In muscle cells, the creatine transporter is predominantly localized to the sarcolemmal membrane. Western blot analysis of creatine transporter expression revealed the presence of two distinc protein bands, migrating at 55kDa and 70kDa on reducing SDS-PAGE gels.[147][148] The 73kDa band has been reported to be the predominant band in humans, with no differences based on gender.[148] A more recent report demonstrated that the 55kDa creatine transporter variant is glycosylated, forming the 73 kDa protein. Therefore, the 55 and 75kDa protein bands are actually immature and mature/processed forms of the creatine transporter protein, respectively.[149]
Studies measuring extracellular water versus intracellular water note similar increases in both, associated with creatine. Creatine does not tend to disturb the ratios of water to dry mass in various tissues measured.[609] At least one study in older men (48-72 years) has failed to find a significant difference in both intracellular and extracellular water concentration after 14 weeks of 5g creatine daily (with gatorade) relative to gatorade in isolation, with the ratio being maintained.[615]
The creatine kinase (CK) enzyme in rat heart tissue appears to have a KM around 6mM of creatine as substrate.[280] and is known to positively influence mitochondrial function as higher cytoplasmic phosphocreatine concentrations (not so much creatine per se) increase the oxidative efficiency of mitochondria[280] This is thought to be due to the transfer of high energy phosphate groups.[280]

However, a much more accurate determination of how much fluid is necessary can be made by performing appropriate weight measurements before and after a typical exercise session, to determine how much fluid is lost during the workout. The greatest source of fluid loss during exercise is through perspiration, but as long as your fluid intake is roughly equivalent to your rate of perspiration, hydration levels will be maintained.[14]

The general sentiment among nutrition experts is that creatine monohydrate is, for most people, the best bet. It’s the cheapest form and more importantly, it’s the most well-researched. Hundreds of studies have been performed on creatine monohydrate and there’s no evidence of ill effects, whereas many of the more novel forms of creatine have one or sometimes no studies supporting them.

Creatine has demonstrated neuromuscular performance enhancing properties on short duration, predominantly anaerobic, intermittent exercises. Bazzucch et al [27] observed enhanced neuromuscular function of the elbow flexors in both electrically induced and voluntary contractions but not on endurance performance after 4 loading doses of 5 g creatine plus 15 g maltodextrin for 5/d in young, moderately trained men. Creatine supplementation may facilitate the reuptake of Ca2+ into the sacroplasmic reticulum by the action of the Ca2+ adenosine triphosphatase pump, which could enable force to be produced more rapidly through the faster detachment of the actomyosin bridges.

While training intensity can be accomplished trough a targeted training program and an ability to adequately stimulate our muscles is something the motivated and determined bodybuilder often has no problem doing, muscle recovery is another issue. It is especially important at a time of the year when social demands and incorrect eating combine to stifle our progress.
Site enhancement oil, often called "santol" or "synthol" (no relation to the Synthol mouthwash brand), refers to oils injected into muscles to increase the size or change the shape. Some bodybuilders, particularly at the professional level, inject their muscles with such mixtures to mimic the appearance of developed muscle where it may otherwise be disproportionate or lagging.[54] This is known as "fluffing".[55][56] Synthol is 85% oil, 7.5% lidocaine, and 7.5% alcohol.[55] It is not restricted, and many brands are available on the Internet.[57] The use of injected oil to enhance muscle appearance is common among bodybuilders,[58][59] despite the fact that synthol can cause pulmonary embolisms, nerve damage, infections, sclerosing lipogranuloma,[60] stroke,[55] and the formation of oil-filled granulomas, cysts or ulcers in the muscle.[59][61][62] Rare cases might require surgical intervention to avoid further damage to the muscle and/or to prevent loss of life.[63]
Maintaining proper form is one of the many steps in order to perfectly perform a certain technique. Correct form in weight training improves strength, muscle tone, and maintaining a healthy weight. Proper form will prevent any strains or fractures.[6] When the exercise becomes difficult towards the end of a set, there is a temptation to cheat, i.e., to use poor form to recruit other muscle groups to assist the effort. Avoid heavy weight and keep the number of repetitions to a minimum. This may shift the effort to weaker muscles that cannot handle the weight. For example, the squat and the deadlift are used to exercise the largest muscles in the body—the leg and buttock muscles—so they require substantial weight. Beginners are tempted to round their back while performing these exercises. The relaxation of the spinal erectors which allows the lower back to round can cause shearing in the vertebrae of the lumbar spine, potentially damaging the spinal discs.

Once training is resumed under these conditions, there may be little in the way of caloric support to ensure that protein synthesis and muscle growth occurs. Muscle may even begin to cannibalize itself as the body enters into a catabolic state. Even with the best of diets this can sometimes happen if training demands override the nutritional balance or imbalance.
A thermogenic is a broad term for any supplement that the manufacturer claims will cause thermogenesis, resulting in increased body temperature, increased metabolic rate, and consequently an increased rate in the burning of body fat and weight loss. Until 2004 almost every product found in this supplement category comprised the "ECA stack": ephedrine, caffeine and aspirin. However, on February 6, 2004 the Food and Drug Administration (FDA) banned the sale of ephedra and its alkaloid, ephedrine, for use in weight loss formulas. Several manufacturers replaced the ephedra component of the "ECA" stack with bitter orange or citrus aurantium (containing synephrine) instead of the ephedrine.
Creatine supplementation has been noted to improve general wellbeing and health status (assessed by St George’s Respiratory questionnaire[582]) of people with COPD over two weeks loading (17.1g daily with carbohydrates) and ten weeks of 5.7g maintenance.[579] The studies that failed to find improvements with creatine supplementation on muscular performance also failed to find improvements in this rating scale, relative to placebo.[580][581]

Activation of NMDA receptors is known to stimulate Na+,K+-ATPase activity[218] secondary to calcineurin,[219] which which has been confirmed with creatine in hippocampal cells (0.1-1mM trended, but 10mM was significant). This is blocked by NMDA antagonists.[220] This increase in Na+,K+-ATPase activity is also attenauted with activation of either PKC or PKA,[220] which are antagonistic with calcineurin.[219][221]

“Compared to training for strength, intensity is going to drop during the hypertrophy phase of a program, with intensity sitting between 50 and 75 percent of the person’s 1RM, the maximum weight he or she can lift for one rep,” says Ava Fitzgerald, C.S.C.S., C.P.T., a sports performance coach with the Professional Athletic Performance Center in New York.
COX-2, a pro-inflammatory enzyme, is sometimes a therapeutic target for both muscle soreness and some degenerative diseases that are exacerbated by inflammation. COX-2 inhibitors (in this study, rofecoxib) and creatine monohydrate both appear to protect dopaminergic neurons from being destroyed by toxins, and can protect in an additive manner, suggesting possible usage of both to reduce the risk of Parkinson’s disease.[230]
Creatine is classified as a "dietary supplement" under the 1994 Dietary Supplement Health and Education Act and is available without a prescription. Creatine is not subjected to FDA testing, and the purity and hygienic condition of commercial creatine products may be questionable [21]. A 1998 FDA report lists 32 adverse creatine-associated events that had been reported to FDA. These include seizure, vomiting, diarrhea, anxiety, myopathy, cardiac arrhythmia, deep vein thromboses and death. However, there is no certainty that a reported adverse event can be attributed to a particular product [22]. A recent survey of 28 male baseball players and 24 male football players, ages 18 to 23, found that 16 (31%) experienced diarrhea, 13 (25%) experienced muscle cramps, 7 (13%) reported unwanted weight gain, 7 (13%) reported dehydration, and 12 reported various other adverse effects [23].
In elite swimmers, the growth hormone response to sprints appears to be attenuated (39%) following creatine loading, although after a 3g maintenance phase (22-27 weeks), this attenuation was reduced to less than 5%.[404] Elsewhere in swimmers, resting growth hormone was unaffected by the loading phase,[397] suggesting that this is an exercise-exclusive effect.
Cooke et al [41] observed positive effects of a prior (0.3 g/d kg BW) loading and a post maintenance protocol (0.1 g/d kg BW) to attenuate the loss of strength and muscle damage after an acute supramaximal (3 set x 10 rep with 120% 1RM) eccentric resistance training session in young males. The authors speculate that creatine ingestion prior to exercise may enhance calcium buffering capacity of the muscle and reduce calcium-activated proteases which in turn minimize sarcolemma and further influxes of calcium into the muscle. In addition creatine ingestion post exercise would enhance regenerative responses, favoring a more anabolic environment to avoid severe muscle damage and improve the recovery process. In addition, in vitro studies have demonstrated the antioxidant effects of creatine to remove superoxide anion radicals and peroxinitrite radicals [42]. This antioxidant effect of creatine has been associated with the presence of Arginine in its molecule. Arginine is also a substrate for nitric oxide synthesis and can increase the production of nitric oxide which has higher vasodilatation properties, and acts as a free radical that modulates metabolism, contractibility and glucose uptake in skeletal muscle. Other amino acids contained in the creatine molecule such as glycine and methinine may be especially susceptible to free radical oxidation because of sulfhydryl groups [42]. A more recent in vitro study showed that creatine exerts direct antioxidant activity via a scavenging mechanism in oxidatively injured cultured mammalian cells [43]. In a recent in vivo study Rhaini et al [44] showed a positive effect of 7 days of creatine supplementation (4 x 5 g CM 20 g total) on 27 recreational resistance trained males to attenuate the oxidation of DNA and lipid peroxidation after a strenuous resistance training protocol.
In addition to the BBB, SLC6A8 is also expressed on neurons and oligodendrocytes,[192] but is relatively absent from astrocytes, including the astrocytic feet[193][194] which line 98% of the BBB.[195] Creatine can still be transported into astrocytes (as well as cerebellar granule cells) via SLC6A8, as incubation with an SLC6A8 inhibitor prevents accumulation in vitro. It seems to be less active in a whole brain model, relative to other brain cells.[196]
Another study demonstrated that females receiving 4 days of high-dose creatine intake (20 g/day) followed by low-dose creatine intake (5 g/day) during 10 weeks of resistance training (3hours/week) increased muscle PCr concentrations by 6%. Also, maximal strength of the muscle groups trained increased by 20-25%, maximal intermittent exercise capacity of the arm flexors increased by 10-25% and fat-free mass increased by 60% [11].