Autism – A Primary-Care Biomedical Perspective

1. Autism – A Primary-Care Biomedical Perspective

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

3. Autism – A Primary-Care Biomedical Perspective • 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 • Thimerosal • Aluminum, formaldehyde – Synergistic Toxicity?

4. 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)

5. “Autism Spectrum Disorder” • Not one disorder, but a group of disorders • Vary widely in presentation; similarities exist • Many known distinct genetic defects • 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. “Autism Spectrum Disorder” • Many known genetic disorders, but very rare • Cannot account for dramatic increase in ASD

7. Autism: A Unique Type ofMercury Poisoning • Bernard, Enayati, Binstock, Roger, Redwood, McGinnis • Medical Hypothesis, 2001 • available on Autism Research Institute Website: • www.autism.com/ari • And on Defeat Autism Now Website:

8. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • Sensory Abnormalities (Bernard, et. al.) • Paresthesias in and around mouth & extremities • Abnormal sensitivity to pain • Touch aversion • Proprioceptive (position sense) difficulty

11. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • Visual Impairments (Bernard, et. al.) • Limited or lack of eye contact • Gaze abnormalities • “Visual impairments” • Light sensitivity • Blurred vision • Constricted visual fields

15. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • 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. Autism & Mercury Poisoning • Central Nervous System Lesions (Bernard, et. al.) • Selective damage • Purkinje and granular cells • Pathology in amygdala and hippocampus • Unable to synthesize glutathione • 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. Autism: A Unique Type ofMercury Poisoning Bernard, Enayati, Binstock, Roger, Redwood, McGinnis Medical Hypothesis, 2001 available on Autism Research Institute Website: www.autism.com/ari And on Defeat Autism Now Website:

20. Autism, Mercury and 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. Autism, Mercury and Vaccines • Mercury binds to sulfhydryl groups on protein • Can be structural proteins or enzymes • Loss of structural integrity or enzyme function • Thimerosal destroys tubulin & actin in neurons • 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

22. Autism, Mercury and Vaccines • 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. Autism, Mercury and Vaccines • 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

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

25. Autism—Testing • 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. Autism—Testing • 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. Autism—Testing • Organic acids—urine • Indicators of Mitochondrial Dysfunction • Partial blocks in Kreb's Cycle—increase intermediates • Uncoupling of oxidative phosphorylation for energy • Elevated fatty acid metabolites • Elevated lactate • Elevated hydroxymethylglutarate

28. Autism—Testing • 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. Autism—Testing • Comprehensive Food Allergy Panel • Uncovers unknown food sensitivities • IgE and IgG • Better to wait until initial treatment completed

30. Autism--Testing • 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. Autism--Testing • 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) • DMPS (sodium 2,3 dimercaptopropane-1-sulfonate)

32. Autism--Testing • 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. Autism--Testing • 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. 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.” • --from Don't GIVE UP – Matthew's Story • by Liz Birt and Maurice Lopez • Mothering, May-June, 2000

35. Autism Treatment – Diet • Casein-free, Gluten-free Diets • Decrease opioid-peptides into circulation • Improves cognitive / behavioral function • Improves gut motility • Decrease allergic reactions

36. Diet • Casein Restriction • All dairy products • Cow's milk, goat's milk, buttermilk • Yogurt • Butter • Cheese • Whey • Caseinates • All foods with dairy products, casein • Reading labels necessary but not always accurate

37. Diet • Casein Restriction • 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. Diet • 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. Diet • 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. Diet • 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. Diet • 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. Mercury/Heavy Metal Detoxification • Throughout treatment • Appropriate nutritional support • Appropriate monitoring tests • See DAN! Consensus Paper • Monitor for side effects and benefits

43. Defeat Autism Now! (DAN!) Mercury Detoxification Consensus Group Position Paper Available online: dan.com; autism.com/ari Mercury/Heavy Metal Detoxification

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

45. Intestinal Dysbiosis • 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. Intestinal Dysbiosis • Attempt to eradicate potential pathogens seen on Stool Analysis and/or Organic Acid Testing • 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) • Oregano Oil (100x more potent than caprylic acid) • Berberine (goldenseal)--broad-spectrum activity against fungi including C. albicans, pathogenic bacteria, protozoa • Garlic

47. Intestinal Dysbiosis • Treat parasites and pathogenic bacteria • Try natural options first • Sulfamethoxazole/trimethoprim • Metronidazole (antifungal and antiparisitic) • Yodoxin (antifungal and antiparisitic)

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