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Minerals, Metals

Mercury, and Miracles in

Autism Spectrum Disorders

Anju Iona Usman, M. D.

True Health Medical Center

Naperville, Illinois

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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

“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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Anju Usman, M.D.

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)

 

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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Anju Usman, M.D.

6 Copyright 2005 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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

Mercury Toxicity

Genetic 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 12 Copyright 2005 Anju Usman, M.D.
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. 14 Copyright 2005 Anju Usman, M.D.
S. Jill James, PhD.
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Anju Usman, M.D.

Cysteine Makes Detox Happen

Methionine

Cysteine Makes Detox Happen Methionine Homocysteine Cystathionine CYSTEINE Coenzyme A Taurine Glutathione Sulfate Metallothionein Alpha Lipoic
Cysteine Makes Detox Happen Methionine Homocysteine Cystathionine CYSTEINE Coenzyme A Taurine Glutathione Sulfate Metallothionein Alpha Lipoic

Homocysteine

Cystathionine

Cystathionine

Cystathionine

CYSTEINE

Cysteine Makes Detox Happen Methionine Homocysteine Cystathionine CYSTEINE Coenzyme A Taurine Glutathione Sulfate Metallothionein Alpha Lipoic

Coenzyme A

Cysteine Makes Detox Happen Methionine Homocysteine Cystathionine CYSTEINE Coenzyme A Taurine Glutathione Sulfate Metallothionein Alpha Lipoic
Taurine
Taurine

Glutathione

Sulfate
Sulfate

Metallothionein

Alpha Lipoic Acid

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Anju Usman, M.D.

Enzymes implicated in ASD: Methylenetetrahydofolate reductase (MTHFR) Methyltransferases Adenosine Deaminase Methionine Synthase(MTR) DPPIV 16 Copyright 2005
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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Anju Usman, M.D.

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= 727

Hippuric=683

C. Difficile Toxin

A negative B negative

 

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Anju Usman, M.D.

Case Study - Z.B.(age 4)

 

Test

Z.B. Levels

Normal range

Optimal range

Serum Copper

130

155

  • 70 90 100

(mcg/dl)

Plasma Zinc

     

(mcg/dl)

70

150

  • 70 100-120

Copper/Zinc

     

Ratio

1.86

0.91 1.39

1.0

Kryptopyrrole

     

(mcg/dl)

3. 1

< 20

< 10

Whole Blood Histamine

43

20 200

40 70

(ng/ml)

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Anju Usman, M.D.

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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Anju Usman, M.D.

Consequences of Zinc Deficiency

Dysfunctional MT (Metallothionein)

Decreased cognitive function

Behavior (aggression, hyperactivity)

 

Increased Copper

Oxidative Stress

Impaired brain function

Poor short term memory

Reasoning

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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

 

High Protein

Diet

 

High Fiber

 

High Antioxidants

 

Filtered Water

 

Preservative-Free

 

Organic

   

Avoid sources of

Copper

Environment

 

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

 

Evening

 

Gut

Super NuThera -

1 tsp

 

Vitamin C

-

300 mg

Probiotics

Vitamin C - 300 mg

 

Vitamin E

 

-

200 iu

Enzymes with 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

 

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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

Clean up the Gut

Daily bowel movements are a must

consider FOS.

Add a plant derived digestive enzyme with meals

Start high potency probiotics (acidophilus and bifidus),

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

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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Anju Usman, M.D.

Thank You for your children.

They are all Miracles of God

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