Negative regulators of the creatine transporter (CrT) are those that, when activated, reduce the activity of the CrT and overall creatine uptake into cells. As noted above, CrT activity is positively regulated by mTOR.[158] Consistent with the well-known role of AMPK as a suppressor mTOR signaling,[177] CrT activity has also been shown to be inhibited in response to AMPK activation in kidney epithelial cells.[178] Since AMPK suppresses mTOR via upstream TSC2 activation,[179] the negative regulation of AMPK on CrT activity in these cells appears to occur through an indirect mechanism. Although indirect, activation of AMPK has been noted to reduce the Vmax of the CrT without altering creatine binding, and is involved in internalizing the receptors.[178] This pathway seems to max out at around 30% suppression, with no combination of mTOR antagonists and AMPK inducers further suppressing creatine uptake.[178]

One of the studies noting a reduction in fatigue in healthy subjects given creatine (8g) for five days prior to a mathematical test noted a relative decrease in oxygenation hemoglobin in the brain and an increase in deoxygenated hemoglobin, which normally indicates a reduction in cerebral oxygenation.[245] The authors made note of how cytoplasmic phosphocreatine can increase oxygen uptake into cells (noted in vitro in a concentration dependent manner between 0-25mM[245]) and suggested that either cells were taking up more oxygen from hemoglobin, or that increased mitochondrial efficiency resulted in less of a need for oxygen.[245]
At the end of the day, you have to focus on how you feel. “Listen to your body,” says Davis. “It tells you when it needs a day off.” As a rule of thumb, take a rest day if your perceived pain is above a seven on a scale of 10, Davis advises. Or, focus on a different body part (say, if your legs are sore, focus on upper-body moves). Can't stop, won't stop—at least, till your next rest day.
The right amount of workout: It is highly possible that the protein powder you are taking doesn’t work on your body. Supplements should only be taken if you have a rigorous workout schedule or else, it will turn out to be of no value. Most people just purchase a box of supplements without really doing the math, which is very important. Unless you find out the dosage that suits you, the amount of time you should dedicate for the workout and so on, you must not expect daydream the results. 

Beast Creature could be another good option for female athletes. It’s tasty, it contains five types of creatine, and it contains ingredients that could improve fat loss by increasing insulin sensitivity. One potential bonus is that it also has 70 percent of your daily biotin, a nutrient often included in women’s multivitamins due its purported benefits for hair and nails.
Syndromes caused by problems metabolizing creatine. Some people have a disorder that prevents their body from making creatine. This can lead to low levels of creatine in the brain. Low levels of creatine in the brain can lead to decreased mental function, seizures, autism, and movement problems. Taking creating by mouth daily for up to 3 years can increase creatine levels in the brain in children and young adults with a disorder of creatine production called guanidinoacetate methyltransferase (GAMT) deficiency. This can help improve movement and reduce seizures. But it doesn't improve mental ability. Arginine-glycine amidinotransferase (AGAT) deficiency is another disorder that prevents the body from making creatine. In children with this condition, taking creatine for up to 8 years seems to improve attention, language, and mental performance. But taking creatine does not seem to improve brain creatine levels, movement, or mental function in children who have a disorder in which creatine isn't transported properly.

^ Jump up to: a b Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM (January 1992). "Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis". The Biochemical Journal. 281 ( Pt 1) (Pt 1): 21–40. doi:10.1042/bj2810021. PMC 1130636. PMID 1731757.
Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) is a synthetic analogue of creatine in a cyclic form. It serves as a substrate for the creatine kinase enzyme system, acting as a creatine mimetic. Cyclocreatine may compete with creatine in the CK enzyme system to transfer phosphate groups to ADP, as coincubation of both can reduce cyclocreatine’s anti-motility effects on some cancer cells.[96]

Similarly to complex training, contrast loading relies upon the enhanced activation of the nervous system and increased muscle fibre recruitment from the heavy set, to allow the lighter set to be performed more powerfully.[41] Such a physiological effect is commonly referred to as post-activation potentiation, or the PAP effect. Contrast loading can effectively demonstrate the PAP effect: if a light weight is lifted, and then a heavy weight is lifted, and then the same light weight is lifted again, then the light weight will feel lighter the second time it has been lifted. This is due to the enhanced PAP effect which occurs as a result of the heavy lift being utilised in the subsequent lighter lift; thus making the weight feel lighter and allowing the lift to be performed more powerfully.
One pilot study using 150mg/kg creatine monohydrate for a five day loading phase followed by maintenance (60mg/kg) for the remainder of the five weeks noted that supplementation was associated with fewer muscle symptoms and complaints alongside improved muscular function,[572] yet a later trial trying to replicate the obsevations using 150mg/kg daily for five weeks noted the opposite, that creatine supplementation exacerbated symptoms.[573]