Creatine monohydrate has a large and growing body of literature to support not only its performance enhancing effects, but also its therapeutic effects in many diseases (muscular dystrophy, parkinsons). Despite this, it has been estimated that as few as 20% of users actually saturate their creatine stores when supplementing and as many as 30% fail to respond at all (1). While we don’t have a precise explanation for the variable response to creatine supplementation, one theory suggests that creatine uptake is the limiting factor in non-responders. As a consequence, current research has focused on modifying creatine in order to improve uptake and hopefully improve performance in non-responders.
Without hitting the chemistry too hard, creatine is a polar molecule that is hydrophilic (water-loving), which limits its ability to freely enter muscle cells by passing through the cell membrane (sarcolemma). Because cell membranes have a hydrophobic (water-phobic) core, creatine requires a specific transporter to cross the cell membrane. The fact that creatine requires a transporter system could limit its ability to enter the target cell, in this case muscle, which can limit creatine loading. There are various ways to modify compounds that can alter their behaviour in solution, and ultimately allow them to freely cross the cell membrane and increase uptake, overcoming the potential transport barrier. So in the case of creatine ethyl ester (CEE), an ethyl ester was linked to creatine in the hopes that this could bypass the transporter system and improve creatine uptake compared to the ‘old’ monohydrate form.Continue Reading