Toxins in Autism: Mercury to PCBs

1
(No Transcript)
2
Toxins in Autism Mercury to PCBs

• Woody R. McGinnis M.D.
• Anaheim, June 28, 2003

3
Irene (Vicky) Colquhoun 1920-2000
4
Parent Pioneers

• Bernard Rimland
• Ellen Bolte
• Brenda OReilly
• Victoria Beck
• Rik Rollens
• The Mercury Team

5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8
(No Transcript)
9
Autism and ADHD are Symptoms

• Multiple underlying problems
• Variation and commonality
• Gut and nutrition paramount

10
Cornerstones

• Suboptimal Nutrition
• Food Intolerances
• Microbial Overgrowths
• Toxins

11
Gut Disease Predominates

• Esophagitis 69
• Gastritis 42
• Duodenitis 67
• Colitis 88

12
Autistic Gut Symptoms

• Abdominal pain 69
• Chronic diarrhea 58
• Constipation 35
• Night-awakening 42

13
Gut Status

• Poor digestion and absorption
• Leaky gut proteins out, toxins
• and antigens in
• Microbial overgrowths
• Poor enzyme production
• Altered signaling to CNS

14
Gut Dysfunction

• Microbes Nutrients
  Peps, Ags,
• Overgrow Low
  Toxins In

15
Laboratory Indices of Vitamin and Mineral
Deficiency in Autism

• Defeat Autism Now
• 27 October 2002
• San Diego
• Tapan Audhya Ph.D.
• Emar Vogelaar Ph.D.

16
Low Nutrient Levels in Autism(187 Autistic,
11-16 y.o vs. 10-17 y.o. controls)
17
Low Nutrient Levels in Autism187 Autistics
(11-16 y.o.) v. Controls (10-17 y.o.)
18
Low Nutrient Levels in Autism
19
Substrate Requirement for Maximal Activity of P5P
Dependent Enzymes
20
Substrate Requirement for Maximal Activity of P5P
Dependent Enzymes
21
Low Minerals in Autism
22
Membrane Fatty Acids
23
Nutrient Blockade

• Absorption
• Transport
• Breakdown
• Excretion
• Inhibition

24
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

25
Blocked Transport

• PCBs block RBP, so low stored
• and circulating Vitamin A
• Cadmium displaces Zinc
• Toxin-lowered Magnesium poor P5P entry
• Caramel coloring blocks P5P entry

26
Increased Breakdown

• Ubiquitous toxins, including polyhalogenated
  hydrocarbons (PCBs, PCDDs, PCDFs) cause
• Vitamin A destruction

27
Increased Excretion

• ETOH and Gentamycin Vitamin B
• Theophylline Magnesium
• Mercury Magnesium and Calcium
• Sulfa and Indocin Folate
• Tartrazine Zinc

28
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

29
Environmental Toxins in Autism?

• Some Clues
• D-glucaric acid increased in 78
• Plasma glutathione low in 46
• Lower glutathione peroxidase (GSHPx)

30
Organic Toxins in Autism
31
Organic Toxins in Autism
32
Elevated Toxins in Autism(41 autistics, 24
controls)
33
Toxins in Autism
34
Metals in autism?

• Clinical Pediatrics, 1988 23(1)41-44
• Temporal association lead and autism
• Am J Dis Chld, 197613047-48
• Higher blood lead levels and response
• to EDTA chelation.
• DAN 2001 case report normal 4 y.o. regresses
  severely to ASD post-amalgams

35
HEAVY METALS AC / DC DANGER DANGER EROTIC
LIQUID CULTURE JEREMY THE SUICIDES MEGA
DEATH METALLICA MOTORHEAD NEAR LIFE
EXPERIENCE NEUROTICA NEW AMERICAN
SHAME PSYCHOTICA VITAMIN F
36
Toxic Metals

• Mercury Nickel
• Lead Tin
• Cadmium Free Copper
• Arsenic Free Iron

37
Metals Toxic Mechanisms

• Membrane damage
• Protein distortion
• Calcium channel block
• Nutrient depletion
• Immune suppression
• Detoxifier depletion
• Oxidative stress

38
Sensitivity to Metals

• Chemical form
• Amount and duration
• Age, gender, genetics
• Nutrition and immunity
• Other toxins

39
Autism / Mercury Clues

• Acidosis Cholinergic block
• Low sulphate Autoimmunity
• TH2 shift Demyelination
• Seizures Visual
• Depressed NK Purkinje / granule
• Se depletion B6 depletion

40
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

41
Pink Disease Apathy
Repetitive rocking Lost play
Repetitive hands Sound / light Poor muscle
tone Touch averse Seizures Head-banging
Infections, insomnia
42
(No Transcript)
43

• Autism / Mercury Traits
• Social deficit Toe-walking
• Speech loss Head-banging
• Echolalia Touch-averse
• Repetitive Sound sensitive
• Lateral gaze Poor eye-hand
• Flapping Rashes
• Circling Poor sleep
• Abnormal G.I. ADHD

44
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)

45
CASE STUDY - C.M.
46
(No Transcript)
47

• Thimerosal Aliases
• Ethyl mercury
• Elcide
• Ethylmercurithiosalicylate
• Mercurothiolate
• Merfamin
• Merthiolate
• Ethylmercuric thiosalicylate
• Timerasol, Thimerosal, Thiomerosal..

48
Mercury Injections

• No safety studies
• Organic forms of Hg most toxic
• Faroes Islands bolus lesson
• Infants poor excretors
• Vaccines open BBB

49
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

50
Metals-Detox Nutrients

• Vitamin 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

51
Calcium and Heavy Metals

• Mercury increases calcium loss
• Calcium aids lead excretion
• Cadmium decreases calcium
• absorption

52
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

53
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

54
DMSA Mechanisms?

• Reduction of Hg and other heavy metals
• Reduction of Cu burdens
• Clear sensitive muscarinic cerebral-
• dilating receptors.

55
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).

56
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

57
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

58
(No Transcript)
59
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.

60
(No Transcript)
61

62
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.

63
Especially Sensitive to Oxidative Stress

• Gut extreme sensitivity of
• mucosa to free-radicals
• Brain high lipid, low GSH,
• low metallothionein levels

64
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

65
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

66
PHF LEVELS
67
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.

68
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

69
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

70
Oxidative Stress Measurement (Biomarkers)

• Anti-oxidant nutrient levels
• Endogenous anti-oxidant compounds
• Oxidized lipids, including breathe
• Oxidized proteins
• Oxidized nucleic acids
• Isoprostanes, Isolevuglandin adducts
• Apoptosis

71
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

72
Mauve Factor Means Pyrroles

• Measurable as Kryptopyrrole
• A core test in the
• the management
• of all behavioral
• disorders
• 1-800-494-7785

73
Urinary Pyrrole The Mauve Factor

• Useful, economical, may be pivotal.
• Elevation makes zinc,Vitamin B6
• and anti-oxidants top priorities
• Careful handling highly labile

74
Autistic Urinary Pyrrole Levels and B6
(10mg/kg/day) Zn (25mg) Mg (400mg)
75
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.

76
(No Transcript)
77
Diketone Neurofilament Injury
78
Conclusion

• Oxidative 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.

79
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)

80
METHIONINE
ATP, Mg
HC
B6 (Mg, Zn)
GSH MT
CYS
TAU
DETOX BILE
SO4
SO4
81
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

82
(No Transcript)
83
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

84
Treatment

• Supplements
• Food avoidance
• Suppress overgrowths
• Detoxify

85
Really Key Nutrients

• Zinc
• Magnesium
• Calcium
• Vitamin B6
• Fatty Acids

• Vitamin A
• Vitamin C
• Vitamin E
• Vitamin B12
• Biotin
• GSH

86
Supplementation

• History, physical, lab, empirical
• Dont be deceived use sensitive measurements
• Keep re-checking to confirm
• Changing needs and variability

87
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

88
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 31

89
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