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Creatine supplementsFor the biochemistry and physiology of creatine, please see Creatine.
History of creatine supplementsIn 1912, Harvard University researchers Otto Folin and Willey Glover Denis found proof that ingesting creatine can dramatically boost the creatine content of the muscle[1]. In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates. While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in The 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 Experimental and Applied Sciences (EAS) introduced the compound to the sports nutrition market under the name Phosphagen.[2] Research conducted afterward showed that the consumption of high glycemic carbohydrates in conjunction with creatine increases creatine muscle stores and performance.[3] In 1998, MuscleTech Research and Development launched Cell-Tech, the first creatine-carbohydrate-alpha lipoic acid supplement. Alpha lipoic acid has been demonstrated to enhance muscle phosphocreatine levels and total muscle creatine concentrations. This approach to creatine supplementation was validated in a study performed in 2003.[4] Another important event in creatine supplementation occurred in 2004 when the first creatine ethyl ester supplements were launched. Creatine ethyl ester (CEE) is becoming a widely used form of creatine, with many companies now carrying both creatine monohydrate-based supplements and CEE supplements, or combinations of both. Creatine and athletic performanceCreatine is often taken by athletes 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 complexed with a molecule of water) and Creatine ethyl ester (CEE). A number of methods for ingestion exist: as a powder mixed into a drink, or as a capsule or caplet. Once ingested, creatine is highly bioavailable, whether it is ingested as the crystalline monohydrate form, the free form in solution, or even in meat. Creatine salts will become the free form when dissolved in aqueous solution. Conventional wisdom recommends the consumption of creatine with high glycemic index carbohydrates.[5] There is scientific evidence that short term creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work (periods of work and rest) by 5 to 15%. This is mainly bouts of running/cycling sprints and multiple sets of low RM weightlifting. Single effort work shows an increase of 1 to 5%. This refers mainly to single sprints and single lifting of 1-2RM weights. However, some studies show no ergogenic effect at all.[6]. Studies in endurance athletes have been less than promising, most likely because these activities are sustained at a given intensity and thus do not allow for significant intra-exercise synthesis of additional creatine phosphate molecules. Ingesting creatine can increase the level of phosphocreatine in the muscles up to 20%. It must be noted creatine has no significant effect on aerobic endurance, though it will increase power during short sessions of high-intensity aerobic exercise.[7][8] Since body mass gains of about 1 kg can occur in a week's time, many studies suggest that the gain is simply due to greater water retention inside the muscle cells.[9] Other studies, however, have shown that creatine increases the activity of satellite cells, which make muscle hypertrophy possible. Creatine supplementation appears to increase the number of myonuclei that satellite cells will 'donate' to damaged muscle fibers, which 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.[10][11]. In another study, researchers concluded that changes in substrate oxidation may influence the inhibition of fat mass loss associated with creatine after weight training when they discovered that fat mass did not change significantly with creatine but decreased after the placebo trial in a 12-week study on ten active men. The study also showed that 1-RM bench press and total body mass increased after creatine, but not after placebo.[12] The underlying effect of creatine on body composition has yet to be determined, as another study with a similar timeframe suggests no effect on body composition, but had less overall emphasis on metabolic effects. [13] There are two scientifically proven ways to supplement with creatine. The first is through a loading phase, in which 20 grams is taken for 5–7 days, followed by a maintenance phase of 3-5 grams a day for periods of 2–3 months at a time. The second consists of taking 3-10 grams of creatine per day for a period of 2–3 months with no loading phase. It is generally recommended to take at least 1–2 weeks off from creatine supplementation in order to maintain a proper response mechanism in the body. [1] Creatine use is not considered doping and is not banned by the majority of sport-governing bodies. However, in the United States, the NCAA recently ruled that colleges could not provide creatine supplements to their players, though the players are still allowed to obtain and use creatine independently. Creatine ethyl esterMain article: Creatine ethyl ester
CEE is a form of commercially available creatine touted to have higher absorption rates and a longer serum half-life than regular creatine monohydrate by several supplement companies. However, no peer-reviewed studies have emerged on creatine ethyl ester which conclusively prove these claims. A study presented at the 4th International Society of Sports Nutrition (ISSN) annual meeting demonstrated that the addition of the ethyl group to creatine actually reduces acid stability and accelerates its breakdown to creatinine. The researchers concluded that creatine ethyl ester is inferior to creatine monohydrate as a source of creatine.[14] As a supplement, the compound was patented, and licensed through UNeMed, the technology transfer entity of the University of Nebraska Medical Center.[15] SafetySome current studies indicate that short-term creatine supplementation in healthy individuals is safe, although those with renal disease should avoid it due to possible risks of renal dysfunction, and before using it healthy users should bear these possible risks in mind.[8][16][17][18] Small-scale, longer-term studies have been done and seem to demonstrate its safety.[19][20][21] There have been reports of muscle cramping with the use of creatine, though a study showed no reports of muscle cramping in subjects taking creatine-containing supplements during various exercise training conditions in trained and untrained endurance athletes.[6][22] The cause of the reported cramping by some users may be due to dehydration, and extra water intake is vital when supplementing with creatine. Side effects that produce lower leg pain may be associated with the use of creatine. Creatine may be the cause of an increase in the anterior pressures of the lower leg. This is usually found in post-creatine use when at rest and after exercise. Normal at-rest pressures have been found to be highly elevated by subjects who used creatine within the prior 35 days when compared to no supplementation. This can produce an extreme amount of pain in the lower leg due to the rigidity of the anterior compartment of the lower leg and lack of fluid drainage out of the compartment. It may also be exacerbated by the increase of water content in the muscle fibers, putting more pressure on the anterior compartment. If the levels remain high for a long period of time, irreversible damage to tissue may occur, particularly to the peroneal nerve. These conditions can further be found under Chronic Compartment Syndrome.[23] In addition, experiments have shown that creatine supplementation improved the health and lifespan of mice.[24] Whether these beneficial effects would also apply to humans is still uncertain. It also led to a rise in allergic lung reactions in an animal test on mice with pre-existent allergic disease.[25] Creatine supplementation, in the dosages commonly used, results in urinary concentrations that are 90 times greater than normal. The long term effects of this have not been investigated, but there is possibility for a variety of nephrotoxic, i.e., kidney damaging, events. There is potential for direct toxicity on renal tubules where urine is formed, and for acceleration of kidney stone formation.[26] Creatine has been shown to accelerate the growth of cysts in rats with Polycystic Kidney Disease (PKD).[27] Studies have not yet determined if Creatine supplementation will accelerate the growth of cysts in humans with PKD. PKD is prevalent in approximately 1 in 1000 people and may not be detectable until affected individuals reach their thirties. As well bladder control may be affected. One case study suggested that there was increased risk of rhabdomyolysis and thence renal failure after the use of a tourniquet during surgery.[28] Creatine and mental performanceCreatine administration was shown to significantly improve performance in cognitive and memory tests in vegetarian individuals involved in double-blind, placebo-controlled cross-over trials.[29] Vegetarian supplementation with creatine seems to be especially beneficial as they appear to have lower average body stores, since meat is a primary source of dietary creatine.[29] References
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