Neurons and the DHA Principle: 1st Edition (Hardback) book cover

Neurons and the DHA Principle

1st Edition

By Raymond C. Valentine, David L. Valentine

CRC Press

287 pages | 16 Color Illus. | 86 B/W Illus.

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pub: 2012-10-26
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Studies with bacteria and other systems suggest that the omega-3 fatty acid DHA confers great benefits to neurons in maximizing both speed of neural impulses and energy efficiency. Unfortunately, studies also show that DHA’s ease of oxidation damages membrane integrity. Exploring this duality, Neurons and the DHA Principle proposes a new model for the causes of neurodegeneration, in which DHA-enriched membranes of neurons become dysfunctional and energetically wasteful, triggering the premature death of neurons.

The challenge of this book is to digest how DHA acts as an essential building block of neurons while also conspiring for their assassination during aging. As the book reviews the extraordinary properties of DHA in life forms from deep-sea bacteria to human neurons, it asks:

  • Is there a trade-off between speed and efficiency of brain function enabled by DHA versus longevity or life span?
  • Has modern medicine advanced significantly in the treatment of the body but not necessarily of the brain?
  • What are the molecular explanations for the decline in brain health during the age of longevity?

A full accounting of the roles of DHA in neurons requires balancing the enormous benefits of these molecules against the risks. Introducing the dual chemical personalities of DHA from an evolutionary perspective, Neurons and the DHA Principle explores DHA from the standpoint of benefit–risk analysis, opening new perspectives for understanding how DHA functions in neurons.

Table of Contents

Section I Evolution and Essential Roles of DHA in Neurons

Nature of Neurons and Their Specialized Membranes

Some Brain Statistics

A Clean, Constant, and Protective Environment Allows Neurons to Perform at Maximum Efficiencies

Microglia Destroy Pathogens and Scavenge Cellular Debris But Have a Dangerous Side

Our Brain Computer Is an Oily Computer

Neurons Have Evolved DHA-Enriched Membranes That Play Essential Roles

The Brain as a Machine

Protecting DHA Membranes of Neurons Is One of the Secrets to the Health and Longevity of the Brain


DHA Contributes Both Benefits and Risks to Mammals



Healthy Heart

Cancer-Free Colon

Risks of DHA Including Vision Impairment


Use It or Lose It Concept of Brain Health Is Linked to DHA

Use It or Lose It Mechanism of Brain Development is a Marvel of Nature

How Many Neurons to Make a Birdsong?

Lifelong Learning Requires Synaptic Plasticity and Selective Axon Growth

Membrane Exocytosis/Endocytosis as a Means to Modulate Synaptic Strength

DHA as a Momentary Memory Molecule?


Evolution and DHA: Redefining the DHA Principle

DHA Maximizes Energy Efficiency in Human Neurons

DHA Likely Came from the Sea

Darwinian Selection of the Fittest Oils for Neurons of Different Animals

DHA Membranes in Our Brain Result from a Delicate Evolutionary Balancing Act

DHA Does Not Work Alone and Is Blended with Cholesterol and Other Lipid Structures to Maintain Energy-Efficient Neuronal Membranes

DHA Plays an Essential Role in Membrane Growth, Development, and Efficiency

Energy Limitation of an Island Environment Might Have Selected the Tiny, Yet Homo sapiens–Like Brain of Hobbit (Homo floresiensis)


Section II Benefits of DHA

DHA Is "King Omega" for Maximizing Mental Speed

DHA’s Twisty Tail Speeds Sensory and Mental Processes

Sensory Perception Depends on Extreme Membrane Motion Contributed by DHA

Membrane Asymmetry Enabling Leaflet-Specific Motion Is Important in Neurons

DHA Speeds Up Rates of Cycling of Synaptic Vesicles Important in Fast-Firing Neurons


DHA Improves Energy Efficiency in Neurons

A Significant Amount of Brain Energy Is Used to Maintain Neurons Ready to Fire Day and Night

Tiny Synaptic Vesicles Show How Energy Efficiency in DHA-Enriched Membranes Is Improved by Using Cholesterol to Plug Proton Leaks

"Use It or Waste It" Concept of Brain Energy Efficiency

Myelination Also Increases Speed and Energy Efficiency

Why Is DHA Favored over EPA in Human Neurons?


Wild Conformational Dynamics of DHA Might Save Energy by Sealing Stretch-Induced Defects as Fast as They Occur in Membranes

Mechanical Stress Model of Sperm Tails

Dynamic Space-Filling Conformations of DHA

Axon Membranes Are Subject to Stretching during Normal Growth and during Brain Trauma

Turgor (Osmotic Pressure) Is Likely Required for Stretch Growth of Axons

Stretch-Induced Defects Likely Occur in Membranes of Cilia, Red Blood Cells, and Heart Muscle Cells


Section III: Risks of DHA

Lipid Whisker Model and Water-Wire Theory of Energy Uncoupling in Neurons

Lipid Whisker Model Applied to Neurons

Oxidatively Truncated Phospholipids Act Directly as Signaling Molecules for Activating Phagocytosis

Lipid Whiskers Might Generate Energy-Uncoupling Water-Wires


Neurons Boost Their Energy State by Using Powerful Antioxidant Systems to Protect Their Membranes against Damage

The Brain Hoards High Levels of Vitamin C: Case History of Scurvy

Mechanisms for Concentrating Ascorbate in Neurons Are Known in Detail

Brief Chemistry of Ascorbate as an Antioxidant

Vitamin E, a Membrane-Based Antioxidant, Works Synergistically with Vitamin C to Protect Neural Membranes


Oxygen-Dependent Damage (Lipid Peroxidation) of DHA Membranes of Neurons Is Inevitable and Requires Novel Mechanisms for Long-Term Protection

Rapid Turnover of Rhodopsin Disks

Rhodopsin and Other Proteins Are Targets of Oxidative Damage

Sperm Tail Membranes as Surrogates for Axons

Slow Turnover of DHA in the Brain Was Not Expected

Sifting through the Lipofuscin "Garbage Pile" for Clues to Neuron Aging

Sequestration of Metals Known to Promote DHA Oxidation Is Vital for Neuron Health

Hypothesis Number 1: Myelin Forms a Protective Shield against Oxidative Damage to Axons

Hypothesis Number 2: Taurine as an Antioxidant

Hypothesis Number 3: Melatonin as an Antioxidant


Section IV Revised Membrane Pacemaker Theory of Aging and Age-dependent Diseases

Revised Mitochondrial Theory of Aging and Brain Span

Nature of Mitochondria as Powerhouses for the Cell

Mitochondrial DNA Is a Circular Miniature Chromosome Encoding 37 Genes Essential for Energy Production

Data Derived from Mutator Mice Have Led to a New Theory of Aging in Which Energy Stress Replaces Oxidative Stress as the Primary Cause of Aging

Humans with Mutator Genes Display Symptoms of Premature Neurodegeneration before Symptoms of Aging

Selective Targeting of DHA Away from Mitochondrial Membranes as a Secret to a Long Human Brain Span


Development of Dual Energy Pacemaker Theory of Aging: Role of the Membrane

Energy Uncoupling and the Importance of the Membrane as Critical Gatekeeper for Conserving or Wasting Energy

Insects Dramatically Increase Life Span by Dietary Manipulation and Optimal Tuning of Polyunsaturated Fatty Acid Synthesis

First Lesson from Hummingbirds: DHA Turbocharges Mitochondria

Second Lesson from Hummingbirds: The Hardest Working Mitochondria Wear Out Fastest

Third Lesson from Hummingbirds: "Energy-Stressed" Mitochondria Accumulate Mutations Faster

Lessons from Small Mammals: Less DHA, Longer Life Span

Membrane Pacemaker Model Is Consistent with the Bowhead Whale as Longest Lived Mammal


Membranes and Cancer

Retinoblastoma Occurs in a Tissue with the Highest Levels of DHA in the Body

Heavy Trafficking of DHA within the Developing Brain Might Potentiate Brain Tumors in Children

DHA Is a Major Building Block for Sperm Membranes: Is There an Increased Risk of Cancer in the Testes?

Correlation between High Levels of DHA in Blood and Aggressive Prostate Cancer

Chemotherapy Patients Are Advised Not to Take Fish Oil Supplements

Asymmetrical Phospholipids as Possible Promoters of Breast Cancer

Does Generalized Cellular Energy Deficiency Govern Rates of Cancer-Causing Nuclear Mutations?


Section V DHA Links Aging and Neurodegeneration

Parkinson’s Disease

Parkinsonian Chemicals Likely Act by Accelerating Energy-Oxidative Stresses via a Chain Reaction Mechanism

MPTP: A Potent Neurotoxin

A Closer Look at MPTP as a Mitochondrial Energy Poison versus an Oxidative Threat

Parkinsonian Neurons Are Likely Predisposed to Energy Stress Making Them Extremely Sensitive to Chemicals in the Environment

Neurotoxic Damage to Parkinsonian Neurons May Recruit Hyperactive Microglia Causing More Damage

Mitochondrial Mutations as a Genetic Pacemaker for Age-Dependent Parkinson’s

Dual Energy-Pacemaker Model of Age-Dependent Parkinson’s Disease


Prion Diseases

A Spongy-Brain Disease in the Highlands of New Guinea

Prion Replication Is an Amazing Process and Depends on Dysfunctional Protein Processing

Does Energy Play a Role in How Prions Pick Their First Neuron Target?

Prion-Infected Neurons Might Be Subjected to Membrane Energy Uncoupling Caused by the Prion

Numerous Pinpoint Brain Lesions Caused by Prions May Spread as the Result of Microglial-Mediated Neuron Damage

A Protective Gene against Kuru Found in Survivors of New Guinea Epidemic


Brain Trauma–Induced Dementia

High Rates of Brain Trauma in Sports and Combat

Axon Stretch Model of Trauma-Triggered Alzheimer’s

Inflammation Model

Suicide Peptide Model

Energy Stress Caused by DHA Might Link the Three Models


Alzheimer’s Disease

An Individual Energy-Stressed or Damaged Neuron Might Generate a Focal Point for Alzheimer’s

Spreading from a Focal Point Might Be Caused by an Inflammatory Cascade Linking DHA and Alzheimer’s Disease

Blocking Neuron Death in a Mouse Model of Alzheimer’s Disease by Knockout of a Key Signaling Receptor on Microglia

Is the Toxic Peptide Tau the Long-Awaited Infective Agent Causing the Spread of Alzheimer’s Disease?

DHA Oxidation Products in Cerebrospinal Fluid Help Validate the DHA Principle

Demyelination Occurring during Aging Might Expose DHA-Enriched Membranes of Axons of White Matter to Lipid Peroxidation

Neuron Membranes Seem to Require Extraordinary Protection: The FOXO Story

Effect of Insulin on Symptoms of Alzheimer’s Disease

Working Model of Alzheimer’s as a Membrane Disease


About the Authors

Raymond C. Valentine is a Visiting Scholar at University of California, Santa Barbara and Professor Emeritus at the University of California, Davis. David L. Valentine is a Professor of Earth Science at the University of California, Santa Barbara.

Subject Categories

BISAC Subject Codes/Headings:
MEDICAL / Nutrition
SCIENCE / Life Sciences / Biology / Molecular Biology
SCIENCE / Life Sciences / Neuroscience