NUTRIENT POWER NATURAL HEALING FOR MENTAL DISORDERS APRIL 26, 2014 William J. Walsh, Ph.D. Walsh Research Institute Naperville, IL

Walsh Research Institute  Nonprofit organization  Expertise in behavior disorders, ADHD, autism, depression, schizophrenia, bipolar disorder, and Alzheimers  International physician training  Research

Clinical Experience William J. Walsh, Ph.D.  10,000 Behavior  5,600 ADHD  3,500 Schizophrenia & Bipolar  3,200 Depression  6,500 Autism

Massive Chemistry Database  Laboratory testing of 30,000 mental health patients and controls.  More than 3 million chemical test results for patients diagnosed with schizophrenia, depression, ADHD, depression, autism, etc.  More than 2 million medical history factors for these populations.

Database Findings Striking blood/urine chemistry differences between mental illness populations and the rest of society. Walsh WJ (2012). Nutrient Power. Skyhorse Publishing, New York, NY. Crayton JW, Walsh WJ (2007). J Trace Elements Med Biol.21:17-21.

High-Incidence Imbalances in Mental Disorders Methylation Disorder Zinc Deficiency Copper Overload Folate Deficiency or Overload Pyrrole Disorder Toxic-Metal Overload EPA, DHA, and/or AA Deficiency These factors have a powerful impact on synthesis of neurotransmitters and regulation of receptor activity.

Frequent Questions From Mainstream Medicine 1. How could vitamins & minerals possibly help a patient with a serious mental illness? 2. Don’t you really need a powerful drug to get the job done?

The Power of Nutrients 1. Neurotransmitter synthesis 2. Epigenetic regulation of gene expression 3. Reuptake processes at synapses 4. Antioxidant Protection 

The Brain Is a Chemical Factory  Serotonin, dopamine, and other NT’s are synthesized in the brain.  The raw materials for NT synthesis are nutrients: vitamins, minerals, and amino acids.  A genetic or epigenetic imbalance in a nutrient needed for NT synthesis or regulation can result in serious mental problems.

Serotonin Synthesis

Norepinephrine Synthesis

Dopamine Synthesis

GABA Synthesis

Pyrrole Disorder  Double deficiency of B-6 and Zinc  Reduced Serotonin, Dopamine, GABA  Depletion of GSH, MT, Cys, SOD, Catalase  Supplements of B-6 and zinc can normalize pyrrole levels, often resulting in elimination of symptoms and the need for psychiatric medication.

The Three Musketeers of Antioxidant Protection in the Brain Glutathione: First line of defense, Metallothionein: Nature’s back-up system, Selenium: Speeds up the process.

Methylation and Mental Health  Methyl is a dominant factor in epigenetic processes,  The methyl/folate ratio has a powerful impact on neurotransmitter activity at synapses,  More than 60% of anxiety, depression and psychosis patients exhibit a serious methylation imbalance.

Epigenetics  >20,000 genes in every cell’s DNA, each capable of producing a specific protein,  Liver, skin, brain, and other tissues require a unique combination of proteins,  During gestation, methyl “bookmarks” attach to DNA to regulate gene expression in each tissue,  Environmental insults at any age can alter gene bookmarks and produce mental disorders and other disease conditions.

Histones – Support Structures for the Fragile DNA  Composed of 8 linear proteins twisted together like a ball of yarn,  Originally believed to serve only as structural support for DNA packaging,  Later found to inhibit or promote gene expression, depending on chemical reactions at histone tails.

Gene Expression Requires Uncoiling of DNA  Gene expression involves direct interaction of RNA polymerase and transcription factors with DNA. These large molecules cannot gain access to DNA/histone regions that are densely compacted,  The gentle attachment of DNA to histones involves electrostatic attraction – DNA is a weak acid and histones are mild bases (pH above 7.0),  Acetylation decreases histone pH, causing uncoiling of DNA; methylation increases histone pH, increasing DNA/Histone compaction.

Methyl-Acetyl Competition  Competition between acetyl and methyl groups often determines whether genes are expressed or silenced,  Acetyl bookmarks promote gene expression,  Methyl bookmarks inhibit expression,  Nutrient therapy can change methyl/acetyl ratios and adjust production of enzymes that control serotonin and dopamine neurotransmission rates.

Reuptake Transport Proteins  Primary determinant of neurotransmitter activity at serotonin & dopamine receptors – concentrations of serotonin and dopamine are less important,  Transmembrane proteins that remove neurotransmitters from the synapse (reuptake) like a vacuum cleaner inhaling dust particles,  Formed by gene expression: the number depends on methyl/acetyl competition at specific DNA regions.

Enzymes Dominate the Methyl-Acetyl Competition  Acetyl-Coenzyme A and SAMe are the donors of acetyl and methyl, respectively – but their concentrations in brain cells are relatively unimportant.  Acetylases, deacetylases, methylases and demethylases dominate attachment or removal of acetyl or methyl groups.  Epigenetic nutrient therapy for adjustment of serotonin or dopamine activity concentrates on the enzymes.  Example: B-3 inhibits a major deacetylase inhibitor, thus increasing expression of SERT, DAT transporters and reducing serotonin and dopamine neurotransmission.

Epigenetic Insights Into Nutrient Therapy  Niacin, niacinamide, and SAH act as dopamine reuptake promoters,  Methionine and SAMe are serotonin reuptake inhibitors,  Folates reduce synaptic activity at serotonin, dopamine, and norepinephrine receptors,  Zinc and glutathione increase NMDA activity,  Many nutrients influence neurotransmitter activity and brain function.

Folate Considerations  Folic Acid, folinic acid, and/or L-methylfolate elevate SAMe/SAH in undermethylated persons.  However, folates also increase gene expression of SERT transport proteins, resulting in reduced serotonin neurotransmission.  Most undermethylated depressives with low- serotonin activity are intolerant to folates..

Epigenetic Disorders Triggered by an Environmental Insult  Abnormal methylation and oxidative overload  Environmental insult  Cases of sudden onset after normalcy  Persistence of condition after onset  A multitude of characteristic symptoms .

Epigenetic Model of Autism  In-utero undermethylation results in weak protection against oxidative stress.  Autism Onset: Environmental insults cause collapse of oxidative protection, resulting in deviant gene regulation marks (epigenetics).  After onset, autism can persist a lifetime since DNA bookmarks survive cell division.

Walsh Theory of Schizophrenia  Methyl imbalances or oxidative stress produce deviant bookmarks during gestation, resulting in weakened protection against oxidative insults,  Mental Breakdown – Triggered by emotional or physical stresses that overwhelm oxidative protectors & produce deviant DNA bookmarks,  SZ disorder doesn’t “go away” since the deviant marks survive cell divisions.

Mounting Evidence of an Epigenetic Gene-Regulation Disorder  Schizophrenia  Bipolar Disorder  Post-Traumatic Stress Disorder  Antisocial Personality Disorder  Paraphilias  Autism  OCD

WRI Bipolar Research W. Walsh and R. DeVito  Manic phase involves excessive neuron firing throughout the brain,  Assumption: High neuron firing caused by reduced ion gradients and threshold voltages throughout the brain,  Leading suspects: (a) Low ATP production at mitochondria; (b) poor glial cell regulation of ion gradients and cell voltages.

Mainstream Psychiatry Misconceptions  Depression regarded as a single entity with variations along a central theme. Treatment of choice -- SSRI antidepressants to elevate serotonin activity at synapses.  Schizophrenia regarded as a single entity, with variations along a central theme. Treatment of choice -- Atypical antipsychotic medications.

Chemical Classification of Depression  My large depression database has identified five high-incidence biotypes,  The biotypes represent very different disorders, each with unique neurotransmitter imbalances and symptoms,  Separate treatment approach needed for each biotype.

SSRI Antidepressants  Increase serotonin activity in brain -- Generally effective for undermethylated and pyrrole- disorder depressives (53%),  Can cause suicidal & homicidal ideation in low- folate depressives, especially young males.  Inexpensive blood tests can identify persons who must avoid SSRI antidepressants.

Nutrient Therapy Outcomes - Separate nutrient therapies developed for each depression biotype, - Outcome studies reveal 80% of patients report treatment effectiveness & ability to reduce or eliminate medication.

Porphyria Homocysteinuria Drug Induced Schizophrenia Cerebral Allergy Thyroid Deficiency Other Forms of Schizophrenia

Schizophrenia Biotypes  Overmethyation: Classic paranoid schizophrenia; Auditory hallucinations, paranoia, high anxiety.  Undermethylation: Delusional beliefs, catatonic tendencies, OCD behaviors.  Pyrrole Disorder: Combination of hallucinations and delusions; severe anxiety and mood swings. NOTE: All biotypes involve oxidative overload.

Biochemical Treatment of Schizophrenia  Therapy using vitamins, minerals, amino acids, and other chemicals that are natural to the body (drug-free),  Separate treatment approach for each biotype.  85% of families report major improvements, reduced dependence on medication, and lessened side effects.

Advanced Treatments for Addictions and OCD  Focus on increasing glutamate activity at NMDA receptors, without increasing glutamate activity at other receptors: D-Serine D-Cycloserine N-Methylglycine (Sarcosine) Glycine

Biochemical Individuality  Humans exhibit great diversity in blood and brain chemistry.  Because of genetics and epigenetics, most people are deficient in several nutrients and overloaded in others.

Nutrient Deficiencies that Impair Brain Function  Zinc  Methionine  Folic Acid  Vitamins B-6 and B-12  Niacin/Niacinamide  DHA, EPA, AA (essential fatty acids)  Antioxidants: Se, GSH, Vitamins C & E, etc.  Magnesium

Nutrient Overloads that Impair Brain Function  Copper  Folic Acid  Iron  Methionine, SAMe  Toxics: Lead, Mercury, Cadmium, etc. NOTE: Multiple vitamin-mineral supplements are usually ineffective and can cause harm.

Individualized Nutrient Therapy  Medical history and review of symptoms,  Special blood/urine lab tests,  Diagnosis of chemical imbalances,  Prescribed nutrient program aimed at normalizing brain chemistry.

Key Laboratory Tests for Mental Health Populations  Plasma Zinc  Serum Copper  Serum Ceruloplasmin  Whole-Blood Histamine  Serum Folate  Urine Pyrroles  Serum Homocysteine  Vitamin D  SAMe/SAH Ratio

Nutrient Therapy Examples Undermethylation: SAMe, methionine, zinc, calcium, inositol, serine, magnesium, vitamins A, B-6, C, D, and E. Excess Dopamine Activity: Folic acid, B-12, niacinamide, zinc, manganese, DMAE, vitamins A, C, and E. Copper Overload: Zinc, molybdenum, vitamins B-6, C and E, MT-Promotion formulation. Pyrrole Disorder: Vitamin B-6, zinc, biotin

Treatment Outcomes: Compliant Assaultive Subjects

High-Incidence Chemical Imbalances in ADHD  Elevated Cu (68%)  Insufficient ceruloplasmin (92%)  Zinc depletion (96%)  Methylation disorder (55%)  Pyrrole Disorder (30%)  Malabsorption (11%)

Summary  Biochemical imbalances are exhibited by most persons with a mental disorder.  These imbalances can adversely impact neurotransmitter synthesis & regulation.  Most families report improvement, following nutrient therapy to normalize chemistry.  The emerging science of epigenetics is leading to vastly improved natural therapies.

Pfeiffer’s Law “For every drug that benefits a patient, there are natural substances that can produce the same effect”. Carl C. Pfeiffer, MD, PhD

THANK YOU! Bill Walsh, PhD Walsh Research Institute