Creatine and New Muscle Growth

July 21, 2003


1- Featured Article: Creatine and New Muscle Growth.

Welcome to the 21st issue of the Creatine Newsletter. One of the best-known facts about creatine is that it increases lean muscle mass. But what does this really mean? Does creatine supplementation actually increase the amount of force-generating proteins contained within our muscles, or merely inflate our muscle with water?

In this newsletter issue I critically review new data comparing the muscle-building capacity of creatine monohydrate with that of other commonly used ergogenic agents with surprising results.

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This Month’s Featured Article:

Creatine and New Muscle Growth.

Muscle Volumizing

It is a widely accepted fact that creatine causes our muscles to grow. The major part of this growth, however, is simply due to the swelling of our muscles with water. A process descriptively referred to as “Muscle Volumizing”, owing to an increase in muscle volume (size). In essence, water follows creatine into our muscles in an attempt to dilute its intramuscular concentration within accepted limits. It thus follows that the degree of muscle volumization is a direct consequence of muscle creatine content.

Although some types of athletes might find an increase in size a desirable side effect, muscle volumizing per se contributes little to an actual improvement in athletic performance. The increase in strength we detect during muscle volumization has to do with an increase in muscle creatine content and only indirectly correlates with muscle size. After discontinuing supplementing our muscle creatine stores eventually return to normal and will be manifested as a partial loss of strength and size. I stress the word partial because other processes most likely also contribute to the physical benefit typically afforded by creatine; the topic of this month’s newsletter…

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Protein Synthesis

Numerous pieces of evidence also indicate that creatine induces the production of new muscle proteins, a process scientifically known as protein synthesis. Most importantly for those of us involved in athletics, creatine increases the production of those muscle proteins involved in generating force, i.e. strength.

First, clinical conditions where creatine is limiting are associated with a decrease in muscle fiber diameter, especially those muscle fibers (type II) which are more reliant on creatine-based energy production.

Secondly, when inactive analogues of creatine are administered to laboratory animals a decrease in the size of type II muscle fibers is also observed, suggesting that the presence of creatine is necessary to maintain existing muscle proteins.

Thirdly, creatine selectively improves exercise performance in those tasks that are most effective at increasing muscle protein synthesis, i.e. those involving maximal efforts interspersed with rest intervals. Common examples of such exercises are weightlifting, jumping, throwing and sprinting.

Finally, there is some indication that the swelling of the muscle cell with water (muscle volumizing) might mistakenly signal to the cell that it has grown. The muscle cell might then respond by increasing protein synthesis.

It is thus not surprising that as a consequence of the combination of all these processes biochemical indicators of protein synthesis increase following creatine use. Increases in physical performance as a result of new muscle proteins would be more enduring than those obtained during muscle volumizing, persisting long after our muscle creatine content has returned to normal..

Something new…

New research has recently appeared suggesting that creatine might posses an even more fundamental approach to inducing muscle development. That is, through the growth of new muscle from progenitor cells.

Your average muscle cell is hundreds of times larger than your average skin cell. The reason for this is that adult muscle is derived from union of hundreds of individual progenitor cells. These progenitor cells lay dormant out side muscle waiting for the correct environmental cues to signal them to start differentiating into myoblasts. These myoblasts then fuse with existing muscle fibers causing the muscle to grow. What biochemical pathways are involved in the differentiation and fusion of myoblasts is currently a major point of interest in both clinical and sport medicine areas.

For experimental purposes, myoblasts can also be isolated from animals and maintained in plastic tissue culture dishes where this fusion event can be studied directly under the microscope. In tissue culture dishes the fusion event commences with myoblasts aligning themselves into long, spindle-shaped, arrays. The product of many individual fusion events are elongated cells known as myotubes. Myotubes are contractile and contain most of the same force-generating proteins as mature muscle fibers formed within the animal and in fact, myotubes are the first stage in the formation of an adult skeletal muscle fiber.

A few years ago a joint Belgian-British study showed that creatine supplementation increases the levels of a particular myoblast differentiating factor known as Myogenic Regulatory Factor 4, or MRF4 (ref. 1). This effect was noticeable during the rehabilitation of a previously immobilized limb when muscle is recuperating the most rapidly. This study administered 5 grams of creatine every few hours to college students. Given that the average person contains a little over 5 liters of plasma volume, the final concentration of creatine in the blood stream was roughly 1 gram per liter. The reason I point this out will become more obvious later. Nevertheless, this provocative study suggested that creatine might promote the formation of new muscle.

Much more recently (May 2003) an American study coming out of Washington State University corroborated this hypothesis, but with some important differences (ref 2). First, the study examined the fusion events of myoblasts isolated from sheep, not humans. Secondly, this study tested the ability 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.

The Study

This study tested the ability of a variety of ergogenic agents to induce the fusion of sheep myoblasts to form myotubes. 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. The cells were kept in the presence of the indicated agent for five days after which the extent of myotube formation was measured.

The Results

Of all the ergogenic agents tested only creatine monohydrate induced myoblasts to fuse over control levels (no ergogenic agent). Specifically, creatine monohydrate added to the bathing medium at a concentration of 0.1% had the greatest effect on myotube formation. In fact, the other ergogenic agents tested had no effect at all! Interestingly, this concentration of creatine corresponds to 1 gram of creatine monohydrate per liter of bathing solution. This is roughly the same concentration of creatine use in the previously mentioned human study.

Oddly, doubling the creatine concentration had basically no effect. So, does this mean that too much creatine is a bad thing? If you are a myoblast trying to fuse in a tissue culture dish, maybe, but if you are a human exercising, who knows?

The Take Home

The authors of the study proposed that new muscle formation accounts for part of the ergogenic benefit normally afforded by creatine monohydrate. Creatine may therefore have important practical implications for muscle recovery following trauma or sports injury.

The Scientific References

1. Hespel, P., Eijnde, B.O., Leemputte, M.V., Urso, B., Greenhaff, P.L., Labarque V., Dymarkowski, S., Hecke, P.V. and Richter, E.A. (October 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.

2. Vierck J.L., Icenoggle D.L., Bucci L. and Dodson M.V. (May 2003) The effects of ergogenic compounds on myogenic satellite cells.. Medicine and Science in Sports and Exercise. Volume 35 (5): pages 769-776.

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