Integrative and Functional Medical Nutrition Therapy: Principles and Practices (Nutrition and Health)

Foreword Preface Contents Contributors Abbreviations I: Global Healthcare Challenge of the Twenty-First Century and the Future of Chronic Disease 1: The History and Evolution of Medicine 1.1 Introduction: The Problem 1.2 Brief History of Medicine 1.3 Changes Needed: Nutrition Education Across All Medical Education Systems, Interprofessional Teams, and New Systems of Care 1.3.1 Nutrition Education Across All Medical Education Systems: The Foundation 1.3.2 Interprofessional Teams: The Way Forward 1.3.3 New Systems of Care: The Way Forward 1.4 Conclusion References 2: Influences of the Nutrition Transition on Chronic Disease 2.1 Nutrition Transition: A Model of Changing Dietary Patterns 2.2 The Changing Face of Food Over Time and Space 2.3 The Globalization of Food 2.3.1 Changing Trajectory of Populations’ Lifestyles 2.3.2 Is the Nutrition Transition Experience Different Between the Developed and Developing World? 2.3.3 A Growing Double Burden of Disease 2.3.4 The Overlap Between Undernutrition and Overnutrition 2.3.5 Metabolic Programming and NCDs 2.4 Pathophysiological Consequences of NT 2.5 Anthropogens and Chronic Inflammation 2.5.1 Behavior Change for Positive Vitality 2.5.2 Initiatives Addressing the Nutrition Transition 2.6 Conclusion References 3: Nutritional and Metabolic Wellness 3.1 Introduction to Human Wellness 3.2 What Is Wellness? 3.3 Biomarkers of Wellness 3.4 Biochemical Individuality/Health Standards Through the Lifespan 3.4.1 In Utero 3.4.2 Infant (From Birth to 6–24 Months) 3.4.2.1 Toddler (12–36 Months) 3.4.2.2 Childhood (3–12 Years) 3.4.2.3 Teenage (13–19 Years) (. Fig. 3.3) 3.4.3 Young Adult (20–34 Years) 3.4.3.1 Middle-Age Adult (35–54 Years) 3.4.3.2 Seniors (54–74 Years) 3.4.3.3 Old-Old Seniors [15] (75–99 Year) 3.4.3.4 Centenarians/Supercentenarians (100+ Years) 3.5 Nutritional Wellness 3.6 Community of Wellness 3.7 Summary References 4: Nutritional Ecology and Human Health 4.1 Introduction 4.2 “Nutrition” and “Ecology” 4.2.1 Human Nutrition 4.2.2 Ecology and Anthropology 4.2.3 Nutritional Ecology and Human Health 4.3 The Importance of Appetite 4.3.1 Multiple Appetites 4.3.2 Appetites Interact 4.4 From Concepts to Models: Introduction to the Geometric Framework for Nutrition 4.4.1 Model Selection 4.4.2 Selecting an Intake Target: Nutritionally Balanced and Complementary Foods 4.4.3 Negotiating a Compromise: When the Intake Target Cannot Be Reached 4.5 The Geometry of Nutrition in Humans: Protein Leverage 4.5.1 Do Humans Select an Intake Target? 4.5.2 What Is the P:NPE Rule of Compromise in Humans? 4.6 Beyond Appetites 4.6.1 The Geometry of Mixtures: Three Components in Two Dimensions 4.6.2 A Hierarchy of Mixtures 4.6.3 Dietary Macronutrient Balance 4.6.4 Relationships Between Macronutrient Balance and Energy Intake 4.6.5 Energy Balance 4.6.6 Beyond Energy: Protein Intake 4.6.7 Interactions of Appetite with the Food Environment 4.7 Conclusions References 5: The Radial: Integrative and Functional MNT 5.1 Background 5.2 Overview 5.3 Core of the Radial: Personalized Nutrition Care 5.4 Mind, Body, Spirit, Community, and Earth 5.5 DNA Strands and Microbes 5.6 Food, Environment, and Lifestyle 5.7 Nutrition Physical Exam and Signs and Symptoms 5.8 Biomarkers 5.9 Laboratory Testing 5.10 Metabolic Pathways and Networks 5.11 Systems 5.12 Gastrointestinal System 5.13 Immune System: Defense and Repair 5.14 Cardiovascular System: Cardiometabolic Comorbidities 5.15 Endocrine System: Hormonal Health Influences 5.16 Respiratory System: Lung and Sinus Illness 5.17 Potential Triggers 5.18 Stress 5.19 Toxins and Toxicants 5.20 Pathogens (See 7 Chap. 21) 5.21 Food Allergies and Intolerances 5.22 Conclusion References 6: The Power of Listening and the Patient’s Voice: “Please Hear Me” 6.1 Introduction: Solutions to Help Build Trust with Patients 6.2 The Need for Improved Practitioner-Patient Communication: Practitioner Know Thyself! 6.3 Behavioral Competency Soft Skills Improve the Practitioner-Patient Experience 6.4 Leading the Interdisciplinary Medical Team 6.5 The Powerful Art of Listening: Learning to Adapt Practitioner Behaviors to Meet the Needs of the Patient 6.6 Telling the Patient’s Story 6.7 Naturally Occurring Patient Tribes: The Power of Communities 6.8 Conclusion References II: Metabolic Characteristics and Mechanisms of Chronic Disease 7: Metabolic Correction Therapy: A Biochemical–Physiological Mechanistic Explanation of Functional Medicine 7.1 Introducing Metabolic Correction 7.2 Implications of Subclinical Nutrient Deficiencies (Nutritional Insufficiencies) 7.3 Nutrient Requirements of Disease States 7.4 Vitamins and Minerals and Hidden Hunger 7.5 Why Metabolic Correction? 7.5.1 Inferior Nutritional Value of Food and Low Availability of Nutrient-Dense Foods 7.5.2 Medication-Induced Nutrient Depletion, Adverse Side Effects of Medication, and Iatrogenic Deaths 7.5.3 To Compensate for the Increased Demand of Nutrients due to the Disease State 7.5.4 Biochemical Mechanism of Metabolic Correction: Molecular Concentrations and Rate of Reactions 7.6 B-Complex and Metabolism Briefing 7.7 B-Complex and Metabolic Correction 7.8 Ten Principles of the Concept of Metabolic Correction in Disease Therapy 7.9 Beyond Metabolic Correction: Improving the Healthcare Management Model 7.10 Conclusion References 8: The Nutrition Assessment of Metabolic and Nutritional Balance 8.1 Introduction 8.2 The Microbiome 8.3 Fiber 8.4 Iodine 8.5 B Vitamins 8.5.1 Thiamine (Vitamin B1) 8.5.2 Riboflavin (Vitamin B2) 8.5.3 Niacin (Vitamin B3) 8.5.4 Pantothenic Acid (B5) 8.5.5 Vitamin B6 8.5.6 Folate (Vitamin B9) 8.5.7 Vitamin B12 8.6 Fat-Soluble Vitamins 8.6.1 Vitamin D and Vitamin K 8.6.2 Vitamin A and Vitamin D 8.6.3 Tocopherols and Tocotrienols 8.7 Minerals 8.7.1 Calcium and Magnesium 8.7.2 Sodium-to-Potassium Ratio and Hypertension 8.7.3 Zinc and Copper 8.7.4 Assessing Zinc Status 8.7.5 Copper-to-Zinc Ratio in Cancer 8.8 Fatty Acids and Phospholipids 8.8.1 Fatty Acid and Phospholipid Balance 8.8.2 Gamma-Linolenic Acid 8.8.3 Conjugated Linoleic Acid 8.8.4 Phospholipids 8.8.5 Short-Chain Fatty Acids 8.8.6 Increasing Beneficial Fatty Acids 8.8.7 Assessing Erythrocyte Fatty Acid Profiles 8.8.8 Hydrogenated Oils 8.8.9 Overall Diet and Macronutrient Distribution 8.9 Summary References 9: IFMNT NIBLETS Nutrition Assessment Differential 9.1 Introduction 9.2 N: Nutrient Deficiencies/Insufficiencies 9.3 I: Inflammation/Immunity 9.4 B: Biochemical Individuality and Genetic/Epigenetic Influences on Chronic Disease 9.5 L: Lifestyle Factors 9.6 E: Energy 9.7 T: Toxic Load 9.8 S: Stress and Sleep 9.9 Sleep 9.10 Conclusion References Other Suggestions: These Might Lead to Some Other Resources 10: Nutritional Role of Fatty Acids 10.1 Introduction 10.2 Saturated Fatty Acids 10.2.1 Short-Chain Saturated Fatty Acids (SCFA): C1–C6 [6, 7] 10.2.2 Medium Chain Triglycerides (MCT): C6–C12 with an Aliphatic Tail [12] 10.2.3 Long-Chain C13–C21 and Very-Long-Chain Fatty Acids C22 or More 10.3 Monounsaturated Fatty Acids 10.4 Polyunsaturated Fatty Acids 10.4.1 Biosynthesis 10.4.2 Functions 10.4.2.1 Skin 10.4.2.2 Immunity and Infection 10.4.2.3 Gene Expression 10.4.2.4 Cholesterol 10.4.2.5 Eicosanoids 10.4.2.6 Specific Role of W3 Fatty Acids 10.4.3 Deficiency 10.4.4 Requirements 10.4.5 W3 Fatty Acids and Health 10.4.6 Food Sources 10.5 Trans-Fatty Acids 10.6 Conjugated Fatty Acids 10.7 Conclusions References Resources 11: Lipidomics: Clinical Application 11.1 Introduction 11.2 History of Dietary Fat 11.2.1 Human History 11.2.2 The Nutrition Transition of Oils and Fats in the Early 20th Century 11.3 The Lipidome and Clinical Application 11.3.1 Clinical Imbalances 11.4 Nutritional Influences on Body Composition and Function 11.4.1 Structure and Functions of the Cell Membrane 11.4.1.1 Cellular Hydration 11.4.1.2 The Membrane Barriers: Organelle, Cell, Tissue, and Organs 11.5 The Eicosanoid Cascade: Acute and Chronic Tissue Inflammation Management 11.5.1 Fatty Acid Elongation (See . Fig. 11.4) 11.5.1.1 Elongase 11.5.2 Fatty Acid Desaturation (See . Fig. 11.4) 11.5.2.1 Delta-6-desaturase (D6D) 11.5.2.2 Delta 5-desaturase (D5D) 11.6 Metabolic Stressors 11.7 Tools of the Trade for Lipid Therapy 11.7.1 Laboratory Principles 11.7.2 Structural Integrity 11.7.2.1 Assessment Checklist for Structural Integrity 11.7.3 Defense and Repair 11.7.3.1 Assessment Checklist for Defense and Repair Blood Markers Vitamin D 25-Hydroxy Vitamin A (Retinol) [61] Gut microbiome [55] Inflammatory Load Assessment 11.8 Key Nutrient Cofactors and Foods Influencing the Eicosanoid Metabolism 11.8.1 Lipids 11.8.1.1 Phospholipids (PL) 11.8.1.2 Fatty Acids: 11.8.2 Sterols 11.8.3 Minerals 11.8.3.1 Zinc 11.8.3.2 Magnesium 11.8.4 Methyl Nutrients 11.8.4.1 B12 and Folate Metabolism 11.8.4.2 Niacin, Vitamin A, Vitamin C, and Zinc 11.8.4.3 Vitamin D, A [72] 11.8.5 Phytonutrients: Protective Support for Lipid Structures 11.9 Key Lifestyle Factors Influencing the Risk of Lipid Damage 11.9.1 Sleep [74] (See 7 Chap. 35) 11.9.2 Stress (See 7 Chap. 47) 11.9.3 Movement (See 7 Chaps. 36 and 54) 11.10 Chronic Disease and Impaired Lipid Metabolism (See Tables . 11.3 and 11.4) 11.10.1 Heart Disease/Cardiovascular Association with the Lipidome 11.10.2 Oncology 11.10.3 Neurological 11.10.3.1 Mitochondrial Dysfunction 11.10.3.2 Alzheimer’s Disease 11.10.3.3 Developmental Plasticity 11.10.4 Respiratory 11.10.5 Autoimmune 11.11 Case Reviews 11.12 Conclusion References Resources 12: Structure: From Organelle and Cell Membrane to Tissue 12.1 Introduction 12.2 Part I: Membrane Structure 12.2.1 Introduction 12.2.2 Biological Structure 12.2.2.1 Phosphatidylcholine 12.2.2.2 Phosphatidylethanolamine 12.2.2.3 Phosphatidylserine 12.2.2.4 Cholesterol 12.2.2.5 Proteins 12.2.2.6 Carbohydrates 12.3 Part II: Dietary and Lifestyle Influences 12.3.1 Introduction 12.3.2 Pathophysiology 12.3.2.1 Reactive Oxygen Species 12.3.2.2 Mitochondria 12.3.3 Evaluation/Assessment 12.3.4 Prevention/Treatment 12.3.4.1 Antioxidants 12.3.4.2 CoQ10 12.3.4.3 Lipoic Acid 12.3.4.4 Phosphotidylethanolamine 12.3.4.5 L-carnitine 12.3.4.6 Mitochondrial Biogenesis 12.4 Part III: Organ Structure and Function 12.4.1 Introduction 12.4.2 Eye 12.4.2.1 Biological Structure 12.4.2.2 Pathophysiology Dry Form Wet Form Reactive Oxygen Species 12.4.2.3 Evaluation/Assessment 12.4.2.4 Treatment/Prevention 12.4.3 Skin 12.4.3.1 Biological Structure 12.4.3.2 Insults to Skin Barrier Integrity 12.4.3.3 Evaluation/Assessment 12.4.3.4 Initial Biomarkers for Assessment of Skin Health Status 12.4.3.5 Treatment 12.4.4 Brain 12.4.4.1 Biological Structure 12.4.4.2 Pathophysiology 12.4.4.3 Evaluation/Assessment 12.4.4.4 Treatment 12.4.5 Barriers 12.4.5.1 Biological Structure 12.4.5.2 Pathophysiology 12.4.5.3 Evaluation/Assessment 12.4.5.4 Prevention/Treatment 12.5 Part V: Musculoskeletal Structure and Influences 12.5.1 Introduction 12.5.1.1 Sarcopenia 12.5.1.2 Osteoarthritis 12.5.2 Evaluation/Assessment 12.5.3 Prevention/Treatment 12.5.3.1 Omega-3 Fatty Acids 12.5.3.2 Vitamin C 12.5.3.3 Strontium 12.5.3.4 Glucosamine Sulfate 12.5.3.5 Osteoporosis and Osteopenia 12.5.4 Pathophysiology 12.5.5 Evaluation/Assessment 12.5.6 Treatment/Prevention 12.6 Conclusion References 13: Protective Mechanisms and Susceptibility to Xenobiotic Exposure and Load 13.1 Introduction 13.2 Biotransformation 13.3 Pathophysiology 13.3.1 Mechanisms 13.3.2 Chronic Diseases Related to Xenobiotic Exposure 13.4 Clinical Considerations 13.4.1 Assessment of Xenobiotic Exposure, Historically and Presently 13.4.2 Assessment of Genetic Susceptibility 13.4.3 Assessment of Diet and Lifestyle 13.5 Clinical Strategies 13.5.1 Reducing or Avoiding Exposure to Xenobiotics 13.5.2 Supporting the Body’s Detoxification Capacity 13.5.2.1 Improve Elimination of Toxins 13.5.2.2 Foods that Support Biotransformation 13.5.2.3 Dietary/Food Supplements that May Support Enhanced Biotransformation 13.6 Conclusions References 14: Detoxification and Biotransformation 14.1 Introduction 14.2 Primary Approach – Avoidance 14.3 Secondary Approach – Caring for Organs of Detoxification 14.3.1 Liver Considerations 14.3.2 Kidney Considerations 14.4 Tertiary Approach – Detoxification Support 14.4.1 Start with Food 14.4.2 Supplementation Use References 15: Drug–Nutrient Interactions 15.1 Effect of Food and Nutrients on Drug Kinetics and Efficacy 15.2 Effect of Drugs on Food and Nutrient Kinetics and Nutrition Status 15.3 Role of the Nutrition Professional References 16: The Enterohepatic Circulation 16.1 Enterohepatic Circulation (EHC) - Definition 16.2 Introduction 16.3 Overview 16.4 Details of Microanatomy, Physiology, and Biochemistry 16.4.1 Portal Vein 16.4.2 Portal Tracts 16.4.3 Liver/Hepatic Lobule 16.4.4 Hepatic Sinusoids and Hepatocytes 16.4.5 Interaction of Sinusoidal Blood with the Hepatocyte Basolateral Cell Membranes 16.4.6 Metabolic Zonation/Organization of Hepatocytes by their Function 16.4.7 Functions of the Liver 16.4.8 Xenobiotics 16.4.9 Where Are Xenobiotics Found? 16.4.10 A Few Examples of Problems Caused by Xenobiotics 16.4.11 Biotransformation 16.4.12 Cytochrome P450 Genes and Enzymes 16.4.13 Single-Nucleotide Polymorphisms 16.4.14 Bile and the Biliary System 16.4.15 Small Intestine 16.4.16 Microbiome/Metabolome 16.4.17 Enteric Nervous System 16.4.18 Gut-Associated Lymphoid Tissue 16.4.19 Enteric Endocrine Cells 16.4.20 Terminal Ileum 16.4.21 Large Intestine 16.5 Conclusion References 17: A Nutritional Genomics Approach to Epigenetic Influences on Chronic Disease 17.1 What Is Epigenetics? 17.1.1 The Epigenetics of Cardiometabolic Disease 17.1.2 The Epigenetics of Psychiatric and Neurodegenerative Diseases 17.2 The Epigenetics of Irritable Bowel Disease and Dysbiosis 17.2.1 The Epigenetics of Nutrient-Associated Diseases 17.3 Epigenetics of Cancer 17.3.1 Epigenetics of Mitochondrial Insufficiency 17.4 Introduction to Pharmacogenetics 17.4.1 Final Thoughts References 18: Nutritional Influences on Methylation 18.1 What Is Nutritional Genomics? 18.2 How Are Diseases Inherited? 18.3 Epigenetics and SNPs 18.4 One-Carbon Metabolism Basics 18.5 Introduction to Methylation 18.6 Homocysteine Metabolism 18.7 Connecting Neurotransmitters to Methylation 18.7.1 Tetrahydrobiopterin (BH4) 18.7.2 Catecholamines 18.7.3 Serotonin 18.7.4 Iron and Neurotransmitters 18.8 Final Thoughts References 19: The Immune System: Our Body’s Homeland Security Against Disease 19.1 Introduction 19.2 The Mucosal Immune System: The First Line of Defense 19.2.1 Intestinal Permeability to Large Macromolecules 19.2.2 Diagnostic Features of the Mucosal Immune System 19.3 An Innate Immune System 19.3.1 Diagnostic Features of the Innate Immune System 19.4 Acquired or Adaptive Immunity 19.4.1 Primary and Secondary Immune Response 19.4.2 IgE and Allergic Reactions 19.4.3 Diagnostic Features of the Adaptive Immune System 19.5 The Three Major Mechanisms of Protection against Autoimmunity 19.5.1 Oral Tolerance 19.5.1.1 Exclusion of Various Antigens by Secretory IgA and IgM Antibodies to Modulate or Inhibit Colonization of Bacteria and Yeast and Dampen Penetration by Dangerous Soluble Luminal Agents 19.5.1.2 Factors Involved in the Induction or Disturbance of Oral Tolerance 19.5.1.3 Breach in Oral Tolerance and Its Association with Food Immune Reactivities 19.5.2 Central Tolerance 19.5.3 Peripheral Tolerance 19.6 Dietary Intervention 19.7 Conclusion References 20: Nutritional Influences on Immunity and Infection 20.1 Introduction 20.2 Impact of Infection on Health and Disease 20.3 Key Metabolic Mechanisms for Defense and Repair 20.4 Insults to Our Defense and Repair Systems 20.4.1 Increased Toxin Load 20.5 Antimicrobial Resistance (AMR) 20.6 Gastrointestinal Dysbiosis: From Mouth to Anus 20.7 Stressors 20.8 Malnutrition, Inflammation, and the Infectious Processes 20.9 Diagnosis of Nutrition Status and Infection-Related Diseases 20.10 Differential for Nutritional Infection Risk 20.10.1 Look for Evidence of Infections 20.11 Chronic Diseases, Nutrition, Microbiome, and Infection 20.11.1 Laboratory 20.11.2 Assessment Laboratory and Clinical Tools 20.11.3 Key Nutrients Influencing the Risk of Infectious Disease (. Fig. 20.8) 20.11.3.1 Vitamin D, A, E [69] 20.12 Homocysteine Catabolism (. Fig. 20.9) 20.12.1 Folate Metabolism 20.12.2 Methionine Metabolism 20.12.2.1 Phytonutrients 20.12.2.2 Minerals: [76] 20.13 Key Lifestyle Factors Influencing the Risk of Infectious Disease 20.13.1 Sleep (see 7 Chap. 45) 20.13.2 Stress (see 7 Chap. 47) 20.14 Movement (see 7 Chap. 36) 20.14.1 Examples of Chronic Disease Connections with Infectious Disease 20.14.1.1 Heart Disease/Cardiovascular Association with Infectious Processes 20.14.1.2 Oncology 20.14.1.3 Neurological 20.14.1.4 Respiratory (see 7 Chap. 52) 20.14.1.5 Autoimmune (see 7 Chap. 49) 20.14.2 Vaccination 20.15 Conclusion References Resources 21: Body Composition 21.1 Introduction 21.2 Body Composition Methods 21.3 Field Methods 21.4 Height, Weight, and Body Mass Index 21.5 Girth Measurements 21.5.1 Waist Circumference (WC) 21.5.2 Waist-to-Hip Ratio 21.5.3 Waist-to-Height Ratio (WHR) 21.5.4 Upper Arm Circumference 21.5.5 Using Circumference Measurements to Calculate Body Fat Percentage 21.5.6 Skinfold Measurement 21.5.7 Bioelectrical Impedance Analysis and Bioimpedance Spectroscopy 21.6 Bioelectrical Impedance Analysis: Non-body Composition Parameters for Nutritional Assessment 21.7 Intracellular Water (ICW)/Extracellular Water (ECW) Hydration 21.8 Basal Metabolic Rate Analyzers 21.8.1 Electrical Impedance Myography 21.8.2 Consumer Apps for Smartphones 21.9 Laboratory Methods 21.9.1 Hydrostatic Weighing 21.9.2 Air Displacement Plethysmography 21.9.3 Dual-energy X-ray Absorptiometry (DXA/DEXA) 21.9.4 Medical Imaging – Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) 21.9.5 Ultrasound 21.10 Classification Based on Percent Fat 21.11 Conclusion References 22: The Therapeutic Ketogenic Diet: Harnessing Glucose, Insulin, and Ketone Metabolism 22.1 The Current Paradigm 22.2 Factors in Choosing an “Ideal” Diet 22.2.1 Genetic and Epigenetic Influences 22.2.2 The Inflammatory Response 22.2.3 Insulin Resistance Adds Fuel to the Flames 22.2.4 Anticipated Weight Loss 22.2.5 Mitochondrial Health [13] 22.3 Glucose and Insulin 22.4 Ketogenesis 22.4.1 Step One [20] 22.4.2 Step Two [20] 22.4.2.1 Simple Schematic of a Triglyceride Ester (. Fig. 22.2) 22.4.3 Step Three 22.4.4 Step Four 22.4.5 Ketogenic Metabolic Pathway 22.5 History of Use in Epilepsy 22.6 Diseases of Insulin Resistance 22.6.1 Obesity 22.6.2 Diabetes 22.6.3 Polycystic Ovary Syndrome 22.7 Cancer 22.7.1 Cancer Cells Are Reliant on Fermentable Fuels 22.8 Neurodegenerative Diseases 22.9 Risk/Benefit Analysis 22.9.1 Baseline Laboratory Evaluation 22.9.2 Blood Panel 22.9.3 Absolute Contraindications 22.9.4 Relative Contraindications 22.10 Macronutrient Calculations 22.10.1 Protein Target 22.10.2 Carbohydrate 22.10.3 Fats 22.10.4 The Question of Calorie Restriction 22.10.5 Food Trackers and Meal Planners 22.11 Food and Supplement Recommendations 22.11.1 Eliminate the Following 22.11.2 Allowed Foods 22.11.3 Diet Supplementation 22.11.3.1 Vitamins 22.11.3.2 Minerals 22.11.3.3 Gut Health 22.11.3.4 Digestive Aids 22.11.3.5 Herbs and Botanicals 22.11.3.6 Antioxidants 22.12 Variations of the Ketogenic Diet 22.12.1 Atkins Diet [44, 67] 22.12.2 Modified Atkins Diet 22.13 Diet Ratio 22.14 Diet Macros 22.15 Short-Term Versus Long-Term Maintenance 22.16 Transitioning to a Ketogenic Diet 22.16.1 Option #1: Fasting 22.16.2 Option #2: A Rigorous Ketogenic Diet 22.16.3 Option #3: A Slow Transition to Ketosis 22.17 Potential Side Effects of the Transition 22.17.1 Hunger and Cravings 22.17.2 “Keto Flu” 22.17.3 Hypoglycemia 22.17.4 Acidosis 22.17.5 Dizzy, Lightheaded, or Shaky 22.17.6 Constipation 22.17.7 Heart Rate or Rhythm Changes, Including Palpitations 22.17.8 Change in Exercise Tolerance or Physical Performance 22.17.9 “Keto Rash” 22.17.10 Increased Risk of Kidney Stones and Gout 22.18 The First Few Weeks: The “Make or Break” Period 22.18.1 Testing Glucose and Ketones 22.18.2 Testing Blood Glucose 22.18.3 Ketone Testing Tools [73] 22.18.3.1 Blood Ketones 22.18.3.2 Urine Testing 22.18.3.3 Breath Analyzer 22.19 Troubleshooting 22.19.1 Ongoing Flu-like Symptoms 22.19.2 Hunger between Meals 22.19.3 Food Cravings 22.19.4 Unsustainable or Rapid Weight Loss 22.19.5 Spikes in Glucose (a Rise of >25–30mg/dL) with a Meal or Snack 22.19.6 Steroid Medications (e.g., Prednisone, Dexamethasone, or Hydrocortisone) 22.19.7 Dropping out of Ketosis 22.19.8 Hidden Carbohydrates in Medicines, Supplements, or Hygiene Products 22.19.9 Nausea or Vomiting 22.19.10 Dissatisfaction with Food Choices 22.19.11 High Blood Glucose Levels 22.20 Conclusion References 23: The GUT-Immune System 23.1 Introduction 23.2 The Digestive System 23.3 The Digestive Process 23.4 The Stomach and the Immune System 23.5 Functional Laboratory Testing 23.5.1 Key Dietary and Lifestyle Recommendations to Raise Gastric Acid 23.6 The GALT and the MALT 23.6.1 Key Dietary and Lifestyle Recommendations to Raise IgA 23.6.1.1 Dietary Supplementation Recommendations 23.6.2 Key Dietary and Lifestyle Recommendations to Break Down Immune Complexes 23.6.2.1 Dietary Supplementation Recommendations 23.7 Small Intestine 23.8 The Gut Microbiota 23.9 The Microbiome: Bacteria 23.10 Biofilm Layer 23.11 Healing the Gut: The 5R Protocol 23.12 Role of Nutrition in Balancing the Gut-Immune System: Therapeutic Diets 23.13 Prebiotics and Benefits 23.14 Selected Therapeutic Foods 23.15 Therapeutic Role of Probiotic Supplements 23.16 Conclusion References 24: Centrality of the GI Tract to Overall Health and Functional Medicine Strategies for GERD, IBS, and IBD 24.1 Impact of the GI Tract on Immunity 24.2 GI Impact on the Brain 24.3 GI Endocrine Effects 24.4 GI Impact on Metabolism 24.5 GERD 24.6 Diet for GERD 24.7 Supplements for GERD 24.8 Irritable Bowel Syndrome 24.9 GI-IBD References 25: The Microbiome and Brain Health 25.1 Introduction 25.2 Dysbiosis 25.3 Probiotics 25.4 Second Brain 25.5 Mood Disorders 25.6 Schizophrenia 25.7 Bipolar Disorder 25.8 General Discussion of Mood Disorders 25.9 Psychobiotics 25.10 Brain-Derived Neurotrophic Factor (BDNF) 25.11 Neurological Disorders 25.12 Alzheimer’s Disease 25.13 Autism 25.14 Parkinson’s Disease 25.15 Aging 25.16 Fecal Transplants 25.17 Food Sources 25.18 Summary References 26: The Role of Nutrition in Integrative Oncology 26.1 Introduction 26.1.1 What Is Cancer? 26.1.2 Types of Cancer 26.1.3 Statistics of Cancer 26.1.3.1 The Functional, Integrative, Holistic, and Nutritional Perspective 26.2 Mechanisms of Oncogenesis and Metastases 26.3 The Hallmarks of Cancer 26.4 Current Conventional Medical Treatment 26.4.1 Chemotherapy and Targeted Therapies 26.4.1.1 Alkylating Agents 26.4.1.2 Plant Alkaloids 26.4.1.3 Antitumor Antibiotics 26.4.1.4 Antimetabolites 26.4.1.5 Topoisomerase Inhibitors 26.4.1.6 Miscellaneous Antineoplastics 26.4.2 Radiation 26.4.3 Surgery 26.5 Terrain Versus Cancer 26.6 Optimization and Protection 26.7 Synergistic Therapies 26.8 Emotional Aspect of Cancer 26.9 Lifestyle Detoxification 26.9.1 Avoid or Remove? 26.9.2 Sepsis 26.9.3 Integrative and Functional Nutrition 26.9.4 Liquid Oral or Enteral Nutrition 26.9.5 Tea Therapy 26.9.6 Turmeric 26.9.7 Ginger 26.9.8 Dandelion 26.9.9 Methyl-Rich Foods 26.9.10 Melatonin-Rich Foods 26.9.11 Honokiol 26.9.12 Limonene 26.9.13 Cruciferous Vegetables 26.9.14 Seeds 26.9.15 Medicinal Mushrooms 26.9.16 Bee Products 26.9.17 Iodine Sufficiency 26.9.18 Seaweed and Algae 26.9.19 Fiber, Prebiotics, and Short-Chain Fatty Acids 26.9.20 Modified Citrus Pectin and Pectin 26.9.21 Fermented Foods and Probiotics 26.9.22 Artemisia 26.9.23 Carotenoid- and Polyphenol-Rich Foods 26.9.24 Essential Oils 26.10 Dietary Interventions 26.10.1 Seasonal Eating and Living 26.10.2 Autoimmune Paleo Diet 26.10.3 Vegetarian Diet 26.10.4 Ketogenic Diet 26.10.4.1 Bio-individual Diets and Protocols 26.11 Integrative Therapies Adjunctive to Nutrition Therapy 26.11.1 Hyperthermia 26.11.2 Mindfulness Practices or Meditation 26.11.3 Movement and Exercise 26.11.4 Massage or Touch Therapy 26.11.5 Posttreatment: Creating an Empowerment Plan 26.12 Conclusion References Further Reading and Research 27: The Microenvironment of Chronic Disease 27.1 Introduction 27.2 The Microenvironment in Malignancies 27.3 Components of Tumor Microenvironments 27.4 Cellular Components 27.5 Molecular Components 27.6 Nutritional Influences on the Tumor Microenvironment 27.6.1 Influences on the Extracellular Matrix 27.6.2 Angiogenesis 27.7 Inflammatory Influences 27.8 The Microenvironment in Chronic Autoimmune Disease and Similarities to Cancer 27.9 Nutritional Influences on the Autoimmune Microenvironment 27.10 The Microenvironment of Arthritic Conditions 27.11 Nutritional Influences on the Microenvironment in Arthritic Conditions 27.12 The Blood as a Potential Reflective Microenvironment 27.13 Conclusion References 28: Chronic Pain 28.1 Introduction 28.1.1 Mechanisms of Pain (See . Fig. 28.2) 28.1.1.1 Nociceptive Pain 28.1.1.2 Neuropathic Pain 28.1.1.3 Central Sensitization 28.1.1.4 Psychological Pain 28.1.1.5 Psychosocial Mediators 28.1.1.6 Sleep, Depression and Chronic Pain 28.1.1.7 Cancer-Related Pain 28.1.1.8 Nutrition and Chronic Pain 28.1.1.9 Obesity 28.1.1.10 Inflammation 28.1.1.11 Gut Microbiome 28.1.1.12 Food Sensitivities 28.1.1.13 Oral Function 28.1.1.14 Nutrition Assessment 28.1.1.15 Functional Labs to Assess Nutritional Status 28.1.1.16 Therapeutic Diets 28.1.1.17 Nutrients and Supplementation in Pain Management 28.1.1.18 Omega-3 Essential Fatty Acids (See . Fig. 28.4) 28.1.1.19 Omega 6 Fatty Acids 28.1.1.20 Vitamin D/Vitamin A 28.1.1.21 Magnesium 28.1.1.22 B Vitamins 28.1.1.23 Essential Nutrients 28.1.1.24 Hydration 28.1.2 Plant Compounds 28.1.2.1 Turmeric (Curcuma longa) 28.1.2.2 Ginger (Zingiber officinale) 28.1.2.3 Boswellia 28.1.2.4 Willowbark 28.1.2.5 Butterbur and Feverfew 28.1.2.6 Cannabinoids 28.1.2.7 Medical Treatment and Nutritional Implications 28.1.2.8 Genetics 28.1.2.9 Epigenetics 28.1.2.10 Lifestyle 28.1.2.11 Language of Pain References 29: Nutrition and Behavioral Health/Mental Health/Neurological Health 29.1 Introduction 29.1.1 Spectrums of Psychiatric Disorders 29.1.2 Serious Mental Illness and Genetics 29.1.3 Depression 29.1.4 Bipolar Disorder 29.1.5 Schizophrenia 29.2 Other Conditions: Conditions that May Be Accompanied by Changes in Mental Status 29.2.1 Brain-Derived Neurotropic Factor (BDNF) 29.2.2 Celiac Disease 29.2.3 Metabolic Syndrome 29.2.4 Hyponatremia/Water Intoxication 29.2.5 Caffeine Intoxication 29.2.6 Food Insecurity 29.3 The Effect of Micro- and Macronutrients on Mental/Behavioral/Neurological Health 29.3.1 Lipids, Glucose, Amino Acids 29.3.1.1 Essential Fatty Acids 29.3.1.2 Cholesterol 29.3.1.3 Amino Acids 29.3.1.4 Carbohydrates: Glucose 29.3.2 Vitamins and Minerals 29.3.2.1 Vitamins Vitamin B1 (Thiamin) Vitamin B2 (Riboflavin) Vitamin B3 (Niacin) Vitamin B6 (Pyridoxine) Vitamin B12 Vitamin C Folate Vitamin A Vitamin D Vitamin K 29.3.3 Minerals 29.3.3.1 Nutrient Minerals Copper Lithium Magnesium Manganese Selenium Zinc 29.3.4 Potentially Toxic Minerals 29.3.4.1 Cadmium 29.3.4.2 Mercury 29.4 Drugs: Nutrition and Mental Status 29.5 Summary Statement References 30: Neurodevelopmental Disorders in Children 30.1 Introduction 30.2 Children Are Not Little Adults 30.3 Toxins and Toxicants 30.4 Family History and Genetics 30.5 Lifestyle Factors 30.6 Autism Spectrum Disorders (ASD) 30.7 History 30.8 Gastrointestinal Symptoms 30.9 Mitochondrial Issues in Autism 30.10 Biomedical Assessment for Autism 30.11 Functional Lab Assessment for Autism 30.12 Family History and Autism 30.13 Polymorphisms in Autism 30.14 Genes Affecting GI Health 30.15 Folate and Methylation Genes 30.16 Transsulfuration Pathway Genes 30.17 Neurotransmitter Genes 30.18 Genes Affecting Detoxification 30.19 Nutritional Support 30.20 ADHD 30.20.1 Lifestyle and Environmental Factors 30.21 Dr. Amen’s Seven Types of ADHD [87] 30.21.1 General Dietary and Lifestyle Strategies for ADHD 30.22 Seizure Disorders 30.22.1 Contraindications to the Ketogenic Diet 30.22.2 Ketogenic Diet Labs 30.22.3 Supplements for the Ketogenic Diet 30.23 PANDAS and PANS 30.23.1 NIMH Guidelines for Diagnosing PANDAS 30.23.1.1 Laboratory Testing for PANDAS 30.23.2 NIMH Guideline for Diagnosing PANS [108] 30.24 Conclusion References 31: Nutritional Influences on Hormonal Health 31.1 Introduction to Hormonal Health 31.2 Insulin 31.2.1 Insulin Resistance 31.2.2 Impaired Glucose Tolerance 31.2.3 Prediabetes 31.2.4 Diabetes Mellitus Type 2 31.2.5 Metabolic Syndrome Vs. Insulin Resistance 31.2.6 Identifying Patients at Risk for Insulin Resistance 31.2.7 Protocol 31.2.8 Staging the Patient 31.2.9 Laboratory Evaluation 31.2.9.1 Hemoglobin A1c 31.2.9.2 HOMA-IR 31.2.9.3 Adiponectin, Insulin, and Proinsulin: Staging the Progression of Insulin Resistance to Prediabetes and Type 2 Diabetes 31.2.10 Treatment 31.2.10.1 Dietary Management 31.2.10.2 Exploring Detoxification 31.2.10.3 Exercise 31.2.10.4 Stress and Autonomic Dysfunction 31.2.10.5 Sleep 31.2.11 A Final Word on Insulin Resistance 31.3 Adrenal Dysfunction 31.3.1 What Is Adrenal Dysfunction? 31.3.2 What Causes Adrenal Dysfunction? 31.3.3 Assessment and Treatment of Adrenal Dysfunction 31.3.4 A Final Word on Adrenal Dysfunction 31.4 Thyroid 31.4.1 Assessment 31.4.2 Treatment 31.5 Sex Steroid Hormones 31.6 Conclusion References 32: Nutritional Influences on Reproduction: A Functional Approach 32.1 Introduction 32.2 Microenvironments and Complexity 32.3 Examining the Structural Layer 32.4 Examining the Functional Layer