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Creatine is a nitrogenous organic acid that naturally occurs in vertebrates and helps to supply energy to muscle cells.
History of creatine
In 1835, the French scientist Michel Eugène Chevreul discovered a component of skeletal muscle that he later named creatine after the Greek word for flesh, Kreas.
In 1912, researchers found that ingesting creatine can dramatically boost the creatine content of the muscle. In the late 1920s, scientists found that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle.
The Russians and other Eastern Bloc countries may have used creatine as a sports supplementation as far back as the 1970s, although this is a matter of debate.
While creatine's influence on physical performance has been well documented since the early twentieth century, it only recently came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in the London Times reported that Linford Christie, the gold medal winner at 100 meters, had utilized creatine prior to the Olympics, and an article in Bodybuilding Monthly named Sally Gunnell, gold medalist in the 400-meter hurdles, as another creatine user. Several medal-winning British rowers also used creatine during their preparations for the Barcelona games.
At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called EAS (Experimental and Applied Sciences) introduced the compound to the sports nutrition market under the name Phosphagen.
Since that time numerous creatine supplements have been introduced, with the most notable advancements coming in 1998, with the launch of the first creatine-carbohydrate-alpha lipoic acid supplement, Cell-Tech, by MuscleTech Research and Development, and in 2003 with the introduction of the first creatine ethyl ester supplements.
To date, the most extensively researched and proven brand-name creatine supplement is Cell-Tech (Parise, G., et al. 2000,. Kalman, D., et al., and 2000 Tarnopolsky et al, 2001) which remains one of the most-used creatine supplements in the world.
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Creatine Ethyl Ester is also becoming a widely used form of creatine, with many companies now carrying both creatine monohydrate-based supplements and Creatine Ethyl Ester supplements. Creatine monohydate ($400 million in annual sales in the United States alone) still easily outsells all other forms of creatine.
In the human body creatine is synthesized in the liver by the use of part from three different amino acids - Arg, Gly, and Met. 95% of it is later stored in the skeletal muscles, with the rest in the brain, heart, and testes.
In the muscles, a fraction of the total creatine binds to phosphate - forming creatine phosphate. The reaction is catalysed by creatine kinases, and the result is phosphocreatine (PCr). Phosphocreatine binds with ADP to convert it back to ATP, an important cellular energy source.
There is scientific evidence that taking creatine supplements can marginally increase athletic performance in high-intensity, anaerobic exercise. Ingesting creatine can increase the level of phosphocreatine in the muscles up to 20%. An additional study (Rae et al, 2003) suggests increased mental capabilities as a result of oral intake of creatine over a 60 day period.
It must be noted creatine has no significant effect on aerobic exercise (Engelhardt et al, 1998).
A majority of studies conclude that creatine supplementation increases both total and fat-free body mass. Since body mass gains of about 1 kg can occur in a week's time, several studies suggest that the gain is simply due to greater water retention inside the muscle cells. However, studies into the long-term effect of creatine supplementation suggest that body mass gains cannot be explained by increases in intracellular water alone. In the longer term, the increase in total body water is reported to be proportional to the weight gains, which means that the percentage of total body water is not significantly changed. The magnitude of the weight gains during training over a period of several weeks argue against the water-retention theory.
It is possible that the initial increase in intracellular water increases osmotic pressure, which in turn stimulates protein synthesis. A few studies have reported changes in the nitrogen balance during creatine supplementation, suggesting that creatine increases protein synthesis and/or decreases protein breakdown.
Also, research has shown that creatine increases the activity of myogenic cells. These cells, sometimes called satellite cells, are myogenic stem cells that make hypertrophy of adult skeletal muscle possible. These stem cells are simply generic or non-specific cells that have the ability to transform themselves into new muscle cells when they are instructed to. Following proliferation (reproduction) and subsequent differentiation (to become a specific type of cell), these satellite cells will fuse with one another or with the adjacent damaged muscle fiber, thereby increasing myonuclei numbers necessary for fiber growth and repair. The study, published in the International Journal of Sports Medicine was able to show that creatine supplementation increased the number of myonuclei donated from satellite cells. This increases the potential for growth of those fibers. This increase in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4 (Hespel, 2001).
Since creatine may allow athletes to train harder and recover faster, the enhanced training stimulus may promote greater muscle hypertrophy in the long term. Ultimately, the increase in muscle mass is probably attributable to a combination of all these factors: greater water retention inside the muscle cells, increase in protein synthesis and/or decrease in protein breakdown and greater training stimulus.
Current studies indicate that short-term creatine supplementation in healthy individuals is safe (Robinson et al., 2000), and a long term study suggests the same thing (Mayhew & Ware, 2002).
In the past, there have been many reports of excessive cramping caused by creatine supplementation. However, there is no direct link to creatine use and muscle cramping or pulls, and research shows that creatine doesn’t impair heat regulation during exercise. Results from a study done at the University of Memphis showed no reports of muscle cramping in subjects taking creatine-containing supplements during various exercise training conditions. Among the test subjects were elite junior swimmers, college football players, and trained and untrained endurance athletes. (Kreider R, et al, 1998)
Creatine use is not considered doping and is currently acceptable to all sports-governing bodies. In some countries however, like France, creatine is banned.
In humans typically half of creatine intake comes from food (mainly from meat and fish).
Creatine is often taken by humans as a supplement for those wishing to gain muscle mass (bodybuilding). There are a number of forms but the most common are creatine monohydrate - creatine bonded with a molecule of water, and Creatine Ethyl Ester (CEE) – which is creatine monohydrate with an ester attached. A number of methods for ingestion exist - as a powder mixed into a drink, as concentrated liquid (known as creatine serum), or as a pill.
The majority of scientific studies have been conducted using creatine monohydrate in powdered form and similar effects may not be obtained from other formulas.
Loading and consumption
Several manufacturers suggest that creatine should be loaded into the body - for the first few days a high dose is taken followed by a lower maintenance dose. Various supplementation strategies have been used in attempts to increase total creatine concentration, particularly phosphocreatine. The most commonly used protocol is to ingest a daily total of 20 to 30 g of creatine, usually creatine monohydrate, in four equal doses of 5 to 7 g dissolved in fluids over the course of a day, for 5 to 7 days. (Greenhaff et al. 2003) suggests this increases the concentration in the muscles.
However, some suggest that the same effects can be gained using a consistent dosage. In testing this, Dr. Hultman and coworkers employed several strategies, including a rapid protocol involving 6 days of creatine supplementation at a rate of 20 g/day, and a slower protocol with supplementation for 28 days at a rate of 3 g/day.4 Following the rapid protocol, they also studied a maintenance dose of 2 g/day for 28 days. Both the rapid and slow loading protocols produced similar findings, about a 20% increase in muscle total creatine concentration. The elevated muscle total creatine concentration was maintained when supplementation was continued at a rate of 2 g/day.
In the early 90's, researchers found that the intake of carbohydrates (such as dextrose) with creatine promoted creatine storage beyond isolated creatine supplementation. (Stout et al. 1993) In fact, these studies suggest that the consumption of creatine with these high-glycemic sugars improves creatine storage by up to 60% on average.
Creatine and the treatment of muscular diseases
Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neurological and neuromuscular diseases (arthritis, congestive heart failure, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, neuroprotection, etc.).
Two scientific studies have indicated that creatine may be beneficial for neuromuscular disorders. First, a study by MDA-funded researcher M. Flint Beal of Cornell University Medical Center demonstrated that creatine was twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). Beal suspects that the neuroprotective effects of creatine in the mouse model of ALS are due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway that leads to cell death.
Second, a study by Canadian researchers Mark Tarnopolsky and Joan Martin of McMaster University Medical Center in Hamilton, Ontario found that creatine can cause modest increases in strength in people with a variety of neuromuscular disorders. Beal's work was published in the March 1999 issue of Nature Neuroscience and the second paper was published in the March 1999 issue of Neurology..
Richard B. Kreider (1998). Creatine: The Ergogenic/Anabolic Supplement, Mesomorphosis, 1(4). 
Michael E. Powers et al. (2003). Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution, Journal of Athletic Training, 38(1): 44-50. 
Mayhew DL, Mayhew JL, Ware JS (2002). Effects of long-term creatine supplementation on liver and kidney functions in American college football players., Int J Sport Nutr Exerc Metab., 12(4): 453-60. PMID 12500988.
Robinson TM et al. (2000). Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function, British Journal of Sports Medicine, 34: 284-288. 
Engelhardt M, Neumann G, Berbalk A, Reuter I (1998). Creatine supplementation in endurance sports., British Journal of Med Sci Sports Exerc., 30(7): 1123-9. PMID 9662683
Rae C, Digney AL, McEwan SR, Bates TC (2003). Oral creatine monohydrate supplementation improves cognitive performance; a placebo-controlled, double-blind cross-over trial., Proceedings of the Royal Society of London - Biological Sciences, 270(1529): 2147-2150.
Greenhaff PL et al. (1993). Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise in men., Clinical Science, 84: 565-571.
Stout JR et al. (1997). The effects of a supplement designed to augment creatine uptake on anaerobic reserve capacity, NSCA National Conference Abstract.
Dangott B, Schultz E, Mozdziak PE. (2000). Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy, International Journal of Sports Medicine, 2000 Jan(21(1):): 13-6.
Hespel P, Op't Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, Dymarkowski S, Van Hecke P, Richter EA. (2001). Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans, J Physiol., 2001 Oct 15(536(Pt 2)): 625-33.
Kreider R, Rasmussen C, Ransom J, Almada AL. (1998). Effects of creatine supplementation during training on the incidence of muscle cramping, injuries and GI distress., J Strength Cond Res., 12(275).
Hultman E, Soderlund K, Timmons JA, et al. (1996). Muscle creatine loading in man., J Appl Physiol(81): 232-237.
Tarnopolsky MA, Parise G, Yardley NJ, Ballantyne CS, Olatinji S, Phillips SM (2001). Creatine-dextrose and protein-dextrose induce similar strength gains during training, Med Sci Sports Exerc., 33(12): 2044-52. 
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