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Creatine: The Next Great Antioxidant?

By Alfredo Franco-Obregon, PhD, author of Creatine: A practical guide

Muscle damage is a natural consequence of exercise. A small amount of muscle damage is not a terrible thing and, in fact, is necessary to stimulate new muscle growth. If, on the other hand, the amount of damage you inflict upon your muscles with exercise exceeds their capacity to repair and rebuild, then you’re in big trouble. You then have a scenario of net muscle breakdown, otherwise known as catabolism. Situating yourself in a catabolic holding pattern by continually overdoing it in the weight room will eventually lead to overall loses in muscle mass and diminished athletic performance. This article focuses one aspect of overtraining and how to minimize its effects.

Two principal forms of muscle damage arise from physical exertion:

The first is mechanical and occurs immediately. In response to the physical stress of exercise, your muscles and associated capillary beds become slightly damaged. These microscopic foci of damage may then prime a robust phase of increased micro-vascularization and new muscle growth (aka, anabolism). That is, conditions permitting, capillary beds will reform to increase blood flow and new muscle tissue will be laid down to replace damaged tissue. The end result, increased blood flow to larger, more efficiently, working muscles. If, on the other hand, the initial amount of damage is too great or insufficient time is given for your muscles to fully recover from the insult, you will lose strength and mass!

The second form of muscle damage is a downstream consequence of the first and is, in actuality, the initiation of the rebuilding process discussed previously. This form of muscle damage results from reactive molecular species produced in response to strenuous exercise, but that exert their degenerative effects a few days later.

Rising from the ashes …

Following the initial insult of exercise, damaged muscle tissue must be cleared away before rebuilding can commence. This process begins with the leakage of chemical agents from damaged cells that attract specialized cells known as phagocytes (neutrophils and macrophages) to sites of damage. Here, phagocytes accumulate, greatly increase in number, and build an appetite. Next, commences a voracious phase of cell eating, otherwise known as phagocytosis (hence, their name), whereby damaged muscle tissue is literally eaten away. The process of phagocytosis is initiated with the release of agents from macrophages that serve to breakdown, or digest, damaged cells in preparation for absorption. Following the removal of all dead tissue, the stage is then set for new muscle growth. New muscle is formed from the fusion of hundreds of progenitor cells that were previously laying dormant waiting for the appropriate signal to act. From start to finish, this entire process takes about 3-4 days.

Free Radicals

To assist in their removal of dead tissue phagocytes release digestive enzymes, toxins, and, most importantly, Reactive Oxygen Species, or ROS, for short. ROS are produced in the burst of metabolic activity known as a "respiratory burst". One of the most powerful of ROS produced by phagocytes is the Superoxide Radical. Superoxide greatly weakens the integrity of the muscle membrane causing small tears that allow calcium ions to leak into the muscle cell. It is a rise in intramuscular calcium that activates a class of enzyme known as proteases that cause the muscle cell to disintegrate. Obviously, a small amount of superoxide plays an essential role in the absorption of damaged cells. On the other hand, overproduction of superoxide surpasses its usefulness and can actually be counterproductive as its destructive capacity becomes unleashed without warrant.

Oxidative stress

Exercise also directly produces ROS. That is, independently of neutrophils and macrophages. Normally, most of the oxygen consumed during cell metabolism is converted into water. A small amount of the consumed oxygen (2-4%), however, is converted into superoxide. Given the fact that exercise can increase muscle oxygen consumption by as much as 200-fold, superoxide levels also increase tremendously with intense exercise, easily surpassing the body’s capacity to neutralize it. This gives rise to a dangerous scenario known as oxidative stress, which slows muscle recovery and increases the chances of injury. In fact, some experts believe that the overproduction of ROS may also accelerate the normal aging process as well as eventually lead to states of disease. 


Our bodies possess a natural line of defense against oxidative stress; special molecules known as antioxidants that neutralize ROS. Vitamins A, C and E are examples of vitamins that can act as antioxidants. Vitamin E is a particularly potent antioxidant, since it is able to act in both aqueous (within the cell) and lipid (within membranes) environments, and is hence very effective at protecting our cellular membranes from degradation following oxidative stress. Our bodies also come equipped with their own antioxidant molecular complexes. Some of the most important enzymatic antioxidants are Superoxide Dismutase, Glutathione Peroxidase, and Catalase. Glutathione is one of our principle non-enzymatic antioxidants.

Athletes are now paying closer attention to their antioxidant status in an attempt to better assist muscle recovery. Proactive measures one can take to enhance the body’s capacity to cope with oxidative stress include eating foods rich in antioxidants, supplementing with antioxidant vitamins, limiting alcohol intake, especially following exercise and getting plenty of rest. It now turn’s out that some athletes were improving their antioxidant defenses in a way they hadn’t previously imagined... 

Is creatine an antioxidant?

A study was recently released suggesting that creatine might act as a superoxide scavenger in its own right. This would be an additional benefit of creatine, independent of its better-understood capacity to increase ATP availability during exercise. It is thus possible that part of the benefit we obtain from creatine derives from its capacity to act as an antioxidant.

The salient points of the study were as follows:

  • The creatine levels used in this study were within physiological limits. In other words, the concentrations of creatine found by this study to be effective at scavenging free radicals were comparable to those found within muscle (20-60 mM, for those interested). This gave relevancy to the study.
  • Creatine, although not as effective as glutathione at neutralizing superoxide, was an effective antioxidant, nonetheless.
  • Creatine’s ability to neutralize superoxide was measured in a test tube, not in an exercising person. And, although it’s reasonable to assume that creatine should behave similarly within athletes, subtle differences may exist. For all we know, creatine may be an even more efficacious antioxidant inside the body! Only further experimentation will tell.
Take Home

This report indicates that creatine possess' antioxidant properties and is able to effectively neutralize Superoxide, one of the more insidious free radicals produced by exercise. Since these findings where obtained in a test tube, however, it remains to be shown if creatine has the same antioxidant properties within an exercising person. Although preliminary, this result is surely worth pursuing and has important practical implications for muscle recovery following strenuous exercise.


About The Author

Dr. Alfredo Franco-Obregon, research scientist, author, and owner of Nutritional Supplements Newsletters. Dr. Alfredo Franco-Obregon has had over 20 years of in depth research experience in major laboratories world-wide. His principal scientific interest is the understanding of the cellular mechanisms leading to muscle cell death.

Dr. Franco-Obregon is also the author of Creatine: A practical guide book.