<body><h2>Creatine</h2><p><br></p><p> </p><p> &nbsp;syn. alpha-methyl guandino-acetic acid syn. creatine (various salts and derivatives)</p><p> &nbsp;image</p><p> </p><h2> &nbsp;Description:</h2><p> &nbsp;Creatine is an amino acid derivative that is synthesized in the body from arginine, glycine, and methionine, mainly in the liver and kidneys. Approximately 95% of the creatine found in the body is stored in skeletal muscle tissue.256 The body manufacturers approximately 1 gram of creatine per day, and the average person (with an omnivorous diet) ingests another 1 gram from meat and fish. Although not considered an essential part of the diet due to endogenous manufacture, creatine remains an extremely important biological component. It is integrally involved in energy metabolism in the muscles, the protein (nitrogen) balance, and cell membrane stability. It is also one of the most widely used sport supplement products, and is commonly applied to help increase muscle size, strength, and exercise performance.</p><p> &nbsp;image</p><p> &nbsp;Creatine supports the resynthesis of ATP (adenosine triphosphate) during anaerobic exercise, which is the primary carrier of cellular energy.257 In a reversible reaction, creatine borrows a phosphate group from ATP to form phosphocreatine and ADP (adenosine diphosphate). When energy is needed, this phosphocreatine will return the borrowed phosphate to ADP, again yielding ATP. This is a constant cyclic process, which allows the muscles to rapidly expend and replenish energy. The phosphocreatine-ATP cycle sustains maximum energy output for only a brief period of time, however. During high intensity output, the ATP resynthesis rate quickly fails to keep up with utilization, resulting in muscle fatigue. The normal biological turnover of creatine is about 2 grams per day.258 Supplementation beyond this level raises tissue creatine/phosphocreatine concentrations, enhancing ATP energy output during anaerobic exercise.</p><p> &nbsp;An increase in the content of creatine inside the muscle cell also produces a shift in the osmotic balance. This causes a phenomenon known as water drag, where the muscle cell pulls in water from the surrounding environment to reestablish osmotic balance. This hydration effect causes an increase in total body water retention. This typically accounts for 2-5 lbs of weight gain within the first week of initiating creatine supplementation.259 This tends to produce a visible increase in the overall size of the muscles, indistinguishable from increases due to protein retention. Since this water tends to be retained in the intracellular compartment, creatine supplementation is usually not associated with visible bloating and loss of definition.260</p><p> &nbsp;While cell hydration may account for much of the initial size increase due to creatine supplementation, its continued use also tends to produce significant muscle cell hypertrophy. Its exact mechanism of action here, however, it not fully understood. Studies examining amino acid kinetics during creatine supplementation have demonstrated a decrease in muscle protein breakdown during exercise (an anti-catabolic effect).261 Creatine also supports the increased expression of IGF-1 in the muscles, a key anabolic hormone.262,263 Studies also show that creatine can increase the expression of myogenin and MRF-4.264 These two transcriptional factors support myosin heavy chain synthesis, which is the main contractile protein in muscle. Creatine also appears to support the satellite cell cycle, which helps expand the functional size capacity of the muscle cell.265</p><p> &nbsp;The body has a threshold for maximum creatine retention in skeletal muscle.266 The saturation point (depending on diet) is usually between 10-40% above normal levels.267 Vegetarians consume less creatine, and tend to have lower levels. Once reaching the saturation point, there is no added benefit to consuming higher doses. The extra will simply be excreted in the urine. The use of a daily dose of 20 grams of creatine (monohydrate) will result in tissue saturation after as little as two to three days. After this point, lower doses will maintain elevated tissues stores. The common recommendation is for a brief loading period of 20 grams daily for five days, followed by maintenance dose of 3-5 grams per day until the end of use.268 One can alternately use as little as 3 grams per day (no loading period), but it can take up to 30 days to achieve tissue saturation.269</p><p> &nbsp;As a nutritional supplement, creatine is available in many different salts and ester forms including creatine monohydrate, ethyl ester, citrate, tricreatine citrate, pyruvate, and magnesium-creatine chelate. Creatine monohydrate is the most common, and also (by far) the most widely investigated and proven in a clinical setting. All creatine products are intended to increase the content of creatine and phosphocreatine in the muscles. This is important to remember. While the various forms may differ slightly from one another with regard to solubility properties, rate of digestion, and free creatine yield per gram, all are subject to the same limits of tissue creatine saturation. Also, bioavailability improvements over creatine monohydrate are unlikely since monohydrate is already estimated to exhibit near 100% absorption from the gastrointestinal tract.270</p><p> </p><p> &nbsp;image</p><p> &nbsp;Creatine is the most widely used ergogenic substance in the world. It is also the most extensively investigated, and has been the subject of more than 100 clinical studies. The results of these studies show that the short-term supplementation can effectively raise the content of creatine in the muscles. This shifts the osmotic balance, resulting in water influx and cell expansion. This also increases the cellular reserves of creatine and phosphocreatine, which support anaerobic energy metabolism. Creatine supplementation also tends to support a positive protein balance over time. Creatine is an effective sport supplement for weightlifting, and other activities where brief repeat bursts of energy are required such as sprinting, jumping, football, soccer, and baseball.271</p><p> &nbsp;Promoted Benefits:</p><p> &nbsp;Creatine is promoted to increase muscle creatine and phosphocreatine stores, support increased muscle mass and strength, and enhance energy and performance during anaerobic exercise. </p><h2> &nbsp;Clinical Studies: </h2><p> &nbsp;Creatine has been the subject of extensive clinical study. This ingredient has been shown to improve body composition and performance in placebo-controlled studies with trained adults. Its Clinical Support Rating is 5 (5/5).</p><h2> &nbsp;creatine monohydrate</h2><p> &nbsp;One of the most widely referenced placebo-controlled studies examined the effects of creatine monohydrate supplementation on resistance training performance in a group of experienced weightlifting men.272 Each subject ingested a loading dose of 25 grams per day for one week, followed by a maintenance dose of 5 grams daily for the remainder of the experiment. The supplementation continued for 12 weeks, during which time all participants underwent a heavy resistance training program. The supplementation of creatine resulted in a statistically significant increase in lean body mass (6.3% versus 3.1%) compared to placebo. Creatine monohydrate also resulted in greater increases in bench press (24% versus 16%) and squat strength (32% versus 24%) compared to placebo. An examination of muscle fiber content showed that subjects taking creatine monohydrate had significantly greater increases in all three fiber types compared to placebo: Type I (35% versus 11%), Type IIA (36% versus 15%), and Type IIAB (35% versus 6%). Training volume was also increased in the creatine monohydrate group.</p><p> &nbsp;Another placebo-controlled study examined the effects of creatine monohydrate supplementation on both muscle and aerobic performance in a group of competitive rugby players.273 One focus of this study was to see if an increase in muscle mass would hinder aerobic performance. The subjects ingested .1 grams of creatine monohydrate per kg of bodyweight per day, for a total period of eight weeks. This equates to a dose of 7 grams per day for a person of 70 kg (154 lbs). During the experiment, players followed their normal training and game schedules. Measures of body composition, muscle endurance (number of repetitions at 75% 1-rep maximum in bench and leg press), and aerobic endurance (shuttle-run test with progressively increasing speed) were taken before and after eight weeks of supplementation. Subjects taking creatine monohydrate noticed a statistically significant improvement in muscle endurance (+5.8 versus +0.9 repetitions) compared to placebo. There was no change in aerobic endurance. While not statistically significant, there was also a trend toward increased lean mass (+1.2 kg) in subjects taking creatine monohydrate.</p><p> &nbsp;In addition to the above, there are many other placebo-controlled studies examining the effects of creatine monohydrate under anaerobic exercise conditions. Some of these investigations have failed to note statistically significant improvements in certain measures of performance and/or body composition.274,275,276 This likely reflects methodological difficulties due to many other confounding variables such as diet, exercise, training experience, and individual genetic factors. The ergogenic properties of creatine with anaerobic exercise are widely accepted as valid. Creatine monohydrate supplementation does not appear to strongly influence oxygen consumption or performance in aerobic activities (such as long distance running).277</p><h2> &nbsp;creatine ethyl ester</h2><p> &nbsp;In one placebo-controlled study, the effect of creatine ethyl ester on body composition and exercise performance was compared to an equal dose of creatine monohydrate in a group of healthy men.278 Subjects consumed 20 grams of either form of creatine each day for five days (loading), followed by 5 grams daily for the remaining six weeks. All participants followed a controlled heavy resistance training program. Creatine ethyl ester was shown to be not as effective as monohydrate at raising serum and muscle creatine content, nor at supporting increases in lean body mass, strength, or muscle power. While exercise improvements were made in the ethyl ester group, it was not possible to attribute them to supplementation. </p><p> &nbsp;The above study did suggest that creatine ethyl ester was much less stable than monohydrate, as serum levels of the main creatine metabolite (creatinine) were significantly higher in comparison. This is in agreement with another incubation study that suggests creatine ethyl ester has a half-life in human serum of only about one minute, which may be too short to reach muscle tissue in significant levels.279 Further research on creatine ethyl ester is needed.</p><p> </p><h2> &nbsp;creatine citrate</h2><p> &nbsp;One placebo-controlled study examined the effects of five weeks of creatine citrate supplementation on handgrip exercise performance in a group of healthy men.280 Subjects consumed 5 grams of creatine citrate per day, which is equivalent to 3 grams of base creatine. Subjects taking creatine citrate noticed statistically significant improvements in mean power and contraction velocity compared to placebo. These results suggest that creatine citrate possesses similar ergogenic activity as creatine monohydrate, although no direct comparison between the two has been made.</p><h2> &nbsp;tricreatine citrate</h2><p> &nbsp;In pharmacokinetic studies, tricreatine citrate was shown to produce a similar increase in the serum creatine level compared to creatine monohydrate (when taken in base-creatine equivalent doses).281 This study suggests that tricreatine citrate possesses similar ergogenic activity as creatine monohydrate.</p><h2> &nbsp;creatine pyruvate</h2><p> &nbsp;The effects of five weeks of creatine pyruvate supplementation on handgrip exercise performance were compared to an equal dose of creatine citrate in a placebo-controlled study with healthy men.282 Subjects consumed 5 grams of either creatine per day, equivalent to 3 grams of base creatine. Both groups noticed statistically significant improvements in mean power and contraction velocity compared to placebo. Creatine pyruvate also produced improvements in relaxation velocity and oxygen consumption not noted with creatine citrate. </p><p> &nbsp;Another study examined the effects of creatine pyruvate on exercise performance in a group of Olympic canoeists.283 Each subject ingested 7.5 grams of creatine pyruvate daily for five days, which is equivalent to about 5 grams of creatine monohydrate (base creatine content). The supplementation of creatine pyruvate resulted in improvements in paddling speed and serum lactate buildup (reduced), suggesting improvements in aerobic metabolism.</p><p> &nbsp;A pharmacokinetic study demonstrated that creatine pyruvate was 17% and 14% more effective at raising serum creatine levels compared to tricreatine citrate and creatine monohydrate, respectively.284 The creatines were administered at base-creatine equivalent doses, which amounted to 7.3 g of creatine pyruvate, 6.7 g of tricreatine citrate, and 5 g of creatine monohydrate.</p><h2> &nbsp;magnesium-creatine chelate</h2><p> &nbsp;One placebo-controlled study examined the effects of magnesium-creatine chelate on exercise performance in a group of healthy subjects.285 Each participant took a dose equivalent to 800 mg of magnesium and 5 grams of creatine per day for a period of two weeks. Subjects taking magnesium-creatine chelate noticed statistically significant improvements in muscle torque and total body water (intracellular compartment), which were better than subjects taking creatine monohydrate plus a seperate magnesium oxide supplement. Other studies suggest that magnesium-creatine chelate possesses similar ergogenic activity to creatine monohydrate.286</p><h2> &nbsp;Empirical Evidence: </h2><p> &nbsp;Creatine is widely available as a stand-alone nutritional supplement. The feedback on its use as a sport supplement has been strongly positive. Creatine is, in fact, one of the most reliable ergogenic supplements in common use today. Most users report a rapid increase in bodyweight (up to five pounds) within the first week of use at tissue saturation levels. The continued use of this supplement for six to eight weeks tends to also lead to a substantial increase in muscle protein content, often amounting to another 5 lbs or more of weight gain. This supplement also seems highly valued in a wide variety of competitive sports where intermitted bouts of high intensity exertion are required. A small percentage of users appear to be non-responsive to creatine use. This seems to be in agreement with studies suggesting that a minority of users (20-30%) are unable to appreciably saturate tissues with creatine, even after loading phases of use, due to some unknown variable.287 Creatine has an Empirical Evidence Rating of 5 (5/5).</p><h2> &nbsp;Effective Dosage: </h2><p> &nbsp;Based on clinical studies, a loading phase of 20 g daily (creatine monohydrate) is recommended for 5 days at the start of use, which is followed by a maintenance dosage of 3-5 grams per day until the end of supplementation. The consumption of simple carbohydrates with creatine monohydrate has been shown to increase tissue creatine stores by an additional 9% over the use of creatine alone.288 To maintain maximum effectiveness, creatine is typically taken for a period of 6-12 weeks, followed by an equal amount of time off. Creatine levels may stay elevated for up to six weeks after stopping supplementation.289</p><h2> &nbsp;Side Effects / Safety:</h2><p> &nbsp;Creatine supplementation appears to be safe in healthy individuals. One long-term study examined the use of 4 grams of creatine monohydrate daily for two years in elderly patients with Parkinson disease.290 The supplementation of creatine was well tolerated, and failed to produce health significant side effects. A small number of subjects reported minor gastrointestinal disturbances, but there were no negative changes in any marker of general or renal health. Note that creatine breaks down to creatinin, which can interfere with diagnostic tests of kidney function. Creatine supplementation according to common guidelines is not believed to harm healthy kidney function.</p><p> </p><p> &nbsp;</p><p>&nbsp;</p></body>