toxins in autism: mercury to pcb’s woody r. mcginnis m.d. anaheim, june 28, 2003
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Toxins in Autism: Mercury to PCB’s
Woody R. McGinnis M.D.
Anaheim, June 28, 2003
Irene (Vicky) Colquhoun
1920-2000
Parent Pioneers
Bernard Rimland Ellen Bolte
Brenda O’ReillyVictoria BeckRik Rollens
The Mercury Team
Autism and ADHD are Symptoms
Multiple underlying problems
Variation and commonality
Gut and nutrition paramount
Cornerstones
Suboptimal Nutrition
Food Intolerances
Microbial Overgrowths
Toxins
Gut Disease Predominates
Esophagitis 69%Gastritis 42%
Duodenitis 67% Colitis 88%
Autistic Gut Symptoms•
Abdominal pain 69% Chronic diarrhea 58% Constipation 35% Night-awakening 42%
Gut Status
Poor digestion and absorption
Leaky gut: proteins out, toxins
and antigens in
Microbial overgrowths
Poor enzyme production
Altered signaling to CNS
Gut Dysfunction
Microbes Nutrients Peps, Ags,
Overgrow Low Toxins In
Laboratory Indices of Vitamin and Mineral Deficiency in Autism
Defeat Autism Now27 October 2002
San Diego
Tapan Audhya Ph.D.
Emar Vogelaar Ph.D.
Low Nutrient Levels in Autism(187 Autistic, 11-16 y.o vs. 10-17 y.o. controls)
0
10
20
30
40
50
60
70
% C
hil
dre
n <
No
rmal
Lev
el
Vit A Carotene Vit C Vit D Vit E
Before supplements After supplements
Low Nutrient Levels in Autism187 Autistics (11-16 y.o.) v. Controls (10-17 y.o.)
0
10
20
30
40
50
60
70
% C
hil
dre
n <
No
rmal
Lev
el
B1 B2 B3 B5
Before supplements After supplements
Low Nutrient Levels in Autism
0
10
20
30
40
50
60
% C
hil
dre
n <
No
rmal
Lev
el
B6 B12 Folate Biotin Inositol
Before supplements After supplements
Substrate Requirement for Maximal Activity of P5P Dependent Enzymes
010203040
506070
KM
Pyridoxal kinase Glutamatetransaminase
Glutamatedecarboxylase
Controls (n=16) v. Autistics (n=8-17)
Controls Autistics
Substrate Requirement for Maximal Activity of P5P Dependent Enzymes
0100200300400500600700800900
1000
DOPAdecarboxylase
Histidinedecarboxylase
5-HTPdecarboxylase
Controls Autistics
Low Minerals in Autism
0
10
20
30
40
50
60
70
% C
hil
dre
n<
No
rmal
Lev
el
RBC Zinc RBC Magnesium RBC Selenium
(132 Autistics, 42 Controls)
Membrane Fatty Acids
0
10
20
30
40
50
60
70
80
90
Low EPA Low GLA High AA High Tran
Nutrient Blockade
Absorption
Transport
Breakdown
Excretion
Inhibition
Blocked Absorption
Heavy metals: direct mucosal injury
Oral contraceptives block managnese
Insecticides: lipase inhibition
Poor acid production from microbial toxins and peptides means poor absorption of magnesium, zinc, B6 and amino acids
Blocked Transport
PCB’s block RBP, so low stored
and circulating Vitamin A
Cadmium displaces Zinc
Toxin-lowered [Magnesium]: poor P5P entry
Caramel coloring blocks P5P entry
Increased Breakdown
Ubiquitous toxins, including polyhalogenated hydrocarbons
(PCB’s, PCDD’s, PCDF’s) cause:
Vitamin A destruction
Increased Excretion
ETOH and Gentamycin: Vitamin B
Theophylline: Magnesium
Mercury: Magnesium and Calcium
Sulfa and Indocin: Folate
Tartrazine: Zinc
Nutrient Inhibition Insecticides and theophylline bind B6-
dependent enzymes
Sulfa drugs antagonize Folate
Lead competes for Calcium binding sites
Benzene binds Pyridoxine (B6)
Hydrazines (jets, corrosion inhibiter) and Hydrazides (“Alar” on fruits, cigarettes and
especially potato chips): B6 look-a-likes
Environmental Toxins in Autism?
Some Clues:
D-glucaric acid increased in 78%
Plasma glutathione low in 46%
Lower glutathione peroxidase (GSHPx)
Organic Toxins in Autism
0
10
20
30
40
50
60
70
% C
hil
dre
n>
No
rmal
L
evel
s
Benzene Iso Acetone Pentane Hexane
Elevated Plasma Levels
Organic Toxins in Autism
0
5
10
15
20
25
30
35
% C
hil
dre
n>
No
rmal
Lev
el
Aroclors(PCB) Perchlorethylene Xylene
Elevated Plasma Levels
Elevated Toxins in Autism(41 autistics, 24 controls)
0
5
10
15
20
25
30
35
% C
hild
ren
>N
orm
al
Le
ve
ls
Aluminum Arsenic Cadmium Lead
Red Blood Cell Levels
Toxins in Autism
0
5
10
15
20
25
30
% C
hil
dre
n>
No
rmal
Lev
el
Total mercury Organic mercury Inorganic mercury
Elevated Red Blood Cell Levels
Metals in autism?
• Clinical Pediatrics, 1988; 23(1):41-44
Temporal association lead and autism
• Am J Dis Chld, 1976;130:47-48
Higher blood lead levels and response
to EDTA chelation.
• DAN 2001 case report: normal 4 y.o. regresses severely to ASD post-amalgams
HEAVY METALS
AC / DCDANGER DANGER
EROTIC LIQUID CULTUREJEREMY & THE SUICIDES
MEGA DEATHMETALLICA
MOTORHEADNEAR LIFE EXPERIENCE
NEUROTICANEW AMERICAN SHAME
PSYCHOTICAVITAMIN F
Toxic Metals
Mercury Nickel
Lead Tin
Cadmium Free Copper
Arsenic Free Iron
Metals: Toxic Mechanisms
Membrane damage
Protein distortion
Calcium channel block
Nutrient depletion
Immune suppression
Detoxifier depletion
Oxidative stress
Sensitivity to Metals
Chemical form
Amount and duration
Age, gender, genetics
Nutrition and immunity
Other toxins
Autism / Mercury Clues
Acidosis Cholinergic block
Low sulphate Autoimmunity
TH2 shift Demyelination
Seizures Visual
Depressed NK Purkinje / granule
Se depletion B6 depletion
Pink Disease
From 1890, often lethal
Often pink cheeks, nose and painful hands (‘acrodynia’)
Calomel teething powder
Typically latent onset
Only 1 in 500 exposed
Pink Disease
Apathy Repetitive rockingLost play Repetitive handsSound / light Poor muscle toneTouch averse SeizuresHead-banging Infections, insomnia
Autism / Mercury Traits
Social deficit Toe-walkingSpeech loss Head-bangingEcholalia Touch-averseRepetitive Sound sensitiveLateral gaze Poor eye-handFlapping RashesCircling Poor sleepAbnormal G.I. ADHD
Case study – C.M.
EPA maximum is 0.1 mcg Hg / kg / day
First Hep-B 12.5 mcg, so X 30 that day
[Presumed] 25 mcg in each DPT and
H-flu. By 6 mos, total Hg 187.5 mcg,
or X 2 EPA (total exposure)
CASE STUDY - C.M.
0
10
20
30
40
50
60
70
80
90
FIRST SECOND THIRD FOURTH
Thimerosal Aliases
Ethyl mercury
Elcide
Ethylmercurithiosalicylate
Mercurothiolate
Merfamin
Merthiolate
Ethylmercuric thiosalicylate
Timerasol, Thimerosal, Thiomerosal..
Mercury Injections
No safety studies
Organic forms of Hg most toxic
Faroes Islands bolus lesson
Infants poor excretors
Vaccines open BBB
Thimerosal and Autism
• CDC: initial suggestion of association, prior to revision of study results
• IOM: thimerosal / autism link “plausible”
• First published epidemiological report: incidence of autism X 6 if received DPT with Hg [Geier M and Geier D, 2003]
Metals-Detox NutrientsVitamin C 250-2000 mg b.i.d ups GSH
Vitamin E 150-400 IU daily helps Se combat Hg and Cd
Selenium 1-4 mg/kg/day
Melatonin up to 0.1 mg/kg
Lipoic Acid 1-10 mg/kg
Support MET pathway
Taurine 200-1000mg/d
Glutathione
Calcium and Heavy Metals
Mercury increases calcium loss
Calcium aids lead excretion
Cadmium decreases calcium
absorption
DMSA Perspectives
Thousands of autistics
No irreversible side effects
Nutritional and gut prep first
Stay up on the zinc
Many excellent responses
Some talk only on DMSA days
Heavy Metals and the Gut Mercury and cadmium avidly bind intestine and are highly caustic
Mercury blocks vitamin B6 and DPPIV
in the gut
Antibiotic-altered flora may recirculate mercury
DMSA Mechanisms?
Reduction of Hg and other heavy metals
Reduction of Cu burdens
Clear sensitive muscarinic cerebral-
dilating receptors.
Definition
Free-radicals are highly-reactive molecules which damage cells by oxidizing lipids,
proteins and nucleic acids.
Some free-radicals are a natural by-product of energy metabolism. Environmental
toxins are either free-radicals themselves, or lead to the generation of free-radicals in the body (as do infections and allergies).
Increase Free-Radicals
Smoking, pollution, ozone, metals Inflammatory cytokines
Infections, allergies Oxidized foods, food additives
Dirty foods (insecticide, herbicide) Unbound Copper and Iron
Depleted anti-oxidant defense
Protect from Free-Radicals Vitamin C Urate
Vitamin E Glutathione (GSH)
Vitamin A Metallothionein (MT)
Vitamin B6 GSHPx Vanilla
Zinc Catalase Phenothiazines
Carnosine SOD Estrogen
Niacinamide Melatonin EPA
Folate CoQ10
Definition
Oxidative Stress is cellular impairment resulting from free-radicals in excess of
available anti-oxidant defense.
The interplay of genes, nutrients and toxins determines the level of oxidative stress.
Metals Increase Oxidative Stress
• Metals with high-affinity for SH-groups (Hg,Pb,Cd,As,) deplete GSH and MT
• Metals with fluctuating valency (Cu, Fe, Mn) generate free radicals directly
• Metals which mimic calcium (Pb,Sn) over-excite the cell via increased intracellular calcium, which generates free radicals.
Especially Sensitive to Oxidative Stress
Gut: extreme sensitivity of
mucosa to free-radicals
Brain: high lipid, low GSH,
low metallothionein levels
Oxidative Stress in Autism?Extensive GI inflammation
Opiod binding blocked by GSH
DPPIV active in reducing conditions
Muscarinic targets
Stim-relieving effect of GSH
DMSO a hydroxyl scavenger
Increased PLA2
Response to DMSA
Autoimmunity
Oxidative Stress in Autism?Poor anti-oxidant nutrient status
Lower GSH and GSHPx
Extreme copper intolerance
Phenolic intolerance
Breathe ethane in ADHD
ApoE4 genotypes
Vitamin C / carnosine trials
B6 blockade in autism
50% high-Mauve
PHF LEVELS
0
1
2
3
4
5
6
ADD ADHD AUT
AVERAGE
MEDIAN
High-PHF Rats
Exceedingly high biomarkers for oxidative stress in these SHR.
Oxidative stress and symptoms in these animals relieved by
vitamin C or MET.
Zinc is Free-Radical Protection
Blocks lipid peroxidation
Protects protein structure by coordination with SH-groups, blocking Cu and Fe.
Essential for maintenance of Vit A level
Supplementation increases GSH
Co-factor for MET pathway
Key constituent for SOD
Deficiency increases SO4 loss
Glutathione (GSH)Ubiquitous FR-quencher, lst-line gut defense
Protects receptor and enzyme function
Key partner to MT
Substrate for GSHPx and Phospholipid Hydroperoxide GSHPx
Excellent responses to I.V. GSH
Significant oral absorption, intact
Excellent responses to oral 10-50mg/kg/d
Oxidative Stress Measurement (“Biomarkers”)
Anti-oxidant nutrient levelsEndogenous anti-oxidant compounds
Oxidized lipids, including breatheOxidized proteins
Oxidized nucleic acidsIsoprostanes, Isolevuglandin adducts
Apoptosis
The Mauve Factor
Excellent response to anti-oxidants across multiple diagnoses
Zinc and B6 deficits, which vary individually and which fluctuate
Putative metric for oxidative stress
“Mauve Factor” Means Pyrroles
• Measurable as “Kryptopyrrole”
• A core test in the the management of all behavioral disorders
• 1-800-494-7785
Urinary Pyrrole: The Mauve Factor
Useful, economical, may be pivotal.
Elevation makes zinc,Vitamin B6
and anti-oxidants top priorities
Careful handling: highly labile
Autistic Urinary Pyrrole Levels and B6 (10mg/kg/day) + Zn (25mg) + Mg (400mg)
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Months of Treatment
mic
rom
ole
s/10
0ml
Mauve Factor Inhibits Heme
Heme Inhibition associated with decreased Zn, increased Fe.
Heme-dependent anti-oxidant enzymes include: catalase,
peroxidase, cystathionine synthase, heme-hemopexin for MT synthesis,
p450, cytochromes for energy production.
Diketone Neurofilament Injury
ConclusionOxidative stress may be the primary,
shared pathological mechanism for diverse factors contributing to autism,
and its reversal may significantly affect the course of the disease.
Biomarker studies underway.
Potential for objective criteria to guide therapy, enhance focus for gene and
tissue studies.
Goal: Lessen Oxidative Stress
Minimize toxins, infections, allergens
Give plenty of anti-oxidants
Support detoxification metabolism:
Vitamins B6, B12, (Folate)
Magnesium, Zn, Selenium (folic acid)
(Methionine)
METHIONINE
HC
GSHMT
CYS
ATP, Mg
B6 (Mg, Zn)
TAU DETOXBILE
SO4SO4
Detoxification Organic foods, pure water Clean living environment
No additives or flavor enhancers Regular bowel movements: fiber, mag-
citrate, vitamin C, bethanecol Plug nutritional holes and suppress
overgrowths DMSA / Lipoic Acid metals protocol
Basic Lab List
Stool studies Mauve Factor RBC minerals Organic acids Serum IgG / IgE
food allergy Vitamins (esp A)
RBC fatty acids Peptides PCR for mycopl.
and chlamydia
Immune profile Toxins Amino acids
Treatment
Supplements
Food avoidance
Suppress overgrowths
Detoxify
Really Key Nutrients
Zinc Magnesium Calcium Vitamin B6 Fatty Acids
Vitamin A Vitamin C Vitamin E Vitamin B12 Biotin GSH
Supplementation
History, physical, lab, empirical
Don’t be deceived: use sensitive measurements
Keep re-checking to confirm
Changing needs and variability
General Approach
Introduce interventions individually
Smaller doses may be necessary at first
Continue interventions unless reason to stop
If combination nutritional formulations are not well-tolerated, add one-at-a-time
Adding Nutrients Individually
Build sequentially Zinc, then P5P/Magnesium Glycinate,
Calcium, Selenium, C, E, Multi-Vit without Copper, Biotin, B12, Cod liver oil (for Vitamin A)
Really assure zinc Away from food, minerals and P5P
Zinc/Manganese about 3:1
Fatty-Acid Basics
Pre-treat with anti-oxidants
Treat low-normal GLA, DGLA and EPA lab values
Dry hair or skin, allergy: usually need fish oil EPA
Infections, leaky gut: usually need evening primrose GLA
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