Creatine is not an essential nutrient as it is naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for methionine to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis these two amino acids are combined by the enzyme arginine:glycine amidinotransferase (AGAT, EC:18.104.22.168) to form guanidinoacetate, which is then methylated by guanidinoacetate N-methyltransferase (GAMT, EC:22.214.171.124), using S-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain.
“Imagine you've fasted for over eight hours,” he says. “At breakfast, you're firing your metabolism off really high. If you don't eat for another five hours, your metabolism starts to slow right down and you have to try and kickstart it again with your next meal. If you eat every two and a half to three hours, it's like chucking a log on a burning fire.”
Every 4-8 weeks, vary your routine. As your body adapts to stress, you'll hit a plateau where the benefits of weight training will begin to diminish. The only way to prevent this from happening is to change things up, such as by increasing weight and changing exercises. Try a week of really piling the weights on, and do six to eight reps per set at the maximum weight you can manage with proper form. The more lifting experience you have, the more often you should vary your routine.
Creatine, through its ability to act as an energy reserve, attenuates neuron death induced by the MPTP toxin that can produce Parkinson’s disease-like effects in research animals, reduces glutamate-induced excitotoxicity, attenuates rotenone-induced toxicity, L-DOPA induced dyskinesia, 3-nitropropinoic acid, and preserves growth rate of neurons during exposure to corticosteroids (like cortisol), which can reduce neuron growth rates. Interestingly, the energetic effect also applies to Alzheimer’s disease, during which creatine phosphate per se attenuates pathogenesis in vitro, yet creatine per se did not.
It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio, and when activated AMPK (active in states of low cellular energy and colocalizes with creatine kinase in muscle tissue) 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. 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.