The Theory of Hypertrophy: Could It Be the Theory of Everything for Muscles?

Hypertrophy is the state of constant swelling that occurs in muscle cells, just like the swelling of existing muscles. About 15 hours after working out the muscle and leaving the gym, the size of the muscle cells returns to its original size and that bloated feeling disappears. However, when these exercises are done regularly and continuously, an increase in the average volume of the muscles is observed after a while. This is called hypertrophy. Although this word gives the theory its name, other theories also refer to muscle growth as “hypertrophy”; so the word is not specific to the theory. So developing a “Theory of Hypertrophy” would mean developing a “theory of everything” for muscle growth.

Satellite Cell Theory

One of the most important mechanisms for explaining exactly how hypertrophy is experienced is the Satellite Cell Theory of Hypertrophy, and it aims to create a holistic picture by taking the most important and data-driven aspects of the theories we have seen up to this point and more and combining them with other observational data.

According to this theory, muscles experience trauma during intense exercise, just as predicted in the Microtrauma Theory. This is called a muscle injury or muscle damage. The muscle damage experienced during the first load exercise will be much higher than during subsequent exercises. Also, since most of the swelling in the first few exercises is oedema, repetitive training is a must for permanent muscle growth. Below, you can see the relationship between the decrease in the effect of oedema and the increase in permanent muscle development with progressive resistance training.

However, during muscle damage, which is known to occur when an untrained muscle is under load, the fibres in the muscles are also damaged and the satellite cells are activated. These cells are located between the muscle fibres, between the basal lamina (i.e. basement membrane/membrane) and the plasma membrane (“sarcolemma”), and upon injury, they multiply rapidly and begin to fuse with each other.

Satellite cells reside in the extracellular matrix, and move and interact with connective tissue and fibroblasts. Satellite cells are dormant when muscle damage is not yet present, so extracellular matrix adhesion is strong. When muscle damage occurs and the integrity (adhesion) of the extracellular matrix is ​​disrupted, the satellite cells begin to move and multiply, while restructuring the tissues.

Therefore, according to this theory, swelling of the damaged muscle fibres is a result of the increase in the muscle cross-sectional area as a result of the fusion of the satellite cells and the fusion of the muscle fibers at the same time. In one place, the cells try to repair the damage, creating a larger muscle area, which is perceived externally as hypertrophy.

“Muscle repair” is not the only mechanism of long-term muscle growth. After a point, the muscle cross-sectional area increases with the direct effect of muscle swelling (hypertrophy). You can see the relationship between these two mechanisms in the graphic below.


Satellite cells have only 1 nucleus and can reproduce by division. As satellite cells proliferate, some acquire organelles from muscle fibers; however, the vast majority undergo differentiation/transformation to become normal muscle cells. In the meantime, they fuse with the surrounding muscle fibers and produce new myofibrils with protein structure (at the same time, they also repair muscle damage). This increases the thickness of the muscle and the number of muscle strips.

The remaining satellite cells act as a source of new cell nuclei for the growing fibers. Thanks to these additional cell nuclei, muscle fibers can synthesize more protein and produce more of contractile myofilaments such as actin and myosin. Slow-twitch muscles have more satellite cells and fast-twitch muscles have fewer satellite cells because slow-twitch muscles have to go through a regular repair process due to daily activities.

According to this theory, growth factors are the leading factors that trigger the division of satellite cells. For example:

  • Hepatocyte growth factor is involved in muscle repair and migration of satellite cells to the damaged muscle area.
  • Fibroblast growth factor plays a role in muscle repair and new capillary formation after exercise.
  • Insulin-like growth factors (1 and 2) are involved in muscle growth, DNA modifications for protein synthesis, and muscle repair.
  • Insulin hormone triggers muscle growth by accelerating protein synthesis and allows glucose, which is the energy source of the cells, to enter the cell.
  • By regulating fat metabolism, growth hormone helps to provide the energy surplus needed by muscle development and accelerates the uptake of amino acids into skeletal muscle.
  • Testosterone triggers growth hormone, accelerating amino acid uptake and protein synthesis. It also enhances tissue growth by increasing neurotransmitter activity in muscle strips. Since it is a steroid hormone, it triggers protein synthesis by interacting with the nuclear receptors of DNA and is thought to have some regulatory roles on satellite cells.

As we mentioned in previous theories, the effect of these hormones is highly controversial; however, in the Satellite Cell Theory, none of this is presented as the main cause of muscle development (as opposed to, for example, in the Hormone Theory). Rather, it plays an auxiliary and secondary role — which is plausible: there is not enough evidence to claim that the muscle growth process is not affected by any hormones or growth factors, and there is an abundance of academic studies to the contrary. In this respect, the Satellite Cell Theory includes the strongest aspects of other theories in the explanation.



As you can see, many different hypotheses and theories have been developed to date about how muscles develop; however, none of these has gained universal acceptance. This is because it is currently possible to find studies that both support and disprove every competing theory. This may indicate that we are looking in the wrong places regarding muscle growth or that our experimental methods for this process are not yet sensitive enough.

However, it is possible to summarize the results obtained from the studies carried out so far under several headings:

  1. Muscle growth is experienced due to increased protein synthesis in strained muscles.
  2. Muscle enlargement experienced in the first few weeks of exercise is not significant and may not be permanent. A significant part of this is thought to be oedema-related. Therefore, muscle development studies conducted by people who have not exercised before may have misleading results if they do not take into account the edema effect.
  3. Muscle growth appears to be an intrinsic quality, not of a systemic nature. So when you work a single muscle, not all of them are developed; Only the muscles and muscle groups you work will develop.
  4. Testosterone has a certain role in muscle development and may explain why men have larger muscles than women. However, its exact role in muscle development is not yet known.
  5. Growth hormone is not directly effective in muscle development (protein anabolism); rather, it is involved in fat breakdown and carbohydrate breakdown. Growth hormone supplements enlarge the tendons, not the muscles themselves.
  6. While increased testosterone levels may result in a certain amount of muscle growth independent of physical activity, the real improvement occurs in locally stressed muscles, not the entire system.
  7. The only tool that allows you to direct muscle development is to go under load. Other physical training can increase your overall strength or stamina, but it will not serve to increase your lean body mass.
  8. Insulin and insulin-related growth factors play some role in muscle development. However, insulin supplementation does not enhance muscle growth and can lead to serious health problems.
  9. Genes influence a person’s ability to build muscle to a certain extent. Different types of muscle fibers can be found in different amounts in different people. This may explain why some people are more successful in certain sports.


If you want to put what you’ve learned here into practise, we can offer the following advice:

  1. Resistance training is most effective when done around 70–90% of the maximum that can be achieved individually in a single set.
  2. Doing 3 sets of each exercise triggers more protein synthesis than doing 1 set.
  3. The first 4 resistance exercises performed by someone who has not developed muscle before will cause oedema-induced muscle swelling and are not meaningful. After about 8–12 exercises, moderate muscle enlargement is seen. After about 18 exercises spread over 6–10 weeks, a significant amount of hypertrophy is observed.
  4. Protein synthesis remains above normal for 24 hours after exercise. This window is an important window for protein supplementation.
  5. Passive movement while lowering the weight is just as important as an active movement when lifting the weight.
  6. Insulin and growth hormone supplements alone cannot improve your muscle growth and may even harm you.
  7. Testosterone supplementation will likely boost your muscle growth, but you may experience infertility, legal problems, etc. Side effects should be noted. No hormonal supplements should be taken without the advice of a physician.
  8. The increase in performance and strength does not necessarily have to be linearly related to your muscle gain. These are influenced by many other factors.
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This article is an excerpt from by Karl Liebermann | Jun, 2022 | Medium