Creatine is thought to improve strength, increase lean muscle mass, and help the muscles recover more quickly during exercise. This muscular boost may help athletes achieve bursts of speed and energy, especially during short bouts of high-intensity activities such as weight lifting or sprinting. However, scientific research on creatine has been mixed. Although some studies have found that it does help improve performance during short periods of athletic activity, there is no evidence that creatine helps with endurance sports. Research also shows that not everyone's muscles respond to creatine; some people who use it see no benefit.
Despite a possible decreasing creatine content in the muscles when maintenance is deemed suboptimal, the overall retention of weight and lean mass is merely additive over time. This is thought to be due to increases in skeletal muscle production (increase in body weight) compensating for the progressive declines in water and glycogen content (decreases in body weight).

Prison food isn’t as bad as people think. Prisoners often get three meals a day. Meals need to meet a certain amount of calories. You don’t need that much protein to build muscle, but prisoners can buy protein powder (and also extra food like oatmeal). Prisoners aren’t underfed in most western countries. The diet may not be optimal, but it’s sufficient to build muscle.

Sound complicated? Fortunately, there's an easy rule of thumb for increasing your training volume: For each exercise, perform three to six sets of six to 12 reps, resting for 30 to 90 seconds between each set, she says. The weight used should be enough that you can get out your last reps with proper form but wouldn't be able to perform any additional reps.
Parashos, S. A., Swearingen, C. J., Biglan, K. M., Bodis-Wollner, I., Liang, G. S., Ross, G. W., Tilley, B. C., and Shulman, L. M. Determinants of the timing of symptomatic treatment in early Parkinson disease: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience. Arch Neurol. 2009;66(9):1099-1104. View abstract.

Safety. In general health terms, most medical opinion is that up to three cups of coffee a day are not harmful, and may even have some benefits, although some people respond to the stimulant properties with more problems than others. Heart palpitations and restlessness are experienced by some caffeine drinkers. In pregnancy, one or two cups each day are thought to be without harm to the fetus.

Carducci, C., Birarelli, M., Leuzzi, V., Carducci, C., Battini, R., Cioni, G., and Antonozzi, I. Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clin Chem 2002;48(10):1772-1778. View abstract. 

Forbes, S. C., Sletten, N., Durrer, C., Myette-Côté, E , Candow, D., & Little, J. P. (2017, June). Creatine monohydrate supplementation does not augment fitness, performance, or body composition adaptations in response to four weeks of high-intensity interval training in young females. Human Kinetics Journals, 27(3), 285-292. Retrieved from
Many other important bodybuilders in the early history of bodybuilding prior to 1930 include: Earle Liederman (writer of some of bodybuilding's earliest books), Zishe Breitbart, Georg Hackenschmidt, Emy Nkemena, George F. Jowett, Finn Hateral (a pioneer in the art of posing), Frank Saldo, Monte Saldo, William Bankier, Launceston Elliot, Sig Klein, Sgt. Alfred Moss, Joe Nordquist, Lionel Strongfort ("Strongfortism"),[6] Gustav Frištenský, Ralph Parcaut (a champion wrestler who also authored an early book on "physical culture"), and Alan P. Mead (who became an impressive muscle champion despite the fact that he lost a leg in World War I). Actor Francis X. Bushman, who was a disciple of Sandow, started his career as a bodybuilder and sculptor's model before beginning his famous silent movie career.

A meta-analysis of 16 studies conducted on creatine and its influence on power and strength,[368][369] (with or without exercise in all age groups above 16, but placebo controlled and without crossover[368]) compiled studies utilizing a 5-7 day loading period with continued maintenance thereafter and studies assessing 1-3 rep bench press strength in trained young men. Seven studies (four of which are online[370][371][372][373]) totaling 70 people using creatine and 73 people in placebo showed a 6.85kg increase in strength relative to placebo, the benefits of which peaked at 8 weeks.[368] This meta-analysis also quantified a significant increase in squat strength (9.76kg) yet failed to find a significant influence on peak bicep contraction power, which may have been influenced by the two null studies[374][375] being in elderly people while the positive study[376] was statistically outweighed, but noted an 1.8-fold increase in power associated with creatine over placebo. The other meta-analysis conducted the following year[369] calculated effect sizes for creatine supplementation and noted no significant differences between genders or when comparing trained and untrained individuals. The mean effect size of exercises lasting below 30s (those that use the creatine-phosphate system) was 0.24+/-0.02 and performed significantly better than placebo, where exercise increased performance by 4.2+/-0.6% while the addition of creatine enhanced this effect to 7.5+/-0.7%.[369]
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.[616] 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.[617] Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis.[618][619][620][621] 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.[622]
Creatine is vital for brain function, which has mechanisms to take up creatine, as well as regulate its intake. Although the diet appears to be the major source of creatine (and thus lack of dietary intake could cause a non-clinical deficiency) excess levels of creatine do not appear to “super-load” the brain similar to muscle tissue. Due to kinetics, creatine appears to be more “preventative” or acts to restore a deficiency in the brain. This is in contrast to creatine effects in muscle cells, where it can affect performance substantially on an acute timescale.

Although creatine supplementation has been shown to be more effective on predominantly anaerobic intermittent exercise, there is some evidence of its positive effects on endurance activities. Branch [28] highlights that endurance activities lasting more than 150s rely on oxidative phosphorylation as primary energy system supplier. From this meta analysis [28], it would appear that the ergogenic potential for creatine supplementation on predominantly aerobic endurance exercise diminishes as the duration of the activity increases over 150s. However it is suggested that creatine supplementation may cause a change in substrate utilization during aerobic activity possibly leading to an increase in steady state endurance performance.
^ Jump up to: a b c d Luckose F, Pandey MC, Radhakrishna K (2015). "Effects of amino acid derivatives on physical, mental, and physiological activities". Crit. Rev. Food Sci. Nutr. 55 (13): 1793–1807. doi:10.1080/10408398.2012.708368. PMID 24279396. HMB, a derivative of leucine, prevents muscle damage and increases muscle strength by reducing exercise-induced proteolysis in muscles and also helps in increasing lean body mass. ... The meta analysis studies and the individual studies conducted support the use of HMB as an effective aid to increase body strength, body composition, and to prevent muscle damage during resistance training.

It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio,[333][334] and when activated AMPK (active in states of low cellular energy[335] and colocalizes with creatine kinase in muscle tissue[336]) appears to inhibit creatine kinase via phosphorylation (preserving phosphocreatine stores but attenuating the rate that creatine buffers ATP). While phosphocreatine technically inhibits AMPK, this does not occur in the presence of creatine at a 2:1 ratio.[334] It seems that if the ratio of phosphocreatine:creatine increases (indicative of excess cellular energy status) that AMPK activity is then attenuated, since when a cell is in a high energy status, there is less AMP to directly activate AMPK.[334][336][337]