Just quoting BN
Section 1. General Information
1.1: What is creatine?
Creatine (also known as alpha-methylguanidinoacetic acid) is perhaps the most popular supplement for improving athletic performance and increasing muscle mass. It also has more scientific support for its use than any other non-hormonal performance enhancing supplement on the market. It is popular among all types of athletes, including amateurs and professionals, teenagers and adults, and men and women.
Creatine, which was first identified in 1832, is an amino acid derivative that occurs naturally in the body. It can be found in the brain, eye, kidney, and testes, but over 95% of the creatine in the body is found in skeletal muscle. It can be obtained through dietary sources and also synthesized within the body from the substrate guanidinoacetate via the enzyme S-adenosyl methionine (SAMe). Guanadinoacetate is derived from the amino acids arginine and glycine. This process primarily occurs in the kidney and liver.
Dietary sources high in creatine include herring, salmon, tuna, beef, and other foods. The combination of dietary creatine and creatine synthesized in the body usually results in the consumption/production of two grams of creatine daily, which is approximately the same rate at which creatine is degraded. Although significant quantities of creatine can be consumed through the diet, the amount is still generally small compared to the intake that can be achieved with supplemental creatine.
Since the early 90's, creatine has been extensively studied for the purpose of improving athletic performance, primarily for high-intensity, short-duration exercise (such as weight lifting and sprinting). There is consistent and overwhelming evidence for a benefit. In addition to research evaluating the effectiveness of creatine in improving athletic performance for a wide variety of types of exercise, research has also begun to evaluate possible benefits in treating muscular, neurological, and cardiovascular diseases.
1.2: How does creatine work?
Research has identified a number of mechanisms involved in creatine's ability to improve athletic performance.
A. The ATP-PCr system
High intensity exercise lasting up to around 2-3 minutes tends to rely on the adenosine triphosphate-phosphocreatine (ATP-PCr) system and anaerobic glycolysis, with the former system being more relied upon during shorter and higher intensity exercises. ATP is the body's primary source of energy, but it is rapidly depleted, forming adenosine diphosphate (ADP).
About 60-70% of the creatine in skeletal muscle is in the form of phosphocreatine (PCr). This is creatine bound to a high energy phosphate, and it is formed by the enzyme creatine kinase. When ATP is utilized for energy and becomes ADP, creatine can donate this phosphate group to the ADP, thus regenerating it back into ATP. By this means, creatine is able to increase the energetic capacity of muscles during high intensity exercise, increasing force output and delaying fatigue.
Although the ATP-PCr system is able to have a significant impact during exercise, PCr quickly becomes depleted. During longer bouts of exercise, energy is primarily derived from glycolysis and fat and carbohydrate oxidation. However, during rest periods, the PCr can be regenerated. Thus, this system is primarily relied upon for very intense bursts of exercise followed by rest periods, such as weight training.
B. Protein synthesis
Creatine may have the ability to increase muscle protein synthesis and/or inhibit protein breakdown, which is supported by the fact that it consistently increases lean body mass in humans. There are multiple mechanisms by which creatine could improve protein balance. The most obvious is that an increase in strength will trigger a greater adaptive response to exercise. A second possible mechanism is that creatine directly serves as a signal for protein synthesis, as it is released following muscle contraction. Also, recent research has indicated the possibility that creatine could increase satellite cell mitotic activity.
It has also been suggested that increasing muscle creatine content leads to an increase in intramuscular water through osmotic action, leading to increased cell hydration, which can stimulate protein synthesis and reduce catabolism. However, whether or not this occurs is still a matter of debate.
Finally, it has been hypothesized that creatine supplementation can increase protein synthesis by downregulating natural creatine production and thus leading to higher levels of the creatine precursor amino acids arginine and glycine, which can then be used for protein synthesis.
C. Muscle relaxation
Creatine loading has been found to shorten muscle relaxation time by about 20% after maximal contraction in humans. It was theorized that shortening muscle relaxation time could improve recovery time after a contraction, thus allowing for quicker recovery. This is possibly because creatine improves the efficiency of the Ca2+-ATPase pump, which regulates muscle relaxation.
D. Cellular protection
The ability of creatine to facilitate membrane stabilization and act as an antioxidant may help in preventing tissue damage during exercise. Maintenance of ATP levels prevents cell damage through multiple mechanisms, and creatine can also act directly as an antioxidant. It is unknown at this time if this plays a role in the performance enhancing effect of creatine.
Section 4. Dosage & Optimal Use
4.1: What dosage should be used? Is a loading phase necessary?
"Loading" refers to the practice of taking larger than normal doses for the first few days of supplementation to maximize muscle creatine stores as quickly as possible. This is followed by a maintenance phase, during which a smaller dose is taken daily to maintain the high levels of creatine.
Loading is not necessary, but it is beneficial. In one study, a maintenance dose (3 g/day) took thirty days to maximize creatine stores. On the other hand, a loading dose (20 g/day) maximized muscle creatine levels in only two days. Normal maintenance doses fall in the 3-5 g range (2 g has been found to be insufficient), although some take as much as 10 g, while 20-30 g (usually 20 g) is used for loading. Some sources recommend a loading phase of 6-7 days, but this appears to be unnecessary. Given that stores are maximized after two days of loading, 2-3 days should be sufficient. One study indicated that resistance training athletes can utilize around 50 mg/kg daily of creatine. A maintenance dose of 5-10 g daily is recommended to ensure that enough is being taken. Taking more than this for maintenance is generally a waste of creatine.
4.2: How and when should creatine be taken?
Creatine usually comes in powder form. Although capsules are available, they are significantly more expensive and most prefer powder. Creatine can be mixed in most drinks. During loading, it is customary to divide the creatine into 3-4 doses spread throughout the day (3 doses of 10 g or 4 doses of 5 g). During maintenance, 1-2 doses daily (usually of 5 g each) are used. Taking one of the doses pre-exercise on exercise days is recommended. Also, if some meals contain more carbohydrates than others, creatine should be taken with the high carbohydrate meals.
Some believe it is best to take creatine throughout the day to maintain elevated blood levels. However, once muscles are saturated with creatine, it takes a long time for muscle creatine levels to return to baseline (30 days). In the big picture, maintaining elevated blood levels around the clock is relatively inconsequential, as muscle creatine levels will be maintained at near-maximum with once daily dosing.
4.3: Is it necessary to cycle creatine?
When exogenous creatine is administered, natural production of creatine is drastically reduced. Creatine transporters also downregulate as creatine stores are maximized. For this reason, some recommend cyclic use of creatine to allow natural production to return to normal. However, there is no evidence that this is necessary. Because supplemental creatine leads to creatine levels much higher than would be produced naturally, there is no reason to try to maintain natural creatine production while trying to take creatine – it will not alter the effectiveness of the creatine. If creatine is taken consistently, muscle creatine levels are maintained at their maximal level, and do not decrease. Some believe that if creatine is taken for too long it could lead to permanent shutdown or a decrease of natural creatine production, but studies have found that natural production is restored very quickly after supplementation discontinues. Therefore, it should be most effective to use creatine on a constant basis.
4.4: How bioavailable is creatine?
The total bioavailability of creatine is unknown. Some creatine is degraded to creatinine in the GI tract, but the amount is probably low (one study estimated about 2%). It is believed that it is actively transported in the intestine by a saturable transporter. As the dosage of creatine increases, the time to maximal concentration and half-life increase. High doses, such as 20 g, cause an increase followed by a plateau in blood creatine levels lasting about six hours before dropping.
The main limiting factor for muscle creatine uptake is the creatine transporter. This transporter is highly selective for creatine. Another naturally occuring compound, beta-guanidinopropionic acid, also competes for the creatine transporter. As levels of creatine in muscle tissue increase, the creatine transporter downregulates. This makes it so muscle tissue can only store a certain limited amount of creatine. Although this amount is not maximized in most individuals not supplementing with creatine, the limiting role of the creatine transporter makes it so creatine supplementation beyond a certain dosage does not yield any additional benefit.
Other than muscle creatine content, there are some other factors that may influence the creatine transporter. These include exercise and the levels of some hormones, such as catecholamines, thyroid hormone, insulin, and insulin-like growth factor 1 (IGF-1).
4.5: I've heard that you should not mix creatine in acidic beverages, because it will destroy the creatine. Is this true?
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