Ketogenic Diet

About one third of patients with epilepsy are pharmacoresistent. For a subgroup of this population, the ketogenic diet can be highly efficacious and should be considered early. This review discusses the different types of ketogenic diet, proposed mechanism of actions and its evidence for use in children and adults with both generalized and focal epilepsies where surgery is not feasible. In addition we discuss a practical approach to diet initiation, maintenance and monitoring for side effects. We also summarize the emerging evidence for the use of ketogenic diet in a broad range of neurological disorders.

[1]  M. Prins,et al.  Cerebral Metabolic Adaptation and Ketone Metabolism after Brain Injury , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  J. Cross,et al.  The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial , 2008, The Lancet Neurology.

[3]  Munhyang Lee,et al.  The role of ketogenic diet in the treatment of refractory status epilepticus , 2011, Epilepsia.

[4]  S. Kang,et al.  Acetoacetate protects neuronal cells from oxidative glutamate toxicity , 2006, Journal of neuroscience research.

[5]  Suvasini Sharma,et al.  The ketogenic diet and the QT interval , 2012, Journal of Clinical Neuroscience.

[6]  Marcela de Almeida Rabello Oliveira,et al.  Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats , 2008, Neuroscience Letters.

[7]  E. Kossoff,et al.  A Modified Atkins Diet Is Effective for the Treatment of Intractable Pediatric Epilepsy , 2006, Epilepsia.

[8]  E. Jeong,et al.  Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures , 2011, Experimental Neurology.

[9]  Hoon-Chul Kang,et al.  Safe and Effective Use of the Ketogenic Diet in Children with Epilepsy and Mitochondrial Respiratory Chain Complex Defects , 2007, Epilepsia.

[10]  J. Cross,et al.  A randomized trial of classical and medium‐chain triglyceride ketogenic diets in the treatment of childhood epilepsy , 2009, Epilepsia.

[11]  Stacey B. B. Dutton,et al.  Protective effect of the ketogenic diet in Scn1a mutant mice , 2011, Epilepsia.

[12]  E. Kossoff,et al.  Tuberous Sclerosis Complex and the Ketogenic Diet , 2005, Epilepsia.

[13]  G. Coppola,et al.  Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet , 2006, Brain and Development.

[14]  L. Nebeling,et al.  Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. , 1995, Journal of the American College of Nutrition.

[15]  G. J. Buse,et al.  Patient with gemfibrozil-controlled hypertriglyceridemia that developed acute pancreatitis after starting ketogenic diet. , 2004, Current surgery.

[16]  M. Funatsuka,et al.  Treatment and Long-Term Prognosis of Myoclonic-Astatic Epilepsy of Early Childhood , 2002, Neuropediatrics.

[17]  R. Caraballo Nonpharmacologic treatments of Dravet syndrome: Focus on the ketogenic diet , 2011, Epilepsia.

[18]  C. Mullett,et al.  Ketogenic Diet: Rapid Onset of Selenium Deficiency-Induced Cardiac Decompensation , 2012, Pediatric Cardiology.

[19]  Rm. Wilder,et al.  The effects of ketonemia on the course of epilepsy , 1921 .

[20]  J. Freeman,et al.  The Epilepsy Diet Treatment: : An Introduction to The Ketogenic Diet , 1994 .

[21]  H. Geyelin Fasting as a method for treating epilepsy , 1921 .

[22]  J. Rho,et al.  Ketogenic diet in the treatment of seizures associated with hypothalamic hamartomas , 2011, Epilepsy Research.

[23]  M. Carniello,et al.  Long-term follow-up of the ketogenic diet for refractory epilepsy: Multicenter Argentinean experience in 216 pediatric patients , 2011, Seizure.

[24]  O. Dulac,et al.  Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: A prospective pilot study , 2011, Epilepsia.

[25]  A. D’Aniello,et al.  Low glycemic index diet in children and young adults with refractory epilepsy: First Italian experience , 2011, Seizure.

[26]  J M Freeman,et al.  A multicenter study of the efficacy of the ketogenic diet. , 1998, Archives of neurology.

[27]  A. Bergqvist,et al.  Current Treatment of Myoclonic Astatic Epilepsy: Clinical Experience at the Children's Hospital of Philadelphia , 2007, Epilepsia.

[28]  B. Rosenblatt,et al.  Sudden cardiac death in association with the ketogenic diet. , 2008, Pediatric neurology.

[29]  R. Guerrini,et al.  The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: An Italian consensus , 2011, Epilepsia.

[30]  A. Negassa,et al.  Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. , 2012, Nutrition.

[31]  I. Scheffer,et al.  Is the ketogenic diet effective in specific epilepsy syndromes? , 2012, Epilepsy Research.

[32]  B. Nelson,et al.  A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation. , 2011, Cancer research.

[33]  J. Gornbein,et al.  n-3 Fatty acids (fish oil) for epilepsy, cardiac risk factors, and risk of SUDEP: Clues from a pilot, double-blind, exploratory study , 2008, Epilepsy & Behavior.

[34]  P. Kwan,et al.  Early identification of refractory epilepsy. , 2000, The New England journal of medicine.

[35]  Suvasini Sharma,et al.  Use of the modified Atkins diet for treatment of refractory childhood epilepsy: A randomized controlled trial , 2013, Epilepsia.

[36]  P. Huttenlocher Ketonemia and Seizures: Metabolic and Anticonvulsant Effects of Two Ketogenic Diets in Childhood Epilepsy , 1976, Pediatric Research.

[37]  J. Smeitink,et al.  Application of a Ketogenic Diet in Children With Autistic Behavior: Pilot Study , 2003, Journal of child neurology.

[38]  L. Morrison,et al.  Optimal clinical management of children receiving the ketogenic diet: Recommendations of the International Ketogenic Diet Study Group , 2009, Epilepsia.

[39]  Hoon-Chul Kang,et al.  Comparison of short‐ versus long‐term ketogenic diet for intractable infantile spasms , 2011, Epilepsia.

[40]  J M Freeman,et al.  The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. , 1998, Pediatrics.

[41]  R. H. Garrett,et al.  Biochemistry, 2nd ed. , 1999 .

[42]  P. Stafford,et al.  The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma , 2012, PloS one.

[43]  P. Klein,et al.  Ketogenic diet treatment in adults with refractory epilepsy , 2010, Epilepsy & Behavior.

[44]  M. Yudkoff,et al.  Ketone Bodies and Brain Glutamate and GABA Metabolism , 1998, Developmental Neuroscience.

[45]  O. Dulac,et al.  Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES) , 2010, Epilepsia.

[46]  Dieter Schmidt,et al.  Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. , 2006, Brain : a journal of neurology.

[47]  E. Kossoff,et al.  The Ketogenic Diet , 2005, The neurologist.

[48]  E. Thiele,et al.  Low-glycemic-index treatment: A liberalized ketogenic diet for treatment of intractable epilepsy , 2005, Neurology.

[49]  E. Thiele,et al.  Low glycemic index treatment: Implementation and new insights into efficacy , 2008, Epilepsia.

[50]  E. Kossoff,et al.  Long‐term use of the ketogenic diet in the treatment of epilepsy , 2006 .

[51]  E. Kossoff,et al.  A randomized, crossover comparison of daily carbohydrate limits using the modified Atkins diet , 2007, Epilepsy & Behavior.

[52]  C. Gottfried,et al.  Ketogenic Diet Increases Glutathione Peroxidase Activity in Rat Hippocampus , 2003, Neurochemical Research.

[53]  P. Stafford,et al.  The ketogenic diet for the treatment of glioma: Insights from genetic profiling , 2012, Epilepsy Research.

[54]  Hoon-Chul Kang,et al.  Efficacy and tolerability of the ketogenic diet according to lipid:nonlipid ratios--comparison of 3:1 with 4:1 diet. , 2007, Epilepsia.

[55]  E. Kossoff,et al.  Efficacy of the ketogenic diet in Lennox–Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature , 2012, Developmental medicine and child neurology.

[56]  H H Wilder,et al.  ANTHROPOMETRIC MEASUREMENTS. , 1921, Science.

[57]  H. Helmholz THE TREATMENT OF EPILEPSY IN CHILDHOOD: FIVE YEARS' EXPERIENCE WITH THE KETOGENIC DIET , 1927 .

[58]  E. Kossoff,et al.  Long-Term Follow-Up of Children Treated With the Modified Atkins Diet , 2012, Journal of child neurology.

[59]  A. Aynsley-Green,et al.  KETOGENIC DIETS IN THE TREATMENT OF EPILEPSY: SHORT‐TERM CLINICAL EFFECTS , 1989, Developmental medicine and child neurology.

[60]  N. Fejerman,et al.  Ketogenic diet in patients with myoclonic-astatic epilepsy. , 2006, Epileptic disorders : international epilepsy journal with videotape.

[61]  K. Bough,et al.  Higher ketogenic diet ratios confer protection from seizures without neurotoxicity , 1999, Epilepsy Research.

[62]  S. Livingston The ketogenic diet in the treatment of epilepsy in children. , 1951, Postgraduate medicine.

[63]  Jong M. Rho,et al.  The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders , 2012, Front. Pharmacol..

[64]  J. Buchhalter,et al.  Ketogenic diet: outpatient initiation, without fluid, or caloric restrictions. , 2004, Pediatric neurology.

[65]  Michael A. Rogawski,et al.  Neuroprotective and disease-modifying effects of the ketogenic diet , 2006, Behavioural Pharmacology.

[66]  R. Brand,et al.  Elevated insulin receptor content in human breast cancer. , 1990, The Journal of clinical investigation.

[67]  E. Kossoff,et al.  Long-term use of the ketogenic diet in the treatment of epilepsy. , 2006, Developmental medicine and child neurology.

[68]  Dr. M. Lucà-Moretti A Comparative , Double-blind , Triple Crossover Net Nitrogen Utilization Study Confirms the Discovery of the Master Amino Acid Pattern , 2002 .

[69]  G. Guelpa La lutte contre l'epiepsie par la desintoxication et par la reeducation alimentaire , 1911 .

[70]  E. Kossoff,et al.  Infantile spasms treated with the ketogenic diet: Prospective single‐center experience in 104 consecutive infants , 2010, Epilepsia.

[71]  D. Mostofsky,et al.  A randomized trial of polyunsaturated fatty acids for refractory epilepsy , 2008, Epilepsy & Behavior.

[72]  C. Chi,et al.  Clinical experience of ketogenic diet on children with refractory epilepsy. , 1999, Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi.

[73]  F. Vigevano,et al.  Ketogenic diet in early myoclonic encephalopathy due to non ketotic hyperglycinemia. , 2012, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[74]  Victoria H. Goode,et al.  Do Patients With Absence Epilepsy Respond to Ketogenic Diets? , 2011, Journal of child neurology.

[75]  J. Lyon,et al.  Efficacy of the Ketogenic Diet as a Treatment Option for Epilepsy: Meta-analysis , 2006, Journal of child neurology.

[76]  L. Wilkins Epilepsy in childhood: II. The incidence of remissions* , 1937 .

[77]  K. Satyamoorthy,et al.  High glucose modulates IL‐6 mediated immune homeostasis through impeding neutrophil extracellular trap formation , 2013, FEBS letters.

[78]  P. Cooper,et al.  Ketogenic diet for epilepsy. , 2003, The Cochrane database of systematic reviews.

[79]  D. D. Fraser,et al.  Elevated polyunsaturated fatty acids in blood serum obtained from children on the ketogenic diet , 2003, Neurology.

[80]  J. Månsson,et al.  CSF levels of dopamine and serotonin, but not norepinephrine, metabolites are influenced by the ketogenic diet in children with epilepsy , 2012, Epilepsy Research.

[81]  S. Auvin Fatty acid oxidation and epilepsy , 2012, Epilepsy Research.

[82]  A. Perzynski,et al.  Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro , 2011, Neurotoxicity Research.

[83]  E. Kossoff,et al.  A Prospective Study of the Modified Atkins Diet for Intractable Epilepsy in Adults , 2008, Epilepsia.

[84]  J. Ferrendelli,et al.  CHRONIC KETOSIS AND CEREBRAL METABOLISM , 1977, Pediatric Research.

[85]  E. Kossoff,et al.  Worldwide Use of the Ketogenic Diet , 2005, Epilepsia.

[86]  J. Rho,et al.  Acetoacetate, Acetone, and Dibenzylamine (a Contaminant in l‐(+)‐β‐Hydroxybutyrate) Exhibit Direct Anticonvulsant Actions in Vivo , 2002, Epilepsia.

[87]  R. Veech The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. , 2004, Prostaglandins, leukotrienes, and essential fatty acids.

[88]  Emily Spellman,et al.  An overview of the ketogenic diet for pediatric epilepsy. , 2008, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[89]  G. Solomon,et al.  Ketogenic diet in pediatric epilepsy patients with gastrostomy feeding. , 2005, Pediatric neurology.

[90]  E. Vining,et al.  Efficacy of the Ketogenic Diet for Intractable Seizure Disorders: Review of 58 Cases , 1992, Epilepsia.

[91]  H. Oguni,et al.  A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome , 2011, Developmental medicine and child neurology.

[92]  E. Kossoff,et al.  Use of the modified Atkins diet for adolescents with chronic daily headache , 2010, Cephalalgia : an international journal of headache.

[93]  P. Huttenlocher,et al.  Medium‐chain triglycerides as a therapy for intractable childhood epilepsy , 1971, Neurology.

[94]  S. Goodman,et al.  A blinded, crossover study of the efficacy of the ketogenic diet , 2009, Epilepsia.

[95]  M. G. Peterman THE KETOGENIC DIET IN THE TREATMENT OF EPILEPSY: A PRELIMINARY REPORT , 1924 .

[96]  B. Zemel,et al.  Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. , 2008, The American journal of clinical nutrition.

[97]  G. Freund,et al.  Standardized ketosis in man following medium chain triglyceride ingestion. , 1966, Metabolism: clinical and experimental.

[98]  A. Mosek,et al.  Ketogenic diet treatment in adults with refractory epilepsy: A prospective pilot study , 2009, Seizure.