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Antioxidant Properties of Creatine and B-Vitamins
It would not surprise anyone that the body needs to produce energy in order to perform even the simplest of tasks. Moreover, the requirement for energy can increase several hundred-fold in response to intense physical activity. Somewhat more surprising however, is the notion that extremely high levels of energy expenditure might produce potentially harmful agents known as free radicals. And, very surprising was the recent finding that creatine possesses an inherent capacity (as an antioxidant) to neutralize these free radicals. This potential benefit of creatine is further strengthened by essential B-vitamins.
Energy metabolism liberates electrons (in reality, an electron accompanied by one proton, H+), which then need to be removed from the cell soon after being produced. Oxygen is the final acceptor of these electrons to produce water (oxygen is the O in H2O). This is one of the principal reasons that our breathing rate increases in response to heavy exercise. This process is not perfect, however, and a small amount of oxygen is inevitably converted into Reactive Oxygen Species (ROS), a class of free radical. Most importantly, the rate at which ROS are produced increases in parallel with exercise intensity, i.e. with increasing consumption of oxygen. ROS are notorious at destabilizing cellular membranes, ultimately causing muscle damage and possibly muscle cell death, especially after strenuous exercise.
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The body normally defends itself from free radical damage with the help of antioxidants that are typically able to neutralize ROS as soon as they are produced. During strenuous exercise, however, the levels of ROS rise to the point where they actually overrun the bodys normal antioxidant defenses, giving rise to a degenerative scenario known as oxidative stress. To combat oxidative stress the body produces its own battalion of antioxidants as well as obtains antioxidants from the diet. Glutathione is one of the most potent antioxidants produced by the body. On the other side of the issue, the superoxide radical is one of the most insidious of ROS produced by heavy exercise, disease or injury. Oxidative stress resulting from the production of free radicals will prolong the times it takes for your muscle to recover following intense exercise in preparation of muscle growth. Therefore, consuming dietary antioxidants is necessary to combat the development of OverTraining Syndrome (OTS).
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Antioxidants are Superoxide Scavengers
Creatine: A recent report has shown that creatine may act as an antioxidant in its own right (1). In fact, creatine is nearly as effective as glutathione in neutralizing the superoxide radical. This raises the intriguing possibility that part of creatines ergogenic benefit arises from its capacity to act as an antioxidant.
Folate: Vitamin B supplementation is effective at reducing oxidative damage (2). For instance, folic acid supplementation has been shown to reduce the production of the superoxide radical (3). The ability of folic acid to act as an superoxide scavenger will effectively reduce an athlete's chances of developing OverTraining Syndrome (OTS).
Vitamin B6: Homocysteine is converted into glutathione with the assistance of vitamin B6. The importance of this antioxidant-sustaining pathway is best exemplified by the finding that rats deprived of dietary vitamin B6 exhibit severely attenuated antioxidant defenses and are more sensitive to oxidative stress (4). It is thus not surprising that another report demonstrated that supplementation with vitamin B6 reduces markers of oxidant stress under conditions where homocysteine levels were exaggeratedly elevated by depriving animals of folic acid (5). Therefore, vitamin B6 represents yet another important way to reduce the harmful effects of oxidative stress following intense exercise.
Creatine, Folic Acid, Vitamin B6 & Nitric Oxide (NO)
One study demonstrated that folic acid increases the production of NO (Nitric Oxide) from the endothelial cells lining the inside of arteries (3). NO is a very important vasodilator and is essential for maintaining overall health. In fact, the name originally given to NO (before it was discovered to be a simple gas) was Endothelium-Derived Relaxing Factor, or EDRF; arteries in a healthy individual are soft and relaxed largely due to the presence of NO. Accordingly, the increased degradation of NO by superoxide is a key step in the development of atherosclerosis (arteriosclerosis - hardening of the arteries). Superoxide's NO-neutralizing effects have earned it the name Endothelium-Derived Constricting Factor, or EDCF. Certainly, creatine, folic acid and vitamin B6, by scavenging superoxide radicals, are essential for cardiovascular health.
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Macrophages are specialized cells of our immune systems that literally eat (phagocytize) foreign invaders. Macrophages use NO to combat the growth of tumors. Accordingly, inhibition of NO production reduces the microbiocidal and tumouricidal activities of macrophages. In fact, the long-standing practice of curing meat with nitrite is an extension of NO's antibacterial properties. Therefore, folic acid will increase your resistance to invading foreign pathogens by potentiating the effects of NO.
Previous studies have shown that NO is also a stimulator of insulin release. Insulin, growth hormone and testosterone are key players in the anabolic hormone response to exercise. Insulin also activates the transport of creatine into the cells of our body. Therefore, folic acid should improve your anabolic status.
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NO also detoxifies homocysteine by chemically combining with it, thereby interfering with its ability to produce superoxide. On the other hand, the fact that homocysteine itself is a prooxidant and produces superoxide radicals (that deplete cellular NO levels) counteracts this positive effect of NO (6). It now appears that homocysteine exerts its prooxidant effect by inducing the expression of a tumor promoting factor (Tumor Necrosis Factor-alpha, or TNF-alpha) that then stimulates the production of superoxide radicals via the actions of an enzyme known as NADH oxidase. These enzymatically produced superoxide radicals then interfere with the relaxation of blood vessels that is usually mediated by NO, commencing the biochemical cascade of events that ultimately lead to atherosclerosis (7). Nevertheless, regardless of downstream biochemical ramifications..., creatine and essential B-vitamins, by reducing serum homocysteine levels and scavenging superoxide radicals, will extend the healthful benefits of NO.
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Click here for a discussion of the other detrimental effects of homocysteine.
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In 1992 Science magazine named NO "Molecule of the Year" for its life-sustaining properties.
Surely, since creatine, folic acid and vitamin B6 help preserve our cellular levels of NO (by neutralizing superoxide), they are a worthwhile addition to any fitness regimen!
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Antioxidant Supplementing Regimen: The combination of creatine and specific B-vitamin supplementation will greatly improve your antioxidant status, accelerate muscle recovery following intense exercise as well as accentuate muscle anabolism. It is for these reasons that I strongly recommend that an athlete combine creatine with vitamin B supplementation during periods of intense training to assist in muscle recovery and growth.
Click here to be directed to a page outlining a creatine/B-vitamin supplementing routine designed specifically for this purpose.
Selected Scientific References:
1. Lawler J. M. et al. (2002) Direct antioxidant properties of creatine. Biochemical and Biophysical Research Communications, Volume 290 (1), pages 47-52.
2. Ullegaddi R. et al. (2004) B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke. Clinical Science, Volume 107, pages 477484.
3. Stroes E. S. G. et al. (2000) Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circulation Research, Volume 86, pages 1129-1134.
4. Taysi. S. (2005) Oxidant / antioxidant status in liver tissue of v itamin B6 deficient rats. Clinical Nutrition, Volume 24, pages 385 389.
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5. Mahfouz M. M. and F. A. Kummerow (2004) Vitamin C or Vitamin B6 supplementation prevent the oxidative stress and decrease of prostacyclin generation in homocysteinemic rats. The International Journal of Biochemistry and Cell Biology, Volume 36 (10), pages 1919-1932.
6. Stamler J. S. et al. (1993) Adverse vascular effects of homocysteine are modulated by endothelium derived relaxing factor and related oxides of nitrogen. Journal of Clinical Investigation, Volume 91, pages 308-318.
7. Ungvari Z. et al. (2003) Increased superoxide production in coronary arteries in hyperhomocysteinemia: role of tumor necrosis factor-alpha, NAD(P)H oxidase, and inducible nitric oxide synthase. Arteriosclerosis, Thrombosis, and Vascular Biology, Volume 23 (3), pages 418-424.
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