In regard to practical interventions, concurrent glycogen loading has been noted to increase creatine stores by 37-46% regardless of whether the tissue was exercised prior to loading phase.[176] It is important to note, however, that creatine levels in response to the creatine loading protocol were compared in one glycogen-depleted leg to the contralateral control leg, which was not exercised.[176] This does not rule out a possible systemic exercise-driven increase in creatine uptake, and the increase in creatine noted above[176] was larger than typically seen with a loading protocol (usually in the 20-25% range). Consistent with an exercise-effect, others have reported that exercise itself increases creatine uptake into muscle, reporting 68% greater creatine uptake in an exercised limb, relative to 14% without exercise.[153]

Without supplementation, approximately 14.6mmol (2g) of creatinine, creatine’s urinary metabolite, is lost on a daily basis in a standard 70kg male ages 20-39. The value is slightly lower in females and the elderly due to a presence of less muscle mass.[35] This amount is considered necessary to obtain in either food or supplemental form to avoid creatine deficiency. Requirements may be increased in people with higher than normal lean mass.[35][198] Creatine excretion rates on a daily basis are correlated with muscle mass, and the value of 2g a day is derived from the aforementioned male population with about 120g creatine storage capacity.[35] Specifically, the rate of daily creatine losses is about 1.6%[199]-1.7%,[25] and mean losses for women are approximately 80% that of men due to less average lean mass.[35] For weight-matched elderly men (70kg, 70-79 years of age) the rate of loss of 7.8mmol/day,[49] or about half (53%) that of younger men.

A typical creatine supplementation protocol of either a loading phase of 20 to 25 g CM/d or 0.3 g CM/kg/d split into 4 to 5 daily intakes of 5 g each have been recommended to quickly saturate creatine stores in the skeletal muscle. However a more moderate protocol where several smaller doses of creatine are ingested along the day (20 intakes of 1 g every 30 min) could be a better approach to get a maximal saturation of the intramuscular creatine store. In order to keep the maximal saturation of body creatine, the loading phase must be followed by a maintenance period of 3-5 g CM/d or 0.03 g CM/kg/d. These strategies appear to be the most efficient way of saturating the muscles and benefitting from CM supplementation. However more recent research has shown CM supplementation at doses of 0.1 g/kg body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Creatine retention by the body from supplementation appears to be promoted by about 25% from the simultaneous ingestion of carbohydrate and/or protein mediated through an increase in insulin secretion. This combination would produce a faster saturation rate but has not been shown to have a greater effect on performance.
It’s perhaps best known for the aesthetic benefits. Creatine increases muscle size relatively quickly and while that’s in part due to an increase in muscle water content — a good thing, since it means we’re better hydrated — it does indeed appear to lead to actual hypertrophy over time. And bigger muscles aren’t just aesthetic: larger muscles can improve work capacity, explosiveness, fat oxidation, injury resilience, and recovery.
Contrary to certain rumors that animal-based protein is more suitable to trigger muscle growth than plant-based protein, a study by Mangano et al. (2017) could not provide any evidence for this. In contrast, if combined properly, plant-based protein can even have a higher biological quality. A combination of one part wheat protein (e.g. seitan) and two parts soy protein (e.g. tofu) has thus been favored by many bodybuilders. Some bodybuilders, such as Patrik Baboumian and Robert Cheeke, follow a strict vegan diet.[37]
D-aspartic acid can also help to reduce cortisol levels. Cortisol is known as the “stress” hormone because its production increases during stressful situations. High cortisol levels can have many negative side effects, such as weight gain, muscle tissue breakdown, or increased blood sugar. Taking a supplement that includes cortisol can reduce stress and prevent excess fat storage or muscle loss.

Creatine, which is synthesized in the liver and kidneys, is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ATP in skeletal muscle is usually 2–5 mM, which would result in a muscle contraction of only a few seconds.[22] During times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of phosphocreatine (PCr) through a reversible reaction with the enzyme creatine kinase (CK). In skeletal muscle, PCr concentrations may reach 20–35 mM or more. Additionally, in most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of ATP are small, changes are difficult to detect because ATP is continuously and efficiently replenished from the large pools of PCr and CK.[22] Creatine has the ability to increase muscle stores of PCr, potentially increasing the muscle’s ability to resynthesize ATP from ADP to meet increased energy demands.[23][24][25]

Legion’s Recharge is a good pick for muscle growth. Besides the creatine itself, it contains a hefty 2.1 grams of l-carnitine l-tartrate, which has solid links with improving muscle repair in addition to increasing focus during workouts. It’s also delicious, naturally sweetened, and it contains ingredients that may improve insulin sensitivity and help the body to better utilize carbs for recovery.
SAMe is the primary methyl donor in the human body, and supplements that preserve SAMe (such as trimethylglycine; TMG) promote a variety of benefits in the human body, like a reduction in homocysteine and reduced risk of fatty liver. Creatine has been implicated in both reducing homocysteine[124] and preventing fatty liver in rodents[125], thought to be secondary to preserving SAMe.
In otherwise sedentary and healthy men given a loading phase of creatine followed by 11 weeks of maintenance, the glucose response to an oral glucose tolerance test is reduced by 11-22% (measurements at 4-12 weeks with no time dependence noted) which was not associated with changes in insulin levels or sensitivity.[350] Elsewhere, a study in vegetarians (5g daily for 42 days) failed to find a reduction in postprandial blood glucose.[351]
Discomfort can arise from other factors. Individuals who perform large numbers of repetitions, sets, and exercises for each muscle group may experience a burning sensation in their muscles. These individuals may also experience a swelling sensation in their muscles from increased blood flow (the "pump"). True muscle fatigue is experienced as a marked and uncontrollable loss of strength in a muscle, arising from the nervous system (motor unit) rather than from the muscle fibers themselves. Extreme neural fatigue can be experienced as temporary muscle failure. Some weight training programs, such as Metabolic Resistance Training, actively seek temporary muscle failure; evidence to support this type of training is mixed at best.[24] Irrespective of their program, however, most athletes engaged in high-intensity weight training will experience muscle failure during their regimens.
Muscle growth is more difficult to achieve in older adults than younger adults because of biological aging, which leads to many metabolic changes detrimental to muscle growth; for instance, by diminishing growth hormone and testosterone levels. Some recent clinical studies have shown that low-dose HGH treatment for adults with HGH deficiency changes the body composition by increasing muscle mass, decreasing fat mass, increasing bone density and muscle strength, improves cardiovascular parameters, and affects the quality of life without significant side effects.[45][46][unreliable medical source?][47]

In contrast to strongman or powerlifting competitions, where physical strength is paramount, or to Olympic weightlifting, where the main point is equally split between strength and technique, bodybuilding competitions typically emphasize condition, size, and symmetry. Different organizations emphasize particular aspects of competition, and sometimes have different categories in which to compete.
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These protective effects are similar to those seen with trimethylglycine, since they both cause an increase in liver concentrations of phosphatidylcholine (PC, causing an increase in vLDL production and efflux of triglycerides from the liver).[497] Both TMG and creatine are thought to work indirectly by preserving SAMe concentrations,[125][498] since PC synthesis requires SAMe as well (via PEMT[499]) and genes involved in fatty acid metabolism in the liver that were not affected by the diet (VLCAD and CD36) were unaffected by creatine.[125]
There are several different available forms of creatine: creatine anhydrous which is creatine with the water molecule removed in order to increase the concentration of creatine to a greater amount than that found in CM. Creatine has been manufactured in salt form: creatine pyruvate, creatine citrate, creatine malate, creatine phosphate, magnesium creatine, creatine oroate, Kre Alkalyn (creatine with baking soda). Creatine can also be manufactured in an ester form. Creatine ethyl ester (hydrochloride) is an example of this, as is creatine gluconate which is creatine bound to glucose. Another form is creatine effervescent which is creatine citrate or CM with citric acid and bicarbonate. The citric acid and bicarbonate react to produce an effervescent effect. When mixed with water the creatine separates from its carrier leaving a neutrally charged creatine, allowing it to dissolve to a higher degree in water. Manufacturers claim that creatine effervescent has a longer and more stable life in solution. When di-creatine citrate effervescent was studied [59] for stability in solution it was found that the di-creatine citrate dissociates to citric acid and creatine in aqueous solutions which in turn forms CM and eventually crystallises out of the solution due to its low solubility. Some of the creatine may also convert to creatinine.
Homocysteine is produced after S-adenosyl methionine is used up (as donating a methyl group creates S-adenosylhomocysteine, which then produces homocysteine) mostly from phosphatidylcholine synthesis[307] and its reduction (via either methylation from trimethylglycine via betaine:homocysteine methyltransferase, urinary excretion, or convertion into L-cysteine via cystathionine beta-synthase[308]) is thought to be therapeutic for cardiovascular diseases.
As Heath talked in the office, Cremona presented him with steak and white rice. It was takeout, from Outback Steakhouse, because the two had just returned from a weeklong trip. Heath reached toward a bouquet of round plastic jars filled with powdered supplements. He scooped powder from one into a water bottle, shook it and drank. He compared himself to a racecar, always in need of fuel and delicate tinkering.

The process of phagocytosis (a macrophage consuming a pathogen) in macrophages appears to be associated with an acute reduction in creatine phosphate stores (45%)[436] and an increase in creatine kinase activity,[290] although prolonged stimulation is met with an increase in creatine phosphate (20%).[290] The creatine kinase activity does not appear to be altered based on creatine availability,[290] but since ATP seems to be preserved in these instances,[436][290] the increase in phosphocreatine may be explained by an overall creatine pool paralleling that found in medium.[290]

Mercimek-Mahmutoglu, S., Stoeckler-Ipsiroglu, S., Adami, A., Appleton, R., Araujo, H. C., Duran, M., Ensenauer, R., Fernandez-Alvarez, E., Garcia, P., Grolik, C., Item, C. B., Leuzzi, V., Marquardt, I., Muhl, A., Saelke-Kellermann, R. A., Salomons, G. S., Schulze, A., Surtees, R., van der Knaap, M. S., Vasconcelos, R., Verhoeven, N. M., Vilarinho, L., Wilichowski, E., and Jakobs, C. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology 8-8-2006;67:480-484. View abstract.

Collectively the above investigations indicate that creatine supplementation can be an effective strategy to maintain total creatine pool during a rehabilitation period after injury as well as to attenuate muscle damage induced by a prolonged endurance training session. In addition, it seems that creatine can act as an effective antioxidant agent after more intense resistance training sessions.