with the adaptive process in a treatment duration-dependent way.”

And.

“In summary, a potent adaptation to lengthening contractions was observed in an experimental model where voluntary control of skeletal muscle contractility by the nervous system was bypassed, which does not support the hypothesis that the repeated bout effect exclusively depends on adaptations of motor unit recruitment strategies. Treatment with diclofenac, a widely used non-steroidal anti-inflammatory drug (NSAID), affected in parallel the concentration of macrophage subpopulations and the adaptive response. These effects were particularly evident when administration was continued after the acute phase of the inflammatory reaction, likely reflecting an impairment of skeletal muscle repair and adaptation. As a whole, these results rather support the cellular and connective tissue hypotheses stating that repair or strengthening of the various muscle components is the basis for the repeated bout effect; it is also suggested that inflammation is likely a key element in this process.”

“The finding that inflammation is intimately implicated in the adaptive response to damaging contractions is in agreement with previous work showing that the inflammatory process is needed for regeneration of skeletal muscle.”

“It, for one, challenges the position that the acute inflammatory process must be repressed to favor recovery of form and function. Repeated use of anti-inflammatory drugs over extended periods covering the repair phase of muscle-tendon unit may not be appropriate in the context that some inflammatory components are needed for both repair and adaptation.”

“Thus inflammation should be seen as an integral and essential step of the repair and adaptive response of skeletal muscle to trauma.”

See also:

J Bone Joint Surg Am 1995 Oct;77(10):1510-9 Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function. Mishra DK, Friden J, Schmitz MC, Lieber RL.

“Early in the recovery period (at three days), significantly fewer fibers of the extensor digitorum longus (2.2 +/- 1.4 per cent) expressed embryonic myosin in the treated animals than in the untreated controls (11.8 +/- 1.9 per cent) (p < 0.001). However, at seven days, the expression of embryonic myosin by the muscles from the treated animals (19.5 +/- 11.9 per cent) actually exceeded that of the muscles from the untreated controls (16.2 +/- 4.1 per cent). This finding suggests either a delayed or an ineffectual regenerative response by the muscles in the treated animals.”

Even the molecular research demonstrates the importance of the inflammatory response.

J Appl Physiol 91: 2079-2087, 2001; 8750-7587/01 Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload Christian J. Carlson1,2, Zhiqiang Fan2, Scott E. Gordon2, and Frank W. Booth2

“Several investigators have observed muscle damage as well as cellular infiltration of overloaded skeletal muscle. Many stimuli are capable of activating the MAPKs. Notably, JNK and p38 MAPK, also described as stress-activated protein kinases, are known to be activated by numerous inflammatory cytokines as well as cytotoxic stimuli such as osmotic shock and oxidative damage… Although the presence of a local inflammatory response during hypertrophy complicates the interpretation, experimental evidence supports the speculation that the inflammatory response is a necessary component of muscle regeneration and hypertrophy. It has been proposed that repeated exposures to muscle damage, and subsequent regeneration, are a necessary component for muscle growth. Furthermore, macrophages, which are known to infiltrate overloaded skeletal muscle, are capable of releasing factors that can activate muscle satellite cells in vitro.”

There are a few more studies, but this should give you a start. Up until now the research has not been equivocal, and has been fairly conclusive concerning the role that the inflammatory response plays in the hypertrophic process. That being said, experimentation trumps all. I would like to see the study repeated with many more subjects, possibly controlling for genotype.


Ryan A. Hall



Joseph said:

“This is extremely interesting. Would the same be true of any anti-inflammatory- say, naproxen?? I have some clients taking naproxen for whatever reason (arthritis, etc). How much would you speculate it could interfere (in terms of results)?? Thanks.

Joseph”

Both maximal over-the-counter dosages of ibuprofen and acetaminophen show decreased 24 hour protein synthesis, largely thought to be influenced by the attenuation in increases in the prostaglandins. My speculation is that naproxen would have a similar effect.

See the following:

J Bone Joint Surg Am 1995 Oct;77(10):1510-9 Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function. Mishra DK, Friden J, Schmitz MC, Lieber RL

and

Am J Physiol Endocrinol Metab 282: E551-E556, 2002. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis T. A. Trappe, F. White, C. P. Lambert, D. Cesar, M. Hellerstein, and W. J. Evans

Ryan A. Hall

Tags: Inflammation, Muscle, Hypertrophy, Recovery, Microtrauma