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03/20/03John L. Kucera, MD Autism – A Primary-Care Biomedical Perspective.

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Presentation on theme: "03/20/03John L. Kucera, MD Autism – A Primary-Care Biomedical Perspective."— Presentation transcript:

1 03/20/03John L. Kucera, MD Autism – A Primary-Care Biomedical Perspective

2 03/20/03John L. Kucera, MD Autism – A Primary-Care Biomedical Perspective Family Medicine Practice Family Medicine Practice Preventive / Nutritional Medicine Focus Preventive / Nutritional Medicine Focus Toxic Metals Issue–Lead in Paints, Gasoline, bullets, pottery, waterpipes, batteries Toxic Metals Issue–Lead in Paints, Gasoline, bullets, pottery, waterpipes, batteries Focus on Lead poisoning by physicians, especially pediatricians Focus on Lead poisoning by physicians, especially pediatricians Lead—possible cause of autism (Cohen. American Journal of Diseases of Children, 1976) Lead—possible cause of autism (Cohen. American Journal of Diseases of Children, 1976) Focus on Lead poisoning by physicians, especially pediatriciansFocus on Lead poisoning by physicians, especially pediatricians

3 03/20/03John L. Kucera, MD Autism – A Primary-Care Biomedical Perspective Toxicity of Mercury in Some Adults Toxicity of Mercury in Some Adults – Amalgam fillings—mercury, tin, etc. – Fish—pregnancy – Largely ignored by physicians, dentists and public health officials Potential Mercury Toxicity of Some Vaccines Potential Mercury Toxicity of Some Vaccines – Thimerosal – Aluminum, formaldehyde – Synergistic Toxicity?

4 03/20/03John L. Kucera, MD Toxicity of Mercury “Methyl Mercury exposure is a widespread and persistent problem in the environment and may cause neurological problems in 60,000 children born in the U.S. each year.” --National Academy of Science (USA, 7/2000) “Methyl Mercury exposure is a widespread and persistent problem in the environment and may cause neurological problems in 60,000 children born in the U.S. each year.” --National Academy of Science (USA, 7/2000)

5 03/20/03John L. Kucera, MD “Autism Spectrum Disorder” Not one disorder, but a group of disorders Not one disorder, but a group of disorders Vary widely in presentation; similarities exist Vary widely in presentation; similarities exist Many known distinct genetic defects Many known distinct genetic defects Similar effects on neurons of particular areas of brain Similar effects on neurons of particular areas of brain – Purkinje neurons in cerebellum often affected – Amygdala damage in Fragile X Syndrome and in other autistic individuals and in mercury toxicity

6 03/20/03John L. Kucera, MD “Autism Spectrum Disorder” Many known genetic disorders, but very rare Many known genetic disorders, but very rare Cannot account for dramatic increase in ASD Cannot account for dramatic increase in ASD

7 03/20/03John L. Kucera, MD Autism: A Unique Type of Mercury Poisoning Bernard, Enayati, Binstock, Roger, Redwood, McGinnis Bernard, Enayati, Binstock, Roger, Redwood, McGinnis Medical Hypothesis, 2001 Medical Hypothesis, 2001 available on Autism Research Institute Website: available on Autism Research Institute Website: www.autism.com/ari www.autism.com/ari And on Defeat Autism Now Website: And on Defeat Autism Now Website:

8 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Psychiatric Traits (Bernard, et. al.) Psychiatric Traits (Bernard, et. al.) – Social withdrawal, shyness – Anxiety, obsessive/compulsive traits – Depression – Irritability, aggression – severe temper tantrums – Impaired face recognition – Paranoid/psychotic thoughts and behavior

9 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Speech/Language/Hearing Deficits (Bernard, et. al.) Speech/Language/Hearing Deficits (Bernard, et. al.) – Speech loss, delay or failure to develop – Dysarthria, slurred or intelligible speech – Echolalia, voice differentiation with other sounds – Sound sensitivity – Hearing loss – Poor performance on language tests

10 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Sensory Abnormalities (Bernard, et. al.) Sensory Abnormalities (Bernard, et. al.) – Paresthesias in and around mouth & extremities – Abnormal sensitivity to pain – Touch aversion – Proprioceptive (position sense) difficulty

11 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Motor Disorder Behaviors (Bernard, et. al.) Motor Disorder Behaviors (Bernard, et. al.) – Flapping, jumping, spinning, jerking – Poor eye-hand coordination, handwriting – Abnormal gait, posture / clumsy / toe walking – Chewing/swallowing problems – Unusual postures – Increase in cerebral palsy; hyper- or hypotonia – Incontinence / toilet training difficulties – Autonomic disturbances: excessive sweating, poor circulation, elevated heart rate

12 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Mental Impairments (Bernard, et. al.) Mental Impairments (Bernard, et. al.) – Borderline or retarded intelligence on previously normal appearing persons – “Reversible” mental retardation in some cases – Poor concentration / short attention span – Difficulty with multiple/complex commands – Deficits with abstract/conceptual thinking

13 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Other Unusual Behaviors (Bernard, et. al.) Other Unusual Behaviors (Bernard, et. al.) – Stereotyped sniffing – Hyperactivity – Insomnia: sleep disturbances – Eating/feeding disorders: food aversion / narrow food preferences – Unprovoked / prolonged crying – Self-injurious behavior – Masturbatory tendencies – Grimacing / staring spells

14 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Visual Impairments (Bernard, et. al.) Visual Impairments (Bernard, et. al.) – Limited or lack of eye contact – Gaze abnormalities – “Visual impairments” – Light sensitivity – Blurred vision – Constricted visual fields

15 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Gastrointestinal Problems (Bernard, et. al.) Gastrointestinal Problems (Bernard, et. al.) – Diarrhea and/or constipation – Abdominal discomfort – Anorexia, poor appetite – Lesions of ileum & colon – Increased intestinal permeability (“leaky gut”) – Inhibition of endopeptidase enzymes (especially dipeptidyl peptidase IV) needed for breakdown of casein and gluten

16 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Biochemical Abnormalities (Bernard, et. al.) Biochemical Abnormalities (Bernard, et. al.) – Sulfate deficiency – Purine / pyrimidine metabolic errors – Tyrosine depletion – Glutathione deficiency, necessary for liver detoxification of heavy metals – Mitochondrial dysfunction, especially in brain

17 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Immune System Abnormalities (Bernard, et. al.) Immune System Abnormalities (Bernard, et. al.) – Increased incidence of allergies & asthma – Autoantibodies to myelin basic protein – Increased Th2 subset of lymphocytes – Reduced Natural Killer T-Cell function

18 03/20/03John L. Kucera, MD Autism & Mercury Poisoning Central Nervous System Lesions (Bernard, et. al.) Central Nervous System Lesions (Bernard, et. al.) – Selective damage – Purkinje and granular cells – Pathology in amygdala and hippocampus Unable to synthesize glutathione Unable to synthesize glutathione Social avoidance, lack of facial expression, lack of eye contact, motor stereotypic behaviors Social avoidance, lack of facial expression, lack of eye contact, motor stereotypic behaviors – Neuronal disorganization – Demyelination – Brain stem damage – peripheral polyneuropathy – Seizures, subtle seizure activities, abnormal EEG

19 03/20/03John L. Kucera, MD Autism: A Unique Type of Mercury Poisoning Bernard, Enayati, Binstock, Roger, Redwood, McGinnis Bernard, Enayati, Binstock, Roger, Redwood, McGinnis Medical Hypothesis, 2001 Medical Hypothesis, 2001 available on Autism Research Institute Website: available on Autism Research Institute Website: www.autism.com/ari www.autism.com/ari And on Defeat Autism Now Website: And on Defeat Autism Now Website:

20 03/20/03John L. Kucera, MD Autism, Mercury and Vaccines Thimerosal—until 2001, in many vaccines Thimerosal—until 2001, in many vaccines – Antibacterial, antifungal – Used as a “preservative” – Removed from animal vaccines years ago – Banned from most over-the-counter products in 1998, but left in vaccines – Vaccine requirements for children birth to age 2 increased from 8 in 1980 to 22 in 2001 – Children could have received >100x EPA safe daily dose in vaccines given one day

21 03/20/03John L. Kucera, MD Autism, Mercury and Vaccines Mercury binds to sulfhydryl groups on protein Mercury binds to sulfhydryl groups on protein Can be structural proteins or enzymes Can be structural proteins or enzymes Loss of structural integrity or enzyme function Loss of structural integrity or enzyme function Thimerosal destroys tubulin & actin in neurons Thimerosal destroys tubulin & actin in neurons Thimerosal is potent inhibitor of many critical enzymes involved in cellular metabolism Thimerosal is potent inhibitor of many critical enzymes involved in cellular metabolism Synergistic effect with aluminum and other chemicals in vaccine mixture Boyd Haley, Ph.D., 7/01 Synergistic effect with aluminum and other chemicals in vaccine mixture Boyd Haley, Ph.D., 7/01

22 03/20/03John L. Kucera, MD Autism, Mercury and Vaccines Complicating Factors Complicating Factors – Infant's hepatic detoxification function not fully developed – Multiple toxic mechanisms of mercury, including to immune system, may contribute to vulnerability to other substances, including vaccines without thimerosal (MMR)

23 03/20/03John L. Kucera, MD Autism, Mercury and Vaccines Thimerosal Study – Centers for Disease Control Thimerosal Study – Centers for Disease Control – Screened 110,000 patients for Speech delay, Neurodevelopmental Disorders, ADD – Official Conclusion: No link to Autism – Primary Investigator says opposite: “This screening suggests a possible association between certain neurological disorders and exposure to mercury from thimerosal-containing vaccines before the age of six months.” --Dr. Thomas Verstraeten “This screening suggests a possible association between certain neurological disorders and exposure to mercury from thimerosal-containing vaccines before the age of six months.” --Dr. Thomas Verstraeten

24 03/20/03John L. Kucera, MD Autism—Testing Basic Biochemical testing Basic Biochemical testing – Establish baseline before interventions – Liver/renal function – treatments can affect – Complete blood chemistry CLUES: low bicarbonate (CO2): acidic stress CLUES: low bicarbonate (CO2): acidic stress Low protein: inadequate intake or absorption Low protein: inadequate intake or absorption High protein: enzyme deficiencies High protein: enzyme deficiencies Low normal AST/ALT: Zinc deficiency Low normal AST/ALT: Zinc deficiency

25 03/20/03John L. Kucera, MD Autism—Testing Other labs Other labs – CBC – Thyroid function – Ammonia level – ANA – Immunoglobin Levels (IgG, A, M, E) – Myelin Basic Protein – Serum Copper, Plasma Zinc for Copper/Zinc ratio

26 03/20/03John L. Kucera, MD Autism—Testing Organic acids—urine Organic acids—urine – Metabolic waste (like analysis of engine exhaust) – Metabolites of carbohydrates, proteins and fats – Waste products of yeast, bacteria – Kreb's Cycle Intermediates

27 03/20/03John L. Kucera, MD Autism—Testing Organic acids—urine Organic acids—urine – Indicators of Mitochondrial Dysfunction Partial blocks in Kreb's Cycle—increase intermediates Partial blocks in Kreb's Cycle—increase intermediates Uncoupling of oxidative phosphorylation for energy Uncoupling of oxidative phosphorylation for energy – Elevated fatty acid metabolites – Elevated lactate – Elevated hydroxymethylglutarate

28 03/20/03John L. Kucera, MD Autism—Testing Comprehensive Stool Analysis—Importante Comprehensive Stool Analysis—Importante – Identifies beneficial bacteria, potential pathogens – Identifies yeast and parasites – Measures digestive and absorptive function of gut – Measures indicators of inflammation and immune function – Measures markers of Intestinal health

29 03/20/03John L. Kucera, MD Autism—Testing Comprehensive Food Allergy Panel Comprehensive Food Allergy Panel – Uncovers unknown food sensitivities – IgE and IgG – Better to wait until initial treatment completed

30 03/20/03John L. Kucera, MD Autism--Testing Toxic and Essential Mineral Screening Toxic and Essential Mineral Screening – Serum—useful only for very recent high exposure – RBC—good only for exposure in prior 3-4 months – Hair metals–reliable only if ability to detoxify intact, but unreliable for infants and children with immature or impaired detoxification – Fecal—more useful if recent exposure/ingestion or after beginning chelation

31 03/20/03John L. Kucera, MD Autism--Testing Toxic and Essential Mineral Screening Toxic and Essential Mineral Screening – Urine Challenge—controversial; best available tool for assessing body burden – Unchallenge urine--unreliable as indicator of mercury exposure (Arch Environ Health 6:480-3, 1963 – Pre-challenge urine baseline unnecessary – Challenge (provocative) agents vary in affinities for each toxic metal and nutrient mineral DMSA (meso-2, 3-dimercaptosuccinic acid) DMSA (meso-2, 3-dimercaptosuccinic acid) DMPS (sodium 2,3 dimercaptopropane-1-sulfonate) DMPS (sodium 2,3 dimercaptopropane-1-sulfonate)

32 03/20/03John L. Kucera, MD Autism--Testing DMSA—Rx Chemet (Sanofi Pharmaceuticals), Succimer (Thorne), DiSulfhydryl (Kirkman) DMSA—Rx Chemet (Sanofi Pharmaceuticals), Succimer (Thorne), DiSulfhydryl (Kirkman) – Sulfur-thiol, forms stable complex with metals – FDA approved – Long-term experience in US with pediatric lead toxicity (Safety and efficacy of DMSA in children with elevated blood lead concentrations. J Toxicol Clin Toxicol 2000; 38(4):365-75) – Majority (40-60%) remains in intestine (little or no chelation of toxic metals); excreted in feces – Three-day dosing before urine collection

33 03/20/03John L. Kucera, MD Autism--Testing DMPS--Dimaval (Heyl); generic available via compounding pharmacies DMPS--Dimaval (Heyl); generic available via compounding pharmacies – Rapidly absorbed orally, peaking in 4 hours – Majority (45-60%) excreted in urine; rest in feces – Appears to have greater affinity for lead and mercury than arsenic and cadmium – Extensively researched in Europe for safety and efficacy – Challenge test is one-time oral dose (50-250 mg) followed by 6-hr collection (one-time collection OK)

34 03/20/03John L. Kucera, MD Autism Treatment “The pathetic fact is that the standard of care in America for a child with 'autism' is no care at all – other than a diagnosis by a psychiatrist after behavioral observations, and a prescription for psychotropic medications.” “The pathetic fact is that the standard of care in America for a child with 'autism' is no care at all – other than a diagnosis by a psychiatrist after behavioral observations, and a prescription for psychotropic medications.” --from Don't GIVE UP – Matthew's Story --from Don't GIVE UP – Matthew's Story by Liz Birt and Maurice Lopez by Liz Birt and Maurice Lopez Mothering, May-June, 2000 Mothering, May-June, 2000

35 03/20/03John L. Kucera, MD Autism Treatment – Diet Casein-free, Gluten-free Diets Casein-free, Gluten-free Diets – Decrease opioid-peptides into circulation Improves cognitive / behavioral function Improves cognitive / behavioral function Improves gut motility Improves gut motility – Decrease allergic reactions –

36 03/20/03John L. Kucera, MD Diet Casein Restriction Casein Restriction – All dairy products Cow's milk, goat's milk, buttermilk Cow's milk, goat's milk, buttermilk Yogurt Yogurt Butter Butter Cheese Cheese Whey Whey Caseinates Caseinates All foods with dairy products, casein All foods with dairy products, casein Reading labels necessary but not always accurate Reading labels necessary but not always accurate

37 03/20/03John L. Kucera, MD Diet Casein Restriction Casein Restriction Milk/casein-free substitutes Milk/casein-free substitutes – Rice, potato, soy – Dairy-free cheeses, yogurts, margarines – Comprehensive IgG food allergy testing very helpful  Uncovers unknown food allergies (e.g., eggs)  Reveals many foods to which child is NOT allergic  Helps in expanding food options safely

38 03/20/03John L. Kucera, MD Diet Gluten (or gliadin) Restriction—more difficult Gluten (or gliadin) Restriction—more difficult – Wheat and most grains: – Barley, Kamut, Oats, Rye, Seminola, Spelt, Triticale – Most bakery, cereals and prepared foods – Often “hidden” in dressings, flavorings, spices, etc. – Reading labels necessary but not always accurate – Not always noted on list of ingredients – Contamination in manufacturing or packaging equipment/materials – Contamination at home—kitchen utensils, etc.

39 03/20/03John L. Kucera, MD Diet Gluten/grain alternatives: Gluten/grain alternatives: – Corn—may have allergen (corn 'gluten') – Soy—may have allergen or sensitivity – Lentils – Potato – Rice – Legumes (bean flours, e.g., garbanzo) – Comprehensive IgG food allergy testing helpful (necessario)

40 03/20/03John L. Kucera, MD Diet Guidelines for dietary, nutritional intervention Guidelines for dietary, nutritional intervention – Be willing to experiment – Observe closely for positive or negative reactions – A “negative” reaction is not always bad—may be sign of new or recovered brain function, “sensory overload” or “withdrawal” – If no obvious improvement after reasonable trial, be willing to stop the treatment—again observe! – Consider retrials later – Record responses /dates of trials (muy importante)

41 03/20/03John L. Kucera, MD Diet Resources Resources – “Special Diets for Special Kids”--Lisa Lewis, Ph.D – “Unraveling the Mystery of Autism and Pervasive Developmental Disorder”--Karyn Seroussi – Website: www.gfcfdiet.com – Autism Network for Dietary Intervention newsletter, The ANDI News, POBox 77111, Rochester, New York USA 14617-0711. E-mail: – AutismNDI@aol.com

42 03/20/03John L. Kucera, MD Mercury/Heavy Metal Detoxification Throughout treatment Throughout treatment – Appropriate nutritional support – Appropriate monitoring tests See DAN! Consensus Paper See DAN! Consensus Paper – Monitor for side effects and benefits

43 03/20/03John L. Kucera, MD Mercury/Heavy Metal Detoxification Defeat Autism Now! (DAN!) Mercury Detoxification Consensus Group Position Paper Available online: dan.com; autism.com/ari

44 03/20/03John L. Kucera, MD Mercury/Heavy Metal Detoxification Pre-treatment testing Pre-treatment testing – see DAN! Consensus paper Locate toxic metal sources and stop exposure Locate toxic metal sources and stop exposure – Food, drinks, toys, clothing/bedding (antimony), wooden playground equipment (arsenic) Correct as much as possible: Correct as much as possible: – Intestinal dysbiosis – Intestinal permeability (leaky gut) – Nutritional derangements

45 03/20/03John L. Kucera, MD Intestinal Dysbiosis Dietary Treatment Dietary Treatment – Sugar restriction – No milk and dairy—lactose promotes Candida – Avoid mold and yeast-containing foods (cheeses, dried fruits, peanuts, alcoholic drinks, juices, some B-vitamins – Address food allergies – Pancreatic enzymes (proteases)

46 03/20/03John L. Kucera, MD Intestinal Dysbiosis Attempt to eradicate potential pathogens seen on Stool Analysis and/or Organic Acid Testing Attempt to eradicate potential pathogens seen on Stool Analysis and/or Organic Acid Testing Yeast Yeast – Nystatin—safe; start low dose to prevent (“die-off”) – Probiotics—1-10 billion L. acidophilus, B. bifidum/d. – Saccharomyces boulardii – Natural agents against Candida Caprylic Acid (enteric-coated, time-release) Caprylic Acid (enteric-coated, time-release) Oregano Oil (100x more potent than caprylic acid) Oregano Oil (100x more potent than caprylic acid) Berberine (goldenseal)--broad-spectrum activity against fungi including C. albicans, pathogenic bacteria, protozoa Berberine (goldenseal)--broad-spectrum activity against fungi including C. albicans, pathogenic bacteria, protozoa Garlic Garlic

47 03/20/03John L. Kucera, MD Intestinal Dysbiosis Treat parasites and pathogenic bacteria Treat parasites and pathogenic bacteria – Try natural options first – Sulfamethoxazole/trimethoprim – Metronidazole (antifungal and antiparisitic) – Yodoxin (antifungal and antiparisitic)

48 03/20/03John L. Kucera, MD Mercury/Heavy Metal Detoxification DMSA–most commonly used DMSA–most commonly used – Usually oral dosing; can be rectal – About every 8 hours; do not interrupt sleep – Usually given for 3 days, then eleven days off – Re-check CBC, biochemical profile and urine metal challenge after two or three cycles – Not effective for aluminum chelation

49 03/20/03John L. Kucera, MD Mercury/Heavy Metal Detoxification DMPS—usually reserved for persistently elevated mercury or other metals DMPS—usually reserved for persistently elevated mercury or other metals – More rapid chelator – More effective chelator of mercury – Can be used for challenge test after DMSA treatment

50 03/20/03John L. Kucera, MD Mercury/Heavy Metal Detoxification Precautions Precautions – Supplement trace minerals Chelators bind with nutritional minerals, too Chelators bind with nutritional minerals, too – Make sure bowels moving Some metals cleared through gut Some metals cleared through gut Increase fiber—e.g., psyllium at bedtime Increase fiber—e.g., psyllium at bedtime Laxatives, if necessary—try Cascara sagrada or senna Laxatives, if necessary—try Cascara sagrada or senna – Support, protect liver—major detoxifying organ Glutathione Glutathione Extra Vitamin C and E Extra Vitamin C and E Milk thistle (Silybum marianum), silymarin flavonoids-- 50-250mg up to three times daily Milk thistle (Silybum marianum), silymarin flavonoids-- 50-250mg up to three times daily

51 03/20/03John L. Kucera, MD Case Studies

52 03/20/03John L. Kucera, MD


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