Mechanisms of Hypertrophy

Individuals might be training for the improvement of sports performance measures or for the benefits of their own health but in both situations, resistance training should play an important part in achieving these aims.

Resistance training can result in increased functional strength, the stabilisation of joints and improved posture, increases in power output and increases in bone mineral density all of which, to some degree, rely on an increase in muscle mass, a process known as hypertrophy. While mechanisms other than hypertrophy also contribute to increases in strength, the muscle's ability to produce force clearly increases as it's cross-sectional area becomes greater (Ikai and Fukunaga,1968).

In order to be effective in programming activities that induce muscular hypertrophy, it’s key to first understand the mechanisms by which hypertrophy occurs. It’s been suggested that they fall broadly into 3 categories; mechanical tension, exercise induced muscular damage and metabolic stress.

This page gives a brief overview of these mechanisms for those that are keen exercisers or early career fitness professionals but also contains links to further, more detailed sources of information for those that are studying this area in greater depth.

Once you've read this page you might like to read the accompanying page on neuromuscular factors.

1. Mechanical Tension

Mechanical tension has been suggested as the primary driver for training induced muscular hypertrophy and results from performing a movement that requires some form of muscular contraction.

Increased mechanical resistance disturbs the structure of skeletal muscle, and causes signals to be sent to the muscle fibres and cells to repair themselves and become stronger by favouring synthesis instead of breakdown. A series of events then follow this signalling process with, for example, increased levels of growth hormone being released. The mechanosensors responsible for initiating the signalling process are sensitive to both magnitude and duration of loading which has implications for the optimisation of training protocols.

Although mechanical tension alone can result in hypertrophy, some training protocols that predominantly employ large amounts of mechanical tension have been shown to induce neural adaptations rather than hypertrophic ones i.e. the participants became stronger without necessarily developing more muscle fibres. While this situation may be desirable in some cases, it places a limit on the potential for development as strength is largely related to the cross-sectional area of the muscles.

See Fry et al (2004) for more on the role of loading on muscle adaptations

For more on the biology of hypertrophy including cellular and molecular mechanisms see Spiering, et al. (2008), Schiaffino et al. (2020).

2. Muscle Damage

Intense exercise, particularly if novel or at an unaccustomed intensity, can cause damage to skeletal muscle. Anyone that’s performed a vigorous exercise for the first time (e.g. ridden a horse, completed a hard plyometric session or a long run) will have experienced the sensation of Delayed Onset Muscle Soreness (DOMS). DOMS along with muscular stiffness, swelling and reduced force-producing capacity are all symptoms of excessive Exercise Induced Muscle Damage (EIMD) which can in turn affect the ability to train at a high level. It’s worth noting at this point though that DOMS is a complex phenomenon and while linked to EIMD and micro-trauma, it has also been linked to inflammation, enzyme efflux, connective tissue damage, muscle spasm and lactic acid accumulation.

For hypertrophy to occur however, EIMD does not have to be so severe that it’s accompanied by DOMS. Although levels of EIMD have been shown to be a key factor in optimising hypertrophy, research has shown that excessive EIMD can be detrimental to hypertrophy for a number of reasons.

EIMD is influenced by the type of muscular action that is being executed and although concentric and isometric exercise can cause EIMD, eccentric exercise will be most likely to cause EIMD.

With regular exposure to a particular activity or exercise the likelihood of muscular microtrauma (EIMD) and particularly the symptoms of more severe damage like DOMS, are decreased. This is known as the repeated bout effect and knowledge of its existence can be useful in supporting those new to exercise but also help us appreciate the need for appropriately periodised and progressive programmes for more experienced trainers.

See Schoenfeld (2012), Schoenfeld and Contreras (2013) and Damas et al (2018) for more on EIMD.

3. Metabolic Stress

While it's important to lift heavy weights (at least in relation to an individual’s capabilities) so that appropriate levels of mechanical tension and exercise-induced muscle damage are created, it's also important that the environment in which the muscle operates and recovers is optimised for muscle growth. A resistance training protocol that utilises moderate to high loads, moderate to high reps and short recovery periods will create an exercise-induced accumulation of metabolites such as lactate, inorganic phosphates and H+ and this is known as metabolic stress.

Hypertrophic adaptations from exercise-induced metabolic stress include mechanisms related to increased fibre recruitment, elevated systemic hormonal production, alterations in local myokines, heightened production of reactive oxygen species (ROS) and cellular swelling.

The process of metabolic stress is that which underpins Blood Flow Restriction (BFR) training and hypoxic resistance training, both of which seek to create heightened levels of ischemia in the working muscle as they contract. For more on BFR see Loenneke et al (2014) and for more on hypoxic training see Scott et al (2015).

See Schoenfeld (2013) for more on metabolic stress

If you only read one article

Schoenfeld, B. J. (2010). The mechanisms of muscle hypertrophy and their application to resistance training. The Journal of Strength & Conditioning Research, 24(10), 2857-2872. https://doi.org/10.1519/jsc.0b013e3181e840f3 [www]

Key Contemporary Guidelines

Schoenfeld, B., & Grgic, J. (2017). Evidence-Based Guidelines for Resistance Training Volume to Maximize Muscle Hypertrophy. Strength & Conditioning Journal. doi: 10.1519/SSC.0000000000000363 [www]

A Recent Paper

Lim, C., Nunes, E. A., Currier, B. S., Mcleod, J. C., Thomas, A. C., & Phillips, S. M. (2022). An Evidence-based Narrative Review of Mechanisms of Resistance Exercise-induced Human Skeletal Muscle Hypertrophy. Medicine & Science in Sports & Exercise, 10-1249. https://doi.org/10.1249/mss.0000000000002929

If you want to watch a video

If you want to buy a book

References and Further Reading

Balshaw, T. G., Massey, G. J., Maden-Wilkinson, T. M., Morales-Artacho, A. J., McKeown, A., Appleby, C. L., & Folland, J. P. (2017). Changes in agonist neural drive, hypertrophy and pre-training strength all contribute to the individual strength gains after resistance training. European journal of applied physiology, 117(4), 631-640. https://doi.org/10.1007/s00421-017-3560-x

Beardsley, C. (n.d.) Hypertrophy Mechanisms www.strengthandconditioningresearch.com/hypertrophy/hypertrophy-mechanisms/

Brentano, M. A., & Martins Kruel, L. F. (2011). A review on strength exercise-induced muscle damage: applications, adaptation mechanisms and limitations. J Sports Med Phys Fitness, 51(1), 1-10. [abstract]

Buckner, S. L., Jessee, M. B., Mouser, J. G., Dankel, S. J., Mattocks, K. T., Bell, Z. W., ... & Loenneke, J. P. (2019). The Basics of Training for Muscle Size and Strength: A Brief Review on the Theory. Medicine and Science in Sports and Exercise. https://doi.org/10.1249/MSS.0000000000002171

Bush-Joseph, C. A. (2012). Muscle Soreness and Delayed-Onset Muscle Soreness. Clin Sports Med, 31, 255-262.[abstract]

Carvalho, L. H. F., Junior, R. M., Barreira, J., Schoenfeld, B. J., Orazem, J., & Barroso, R. (2022). Muscle hypertrophy and strength gains after resistance training with different volume matched loads: a systematic review and meta-analysis. Applied Physiology, Nutrition, and Metabolism, 47(4) https://doi.org/10.1139/apnm-2021-0515

Chapman, D., Newton, M., Sacco, P., & Nosaka, K. (2006). Greater muscle damage induced by fast versus slow velocity eccentric exercise. International Journal of Sports Medicine, 27(08), 591-598. https://doi.org/10.1055/s-2005-865920

Clarkson, P. M., & Hubal, M. J. (2002). Exercise-induced muscle damage in humans. American Journal of Physical Medicine & Rehabilitation, 81(11), S52-S69.[abstract]

Damas, F., Libardi, C. A., & Ugrinowitsch, C. (2018). The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis. European journal of applied physiology, 118(3), 485-500. https://doi.org/10.1007/s00421-017-3792-9

Dankel, S. J., Mattocks, K. T., Jessee, M. B., Buckner, S. L., Mouser, J. G., Counts, B. R., ... & Loenneke, J. P. (2017). Frequency: the overlooked resistance training variable for inducing muscle hypertrophy?. Sports Medicine, 47(5), 799-805. https://doi.org/10.1007/s40279-016-0640-8

Davies, T., Halaki, M., Orr, R., Mitchell, L., Helms, E., Clarke, J., Hackett, D. (2021) Effect of Set-Structure on Upper-Body Muscular Hypertrophy and Performance in Recreationally-Trained Male and Female, Journal of Strength and Conditioning Research doi: 0.1519/JSC.00000000000039

de Salles, B. F., Simao, R., Miranda, F., da Silva Novaes, J., Lemos, A., & Willardson, J. M. (2009). Rest interval between sets in strength training. Sports Medicine, 39(9), 765-777. https://doi.org/10.2165/11315230-000000000-00000

Feriche, B., García-Ramos, A., Morales-Artacho, A. J., & Padial, P. (2017). Resistance Training Using Different Hypoxic Training Strategies: a Basis for Hypertrophy and Muscle Power Development. Sports Medicine-Open, 3(1), 12.

Folland, J. P., & Williams, A. G. (2007). Morphological and neurological contributions to increased strength. Sports Medicine, 37(2), 145-168. https://doi.org/10.2165/00007256-200737020-00004

Fry, A. C. (2004). The role of resistance exercise intensity on muscle fibre adaptations. Sports Medicine, 34(10), 663-679. https://doi.org/10.2165/00007256-200434100-00004

Grgic, J., Schoenfeld, B. J., Orazem, J. & Sabol, F. (2021) Effects of resistance training performed to repetition failure or non-failure on muscular strength and hypertrophy: a systematic review and meta-analysis Journal of Sport and Health Science https://doi.org/10.1016/j.jshs.2021.01.007

Haun, C. T., Vann, C. G., Roberts, B. M., Vigotsky, A. D., Schoenfeld, B. J., & Roberts, M. D. (2019). A critical evaluation of the biological construct skeletal muscle hypertrophy: size matters but so does the measurement. Frontiers in Physiology, 10. https://doi.org/10.3389/fphys.2019.00247

Hody, S., Croisier, J. L., Bury, T., Rogister, B., & Leprince, P. (2019). Eccentric muscle contractions: risks and benefits. Frontiers in Physiology, 10, 536. https://doi.org/10.3389/fphys.2019.00536

Hornberger, T. A. (2011). Mechanotransduction and the regulation of mTORC1 signaling in skeletal muscle. The international journal of biochemistry & cell biology, 43(9), 1267-1276. https://doi.org/10.1016/j.biocel.2011.05.007

Howe, L. P., Read, P., & Waldron, M. (2017). Muscle hypertrophy: A narrative review on training principles for increasing muscle mass. Strength & Conditioning Journal, 39(5), 72-81. doi: 10.1519/SSC.0000000000000330

Ikai, M., & Fukunaga, T. (1968). Calculation of muscle strength per unit cross-sectional area of human muscle by means of ultrasonic measurement. Internationale Zeitschrift für Angewandte Physiologie Einschliesslich Arbeitsphysiologie, 26(1), 26-32.

Kraemer, W. J., & Ratamess, N. A. (2005). Hormonal responses and adaptations to resistance exercise and training. Sports Medicine, 35(4), 339-361.

Krzysztofik, M., Wilk, M., Wojdała, G., & Gołaś, A. (2019). Maximizing muscle hypertrophy: a systematic review of advanced resistance training techniques and methods. International journal of environmental research and public health, 16(24), 4897. https://dx.doi.org/10.3390%2Fijerph16244897

Lewis, P. B., Ruby, D., & Bush-Joseph, C. A. (2012). Muscle soreness and delayed-onset muscle soreness. Clinics in Sports Medicine, 31(2), 255-262. [abstract]

Loenneke, J. P., Wilson, G. J., & Wilson, J. M. (2010). A mechanistic approach to blood flow occlusion. International Journal of Sports Medicine, 31(01), 1-4.

Loenneke, J. P., Buckner, S. L., Dankel, S. J., & Abe, T. (2019). Exercise-induced changes in muscle size do not contribute to exercise-induced changes in muscle strength. Sports Medicine, 1-5. https://doi.org/10.1007/s40279-019-01106-9 [See Taber et al below for counterpoint]

Loenneke, J. P., Dankel, S. J., Bell, Z. W., Buckner, S. L., Mattocks, K. T., Jessee, M. B., & Abe, T. (2019). Is muscle growth a mechanism for increasing strength?. Medical hypotheses, 125, 51-56. https://doi.org/10.1016/j.mehy.2019.02.030

Lopez, P., Radaelli, R., Taaffe, D. R., Newton, R. U., Galvão, D. A., Trajano, G. S., Teodoro, J., Kraemer, W. J., Häkkinen, K., & Pinto, R. S. (2020). Resistance Training Load Effects on Muscle Hypertrophy and Strength Gain: Systematic Review and Network Meta-analysis. Medicine and science in sports and exercise, https://doi.org/10.1249/MSS.0000000000002585

McHugh, M. P. (2003). Recent advances in the understanding of the repeated bout effect: the protective effect against muscle damage from a single bout of eccentric exercise. Scandinavian Journal of Medicine & Science in Sports, 13(2), 88-97.

McKendry, J., Pérez‐López, A., McLeod, M., Luo, D., Dent, J. R., Smeuninx, B., ... & Breen, L. (2016). Short inter‐set rest blunts resistance exercise‐induced increases in myofibrillar protein synthesis and intracellular signalling in young males. Experimental physiology, 101(7), 866-882. https://doi.org/10.1113/EP085647

Morton, R. W., Colenso-Semple, L., & Phillips, S. M. (2019). Training for Strength and Hypertrophy: An Evidence-based Approach. Current Opinion in Physiology. https://doi.org/10.1016/j.cophys.2019.04.006

Morton, R. W., Oikawa, S. Y., Wavell, C. G., Mazara, N., McGlory, C., Quadrilatero, J., ... & Phillips, S. M. (2016). Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men. Journal of applied physiology, 121(1), 129-138. http://dx.doi.org/10.1136/bjsports-2017-097608

Muscle and Sport Science (M.A.S.S.) (2012) The role of muscle damage in hypertrophy http://muscleandsportsscience.com/the-role-of-muscle-damage-in-hypertrophy/

Nosaka, K., Lavender, A., Newton, M., & Sacco, P. (2003). Muscle damage in resistance training: Is muscle damage necessary for strength gain and muscle hypertrophy? International Journal of Sport and Health Science, 1(1), 1-8.

Phillips, S. M. (2014). A brief review of critical processes in exercise-induced muscular hypertrophy. Sports Medicine, 44(1), 71-77. https://doi.org/10.1007/s40279-014-0152-3

Roberts, M. D., Haun, C. T., Vann, C. G., Osburn, S. C., & Young, K. C. (2020). Sarcoplasmic hypertrophy in skeletal muscle: A scientific “unicorn” or resistance training adaptation?. Frontiers in Physiology, 11, 816. https://doi.org/10.3389/fphys.2020.00816

Sartori, R., Romanello, V. & Sandri, M. (2021) Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun 12, 330 https://doi.org/10.1038/s41467-020-20123-1

Scarpelli, M. C., Nóbrega, S. R., Santanielo, N., Alvarez, I. F., Otoboni, G. B., Ugrinowitsch, C., & Libardi, C. A. (2020). Muscle hypertrophy response is affected by previous resistance training volume in trained individuals. J Strength Cond Res, 27. https://doi.org/10.1519/jsc.0000000000003558

Schiaffino, S., Reggiani, C., Akimoto, T., & Blaauw, B. (2020). Molecular Mechanisms of Skeletal Muscle Hypertrophy. Journal of Neuromuscular Diseases, (Preprint), 1-15. https://doi.org/10.3233/jnd-200568

Schoenfeld, B., & Grgic, J. (2017). Evidence-Based Guidelines for Resistance Training Volume to Maximize Muscle Hypertrophy. Strength & Conditioning Journal.doi: 10.1519/SSC.0000000000000363

Schoenfeld, B. J., & Grgic, J. (2019). Does training to failure maximize muscle hypertrophy?. Strength & Conditioning Journal, 41(5), 108-113. https://journals.lww.com/nsca-scj/Abstract/2019/10000/Does_Training_to_Failure_Maximize_Muscle.14.aspx

Schoenfeld, B. J. (2013). Potential mechanisms for a role of metabolic stress in hypertrophic adaptations to resistance training. Sports Medicine, 43(3), 179-194.

Schoenfeld, B. J. (2012). Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy?. The Journal of Strength & Conditioning Research, 26(5), 1441-1453. [abstract]

Schoenfeld, B. J., & Contreras, B. (2013). Is postexercise muscle soreness a valid indicator of muscular adaptations?. Strength & Conditioning Journal, 35(5), 16-21. doi: 10.1519/SSC.0b013e3182a61820

Schoenfeld, B. J., Grgic, J., Ogborn, D., & Krieger, J. W. (2017). Strength and hypertrophy adaptations between low-vs. high-load resistance training: a systematic review and meta-analysis. The Journal of Strength & Conditioning Research, 31(12), 3508-3523. https://doi.org/10.1519/jsc.0000000000002200

Schroeder, E. T., Villanueva, M., West, D. D., & Phillips, S. M. (2013). Are acute post-resistance exercise increases in testosterone, growth hormone, and IGF-1 necessary to stimulate skeletal muscle anabolism and hypertrophy?. Medicine and science in sports and exercise, 45(11), 2044–2051. https://doi.org/10.1249/MSS.0000000000000147

Scott, B. R., Slattery, K. M., & Dascombe, B. J. (2015). Intermittent hypoxic resistance training: Is metabolic stress the key moderator?. Medical Hypotheses, 84(2), 145-149.

Shaw, B. S., Shaw, I., & Brown, G. A. (2015). Resistance exercise is medicine: Strength training in health promotion and rehabilitation. International Journal of Therapy and Rehabilitation, 22(8), 385-389.

Smilios, I., Pilianidis, T., Karamouzis, M., & Tokmakidis, S. P. (2003). Hormonal responses after various resistance exercise protocols. Medicine and Science in Sports and Exercise, 35(4), 644.

Spiering, B. A., Kraemer, W. J., Anderson, J. M., Armstrong, L. E., Nindl, B. C., Volek, J. S., & Maresh, C. M. (2008). Resistance exercise biology: Manipulation of Resistance Exercise Programme Variables Determines the Responses of Cellular and Molecular Signalling Pathways. Sports Medicine, 38(7), 527-540. http://dx.doi.org/10.2165/00007256-200838070-00001

Taber, C. B., Vigotsky, A., Nuckols, G., & Haun, C. T. (2019). Exercise-induced myofibrillar hypertrophy is a contributory cause of gains in muscle strength. Sports Medicine, 1-5. https://doi.org/10.1007/s40279-019-01107-8 [see Loenneke et al above for counterpoint and audio debate in recommended resources]

Thiebaud, R. S. (2012). Exercise-Induced Muscle Damage: Is it detrimental or beneficial?. Journal of Trainology, 1(2), 36-44.

Tipton, K. D., & Ferrando, A. A. (2008). Improving muscle mass: response of muscle metabolism to exercise, nutrition and anabolic agents. Essays in biochemistry, 44, 85-98. DOI: 10.1042/BSE0440085 [www]

Wackerhage, H., Schoenfeld, B. J., Hamilton, D. L., Lehti, M., & Hulmi, J. J. (2019). Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise. Journal of applied physiology, 126(1), 30-43. https://doi.org/10.1152/japplphysiol.00685.2018

Wernbom, M., Augustsson, J., & Thomeé, R. (2007). The influence of frequency, intensity, volume and mode of strength training on whole muscle cross-sectional area in humans. Sports Medicine, 37(3), 225-264. https://doi.org/10.2165/00007256-200737030-00004

West, D. W., Burd, N. A., Staples, A. W., & Phillips, S. M. (2010). Human exercise-mediated skeletal muscle hypertrophy is an intrinsic process. The international journal of biochemistry & cell biology, 42(9), 1371-1375. https://doi.org/10.1016/j.biocel.2010.05.012 [www]

Wilson, J. (2015) Mass Class Training: The fundamentals of Muscle Growth Available at https://www.bodybuilding.com/fun/mass-class-training-the-fundamentals-of-muscle-growth.html