Omega-3 Fatty Acids in Brain and Neurological Health

Front Cover

Omega-3 Fatty Acids in Brain and Neurological Health

Copyright Page

Contents

Preface

List of Contributors

Acknowledgments

1 Enhanced Longevity and Role of Omega-3 Fatty Acids

Introduction

Longevity

Food Restriction for Enhanced Longevity

Calorie Restriction for Longevity

Smoking and Reduced Longevity

Genetics, a Key Modifier of Longevity

Genetic Diseases and Longevity

Genomics

Environmental Factors and Longevity

Animal Tests and Longevity

Omega-3 Fatty Acids and Longevity

References

Further Reading

2 Molecular Gerontology: Principles and Perspectives for Interventions

Introduction

Homeostasis Versus Homeodynamics

Molecular Basis of Aging

Free Radical Theory of Aging

Protein Error Theory of Aging

From FRTA and PETA to Higher Order Theories

Genetics, Post-Genetics, and Epigenetics of Aging

Epigenetics of Aging

Aging Interventions

Gene Therapy

Manipulating the Milieu

Hormetics, Hormesis, and Hormetins

References

3 Peroxisomal Pathways, their Role in Neurodegenerative Disorders and Therapeutic Strategies

Peroxisomes

Ether Lipid Synthesis

a-oxidation

ß-oxidation

Peroxisomal Pathologies

Leukodystrophies

X-linked Adrenoleukodystrophy

Lipid and Steroid Hormone Modifications

Biological Markers of X-ALD

Therapeutic Strategies

Fatty Acids and Dietary Intervention

Hormone Replacement Therapy

Gene Therapy

Demyelination and Other Leukodystrophies

Conclusion

References

4 Unregulated Lipid Peroxidation in Neurological Dysfunction

Introduction

Lipid Oxidation Biomarkers for Neurological Dysfunction

Lipid Peroxidation Products from Linoleic Acid

Lipid Peroxidation Products from AA

Hydroxyeicosatetraenoic Acids

F2-Isoprostanes

Isofurans

Lipid Peroxidation Products from Docosahexaenoic Acid

Neuroprostanes

Neurofurans

Lipid Peroxidation-Derived Short-Chain Aldehydes

Lipid Peroxidation Products from Cholesterol

Neurological Dysfunction Associated with Lipid Peroxidation

Mechanisms of Free Radical Production in Neurological Disorders

Alzheimer’s Disease

Parkinson’s Disease

Amyotrophic Lateral Sclerosis

Stroke

Down Syndrome

Other Neurological Dysfunctions in Childhood

Therapeutic Intervention with Antioxidants for Neurological Dysfunction

References

Additional References

5 Obesity, Western Diet Intake, and Cognitive Impairment

Obesity and Cognitive Impairment

Western Diet Intake and Cognitive Impairment

Western Diet Intake and Cognitive Impairment: Underlying Neuroendocrine Mechanisms

Summary

References

6 Genetic Risk Factors for Diabetic Neuropathy

Diabetes Mellitus and Its Complications

Diabetic Neuropathy: General Characteristics

Risk Factors for Diabetic Neuropathy and pathophysiological Mechanisms

Genetic Risk Factors for Diabetic Neuropathy

Potential Use of Genetic Risk Factors in Clinical Practice

References

7 n-3 Fatty Acid-Derived Lipid Mediators against Neurological Oxidative Stress and Neuroinflammation

Overview

DHA in the Brain

EPA-Derived Lipid Mediators in the Brain

DHA-derived Lipid Mediators in the Brain

DHA-derived D-series Resolvins

DHA-derived Protectins and Neuroprotectins

Effect of EPA and DHA in Neurological Disorders

Conclusion

References

8 The Impact of Omega-3 Fatty Acids on Quality of Life

Introduction

Assessment of QoL

Current Evidence on Omega-3 Fatty Acids and QoL

Evidence from Observational Studies

Evidence from Clinical Trials

Discussion

Conclusion and Recommendations

References

9 Mammalian Fatty Acid Amides of the Brain and CNS

Introduction

Primary Fatty Acid Amides

N-Acylethanolamines (NAEs)

N-Acyl Amino Acids (NAAs)

NAGs, a Specific Class of the NAAs

N-Acyl Taurines, a Specific Class of the NAAs

Other N-Acyl Amino Acids

N-Acyldopamines

The Relevance of the Fatty Acid Amides to Neurological Disease

Acknowledgements

References

10 Low Omega-3 Fatty Acids Diet and the Impact on the Development of Visual Connections and Critical Periods of Plasticity

Introduction

Nutrition and the Impact of Omega-3 Fatty Acids on Brain Development

The Development of Visual Topographical Maps

Critical Periods for Brain Development

Role of Omega-3 on Development of Central Visual Connections

References

11 The Effects of Omega-3 Polyunsaturated Fatty Acids on Maternal and Child Mental Health

Introduction

The Role of Omega-3 Fatty Acids in Neurotransmission

DHA and Maternal Mental Health

Postpartum Depression

Omega-3 Fatty Acids in Postpartum Depression

Omega-3 Fatty Acids and Child Mental Health

Neurodevelopmental Outcomes: Infancy through Childhood

Infancy

Childhood

Childhood Developmental Disorders

Attention Deficit Hyperactivity Disorder

Childhood Depression

Autistic Spectrum Disorders

Conclusion

References

12 Pain as Modified by Polyunsaturated Fatty Acids

Introduction

Factors Involved in the Supply and Physiological Function of Fatty Acids in the Brain

Blood–Brain Barrier

Fatty Acid Transporter Protein

Fatty Acid Binding Protein

Long-Chain Fatty Acid Receptor GPR40

Toll Like Receptor 4

Involvement of Lipids, Fatty Acids, and Their Metabolites in Pain Regulation

Dietary Lipids

Omega-3 Fatty Acids

DHA

Metabolites Derived from Omega-3 Fatty Acids

Omega-6 Fatty Acids and Their Metabolites

Prostaglandins

Leukotrienes

Platelet-Activating Factor

Lysophosphatidic Acid

Future Prospects

References

13 Fish Oil Supplementation Prevents Age-Related Memory Decline: Involvement of Nuclear Hormone Receptors

Introduction

Effects of Aging on Incorporation of Docosahexaenoic Acid in Brain Phospholipids

Effects of Aging on DHA Biosynthesis

DHA is Involved in Learning and Memory

Dietary Fish Oil and Prevention of Age-Related Memory Decline

Animal Studies

Human Studies

DHA Improves Synaptic Plasticity During Aging: Involvement of Retinoid X Receptors and Peroxisome Proliferator-Activated Re...

Summary and Concluding Remarks

References

14 Role of Omega-3 Fatty Acids in Brain and Neurological Health with Special Reference to Clinical Depression

Introduction

Omega-3 Fatty Acids

Factors that Interfere with Conversion of ALA

Omega-3 to Omega-6 Ratio

Genetic Factors

Dietary and Lifestyle Factors

Saturated fat – trans-fat

Caffeine, Nicotine, Alcohol, Sugar

Stress

Co-nutrients

Status of Omega-3 Fatty Acids in Clinical Depression

Nutrient Co-Factor Deficiencies

Zinc Deficiency

Selenium Deficiency

Folic Acid Deficiency

Antioxidants

Vitamin B6, Tryptophan, and Serotonin

Omega-3 Fatty Acids

Neurological Alterations in Depression

Possible Mechanisms for Links Between Omega-3 Fatty Acids and Depression

Omega-3 Fatty Acids Affect Cell Membrane Integrity and Fluidity

Omega-3 Fatty Acids Decrease the Production of Pro-Inflammatory Cytokines

Omega-3 Fatty Acids and Hippocampal Neurogenesis

Impact of Diet on AHN

Clinical Trials Supporting the Role of Omega-3 Fatty Acids in MDD

Conversion of ALA to EPA and DHA from Flax Seed Oil

Probable Mode of Action of Flax Seed Oil in Depression

Conclusion

References

Further Reading

15 Omega-3 Fatty Acid Supplementation for Major Depression with Chronic Disease

Introduction

Omega-3 Fatty Acids

Major Depressive Disorder

Omega-3 Fatty Acids and Depression

Effects of Omega-3 Fatty Acids on Depression with Cardiovascular Disorders

Effects of Omega-3 Fatty Acids on Depression with Diabetes

Effects of Omega-3 Fatty Acids on Depression and Pregnancy

Effects of Omega-3 Fatty Acids on Depression and Old Age

Effect of Omega-3 Fatty Acids on Anxiety and Depression in Students

Summary

References

16 The Effectiveness of Fish Oil as a Treatment for ADHD

A review of the Literature

Purpose

Analyzing the Studies

Findings

The Effect of Fish Oil on the Behavioral/Physical Symptoms of ADHD

Omega 3

Omega-3 and Omega-6

Combination of Essential Fatty Acids and other Supplements

Fatty Acid Levels in Blood of Patients with ADHD

Omega 3

No Supplements were Given

Conclusion

Final Thought

References

Further Reading

17 Fatty Acids and the Aging Brain

Introduction

Physiologic Brain Aging

Structural Changes

Macro-Structural Changes

Micro-Structural Changes

Chemical Changes

Dopamine

Serotonin

Glutamate

Cognitive Changes

Changes in Attention

Changes in Memory

Changes in Orientation

Changes in Perception

Changes in Executive Control

Fatty Acids and Brain Aging

Fatty Acid Basics: An Introduction to the Biochemistry of Fatty Acids

Fatty Acid Composition of the Brain

Omega Fatty Acids

Function of Omega-3 Fatty Acids in the Brain

Neural Mechanisms

Neurogenesis

Neurotransmission

Reduction of Amyloid-ß Production

Increasing Brain-Derived Neurotrophic Factor

Vascular Mechanisms

Reduction of Inflammation

Lowering of Thrombosis

Blood Pressure Reduction

Lowering Triglyceride Levels

Sources of Omega Fatty Acids

Omega Fatty Acid Metabolism

Pathological Brain Aging

Alzheimer’s Disease

Disease Characteristics

Structural Differences from Normal Aging

Chemical Differences

Cognitive Differences

Disease Mechanisms

Vascular Dementia

Disease Characteristics

Structural Changes

Cognitive Changes

Chemical Changes

Disease Mechanisms

Mixed Dementia

Protective Effect of Omega-3 Fatty Acids against Dementia

Conclusion

References

Further Reading

18 Cerebrovascular Changes: The Role of Fat and Obesity

Introduction

Vascularization of the Brain

The Blood–Brain Barrier

Effects of a High Fat Diet and Obesity on Overall Health and Proposed Mechanisms

Clinical Studies: Vascular Changes Due to a High Fat Diet and Obesity

Animal Studies: Vascular Changes Due to a High Fat Diet and Obesity

Impact of Omega-3 Fatty Acids on Vascular Health

Conclusion

References

19 Effects of Omega-3 Fatty Acids on Alzheimer’s Disease

Introduction

Omega-3 Fatty Acids Biology in Health

Alzheimer’s Disease

Omega-3 Fatty Acid: a Role in Alzheimer’s Disease?

DHA Deficiency and Neurological Function Affected by Diabetes in Alzheimer’s Disease

Animal Models, Diabetes, and Alzheimer’s Disease

Omega-3 Fatty Acids in Prevention and Treatment of Alzheimer’s Disease

References

20 Substantia Nigra Modulation by Essential Fatty Acids

Importance of Essential Fatty Acids as Neuroprotectors During Brain Development and Aging

Substantia Nigra Vulnerability to Neurodegeneration

Substantia Nigra Dopamine Cell Populations Display Differential Vulnerability to Lesions

Repercussion of EFA Deficiency or Supplementation on Midbrain Dopaminergic Systems

Potential Mechanisms Involved in Substantia Nigra Dopamine Cell Loss Induced by EFA Dietary Restriction

Acknowledgments

References

Further Reading

21 The Role of Omega-3 Fatty Acids in Hippocampal Neurogenesis

Introduction

Adult Neurogenesis

Measurement of Neurogenesis (Markers of Proliferation)

Omega-3 PUFAs and Hippocampal Neurogenesis

Developmental Neurogenesis

Adult Hippocampal Neurogenesis

Mechanisms of Action

References

22 Imaging Brain DHA Metabolism in Vivo, in Animals, and Humans

Introduction

Quantitative Imaging of Brain DHA Metabolism in Rodents

Incorporation of Circulating PUFAs into Brain Membrane Lipids

Methods and models for determining PUFA incorporation into brain

Imaging Membrane Synthesis

Neuroplasticity with Ocular Enucleation

Brain Tumor Imaging

Upregulated DHA and AA Releasing Enzymes in an Animal Model of the Metabolic Syndrome

Neurotransmission

Human Mutations and Mouse Knockouts of iPLA2ß

Quantitative Imaging of Brain DHA Metabolism in Human Subjects

Baseline Brain DHA Incorporation

Upregulated Incorporation Coefficients in Chronic Alcoholics

Summary and Conclusions

Acknowledgments

References

23 Obesity and Migraine in Children

Introduction

Epidemiological Relationship Between Migraine and Obesity

Comorbidity

Cognitive Profile, Migraine, and Obesity

Proposed Mechanism for the Relationship Between Obesity and Migraine

Lifestyle Factors

Influence of Weight Loss on Chronic Headache in Obese People and Effects of the Preventive Treatment of Migraine on Weight ...

Conclusions

References

24 Dietary Omega-3 Sources during Pregnancy and the Developing Brain: Lessons from Studies in Rats

Introduction

ALA Supplementation and Brain Fatty Acid Composition

Long-chain Omega-3 PUFA Supplementation and Brain Fatty Acid Composition

Direct Comparison of ALA and Long-chain Omega-3 PUFA Supplementation on Brain Fatty Acid Composition

Conclusions

References

25 Omega-3 Fatty Acids and Cognitive Behavior

Introduction

Infants and Children

Maternal Supplementation

Supplementation During Infancy

Supplementation During Childhood

Young Adults

Older Adults

Epidemiological Studies: The Association Between Omega-3 PUFA Intake, Omega-3 PUFA Levels, and Cognitive Decline

RCTs: Healthy Older Adults

RCTs: Older Adults with Mild Cognitive Impairment or Alzheimer’s Disease

Conclusion

References

26 Lipids and Lipid Signaling in Drosophila Models of Neurodegenerative Diseases

Introduction

Drosophila as a Model System of Neurodegenerative Diseases

Genetic Tools for Making Neurodegenerative Disease Models in Drosophila

P-Element-Mediated Mutagenesis

UAS-GAL4-Based Gene Expression System

Reporters for Amyloid Precursor Protein .-secretase Activity in Drosophila

Representative Drosophila Models for Neurodegenerative Diseases

Effects of Lipids and Lipid Signaling on Drosophila Models of Neurodegenerative Diseases

Effects of PUFA and Cholesterol Levels on Drosophila AD Models Expressing Human Aß42

Effect of Phosphatidylethanolamine Depletion on .-secretase-Mediated APP Processing in Transgenic Drosophila

Effects of Lipid Signaling Enzyme Diacylglycerol Kinase e Inhibition on Mutant Huntingtin Toxicity

Drosophila Mutant of Very Long-Chain Acyl Coenzyme a Synthetase and Glyceryl Trioleate Oil

Lipids, TRP Channels, and Neurodegeneration in Drosophila

Points to Consider When Drosophila Models are Used for Studying the Role of Lipids

Perspective

References

27 Polyunsaturated Fatty Acids in Relation to Sleep Quality and Depression in Obstructive Sleep Apnea Hypopnea Syndrome

Introduction

OSAHS

Sleepiness

OSAHS and Associated Complications

Polyunsaturated Fatty Acids

PUFAs and Health

Depression

Link Between PUFAs and Depression in OSAHS

Sleep Quality

Link Between PUFAs and Sleep Quality in OSAHS

Conclusion

References

Further Reading

28 Omega-3 Fatty Acids in Intellectual Disability, Schizophrenia, Depression, Autism, and Attention-Deficit Hyperactivity D...

Introduction

Background

Plasma Lipids in Adults with Intellectual Disability and the Efficacy of Omega-3 Fatty Acids

Adrenoleukodystrophy and Adrenomyeloneuropathy

Fatty Acid, Lipid, and Cholesterol Levels

Plasma Lipids in Schizophrenia and the Efficacy of Omega-3 Fatty Acids

Plasma Lipids in Depressive Illness and Efficacy of Omega-3 Fatty Acids

Plasma Lipids in Autism and Efficacy of Omega-3 Fatty Acids

Plasma Lipids in ADHD and Efficacy of Omega-3 Fatty Acids

Conclusions

References

29 Effect of Omega-3 Fatty Acids on Aggression

Introduction

First Trial of Omega-3 PUFAs and Aggression in Young Adults

Effect of Omega-3 PUFAs on Aggression in Schoolchildren

Effect of Omega-3 PUFAs on Aggression in the Elderly

Effect of Omega-3 PUFAs on Aggression in Prisoners

Effect of Omega-3 PUFAs on Aggression in Patients with ADHD

Association Between Omega-3 PUFAs and Hostility in Patients with Schizophrenia

Mechanism of Action of Omega-3 PUFAs

Serotonin

Noradrenalin

Cortical-Hippocampal-Amygdala Pathway

Endocannabinoids

Brain-Derived Neurotrophic Factor

Conclusion

References

30 Multiple Sclerosis: Modification by Fish Oil

Introduction

Overview

Cellular Level of Multiple Sclerosis

Omega-3 Supplementation of MS Patients

Varying Results Amongst Researchers

Summary

Acknowledgement

References

31 Deuterium Protection of Polyunsaturated Fatty Acids against Lipid Peroxidation: A Novel Approach to Mitigating Mitochond...

Introduction

PUFAs in Mitochondrial Membranes and Oxidative Stress

Mitochondrial Dysfunction, Oxidative Stress, and PD

Isotope Protection of PUFAS Against autoxidation

Yeast Models Confirm the Non-Linear Protective Effect of D-PUFAs in vivo

Isotope Reinforcement of PUFA in Pre-Clinical PD Modeling

Pre-Clinical Efficacy

Conclusion

References

32 Obesity, Cognitive Functioning, and Dementia: A Lifespan Prospective

Introduction

Weight-Related Variables and Dementia

Prospective Studies with a Focus on Dementia

Prospective Studies Focusing on Cognitive Functioning

Weight and Cognitive Function: Role of CVD Factors

Interactions of Obesity and CVD Risk Factors

Controls and Potential Mediators

Initial Summary

MetS

Mechanisms: General

Early Influences on Relations between Obesity and Cognition

Morbid Obesity and Clinically Important Cognitive Deficit

Treatment of Overweight and Obesity

Treatment of Obesity with Omega-3 Fatty Acids

Omega-3 Fatty Acid Mechanisms for Reducing Weight Loss

Methodologies: General Issues

Measurement of Cognitive Function

Diagnosis of Dementia

Formal Definitions of Mild Cognitive Impairment

Prospective Designs

Neuroimaging Studies

Trials

Final Summary and Conclusions

References

33 Dairy Products and Cognitive Functions

Introduction

Review of the Literature

Early Cross-Sectional and Prospective Research Findings in Associations between Dairy and Cognition

Cross-Sectional Studies

Prospective Studies

Summary of These Study Findings

Focused Dairy–Cognition Studies

Cross-Sectional Studies

Randomized Controlled Trials

Discussion

Limitations of this Literature

Assessment of Cognitive Functioning

Control of Confounding Variables

Dietary Assessment

Mechanisms of Action

Epidemiological and Clinical Significance

Summary

Directions for Future Research

References

34 Obesity and Chronic Low Back Pain: A Kinematic Approach

Introduction

Quantitative Movement Analysis

Equipment

Obesity and LBP: Our Experience

Gait Analysis

Trunk Movement

Quantification of Functional Limitation

Quantification of the Effects of Osteopathic Manipulative Treatment

Conclusions

References

Further Reading

35 Fatty Acids and the Hippocampus

Introduction

Fatty Acids and Memory/Hippocampus

SFAs, Memory, and the Hippocampus – Evidence from Animal Models

Neurological Impact of Saturated Fat Consumption

BDNF

Oxidative Stress

Neuroinflammation

SFAs, Memory, and the Hippocampus – Human Data

Omega-3 Fatty Acids, Memory, and the Hippocampus – Evidence from Animal Studies

Can Omega-3 Fatty Acids Remediate Damage to the Hippocampus in Humans?

Omega-3 Fatty Acids and Depression

Omega-3 Fatty Acids and their Effect on Memory and Cognition

Conclusion on Human Data

General Conclusion: Fatty Acids and their Impact on the Hippocampus

Fatty Acids and AD

SFAs and Risk of AD

Putative Causal Basis for Link between SFAs and AD

Omega-3 Fatty Acids, Cognitive Decline, and Dementia

Global Prevalence

Matched Group Studies

Longitudinal Studies of Cognitive Decline

Cognitive Decline and Self-Report Measures of Dietary Intake

Dementia Diagnosis and Self-Report Measures of Dietary Intake

Cognitive Decline and Plasma Lipid Estimates

Dementia Diagnosis and Plasma Lipid Estimates

Prevention and Treatment Studies

Human Data – Conclusions

Omega-3 Fatty Acids, AD, and Memory Impairment – Evidence from Animal Models

General Discussion

References

Further Reading

36 Fish Oil Supplements, Contaminants, and Excessive Doses

Introduction

Mercury

Lead

Selenium

Arsenic

Cadmium

PCBs

Dichlorodiphenyltrichloroethane

Dieldrin

Conclusion

Acknowledgment

References

37 Introduction to Fish Oil Oxidation, Oxidation Prevention, and Oxidation Correction

Introduction

Oxidation Process

Oxidation Indicators

Prevention of Oxidation and Oxidative Stability

Oxidation Correction

Summary

References

Further Reading

Index