Introduction
There is a lot of controversy on nutritional supplements and performance/health claims that go along with them. Many claims come and go without a lot of hassle, but none has generated the commotion of the interest or debate surrounding creatine (Cr). Many people believe Cr is another weight gaining powder or steroid alternative (Plisk and Kreider, 1999). What those people do not know is Cr is also found in the human body naturally as opposed to supplementation.
Individuals know the name creatine but may not understand the science behind it. The use of Cr has become very widespread, usually in the supplement form Cr monohydrate. Every since the discovery of the ability to increase Cr and phosphocreatine (PCr) inside the human muscles by oral ingestion of supplemental Cr has led to many studies showcasing the benefits of exercise performance. Cr monohydrate supplementation shows significant results to increase the human body’s ability to maintain power output during high-intensity exercise and increase the rate of PCr to resynthesis during the recovery phase of intermittent high intensity exercise (Volek and Kraemer, 1996). My goal is to provide significant information on natural Cr functions, Cr as a supplement, ways the human body utilize Cr to enhance athletic performance, and how society views/uses Cr.
Effects of Creatine in the Human Body Creatine was discovered by a French scientist named Chevreul in 1832 but it was not until 1847 did another scientist Lieberg discover that Cr in the body was directly involved in producing muscle work. Cr can be found naturally in foods like: beef, pork, and some types of fish (Grande and Graves, 2005). To understand the process of which Cr goes through the body can be complex. As previously stated Cr is present in meat, fish, and poultry, from there it is absorbed intact by the stomach when ingested. Cr is further synthesized in the kidney, liver, and pancreas from amino acid precursor’s arginine, glycine, and methionine. After synthesization occurs Cr is released into the bloodstream and is taken up via insulin-modulated active transport, stored and used by tissues with explosive or variable energy demands, especially the neuromuscular system and the heart which uses ~95% (Plisk and Kreider, 1999). Although Cr is commonly known to participate in the high energy system ATP-PC/Phosphagen system, this stipulation may be over simplified without being fully explained (Plisk and Kreider, 1999). . After absorption, a portion of free Cr combines with phosphate to form phosphocreatine (PCr). This becomes a vital storage for energy since Cr and PCr allows rapid resynthesis of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to meet energy demands (Grande and Graves, 2005). The body only has very limited storage of ATP and ADP. When these energy demands are made between the relationship of Cr, PCr, and ATP a reaction happens allowing the ATP to be resynthesized by Cr and PCr via creatine kinase (CK) reaction (Grande and Graves, 2005). Once utilization by the CK reaction occurs, Cr is most likely resynthezied into PCr within the mitochondria by the oxidative metabolism. Inside cells, CK activity is the primary regulator of PCr breakdown. As ADP concentrations increase, simultaneously an increase in CK activity occurs. Consenquencely, as ATP concentrations increase, CK activity will decrease. Hypothetically, Cr supplementation will increase Cr and PCr stores, aiding more PCr to be utilized in CK reactions (Grande and Graves, 2005). Table 1 The Creatine Kinase Reaction | Creatine Kinase (Grande and Graves 2005)
PCr + ADP ATP + Cr |

A standard of supplementation has been developed on Cr dosages. The ideal goal behind Cr supplementation is to increase the total creatine concentration (TCr). Supplementing 20g/daily for a period of 4-6days has shown to increase TCr by approximately 20% (Ehrlich, 2010). Thus, supplementation regimens have been reported to sustain ATP resynthesis and positively affect high intensity, short-duration maximal exercise performance (Grande and Graves, 2005). Cr supplementation is also found to enhance resynthesis of PCr during rest periods between repeated bouts of exercise, and prolonged Cr supplementation may increase myofibril protein synthesis, resulting to muscle growth (Grande and Graves, 2005). There are currently 5 different ways to supplement Cr; pills, capsules, stabilized liquids, and 2 forms of powders (Antonio, 2004). One form of powder is Cr alone and the other powder obtains Cr and carbohydrates (CHO), either dextrose or maltodextrin (CHO-Cr). The supplement with the least amount of known literature for research is in the form of liquid, there has been no peer-reviewed studies to validate the effectiveness (Grande and Graves, 2005).There may a significant difference between powder Cr and CHO-Cr. CHO raises insulin in blood stimulating more blood flow. Insulin is also a main transporter of Cr to muscles; therefore increased levels of blood insulin have been shown to increase muscle Cr uptake. As a result 60% greater increase in TCr stores over that of Cr powder when CHO-Cr supplement is ingested. (Grande and Graves, 2005). Creatine and Exercise
Most clinical studies have shown that Cr supplements improve strength and lean muscle mass during high-intensity, short-duration exercise, such as weight lifting (Ehrlich, 2010). The athletes that will find the best results are those with the demand of short bouts of energy use (Ehrlich, 2010). Most investigations have demonstrated that Cr supplementation can significantly increase strength, power, sprint performance, and work performed during maximal-effort muscular contractions. It is very important to note that the benefits that Cr demonstrates is an ergogenic effect employed by very short rest periods (Haff and Kirksey, 1999). Thus, work performed in multiple bouts of exercise separated by short rest intervals of <5minutes. On the other end of the spectrum, endurance athletes can almost expect to see no performance benefit from Cr supplementation. It is found that athletes whom perform exercise lasting >60seconds should not supplement with Cr in their diets due to negative benefits of Cr (Haff and Kirksey, 1999). Studies which looked at endurance exercise failed to show any benefit of creatine compared to placebo (Jenkins, 2006). In fact, one study measured running performance over a 6 km course, found slower times in the creatine supplemented group (Jenkins, 2006). This effect is possibly related to the weight gain associated with creatine use. Since the ATP system is not used by endurance athletes, the weight gain is "dead weight" and provides no help to the athlete moving forward. Instead, the extra weight makes the athlete less efficient (Jenkins, 2006).
Opponents of creatine supplementation have claimed that it is not safe for children and adolescents (Buford, 2007). While fewer investigations have been conducted in using younger participants, no study has shown Cr supplementation to have adverse effects in children. In fact, long-term Cr supplementation (4-8g/day for up to 3 years) has been used as an adjunctive therapy for a number of creatine synthesis deficiencies and neuromuscular disorders in children (Buford, 2007). Nevertheless, as less is known about the effects on children and adolescents supplementing with Cr, it is the view of the International Society of Sports Nutrition (ISSN) that younger athletes should consider a Cr supplement only if the following conditions are met (Buford, 2007):
1. The athlete is past puberty and is involved in serious/competitive training that may benefit from Cr supplementation;
2. The athlete is eating a well-balanced, performance-enhancing diet;
3. The athlete and his/her parents understand the truth concerning the effects of Cr supplementation;
4. The athlete’s parents approve that their child takes supplemental Cr;
5. Cr supplementation can be supervised by the athlete’s parents, trainers, coaches, and/or physician;
6. Quality Cr supplementation is used;
7. The athlete does not exceed recommended dosages If these conditions are met, then it would seem reasonable that children and/or adolescents should be able to take a Cr supplement. By doing so may provide a safe nutritional advantage so the children/adolescents view Cr as an alternative to illegal anabolic steroids (Buford, 2007). In turn, if the above conditions are not met then Cr supplementations may not be appropriate. The reasoning is to teach the young athletes the importance of proper training and dietary strategies to optimize performance (Buford, 2007). Creatine should not be viewed as a short cut to athletic success in young athletes or to any other users. However, it is able to offer some benefits to optimize training of athletes involved in intense exercise in a similar manner that ingesting a high-carbohydrate diet, sports drinks, and/or carbohydrate loading can optimize performance of an endurance athlete (Buford, 2007).
Medical Safety and Ethics of Cr Supplementation While the only clinically significant side effect reported in the research literature is that of weight gain, many anecdotal claims of side effects including dehydration, cramping, kidney and liver damage, musculoskeletal injury, gastrointestinal distress, and anterior leg compartment syndrome still exist in the media and popular literature (Buford, 2007). While athletes who are taking Cr supplementation may experience these symptoms, the scientific literature suggests that these athletes have no greater, and a possibly lower risk of these symptoms than those not supplementing with Cr (Buford, 2007). Many of these fears have been generated by the media and data taken from case studies. The numbers of individuals are increasing that have a variety of disorders that are using therapeutic exercise (i.e., post-MI, neuromuscular disease, postoperative orthopedic surgery, ect.). Many conditions of these diseases exhibit muscle atrophy and premature muscle fatigue and strategies that may temper these effects may have functional significance to these individuals (Terjung and Clarkson, 2000). There is evidence of a beneficial effect in particular patients with Cr supplementations. Thus, there is hope that Cr supplementation can influence morbidity, at least in some patients; the outlook is strongest where the clinical problems most carefully match the physiological and biochemical effects of Cr in the cell (Terjung and Clarkson, 2000). Congestive heart failure is known that cardiac CK activity and Cr content are reduced in patients with left ventricular hypertrophy (Ingwall, 1996). Therefore, improving contractile function and/or recovery of Cr supplementation might improve cardiac function in patients with congestive heart failure (Terjung and Clarkson, 2000). Although there was no effect of Cr supplementation on the ejection fraction of such patients, exercise at a greater intensity could be performed after Cr supplementation (Gordon, 1995). Neuromuscular disease is related to a decrease in muscle PCr concentrations and is found in conditions of inflammatory myopathy, mitochondrial cytopathy, and muscle dystrophy (Tarnopolsky and Martin, 1999). Muscle weakness and atrophy are common outcomes in these disorders and contribute to disability and handicap (Terjung and Clarkson, 2000). In a randomized, double-blind, cross-over study, it was found that Cr supplementation resulted in an increase in high-intensity, intermittent exercise performance in seven patients with mitochondrial cytopathy (Terjung and Clarkson, 2000). In a subsequent study, this group found that a similar Cr supplementation strategy resulted in enhanced muscle performance in an open and single-blind trial in patients with a variety of neuromuscular disorders (Tarnopolsky and Martin, 1999). Several athletic governing bodies and special interest groups have always questioned whether it is ethical for athletes to take Cr supplements as a method of enhancing performance (Buford, 2007). With a lot of recent studies indicating Cr supplementation has the ability to improve performance, it would be difficult to ingest enough creatine from food in the diet, making it rationalized that it is unethical to do so (Buford, 2007). In this age of steroid suspicion in sports, some argue that if you allow athletes to take creatine, they may be more predisposed to try other dangerous supplements and/or drugs. Still others have attempted to directly lump Cr in with anabolic steroid and/or banned stimulants and have called for a ban on the use of Cr supplements among athletes (Buford, 2007). Cr supplementations are not currently banned by any athletic organization although the NCAA does not allow institutions to provide Cr supplements or other “muscle building” supplements to their athletes (NCAA Academic and Membership Affairs Staff, 2010). There is merely no difference in the use of Cr supplementation and ethical methods of gaining athletic advantage such as using advanced training techniques and proper nutritional methods (Buford, 2007). Carbohydrate loading is a nutritional technique used to enhance performance by enhancing glycogen stores, the difference between such a practice and supplementing Cr to enhance skeletal muscle Cr and PCr stores (Buford, 2007). If any concerns, it could be argued that banning the use of creatine would be unethical as it has been reported to decrease the incidence of musculoskeletal injuries, heat stress, provide neuroprotective effects, and expedite rehabilitation from injury (Buford, 2007).

Conclusion
Despite lingering myths concerning creatine (Cr) supplementation in conjunction with exercise, Cr supplements remain one of the most extensively studied, as well as effective, nutritional aids available to athletes. Hundreds of studies have shown the effectiveness of Cr supplementation in improving anaerobic capacity, strength, and lean body mass in conjunction with training. In addition, Cr has repeatedly been reported to be safe for adults and adolescents under parental supervision, as well as possibly beneficial in preventing injury. Finally, the future of creatine research looks bright in regard to the areas of transport mechanisms, improved muscle retention, as well as treatment of numerous clinical supplementations.

References

Antonio, J. (2004). Creatine Loading and Maintenance Dosing. National Strength and Conditioning Association, 26(1), 26-27.
Buford T. (2007). Creatine Supplementation and Exercise. Journal of the International Society of Sports Nutrition, 4(2), 10-20.
Ehrlich, S. (2010). Creatine. University of Maryland Medical Center. Retrieved December 1, 2010, from http://www.umm.edu/altmed/articles/creatine-000297.htm
Gordon, A. (1995). Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc. Res. 30:413– 418, 1995.
Grande, B., & Graves, S. (2005). Creatine Supplementations: Forms, Function, and Effects. National Strength and Conditioning Association, 27(1), 62-68.
Haff, G., & Kirksey, B. (1999). Creatine Supplementation. National Strength and Conditioning Association, 21(4), 13-23.
Ingwall, J. S. (1999) Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ. Res. 38:115–123
Jenkins, M. A. (2006). Creatine Supplementation in Athletes: Review. Rice University. Retrieved December 1, 2010, from http://www.rice.edu/~jenky/sports/creatine
NCAA Academic and Membership Affairs Staff. (2010). 2010-2011 NCAA Manual. National Collegiate Athletic Association 1, 1-434
Plisk, S., & Kreider, R. (1999). Creatine Controversy. National Strength and Conditioning Association, 21(1), 14-23.
Tarnopolsky, M., and Martin, J. (1999). Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology 52:854–857, 1999.
Terjung, R., & Clarkson, P. (2000). The Physiological and Health Effects of Oral Creatine Supplementations. American College of Sports Medicine, 32(3), 706- 717.
Volek, J., & Kraemer, W. (1996). Creatine Supplementation: Its Effect on Human Muscular Performance and Body Composition. Journal of Strength and Conditioning Research, 10(3), 200-210.