How does creatine cause muscle growth?

Creatine promotes muscle growth in two principal ways.

Muscle Volumizing: The first, and most rapid, form of muscle growth involves the movement of fluids from the blood stream into skeletal muscle, causing muscles to swell. This process has been termed muscle volumizing (see Question #11), since muscles increase in volume (size) as a result of muscle fluid retention. This early phase of muscle growth can account for as much as 1-2 kilograms (2-5 pounds) of additional body mass during just the first few weeks of supplementation.

Protein Synthesis: The second form of muscle growth is slower to be realized and involves the production of new muscle proteins, a process scientifically termed protein synthesis, which is, in fact, the commencement of muscle anabolism. On one level, available evidence seems to indicate that the process of muscle volumizing itself directly stimulates muscle protein synthesis. On another level, the fact that creatine supplementation increases our exercise capacity should also result in greater increments in protein synthesis in response to a training stimulus. Remember, exercise is an essential stimulus for muscle development. However, unlike the effects of muscle volumizing that disappear about one month of terminating supplementation, the ergogenic (performance enhancing) effects of protein synthesis will persist long after discontinuing supplementation.

Other Anabolic Effects: Preliminary evidence now seems to indicate that creatine supplementation might also influence growth hormone release independently of an exercise stimulus. Growth hormone is one of our most important anabolic hormones. Two other extremely important anabolic hormones are insulin and testosterone. The consequence of this novel effect of creatine would be a greater anabolic drive for the supplementing athlete. New evidence also suggests that creatine might possess antioxidant properties, which would translate into more effective muscle recovery following intense training sessions, helping to offset the onset of overtraining syndrome. These other possible attributes of creatine certainly merit further examination in controlled scientific settings and have important practical implications for the serious strength athlete.

Cellular Methylation: It is becoming increasingly apparent that many of the “unexpected benefits” of creatine supplementation are, in fact, downstream consequences of methylation reactions, one of the most ubiquitous, and important, of biochemical regulatory mechanisms. In essence, methylation sets the stage on which anabolism is played out! Moreover, combining creatine supplementation with targeted Vitamin B intervention is the most effective way of optimizing your body’s methylation status. How to fully utilize this aspect of creatine-induced muscle anabolism is thoroughly discussed in my creatine guide.

TAKE HOME: The key to making the most of creatine supplementation lies in taking full advantage of this later (protein synthetic) phase of muscle growth.


Myogenesis simply refers to the creation (genesis) of muscle (myo). There are two principal forms of muscle development: (1) hypertrophy, the increased growth of existing muscle fibers and; (2) hyperplasia, the creation of entirely new muscle fibers from progenitor cells. Current evidence indicates that hypertrophy is the predominant form of muscle growth observed in response to an exercise stimulus.

Hypertrophy: It is well agreed upon that creatine, by increasing our ability to perform brief bouts of intense exercise (anaerobic exercise, or resistance exercise) stimulates muscle hypertrophy. Hypertrophic muscle growth involves the addition of new muscle proteins (protein synthesis) to an existing muscle fiber. The proteins whose synthesis is preferentially upregulated are those involved in force-generation (contractile proteins) and those that provide the muscle cell with energy resources (metabolic proteins).

Hyperplasia: Recent studies now provides proof that creatine supplementation also activates previously dormant satelite cells (myoblasts) to produce new muscle fibers (myotubes). One study U.S.A. found that creatine induces the proliferation of statelite cells in preparation for fusion into myotubes (1). A subsequent Belgian-British study extended these results with the finding that creatine supplementation increases the levels of a particular myoblast differentiating factor known as Myogenic Regulatory Factor 4, or MRF4 (2). This effect was noticeable during the rehabilitation of a previously immobilized limb when muscle is recuperating the most rapidly. More recently (May 2003) an American study coming out of Washington State University corroborated this hypothesis, but with some important differences (3). First, the study examined the fusion events of myoblasts (raised outside the animal in tissue culture) under the influence of several ergogenic agents commonly used by athletes to increase muscle growth to promote myoblasts fusion. Some of the agents were hormonal precursors, some were herbal in origin and others were amino acids or derivative thereof, namely creatine. Specifically, the agents tested included two forms of creatine (monohydrate and pyruvate), L-glutamine, dehydroepiandrosterone (DHEA), androstenedione, Ma Huang (Ephedra sinensis) extract, and Zhi Shi (Citrus aurantium) extract. Of all the ergogenic agents tested only creatine monohydrate induced myoblasts to fuse into myotubes. In fact, the other ergogenic agents tested had no effect at all! The effect was clear; only creatine monohydrate induced myoblasts to fuse themselves into myotubes-the first stage in the formation of new muscle fibers!

Oddly, doubling the concentration of creatine monohydrate in the bathing medium (from 0.1% to 0.25%) REDUCED the extent of myotube formation. So, does this mean that too much creatine is anti-anabolic? If you are a myoblast trying to fuse in a tissue culture dish, maybe, but if you are a human exercising, who knows? Nevertheless, the effect seemed clear. Other advantages of taking smaller doses of creatine monohydrate can be viewed here.

Read an interview specifically discussing the details and implications of the third study comparing effects of creatine monohydrate and creatine pyruvate over muscle development in tissue culture.

Selected Scientific References:

1. Dangott B. et al. (2000) Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. International Journal of Sports Medicine, Volume 21 (1), pages 13-16.

2. Hespel P. et al. (2001) Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. Journal of Physiology, Volume 536 (2), pages 625-633.

3. Vierck, J. L. et al. (2003) The effects of ergogenic compounds on myogenic satellite cells. Medicine & Science in Sports & Exercise, Volume 35 (5), pages 769-776.

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