Because so many product labels list scientific references to back up the manufacturers' claims of performance and efficacy, or effectiveness, it's important to understand what constitutes a solid scientific study. A single study, even an optimally designed one, isn't considered scientific proof. The results have to be replicated several times before they're officially accepted as fact.
In otherwise healthy adults subject to leg immobilization for two weeks while taking 20g creatine daily during immobilization and then 5g daily during eight weeks of rehabilitation, it was noted that the creatine group failed to reduce atrophy during the immobilization (10% reduction in cross sectional area and 22-25% reduction in force output) despite preventing a decrease in phosphocreatine, yet experienced a significantly enhanced rate of regrowth and power recovery. A similarly structured and dosed study has also noted greater expression of skeletal muscle, GLUT4 expression, and a 12% increase in muscle phosphocreatine content.
Creatine has been shown before in vitro to protect from MPTP-induced toxicity, which targets dopaminergic neurons in the substantia nigra and induce Parkinson’s disease in research animals. Creatine also protected these cells from death induced by low oxygen or glucose. One study noted that dopaminergic cell survival under the influence of creatine was 1.32-fold higher than control cells, the soma (cell body) was enlarged by 1.12-fold in these cells, and creatine showed some growth-enhancing effects while helping reducing destruction of dopaminergic neurons by various insults.
Bodybuilding is the use of progressive resistance exercise to control and develop one's musculature for aesthetic purposes. An individual who engages in this activity is referred to as a bodybuilder. In professional bodybuilding, bodybuilders appear in lineups and perform specified poses (and later individual posing routines) for a panel of judges who rank the competitors based on criteria such as symmetry, muscularity, and conditioning. Bodybuilders prepare for competitions through the elimination of nonessential body fat, enhanced at the last stage by a combination of intentional dehydration and carbohydrate loading, to achieve maximum muscular definition and vascularity, as well as tanning to accentuate the contrast of the skin under the spotlights. Bodybuilders may use anabolic steroids and other performance enhancing drugs to build muscles.
A 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant. The most prevalent of these contaminants was creatinine, a breakdown product of creatine also produced by the body. Creatinine was present in higher concentrations than the European Food Safety Authority recommendations in 44% of the samples. About 15% of the samples had detectable levels of dihydro-1,3,5-triazine or a high dicyandiamide concentration. Heavy metals contamination was not found to be a concern, with only minor levels of mercury being detectable. Two studies reviewed in 2007 found no impurities.
In standard dosages (5-10g creatine monohydrate) the bioavailability of creatine in humans is approximately 99%, although this value is subject to change with different conjugates (forms) of creatine and dosages. Coingestion of cyclocreatine (an analogue) can reduce uptake by about half and coincubation of taurine, choline, glycine, or beta-alanine had minimal attenuation of absorption, which is likely not practically relevant. The inhibition noted with cyclocreatine may be due to receptor saturation.
Reducing creatine synthesis by supplementing it has preliminary evidence supporting its ability to reduce homocysteine concentrations in the body, since the synthesis of creatine would normally produce some homocysteine as a byproduct. This may apply to a certain subset of people (MTHFR TT homozygotes, about 10% of North Americans) but at the moment there is not enough evidence to suggest that this occurs in all people supplementing creatine.
^ Jump up to: a b c d e f g h Momaya A, Fawal M, Estes R (April 2015). "Performance-enhancing substances in sports: a review of the literature". Sports Med. 45 (4): 517–531. doi:10.1007/s40279-015-0308-9. PMID 25663250. Wilson et al.  demonstrated that when non-resistance trained males received HMB pre-exercise, the rise of lactate dehydrogenase (LDH) levels reduced, and HMB tended to decrease soreness. Knitter et al.  showed a decrease in LDH and creatine phosphokinase (CPK), a byproduct of muscle breakdown, by HMB after a prolonged run. ... The utility of HMB does seem to be affected by timing of intake prior to workouts and dosage .
High extracellular creatine concentrations induce the expression of a factor that inhibits the creatine transporter (CrT). To date, neither the identity of nor mechanism for this putative CrT-suppressing factor has come to light. Future studies that are able to identify this creatine transport-suppressing factor and how it works may provide valuable insight into possible supplementation strategies that might be used to increase creatine uptake into muscle cells.
Extracellular creatine (creatine outside of a cell) appears to influence creatine uptake into a cell. It seems that prolonged and excessive levels of creatine actually suppress uptake (a form of negative regulation to prevent excessive influx). In vitro studies in rat muscle cells have shown that including 1mM creatine into cell culture medium substantially reduces creatine uptake into cells. The inhibitory effect was partially negated by protein synthesis inhibitors, suggesting that high levels of creatine induce the expression of a protein that suppresses creatine transporter activity. Similar findings were reported in a later study in cultured mouse myoblasts, which noted a 2.4-fold increase in intracellular creatine levels in the presence of the protein synthesis inhibitor cyclohexamide.
“Reg Park’s theory was that first you have to build the mass and then chisel it down to get the quality; you work on your body the way a sculptor would work on a piece of clay or wood or steel. You rough it out””the more carefully, the more thoroughly, the better”” then you start to cut and define. You work it down gradually until it’s ready to be rubbed and polished. And that’s when you really know about the foundation. Then all the faults of poor early training stand out as hopeless, almost irreparable flaws. [..]
Bodybuilders also train small muscles with a similar volume, frequency and intensity of their larger muscles. Strength athletes laugh at this. “Curls are a waste of time” is a common phrase you will hear hurled at a bodybuilder. This is SILLY. Although big compound movements should be most people’s resistance training priority, smaller muscle group focus work has some benefits for every athlete. Bicep tears are quite common among strength athletes, especially strong men and powerlifters. This happens because these competitors will lift tremendous weights with their backs, but their biceps are the weak link. Many of these injuries could be prevented with some good old-fashioned bodybuilder type isolation work. If you are only as strong as your weak link, doesn’t it make sense to make those weak links strong ones?
Many trainees like to cycle between the two methods in order to prevent the body from adapting (maintaining a progressive overload), possibly emphasizing whichever method more suits their goals; typically, a bodybuilder will aim at sarcoplasmic hypertrophy most of the time but may change to a myofibrillar hypertrophy kind of training temporarily in order to move past a plateau. However, no real evidence has been provided to show that trainees ever reach this plateau, and rather was more of a hype created from "muscular confusion".[clarification needed]
One case study exists of a man with focal segmental glomerulosclerosis who experienced an accelerated rate of GFR decline during supplementation (5g thrice daily for loading, then a 2g maintenance for seven weeks) which was partially reversed upon supplement cessation. This was deemed strong circumstantial evidence, and the brand of supplement was not named. Elsewhere, interstitial nephritis associated with creatine supplementation has been reported in a man, although symptoms arose four weeks after supplementation started with no evidence to support correlation. Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis. Finally, one study in a diabetic person ingesting both metformin and creatine resulting in metabolic acidosis has attempted to place causation on creatine, but it did not establish causation or circumstantial evidence.