Minerals, Metals Mercury, and Miracles in Autism Spectrum Disorders

Anju Iona Usman, M. D. True Health Medical Center Naperville, Illinois

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Predisposing Factors for ASD

Genetics
Blood Type HLA- Type Family History of Autoimmunity Single Nucleotide Polymorphisms (SNP) causing impaired detoxification

Heavy Metal Burden

Mom (amalgams, fish consumption, rhogam, vaccines) Patient (immunizations, environment, antibiotic)

Infectious Agents
Virus (Measles, HHV6, RSV) Bacteria (Streptococcus, Clostridia) Fungal (Candida)
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Aftermath
Gastrointestinal Dysfunction
Maldigestion ( Abnormal Peptides, IgG Food Sensitivities, Enzyme Deficiencies) Malabsorption ( Fat Soluble Vitamin Deficiencies, Essential Fatty Acid Deficiencies, Essential Amino Acid Deficiencies ) Dysbiosis (Aerobic and Anaerobic Bacterial, Fungal, and Viral )

Mineral Metabolism
Mineral Deficiencies

Impaired Detoxification
Methylation, Sulfation, Glutathione, Metallothionein Heavy Metal Overload Oxidative Stress

Immunological Dysregulation

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Th1 and Th2 skewing Decreased Natural Killer Cells Pro-inflammatory Cytokines Increased Autoimmune Markers
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Nothing in life is to be feared, it is only to be understood

Unknown

Treatment Options Educational Therapies (ABA, AIT, RDI, Floortime) Neurofeedback Energetic Techniques (NAET, Craniosacral, Homeopathy) Dietary Interventions (Casein and Gluten Free, Specific Carbohydrate) Nutrient Therapy Heavy Metal Detoxification
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Autism is a Medical Disorder Not A Mental Disorder

Most Frequently Used Interventions
Educational Techniques 89% Sensory Therapies 71% Prescription Drugs 50%

CAM Therapies (70% USA, 90% Canada)

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Modified Diet 40% Vitamin/Minerals 30% Food Supplements 23% Homeopathy -30% Anti- yeast 30% Prayer 16% More severe symptoms Unacceptable side effects Concern about side effects Safety of prescription drugs
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Why people use CAM?

Anju Usman, M.D.

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Is Autism Related to Impaired Detoxification?

Detoxification - process of eliminating toxins by converting them from fat soluble to water soluble molecules
Requires a great deal of energy (ATP) nutritional support, and vitamin cofactors First line of defense is our gastrointestinal lining Impaired detoxification leads to an overload of toxins in the body Excess toxins can lead to oxidative stress and chronic inflammatory conditions Primarily occurs in the liver, in 2 Phases
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Reduced levels of mercury in first baby haircuts of autistic children

Holmes AS, Blaxill MF, Haley BE.
Int J Toxicol. 2003 Jul-Aug;22(4):277-85.

SafeMinds, Cambridge, Massachusetts, USA. Reported rates of autism have increased sharply in the United States and the United Kingdom. One possible factor underlying these increases is increased exposure to mercury through thimerosal-containing vaccines, but vaccine exposures need to be evaluated in the context of cumulative exposures during gestation and early infancy. Differential rates of postnatal mercury elimination may explain why similar gestational and infant exposures produce variable neurological effects. First baby haircut samples were obtained from 94 children diagnosed with autism using Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria and 45 age- and gender-matched controls. Information on diet, dental amalgam fillings, vaccine history, Rho D immunoglobulin administration, and autism symptom severity was collected through a maternal survey questionnaire and clinical observation. Hair mercury levels in the autistic group were 0.47 ppm versus 3.63 ppm in controls, a significant difference. The mothers in the autistic group had significantly higher levels of mercury exposure through Rho D immunoglobulin injections and amalgam fillings than control mothers. Within the autistic group, hair mercury levels varied significantly across mildly, moderately, and severely autistic children, with mean group levels of 0.79, 0.46, and 0.21 ppm, respectively. Hair mercury levels among controls were significantly correlated with the number of the mothers' amalgam fillings and their fish consumption as well as exposure to mercury through childhood vaccines, correlations that were absent in the autistic group. Hair excretion patterns among autistic infants were significantly reduced relative to control. These data cast doubt on the efficacy of traditional hair analysis as a measure of total mercury exposure in a subset of the population. In light of the biological plausibility of mercury's role in neurodevelopmental disorders, the present study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism. PMID: 12933322 [PubMed - in process]

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Impaired Mercury Excretion

Baby Hair Data (Amy Holmes, M.D.,2003)
Collected first hair cuts in fully immunized infants 94 autistics and 45 controls Average Hair Mercury: 0.25mcg/g autistics 4.90mcg/g controls

Conclusions:
Autistics higher prenatal Hg exposure, Hg was demonstrated when chelating agents used Autistics have an inherent problem excreting heavy metals which implies a large risk of toxicity with very small exposures

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Excretion of Mercury higher in ASD post provocation with DMSA

Jeff Bradstreet, M.D. measured urinary excretion of mercury following DMSA challenge of 10 mg/kg/dose TID for 3 days, urine collected the following morning. Children ages 1-15 yrs with ASD (n=221) 87% (193) and 15/19 (80%) of neurotypical controls had detectable Hg. The average urinary post-DMSA mercury in the 193 ASD children was 8.63 mcg/24hr vs 1.48 mcg/24hr in the controls or 5.8 times higher.

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Mercury Toxicity
Genetic Susceptibility and Synergistic Effects

Boyd Haley, PhD.

University of Kentucky, Department of Chemistry, Chairman

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2.

3.

There appears to be a subset of the population that can not effectively excrete mercury and are at a greater risk to exposures to mercury than are the general population. Genetic susceptibility is critical. Presence of other heavy metals, antibiotics, etc. may enhance the toxicity of thimerosal. Synergistic toxicities must be considered. Estrogen is protective against thimerosal toxicity. Testosterone increases the toxicity of thimerosal. Gender plays a role in toxicity.
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J. James, PhD. DAN October 2003

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Jill James, PhD. : Findings of Cysteine and Methionine Transulfuration Abnormalities

Presentation DAN Conference Oct. 2003

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Impaired transsulfuration and oxidative stress in autism: Improvement with targeted nutritional intervention
S. Jill James, PhD.

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Cysteine Makes Detox Happen

Methionine Homocysteine Cystathionine

CYSTEINE Glutathione Metallothionein

Sulfate
Alpha Lipoic Acid

Coenzyme A

Taurine

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Enzymes implicated in ASD:

Methylenetetrahydofolate reductase (MTHFR)

Methyltransferases Adenosine Deaminase Methionine Synthase(MTR) DPPIV

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Case Study - Z.B.

Preconception infertility drugs Pregnancy/Delivery mom 12 amalgams, low progest. Infancy - colic reflux, trouble sleeping, eczema, cough 4 mo - RSV hospitalized 12 mo - frequent URI, OM, chronic sinusitis, loose stools 18 mo - Evaluation - Severe language/motor delays 24 mo - Speech and OT , 3 words, immunizations- UTD 34 mo - Diagnosed with autism

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Severe hyperactivity, tantrums, screaming fits Sensory - biting, spinning, light, sound, touch Socialization isolation Language - expressive delay, receptive delay Compulsive, ritualistic
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Case Study - Z.B. (age 4)

Peptides Allergy Stool High Caseomorphine High Gliadorphin Elisa IgG = 3+ dairy, 3+ soy

Rast IgE = dust, dander, pollen

Low chymotrypsin, low SCFA, low Butyrate 4+ Klebsiella, 2+ Bacillus, Yeast no growth Parasite - negative OAT (urine) C. Difficile Toxin
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DHPPA= 727 Hippuric=683 A negative B negative

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Case Study - Z.B.(age 4)

Test Serum Copper
(mcg/dl)

Z.B. Levels 130 70 1.86 3. 1

Normal range Optimal range 70 155 70 150 0.91 1.39 < 20 90 100 100-120 1.0 < 10

Plasma Zinc
(mcg/dl)

Copper/Zinc Ratio Kryptopyrrole

(mcg/dl)

Whole Blood Histamine

(ng/ml)
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20 200

40 70
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Abnormal Metal-Metabolism Observed in Test Subjects

Pfeiffer Treatment Center Data, May 2001

99% of test subjects had abnormal Cu/Zn ratios (499/503) Extremely disordered levels of Cu and Zn, indicating absence of blood homeostasis for these metals in 428 subjects (85%), Moderately disordered Cu/Zn levels despite ongoing zinc therapy in 41 subjects (8%), Severe pyrrole disorder in an additional 30 subjects (6%), indicating severe zinc depletion, Only 4 of the 503 autism-spectrum patients did not exhibit a serious metal-metabolism disorder.
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Consequences of Zinc Deficiency

Dysfunctional MT (Metallothionein) Increased Copper Oxidative Stress Impaired brain function
Decreased cognitive function Poor short term memory Reasoning Behavior (aggression, hyperactivity) Decreased number of post synaptic NMDA specific glutamate mediated Calcium channels Poor neuromotor coordination, ataxia

Impaired production of active B vitamins Cancer Skin disorders- Acne, Psoriasis, poor wound healing
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Signs and Symptoms of Zinc Deficiency

Hx: Poor appetite, anorexia Taste sensitivities Poor wound healing Frequent infections Stunted growth Night blindness Light sleeper Irritability, episodic anger Chronic diarrhea Fly hx of leukemia H2 blockers, antacid, prednisone, or OCP use
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PE: Sparse head hair Groove across nails or white spots Nasal polyps Dark skin Canker sores Acne Psoriasis Body odor Labs: Plasma zinc (<90ug/dl)
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Consequences of Copper Excess

Liver Toxicity Brain Inflammation Gastrointestinal Inflammation, Intestinal Permeability Neurological Swallowing Speech and Learning Disabilities Hyperactivity Psychological Violence, temper Tantrums Depression Osteoarthritis Membrane lipid peroxidation Oxidative damage to glutathione reductase and hexokinase Free radical damage
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Signs and Symptoms of Copper Excess

Hx: Hyperactivity Jekyll- Hyde behavior Frequent yeast infections Poor short term memory Night blindness Light sleeper Depression Hx of Oral Contraceptive Use
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PE: Red Hair Kaiser-Fleisher Rings Labs: Serum Copper (>100mcg/dl)

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Treatment of High Cu/Zinc Ratios

Treat Zinc deficiency until Zinc level optimized (100mcg/dl) Induce Metallothionein (MT) production (Selenium, Glutathione) Add Manganese and Molybdenum Provide adequate amounts of vitamin B6/Magnesium Optimize Vitamin C dose Avoid Sources of Copper Tap water (Cu pipes) Swimming pools and hot tubs (Cu algaecide) Chocolate, Carob, Soy, Shellfish, Liver Avoid Red/ Yellow dyes (deplete Zn)

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Case Study - Z.B.(age 4)

Diagnosis:
Mineral-metabolism disorder (high Cu/Zn) Heavy metal overload Dysbiosis anaerobic and aerobic bad bacteria, yeast overgrowth Food sensitivities, inhalant allergies Impaired Detoxification - methylation and sulfation defects
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Case Study - Z.B.(age 4)

Treatment Plan
Casein Free / Gluten Free Soy Free

Diet

High Protein
High Fiber High Antioxidants

Filtered Water
Preservative-Free Organic

Avoid sources of Copper

Environment
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Avoid sources of Aluminum

Avoid sources of Lead Avoid sources of Antimony

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Case Study - Z.B.(age 4)

Treatment Program
Morning
Super NuThera - 1 tsp Vitamin C - 300 mg B6 - 200 mg P5P - 40 mg

Evening
Vitamin C - 300 mg Vitamin E - 200 iu Manganese - 5 mg Zinc - 60 mg

Gut
Probiotics Enzymes with DPP IV Nystatin Advanced Biocidin

TMG - 175 mg
DMAE - 40 mg Calcium/Magnesium 200/200 mg

TMG - 175 mg
SuperEPA - 500 mg Calcium/Magnesium 200/200 mg

Vancomycin

Cod Liver Oil - 2500 IU of Vit A

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S-adenosyl methionine
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Case Study - Z.B.

Age 6 Started mainstream Kindergarten No Aide in classroom No diagnosis of Autism Remaining symptoms
Occasional temper tantrums Minimal fine motor delay Easily frustrated, minimal anxiety Continues nutrient program, CF/GF diet, methyl B12 shots, glutathione, low dose DMSA

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Methylcobalamin(B12) Injections
Helps pivotal step in the methylation cycle Bypasses impairments along folate pathway Methylates dopamine Shown to help cognitive ability, abstract thinking, attention, focus, awareness, language, behavior, OCD, anxiety, . Highly concentrated, injected subcutaneous in gluteal tissue, slow release, painless, no toxicity associated with high dose vitamin B12 No test for methylB12 deficiency Side effect increased energy, hyperactivity
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Case Study
Alex - age 11.5 yrs BHx: FT, NSVD, mom - many amalgams, yeast infect., fibromyalgia Med Hx: severe eczema, allergies, reflux, freq. otitis media, 11 rounds of antibiotics age 1mo 21mo., diarrhea for years followed by constipation, chemical sensitivities Dev Hx: no regression, anxiety, stims, sound sensitivity, fine and gross motor delays, major language delay, sensory issues Past Interventions: GF/CF, soy-free diet, AIT/Tomatis, DMSA, Gut Therapies, Secretin, Nutrient Therapy
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Case Study
2 yr. Diagnosed with autism, numerous antibiotics, chronic diarrhea, reflux, vomiting, played for hours with fingers 3yr. Tactile defensiveness, severe cravings for pasta, urine milky smelled like asparagus, flapping ears, hi pain tolerance, no speech, diarrhea 5yr. 4+ Casein and gluten peptides, CF/GF diet, better eye contact, decreased tactile defensiveness, appropriate response to pain, no speech, no longer craving gluten, diarrhea now constipation 6.5 yr. Treated with Nystatin, severe die-off reaction, high CD8, low NK cells and activity, high cmv titers 7yr. High CMV titer, Ganciclovir for 6 months, no change. High dose DMG, imitated animal sounds, still no speech, severe constipation, eczema 7.5 yr.RX= p5p, Mg, niacin, GSH, DMG, EPO, Flax oil, Epsom salts baths, herbalax, protein powder, mvi, nystatin, probiotics, folic acid caused yelling, screaming, and insomnia, IV Secretin times one, improved constipation for 3 weeks 8 yr. Abnormal fungal metabolites treated with uva ursi, lamisil. Hair and urine with high Hg. DMSA started. 10 yr. Chelation therapy with DMSA and ALA.
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Case Study Alex (age 11.5)

HPI: severe apraxia, unintelligible speech, receptive language, verbal stims, foot stims, eye stims, sound sensitivities, not reading, sensory, couldnt take him anywhere, fine and gross motor delays,eczema,constipation PE: 59, 130 lbs, dry patches, red eyes, red ears, splitting nails, poor balance, low tone upper body Labs: Cu-117, Zn-71, Kp-46.4, Histamine-62,
Hair - Sb, Ni Stool - 3+ Pseudo, 1+ Staph, No Yeast,No Lactobacillus
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Case Study - Alex

Dx: Heavy Metal Overload Cu/Zinc imbalance, Probable Metallothionein dysfunction Pyroluria (causes severe B6 and Zinc deficiency) Dysbiosis bacterial ,fungal, viral Impaired Detox- undermethylation, undersulfation, low GSH, low glycination, low glucuronidation Immune imbalance Food Allergies and Allergic Rhinitis Eczema Severe Constipation

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Case Study- Alex

RX: Diet - Casein-free, Gluten-free, Soy-free, Low phenol diet, High Fiber, Ground flaxseeds Vit C, Vit E ,B6, p5p, Zinc, DMG, Cal/Mag, Biotin, Molybdenum Essential Fatty Acids (EPO,CLO) Gut Rx - Probiotics, Digestive enzymes, Antifungals(Nystatin), Antibacterial (Gentamicin/Advanced Biocidin) Metallothionein Promotion(Glutathione, Se) Epsom Salts Baths
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Clean up the Childs 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 cleaner with a HEPA filter in the bedroom Avoid 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)
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Clean up the Diet

Casein-free/Gluten-free/Soy-free Diet Trial for 3-6 months Avoid sugar and refined starch, high protein, high fiber diet, high good fats, maximize antioxidants, increase cruciferous veggies, blue foods, garlic, turmeric, and fermented foods Limit processed and preserved foods, organic is best Avoid excitotoxins (ex. Caffeine, MSG(glutamate), NutraSweet, red/yellow food dyes, nitrites, sulfites, phenolics, salicylates) Drink plenty of filtered water Never microwave in plastics or Styrofoam Eliminate seafood Add raw, soaked nuts/seeds/ground flaxseeds 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
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Clean up the Gut

Daily bowel movements are a must Add a plant derived digestive enzyme with meals Start high potency probiotics (acidophilus and bifidus), consider FOS. Treat empirically for yeast, rule out parasites, clostridium, aerobic bacterial overgrowth Consider referral to GI specialist if no improvement Keep close eye on gut during any detox regimen Consider antiviral therapy Consider colostrum, transfer factor, oral immunoglobulin, or IV IG if symptoms persist Castor Oil Packs- increase sIgA

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Basic Nutrient Program

Vitamin B6/P5P Antioxidants (Vit C, E, A) Minerals - Magnesium, Selenium, Molybdenum, Manganese Omega 3 EFA (Cod liver oil) DMG or TMG Active folate (folinic, methyl THF) Methyl B12
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Heavy Metal Detox Options

Chelators- bind a free metal ion into a ring structure thereby
neutralizing its reactive state
DMSA EDTA(not recommended for Hg) DMPS(not FDA approved)

Clathrating agents- free metal trapped within a colloid (NDF, PCA-Rx,

Metal-free)

TTFD/Allithiamine (Transdermal, Suppository) Methylcobalamin/methylB12 (Sublingual, oral, transdermal, SQ

injection)

Glutathione (IV, Transdermal, PO, nebulized, IV) Alpha Lipoic Acid (PO, Transdermal) N-Acetyl Cysteine (PO, Transdermal, IV) Homeopathics Herbals (garlic, cilantro, chlorella, spirulina) RNA Therapy
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Case Study - Alex

Alex age 13.5 HPI: speech dramatic improvement, understands everything, appropriate use of humor, fun to be with, loves to travel, enjoys reading the sports page, likes to spell, major progress since age 9. Continues to struggle with constipation, verbal stims, fine motor, speech pragmatics Labs: Cu-82 , Zn-106, Kp-7.7 , Histamine-113,
Hair-high Bi, Sn Metabolic Analysis Profile- high arabinose, high MHPG, high MMA, high FiGlu
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Case Study - Alex

RX: Diet - Casein-free, Gluten-free, Soy-free, Low phenol diet, High Fiber, Ground flaxseeds, psyllium Basic Nutrients- plus folinic, TMG, milk thistle, Evening Primrose Oil, Manganese, multivitamin, acyl-carnitine, Biotin, Molybdenum Gut Rx- probiotics, enzymes, nystatin MT Promotion Epsom Salts Baths TTFD/GSH cream- unable to tolerate Methyl B12 explosion in language, humor Transdermal DMPS continued steady gains
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Thank You for your children. They are all Miracles of God

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