The ketogenic diet (KD) is an effective approach that has been used for over a century to treat a variety of diseases, from cancer to migraine. KD therapy – characterised by a diet high in fat and low in carbohydrate – lowers blood sugar levels, and stimulates production of ketone bodies (mainly β-hydroxybutyrate, acetoacetate and acetone). These ketone bodies provide an alternative substrate to glucose for energy use and form essential building blocks for the biosynthesis of cell membranes and lipids in the developing brain.
KD therapy has been shown to improve mitochondrial function and also has direct neuronal effects, including: ATP-sensitive potassium channel modulation; enhanced neurotransmission; attenuation of neuroinflammation; and modulation of lipid metabolism. As such, the KD exhibits disease-modifying and neuroprotective properties. KD therapy has been recognized to reduce anti-epileptic exposure and improve patients’ cognitive and behavioural profiles, and there is a growing body of evidence supporting the anti-seizure efficacy, safety profile, and feasibility of the use of KD in childhood epilepsy. Moreover, it has also been questioned whether a KD regimen may useful in hypomyelinating disease and for seizures caused by metabolic disorders. As an anticonvulsant therapy, current indications for KD therefore include refractory epilepsy syndromes (such as Dravet syndrome) – for which KD therapy is the main treatment –, selected metabolic disorders (such as pyruvate dehydrogenase deficiency), and a variety of neurological diseases.
Application of the KD is known to have other potentially disease-modifying effects, improving many clinical conditions such as autism, Rett syndrome, traumatic brain injury, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, brain tumor, prostate cancer, diabetes, and obesity. It should be noted that some of these disorders coexist and the KD therefore offers an opportunity to help cure more than one disease with a single therapy.
The rate and type of KD should be adjusted according to personal characteristics, with treatment being individualized according to the sociocultural and economic status of the patient and family, nutritional habits, comorbid conditions, ketone production, frequency and severity of seizures. However, efficacy of KD therapy in patients varies between individuals. For example, Glut-1 deficiency and certain molecular genetic epilepsies are sensitive and respond positively to the KD, whilst such treatments are not effective in others (e.g., CDKL5 mutations). Sharing experiences on this subject is important in terms of precision medicine, as detection of many molecular genetic causes of epilepsies, including encephalopathies, will be facilitated by further advances in precision diagnostics, continued great collaborations, and wider availability of whole-exome and whole-genome sequencing in clinical practice.
In this Research Topic, we will include articles on the use of Ketogenic Diet therapy in individualized medicine, welcoming submissions including but not limited to the following sub-topics:
• Effects of KD therapy on clinical and physiological outcomes (e.g., neuronal effects, seizures, sleep, psychological wellbeing, but also other outcomes such as obesity and cancer);
• Effectiveness of KD in epilepsy compared to conventional drug treatments or in drug-resistant epilepsy;
• Cost effectiveness of KD therapy;
• The role of nutritional supplements on the long-term monitoring of KD therapy;
• Mechanism and immunologic imprinting of KD therapy;
• Determination of individualized KD therapy regimens by biochemical and imaging methods.
Submissions of the following article types will be accepted: Brief Research Report, Case Report, Clinical Trial, Data Report, Editorial, Mini Review, Original Research, Systematic Review.
The ketogenic diet (KD) is an effective approach that has been used for over a century to treat a variety of diseases, from cancer to migraine. KD therapy – characterised by a diet high in fat and low in carbohydrate – lowers blood sugar levels, and stimulates production of ketone bodies (mainly β-hydroxybutyrate, acetoacetate and acetone). These ketone bodies provide an alternative substrate to glucose for energy use and form essential building blocks for the biosynthesis of cell membranes and lipids in the developing brain.
KD therapy has been shown to improve mitochondrial function and also has direct neuronal effects, including: ATP-sensitive potassium channel modulation; enhanced neurotransmission; attenuation of neuroinflammation; and modulation of lipid metabolism. As such, the KD exhibits disease-modifying and neuroprotective properties. KD therapy has been recognized to reduce anti-epileptic exposure and improve patients’ cognitive and behavioural profiles, and there is a growing body of evidence supporting the anti-seizure efficacy, safety profile, and feasibility of the use of KD in childhood epilepsy. Moreover, it has also been questioned whether a KD regimen may useful in hypomyelinating disease and for seizures caused by metabolic disorders. As an anticonvulsant therapy, current indications for KD therefore include refractory epilepsy syndromes (such as Dravet syndrome) – for which KD therapy is the main treatment –, selected metabolic disorders (such as pyruvate dehydrogenase deficiency), and a variety of neurological diseases.
Application of the KD is known to have other potentially disease-modifying effects, improving many clinical conditions such as autism, Rett syndrome, traumatic brain injury, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, brain tumor, prostate cancer, diabetes, and obesity. It should be noted that some of these disorders coexist and the KD therefore offers an opportunity to help cure more than one disease with a single therapy.
The rate and type of KD should be adjusted according to personal characteristics, with treatment being individualized according to the sociocultural and economic status of the patient and family, nutritional habits, comorbid conditions, ketone production, frequency and severity of seizures. However, efficacy of KD therapy in patients varies between individuals. For example, Glut-1 deficiency and certain molecular genetic epilepsies are sensitive and respond positively to the KD, whilst such treatments are not effective in others (e.g., CDKL5 mutations). Sharing experiences on this subject is important in terms of precision medicine, as detection of many molecular genetic causes of epilepsies, including encephalopathies, will be facilitated by further advances in precision diagnostics, continued great collaborations, and wider availability of whole-exome and whole-genome sequencing in clinical practice.
In this Research Topic, we will include articles on the use of Ketogenic Diet therapy in individualized medicine, welcoming submissions including but not limited to the following sub-topics:
• Effects of KD therapy on clinical and physiological outcomes (e.g., neuronal effects, seizures, sleep, psychological wellbeing, but also other outcomes such as obesity and cancer);
• Effectiveness of KD in epilepsy compared to conventional drug treatments or in drug-resistant epilepsy;
• Cost effectiveness of KD therapy;
• The role of nutritional supplements on the long-term monitoring of KD therapy;
• Mechanism and immunologic imprinting of KD therapy;
• Determination of individualized KD therapy regimens by biochemical and imaging methods.
Submissions of the following article types will be accepted: Brief Research Report, Case Report, Clinical Trial, Data Report, Editorial, Mini Review, Original Research, Systematic Review.