Ketogenic Diet and Metabolic Therapies

Expanded Roles in Health and Disease

Edited by Susan A Masino

Clinical approach to ketogenic diet and alternative medicine in epilepsy;
Illustrated with figures, tables, and boxes;
Brings together the expertise of section editors Detlev Boison, PhD, Dominic P. D'Agostino, PhD, Eric H. Kossoff, MD, Jong M. Rho, MD.

Ketogenic Diet and Metabolic Therapies

Expanded Roles in Health and Disease

Edited by Susan A Masino

Description

Ketogenic diets have been used to successfully treat epilepsy and stop seizures for nearly a century. When more traditional therapies, such as pharmacology, reach their limitations for treatment, the metabolic approach surpasses, targeting the overall physiology and homeostatic functions of the patient.

Ketogenic Diet and Metabolic Therapies is the first comprehensive scientific resource on the ketogenic diet, covering the latest research including the biomedical mechanisms, established and emerging applications, metabolic alternatives, and implications for health and disease. Experts in clinical and basic research share their research into mechanisms spanning from ion channels to epigenetics, their insights based on decades of experience with the ketogenic diet in epilepsy, and their evidence for emerging applications ranging from autism to Alzheimer's disease to brain cancer. Research in metabolic therapies has spread into laboratories and clinics of every discipline, and is yielding to entirely new classes of drugs and treatment regimens.

The book's editor, Susan A. Masino, brings her unique expertise in clinical and research neurology to the overall scope of this work. To further enhance the scope and quality of this one of a kind book, section editors Eric Kossoff, Jong Rho, Detlev Boison, and Dominic P. D'Agostino lend their oversight on their respective sections.

Ketogenic Diet and Metabolic Therapies

Expanded Roles in Health and Disease

Edited by Susan A Masino

Table of Contents
Preface
Contributors List

Section I Ketogenic Diet for Epilepsy in the Clinic
Eric Kossoff, MD, Section Editor

Chapter 1 Overview- Ketogenic Diets and Pediatric Epilepsy: An Update
Eric Kossoff, MD
Chapter 2 'Alternative' Ketogenic Diets
Elizabeth Neal, RD, MSc, PhD
Chapter 3 Dietary Therapy in Adults: History, Demand, and Results
Emily L. Johnson, MD and Mackenzie C. Cervenka, MD
Chapter 4 How Do You Implement the Diet?
Christina Bergqvist, MD
Chapter 5 Glut1 Deficiency and the KD
Joerg Klepper, MD, PhD
Chapter 6 Ketogenic Diet in Established Epilepsy Indications
Ann Bergin, MD, MB, ScM, MRCP
Chapter 7 Ketogenic Diet for Other Epilepsies
David T. Hsieh, MD and Elizabeth A. Thiele, MD, PhD
Chapter 8 The Ketogenic Diet and Related Therapies in "Novel" Situations: Idiopathic Generalized Epilepsy Syndromes
Sudha Kilaru Kessler MD, MSCE
Chapter 9 Ketogenic Diet in Status Epilepticus
Rima Nabbout, MD, PhD
Chapter 10 Preventing Side Effects and Diet Discontinuation
Cherie L. Herren, MD and Rana R. Said, MD

Section II Ketogenic Diet - Emerging Clinical Applications and Future Potential
Jong M. Rho, MD, Section Editor

Chapter 11 Overview: Expanded Uses of Ketogenic Therapies
Jong M. Rho, MD
Chapter 12 Metabolism-Based Treatments to Counter Cancer: Scientific Rationale
Thomas N. Seyfried, PhD and Laura Shelton, PhD
Chapter 13 Ketogenic Diet as Adjunctive Therapy for Malignant Brain Cancer
Eric C. Woolf, PhD and Adrienne C. Scheck, PhD
Chapter 14 Metabolic Therapy for Autism Spectrum Disorder and Co-Morbidities
Ning Cheng, PhD, Susan A. Masino, PhD, and Jong M. Rho, MD
Chapter 15 Glucose and Ketone Metabolism in the Aging Brain: Implications for Therapeutic Strategies to Delay the Progression of Alzheimer's Disease
Stephen C. Cunnane, PhD, Alexandre Courchesne-Loyer, MSc, Valerie St-Pierre, BSc, Camille Vandenberghe, PhD, Etienne Croteau, PhD, and Christian-Alexandre Castellano, PhD
Chapter 16 Ketogenic Diet and Ketones for the Treatment of Traumatic Brain and Spinal Cord Injury
Femke Streijger, PhD, Ward T. Plunet, PhD, and Wolfram Tetzlaff, MD, Dr.Med, PhD
Chapter 17 Anti-Inflammatory Effects of a Ketogenic Diet: Implications for New Indications
Nina Dupuis, PhD and Stéphane Auvin, MD, PhD
Chapter 18 Dietary Therapy for Neurological Disorders: Focus on Amyotrophic Lateral Sclerosis, Parkinson's Disease, Mood Disorders, and Migraine
Carl E. Stafstrom, MD, PhD

Section III Ketogenic Diet in the Laboratory
Detlev Boison, PhD Section Editor

Chapter 19 Overview of Ketogenic Diet in the Laboratory: Progress on Models and Mechanisms
Detlev Boison PhD
Chapter 20 Ketogenic Diet and PPARg
Timothy A. Simeone, PhD
Chapter 21 Ketogenic Diet in a Hippocampal Slice: Models and Mechanisms
Masahito Kawamura, Jr, PhD
Chapter 22 Metabolic Therapy and Pain
David N. Ruskin, PhD
Chapter 23 Ketogenic Diet, Adenosine, Epigenetics, and Antiepileptogenesis
Theresa A. Lusardi, PhD and Detlev Boison, PhD
Chapter 24 Ketogenic Diet, Aging, and Neurodegeneration
Kui Xu, MD, PhD, Joseph C. LaManna, PhD and Michelle A. Puchowicz, PhD
Chapter 25 Endocrine and Reproductive Effects of Ketogenic Diets
Jacob P. Harney, PhD, Kathryn Gudsnuk, MS, Ami Patel, MD Anantha R. Vellipuram, MD, Sathyajit Bandaru, MS and David Butler, PhD
Chapter 26 Alzheimer's Disease: Causes and Treatment
Richard L. Veech, MD, PhD, DPhil and M. Todd King
Chapter 27 Mitigation of Damage from Reactive Oxygen Species and Ionizing Radiation by Ketone Body Esters
William Curtis, Martin Kemper, PhD, Alexandra Miller, PhD, Robert Pawlosky, PhD, M. Todd King, and Richard L. Veech, MD, PhD, DPhil
Chapter 28 Metabolic Seizure Resistance via BAD and KATP Channels
Juan Ramón Martínez-François, PhD, Nika Danial, PhD, and Gary Yellen, PhD
Chapter 29 Lactate Dehydrogenase: A Novel Metabolic Target
Nagisa Sada, PhD and Tsuyoshi Inoue, PhD
Chapter 30 Effects of the Ketogenic Diet on the Blood-Brain Barrier
Manoj Banjara, PhD and Damir Janigro, PhD

Section IV Ketone-Based Metabolism: General Health and Metabolic Alternatives
Dominic P. D'Agostino, PhD Section Editor

Chapter 31 Overview of Ketone-Based Metabolism: General Health and Metabolic Alternatives
Dominic P. D'Agostino, PhD
Chapter 32 Ketone Supplementation for Health and Disease
Angela M. Poff, PhD, Shannon L. Kesl, PhD, and Dominic P. D'Agostino, PhD
Chapter 33 Identifying the Molecular Mechanism of the MCT (Ketogenic) Diet
Matthew C. Walker, PhD and Robin S.B. Williams, PhD
Chapter 34 Triheptanoin in Epilepsy and Beyond
Karin Borges, PhD
Chapter 35 Amino Acids in the Treatment of Neurological Disorders
Adam L. Hartman, MD
Chapter 36 2-Deoxyglucose: Metabolic Control of Seizures through Inhibition of Glycolysis
Carl E. Stafstrom, MD, PhD and Thomas P. Sutula, MD, PhD
Chapter 37 Ketogenic Diets as Highly Effective Treatments for Diabetes Mellitus and Obesity
Eric C. Westman, MD, MHS, Emily Maguire, MSc, and William S. Yancy Jr., MD, MHS
Chapter 38 Keto-Adaptation in Health and Fitness
Parker Hyde, CSCS, CISSN, Vincent J. Miller, PhD, and Jeff S. Volek, PhD, RD
Chapter 39 Advancing the Awareness and Application of Ketogenic Therapies Globally: The Charlie Foundation and Matthew's Friends
Beth Zupec-Kania, RD, CD, Jim Abrahams, Emma Williams, MBE, Susan A. Masino, PhD

Ketogenic Diet and Metabolic Therapies

Expanded Roles in Health and Disease

Edited by Susan A Masino

Author Information

Susan A. Masino is the Vernon Roosa Professor of Applied Science at Trinity College. Her research is focused on adenosine, an endogenous molecule that promotes homeostasis and links between metabolism and brain activity. In 2008 she proposed that adenosine is a key mechanism underlying ketogenic diet therapy; based on this, her research spans multiple conditions. Dr. Masino is also dedicated to educational, environmental and public policy issues affecting brain health.

Contributors:

Jim Abrahams
Charlie Foundation for Ketogenic Therapies

Stéphane Auvin MD, PhD
AP-HP
Hôpital Robert Debré
Service de Neurologie Pédiatrique
Paris, France
Sathyajit Bandaru, MS
Neuroscience Graduate Program
University of Hartford
West Hartford, CT

Manoj Banjara, PhD
Departments of Biomedical Engineering
Cerebrovascular Research
Cleveland Clinic Foundation
Cleveland, OH

Ann Bergin, MD, MB, ScM, MRCP
Assistant Professor of Neurology
Harvard Medical School
Children's Hospital of Boston
Boston, MA

Christina Bergqvist, MD
Medical Director, Dietary Treatment Program
Pediatric Neurologist
Children's Hospital of Philadelphia
Philadelphia, PA

Detlev Boison, PhD
Robert Stone Dow Chair and Director of Neurobiology
Director of Basic and Translational Research
Legacy Research Institute
Portland, OR

Karin Borges, PhD
Department of Pharmacology
School of Biomedical Sciences
The University of Queensland
St. Lucia, Australia

David Butler, PhD
Neuroscience Graduate Program
University of Hartford
West Hartford, CT

Christian-Alexandre Castellano, PhD
Research Center on Aging
Departments of Medicine and Pharmacology & Physiology
Université de Sherbrooke
Sherbrooke, Québec, Canada

Mackenzie C. Cervenka, MD
Director, Adult Epilepsy Diet Center
Assistant Professor of Neurology
Johns Hopkins Hospital
Baltimore, MD

Ning Cheng, PhD
Department of Pediatrics
Alberta Children's Hospital Research Institute
Cumming School of Medicine University of Calgary
Calgary, Canada

Alexandre Courchesne-Loyer, MSc
Research Center on Aging
Departments of Medicine and Pharmacology & Physiology
Université de Sherbrooke
Sherbrooke, Québec, Canada

Etienne Croteau, PhD
Research Center on Aging
Departments of Medicine and Pharmacology & Physiology
Université de Sherbrooke
Sherbrooke, Québec, Canada

Stephen C. Cunnane, PhD
Research Center on Aging
Departments of Medicine and Pharmacology & Physiology
Université de Sherbrooke
Sherbrooke, Québec, Canada

William Curtis, PhD
Guest Worker, Lab of Metabolic Control
National Institute of Alcohol Abuse and Alcoholism
Rockville, MD

Dominic P. D'Agostino, PhD
Assistant Professor
Department of Molecular Pharmacology and Physiology
Morsani College of Medicine
University of South Florida
Tampa, FL

Nika Danial, PhD
Department of Cancer Biology
Dana-Farber Cancer Institute
Department of Cell Biology
Harvard Medical School
Boston, MA

Nina Dupuis, PhD
Université Paris Diderot
Sorbonne Paris Cité
INSERM UMR1141
Paris, France

Kathryn Gudsnuk, MS
Neuroscience Graduate Program
University of Hartford
West Hartford, CT

Jacob P. Harney, PhD
School of Mathematics and Sciences
Reinhardt University
Waleska, GA
Neuroscience Graduate Program
University of Hartford
West Hartford, CT

Adam L. Hartman, MD
Associate Professor of Neurology and Pediatrics
Johns Hopkins Medicine
Baltimore, MD

Cherie L. Herren, MD
Medical Director, OU Children's Physicians Ketogenic Diet Program
Department of Neurology
Oklahoma University
Oklahoma City, OK

David T. Hsieh, MD
Division of Child Neurology
Department of Pediatrics
San Antonio Military Medical Center
Ft Sam Houston, TX

Parker Hyde, CSCS, CISSN
Department of Human Sciences
The Ohio State University
Columbus, OH

Tsuyoshi Inoue, PhD
Department of Biophysical Chemistry
Graduate School of Medicine
Dentistry and Pharmaceutical Sciences
Okayama University
Okayama, Japan

Damir Janigro, PhD
Flocel, Inc.
Cleveland, OH

Emily L. Johnson, MD
Department of Neurology
Johns Hopkins Hospital
Baltimore, MD

Masahito Kawamura, Jr., PhD
Department of Pharmacology
Jikei University School of Medicine
Tokyo, Japan

Martin Kemper, PhD
Lab of Metabolic Control
National Institute of Alcohol Abuse and Alcoholism
National Institute of Health
Rockville, MD

Shannon L. Kesl, PhD
Department of Molecular Pharmacology and Physiology
Morsani College of Medicine
University of South Florida
Tampa, FL

Sudha Kilaru Kessler MD, MSCE
Assistant Professor of Neurology and Pediatrics
Children's Hospital of Philadelphia
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

M. Todd King, PhD
Lab of Metabolic Control
National Institute of Alcohol Abuse and Alcoholism
National Institute of Health
Rockville, MD

Joerg Klepper, MD, PhD
Chief Physician
Childrens' Hospital Aschaffenburg
Aschaffenburg, Germany

Eric Kossoff, MD
Professor, Neurology and Pediatrics
Medical Director, Ketogenic Diet Center
Director, Pediatric Neurology Residency Program
Johns Hopkins Hospital
Baltimore, MD

Joseph C. LaManna, PhD
Departments of Physiology and Biophysics
Case Western Reserve University
Cleveland, OH

Theresa A. Lusardi, PhD
Robert Stone Dow Neurobiology Laboratories
Legacy Research Institute
Portland, OR

Emily Maguire, MSc
Edinburgh, Scotland, UK

Juan Ramón Martínez-François, PhD
Department of Neurobiology
Harvard Medical School
Boston, MA

Susan A. Masino, PhD
Vernon Roosa Professor of Applied Science
Professor of Psychology and Neuroscience
Trinity College
Hartford, CT

Alexandra Miller, PhD
Armed Forces Radiobiology Research Institute
Uniformed Services University of the Health Sciences
Bethesda, MD

Vincent J. Miller, PhD
Department of Human Sciences
The Ohio State University
Columbus, OH

Rima Nabbout, MD, PhD
Reference Centre for Rare Epilepsies
Department of Pediatric Neurology
Necker Enfants Malades Hospital
Paris Descartes University
Paris, France

Elizabeth Neal, RD, MSc, PhD
Specialist Ketogenic Dietitian
Matthews Friends Clinics
Lingfield, UK
Honorary Research Associate
Department of Neuroscience
UCL-Institute of Child Health
London, UK

Ami Patel, MD
Neuroscience Graduate Program
University of Hartford
West Hartford, CT

Robert Pawlosky, PhD
Lab of Metabolic Control
National Institute of Alcohol Abuse and Alcoholism
National Institute of Health
Rockville, MD

Ward T. Plunet, PhD
International Collaboration on Repair Discoveries (ICORD)
University of British Columbia
Blusson Spinal Cord Centre
Vancouver, Canada

Angela M. Poff, PhD
Department of Molecular Pharmacology and Physiology
Morsani College of Medicine
University of South Florida
Tampa, FL

Michelle A. Puchowicz, PhD
Departments of Nutrition
Case Western Reserve University
Cleveland, OH

Jong M. Rho, MD
Professor of Pediatrics and Clinical Neurosciences
Dr. Robert Haslam Chair in Pediatric Neurology
Cumming School of Medicine, University of Calgary
Calgary, Canada

David N. Ruskin, PhD
Department of Psychology and Neuroscience Program
Trinity College
Hartford, CT

Nagisa Sada, PhD
Department of Biophysical Chemistry
Graduate School of Medicine
Dentistry and Pharmaceutical Sciences
Okayama University
Okayama, Japan

Rana R. Said, MD
Director, Pediatric Neurology Residency Program
Department of Pediatrics, Neurology, and Neurotherapeutics
UT Southwestern Medical Center
University of Texas Southwestern
Dallas, TX

Adrienne C. Scheck, PhD
Neuro-Oncology Research
Barrow Brain Tumor Research Center
Barrow Neurological Institute® dba St. Joseph's Hospital and Medical Center
Phoenix, AZ
School of Life Sciences
Arizona State University
Tempe, AZ

Thomas N. Seyfried, PhD
Biology Department
Boston College
Boston, MA

Laura Shelton, PhD
Scientific Project Coordinator
Human Metabolome Technologies America
Boston, MA

Timothy A. Simeone, PhD
Creighton University School of Medicine
Department of Pharmacology
Omaha, NE

Valerie St-Pierre, BSc
Research Center on Aging
Departments of Medicine and Pharmacology & Physiology
Université de Sherbrooke
Sherbrooke, Québec, Canada

Carl E. Stafstrom, MD, PhD
Professor of Neurology and Pediatrics
Lederer Chair in Pediatric Epilepsy
Johns Hopkins School of Medicine
Director, Division of Pediatric Neurology
Johns Hopkins Hospital
Baltimore, MD

Femke Streijger, PhD
International Collaboration on Repair Discoveries (ICORD)
University of British Columbia
Blusson Spinal Cord Centre
Vancouver, Canada

Thomas P. Sutula, MD, PhD
Department of Neurology
School of Medicine and Public Health
University of Wisconsin
Madison, WI

Wolfram Tetzlaff, MD, Dr.Med, PhD
Department of Zoology
International Collaboration on Repair Discoveries (ICORD)
University of British Columbia
Blusson Spinal Cord Centre
Vancouver, Canada

Elizabeth A. Thiele, MD, PhD
Pediatric Epilepsy Program
Department of Neurology
Massachusetts General Hospital
Boston, MA

Camille Vandenberghe, PhD
Research Center on Aging
Departments of Medicine and Pharmacology & Physiology
Université de Sherbrooke
Sherbrooke, Québec, Canada

Richard L. Veech, MD, PhD, DPhil
Lab of Metabolic Control
National Institute of Alcohol Abuse and Alcoholism
National Institute of Health
Rockville, MD

Anantha R. Vellipuram, MD
Neuroscience Graduate Program
University of Hartford
West Hartford, CT

Jeff S. Volek, PhD, RD
Department of Human Sciences
The Ohio State University
Columbus, OH

Matthew C. Walker, PhD
Department of Clinical and Experimental Epilepsy
Institute of Neurology
University College London
London, UK

Eric C. Westman, MD MHS
Division of General Internal Medicine
Department of Medicine
Duke University Medical Center
Durham, NC

Emma Williams, MBE
Matthew's Friends
Lingfield, UK

Robin S.B. Williams, PhD
Centre for Biomedical Sciences
School of Biological Sciences
Royal Holloway University of London
Egham, UK

Eric C. Woolf, PhD
Neuro-Oncology Research
Barrow Brain Tumor Research Center
Barrow Neurological Institute® dba St. Joseph's Hospital and Medical Center
Phoenix, AZ
School of Life Sciences
Arizona State University
Tempe, AZ

Kui Xu, MD, PhD
Departments of Physiology and Biophysics
Case Western Reserve University
Cleveland, OH

William S. Yancy Jr., MD MHS
Division of General Internal Medicine
Department of Medicine
Duke University Medical Center
Center for Health Services Research in Primary Care
Durham Veterans Affairs Medical Center
Duke Diet and Fitness Center
Duke University Health System
Durham, NC

Gary Yellen, PhD
Department of Neurobiology
Harvard Medical School
Boston, MA

Beth Zupec-Kania, RD, CD
Ketogenic Therapies LLC