Metabolic Neuroprotection:Creatine Supplementation in Human Brain

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DESCRIPTION (provided by applicant): Oral creatine supplementation has been demonstrated by several groups to increase muscle performance and mass. High concentrations of PCr and creatine are also found in the brain, which with its relatively high oxygen consumption means that, similar to muscle, brain tissue may be metabolically affected by exogenous creatine. However while there is extensive work examining how use of creatine affects muscle performance, there is relatively less work available in the brain. In this proposal we will begin to fill this gap, with non-invasive MR measurements of high energy phosphates, NAA, creatine and perfusion/oxidative metabolism in healthy controls. Furthermore, because of the increasing data that progressive metabolic dysfunction may contribute directly to the pathophysiology of epilepsy, we will also examine the metabolic and clinical effects of oral creatine supplementation in patients with temporal lobe epilepsy. This work is done in collaboration with R. Kuzniecky , MD with the NYU Comprehensive Epilepsy Center. In particular, epilepsy is known to respond to another form of "metabolic therapy", the high fat ketogenic diet. As we have previously shown using MR spectroscopy, patients placed on the ketogenic diet demonstrated increases in cerebral PCr/ATP, known to be decreased in epilepsy patients. If successful, this project may show that creatine 1) can provide a supplementary avenue of therapy and 2) contribute additional evidence for a metabolic pathophysiologic component to epilepsy.