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).
By increasing the overall pool of cellular phosphocreatine, creatine supplementation can accelerate the reycling of ADP into ATP. Since ATP stores are rapidly depleted during intense muscular effort, one of the major benefits of creatine supplementation is its ability to regenerate ATP stores faster, which can promote increased strength and power output. Over 95% of creatine is stored in muscle at a maximum cellular concentration of 30uM. Creatine storage capacity is limited, though it increases as muscle mass increases.[24] A 70 kg male with an average physique is assumed to have total creatine stores of approximately 120g.[25] The body can store a lot more energy as glycogen in the liver, brain, and muscles,[26][27] and even more as fat.
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The first published results (not blinded) noted that a loading phase of 20g of creatine for a week, followed by 3g daily for up to six months, was able to enhance maximal voluntary isometric muscular contraction (MVIC) on a dynamometer for both the knee and elbow joints, with enhanced fatigue resistance on the same joints in more than half of subjects (53-70% response rate).[545]
Longer rest periods are more ideal for making progressive tension overload happen, and shorter rest periods are more ideal for generating metabolic fatigue. So, if you’re doing an exercise that is better suited for progressive overload (i.e. primary compound exercises), you’re going to want to rest longer between sets to maximize strength output. And if you’re doing an exercise that is better suited for metabolic fatigue (i.e. isolation exercises), you’re going to want to rest less between sets to make that happen. And if you’re doing an exercise that is suited equally for a combination of the two (i.e. secondary compound exercises), you’re usually going to want a moderate rest period somewhere in between.
Guanidoacetate (made by AGAT) then receives a methyl donation from S-adenosyl methionine via the enzyme guanidinoacetate methyltransferase (GAMT), which produces S-adenosylhomocysteine (as a byproduct) and creatine. Deficiencies in GAMT are more severe (although equally rare) relative to AGAT, resulting in severe mental retardation and autism-like symptoms.[31]

Creatine is a hydrophilic polar molecule that consists of a negatively charged carboxyl group and a positively charged functional group [64]. The hydrophilic nature of creatine limits its bioavailability [65]. In an attempt to increase creatines bioavailability creatine has been esterified to reduce the hydrophilicity; this product is known as creatine ethyl ester. Manufacturers of creatine ethyl ester promote their product as being able to by-pass the creatine transporter due to improved sarcolemmal permeability toward creatine [65]. Spillane et al [65] analyzed the effects of a 5 days loading protocol (0.30 g/kg lean mass) followed by a 42 days maintenance phase (0.075 g/kg lean mass) of CM or ethyl ester both combined with a resistance training program in 30 novice males with no previous resistance training experience. The results of this study [65] showed that ethyl ester was not as effective as CM to enhance serum and muscle creatine stores. Furthermore creatine ethyl ester offered no additional benefit for improving body composition, muscle mass, strength, and power. This research did not support the claims of the creatine ethyl ester manufacturers.
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