Hypertrophy Mechanisms: Part 1

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Written by Stefan Ianev (Clean Health Research & Development Specialist)

In 2010, Brad Schoenfeld published a study titled ‘The Mechanisms of Muscle Hypertrophy and Their Application to Resistance Training’, which has since become one of the most cited studies on the topic of hypertrophy (1).

In the study, Schoenfeld proposed that there are 3 primary mechanisms for increasing muscle hypertrophy including: 

  1. Mechanical Tension
  2. Muscle Damage
  3. Metabolic Stress

This led to many theories by coaches and authors alike about how multiple rep ranges and training methods should be utilized to maximize hypertrophy by specifically targeting each of the pathways. For example, using heavy loads with long rest periods to increase mechanical tension, maximal eccentrics and loaded stretching to increase muscle damage, and higher repetitions with short rest periods to increase metabolic stress. 

However, more recent research seems to suggest that mechanical tension is the primary driver of muscle hypertrophy, while muscle damage and metabolic stress are indirect side effects.    

Some researchers have suggested that muscle damage contributes to muscle growth because the training methods that produce the most hypertrophy such as eccentric training also cause more muscle damage. Also, when muscles are damaged after strength training, this triggers a large increase in muscle protein synthesis and an increase in satellite cell activation.  

However, some researchers believe that muscle damage does not contribute to muscle growth and is just an unnecessary side-effect of strength training, rather than a contributing factor. 

This argument is based on the following evidence:

  • Exercise-induced muscle damage can cause muscle loss, rather than muscle gain (2).
  • The increase in muscle protein synthesis appears to be directed towards the repair of muscle damage rather than the growth of new muscle tissue (3). 
  • The superior effects of eccentric training are closely related to the greater mechanical tension that is produced (4).
  • The increase in satellite cell activation does not always convert to increased nuclei inside the muscle fibers but also plays a role in muscle repair (5).
  • The hypertrophic response to a workout is not blunted following an adaptation period whereby muscle damage is attenuated (6).
  • Prolonged, strenuous endurance exercise induces muscle damage and impairs muscle function without causing any hypertrophy (7).

As you can see, there is a high likelihood that muscle damage does not directly contribute to hypertrophy given the emerging evidence. In fact, excess muscle damage might actually be counterproductive if you end using up all your resources to repair damaged tissue rather than synthesising new tissue. 

Therefore, muscle damage is not something you should seek out on purpose. This is where lots of people make the mistake of trying to kill themselves in the gym every workout, and if they are not sore, they feel as though they did not have a good workout. Muscle soreness is not an indicator of a good workout. In fact, it may be best to start out with a lower workload and build up gradually, in order to keep muscle damage in check. The only indicator of a good workout is load or rep progression.

There is also evidence to suggest that metabolic stress does not contribute to muscle growth as we once thought. Metabolic stress is believed to contribute to muscle growth for several reasons including increased motor unit recruitment, systemic hormone release, and muscle cell swelling. 

However, acidosis and metabolite accumulation are not necessary to increase motor unit recruitment. Motor unit recruitment increases when there is a need to produce a greater effort (8). Whether that effort is needed to lift a heavier load, or to lift the same load under fatigue, the underlying mechanism that causes fatigue is irrelevant. 

Also, the role of post-exercise systemic hormone release has recently come into question, with some researchers speculating that the purpose of post-exercise hormonal elevations is to mobilize fuel stores rather than to promote tissue anabolism (9). In fact, studies have shown that longer rest periods are more effective for increasing hypertrophy, even though shorter rest periods are associated with greater systemic hormone release (10,11).

In addition, studies using blood flow restriction for 3-5 minutes post workout to increase metabolite accumulation have reported detrimental effects on hypertrophy (12,13). This suggests that metabolic stress does not cause hypertrophy in the absence of mechanical tension, and too much metabolic stress can be detrimental. This may be because metabolic stress stimulates the release of reactive oxygen species, causing oxidative stress, which has been linked to muscle damage (14,15). As we mentioned previously, excess muscle damage can impede hypertrophy.  

Now that we have made an argument for why muscle damage and metabolic stress don’t contribute to hypertrophy, that leaves us with mechanical tension. Mechanical tension is detected by mechanoreceptors which triggers the signalling cascade that leads to muscular hypertrophy. The mechanically induced conformational change of individual muscle fibers may directly activate downstream signalling and may trigger messenger systems to activate signalling indirectly (16).

It is important to note that mechanical tension doesn’t necessarily mean you need to lift heavy loads. There are several factors that affect the level of mechanical tension that is experienced by a muscle fiber which we will discuss in more detail in part 2 of this blog. 

To learn how to create results producing program design for clients from all walks of life to maximize results with fat loss, hypertrophy and body composition, click here to register for the Performance PT Coach Certification Level 1 online course!


  1. Foley JM, Jayaraman RC, Prior BM, Pivarnik JM, Meyer RA. MR measurements of muscle damage and adaptation after eccentric exercise. J Appl Physiol (1985). 1999 Dec;87(6):2311-8. doi: 10.1152/jappl.1999.87.6.2311. PMID: 10601183.
  1. Damas F, Phillips SM, Libardi CA, Vechin FC, Lixandrão ME, Jannig PR, Costa LA, Bacurau AV, Snijders T, Parise G, Tricoli V, Roschel H, Ugrinowitsch C. Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. J Physiol. 2016 Sep 15;594(18):5209-22. doi: 10.1113/JP272472. Epub 2016 Jul 9. PMID: 27219125; PMCID: PMC5023708.
  1. Ashida Y, Himori K, Tatebayashi D, Yamada R, Ogasawara R, Yamada T. Effects of contraction mode and stimulation frequency on electrical stimulation-induced skeletal muscle hypertrophy. J Appl Physiol (1985). 2018 Feb 1;124(2):341-348. doi: 10.1152/japplphysiol.00708.2017. Epub 2017 Oct 26. PMID: 29074713.
  1. Damas F, Libardi CA, Ugrinowitsch C, Vechin FC, Lixandrão ME, Snijders T, Nederveen JP, Bacurau AV, Brum P, Tricoli V, Roschel H, Parise G, Phillips SM. Early- and later-phases satellite cell responses and myonuclear content with resistance training in young men. PLoS One. 2018 Jan 11;13(1):e0191039. doi: 10.1371/journal.pone.0191039. 
  1. Flann KL, LaStayo PC, McClain DA, Hazel M, Lindstedt SL. Muscle damage and muscle remodeling: no pain, no gain? J Exp Biol. 2011 Feb 15;214(Pt 4):674-9. doi: 10.1242/jeb.050112. PMID: 21270317.
  1. de Morree HM, Klein C, Marcora SM. Perception of effort reflects central motor command during movement execution. Psychophysiology. 2012 Sep;49(9):1242-53. doi: 10.1111/j.1469-8986.2012.01399.x. Epub 2012 Jun 21. PMID: 22725828.
  1. Grobler LA, Collins M, Lambert MI, et alSkeletal muscle pathology in endurance athletes with acquired training intolerance. British Journal of Sports Medicine 2004;38:697-703.
  1. de Morree HM, Klein C, Marcora SM. Perception of effort reflects central motor command during movement execution. Psychophysiology. 2012 Sep;49(9):1242-53. doi: 10.1111/j.1469-8986.2012.01399.x. Epub 2012 Jun 21. PMID: 22725828.
  1. Schoenfeld BJ. Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design. J Strength Cond Res. 2013 Jun;27(6):1720-30. doi: 10.1519/JSC.0b013e31828ddd53. PMID: 23442269.
  1. Henselmans, M., Schoenfeld, B.J. The Effect of Inter-Set Rest Intervals on Resistance Exercise-Induced Muscle Hypertrophy. Sports Med. 2014;44, 1635–1643. https://doi.org/10.1007/s40279-014-0228-0
  1. McKendry J, Pérez‐López A, McLeod M, Luo D, Dent JR, Smeuninx B, Yu J, Taylor AE, Philp A, Breen L. Short inter‐set rest blunts resistance exercise‐induced increases in myofibrillar protein synthesis and intracellular signalling in young males. Exp Physiol. 2016;101: 866-882. doi:10.1113/EP085647
  1. Dankel SJ, Buckner SL, Jessee MB, Mattocks KT, Mouser JG, Counts BR, Laurentino GC, Abe T, Loenneke JP. Post-exercise blood flow restriction attenuates muscle hypertrophy. Eur J Appl Physiol. 2016 Oct;116(10):1955-63. doi: 10.1007/s00421-016-3447-2. Epub 2016 Aug 1. PMID: 27480315.
  1. Madarame H, Nakada S, Ohta T, Ishii N. Postexercise blood flow restriction does not enhance muscle hypertrophy induced by multiple-set high-load resistance exercise. Clin Physiol Funct Imaging. 2018 May;38(3):360-365. doi: 10.1111/cpf.12421. Epub 2017 Apr 27. PMID: 28448687.
  1. Uchiyama S, Tsukamoto H, Yoshimura S, Tamaki T. Relationship between oxidative stress in muscle tissue and weight-lifting-induced muscle damage. Pflugers Arch. 2006 Apr;452(1):109-16. doi: 10.1007/s00424-005-0012-y. Epub 2006 Jan 10. PMID: 16402246.
  1. Duarte JA, Appell HJ, Carvalho F, Bastos ML, Soares JM. Endothelium-derived oxidative stress may contribute to exercise-induced muscle damage. Int J Sports Med. 1993 Nov;14(8):440-3. doi: 10.1055/s-2007-1021207. PMID: 8300269.
  1. Burkholder TJ. Mechanotransduction in skeletal muscle. Front Biosci. 2007;12:174-191. Published 2007 Jan 1. doi:10.2741/2057

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