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Micronutrients in Health and Disease, Second Edition
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Main description:

Growing sentiments against using micronutrient supplements for improving health and preventing disease have created uncertainty in the minds of many health professionals. Following its predecessor, this new edition supports the use of multiple micronutrients combined with proper diet to prove successful in the prevention and management of chronic diseases. It provides basic information on micronutrients, oxidative stress, inflammation, and the immune system. The book goes further to explore use of multiple micronutrients in prevention and treatment of diseases including arthritis, cancer, diabetes, heart diseases, traumatic brain injury, PTSD, prion diseases, and autism spectrum disorder. Key Features Proposes sevidence-based micronutrient supplementation strategies for healthy aging and disease management and prevention. Contains three new chapters on Huntington's Disease, prion diseases, and autism spectrum disorder. All chapters include new studies on etiology, incidence, and mechanisms of several diseases. Discusses role of microRNAs in the initiation and progression for each disease.


Contents:

Contents

Preface..........................................................................................................................................xxvii

Acknowledgments .........................................................................................................................xxix

Author ...........................................................................................................................................xxxi

Chapter 1 Basic Facts about Micronutrients .................................................................................1

Introduction ..................................................................................................................1

Evolution of the Antioxidant System ............................................................................1

History of the Discovery of Micronutrients .................................................................1

Sources and Forms of Vitamins ...................................................................................2

Solubility of Micronutrients .........................................................................................4

Distribution of Antioxidants in the Body .....................................................................4

Storage of Antioxidants ................................................................................................6

Can Antioxidants Be Destroyed during Cooking? .......................................................6

Absorption of Antioxidants and Its Significance .........................................................6

Functions of Individual Antioxidants ...........................................................................7

Antioxidant Defense Systems .......................................................................................8

Antioxidant Enzymes ..............................................................................................8

Dietary Antioxidants ...............................................................................................8

Endogenous Antioxidants ........................................................................................8

Known Functions of Antioxidants ...............................................................................8

Current Controversies about Antioxidants ...................................................................9

Misuse of Antioxidants in Clinical Studies .................................................................9

Conclusions ................................................................................................................ 12

References .................................................................................................................. 12

Chapter 2 Basic Facts about Oxidative Stress, Inflammation, and the Immune System ............ 13

Introduction ................................................................................................................ 13

Oxidative Stress .......................................................................................................... 14

What Are Free Radicals? ....................................................................................... 14

Types of Free Radicals .......................................................................................... 14

Formation of Free Radicals Derived from Oxygen and Nitrogen ......................... 14

Oxidation and Reduction Processes ........................................................................... 16

What Is Inflammation? ............................................................................................... 16

Types of Inflammatory Reactions ......................................................................... 17

Products of Inflammatory Reactions .......................................................................... 17

Cytokines ............................................................................................................... 17

Complement Proteins ............................................................................................ 18

Arachidonic Acid (AA) Metabolites ..................................................................... 18

Endothelial/Leukocyte Adhesion Molecules ........................................................ 18

Immune System .......................................................................................................... 18

What Is the Immune System? ..................................................................................... 19

Innate Immunity ......................................................................................................... 19

Adaptive Immunity ....................................................................................................20

Conclusions ................................................................................................................20

References .................................................................................................................. 21

Chapter 3 Scientific Rationale of Current Trends in Clinical Studies of Micronutrients ...........23

Introduction ................................................................................................................23

Levels of Oxidative Stress and Chronic Inflammation in High-Risk Populations ....24

High-Risk Populations of Cancer ..........................................................................24

High-Risk Populations of Coronary Artery Disease (CAD) .................................24

High-Risk Populations of Alzheimer's Disease (AD) and Parkinson's

Disease (PD) ..........................................................................................................24

Distributions and Function of Antioxidants ...............................................................25

Results of Clinical Trials with a Single Antioxidant in High-Risk Populations ........26

Cancer ....................................................................................................................26

Coronary Artery Disease (CAD) ...........................................................................26

Alzheimer's Disease (AD) and Parkinson's Disease (PD) ....................................27

Why the Use of a Single Antioxidant Produced Inconsistent Results .......................28

Results of Clinical Studies with Multiple Dietary Antioxidants in Cancer ...............29

Results of Clinical Studies with Fat and Fiber ...........................................................30

Rationale for Using a Mixture of Micronutrients for Reducing the Risk and

Progression of Chronic Diseases ................................................................................30

Proposed Mixture of Micronutrients for Reducing the Risk and Progression

of Chronic Diseases.................................................................................................... 31

Proposed Changes in Diet and Lifestyle for Reducing the Risk and Progression

of Chronic Diseases.................................................................................................... 31

Conclusions ................................................................................................................ 32

References .................................................................................................................. 32

Chapter 4 Micronutrients in Healthy Aging and Age-Related Decline in Organ Functions ...... 35

Introduction ................................................................................................................ 35

Trends of Aging Population .......................................................................................36

Evidence for Increased Oxidative Stress During Aging ............................................36

Extracellular Sources for Production of Free Radicals ..............................................36

Cellular Sites of Production of Free Radicals ............................................................ 37

Oxidative Stress-Induced Age-Related Decline in Organelle Functions ...................38

Mitochondrial Dysfunction ...................................................................................38

Impairment of Proteasome and Lysosomal-Mediated Proteolytic Activities ....... 39

Oxidative Stress-Induced Changes in Cell Culture Models .................................. 39

Oxidative Stress-Induced Changes in Animal Models ......................................... 39

Oxidative Stress-Induced Shortening of the Length of Telomere ......................... 39

Evidence for Chronic Inflammation During Aging ...................................................40

Impaired Immune Function in Aging ...................................................................40

Changes in the Antioxidant Defense Systems During Aging .................................... 41

Antioxidant Enzymes ............................................................................................ 41

Changes in Antioxidant Enzymes Activities in Animals ...................................... 42

Changes in Antioxidant Enzymes Activities in Humans ...................................... 42

Changes in Dietary and Endogenous Antioxidants Levels ........................................ 43

Vitamin C .............................................................................................................. 43

Glutathione ............................................................................................................44

Vitamin E ..............................................................................................................44

Coenzyme Q10 ......................................................................................................44

MicroRNAs in Aging ................................................................................................. 45

MicroRNAs ........................................................................................................... 45

MicroRNAs in Age-Related Diseases ................................................................... 45

MicroRNAs and Their Target Proteins in Aged Animals .................................... 45

Oxidative Stress and Pro-inflammatory Cytokine Regulate Expression of

MicroRNAs ........................................................................................................... 47

Antioxidants Regulate Expression of MicroRNAs ............................................... 47

Effects of Individual Antioxidants on Age-Related Functional Deficits ................... 47

Vitamin E .............................................................................................................. 47

Coenzyme Q10 ......................................................................................................48

Carotenoids and Zinc ............................................................................................48

Melatonin ...............................................................................................................48

Flavonoids ..............................................................................................................48

Glutathione and N-Acetylcysteine (NAC) .............................................................48

Alpha-Lipoic Acid .................................................................................................49

Multiple Dietary Antioxidants...............................................................................49

Studies with Individual Antioxidants on Age-Related Neurodegenerative

Diseases in Humans ...................................................................................................49

Regulation of Activation of Nrf2 ...............................................................................50

Reactive Oxygen Species (ROS) Activates Nrf2 ...................................................50

Binding of Nrf2 with ARE in the Nucleus ............................................................50

Existence of ROS-Resistant Nrf2 ..........................................................................50

Antioxidants and Phytochemicals Activate ROS-Resistant Nrf2 ......................... 51

L-Carnitine Activates Nrf2 by a ROS-Dependent Mechanism ............................ 51

Activation of Nrf2 by MicroRNAs ........................................................................ 51

Suppression of Chronic Inflammation ....................................................................... 51

Proposed Mixture of Micronutrients for Healthy Aging and for Reducing

Age-Related Functional Deficits ................................................................................ 51

Proposed Changes in Diet and Lifestyle for Healthy Aging and for Reducing

Age-Related Functional Deficits ................................................................................ 52

Conclusions ................................................................................................................ 52

References .................................................................................................................. 53

Chapter 5 Role of Micronutrients in Prevention of Coronary Artery Disease and

Improvement of the Standard Therapy ......................................................................63

Introduction ................................................................................................................63

Prevalence, Incidence, and Cost .................................................................................64

Evidence for Increased Oxidative Stress in CAD ......................................................64

Consequences of Increased Oxidative Stress ........................................................65

Evidence for Increased Chronic Inflammation in CAD.............................................65

Evidence for Increased Levels of Homocysteine in CAD ..........................................66

MicroRNAs in CAD ..................................................................................................66

MicroRNAs ........................................................................................................... 67

Circulating MicroRNAs in CAD .......................................................................... 67

Cellular MicroRNAs in CAD ................................................................................68

Oxidative Stress and Pro-inflammatory Cytokine Regulate Expression of

MicroRNAs ...........................................................................................................69

Antioxidants Regulate Expression of MicroRNAs ............................................... 70

Role of Antioxidants in CAD ..................................................................................... 70

Animal Studies after Treatment with Antioxidants .............................................. 70

Epidemiologic Studies with Antioxidants ............................................................. 70

Intervention Human Studies after Treatment with Antioxidants .......................... 71

Vitamin E Alone Producing Beneficial Effects .................................................... 74

Vitamin C Alone Producing Beneficial Effects .................................................... 74

Dietary Antioxidants Producing No Effects or Adverse Effects .......................... 74

Endogenous Antioxidants Producing No Effects or Beneficial Effects ................ 76

Dietary and Endogenous Antioxidants with Cholesterol-Lowering Drugs ............... 76

Multiple Dietary Antioxidants with Cholesterol-Lowering Drugs ............................77

Resveratrol and Omega-3 Fatty Acids ........................................................................77

Resveratrol .............................................................................................................77

Omega-3 Fatty Acids ............................................................................................. 78

Intervention Studies with B-Vitamins to Lower Homocysteine Levels ..................... 79

Potential Reasons for the Failure of Individual Micronutrients in Producing

Sustained and Consistent Benefits in CAD ................................................................80

Regulation of Activation of Nrf2 ............................................................................... 81

Reactive Oxygen Species (ROS) Activates Nrf2 ................................................... 81

Binding of Nrf2 with ARE in the Nucleus ............................................................ 81

Existence of ROS-Resistant Nrf2 in CAD ............................................................ 81

Antioxidants and Phytochemicals Activate ROS-Resistant Nrf2 ......................... 81

L-Carnitine Activates Nrf2 by a ROS-Dependent Mechanism ............................ 81

Activation of Nrf2 by MicroRNAs ........................................................................82

Suppression of Chronic Inflammation .......................................................................82

Proposed Mixture of Micronutrients for Prevention and Improved

Management of CAD .................................................................................................82

Proposed Changes in Diet and Lifestyle for Prevention and Improved

Management of CAD .................................................................................................82

Prevention and Improved Management of CAD ........................................................83

Primary Prevention ................................................................................................83

Secondary Prevention ............................................................................................83

Improved Management of CAD ............................................................................84

Conclusions ................................................................................................................84

References ..................................................................................................................84

Chapter 6 Micronutrients in Prevention and Improvement of the Standard Therapy in

Diabetes ......................................................................................................................95

Introduction ................................................................................................................95

Incidence, Prevalence, and Cost .................................................................................96

Incidence ................................................................................................................96

Prevalence ..............................................................................................................96

Cost ........................................................................................................................96

Types of Diabetes .......................................................................................................96

Type 1 Diabetes .....................................................................................................96

Type 2 Diabetes .....................................................................................................96

Gestational Diabetes ..............................................................................................97

Other Types of Diabetes ........................................................................................97

Pre-diabetes and Metabolic Syndrome .................................................................97

Complications of Diabetes .........................................................................................97

Evidence for Increased Oxidative Stress in Diabetes.................................................97

Type 1 Diabetes .....................................................................................................97

Type 2 Diabetes .....................................................................................................98

Metabolic Syndrome .............................................................................................99

Evidence for Increased Chronic Inflammation in Diabetes .......................................99

MicroRNAs in Diabetes ........................................................................................... 100

MicroRNAs ......................................................................................................... 100

Circulating MicroRNAs in Diabetes ................................................................... 100

Cellular MicroRNAs in Diabetes (Humans) ....................................................... 102

Cellular MicroRNAs in Diabetes (Animal Models)............................................ 103

Oxidative Stress and Pro-inflammatory Cytokines Regulate Expression

of MicroRNAs ..................................................................................................... 103

Antioxidants Regulate Expression of MicroRNAs ............................................. 103

Reducing Oxidative Stress and Chronic Inflammation in Diabetes ........................ 104

Role of Antioxidants and Phytochemicals in Protecting Against Diabetes ............. 104

Vitamin A (Animal and Human Studies) ............................................................ 104

Vitamin C (Human Studies) ................................................................................ 104

Vitamin C (Animal Studies) ................................................................................ 105

Vitamin D3 (Animal Studies) .............................................................................. 105

Vitamin E (Animal Studies) ................................................................................ 105

Vitamin E (Human Studies) ................................................................................ 106

Alpha-Lipoic Acid (Human Studies) ................................................................... 106

Alpha-Lipoic Acid (Animal Studies) ................................................................... 106

N-Acetylcysteine (Human Studies) ..................................................................... 107

N-Acetylcysteine (Animal Studies) ..................................................................... 107

L-Carnitine (Human Studies) .............................................................................. 107

L-Carnitine (Animal Studies) .............................................................................. 108

Coenzyme Q10 (Human Studies) ........................................................................ 108

Coenzyme Q10 (Animal Studies) ........................................................................ 109

Omega-3 Fatty Acids (Animal Studies) ............................................................... 109

Omega-3-Fatty Acids (Epidemiologic Studies) ................................................... 110

Omega-3-Fatty Acids (Intervention Studies) ....................................................... 110

Antioxidant Mixtures (Human Studies) .............................................................. 110

Antioxidant Mixture (Animal Studies) ............................................................... 111

Folic Acid and Thiamine (Human Studies) ......................................................... 111

Folic Acid and Thiamine (Animal Studies) ........................................................ 112

Chromium (Human Studies) ............................................................................... 112

Antioxidants with Diabetic/Cardiovascular Drugs and/or Insulin (Human

Studies) ................................................................................................................ 112

Antioxidants with Diabetic/Cardiovascular Drugs and/or Insulin (Animal

Studies) ................................................................................................................ 113

Treatments of Diabetes ............................................................................................. 113

Standard Treatments ............................................................................................ 113

Aspirin (Human Studies) ..................................................................................... 113

Aspirin Resistance ............................................................................................... 114

Aspirin (Animal Studies)..................................................................................... 114

Potential Reasons for Inconsistent Results with Individual Micronutrients or

Aspirin ...................................................................................................................... 114

Regulation of Activation of Nrf2 ............................................................................. 115

Reactive Oxygen Species (ROS) Activates Nrf2 ................................................. 115

Binding of Nrf2 with ARE in the Nucleus .......................................................... 115

Existence of ROS-Resistant Nrf2 in Diabetes ..................................................... 116

Antioxidants and Phytochemicals Activate ROS-Resistant Nrf2 ....................... 116

L-Carnitine Activates Nrf2 by a ROS-Dependent Mechanism .......................... 116

Activation of Nrf2 by MicroRNAs ...................................................................... 116

Suppression of Chronic Inflammation ..................................................................... 116

Recommended Mixture of Micronutrients for the Prevention of Diabetes ............. 117

Recommended Changes in Diet and Lifestyle for the Prevention and

Improved Management of Diabetes ......................................................................... 117

Prevention of Diabetes ............................................................................................. 117

Primary Prevention .............................................................................................. 117

Secondary Prevention .......................................................................................... 118

Improved Management of Diabetes .................................................................... 118

Conclusions .............................................................................................................. 118

References ................................................................................................................ 118

Chapter 7 Micronutrients in Cancer Prevention ....................................................................... 131

Introduction .............................................................................................................. 131

Incidence, Prevalence, Mortality, and Cost .............................................................. 132

Proposed Stages of Carcinogenesis .......................................................................... 132

Two-Stage Model of Animal Carcinogenesis ...................................................... 132

Some Examples of Tumor Initiators and Tumor Promoters ..................................... 133

Three-Stage Model of Human Carcinogenesis ................................................... 133

Diagrammatic Representation of Three-Stage Model of Human Carcinogenesis ........133

Some Examples of Environmental-Related Carcinogens ........................................ 134

Some Examples of Diet-Related Carcinogens ......................................................... 134

Some Examples of Diet-Related Cancer Protective Agents ..................................... 135

Some Examples of Lifestyle-Related Carcinogens .................................................. 135

Alcohol ................................................................................................................ 135

Cell Phone ........................................................................................................... 135

Smoking ............................................................................................................... 136

Coffee and Caffeine ............................................................................................. 136

Evidence for Increased Oxidative Stress .................................................................. 137

Evidence for Increased Chronic Inflammation ........................................................ 137

MicroRNAs in Cancer Prevention ........................................................................... 138

MicroRNAs ......................................................................................................... 138

Changes in MicroRNAs after Exposure to Chemical Carcinogens and

Oncogenic Virus ....................................................................................................... 138

Functions of Antioxidants Relevant to Cancer Prevention ...................................... 140

Antioxidants and Phytochemicals Regulate Expression of MicroRNAs ................. 141

Reducing Oxidative Stress and Chronic Inflammation in Cancer Prevention ......... 141

Cell Culture Models ............................................................................................ 141

Animal Models .................................................................................................... 141

Epidemiologic Studies ......................................................................................... 142

Intervention Studies with Single Antioxidants (Lung Cancer) ........................... 143

Intervention Studies with a Single Antioxidant (Other Cancers) ........................ 144

Intervention Studies with Multiple Dietary Antioxidants ................................... 144

Intervention Studies with Vitamin D and Calcium ............................................. 145

Intervention Studies with Folate and B-Vitamins ............................................... 145

Intervention Studies with Fat and Fiber .............................................................. 146

Intervention Studies with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) ........146

Potential Reasons for Inconsistent Results with Individual Micronutrients

or Aspirin in Cancer Prevention Studies .................................................................. 146

Regulation of Activation of Nrf2 ............................................................................. 147

Reactive Oxygen Species (ROS) Activates Nrf2 ................................................. 147

Binding of Nrf2 with ARE in the Nucleus .......................................................... 147

Existence of ROS-Resistant Nrf2 in Cells Following Exposure to Carcinogens .......147

Antioxidants and Phytochemicals Activate ROS-Resistant Nrf2 ....................... 148

L-Carnitine Activates Nrf2 by a ROS-Dependent Mechanism .......................... 148

Activation of Nrf2 by MicroRNAs ...................................................................... 148

Suppression of Chronic Inflammation ..................................................................... 149

Recommended Mixture of Micronutrients for the Prevention of Cancer ................ 149

Recommended Changes in Diet and Lifestyle for the Prevention of Cancer ........... 149

Proposed Cancer Prevention Strategies ................................................................... 150

Primary Prevention .............................................................................................. 150

Secondary Prevention .......................................................................................... 150

Can Cancer with a Family History Be Prevented? .................................................. 150

Problems Associated with Implementation of Dietary and Lifestyle

Recommendations .................................................................................................... 150

Toxicity of Micronutrients ........................................................................................ 151

Conclusions .............................................................................................................. 151

References ................................................................................................................ 152

Chapter 8 Micronutrients in Improvement of the Standard Therapy in Cancer ....................... 163

Introduction .............................................................................................................. 163

MicroRNAs in Cancer Cells .................................................................................... 164

MicroRNAs ......................................................................................................... 164

MicroRNAs Acting as Tumor Suppressors or Anti-oncogenes ............................... 165

Colon Cancer ....................................................................................................... 165

Gastric Cancer Cells ............................................................................................ 165

Non-Small Cell Lung Cancer (NSCLC) ............................................................. 165

Retinoblastoma .................................................................................................... 166

Breast Cancer Cells ............................................................................................. 166

Hepatocellular Carcinoma ................................................................................... 167

Bladder Cancer .................................................................................................... 167

Cervical Cancer ................................................................................................... 167

MicroRNAs Acting as Oncogenes ........................................................................... 168

Bladder Cancer .................................................................................................... 168

Lung Cancer ........................................................................................................ 168

Non-Small-Cell Lung Cancer .............................................................................. 168

Prostate Cancer, Gastric Cancer, and Esophageal Cancer .................................. 168

Cervical Cancer, Colorectal Cancer, and Breast Cancer ..................................... 168

Nrf2 in Cancer Cells ................................................................................................ 169

Normal Cell Response to Activated Nrf2............................................................ 169

High Expression of Nrf2 Promotes Cancer Growth and Drug-Resistant ................ 169

Individual Antioxidants Inhibit Cancer Growth in the Presence of Elevated

Levels of Nrf2 .......................................................................................................... 170

Luteolin ............................................................................................................... 170

Pterostilbene ........................................................................................................ 170

Antioxidants Activate ROS-Resistant Nrf2 ......................................................... 170

Synthetic Triterpenoid RTA 405 ......................................................................... 171

Curcumin ............................................................................................................. 171

Tert-Butylhydroquinone ...................................................................................... 171

Vitamin E Succinate ............................................................................................ 171

Vitamin C ............................................................................................................ 172

Vitamin A and Carotenoids ................................................................................. 173

Selenium .............................................................................................................. 173

N-Acetylcysteine (NAC) and Alpha-Lipoic Acid................................................ 173

Antioxidant-Induced Changes in Gene Expression Profiles in Cancer Cells .......... 173

Effects of Therapeutic Doses of Individual Antioxidants in Combination

with Radiation Therapy on Cancer Cells and Normal Cells .................................... 174

Cell Culture Studies ............................................................................................ 174

Animal Studies .................................................................................................... 174

Human Studies .................................................................................................... 176

Effects of Therapeutic Doses of Individual Antioxidants in Combination

with Chemotherapeutic on Cancer Cells and Normal Cells .................................... 176

Cell Culture Studies ............................................................................................ 176

Animal Studies .................................................................................................... 179

Human Studies .................................................................................................... 179

Reasons for Growth-Inhibitory Effects Antioxidants in the Presence of

Elevated Levels of Nrf2 ............................................................................................ 179

Preventive Doses of Individual Antioxidants Reduce the Efficacy of

Therapeutic Agents .................................................................................................. 180

Effects of Therapeutic Doses of Individual Antioxidants in Combination with

Experimental Therapies on Cancer Cells ................................................................. 180

Hyperthermia....................................................................................................... 180

Sodium Butyrate and Interferon-Alpha2b ........................................................... 181

Immunotherapy and Gene Therapy ..................................................................... 182

Proposed Mixture Therapeutic Doses of Antioxidants During Cancer Therapy ......182

Conclusions .............................................................................................................. 182

References ................................................................................................................ 183

Chapter 9 Micronutrients in the Prevention and Improvement of the Standard Therapy for

Alzheimer's Disease ................................................................................................. 191

Introduction .............................................................................................................. 191

Prevalence, Incidence, and Cost of AD .................................................................... 192

Estimated Cost of Treatment of AD ......................................................................... 193

Etiology of AD ......................................................................................................... 193

Neuropathology of AD ............................................................................................. 193

MicroRNAs in the Pathogenesis of AD ................................................................... 193

MicroRNAs ......................................................................................................... 193

Changes in the Expressions of MicroRNAs in Human AD ..................................... 194

Elevated Expressions of MicroRNAs .................................................................. 194

Decreased Expressions of MicroRNAs ............................................................... 195

Changes in MicroRNAs in Animal and Cell Culture AD Models .......................... 196

Elevated Expressions of MicroRNAs .................................................................. 196

Decreased Expression of MicroRNAs ................................................................ 196

ROS and Pro-inflammatory Cytokines Regulate the Expressions of MicroRNAs ......197

ROS Upregulates the Expressions of MicroRNAs Causing Neurodegeneration .......197

ROS Downregulates the Expressions of MicroRNAs Causing

Neurodegeneration............................................................................................... 198

Pro-inflammatory Cytokines Upregulate the Expressions of MicroRNAs

Causing Neurodegeneration ................................................................................ 198

Micronutrients Regulate the Expressions of MicroRNAs ....................................... 199

Resveratrol Enhances the Expressions of MicroRNAs ....................................... 199

Resveratrol Decreases the Expressions of MicroRNAs ...................................... 199

Isoflavone Increases the Expressions of MicroRNAs ......................................... 199

Genistein Decreases the Expressions of MicroRNAs .........................................200

Quercetin Enhances the Expressions of MicroRNAs .........................................200

Curcumin Decreases the Expressions of MicroRNAs ........................................200

Curcumin Enhances the Expressions of MicroRNAs .........................................200

Coenzyme Q10 Regulates the Expressions of MicroRNAs ................................200

Vitamin D3 Regulates the Expressions of MicroRNAs ......................................200

Nicotinamide (Vitamin-B3) Regulates the Expressions of MicroRNAs ............ 201

Selenium Regulates the Expressions of MicroRNAs .......................................... 201

Vitamin E and Delta-Tocotrienol Regulate the Expressions of MicroRNAs ...... 201

Vitamin A (Retinoic Acid) Regulates the Expressions of MicroRNAs .............. 201

Vitamin C Regulates the Expression of a MicroRNA ........................................202

Sources of Free Radicals in the Normal Brain ........................................................203

Evidence for Increased Oxidative Stress as an Early Event in the Initiation of AD ......203

Studies on Cell Culture Model of AD .................................................................203

Studies on Animal Models of AD .......................................................................204

Studies on Asymptomatic Individuals Carrying Mutated AD Specific Genes ........204

Studies on Increased Oxidative Stress in an Early Phase of AD ........................204

Studies on Increased Oxidative Stress in Established Human AD

(Autopsied Brain Tissue) ..........................................................................................205

Studies on Increased Oxidative Stress in Established Human AD

(Peripheral Tissue) ....................................................................................................205

Mitochondrial Dysfunction ......................................................................................206

Processes of Generating Beta-Amyloid Fragments (Ass1-42) and Their Toxicity .........206

Oxidative Stress Increases Production of Beta Amyloids (Ass1-42 Peptides) ..........206

Ass1-42 Peptides Cause Neuronal Degeneration by Inducing Free Radicals ...........207

Mutations in AD Specific Genes Increases the Production of Beta-Amyloids ........207

Oxidative Stress Increases Hyperphosphorylated Tau (P-Tau) Protein in AD ........207

Oxidative Stress Inhibits Proteasome Activity in AD .............................................207

Evidence for Increased Levels of Markers of Chronic Inflammation in AD ...........208

Cholesterol-Induced Generation of Beta-Amyloids .................................................209

Genetic Defects in Idiopathic AD ............................................................................209

Mutated AD Genes Induce Neurodegeneration by Producing of Beta-Amyloids ... 210

Neuroglobin in AD ................................................................................................... 211

Laboratory and Clinical Studies with Individual Micronutrients in AD ................. 211

Alpha-Lipoic Acid ............................................................................................... 211

Coenzyme Q10 .................................................................................................... 212

Melatonin ............................................................................................................. 212

Nicotinamide (Vitamin B3) ................................................................................. 212

Vitamin A, Vitamin E, and Vitamin C ............................................................... 212

Serum Levels of Antioxidants ............................................................................. 213

B-Vitamins ........................................................................................................... 213

Curcumin ............................................................................................................. 214

Resveratrol ........................................................................................................... 214

Ginkgo biloba and Omega-3 Fatty Acids ............................................................ 214

Green Tea Epigallocatechin-3-Gallate (EGCG) and Caffeine ............................ 214

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in AD .................................... 215

Potential Reasons for Inconsistent Results with Individual Micronutrients

or Aspirin in AD ...................................................................................................... 215

Activation of Nrf2 (Nuclear Factor-Erythroid-2-Related Factor 2) ......................... 216

Nrf2 ..................................................................................................................... 216

ROS Activates Nrf2 ............................................................................................. 216

ROS-Resistant Nrf2 ............................................................................................. 216

Antioxidants Activate ROS-Resistant Nrf2 ......................................................... 216

Binding of Nrf2 with ARE in the Nucleus ............................................................... 216

Suppression of Chronic Inflammation ..................................................................... 216

Nrf2 in AD .......................................................................................................... 216

Proposed Micronutrient Mixture for Optimally Reducing Oxidative Stress

and Chronic Inflammation in AD ............................................................................ 217

Proposed Micronutrient Strategies for Prevention of AD ........................................ 217

Primary Prevention for AD ................................................................................. 217

Can AD Symptoms Be Prevented or Delayed in Individuals Carrying Mutated

Gene? ........................................................................................................................ 218

Secondary Prevention for AD ............................................................................. 218

Proposed Micronutrient Mixture for Improving the Management of AD ............... 218

Current Drug Therapy for AD............................................................................. 218

Proposed Micronutrient Mixture in Combination with Drug Therapy for AD .........219

Diet and Lifestyle Recommendations for AD .......................................................... 219

Conclusions .............................................................................................................. 219

References ................................................................................................................220

Chapter 10 Micronutrients for the Prevention and Improvement of the Standard Therapy

for Parkinson's Disease ............................................................................................ 235

Introduction .............................................................................................................. 235

Incidence, Prevalence, and Cost of PD ....................................................................236

Etiology of PD ..........................................................................................................236

Neuropathology and Symptoms of PD ..................................................................... 237

Genetic of PD ........................................................................................................... 237

PD Genes and Oxidative Stress ................................................................................238

DJ-1 Gene ............................................................................................................238

Alpha-Synuclein Gene ......................................................................................... 238

PTEN-Induced Putative Kinase 1 (PINK1) ........................................................ 239

PARKIN Gene .....................................................................................................240

MicroRNAs in the Pathogenesis of PD ....................................................................240

MicroRNAs .........................................................................................................240

Changes in the Expressions of MicroRNAs in Neuronal Cell Culture

Models of PD .........................................................................................................240

1-Methyl-4-Phenylpyridinium (MPP+) Treatment..............................................240

6-Hydroxydopamine (6-OHDA) Treatment ........................................................ 241

Rotenone Treatment ............................................................................................. 241

Changes in the Expressions of MicroRNAs in Animal Models of PD .................... 241

Changes in the Expressions of MicroRNAs in Human PD .....................................242

Changes in the Expressions of MicroRNAs in Impaired Non-motor

Symptoms in PD ....................................................................................................... 243

Reactive Oxygen Species (ROS) Regulates the Expressions of MicroRNAs in

Neuronal Cells .......................................................................................................... 243

Pro-inflammatory Cytokines Upregulate the Expressions of MicroRNAs ............. 243

Antioxidants Regulate the Expressions of MicroRNAs ........................................... 243

Evidence for Increased Oxidative Stress in PD........................................................ 243

Mitochondrial Dysfunction in PD ............................................................................244

Evidence for Increased Chronic Inflammation in PD ..............................................245

Evidence for Increased Glutamate in PD .................................................................245

Laboratory and Human Studies in PD after Treatment with Micronutrients ..........246

In Vitro Studies with Micronutrients...................................................................246

Cell Culture Studies with Micronutrients ...........................................................246

Antioxidant Studies in Animal Models of PD ....................................................246

Antioxidant Studies in Human PD ........................................................................... 247

Potential Reasons for Inconsistent Results with Individual Micronutrients in

AD Prevention Studies .............................................................................................248

Activation of Nrf2 (Nuclear Factor-Erythroid-2-Related Factor 2) .........................249

Nrf2 .....................................................................................................................249

ROS Activates Nrf2 ..................................................................................................249

Nrf2 in PD ................................................................................................................250

Reducing Glutamate Release and Toxicity ...............................................................250

Proposed Micronutrient Mixture for Prevention and Improved

Management of PD ...................................................................................................250

Primary Prevention .............................................................................................. 251

Secondary Prevention .......................................................................................... 251

Current Treatments of PD ........................................................................................ 251

Proposed Micronutrient Mixture in Combination with Standard Therapy ............. 251

Diet and Lifestyle Recommendations for PD ........................................................... 252

Conclusions .............................................................................................................. 252

References ................................................................................................................ 252

Chapter 11 Micronutrients in Prevention and Improvement of the Standard Therapy in

Hearing Disorders ....................................................................................................263

Introduction ..............................................................................................................263

Prevalence and Cost .................................................................................................264

Prevalence ............................................................................................................264

Cost ......................................................................................................................264

Types of Hearing Disorders .....................................................................................264

Conductive Hearing Loss ....................................................................................264

Sensorineural Hearing Loss ................................................................................264

Tinnitus ................................................................................................................265

Meniere's Disease (MD) ......................................................................................265

Agents or Health Conditions Causing Hearing Disorders .......................................265

Measurements of Hearing Loss ................................................................................266

Evidence for Increased Oxidative Stress in Hearing Disorders ...............................266

Noise-Induced Oxidative Stress (NIHL) .............................................................266

Noise and/or Vibration-Induced Oxidative Stress ............................................... 267

xvi Contents

Cisplatin-Induced Oxidative Stress ..................................................................... 267

Advanced Age-Induced Oxidative Stress ............................................................ 267

Oxidative Stress in the Meniere's Disease (MD) ................................................ 267

Evidence for Inflammation in Hearing Disorders .................................................... 267

Noise-Induced Inflammation ............................................................................... 267

Gentamicin- and Cisplatin-Induced Inflammation .............................................268

Bacterial Infection-Induced Inflammation ..........................................................268

Health Conditions-Induced Inflammation ...........................................................268

Advanced Age-Induced Inflammation ................................................................268

Evidence for Increased Glutamate Level in Hearing Disorders...............................268

Noise Releases Glutamate ...................................................................................268

Salicylate Activates Glutamate Receptor ............................................................269

Aminoglycoside, Cochlea Ischemia, or Trauma-Induced Release

of Glutamate ................................................................................................... 269

MicroRNAs in the Pathogenesis of Hearing Disorders ...........................................269

MicroRNAs .........................................................................................................269

Expression of MicroRNAs in the Normal Ears...................................................269

Alterations in MicroRNAs Expression in Hearing Disorders.................................. 270

Changes in the Expressions of MicroRNAs in Age-Related Hearing Disorders .....270

Mutation in MicroRNA Induces Nonsyndromic Hearing Loss (NSHL) ............ 271

Changes in the Expressions of MicroRNAs in Noise-Induced Hearing Loss .........271

Changes in the Expressions of MicroRNAs in Kanamycin-Induced Hearing

Disorders.............................................................................................................. 271

Changes in the Expressions of MicroRNAs in Damaged Auditory

Nervous System ................................................................................................... 272

Oxidative Stress Regulates the Expression of MicroRNAs in Hearing Disorders .......273

Auditory Cells ..................................................................................................... 273

Non-auditory Cells (Neurons and Non-neuronal Cells) ...................................... 273

Pro-inflammatory Cytokines Could Upregulate the Expressions of MicroRNAs

in Hearing Disorders ................................................................................................ 273

Antioxidants Could Regulate the Expressions of MicroRNAs in Hearing

Disorders ...............................................................


PRODUCT DETAILS

ISBN-13: 9781138500020
Publisher: Taylor & Francis
Publication date: April, 2019
Pages: 528
Weight: 571g
Availability: Available
Subcategories: Nutrition

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Dr. Kedar N. Prasad obtained a Masters degree in Zoology from the University of Bihar, Ranchi, India, and a Ph.D. degree in Radiation Biology from the University of Iowa, Iowa City, in 1963. He received Post-doctoral training at the Brookhaven National Laboratory, Long Island. New York, and joined the Department of Radiology at the University of Colorado Health Sciences Center where he became Professor and Director for the Center for Vitamins and Cancer Research. He has published over 250 articles in peer-reviewed journals, and authored and edited 25 books in the area of radiation biology, nutrition and cancer, and nutrition and neurological diseases particularly Alzheimer's disease and Parkinson's disease. These articles were published in highly prestigious journals such as Science, Nature, and Proceedings of the National Academic of Sciences, USA. Dr Prasad has received several honors which include: Invitation by the Nobel Prize Committee to nominate a candidate for the Nobel Prize in Medicine for 1982; The 1999 Harold Harper Lecture at the meeting of the American College of Advancement in Medicine; An award for the best review of 1998-1999 on antioxidant and cancer; and 1999-2000 on antioxidants and Parkinson's disease by the American College of Nutrition. He was a Fellow of the American College of Nutrition, and served as a President of the International Society of Nutrition and Cancer, 1992-2000. In 2017, he was invited to become the member of The Royal Society of Medicine, London. Currently, he is Chief Scientific Officer of the Engage Global.