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Excitotoxicity in ASD Autism ONE Conference May 2008 Anju Usman, M. D. True Health Medical Center Naperville, Illinois.

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Presentation on theme: "Excitotoxicity in ASD Autism ONE Conference May 2008 Anju Usman, M. D. True Health Medical Center Naperville, Illinois."— Presentation transcript:

1 Excitotoxicity in ASD Autism ONE Conference May 2008 Anju Usman, M. D. True Health Medical Center Naperville, Illinois

2 Our kids carry the burdens of a physically and emotionally toxic world! Genetic predispositions Mother’s Burdens Heavy Metals Environmental Pollutants Electromagnetic Fields Excess Sensory Input Stress/Internal Conflicts Dietary Factors Microbial/Biofilm Immune/Inflammatory Burden

3 Metabolic Imprint of the Body Burdens Oxidative Stress Oxidative Stress –Thimerosal (Mercury), Arsenic, Lead, Aluminum Overload –Depletion of Antioxidants, Glutathione, and Metallothionein Mitochondrial Dysfunction Mitochondrial Dysfunction –Elevated Oxidative Stress Markers –Abnormal Ammonia, Lactic Acid, Pyruvate Acid –Low Carnitine Impaired Detoxification Impaired Detoxification –Methylation Defects –Sulfation Defects –Cysteine Deficiency –Glutathione Deficiency (GSH) Gastrointestinal Dysfunction Gastrointestinal Dysfunction –Dysbiosis (Yeast, Bad Bacteria, Parasites, Virus…) –Malabsorption –Maldigestion (enzyme deficiency, IgG food sensitivities, urinary peptides) –Autistic Enterocolitis/ Lymphonodular Hyperplasia Immune System Dysregulation/Inflammation Immune System Dysregulation/Inflammation –Proinflammatory Cytokines –Microglial Activation –Th1/ Th2 skewing –Decreased Natural Killer Cell Activity –Increased Autoimmune Markers

4 What exactly is causing my child’s symptoms that are being diagnosed as autism? Verbal stims/ Perseverative/ Repetitive/ Has language but not motivated to use it/ Rigid behaviors/ Scripted language/ Constipated/Anxiety/OCD/ Motor Tics Differential Diagnosis Chronic Infections StrepVirusesGlutamateAmmoniaMercuryAluminumLeadPesticides Vaccine Adjuvants (viral fragments) All of these lead to Excitotoxicity in the brain!!!!

5 Excitotoxicity is the pathological process by which nerve cells are damaged and killed by glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are overactivated. Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. Excitotoxicity is the pathological process by which nerve cells are damaged and killed by glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are overactivated. Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.nerve cellsreceptorsglutamateNMDA receptorAMPA receptorNMDAkainic acidcalciumcellphospholipases endonucleasesproteasescalpaincytoskeletonmembranenerve cellsreceptorsglutamateNMDA receptorAMPA receptorNMDAkainic acidcalciumcellphospholipases endonucleasesproteasescalpaincytoskeletonmembrane The toxicity of glutamate was then observed by D. R. Lucas and J. P. Newhouse in 1957 when the feeding of monosodium glutamate to newborn mice destroyed the neurons in the inner layers of the retina. Later, in 1969, John Olney discovered the phenomenon wasn't restricted to the retina but occurred throughout the brain and coined the term excitotoxicity. The toxicity of glutamate was then observed by D. R. Lucas and J. P. Newhouse in 1957 when the feeding of monosodium glutamate to newborn mice destroyed the neurons in the inner layers of the retina. Later, in 1969, John Olney discovered the phenomenon wasn't restricted to the retina but occurred throughout the brain and coined the term excitotoxicity.D. R. LucasJ. P. Newhousemonosodium glutamatemiceretinaJohn OlneybrainD. R. LucasJ. P. Newhousemonosodium glutamatemiceretinaJohn Olneybrain Excitotoxicity can occur from substances produced within the body (endogenous excitotoxins). Glutamate is a prime example of an excitotoxin in the brain, and it is paradoxically also the major excitatory neurotransmitter in the mammalian CNS. Excitotoxicity can occur from substances produced within the body (endogenous excitotoxins). Glutamate is a prime example of an excitotoxin in the brain, and it is paradoxically also the major excitatory neurotransmitter in the mammalian CNS.endogenous One of the damaging results of excess calcium in the cytosol is the opening of the mitochondrial permeability transition pore, a pore in the membranes of mitochondria that opens when the organelles absorb too much calcium. Opening of the pore may cause mitochondria to swell and release proteins that can lead to apoptosis. The pore can also cause mitochondria to release more calcium. One of the damaging results of excess calcium in the cytosol is the opening of the mitochondrial permeability transition pore, a pore in the membranes of mitochondria that opens when the organelles absorb too much calcium. Opening of the pore may cause mitochondria to swell and release proteins that can lead to apoptosis. The pore can also cause mitochondria to release more calcium. mitochondrial permeability transition mitochondria apoptosis mitochondrial permeability transition mitochondria apoptosis

6 Excitotoxicity (Excess excitatory neurotransmission) –Causes brain atrophy –Neuronal loss –Brain more susceptible to Toxins –Neuroinflammation –Proinflammatory Cytokines Increased TNF alpha Increased TNF alpha Increased IL-1, High IL-6 Increased IL-1, High IL-6 –Upregulation of Brain Immune System Microglial Activation Microglial Activation –“Sickness Behavior” Russell Blaylock, “Vaccines, Neurodevelopment, and ASD” Russell Blaylock, “Vaccines, Neurodevelopment, and ASD”

7 Sickness Behavior What does if feel like to be chronically sick???? RestlessIrritable Disturbed Sleep Fatigue Difficulty Thinking… Russell Blaylock, “Vaccines, Depression and Neurodegeneration”

8 Microglial Activation RESTING MICROGLIA Support brain growth Support brain growth Protect brain cells Protect brain cells ACTIVATED MICROGLIA Ready to fight foreign invader Ready to fight foreign invader Inflammatory cytokines Free radicals Lipid Peroxidation Glutamate production Quinolinic acid

9 Autism and the Immune system Autism and the Immune system It remains unclear how and when microglia and astroglia become activated in the brains of patients with autism. Glial responses in autism may be part of intrinsic, or primary, reactions that result from disturbances in glial function or neuronal-glial interactions during brain development. They may also be secondary, resulting from unknown disturbances (such as infections or toxins) in prenatal or postnatal CNS development. Nevertheless, the findings of this study highlight the existence of neuroimmunological processes in autism and provide a setting for new research approaches to the diagnosis and treatment of this debilitating neurological disorder. It remains unclear how and when microglia and astroglia become activated in the brains of patients with autism. Glial responses in autism may be part of intrinsic, or primary, reactions that result from disturbances in glial function or neuronal-glial interactions during brain development. They may also be secondary, resulting from unknown disturbances (such as infections or toxins) in prenatal or postnatal CNS development. Nevertheless, the findings of this study highlight the existence of neuroimmunological processes in autism and provide a setting for new research approaches to the diagnosis and treatment of this debilitating neurological disorder. Slides A and C, from patients with autism, show an increase in neuron-supporting cells called glia. This increase is likely a sign of a neuroimmunological response to the disorder. © 2005 Pardo et al. Slides A and C, from patients with autism, show an increase in neuron-supporting cells called glia. This increase is likely a sign of a neuroimmunological response to the disorder. © 2005 Pardo et al.

10 Microglial Activation should only last a few days. If insults persist…. it can last years Vaccine induced microglial activation, especially when numerous vaccines are given simultaneously, can last YEARS. Russell Blaylock, “Vaccines, Depression and Neurodegeneration”

11 Activated Immune System Infection/Toxin Acidosis CalciumGlutamateAmmonia Inflammation ImmuneActivation Once the system is turned on or activated the cycle persists. This persistent immune upregulation creates autoimmunity in the body and microglial activation in the brain.

12 The principle excitatory receptor, the N-Methyl-D-Aspartate (NMDA) receptor, and its associated calcium (Ca2+) permeable ion channel are activated by glutamate and co-agonist glycine.

13 Calcium Homeostasis Calcium is one of the most important 2 nd messengers Calcium is one of the most important 2 nd messengers Tightly regulated by stores, pumps and buffers Tightly regulated by stores, pumps and buffers VGCC- Voltage Gated Calcium Channels VGCC- Voltage Gated Calcium Channels –L type (LTCC) CNS CNS Immune system Immune system GI tract GI tract Inner Ear Inner Ear Symptoms of abnormal Calcium homeostasis Symptoms of abnormal Calcium homeostasis –Excitation/Hyperactivity/Stimming Behaviors –Muscle Tone /Coordination Issues –GI Motility –Visual Disturbances –Auditory Sensitivity –History of Kidney Stones, Fractures, Excess Oxalates “Central Role of Voltage Gated Calcium Channels and Intracellular Calcium Homeostasis in ASD” N.B.S. Lozac Feb. 2007

14 Effects of Abnormal Calcium Homeostasis Neurotransmitters Neurotransmitters –Decreased Nicotinic Acetylcholine, Increased Glutamate, Decreased Dopamine Endocrine/Hormone Endocrine/Hormone –Impaired Insulin, Oxytocin, Vasopressin, Melatonin, Cortisol, IGF1 Immune/Inflammatory Immune/Inflammatory –Microglial activation, Th2 skewing, Proinflammatory cytokines –Viral induced immune suppression Vascular/Smooth Muscle Vascular/Smooth Muscle Gastrointestinal Gastrointestinal –Increased Gastric Acid, Abnormal Motility, Increased Insulin release, Phopholipase C Membranes Membranes –Decreased Cholesterol Mitochondria Mitochondria –Stores excess Calcium which inhibits Oxidative Phosphorylation  Poor Energy Production and Elevation of ROS (reactive oxygen species) Oxidative Stress Oxidative Stress –Cross Talk between Calcium and ROS(peroxide, nitrous oxide, superoxide) –Cause Damage to Endothelial Cells Motor – Sensory Motor – Sensory “Central Role of Voltage Gated Calcium Channels and Intracellular Calcium Homeostasis in ASD” N.B.S. Lozac Feb. 2007

15 Potential Biomarkers of Abnormal Calcium Homeostasis Decreased Antioxidant Status Decreased Antioxidant Status Elevated Pro-oxidants Elevated Pro-oxidants Elevated extracellular and intracellular Ca+2 Elevated extracellular and intracellular Ca+2 Elevated ionized Calcium, elevated hair Ca+2 Elevated ionized Calcium, elevated hair Ca+2 Elevated osteocalcin Elevated osteocalcin Elevated Alkaline Phosphatase (isoenzyme-bone) Elevated Alkaline Phosphatase (isoenzyme-bone) High CO2 High CO2 Low Vitamin D Low Vitamin D Elevated urinary oxalates Elevated urinary oxalates Hypoglycemia Hypoglycemia

16 Treating Excitotoxicity 1. Avoid Excitotoxins/Dietary Modifications 2. Use Glutamate Modulators 3. Maximize Antioxidants 4. Eliminate Toxins 5. Treat and Identify Chronic Infections 6. Alkalinize the Gut 7. Limit excess Calcium, Ammonia, and Glutamate 8. Support ATP production and the Mitochondria 9. Provide adequate Methylation support 10. Natural Anti-Inflammatories

17 Avoid Excitotoxins Substances that cause an excess of excitatory neurotransmission in the brain. The excess excitation may lead to microglial activation and chronic inflammation in the brain. Substances that cause an excess of excitatory neurotransmission in the brain. The excess excitation may lead to microglial activation and chronic inflammation in the brain. Chronic Infections Chronic Infections Pesticides Pesticides Heavy Metals Heavy Metals Glutamate/MSG Glutamate/MSG Sulfites/Hydrogen Sulfide Sulfites/Hydrogen Sulfide Nitrites Nitrites Propionates Propionates Benzoates Benzoates

18 Excitotoxic Triggers Glutamate Glutamate –Monosodium Glutamate (MSG) –Hydrolyzed Protein –Modified Food Starch –Natural Flavors –Peas, Mushrooms, Tomatoes –Parmesan Cheese –Excess Protein Excess Calcium Excess Calcium Excess Ammonia Excess Ammonia Excess Sulfur/Sulfite/ Excess Sulfur/Sulfite/ Hydrogen Sulfide Hydrogen Sulfide Lead Lead Aluminum Aluminum Mercury Mercury EMF EMF

19 Glutamate Modulators –Magnesium –Antioxidants –Leucine, Isoleucine, and Lysine –Pycnogenol –Rosemary, Lemon Balm –Skull Cap, Chamomile –Taurine –GABA –L- Theanine –Vitamin K –Gingko biloba –Silymarin –Flavinoids (curcumin, quercetin) –Namenda (drug) –Minocycline (antibiotic)

20 Anti-oxidants Excessive free radical formation/inadequate antioxidant status is a major pathway of excitotoxic damage. Excessive free radical formation/inadequate antioxidant status is a major pathway of excitotoxic damage. Various free radicals (ROS), including superoxide, peroxide, hydroxyl and peroxynitrite, are generated through the inflammatory prostaglandin/leukotriene pathways triggered by excitotoxic intracellular calcium excess. Various free radicals (ROS), including superoxide, peroxide, hydroxyl and peroxynitrite, are generated through the inflammatory prostaglandin/leukotriene pathways triggered by excitotoxic intracellular calcium excess. These free radicals can damage or destroy virtually every cellular biomolecule: proteins, fatty acids, phospholipids, glycoproteins, even DNA, leading to cell injury or death. These free radicals can damage or destroy virtually every cellular biomolecule: proteins, fatty acids, phospholipids, glycoproteins, even DNA, leading to cell injury or death. Although vitamins C and E are the two most important nutritional antioxidants. Brain cells may concentrate C to levels 100 times higher than blood levels. Although vitamins C and E are the two most important nutritional antioxidants. Brain cells may concentrate C to levels 100 times higher than blood levels. Vitamin C, E, alpha-lipoic acid, Co Q10 and NADH act as a team. Vitamin C, E, alpha-lipoic acid, Co Q10 and NADH act as a team. One of the many ways excitotoxins damage neurons is to prevent the intracellular formation of glutathione. One of the many ways excitotoxins damage neurons is to prevent the intracellular formation of glutathione. The combination of E and Idebenone may provided complete antioxidant neuronal protection in spite of extremely low glutathione levels caused by glutamate excitotoxic action. The combination of E and Idebenone may provided complete antioxidant neuronal protection in spite of extremely low glutathione levels caused by glutamate excitotoxic action.

21 Antioxidant Phytonutrients

22 Infections produce triggers that cause excitotoxicity! Viruses Viruses Bacteria- especially Strep and Clostridia……….. Bacteria- especially Strep and Clostridia……….. Yeast Yeast Parasites Parasites Lyme Lyme Mycoplasma Mycoplasma Chronic infections need to be effectively treated to stop persistent activation of the immune system. Infections are common in ASD patients. These infections are often resistant to treatment. Persistent organisms often produce biofilm. Toxic Foci include tonsils, adenoids, ears, lymph nodes, GI tract… Some infections produce excess ammonia.

23 Keys to treating chronic infections Identify type and location Identify type and location Aggressively clean up the gut Aggressively clean up the gut Breakdown biofilm (diet, nutrition, and alkalinize) Breakdown biofilm (diet, nutrition, and alkalinize) Treat infections with homeopathics and natural agents if possible Treat infections with homeopathics and natural agents if possible Be patient Be patient Keep ammonia levels low Keep ammonia levels low Have a plan to manage die off Have a plan to manage die off

24 Ammonia If severely elevated rule out urea cycle disorder If severely elevated rule out urea cycle disorder If mildly elevated consider possible causes If mildly elevated consider possible causes –Dysbiosis –Recent infection –Liver stress –High protein diet or supplements –BH4 (tetrahydrobiopterin deficiency) Symptoms Symptoms –Irritability, aggression, headache, head-banging, hyperactivity Treatment Strategies Treatment Strategies –Avoid excess protein in diet –Activated Charcoal, Fiber, Pectin, Zeolites –Yucca / Aloe –BH4 –Butyrate –Ammonia RNA (Yasko)

25 Vitamin K Protocol (Catherine Tamaro) Vit K Vit K Vit D Vit D Vit A Vit A DHA DHA Bicarbonate Bicarbonate Melatonin Melatonin Avoid Calcium supplementation Avoid Calcium supplementation This Protocol is good for addressing excess extracellular calcium. excess extracellular calcium.

26 The Mitochondria is the powerhouse of each cell. Inside the Mitochondria, the Citric Acid Cycle produces ATP. ATP is the fuel for the cell. ATP provides energy.

27 ATP (adenosine triphosphate) ATP is the energy "currency" of all cells, including neurons. Each neuron must produce all the ATP it needs - there is no welfare state to take care of needy but helpless neurons. ATP is the energy "currency" of all cells, including neurons. Each neuron must produce all the ATP it needs - there is no welfare state to take care of needy but helpless neurons. ATP is needed to pump glutamate out of the synaptic gap into either the glutamate-secreting neuron or into astrocytes. ATP is needed by atrocytes to convert glutamate into glutamine. ATP is needed to pump glutamate out of the synaptic gap into either the glutamate-secreting neuron or into astrocytes. ATP is needed by atrocytes to convert glutamate into glutamine. ATP is needed by sodium and calcium pumps to get excess sodium and calcium back out of the neuron after neuron firing. ATP is needed to maintain neuron resting electric potential, which in turn maintains the magnesium-block of the glutamate-NMDA receptor. With enough ATP bioenergy, neurons can keep glutamate and aspartate in their proper role as neurotransmitters. ATP is needed by sodium and calcium pumps to get excess sodium and calcium back out of the neuron after neuron firing. ATP is needed to maintain neuron resting electric potential, which in turn maintains the magnesium-block of the glutamate-NMDA receptor. With enough ATP bioenergy, neurons can keep glutamate and aspartate in their proper role as neurotransmitters. Neurons produce ATP by "burning" glucose (blood sugar) through 3 interlocking cellular cycles: the glycolytic and Krebs' cycles, and the electron transport chain, with most of the ATP coming from the electron transport chain. Neurons produce ATP by "burning" glucose (blood sugar) through 3 interlocking cellular cycles: the glycolytic and Krebs' cycles, and the electron transport chain, with most of the ATP coming from the electron transport chain. Various enzyme assemblies produce ATP from glucose through these 3 cycles, with the Krebs' cycle and electron transport chain occurring inside mitochondria, the power plants of the cell. Various enzyme assemblies produce ATP from glucose through these 3 cycles, with the Krebs' cycle and electron transport chain occurring inside mitochondria, the power plants of the cell.

28 Mitochondrial Support and ATP Production The various enzyme assemblies require vitamins B1, B2, B3 (NADH), B5, biotin, and alpha-lipoic acid as coenzymes. The various enzyme assemblies require vitamins B1, B2, B3 (NADH), B5, biotin, and alpha-lipoic acid as coenzymes. Magnesium is also required by most of the glycolytic and Krebs' cycle enzymes as a mineral co-factor. Magnesium is also required by most of the glycolytic and Krebs' cycle enzymes as a mineral co-factor. The electron transport chain especially relies on NADH and Co Q10 to generate the bulk of the cell's ATP. The electron transport chain especially relies on NADH and Co Q10 to generate the bulk of the cell's ATP. NADHCo Q10NADHCo Q10 Idebenone is a synthetic variant of Co Q10 that may work better than CoQ10, especially in low oxygen conditions, to keep ATP production going in the electron transport chain. Idebenone is a synthetic variant of Co Q10 that may work better than CoQ10, especially in low oxygen conditions, to keep ATP production going in the electron transport chain. Idebenone Acetyl l-carnitine may regenerate aging mitochondria that are suffering from a lifetime of accumulated free radical damage. Acetyl l-carnitine may regenerate aging mitochondria that are suffering from a lifetime of accumulated free radical damage. Potential Krebs Cycle Support Potential Krebs Cycle Support –Malic Acid –Fumaric Acid –Succinic Acid –Alpha Keto Glutarate (careful)

29 Text Methylation & Beyond...

30 Methylation Support and Glutathione Production Combination of Pfeiffer Treatment Center, Defeat Autism Now, and Yasko Approach Combination of Pfeiffer Treatment Center, Defeat Autism Now, and Yasko Approach Understanding the underlying genetics is helpful in difficult cases Understanding the underlying genetics is helpful in difficult cases CBS status, MTHFR, MTR, MTRR and COMT are helpful for understanding methylation issues CBS status, MTHFR, MTR, MTRR and COMT are helpful for understanding methylation issues Amino Acid testing and Cysteine, Glutathione, and Sulfate levels define picture. Amino Acid testing and Cysteine, Glutathione, and Sulfate levels define picture. Undermethylation, COMT (- -), High Histamine Undermethylation, COMT (- -), High Histamine Overmethylation, COMT (++), Low Histamine Overmethylation, COMT (++), Low Histamine

31 COMT - - Treatment approach DAN Methyl B12 TMGDMGP5P Folinic Acid Creatine L Carnitine Glutathione(GSH) Yasko Intrinsic B12 NucleotidesMethylfolateBH4GSH(limited) Emphasis on Methyl Donors: Methyl B12 SAMeQuercetinGingkoCurcumin Green Tea Phosphatidyl Serine PfeifferMethionine/SAMe Methyl B12 CalciumMagnesiumP5P/B6Zinc Vitamin C Phosphatidyl Serine Avoid Methyl Consumers: FolatesDMAE Cyano B12 Niacinamide

32 COMT + + Treatment approach DAN Methyl B12 TMGDMGP5P Folinic Acid Creatine L Carnitine Glutathione Yasko Intrinsic B12 NucleotidesMethylfolate Hydroxy B12 Cyano B12 BH4 Limit Methyl Donors: Methyl B12 QuercetinGingkoCurcumin Green Tea Phosphatidyl Serine Pfeiffer Folic Acid Cyano B12 Niacinamide P5P, Vit B6 Zinc, Mb, Mn Vitamin C DMAE/Phosphatidyl Choline Avoid Methyl Donors: Methyl B12 Methyl Folate MethionineSAMe

33 Natural Anti-inflammatory Agents The excitotoxic process does much of its damage through initiating excessive production of prostaglandins, thromboxanes, and leukotrienes. The excitotoxic process does much of its damage through initiating excessive production of prostaglandins, thromboxanes, and leukotrienes. Inflammatory prostaglandins and thromboxanes are produced by the action of cyclooxygenase 2 (COX-2) on arachidonic acid liberated from cell membranes Leukotrienes are produced by lipoxygenases (LOX). Inflammatory prostaglandins and thromboxanes are produced by the action of cyclooxygenase 2 (COX-2) on arachidonic acid liberated from cell membranes Leukotrienes are produced by lipoxygenases (LOX). Trans-resveratrol is a powerful natural inhibitor of both COX-2 and LOX Trans-resveratrol is a powerful natural inhibitor of both COX-2 and LOX Quercetin is a powerful LOX-inhibitor. Quercetin is a powerful LOX-inhibitor. Boswellia is a COX-2 and LOX-inhibitor. Boswellia is a COX-2 and LOX-inhibitor. Curcumin (turmeric extract), rosemary extract, green tea extract, ginger and oregano are also effective natural COX-2 inhibitors. Curcumin (turmeric extract), rosemary extract, green tea extract, ginger and oregano are also effective natural COX-2 inhibitors. Glutathione is also a LOX- inhibitor and potent Antioxidant. Glutathione is also a LOX- inhibitor and potent Antioxidant. Antioxidants have anti-inflammatory effects. Antioxidants have anti-inflammatory effects. Fat Soluble Vitamins A,D,E, and K. Fat Soluble Vitamins A,D,E, and K. Essential Fatty Acids, Omega 3 especially DHA. Essential Fatty Acids, Omega 3 especially DHA.

34 Keys to Excess Glutamate Removal Avoid dietary Excitotoxins will help to minimize synaptic glutamate/aspartate. Avoid dietary Excitotoxins will help to minimize synaptic glutamate/aspartate. Keep neuronal ATP energy maximal by support of the Mitochondria Keep neuronal ATP energy maximal by support of the Mitochondria –Avoidance of hypoglycemia –ATP Production will assist glutamate pumps to remove excess extracellular glutamate –ATP Production will assist glutamate pumps to remove excess extracellular glutamate –ATP promotes astrocyte conversion of glutamate to glutamine, the chief glutamate removal mechanism. –ATP promotes astrocyte conversion of glutamate to glutamine, the chief glutamate removal mechanism. –ATP will also keep calcium and sodium pumps active, preventing excessive intracellular calcium build-up. Intracellular calcium excess itself promotes renewed secretion of glutamate into synapses, in a positive feedback vicious cycle. Maintain function of the enzyme "glutamatic acid dehydrogenase (GAD)" Maintain function of the enzyme "glutamatic acid dehydrogenase (GAD)" –Helps neurons dispose of excess glutamate by converting glutamate to alpha- ketoglutarate, a Krebs' cycle fuel. –Glutamate dehydrogenase is activated by NADH, it promotes breakdown of glutamate. –Treat toxins that inhibit GAD, like aluminum, lead, mercury, and pesticides… Consume plenty of antioxidants which aid in removal of synaptic glutamate. Consume plenty of antioxidants which aid in removal of synaptic glutamate. –Avoid use of glutamine. Glutamine easily passes the blood-brain barrier and enters the astrocytes and neurons, where it can be converted to glutamate. –Avoid use of glutamine. Glutamine easily passes the blood-brain barrier and enters the astrocytes and neurons, where it can be converted to glutamate.

35 p5p Succinic Acid Krebs/Mitochondria GABA Amino acids p5p Proline Decarboxylase (brain, kidney) p5p NAD NADP NADH NADPH AKG Krebs/Mitochondria Glutamic acid dehydrogenase Mg ADP ATP Glutamine Glutamic Acid NH3/ Ammonia GABA/Glutamate Cycle

36 Additional Sources of Information Healing the New Childhood Epidemics (Autism, ADHD, Asthma and Allergies, Ken Bock MD Healing the New Childhood Epidemics (Autism, ADHD, Asthma and Allergies, Ken Bock MD Autism: Effective Biomedical Treatments, Pangborn and Baker Autism: Effective Biomedical Treatments, Pangborn and Baker Changing the Course of Autism, Jepson and Johnson Changing the Course of Autism, Jepson and Johnson Excitotoxins, the Taste that Kills, Russell Blaylock MD Excitotoxins, the Taste that Kills, Russell Blaylock MD Envisioning a Brighter Future, Patty Lemur Envisioning a Brighter Future, Patty Lemur Websites Websites –www.autism.com –www.safeminds.org –www.autismone.org –www.generationrescue.org –www.vaccineawareness.org –www.ddr.org

37 Thank You and Never Give Up Hope.


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