McArdle’s disease is a myopathic disorder associated with fatigue and contractile dysfunction as a result of alterations in the release of glucose from glycogen (via defects in myophosphorylase enzyme function) resulting in an inability to conduct high intensity work as easily. Creatine is thought to be therapeutic because beyond the general strength enhancing properties of creatine, people with McArdle’s disease have an upregulation of phosphofructokinase (PFK) enzyme activity  and increasing phosphocreatine storages suppresses the activity of this enzyme.
Synthesis primarily takes place in the kidney and liver, with creatine then being transported to the muscles via the blood. The majority of the human body's total creatine and phosphocreatine stores is located in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues. Typically, creatine is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults. Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet. Some small studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, as expected since foods of animal origin are the primary source of creatine. However, subjects happened to show the same levels after using supplements.