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Creatine: How It Boosts Muscle Growth (Mechanisms of Action)

Updated: Jan 16

Evidence-Based. Scientifically Reviewed.

The mechanisms which creatine influences muscle growth are complex.

These include its osmotic effect, modulation of factors like Myostatin, and the modulation of key anabolic pathways such as mTOR.

Creatine also plays a significant role in myogenic regulation, affecting the function of satellite cells vital for muscle repair and growth.

Furthermore, its impact on muscle energy metabolism cannot be overstated, as it enhances energy availability essential for muscle contraction and growth.

Additionally, creatine activates antioxidant defense mechanisms in muscle cells and stimulates the production of Insulin-like Growth Factor-1 (IGF-1), a key component in muscle development.

This article goes into the various aspects of creatine's impact on muscle physiology, exploring the scientific consensus on each mechanism and pathway.


Creatine is a popular supplement, particularly among athletes, for its potential in enhancing muscle growth and sports performance.

It is naturally found in small amounts in certain foods, such as red meat and fish, and is also synthesized in the human body.

The safety and efficacy of creatine have been widely studied, with evidence supporting its safe use in healthy individuals.

Creatine's primary action is to increase the availability of creatine phosphate, a key molecule in energy production in muscles, thereby enhancing the body's ability to produce energy rapidly during intense physical activity.

Besides muscle growth, creatine has shown benefits in improving cognitive function, reducing muscle atrophy, and potentially exerting antioxidant effects. (Young et al., 2010)

How Creatine Affects Muscle

Creatine affects muscle growth and development through several mechanisms and pathways, as listed below.

The scientific consensus varies for each mechanism, with some being well-established and others more theoretical.

1. Osmotic Effect

Creatine supplementation can act as an osmotic stressor, stimulating protein synthesis pathways and promoting muscle hypertrophy (Farshidfar et al., 2017).

The osmotic effects of creatine on muscle cells are a significant aspect of its action in muscle growth and hypertrophy.

Creatine, being an osmotically active substance, can draw water into muscle cells.

This osmotic action serves as a cellular stressor, which in turn acts as an anabolic stimulus for protein synthesis signal pathways.

This process can lead to muscle cell swelling, a phenomenon that has been suggested to signal muscle growth through increased protein synthesis and decreased protein breakdown (Farshidfar et al., 2017).

Moreover, the increased intracellular hydration status may also affect the myogenic process by altering the secretion of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors.

This can result in enhanced satellite cell mitotic activities and differentiation into myofibers, contributing to muscle growth (Dangott, Schultz, & Mozdziak, 2000).

2. mTOR Pathway Modulation

Creatine supplementation has been shown to affect the mammalian target of rapamycin (mTOR) pathway in skeletal muscle cells, which is critical for muscle growth and development.

  1. Modulation of mTOR Pathway: Creatine appears to directly affect muscle protein synthesis by modulating components in the mTOR pathway. This pathway plays a crucial role in regulating cell growth, proliferation, and survival, especially in response to nutrients and growth factors (Farshidfar et al., 2017).

  2. Enhancing Protein Synthesis: By impacting the mTOR pathway, creatine can enhance protein synthesis in muscle cells. This effect contributes to muscle hypertrophy (growth) and helps in the maintenance and repair of muscle tissue.

  3. Interaction with Other Pathways: The interaction of creatine with the mTOR pathway may also involve other signaling molecules and pathways that contribute to muscle growth and differentiation.

  4. Impact on Myogenic Regulation: Apart from influencing protein synthesis, creatine's effect on the mTOR pathway may also play a role in myogenic regulation – the process by which muscle tissue forms. This involves changes in myokine secretions and expressions of myogenic regulatory factors.

The detailed mechanisms through which creatine modulates the mTOR pathway and its impact on muscle physiology continue to be an area of active research.

The current evidence suggests a beneficial role of creatine in promoting muscle growth through multiple cellular mechanisms, with the mTOR pathway being a key player.

3. Myogenic Regulation

Creatine alters myokines like myostatin and IGF-1, enhancing satellite cell activities and differentiation into muscle fibers.

  1. Myogenic Regulatory Factors (MRFs): Creatine influences the expression of MRFs such as MyoD, Myogenin, Myf5, and MRF4. These factors play a significant role in the myogenic process, controlling the formation and development of muscle tissue (Willoughby & Rosene, 2003)(Busekrus, Torok, & Hydock, 2019).

  2. Inhibition of Myostatin Expression: Creatine can reduce the expression of myostatin in muscle cells. Myostatin acts as a negative regulator of muscle growth, and its inhibition by creatine may contribute to muscle hypertrophy (Farshidfar, Pinder, & Myrie, 2017).

  3. Influence on Satellite Cells: Satellite cells are essential for muscle growth and regeneration. Creatine appears to affect satellite cell mitotic activities and differentiation into myofibers. This could lead to enhanced muscle repair and growth. (Dangott, Schultz, & Mozdziak, 2000)

  4. Interaction with Other Regulatory Proteins: Creatine may interact with various regulatory proteins and enzymes such as creatine kinase, which is vital for muscle energy metabolism and plays a role in the differentiation process. (Willoughby & Rosene, 2003)(Seraydarian & Artaza, 1976)(Hornemann et al., 2003)

  5. Modulation of Gene Expression: Creatine can modulate the expression of genes related to muscle development and repair. (Jaynes et al., 1988)

This intricate interplay of factors and pathways highlights the complexity of creatine's role in muscle development.

4. Energy & Metabolism

By increasing creatine phosphate in muscles, it enhances energy availability, crucial for muscle contraction and growth.

Creatine plays a vital role in muscle energy metabolism, particularly during high-intensity exercise.

  • ATP and Creatine Phosphate Relationship: Creatine phosphate is essential in the rapid regeneration of adenosine triphosphate (ATP), the primary energy currency of the cell. During intense exercise, ATP is quickly depleted, and CrP donates a phosphate group to adenosine diphosphate (ADP) to regenerate ATP, providing a rapid source of energy to muscles. This process is crucial for short-duration, high-intensity activities like sprinting or lifting weights (Wilson, Nishiki, & Erecínska, 1981).

  • Creatine Kinase Reaction: The conversion of CrP to creatine and the regeneration of ATP from ADP are catalyzed by the enzyme creatine kinase. This enzyme plays a pivotal role in maintaining the balance of ATP and ADP during muscle contraction and relaxation (Nabuurs et al., 2013).

Increased Energy Availability

By increasing the concentration of CrP in muscles, creatine supplementation enhances the availability of energy, particularly during bursts of quick and intense muscle contraction.

This additional energy reserve helps delay muscle fatigue and enhances overall performance during high-intensity exercise.

Through its role in increasing creatine phosphate levels in muscles, creatine supplementation enhances the rapid regeneration of ATP, crucial for sustained muscle contraction and therefore muscle growth, directly and indirectly.

5. Antioxidant Defense Activation

Creatine can improve the antioxidant defense in muscle cells, contributing to better muscle health and function (Young et al., 2010).

6. Insulin-like Growth Factor-1 Stimulation

Creatine supplementation has been found to stimulate the production of Insulin-like Growth Factor-1 (IGF-1), which is a key factor in muscle growth and development.

IGF-1 plays a significant role in promoting muscle cell proliferation and differentiation, contributing to muscle hypertrophy.

One study found that creatine supplementation, in conjunction with resistance exercise training, increases intramuscular IGF-1 concentration (Burke et al., 2008).

This suggests that creatine can enhance the production of IGF-1 within muscle cells, thereby contributing to muscle hypertrophy through its anabolic effects on muscle tissue.

Does Creatine Boost Muscle Growth?

Creatine likely contributes to muscle growth, primarily through energy provision and protein synthesis pathways.

The bulk of evidence, including systematic reviews and meta-analyses, supports its efficacy in increasing muscle mass, particularly when combined with resistance training.

Does It Boost Strength / Power Output?

Creatine is likely to increase strength and power output.

This is attributed to its role in rapidly regenerating ATP during high-intensity activities, thus enhancing short-duration, high-intensity exercise performance.

Does It Boost Exercise Performance?

There is a consensus that creatine can improve exercise performance, especially in activities requiring bursts of speed and power.

It enhances muscle endurance and reduces fatigue, allowing for increased training intensity and volume.


Creatine is an effective and safe supplement for promoting muscle growth and enhancing strength, power output, and overall exercise performance.

Its benefits are well-supported by scientific evidence, making it a viable option for athletes and individuals engaged in resistance training.

The general scientific consensus acknowledges creatine's efficacy in these areas, backed by its well-understood mechanisms of action in muscle physiology.

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