Anju Usman, M.D. Copyright 2005 1 Minerals, Metals Mercury, and Miracles in Autism Spectrum Disorders Anju Iona Usman, M. D. True Health Medical Center

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Anju Usman, M.D. Copyright 2005

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– 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 DisorderNot A Mental Disorder

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

• CAM Therapies (70% USA, 90% Canada)– Modified Diet – 40%– Vitamin/Minerals – 30%– Food Supplements – 23%– Homeopathy -30%– Anti- yeast – 30%– Prayer – 16%

• Why people use CAM?– More severe symptoms– Unacceptable side effects– Concern about side effects– Safety of prescription drugs

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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 childrenHolmes 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 ToxicityGenetic Susceptibility and Synergistic Effects

Boyd Haley, PhD. University of Kentucky, Department of Chemistry, Chairman

1. 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.

2. Presence of other heavy metals, antibiotics, etc. may enhance the toxicity of thimerosal. Synergistic toxicities must be considered.

3. 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

AbnormalitiesPresentation 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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Cystathionine

Cysteine Makes Detox Happen

Methionine

Homocysteine

CYSTEINE

Glutathione

Metallothionein

Coenzyme A

Alpha Lipoic Acid

Taurine

Sulfate

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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

• 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 High Caseomorphine

High Gliadorphin

Allergy Elisa IgG = 3+ dairy, 3+ soy

Rast IgE = dust, dander, pollen

Stool Low chymotrypsin, low SCFA, low Butyrate

4+ Klebsiella, 2+ Bacillus,

Yeast – no growth

Parasite - negative

OAT (urine)

DHPPA= 727Hippuric=683

C. Difficile Toxin

A negativeB negative

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Case Study - Z.B.(age 4)

Test Z.B. Levels

Normal range

Optimal range

Serum Copper(mcg/dl)

130 70 – 155 90 – 100

Plasma Zinc

(mcg/dl)

70 70 – 150 100-120

Copper/Zinc Ratio 1.86 0.91 – 1.39 1.0

Kryptopyrrole

(mcg/dl)

3. 1 < 20 < 10

Whole Blood

Histamine(ng/ml)

43 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

• 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

• 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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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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Treatment Plan

Diet

Casein Free / Gluten Free

Soy Free

High Protein

High Fiber

High Antioxidants

Filtered Water

Preservative-Free

Organic

EnvironmentAvoid sources of Copper

Avoid sources of Aluminum

Avoid sources of Lead

Avoid sources of Antimony

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Morning Evening Gut

Super NuThera - 1 tsp Vitamin C - 300 mg Probiotics

Vitamin C - 300 mg Vitamin E - 200 iu Enzymeswith DPP IV

B6 - 200 mg Manganese - 5 mg Nystatin

P5P - 40 mg Zinc - 60 mg Advanced Biocidin

TMG - 175 mg TMG - 175 mg Vancomycin

DMAE - 40 mg SuperEPA - 500 mg

Calcium/Magnesium 200/200 mg

Calcium/Magnesium 200/200 mg

Cod Liver Oil - 2500 IU of Vit A

S-adenosyl methionine

Treatment Program

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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, “couldn’t 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 - AlexDx: • 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 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 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


Thank You for your children. They are all Miracles of God

Documents

Anju Usman, M.D. Copyright 2005 1 Minerals, Metals Mercury, and Miracles in Autism Spectrum Disorders Anju Iona Usman, M. D. True Health Medical Center