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] 
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[26] Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in GATM and guanidinoacetate methyltransferase deficiency, caused by variants in GAMT. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.[27]
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I always recommend starting on the low end of the scale. Only increase volume when you absolutely need to. So, if you’re training chest, you could do 6 work sets of dumbbell bench presses to start out, breaking down to two sets per workout for three sessions per week. You can gradually add sets from there, experimenting with different training splits that will allow you to get in more volume without overtraining (we’ll discuss training splits next).
According to BodyBuilding.com, adenosine triphosphate (ATP) is made up of a nucleotide bonded to three phosphate groups. When one of those phosphate groups is cleaved from the ATP molecule, a lot of energy is made available. That energy is used to fuel chemical reactions in cells, and ATP becomes adenosine diphosphate (ADP). Creatine enables the release of energy from stored ATP and is converted to creatinine.
Children: Creatine is POSSIBLY SAFE in children when taken by mouth appropriately. Creatine 3-5 grams daily for 2-6 months has been taken safely in children 5-18 years of age. Creatine 2 grams daily for 6 months has been taken safely in children 2-5 years of age. Additionally, creatine 0.1-0.4 grams/kg daily for up to 6 months has been taken safely in both infants and children.
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.
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.
Collectively the above investigations indicate that creatine supplementation can be an effective strategy to maintain total creatine pool during a rehabilitation period after injury as well as to attenuate muscle damage induced by a prolonged endurance training session. In addition, it seems that creatine can act as an effective antioxidant agent after more intense resistance training sessions.
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