Dr Usman Power Point

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Published on January 10, 2008

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Journey to Recovery… Finding a Safe Path to Heavy Metal Detoxification:  Journey to Recovery… Finding a Safe Path to Heavy Metal Detoxification Anju I. Usman, M.D. Autism One Conference Chicago, Illinois May 2006 Autism is a MEDICAL disorder, not a MENTAL disorder. Most Autistic patients have environmentally-induced toxicity. Autism is therefore preventable, reversible, and treatable. :  Autism is a MEDICAL disorder, not a MENTAL disorder. Most Autistic patients have environmentally-induced toxicity. Autism is therefore preventable, reversible, and treatable. Predispostion:  Predispostion Genetics Male Gender HLA- Type (C4B null allele) Family History of Autoimmunity (Hornig, 2004) Allergies, asthma, diabetes, arthritis, colitis, celiac, thyroiditis Single Nucleotide Polymorphisms (SNP) MTHFr- Methylene Tetrahydrofolate Reductase COMT- Catecholamine O- Methyltransferase MTRR/MTR- Methionine Synthase and Methionine Synthase Reductase (Deth, 2004) BHMT – Betaine Homocysteine Methyltransferase TCII – Transcobalamin GABRB3- Gaba Receptor ADA - Adenosine Deaminase Mutant UBE3A (ubiquitin ligase) Inciting Factors:  Inciting Factors Environmental Toxicity Mom Amalgams Fish consumption (tuna) Rhogam Vaccines (Yazbak, 2004) Environmental and Occupational Exposures Heavy Metals Persistent Organic Pollutants (POPs) Pharmaceuticals (oral contraceptives, antibiotics) Comorbid Conditions Immune Issues Inciting Factors :  Inciting Factors Toxicity Patient Thimerosal Exposure From Vaccines Mercury Exposure Other Amalgams, Food, Coal burning plants, Refinery (Palmer 2005)… Other Heavy Metals Lead, Antimony, Arsenic, Aluminum Environmental Toxins Persistent Organic Pollutants (POPs) Dietary Sources Pharmaceuticals Comorbid Conditions Gastrointestinal Permeability Immune Issues Inciting Factors:  Inciting Factors Biologic and Immunologic Triggers Virus (Measles, Rubella, Polio, CMV…) (Viral Model for Developmental Disorders- Borna Virus, Hornig 1999) Measles (Wakefield, Singh) HHV6 CMV Bacteria (Clostridia, Streptococcus, Gram Negative Rods…) Fungal (Yeast [candida], Mold) Other (Lymes) Some of these biologic agents produce neurotoxins. Our body may produce antibodies to these agents. These antibodies may cross react with our own tissue creating an autoimmune reaction. This is called molecular mimicry Mercury (Hg) Toxicity :  Mercury (Hg) Toxicity Potent Neurotoxin Exposure is common Seafood, Amalgams, Air, Thimerosal (vaccines) Symptoms of toxicity similar to autistic symptoms (Bernard, 2000) Glutathione is the primary mechanism of excretion Autistics have low glutathione levels (James, 2004) Tylenol and Antibiotics decrease excretion of mercury Baby teeth study found 3x higher Hg in autism vs. control (Adams, 2005) Baby hair study found very low levels of Hg in autism vs. control consistent with poor excretion of Hg (Holmes, 2003) On DMSA challenge testing autistics excreted 5.8x higher Hg than controls (Bradstreet, 2003) Recovery is possible with Mercury Detox (Holmes,Buttar) Slide8:  There is no safe level of mercury, and no one has actually shown that there is a safe level. Dr. Lars Friberg Chief Adviser to the WHO (World Health Organization) on mercury safety Lead (Pb) Toxicity:  Lead (Pb) Toxicity Most common toxic heavy metal Pervasive in the environment EPA #1 priority hazardous substance Exposure mostly from food and exhaust Deficiency of protein, Ca, Zinc, Se, Fe, or Vit E cause increase Pb absorption. Fluoride increases Pb absorption Children absorb Pb more readily than adults Safe threshold changed from 80ug/dl to 10ug/dl Children with blood levels of 10 mcg/dl, the upper limit of the “safe range”, have IQs 7.5 points below those of kids whose blood Pb levels are 0-1mcg/dl Combination with Hg increases toxicity exponentially Chelation generally approved for Acute Lead Toxicity (blood Lead > 45ug/dl) POPs (persistant organic pollutants):  POPs (persistant organic pollutants) Phthalates, Pesticides, Herbicides, Bisphenol A, PCB, PCBD, DDT… Difficult to detox, Stored in Fat indefinitely Endocrine Disruptors – Substances that may at tiny doses interfere with hormonal signals that regulate human organs, development, metabolism, and other functions. Low Dose Hypothesis – No safe levels (pp trillion have biologic effects) Damage DNA (affect DNA methylation) – 90% inherited Harm developing nervous system Carcinogenic Gender bending chemicals Alter brain structure, neurochemistry, behavior, reproduction and immune response in animals Damage sperm and cause genital malformations Precocious Puberty Allergies, Asthma, Diabetes, Heart Disease, Thyroid disease Used in flexible plastics, cosmetics, perfumes, food Found in breast milk, cord blood, and infants Slide11:    In harm's way: toxic threats to child development. Stein J, Schettler T, Wallinga D, Valenti M. J Dev Behav Pediatr. 2002 Feb;23(1 Suppl):S13-22 The developing brain is uniquely susceptible to permanent impairment by exposure to environmental substances during time windows of vulnerability. Lead, mercury, and polychlorinated biphenyls (PCBs) have been extensively studied and found to impair development at levels of exposure currently experienced by significant portions of the general population. High-dose exposures to each of these chemicals cause catastrophic developmental effects. More recent research has revealed toxicity at progressively lower exposures, illustrating a "declining threshold of harm" commonly observed with improved understanding of developmental toxicants. For lead, mercury, and PCBs, recent studies reveal that background-population exposures contribute to a wide variety of problems, including impairments in attention, memory, learning, social behavior, and IQ. Unfortunately, for most chemicals there is little data with which to evaluate potential risks to neurodevelopment. Among the 3000 chemicals produced in highest volume (over 1 million lbs/yr), only 12 have been adequately tested for their effects on the developing brain. This is a matter of concern because the fetus and child are exposed to untold numbers, quantities, and combinations of substances whose safety has not been established. PMID: 11875286 [PubMed - indexed for MEDLINE] Brick Township – Autism Cluster:  Brick Township – Autism Cluster Kreiling J, Stephens R, Reinisch C. 2005. A mixture of environmental contaminants increases cAMP-dependent protein kinase in Spisula embryos. Environmental Toxicology and Pharmacology 19 (2005) 9-18 19:9-18. Abstract: Using the surf clam embryo, we investigated the effects of the combination of bromoform, chloroform, and tetrachloroethylene, three pollutants found in high concentrations in the municipal water supply in Brick, New Jersey. Exposure produced an increase in an isoform of the regulatory subunit (RII) of cAMP-dependent protein kinase, demonstrated by confocal microscopy and western blotting. Embryos showed an increase in RII where the primordial gill and ciliated velar epithelium are innervated. This increase correlated with increased ciliary activity, indicating a corresponding rise in the catalytic subunit. Treatment resulted in decreased threonine phosphorylation of actin. There was no effect on neurotransmitters or receptors of the serotonergic-dopaminergic nervous system. These effects occurred only with the ternary mixture. No significant effect was seen with individual or paired components. This is the first report showing that bromoform, chloroform, and tetrachloroethylene act synergistically to alter a key regulator of neuronal development. Aftermath of Genetics, Toxins, and Biologic Triggers … the Metabolic Train Wreck :  Aftermath of Genetics, Toxins, and Biologic Triggers … the Metabolic Train Wreck Heavy Metal Overload Elevated levels of Mercury, Lead, Aluminum… Mineral Deficiencies (Zinc, Magnesium, Selenium…) Oxidative Stress (James 2004, Salomon 2004) Impaired Methylation Sulfation Abnormalities Impaired Detoxification Depletion of antioxidants, vitamin cofactors Depletion of reduced Glutathione Gastrointestinal Dysfunction Immune System Dysregulation Gastrointestinal Dysfunction:  Gastrointestinal Dysfunction Maldigestion Decreased activity of digestive enzymes (Horvath,1999. Buie, 2004) High levels of opioid peptides found in urine of autistics. (Reichelt, 1997) IgG Food Sensitivities Malabsorption Fat Soluble Vitamin Deficiencies Essential Fatty Acid Deficiencies Essential Amino Acid Deficiencies Dysbiosis Dysbiosis or altered bowel flora (Rossenau, 2004) Clostridial overgrowth (Sandler, 2002) Persistent measles virus (Wakefield) Inflammation Autistic Enterocolitis, Lymphoid Hyperplasia (Wakefield,1998) Increased intestinal permeability leading to food sensitivities and autoimmunity (Vodjani, 2002) Increased pro-inflammatory cytokines – LP, TNF alpha, IFN gamma (Ashwood, 2004) Proinflammatory response to dietary proteins (Jyonuchi, 2004) Immune Dysregulation:  Immune Dysregulation Th1 and Th2 skewing Abnormal cell-mediated immunity Abnormal T-cell subsets, decreased NK cells, abnormal cytokines, Th2 skewing (Zimmerman, 1998) Decreased secretory IgA Pro-inflammatory Factors in the Gut (Ashwood, Jyonuchi) Pro-inflammatory Cytokines in the Brain MCP-1, TGF beta-1 (Vargas, 2005) Abnormal EEG, Seizure activity Microglial Activation Increased Autoimmunity Autoantibodies to neural antigens (Connolly, 1999) Mylein basic protein and Neuronal Axonal Filament Protein Antibodies (Gupta, 1996 /Singh, 1997) Basic Strategy:  Basic Strategy History and Physical Examination Laboratory Testing Clean Up Environmental Controls Dietary Interventions Address Gastrointestinal Health Foundational Nutrients Treat underlying Immune Issues and Inflammation Support Detoxification Pathways Heavy Metal Detoxification History - Heavy Metals :  History - Heavy Metals Mercury (Hg) Oral ulcers, tremors, failure to thrive, abdominal distention, red lips, red finger tips, increased salivation, pale stools, watery stools, detached, disconnected, disinterested, poor eye contact Lead (Pb) Allergies, ADD symptoms, constipation, coordination, delinquency, dyslexia, headaches, hyperactivity, hypothyroidism, insomnia, irritability, mood swings, muscle weakness, dyspraxia, low muscle tone, visual and auditory processing issues, pica Aluminum (Al) Anemia, poor appetite, odd behaviors, constipation, dry mouth, dry skin, fatigue, hyperactivity, poor memory, numbness, weak upper body muscles Mineral interactions and symptoms:  Mineral interactions and symptoms Zinc (Zn) Deficiency can cause immune, language, attention/ focus issues Magnesium (Mg) Deficiency can cause hyperactivity, anxiety, muscle spasms, enuresis Reduces Aluminum, Antagonizes Calcium Calcium (Ca) Excess leads to hyperexcitability Deficiency leads to poor bone mineralization, rigidity in muscles Reduces Lead and Aluminum Molybdenum (Mb) Deficiency leads to yeast and sulfation issues Reduces Tungsten and Copper Copper (Cu) Excess can cause erratic behavior, hyperactivity, poor focus, yeast issues Reduces Zinc and Molybdenum Laboratory Analysis:  Laboratory Analysis CBC Comprehensive Metabolic Panel Serum Copper Plasma Zinc Ceruloplasmin Hair Analysis Ammonia Intracellular Minerals and Metals Essential Fatty Acids Amino Acids Plasma cysteine, sulfate, rGSH Urine Organic Acids Stool Microbiology Stool Mycology Stool Parasitology Immune Markers Immunoglobulin Levels T lymphocyte Panel Natural Killer Cell Activity PANDA’s Profile Anti MBP Ab Anti NAFP Ab IgG Food Ab Panel Vaccine Titers Viral Titers Urinary Peptides Hormone Studies Neurotransmitter Levels Genomics – SNPs Urine/ Fecal Toxic Metals Urinary Porphyrins (future) Clean up the Child’s Environment:  Clean up the Child’s Environment Use natural, biodegradable and perfume free detergents and cleaning agents, do not dry clean clothes. Avoid chlorine: use water filters, limit pool and hot tubs. Wear 100% cotton clothes, avoid flame retardant materials (antimony). Use fluoride-free toothpaste (tin,titanium). Avoid playing on pressure treated wood (arsenic). Eliminate exposure to Mercury and thimerosal products. Use an air purifier, especially in the bedroom. Avoid prolonged exposure to batteries (light up shoes). No plastic furniture (polyvinyl chloride). Use aluminum-free baking powder, deodorant. Do not cook in aluminum foil or drink from aluminum cans. Avoid use of herbicides or pesticides, on lawns, garden, or home. Use natural shampoos, soaps, and make-up (lipstick-Pb, foundation-Bi). Clean up the Child’s Diet:  Clean up the Child’s Diet Casein-free/Gluten-free/Soy-free Diet Trial for 3-6 months. Avoid sugar and refined starch, high fiber diet, maximize antioxidants, cruciferous veggies, turmeric, garlic… Limit processed and preserved foods; organic is best. Avoid excitotoxins (ex. Caffeine, MSG, NutraSweet, red/yellow food dyes, nitrites, sulfites, glutamates, preservatives). Limit intake of phenolics (apples, grapes, strawberries). Limit sources of Copper (chocolate, shellfish, tap water, artificial food dyes). Drink plenty of filtered water. Never microwave in plastics or Styrofoam, do not store food in plastic or foil, or cook on Teflon coated pans. Eliminate seafood. Begin meals with raw fruits and veggies. Add good fats (olive, coconut, flax). Avoid hydrogenated and trans fats. Buy hormone-free, antibiotic-free, organic meat and eggs. Limit Genetically Modified Foods (GMO). Add fermented foods (coconut kefir, cabbage, goat milk yogurt) Excitotoxins - Glutamate:  Excitotoxins - Glutamate Glutamates Monosodium Glutamate (MSG) Hydrolyzed Protein Modified Food Starch Natural Flavors Peas, Mushrooms, Tomatoes Parmesan Cheese Protein Anti-Glutamates Pycnogenol Rosemary Chamomile Lemon Balm GABA L- Theanine Namenda (drug) Excitotoxins = Substances that cause an excess of excitatory neurotransmission in the brain. If inhibitory neurotransmission is lacking, the excess excitation may lead to neuronal death. Neuronal death leads to chronic inflammation in the brain. Clean up the Child’s Gut:  Clean up the Child’s Gut Daily bowel movements are a goal. Add digestive enzymes with meals. Start high potency probiotics (acidophilus and bifidus). Start treatment for dysbiosis depending on symptoms and labs. If persistent symptoms: Eliminate disaccharides from diet for 3-6 months Specific Carbohydrate Diet Consider referral to knowledgeable GI specialist Consider trial of IV Secretin Add natural anti-inflammatory agents. Keep close eye on gut during any detox regimen. Foundational Nutrients:  Foundational Nutrients Antioxidants (Vit A, C, E, Se, CoQ10) Vitamin B6/P5P, B-complex Minerals (Zinc, Magnesium, Molybdenum…) Omega 3 EFA (Cod liver oil) Methyl B12, Folinic Acid Epsom Salts Baths Probiotics Slide25:  Children with ASD have poor detoxification mechanisms. Children with ASD do not excrete heavy metals, such as Mercury, effectively. Heavy metal toxicity causes neurologic, immunologic, gastrointestinal, and psychiatric abnormalities. When looking for heavy metal overload, what you find is the tip of the iceberg. Even on challenge testing it may take months for a child to start excreting heavy metals, such as mercury. Suspicion of heavy metal toxicity is based on symptoms. Initial laboratory evidence is often unconvincing. Lab Work-up Options for Heavy Metal Toxicity:  Lab Work-up Options for Heavy Metal Toxicity Hair Analysis Intracellular Minerals and Toxic Metals Detoxification Markers Glutathione, Cysteine, and Sulfate Levels Urine or Fecal Toxic Metals - provoked Urinary Porphyrins Evaluation of Heavy Metal Toxicity:  Evaluation of Heavy Metal Toxicity Provocative Testing is often unconvincing in ASD due to impaired detoxification. Urine Toxics, Fecal Toxics, and Hair Analysis show excretion of toxic metals. We have no way to determine total body burden. RBC Blood testing is a poor measure of chronic heavy metal burden. However, blood may show acute exposure. There are no standards for diagnosing chronic toxicity. There are no tests to determine body burden of metals. Lead is a bone seeker and can only be measured in blood 12 hrs after exposure, therefore blood Pb is not an adequate indicator of chronic toxicity. Mercury has an affinity for fatty tissue and a developing brain, and is very rarely seen in blood. Urinary porphyrin testing – promising. Treat underlying Nutritional and Biochemical Imbalances :  Treat underlying Nutritional and Biochemical Imbalances Anti-viral, Anti-parasitic, Anti-bacterial agents Targeted Amino Acids Essential Fatty Acids Omega 6 Omega 3 Immune Modulators IVIG, oral immunoglobulins, transfer factor, colostrum, lauricidin, alpha and beta glycans, sterols, LDN (low dose Naltrexone) Anti-inflammatory Agents Antihistamines, Singulair, Actos, Namenda Curcumin, Boswellia, Green Tea Support Detoxification Pathways:  Support Detoxification Pathways Methylation Sulfation Glycine Conjugation Taurine Conjugation Glutathione Conjugation Acetylation Glucuronidation Methylation :  Methylation Trimethylglycine Dimethylglycine S-adenosyl Methionine Methionine NADH Vitamin B2 Active Folates (folinic, methylTHF) Methylcobalamin (methyl B12) Creatine, CoQ10 Sulfation:  Sulfation Magnesium Sulfate (Epsom Salts) Molybdenum, Biotin Vitamin B1, Allithiamine (TTFD) Vitamin C N- Acetyl Cysteine (NAC) Reduced Glutathione (GSH) Glucosamine Sulfate, Chondroitan Sulfate Glutathione Conjugation:  Glutathione Conjugation TMG, Folinic, Methyl B12 Glutathione precursors N- Acetyl Cysteine Glycine Vitamin C, Vitamin E, Selenium, Zinc, Metallothionein, Alpha Lipoic Acid Reduced L-Glutathione transdermal, oral, intranasal, nebulized, suppository, lipoceutical, intravenous preparations Support Detoxification Pathways continued:  Support Detoxification Pathways continued Amino Acid Conjugation Glycine, DMG, TMG Taurine (always give with Magnesium) Glucuronidation Calcium d-glucarate Acetylation N-Acetyl Cysteine N-Acetyl Glucosamine Coenzyme A Heavy Metal Detox Options:  Heavy Metal Detox Options Pharmaceutical Chelators Clathrating agents TTFD/Allithiamine Glutathione Alpha Lipoic Acid N-Acetyl Cysteine Metallothionein Promotion Methylcobalamin Injections Herbals- garlic, cilantro, chlorella, spirulina RNA Therapy Homeopathics Far infra-red Sauna Heavy Metal Detox General Guidelines :  Heavy Metal Detox General Guidelines Support Emunctories Liver, Kidney, Lymphatics, Skin, Lungs Organ Support Liver, Kidney, Pancreas, Adrenal… Regular bowel movements Adequate hydration Antioxidants Extra Minerals Probiotics Consider prophylactic antifungals Chronic Constipation:  Chronic Constipation Check KUB xray to rule out impaction Increase fiber and fluids Soluble Fiber Insoluble Fiber Optimize vitamin C, buffered Add magnesium citrate or milk of magnesia Smooth-Move tea (Traditional Medicinals) – brew strong, give 1-2 tablespoons at bedtime Olive Oil daily or short course of Castor Oil If peristalsis is an issue, consider Bethanecol If overall tone is an issue, consider Creatine If persistent, suspect lead and aluminum toxicity, consider homeopathic remedies Die Off or Detox Reactions:  Die Off or Detox Reactions Symptoms Sleep disruption, waking between 3-5 am Irritability, Aggression, Behavioral Issues May resemble yeast flare-up Increased stimming Loose stools, frequent urination Diaper rashes, Skin rashes Fever Treatment Approach Activated charcoal and/or Alka Seltzer Gold Decrease supplement doses by ½ for 1-2 weeks, then increase dose slowly Milk Thistle at bedtime or other Liver Tonifiers If lasts longer than one week, notify physician Pharmaceutical Chelation:  Pharmaceutical Chelation Chelators- DMSA, DMPS, EDTA Bind a free metal ion into a ring structure thereby neutralizing its reactive state, the bond between chelator and heavy metal is considered irreversible. Chelators have varying affinities for different heavy metals. Do not cross Blood Brain Barrier. Heavy Metal/Chelator Complex is excreted thru kidney and liver thereby placing a burden on these organs. Side effects include abnormal kidney and liver functions, leukopenia, mineral depletion, gut dysbiosis, rashes, nausea, and fatigue. Stevens-Johnson’s rare possibility. Monitor cbc, liver, kidney, electrolytes, mineral stores, and GI status during process Pharmaceutical Chelators:  Pharmaceutical Chelators DMSA (dimercaptosuccinic acid) Good affinity for mercury and lead Excellent safety record Treat gut before starting Monitor cbc, liver and kidney function Causes Zinc depletion Oral Protocols Newer Transdermal Protocols ALA (alpha lipoic acid) Antioxidant, Regenerates Glutathione, Donates Sulfur Not for initial use, or if severe dysbiosis Potential for crossing blood brain barrier Oral Transdermal Pharmaceutical Chelators:  Pharmaceutical Chelators EDTA (ethylenediaminetetraacetic acid) Low affinity for Mercury, good affinity for Lead, Aluminum, and Copper CaNa2 EDTA FDA approved for Lead Toxicity, only chelator proven to improve IQ MgNa2 EDTA when given IV is used predominantly for arteriosclerosis, may cause fatal hypocalcemia if given rapidly Pulls Lead from bone, DMSA does not Preparations: Oral Transdermal Intravenous Other (ionized, lipoceutical) Suppository Pharmaceutical Chelators:  Pharmaceutical Chelators DMPS (dimercaptopropanesulfonic acid) Excellent chelator of Mercury, poor affinity for Lead U.S. FDA approved for prescription compounding Excretion is predominantly thru kidney Transdermal DMPS Dr. Rashid Buttar Protocol Oral 50% absorbed, may cause GI distress Suppository Intravenous Heavy Metal Detox Options:  Heavy Metal Detox Options Clathrating Agents Trap heavy metal into a colloidal mesh, rendering the heavy metal innocuous. Many are found naturally, ex. Chlorella and Spirulina. Affinity is very strong, therefore agents can become contaminated with heavy metals easily. May help detox POPs. Heavy Metal Detox Options:  Heavy Metal Detox Options TTFD/Allithiamine (thiamine tetrahydofurfuryl disulfide) Active form of Vitamin B1 Supports methylation and sulfation pathways Supports ATP production in Krebs Cycle Increases Arsenic excretion Decreased ATEC scores in autistics (Lonsdale, 2003) Transdermal preparations Side effects – foul odor when sweating (skunk smell) Heavy Metal Detox Options:  Heavy Metal Detox Options Methylcobalamin(B12) Injections Helps pivotal step in the methylation cycle. Bypasses impairments along folate pathway. Methylates Dopamine-4 Receptor. Shown to help cognitive ability, abstract thinking, attention, focus, awareness, language, behavior, OCD, anxiety, ….(Neubrander, 2004). Highly concentrated, injected subcutaneous in gluteal tissue, slow release, painless, no toxicity associated with high dose vitamin B12. No test for methylB12 deficiency. Side effects – increased energy, hyperactivity, agitation, detox reaction. Heavy Metal Detox Options:  Heavy Metal Detox Options Far Infra-Red Sauna Deep penetration of heat Increases core temperature Enhances circulation, lymphatic flow, and natural release of stored toxins Increases release of toxins thru sweat, liver, and kidney Helpful for detox of POPs (persistent organic pollutants) Protocol Additional Sources of Information:  Additional Sources of Information “Autism, A Novel Form of Mercury Poisoning”, Bernard, et al., 2000 (www.safeminds.org and autism.org) Children with Starving Brains, Jaquelyn McCandless MD Special Diets for Special Kids, Lisa Lewis Evidence of Harm, David Kirby Websites www.autismresearchinstitute.org www.safeminds.org www.autismone.org www.generationrescue.org www.vaccineawareness.com www.ddr.org Thank You and Good Luck on your Journey :  Thank You and Good Luck on your Journey

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