Adenosine pp 581-598 | Cite as

Ketogenic Diet and Epilepsy: The Role of Adenosine



The ketogenic diet (KD) debuted in the 1920s as a metabolic treatment for epilepsy, based on the historical observation that fasting could prevent seizures. Similar to fasting, the high-fat, low-carbohydrate KD restricts glucose and favors oxidation of fatty acids, which in turn generates ketones for energy. Despite nearly a century of clinical use, proof of efficacy was only recently established, and little is known about how the KD works. The lure of a continually growing armamentarium of pharmacological options and the inherent challenges in implementing a dietary treatment versus a drug have combined to relegate the KD to a therapy of last resort. Indeed, better knowledge of how the KD exerts broad-spectrum clinical activity would be required to develop enhanced metabolism-based treatments, and perhaps even a “diet in a pill.” Recent evidence strongly implicates adenosine as a mediator of KD action, as it is well known that adenosine is a fundamental link between metabolism and neuronal membrane excitability. Through a greater mechanistic understanding of how the KD―and adenosine in particular―works to dampen aberrant excitation in the brain, novel insights and molecular targets are bound to emerge. However, given the complexity of metabolic pathways in both normal and disease states, it will be important to determine specific cause-and-effect relationships. At present, given growing interest in metabolic dysfunction as a major pathophysiological substrate for a multiplicity of disease states, as well as urgent concerns regarding unbridled healthcare costs worldwide, we predict that research in the area of “translational metabolism” will gain further momentum. Here we highlight current research on mechanism(s) of KD action, with a focus on adenosine, and promote the concept that the KD is both an accessible and affordable therapy by describing an international case study of recent KD training and initial outcomes in the Republic of Georgia.


Ketogenic Diet Anticonvulsant Effect Refractory Status Epilepticus Adenosine Kinase Electrographic Seizure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to acknowledge the National Institutes of Health, National Science Foundation, Trinity College, the Alberta Children’s Hospital Research Institute, and the Charlie Foundation to Cure Pediatric Epilepsy for support.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jong M. Rho
    • 1
  • Beth Zupec-Kania
    • 2
  • Susan A. Masino
    • 3
  1. 1.Departments of Pediatrics and Clinical Neurosciences, Alberta Children’s HospitalUniversity of CalgaryCalgaryCanada
  2. 2.Ketogenic SeminarsThe Charlie FoundationSanta MonicaUSA
  3. 3.Neuroscience Program and Psychology DepartmentTrinity College, Life Sciences Center 210HartfordUSA

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