Different forms of creatine in combination with other sports supplements as well as varying doses and supplementation methodology should continue to be researched in an attempt to understand further application of creatine to increase sports and exercise performance of varying disciplines. It is important to remain impartial when evaluating the safety of creatine ingested as a natural supplement. The available evidence indicates that creatine consumption is safe. This perception of safety cannot be guaranteed especially that of the long term safety of creatine supplementation and the various forms of creatine which are administered to different populations (athletes, sedentary, patient, active, young or elderly) throughout the globe.

If you’re exercising at your maximum intensity, your body literally can’t produce enough ATP to keep up. (10) That’s where creatine supplements come in: They can help increase your body’s stores of phosphocreatine (an organic compound of creatine and phosphoric acid that’s stored in your muscle tissue) to produce new ATP during high-intensity exercise.

It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio,[333][334] and when activated AMPK (active in states of low cellular energy[335] and colocalizes with creatine kinase in muscle tissue[336]) appears to inhibit creatine kinase via phosphorylation (preserving phosphocreatine stores but attenuating the rate that creatine buffers ATP). While phosphocreatine technically inhibits AMPK, this does not occur in the presence of creatine at a 2:1 ratio.[334] It seems that if the ratio of phosphocreatine:creatine increases (indicative of excess cellular energy status) that AMPK activity is then attenuated, since when a cell is in a high energy status, there is less AMP to directly activate AMPK.[334][336][337]