European Journal of Applied Physiology

, Volume 118, Issue 3, pp 485–500 | Cite as

The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis

  • Felipe Damas
  • Cleiton A. Libardi
  • Carlos Ugrinowitsch
Invited Review


Resistance training (RT)-induced skeletal muscle hypertrophy is a highly intricate process. Despite substantial advances, we are far from understanding exactly how muscle hypertrophy develops during RT. The aim of the present review is to discuss new insights related to the role of skeletal muscle damage and muscle protein synthesis (MPS) in mediating RT-induced hypertrophy. Specifically, the thesis that in the early phase of RT (≤ 4 previous RT sessions) increases in muscle cross-sectional area are mostly attributable to muscle damage-induced muscle swelling; then (after ~ 10 sessions), a modest magnitude of muscle hypertrophy ensues; but only during a latter phase of RT (after ~ 18 sessions) is true muscle hypertrophy observed. We argue that the initial increases in MPS post-RT are likely directed to muscle repair and remodelling due to damage, and do not correlate with eventual muscle hypertrophy induced by several RT weeks. Increases in MPS post-RT session only contribute to muscle hypertrophy after a progressive attenuation of muscle damage, and even more significantly when damage is minimal. Furthermore, RT protocols that do not promote significant muscle damage still induce similar muscle hypertrophy and strength gains compared to conditions that do promote initial muscle damage. Thus, we conclude that muscle damage is not the process that mediates or potentiates RT-induced muscle hypertrophy.


Skeletal muscle Resistance exercise Myofibrillar protein synthesis Edema Soreness Satellite cells 



5′ Adenosine monophosphate activated protein kinase


Cross-sectional area


Creatine kinase


Delayed onset muscle soreness


Dual-energy X-ray absorptiometry


Muscle fibre cross-sectional area


Interleukin 1 beta


Interleukin 6




Muscle protein breakdown


Muscle protein synthesis


Magnetic resonance imaging


Mechanistic target of rapamycin


Maximum voluntary isometric contraction


Myofibrillar protein synthesis


Peroxisome proliferator activated receptor gamma coactivator 1 alpha


Resistance exercise


Resistance training


Satellite cells


Tumour necrosis factor alpha





We would like to acknowledge the participants of our studies and funding agencies: the São Paulo Research Foundation (FAPESP; Grants #2012/24499-1, 2013/21218-4, 2014/19594-0, 2016/24259-1 and 2017/04299-1), the National Council for Scientific and Technological Development (CNPq; Grants #303085/2015-0 and 448387/2014-0), and the Natural Science and Engineering Research Council (NSERC).

Author contributions

FD, CAL and CU wrote, reviewed and approved the final content of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors do not have any conflicts of interest financial or otherwise to declare.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.School of Physical Education and SportUniversity of São PauloSão PauloBrazil
  2. 2.Laboratory of Neuromuscular Adaptations to Resistance Training-MUSCULAB, Department of Physical EducationFederal University of São CarlosSão CarlosBrazil

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