New insights into the mechanisms of the ketogenic diet

Boison, Detlev

doi:10.1097/wco.0000000000000432

Cited by 209 publications

(174 citation statements)

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“…Today, KDs and related metabolic therapies are established therapies for difficult‐to‐treat epilepsies in addition to a wider use in a variety of neurological disorders (Stafstrom & Rho, ). Core mechanisms of the diet have been covered in recent review articles (Boison, ; Masino & Rho, ; Rho, ; Yellen, ). Here, we will focus on those mechanisms directly related to energy homeostasis in the epileptic brain.…”

Section: Metabolic Therapiesmentioning

confidence: 99%

Epilepsy and astrocyte energy metabolism

Boison

Steinhäuser

2017

Glia

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Epilepsy is a complex neurological syndrome characterized by neuronal hyperexcitability and sudden, synchronized electrical discharges that can manifest as seizures. It is now increasingly recognized that impaired astrocyte function and energy homeostasis play key roles in the pathogenesis of epilepsy. Excessive neuronal discharges can only happen, if adequate energy sources are made available to neurons. Conversely, energy depletion during seizures is an endogenous mechanism of seizure termination. Astrocytes control neuronal energy homeostasis through neurometabolic coupling. In this review, we will discuss how astrocyte dysfunction in epilepsy leads to distortion of key metabolic and biochemical mechanisms. Dysfunctional glutamate metabolism in astrocytes can directly contribute to neuronal hyperexcitability. Closure of astrocyte intercellular gap junction coupling as observed early during epileptogenesis limits activity-dependent trafficking of energy metabolites, but also impairs clearance of the extracellular space from accumulation of K and glutamate. Dysfunctional astrocytes also increase the metabolism of adenosine, a metabolic product of ATP degradation that broadly inhibits energy-consuming processes as an evolutionary adaptation to conserve energy. Due to the critical role of astroglial energy homeostasis in the control of neuronal excitability, metabolic therapeutic approaches that prevent the utilization of glucose might represent a potent antiepileptic strategy. In particular, high fat low carbohydrate "ketogenic diets" as well as inhibitors of glycolysis and lactate metabolism are of growing interest for the therapy of epilepsy.

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Section: Metabolic Therapiesmentioning

confidence: 99%

Epilepsy and astrocyte energy metabolism

Boison

Steinhäuser

2017

Glia

Self Cite

174

154

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“…It is more likely that the efficacy of the KD depends on many different mechanisms acting synergistically [28,34]. We will look at some of these theories in more detail.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Use of the Ketogenic Diet to Treat Intractable Epilepsy in Mitochondrial Disorders

Paleologou

Ismayilova

Kinali

2017

JCM

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Mitochondrial disorders are a clinically heterogeneous group of disorders that are caused by defects in the respiratory chain, the metabolic pathway of the adenosine tri-phosphate (ATP) production system. Epilepsy is a common and important feature of these disorders and its management can be challenging. Epileptic seizures in the context of mitochondrial disease are usually treated with conventional anti-epileptic medication, apart from valproic acid. However, in accordance with the treatment of intractable epilepsy where there are limited treatment options, the ketogenic diet (KD) has been considered as an alternative therapy. The use of the KD and its more palatable formulations has shown promising results. It is especially indicated and effective in the treatment of mitochondrial disorders due to complex I deficiency. Further research into the mechanism of action and the neuroprotective properties of the KD will allow more targeted therapeutic strategies and thus optimize the treatment of both epilepsy in the context of mitochondrial disorders but also in other neurodegenerative disorders.

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“…Data from cellular and animal studies support and extend Warburg's conclusions (13)(14)(15)(16) . Reviews concentrating on tumour-suppressive mechanisms behind the diet combine the available data from cellular, animal and clinical studies (14,(17)(18)(19) . Clinical evidence alone was reviewed in four articles.…”

Section: Introductionmentioning

confidence: 99%