In humans, studies that investigate links between serotonin and creatine supplementation find that 21 trained males, given creatine via 22.8g creatine monohydrate (20g creatine equivalent) with 35g glucose, relative to a placebo of 160g glucose, was found to reduce the perception of fatigue in hot endurance training, possibly secondary to serotonergic modulation, specifically attentuating the increase of serotonin seen with exercise (normally seen to hinder exercise capacity in the heat) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat).
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Creatine has been incubated in various cell lines (HUVEC, C2C12, U937) and noted to reduce cellular death from various pro-oxidant stressors, such as H2O2 or peroxynitrate in an intracellular range between 0.1-10mM. This protective effect was only noted with preincubation and was comparable to 10-100µM of Trolox. This protective effect did not require conversion into phosphocreatine nor a buffering of ATP, and only worked during a preloading to the stressor, rather than in a rehabilitative manner.
Weight training also requires the use of 'good form', performing the movements with the appropriate muscle group, and not transferring the weight to different body parts in order to move greater weight (called 'cheating'). Failure to use good form during a training set can result in injury or a failure to meet training goals; since the desired muscle group is not challenged sufficiently, the threshold of overload is never reached and the muscle does not gain in strength. At a particularly advanced level; however, "cheating" can be used to break through strength plateaus and encourage neurological and muscular adaptation.
I'm 6'1" 175 pounds 27 years old. I would like to increase my general muscle mass and reduce my stomach fat. I would consider myself and ectomorph (hard gainer) as I have never really developed much muscle while I've always been very active in sports and periodic weight training. Over the past year I lost about 30 pounds (nearly all fat) by reducing my caloric intake effectively and regular whole body exercises. I was on my way to my ideal body composition until I became a bike courier. I've been a bike messenger for 9 months and recently my stomach fat has started to return. I'm riding 50+ miles each weekday riding for 9 hours a day. How many calories should I be eating? I've tried everywhere between 2400-3,500 cal/day. Is it possible for me to be eating too few calories while still accumulating stomach fat? Is it realistic for me to be able to maintain or even build muscle mass in this scenario? Please help, thanks.
Yang, L., Calingasan, N. Y., Wille, E. J., Cormier, K., Smith, K., Ferrante, R. J., & Beal, M. F. (2009, June). Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases [Abstract]. Journal of Neurochemistry. 109(5):1427-39. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19476553
Based on the limited data on performance and safety, some authors have not identified any conclusions and do not recommend its consumption in regards to creatine supplementation in children and adolescents [52,54]. Conversely, according to the view of the ISSN , younger athletes should consider a creatine supplement under certain conditions: puberty is past and he/she is involved in serious competitive training; the athlete is eating a well-balanced caloric adequate diet; he/she as well as the parents approve and understand the truth concerning the effects of creatine supplementation; supplement protocols are supervised by qualified professionals; recommended doses must not be exceeded; quality supplements are administered.
It’s important to remember that since everybody is different, these estimates are just that. How the numbers work out for each person will definitely vary. So many factors—like genetics, hormones, sleep, and diet—can change the rate at which our bodies burn calories. And some people may have a harder time than others when it comes losing fat or gaining muscle—again, there are so many factors at play and our body chemistries are all different. Strength training is important for many, many, many other reasons (more on that later), but if you’re looking to increase your metabolism, it’s important to have realistic expectations and know that strength training can make a difference, but probably won’t drastically affect how many calories you burn from one day to the next.
The majority of creatine in the human body is in two forms, either the phosphorylated form making up 60% of the stores or in the free form which makes up 40% of the stores. The average 70 kg young male has a creatine pool of around 120-140 g which varies between individuals [10,11] depending on the skeletal muscle fiber type  and quantity of muscle mass . The endogenous production and dietary intake matches the rate of creatinine production from the degradation of phosphocreatine and creatine at 2.6% and 1.1%/d respectively. In general, oral creatine supplementation leads to an increase of creatine levels within the body. Creatine can be cleared from the blood by saturation into various organs and cells or by renal filtration .
Heart Failure is one of the single most common complications that face many people today. When a heart ages, the cells collect a yellow-brown layer which is waste and can lead to heart complications. This process is known as lipofuscin, or “aging pigment” which leads to death opposed to someone who can delay that as far as possible.  In mice, a study was performed where two groups of mice who had lipofuscin underwent different experiments, one group received creatine supplementation, and one group did not receive supplementation. What they found was that the mice who supplemented creatine lived 9% longer than the ones who did not receive creatine. 9% translated into human years results in almost 7 years, which could suggest that if you suffer from this deterioration, creatine supplementation could potentially increase your longevity by 7 years. 
In vitro studies on endothelial cells have noted that the benefits of creatine against atherosclerosis (via immune cell adhesion to the endothelial cell) are blocked with the pharmaceutical ZM241385, a high affintiy adenosine A2A receptor antagonist. This particular receptor subset (A2A rather than other adenosine receptors) and its inhibition are similar to caffeine, suggesting that caffeine may have an inhibitory effect on this mechanism of creatine.
Polyethylene glycol is a non-toxic, water-soluble polymer that is capable of enhancing the absorption of creatine and various other substances . Polyethylene glycol can be bound with CM to form polyethylene glycosylated creatine. One study  found that 5 g/d for 28 days of polyethylene glycosylated creatine was capable of increasing 1RM bench press in 22 untrained young men but not for lower body strength or muscular power. Body weight also did not significantly change in the creatine group which may be of particular interest to athletes in weight categories that require upper body strength. Herda et al  analyzed the effects of 5 g of CM and two smaller doses of polyethylene glycosylated creatine (containing 1.25 g and 2.5 g of creatine) administered over 30 days on muscular strength, endurance, and power output in fifty-eight healthy men. CM produced a significantly greater improvement in mean power and body weight meanwhile both CM and polyethylene glycosylated form showed a significantly (p < 0.05) greater improvement for strength when compared with control group. These strength increases were similar even though the dose of creatine in the polyethylene glycosylated creatine groups was up to 75% less than that of CM. These results seem to indicate that the addition of polyethylene glycol could increase the absorption efficiency of creatine but further research is needed before a definitive recommendation can be reached.
The pancreas is one of the extrahepatic (beyond the liver) organs that can synthesize creatine, alongside the kidneys. Freshly prepared pancreatic β-cells will normally secrete insulin in response to glucose stimulation, and it appears that phosphocreatine is required for this effect, since phosphocreatine is increased in response to glucose alongside an increase of the ADP:ATP ratio. They appear to close ATP sensitive potassium channels (KATP channels), causing a release of insulin secondary to calcium release. Both phosphocreatine and ADP are implicated, but it seems that despite the channel being sensitive to ATP, the concentration of ATP in a pancreatic cell (3-5mM) is already above the activation threshold (in the micromolar range) and thus a further increase would not have an appreciable effect.
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?
Those micro-tears that are such a key factor for muscle-building need rest to rebuild themselves and grow stronger. When do they do that? When you’re asleep! “You have to rest and feed your muscles between workouts or you will tear them down and they will become weaker,” says Olson. “Over time, you run the risk of over-training, which can result in injury, and possibly even more sleep troubles.”