Potential role of creatine as an anticonvulsant agent: evidence from preclinical studies

Abstract

Epilepsy is one of the most common neurological disorders affecting people of all ages representing a significant social and public health burden. Current therapeutic options for epilepsy are not effective in a significant proportion of patients suggesting a need for identifying novel targets for the development of more effective therapeutics. There is growing evidence from animal and human studies suggesting a role of impaired brain energy metabolism and mitochondrial dysfunction in the development of epilepsy. Candidate compounds with the potential to target brain energetics have promising future in the management of epilepsy and other related neurological disorders. Creatine is a naturally occurring organic compound that serves as an energy buffer and energy shuttle in tissues, such as brain and skeletal muscle, that exhibit dynamic energy requirements. In this review, applications of creatine supplements in neurological conditions in which mitochondrial dysfunction is a central component in its pathology will be discussed. Currently, limited evidence mainly from preclinical animal studies suggest anticonvulsant properties of creatine; however, the exact mechanism remain to be elucidated. Future work should involve larger clinical trials of creatine used as an add-on therapy, followed by large clinical trials of creatine as monotherapy.

Towards a better understanding of idiopathic epilepsy through metabolic fingerprinting of cerebrospinal fluid in dogs.

“…Creatinine is the breakdown product of creatine. The latter is a nitrogenous guanidine compound playing a key role in cellular energy metabolism, especially in tissue with high energy demands, like the brain 32 . Degradation of creatine to creatinine occurs non-enzymatically on a daily basis in healthy individuals 33 .…”

Towards a better understanding of idiopathic epilepsy through metabolic fingerprinting of cerebrospinal fluid in dogs

“…Creatinine is the breakdown product of creatine. The latter is a nitrogenous guanidine compound playing a key role in cellular energy metabolism, especially in tissue with high energy demands, like the brain 33 . Degradation of creatine to creatinine occurs non-enzymatically on a daily basis in healthy individuals 34 .…”

Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review

“…While most seizures are drug responsive, severe epilepsy and status epilepticus were also reported [16,18]. There is growing evidence suggesting a strong involvement of brain energy depletion and mitochondrial dysfunction in the development of epilepsy [38]. Creatine supplementation was demonstrated to have potential anticonvulsant effects, yet the exact mechanism remains to be elucidated [39][40][41].…”

“…Future work should involve larger clinical trials with creatine as monotherapy and creatine with precursors. In addition, little is known regarding the optimal dosing for CTD, and the protocols used in the literature for creatine supplementation are heterogeneous [38,51]. Therefore, dose-response studies are required.…”