Dr.

Praveen Kumaar
Saxenaa

 1. the numbers really going up?

2. Genes, environment and
epigenetics can interact

Gene-Environment
Interactions:
Not Either-Or but Both-And,

G and E probably affect most cases

ASD can be 80% genetic AND 80% environment
Example: if everyone smoked, then who gets cancer is
genetic
Population-attributable fractions do not have to add up to
100%
AUTISM AND ENVIRONMENTAL GENOMICS
Herbert MR, Russo JP, Yang S, Roohi J, Blaxill M, Kahler SG,
McCoy L, Ziegler DA, Hatchwell E
Neurotoxicology, 2006 also Autism and
Environmental Genomics
Chapter in AUTISM, Amaral/Dawson,Geschwind, 2011

Environmental Role in
Autism

Growing body of associations

of environmental exposures
with autism risk and
prevalence

start?
Kanner 1943 on body
symptoms

Case 1: Eating has always been a problem .. for him. He has never shown
normal appetite.
Case 2: large and ragged tonsils.
Case 3: diarrhea and fever following smallpox vaccination . healthy except
for
large tonsils and adenoids.
Case 4: vomited a great deal during his first year feeding formulas were
changed
frequently tonsils were removed
Case 5: nursed very poorly quit taking any kind of nourishment at three
months
tube-fed five times daily up to one year of ageAt camp she slid into
avitaminosis and malnutrition but offered almost no verbal complaints.
Case 7: vomited all food from birth through the third month.
Case 8: feeding formula caused concern. colds, bronchitis, streptococcus
infection, impetigo
Case 9: none of the usual childrens diseases. [? Overactive immune system
Case 10: frequent hospitalizations because the feeding problem repeated
colds
and otitis media
Case 11: was given anterior pituitary and thyroid preparations for 18 months
Kanners original paper, discussed in Jepson 2007

Environment,Diet

medical

Glutathione - critical antioxidant and detox chemical - low

levels in brains of depressed patients,
lower in brains in Chronic Fatigue Syndrome
And low systemically in Autism

Suh, J., W. Walsh, et al. (2008). American

Journal of Biotechnology and Biochemistry
4(2): 105-113,

GI Tract:

Detox

Oxidative stress

 Lack of essential minerals (zinc, magnesium,

iodine, lithium, and potassium may be
especially important).
Pesticides and other environmental toxins.
Advice for Parents of Young Autistic
Children: Spring (2004). James Adams PhD,
Stephen Edelson PhD, Temple Grandin PhD,
Bernard Rimland PhD

Likely Chain of Events

that Leads to Autism
Genetics of suboptimal metabolism
of : one-carbon groups or folate,
transmethylation, transsulfuration,
adenosine, or glutathione.
Food allergies, especially milk or
wheat allergy, add concern.

chain
Nutritional status may be
suboptimal, particularly for vitamins
A, B6,B12, magnesium and zinc.
Cell defenses against toxicity and
infection are hampered.
Toxic exposures occur

 Toxic exposures occur: mercury or

thimerosol, antimony, arsenic,
organophosphate pesticides,
petrochemicals, and solvents.
Hampered are: DPP4 (adenosine
deaminase and exorphin digestion),
methionine synthase, folate
chemistry, glutathione.

Likely Chain of Events

that Leads to Autism

Methionine
metabolism and methylation become deficient

Phosphate delivery to neurons via creatine is subnormal,

causing unreliable and inadequate energy for neurons and
networks to operate and coordinate.
Compromised cell defenses allow measles and other
viruses to invade cells;
abnormal immunity allows infections to become
persistent, measles in particular. Inflammation and gut
dysbiosis occur

 Methylation of phospholipids near

dopamine D4 receptors in neurons
becomes deficient.
Persistent brain infection by
measles may also cause lack of
neuronal phospholipid
methylation.

 Deficient frequency modulation

(synchrony) and deficient energy
modulation of
neuronal networks, during the first
two years of life, prevent adequate
interconnection of neuronal networks.
Coordinated thoughts, organized
responses
and expressive speech regress or do
not develop, depending on age.

Likely Chain of Events

that Leads to Autism
Inflammation (gut or brain) results in cytokine and
oxidant-induced epigenetic changes, such as
upregulation of ubiquitin ligase (chromosome 15).
Methionine metabolism is routed away from
methylation towards transulfuration (cysteine, GSH),
but transsulfuration is disabled and metabolic response
to inflammation is chronically deficient.

Biochemical, epistatic, and infectious gridlock

occurs, and neuronal network coordination
remains deficient = autism.
Pangborn, Jon, PhD, & Sidney MacDonald Baker, MD. Autism:
Effective Biomedical Treatments. Sept 2005. ARI DAN! Project.
San Diego, CA.

 Metabolites
Mostly reduced or no change; few
reports of increase
Most studies done on 1.5T which has
poor signal to noise ratio (only 1of 22
done on 3T) and could miss differences
Shetty, Ratai, Ringer, Herbert, 2009
Dager review chapter 2008 and
many papers

 Metabolite level
correlating with
brain Activation

More NAA in controls

than in autism
Linear correlation of
amount of functional
activation to amount
of NAA
NAA = Nacetylaspartate

 White matter FA was significantly

lower in key regions of prefrontal lobe
and right ventral temporal lobe.
Lower FA linked to higher (worse)
diagnostic symptom scores
Author interpretation:
In light of spectroscopy showing
lower NAA less neuronal integrity or
number, lower structural integrity
may be consistent with
neuroinflammation
Cheung et al., 2009

 Connectivity
Sensory processing
Are these caused by the large-scale
structural problems?
Or are they caused by cell
metabolism problems?
Most research has assumed the
former, but not
tested it as a hypothesis

Thinking Outside the Box

Lising what is biologically different

Inflam. Bowel Disease
Opioids
Persistent Measles
Reflux Esophagitis
Gastritis
Leaky Gut
Food Allergy
Heavy Metal Burden
Brain Autoimmunity
Dysbiosis
Thrombophilia

Seizures/Sensory Issues
Perfusion Defects
Purine Disorders
Elevated Ammonia
Omega 3 deficit
Sulfation Defect
Serotonin Defect
Dopamine Defect
Nutritional Deficit
Melatonin Deficit

None Can Be Ignored,

But we need to prioritize
Progress requires attention to details
All issues must be addressed eventually
The priority is unique to each child
However, the Gut is generally the
best place to start
Actually, SLEEP is first, but
usually fixing the gut can
remedy many of the sleep issues

Gut Issues
Core Focus (Wakefield)
Inflammatory bowel disease/Measles
Opioids
Dysmotility =
Constipation/Diarrhea/Reflux
Leaky Gut Matrix Metaloproteinases
Dysbiosis

Biomedical Rx
Reducing neuroinflammation
by enhancing natural
detoxification pathways may
improve the clinical course
of autism spectrum
disorders

Inflammation
Brain Nervous system

Immune system

Gut

Autism Treatment?

By FDA standards ALL treatment for Autism is OFF

LABEL meaning they have not approved any
treatments for Autism.
Every treatment is therefore at the discretion of
the treating physician and the parent/patient.
However, subcomponents e.g. allergy,
inflammatory bowel disease, vitamin
deficiencies, etc, DO have FDA approval.
ADHD has numerous approved medications for
children,
ASD none, but there are numerous studies
using SSRI, novel antipsychotics (Risperdal)

Precautionary Principle
We (as physicians) must act on facts
and on the most accurate interpretation of
them, using the best scientific information.
That does not mean that we must sit back
until we have 100% evidence about
everything.
When the state of the health of the people
is at stake we should be prepared to take
action to diminish those risks even when
the scientific knowledge is not conclusive.
Horton. Lancet. 1998;352(9124):251

Rx deals with
Toxic Environment
Toxic Food
Nutritionally Deficient Foods
Immune Systems are over
stimulated
Oxidative Stress

General Principles:
Detoxification

Reduce Toxic Load: Minimize exposure

Increase Mobilization: Toxic metal
chelation as necessary
Maximize Biotransformation: Balanced,
effective, and supported phase I and II
detoxification
Minimize Redistribution: Bowel health

Dental Amalgams?

Documented source of Hg
Removal associated with 50% or more
reduction in body burden on provocation
testing
Safe removal essential
www.iaomt.org
Support during removal options
Chelation before, during and after?

Preparation for Treatment

Remove sources of toxinsFish (Hg
containing)
Dental amalgams
Fix the gut
Importance of fiber and regular BM
Optimize Detoxification Routes urine,
stool, sweat saunas
Optimize Antioxidant Status
Buffered vitamin C, vitamin E, CH3-SH

Preparation: Optimize Nutrient

Status
Detoxification diet (crucifers, allium,
green tea, protein)
Adequate mineralization (Zn, Se, Mg
especially)
Amino acid replacement (empiric or
based on testing)
Optimization methylation and
sulfation status-Methyl folate,
methylcobalamin, B6, TMG, NAC,
whey protein
Herbal support (milk thistle, garlic)

Treatment
Continue pre-treatment strategies
Gut support, minerals, amino acids,
sulfation/methylation support,
antioxidants, herbs
Chelating Agents (DMPS, DMSA,
CaETDA, Zinc DTPA)Informed consent
needed
Intravenous Support (GSH, vitamin C,
PC)
Fluids, fiber, exercise
Sauna Therapy

Adjunctive Use of Supplements

Support Phase 1 and Phase 2 Detox
EssentialMultivitamin and mineral
Additional zinc citrate 20-50 mg/d
Additional selenium 100 200 mcg/d
Methylationsupport (B6, MF, MeCbl)
GSH support (NAC, lipoicacid, whey
protein, milk thistle, green tea,
elagicacid)
EFAs1000-2000 mg n3,
vitamin D3 2000-4000 U/d
Other options Phosphatidylcholine
Alginates (to bind Hg in the gut)

Support for Optimal Phase I and

Phase II
Phase I: Broad-spectrum nutritional support:
magnesium, copper, zinc, carotenoids, vitamin
C, vitamins B2, B3, B6, B12, folic acid
Phase II: Cofactor supplementation: whey, NAC,
glutamine, glycine, sulfur donors (taurine,
sodium sulfate), pantothenic acid, magnesium,
methyl donors (folic acid, choline, methionine,
TMG, SAMe)Specifically:Lglutathione is critical
for neutralization of functionalized toxins.
Glycine and taurine support phase II
conjugation reactions.
Sodium sulfate and N-acetylcysteinesupport
phase II sulfation clearance.

Biology of Metal Toxicity

Enzyme disruption Irreversibly binds to sulfhdryl
groups (SH) on enzymes (like MS and porphryins)
Lowers glutathione
Direct cellular and neurotoxin
Mitochondria toxin and increases oxidative stress
Dose dependent
Immunotoxicity Low level toxicity dose
independent
Autoimmunity

Neurochemistry of Mercury
Poisoning

Disrupts serotonin metabolism

Alters dopamine system
Increases glutamate
Poisons enzyme that degrades epinephrine
Decreases muscarinic (acetylcholine)
binding density in hippocampus and
cerebellum

Impaired Metallothionein:Native
Intracellular Metal Chelator

Inability to handle toxic metals

Oxidative stress
Decrease in reduced glutathione
Proinflammatory state
Zinc depletion

Biology of Detoxification:Genetics,
Environment, Nutrients

The central role of

methylation and sulfation
in health and in diagnosis
and treatment of chronic
illness and metal toxicity

Nutrition
and
Neurology

Fatty acids
N-6 Fatty Acids
Impaired growth
Dry and scaly skin
Polydipsia
Polyuria

ADHD Children
Polydipsia
Eczema
Asthma
Allergies

Nervous System and Fatty Acids

The nervous system is the organ with the
second largest concentration of lipids,
exceeded only by adipose tissue.
35% lipids are long-chain polyunsaturated
fatty acids (LC-PUFAs), such as arachidonic
acid and docosahexaenoic acid , which are
known to play an essential role in brain
development and functions.
AA and DHA could be either provided in diet
or synthesized in the body from the essential
fatty acid (EFA) linoleic acid (LA; 18:2n-6) and
alpha linolenic acid (18:3n-3).

The n3 and n6 PUFAs comprise 14% and

17% of the total FAs in the human brain
and are predominantly DHA and
arachidonic acid (AA;20:4n6), respectively.
Essential fatty acids are required for
optimal growth and development in
children.
In humans, alpha-linolenic acid (ALA) is
converted into the long-chain n-3 (omega3) fatty acid docosahexaenoic acid (DHA),
a major constituent in membranes of the
brain and retina and important for the
maintenance of optimal brain function.

EFA
Children with Autism have also been
shown to have lower plasma or red
blood cell DHA concentrations and
symptoms such as increased thirst
and urination that are characteristic
of essential fatty acid deficiency,
which suggests alterations in FA
metabolism that may share a
common genetic susceptibility.

AMINO ACIDS

MAKE OTHER SMALL MOLECULES

BECOME UNITS IN BIG PROTEIN
MOLECULES
WHEN JUST A FEW ARE JOINED
THEY ARE CALLED PEPTIDES

Thiol

Thiol chemistry is the core of human

chemistry.
It is a vehicle for detoxification.
It is a target of toxin mercury
It is a therapeutic landscape of autism.
It is a stage where individuality plays.

Glutathione: Master Antioxidant

Present in all living cells including the brain
Primary free radical protector for the cell
Detoxifies external toxicants, carcinogens,
drugs
Maintains cell membrane stability
Maintains mitochondrial redox potential balance
Regulates protein, DNA biosynthesis, and cell
growth
Enhances immunological function via
lymphocytes
Prostaglandin synthesis
Amino acid transport

Dietary Supplements to Optimize

Reduced Glutathione Levels
Reduced glutathione, 0.6-1.2 g/day
N-acetyl cysteine, 600-3000 mg/day
Lipoicacid, 200-1000 mg/day
Whey protein concentrates, 2-3 servings/day
Magnesium, 400+ mg
Vitamin C, 500+ mg
Vitamin E, 400 IU
Pantothenic acid, 500-1000 mg/day
SAMe, 400-800 mg/day

Intravenous Support

Intravenous GSH 600-1200mg (during

treatment or 2-3 xweek)
Methylcobalamin 5 mg (5000 mcg) SC
2 xweek
Intravenous phospholipids (PC) 3-5
vials (Lipostabil)
NAC, , MeCbl daily to weekly
High dose vitamin C 25-50 grams weekly

Methionine

THE MOST ESSENTIAL OF AMINO

ACIDS
THE SOUCE OF METHYL GROUPS
THE MOTHER OF THIOL CHEMISTRY
A CONSTANT SUPPLY IS NEEDED

Zinc and Neurology

Essential for brain development.
Essential for Central Nervous System
function.
Very potent inhibitor of the NMDA (Nmethyl-D-aspartate) receptor complex.
Involved with Adenosine A1 and A2A
receptors.
Important for the production and
modulation of Melatonin.

Zinc
May also influence the N2 wave in
the frontal and parietal regions of the
brain. Information processing and
inhibitory processes.
Zinc is required for the conversion of
dietary pyridoxine to its active form,
pyridoxal 5 phosphate, which is
necessary for the conversion of
tryptophan to serotonin.

Iron and asd

Serum ferritin levels <45 mcg/L
might indicate a risk for sleep wake
transition disorders, including
abnormal sleep movements, in
children with ASD.
Eur Child Adolesc Psychiatry(2009)

Serum ferritin was found to be

significantly lower in children with
ASD

Glutathione
The complete transsulfuration of methionine
to GSH occurs primarily in the liver, plasma
concentrations of cysteine and GSH generally
reflect hepatic synthesis and export.
Approximately 80% of GSH synthesized in
the liver is exported to the plasma where it is
hydrolyzed to cysteinylglycine and cysteine
for uptake by tissues, such as the brain, that
lack or weakly express the complete
transsulfuration pathway.
Clin Chim Acta (2003)
Biochem Soc Trans (1982)
Adv Enzymol Relat Areas Mol Biol (1999)

Factors that affect

Glutathione
Viral infection
Nutritional deficiencies
Impaired detoxification - Negatively affect
GSH synthesis in the liver and can
indirectly affect peripheral redox status in
brain and immune cells that require
cyst(e)ine import from the liver to
complete transsulfuration and GSH
synthesis.
Adv Enzymol Relat Areas Mol Biol (1999)

Ascorbate and Glutathione

Ascorbate and glutathione compete for free
radicals in cells, it is logical that an increase in the
concentration of ascorbate will spare glutathione
because ascorbate scavenges a greater
percentage of free radicals.
Ascorbate readily reacts with glutathione radicals
arising from the reaction of glutathione and free
radicals.
Ascorbate spares glutathione first by competing
with glutathione for free radicals and second by
converting thiol radicals back to glutathione.
Each 1-mol change in ascorbate is associated
with a change of 0.5 mol in glutathione.
AJCN (1/2003)

Inflammation and Autism

A recent report documented the presence of
chronic inflammation in the autistic brain that
seems mediated by innate microglial activation
and proinflammatory cytokines.
The inflammatory response is augmented when
GSH concentrations are low, and chronic
inflammation depletes GSH further and promotes
a self-perpetuating cycle that could exacerbate
gastrointestinal and central
nervous system inflammation associated with
autism.
Int Rev Psychiatry (2005)
Ann Neurol (2005)

Gastrointestinal Inflammation and

Autism
Several clinical studies documented
an increased prevalence of
gastrointestinal inflammation and
increased mucosal permeability in
the upper and lower intestines in
autistic children.
Autism (2003)
Curr Gastroenterol Rep (2002)
Exp Biol Med (Maywood) (2003)

Diagnostic interventions

Scheme for
considering
options for
diagnostic trials
in children with
Autism Spectrum
Disorder.

Tantrums and Meltdowns

Transition Issues
Suspect
Gluten/Casein leaks
Look for offending
agent or setting
Clean diet
Excitotxins, MSG,
hydrolyzed vegetable
proteins, color
additives, corn syrup
etc are all offenders

GABA 500-1000mg
daily
Taurine 1000-3000mg
daily
L-theanine 100mg 1-2
times daily

Magnesium
Deficiency increased with:
High CHO intake
Stress
Diabetes
Alcohol
Caffeine
Diuretic therapy

Magnesium and Dopamine

Pharmacologic use of Mg can decrease
neurologic deficit in experimental head
trauma, possibly by blockade of Nmethyl-D aspartate receptors.
In conjunction with high doses of
pyridoxine, Mg salts benefit 40% of
patients with autism, possibly by an
effect on dopamine metabolism.
Magnes Trace Elem (1991-1992)

Coenzyme Q10
Mitochondrial Relationship
Proton-electron translocation in
mitochondria.
Protects mitochondria from oxidation.
Plays a role in permeability transition of
the
inner mitochondrial membrane.
Lowers serum lactate and pyruvate levels.
> 50% reduction post 3 months
Dosage 150 mg/day

Methylation Capacity vs. Antioxidant

Capacity
Biochemical findings with Autistic Children
Significant decrease in methylation capacity
( SAM:SAH)
S-adenosylmethionine (SAM)
S-adenosylhomocysteine (SAH)
Decrease antioxidant/detoxification capacity
( GSH:GSSG)
Reduced glutathione (GSH)
Oxidized disulfide form of glutathione
(GSSG)
Increase in oxidative stress (GSSG)

Transmethylation and
Autism
Significant improvements observed
in transmethylation metabolites and
glutathione redox status after
treatment suggest that targeted
nutritional intervention with
methylcobalamin and folinic acid
may be of clinical benefit in some
children who have autism.

Homocysteine

Choline

Choline
Deficient in cluster headaches
Component of acetylcholine
Lowers Homocysteine levels
Found in lecithin
Liver disorders may be prone to
deficiency.

The PK Protocol
First --- Heal the Membrane
Detoxication and essential fatty
acids
Very essential to balance omega 6
before supplementing omega
3s

Treatment of neuroinflammation
Oral & iv lipid therapy
Aberrant lipid metabolism may follow
exposure to neurotoxins in patients with
autism,ms,epilepsy,parkinsons
Targetted IV therapy with
phosphatidylcholine,Folinic
acid,Glutathione is an attempt to clear
neurotoxins ,address phospholipid integrity
, and stabilise the neuroinflammation

Protocol
6 months period weekly infusion of IV
phosphatidyl choline, folinic acid,
glutathione
Oral therapy with phosphatidyl choline
,evening primrose oil, balanced 4:1 omega
6:omega 3 ratio oil , folinic acid,
methylcobalamine,
mitochondrial/peroxisomal cocktails
( thiamin,riboflavin,pyridoxine,biotin,
pantothenic acid,NADH,carnitine , co Q 10)
trace minerals & electrolytes

Clean 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 purifier, especially in the bedroom.

Avoid prolonged 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

Casein-free/Gluten-free/Soy-free Diet Trial for 3-6

months.
Avoid sugar and refined starch, high fiber diet,
maximize antioxidants,
cruciferous veggies,
turmeric, garlic
Limit processed and preserved foods; organic is best.
Avoid EXCITOTOXINS eg. Caffeine, MSG, NutraSweet, red/yellow
food dyes, nitrites, sulfites, glutamates, preservatives).

Limit intake of PHENOLICS (apples, grapes, strawberries).

Limit sources of Copper (chocolate, shellfish, tap water, artificial
food dyes).

Drink plenty of filtered water.

Never microwave in plastics or Styrofoam, do not

store food in plastic or foil, or cook on Teflon
coated pans.
Eliminate seafood.
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.
Limit Genetically Modified Foods (GMO).
Add fermented foods (coconut kefir, cabbage, goat
milk yogurt

Excitotoxins Glutamate
Excitotoxins = Substances that cause an excess
of excitatory neurotransmission in the brain. If
inhibitory neurotransmission is lacking, the excess
excitation may lead to neuronal death. Neuronal
death leads to chronic inflammation in the brain

Glutamates

Monosodium Glutamate (MSG)

Hydrolyzed Protein
Modified Food Starch
Natural Flavors
Peas, Mushrooms, Tomatoes

Gut cleansing
Daily bowel movements are a goal.
Add digestive enzymes with meals.
Start high potency probiotics
(acidophilus and bifidus).
Start treatment for dysbiosis
depending on symptoms and labs.

If persistent symptoms:
Eliminate disaccharides from diet
for 3-6 months
Specific Carbohydrate Diet

Consider referral to knowledgeable

GI specialist
Consider trial of IV Secretin
Add natural anti-inflammatory
agents.

Keep close eye on gut during any

detox regimen.

Summary
Dietary restriction (gluten-free, caseinfree, soya-free)
Nutrient therapy (vitamin/mineral
supplementation)
GI pathogen treatment (antibiotic eg
metronidazole/gentamycin/vancomycin)
(antifungal eg
fluconazole/itroconazole/nystatin)
Methylation strategies (methylcobalamin)

Food and Additive Allergy

Avoid artificial colorings and additives.
Especially avoid tartrazine, yellow food coloring.
Avoid artificial sweeteners = aspartame & sucralose.
Consider an Allergy Elimination Diet:
Doris Rapp M.D. documented alterations in EEGs
while children were challenged with allergens.The
EEG results corresponded with dramatic behavior
changes in the children, including hyperactivity.-Is
this Your Child? Discovering and Treating
Unrecognized Allergies in Children and Adults by
Doris Rapp.

Favourable effect of a standard elimination diet

on the behavior of young children with
attention deficit hyperactivity disorder (ADHD):
a pilot study.
40 ADHD kids -62% showed at least 50%
improved behaviouron both the Connerslist and
the ADHD Rating Scale at the end of a 2-week
elimination diet.
PelsserLM, Ned TijdschrGeneeskd.2002 Dec
28;146(52):2543-7. (in Dutch) PMID: 12532668
Test for inhalant allergies with end-point
titrationand oral drop desensitization .

24 hyperactive preschool-aged boys .

Baseline 3 weeks, a placebo-control 3 weeks,
experimental diet of 4 weeks.
> 50% exhibited a reliable improvement in
behavior and negligible placebo effects.
Several non-behavioral variables improved on
the experimental diet, particularly halitosis,
night awakenings, and latency to sleep onset.
Kaplan, BJ et al: Dietary replacement in
preschool-aged hyperactive boys, Pediatrics,
vol83, 1989, pp7-17.

Crook, WG: Treatment of attention deficit hyperactivity

disorder (comment/letter), Annals of Pharmacotherapy,
26(4):565-566, 1992, April.
Egger, J, et al: Controlled Trial of hyposensitizationin
Children with Food Induced Hyperkinetic Syndrome,
Lancet, May 9, 1992, 339: 1150-1153.
Hughes, EC, et al: Food sensitivity in attention deficit
disorder with hyperactivity: a procedure for differential
diagnosis, Annals of Allergy, vol49, pp 276-280, 198
Mayron, LW: Allergy, learning and behavioral problems,
Journal of Learning Disabilities, vol12(1), 1979, pp 3241.
McGovern, J et al: International Journal of Biosocial
Research, vol4, 1983, pp 40-42.
OShea, JA et al: Double-blind study of children with
hyperkinetic syndrome treated with
multiallergenextract sublingually, J of Learning
Disabilities, vol14(4), 1981, pp 189-191 & 237.
Rapp, D: Does diet affect hyperactivity? Journal of
Learning Disabilities, vol11(6), 1978, pp 383-388.

Nutrient Supplements
Rational dosages of nutrients have a prolonged
effect on learning disabilities.19 L.D. kids in
crossover RCT with nutrient supplementsx 2 yrs.
All showed significant academic and behavioral
improvements within a few weeks or months.
Some children gained 3 to 5 years in reading
comprehension within the first year of treatment.
All children in special education classes became
mainstreamed, and their grades rose significantly.
2 more yrs open label-the difference in scores between
the 2 groups reached statistical significance (P < .01).
Carlton RM. AlternTherHealth Med.2000
May;6(3):85-91.

Do nutrient supplements and dietary changes

affect learning and emotional reactions of
children with learning difficulties? A controlled
series of 16 cases.
16/32 L.D. kids in RCT nutrient supplementsx 22
wks.
Significantly-improved behaviourat school, at
home, and in the clinic.
Significantly-greater gains in reading skills.
Increased IQ scores of 5 to 35 points (mean =
17.9) for the experimental group were twice the
control group (mean = 8.4).
ColganM,NutrHealth.1984;3(1-2):69-77.

Vitamin B Deficiency
Coleman , M, et al: A preliminary study of the
effect of pyridoxine administration in a subgroup
of hyperkinetic children: a double blind crossover
comparison with methlyphenidate, Biological
Psychiatry, vol4(5), 1979, pp. 741-751.
Hoffer, A: Treatment of hyperkinetic children with
nicotinamideand pyridoxine, Can Med Assoc
J,vol107, 1972, pp. 111-112.
Longnecker, J, et al: Effects of prolonged subclinical dietary deficiencies on one or more
nutrients, Federal Proceedings, vol46, 1987, p
903.

Mineral Deficiencies:
Magnesium
Improvement of neurobehavioral disorders in children
supplemented with magnesium-vitamin B6. I.
Attention deficit hyperactivity disorders.
40 ADHD kids Rx with Mg & B6 (6 mg/kg/d Mg, 0.6
mg/kg/d vit-B6) > 8 weeks.
Started with lower RBC Mg levels than 36 controls.
Hyperactivity and aggressiveness were reduced
School attention was improved.
Significant increase in RBC Mg. When the Mg-B6
treatment was stopped, clinical symptoms
reappeared in few weeks, with a decrease in RBC Mg
values.
Mousain-BoscM,MagnesRes.2006 Mar;19(1):46-52.

Hansen, C, et al: Copper and zinc deficienciesin

association with depression and neurological findings,
Biological Psychiatry, vol. 18(3), 1983, pp. 395-401.
Walther, B, et al: Does dietary phosphate change the
neurophysiologic functions and behavioral signs of
hyperkinetic and impulsive children,
MonatsschrKinderheilkd, vol. 128(5), 1980, pp 382-385.
Ward, NI et al: The influence of the chemical additive
tartrazineon the zinc statusof hyperactive children
a double blind placebo-controlled study, Journal of
Nutritional Medicine, vol. 1, 1990, pp. 51-57.

Amino Acid Deficiencies

Nezmer, E D, et al: Amino acid supplementation as therapy
for attention deficit disorder, Journal of the American
Academy of Child Psychiatry, vol. 25 , 1986, pp 509-513.
Reimherr, FW, et al: An open trial of l-tyrosine in the
treatment of attention deficit disorder, residual type,
American Journal of Psychiatry, Aug. 1987, 144:8, 10711073.
Wender, P.H., et al: Amino acid precursors for the treatment
of add-residual type, Psychopharmacological Bulletin, vol.
21, 1985, pp 146-149.
Wood, DR, et al: Treatment of attention deficit disorder with
di-phenylalanine, Psychiatry Res. Vol. 16, 1985, pp. 21-26.

Detoxification (heavy metal chelation

eg EDTA, DMSA, DMPS)
Immune enhancement (omega-3 fatty
acids, glutathione, probiotics)
Antiviral treatment (natural antivirals
eg garlic, olive leaf extract, oregano oil)
(pharmaceutical antivirals eg
valaciclovir, famciclovir, aciclovir)
Hyperbaric oxygen therapy/Ozone ,

My perspective
Five years ago I wouldnt have said this even a
year ago I wouldnt have said it but the more
success weve had ,the clearer it has become.
All chronic disease is toxicity
you get rid of the toxicity and you put out the
fire
you may need to rebuild afterward but you
must put the fire out
We have to learn the best ways to detoxify and
chelate while we re-mineralize with magnesium
and other much needed minerals like iodine
selenium and zinc

Heavy Metal Testing

Provocative Testing is often unconvincing

in ASD due to impaired detoxification.
Urine Toxics, Fecal Toxics, and Hair
Analysis show excretion of toxic
metals. We have no way to determine
total body burden.
RBC Blood testing is a poor measure of
chronic heavy metal burden. However,
blood may show acute exposure.

Testing
There are no standards for diagnosing chronic
toxicity.
There are no tests to determine body burden
of metals.
Lead is a bone seeker and can only be
measured in blood 12 hrs after exposure,
therefore blood Pb is not an adequate
indicator of chronic toxicity.
Mercury has an affinity for fatty tissue and a
developing brain, and is very rarely seen in
blood.
Urinary porphyrin testing promising.

Heavy Metal Detox:

Reduce Exposures.
Nutrients to support detoxpathways,
especially methylation, sulfation, and
glutathione production.
Natural Chelators.
Synthetic Chelators.

Reduce Toxic Exposure:

Avoid amalgam fillings.
Avoid Hg-containing fish.
Drink purified water.
Eat organic foods.
Avoid hydrogenated fats.

POPs (persistant organic pollutants)

Phthalates, Pesticides, Herbicides, Bisphenol A,
PCB, PCBD, DDT
Difficult to detox, Stored in Fat indefinitely
Endocrine Disruptors Substances that may
at tiny doses interfere with hormonal signals
that regulate human organs, development,
metabolism, and other functions.
Low Dose Hypothesis No safe levels
(pp trillion have biologic effects)

POPs
Damage DNA (affect DNA methylation) 90% inherited
Harm developing nervous system
Carcinogenic
Gender bending chemicals
Alter brain structure, neurochemistry, behavior,
reproduction and
immune response in animals
Damage sperm and cause genital malformations
Precocious Puberty
Allergies, Asthma, Diabetes, Heart Disease, Thyroid
disease

Used in flexible plastics, cosmetics, perfumes,

food
Found in breast milk, cord blood, and infants

Methylation:
methyl donors

Glutathione (GSH)
Cysteine
B6, B12
Methionine
SAM-e
Folate, DMG, TMG

Sulfation

To convert into a sulfate; an important

role in the second phase of liver
detoxification.
What you need to know about sulfation
is that it is an important part of:
Detoxification including heavy metal
detoxification

Nutrients:

Mg, Zn, Vit C, B-12, B6 (P5P), Se.

EFAs as Hg-free fish oil.
Vit D to 25-OH-D level >40 (<60).
Iron until ferritin > 50 (<100).
Avoid copper unless tested to be low.
Probiotics and fiber.

Support Glutathione:

Vit C, 250-500 mg BID

Folinic acid, 400 mcg BID
TMG, 500 mg BID
B6 as P5P, 25 mg QD.
Methyl-B12, 75 mcg/kg SQ BIW

Chelators- DMSA, DMPS, EDTA

Bind a free metal ion into a ring structure thereby
neutralizing its reactive state, the bond between
chelator and heavy metal is considered irreversible.
Chelators have varying affinities for different heavy
metals.
Do not cross Blood Brain Barrier.
Heavy Metal/Chelator Complex is excreted thru
kidney and liver thereby placing a burden on these
organs.
Side effects include abnormal kidney and liver
functions, leukopenia, mineral depletion, gut
dysbiosis, rashes, nausea, and fatigue. StevensJohnsons rare possibility.
Monitor cbc, liver, kidney, electrolytes, mineral
stores, and GI status during process

Chelators- DMSA, DMPS, EDTA

DMSA (dimercaptosuccinic acid)

Good affinity for mercury and lead

Excellent safety record
Treat gut before starting
Monitor cbc, liver and kidney function
Causes Zinc depletion
Oral Protocols
Newer Transdermal Protocols
ALA (alpha lipoic acid)

Antioxidant, Regenerates Glutathione,

Donates Sulfur
Not for initial use, or if severe dysbiosis
Potential for crossing blood brain barrier
Oral

(ethylenediaminetetraacetic
acid)
Low affinity for Mercury,
good affinity for Lead,

Aluminum, and Copper

CaNa2 EDTA FDA approved for Lead Toxicity, only
chelator proven to improve IQ
MgNa2 EDTA when given IV is used predominantly
for arteriosclerosis, may cause fatal hypocalcemia if
given rapidly
Pulls Lead from bone, DMSA does not
Preparations:

Oral
Transdermal
Intravenous
Other (ionized, lipoceutical)
Suppository

DMPS
(dimercaptopropanesulfonic
Excellent chelator ofacid)
Mercury, poor affinity for

Lead
U.S. FDA approved for prescription compounding
Excretion is predominantly - kidney
Transdermal DMPS

Dr. Rashid Buttar Protocol

Oral

50% absorbed, may cause GI distress

Suppository
Intravenous

IV CHELATION
Pre-Load Vitamin C, Pediatric Multi-Trace Minerals
and Glutathione (sometimes also NAC)
DMPS used as 2 mg/kg in 50 cc NS over 5 10
minutes. (After Vit C, minerals etc as Preload)
CaNa2-EDTA used as 10 mg/kg in 50 to 100 cc NS
over 5-10 minutes. (After Vit C, minerals etc as
Preload)
Collect 6 hour post urine at least monthly for toxic
metals
Monitor CBC and Chemistries
Be Prepared for IV Emergency, Bronchospams etc.

Suppository Route: DMPS or

DMSA or CaNa2-EDTA
Due to excessive GI side-effects this route
may be better than oral for DMPS or
DMSA
Well Absorbed with nearly comparable
metal excretion results
Minimal Side-effects
Cost Effective
Home Based treatment
Dosing 2-4 mg per kg DMPS and 10 mg per
kg for DMSA

Clathrating Agents
Trap heavy metal into a colloidal mesh,
rendering the heavy metal innocuous.
Many are found naturally, ex. Chlorella
and Spirulina.
Affinity is very strong, therefore agents
can become contaminated with heavy
metals easily.
May help detox POPs.

TTFD/Allithiamine
(thiamine tetrahydofurfuryl
disulfide
Active form of Vitamin B1
Supports methylation and sulfation pathways
Supports ATP production in Krebs Cycle
Increases Arsenic excretion
Decreased ATEC scores in autistics (Lonsdale,
2003)
Transdermal preparations
Side effects foul odor when sweating (skunk
smell

Methylcobalamin(B12) Injections
Helps pivotal step in the methylation cycle.
Bypasses impairments along folate pathway.
Methylates Dopamine-4 Receptor.
Shown to help cognitive ability, abstract
thinking, attention, focus, awareness,
language, behavior, OCD, anxiety, .
(Neubrander, 2004).
Highly concentrated, injected subcutaneous in
gluteal tissue, slow release, painless, no
toxicity associated with high dose vitamin B12.
No test for methylB12 deficiency.
Side effects increased energy, hyperactivity,
agitation, detox reaction.

Far Infra-Red Sauna

Deep penetration of heat
Increases core temperature
Enhances circulation, lymphatic flow,
and natural release of stored toxins
Increases release of toxins thru
sweat, liver, and kidney
Helpful for detox of POPs (persistent
organic pollutants)
Protocol

Ozone Therapy
Oxidation & oxygenation
Correct the chronic oxidative stress by up
regulating the antioxidant system.
Possible improvement of the cellular
redox potential.
Induce a mild activation of the immune
system
Auricular & rectal route preferred
Autohemotherapy minor

Natural Chelators:

Garlic, Onions, and Eggs.

Chlorella and Cilantra.
Fermented, broken-walled chlorellacilantro products.
Ionic or clay footbaths.
Zeolites.

Blood Test Not Enough

Most physicians still rely upon blood tests to

diagnose lead toxicity -rarely even look for other
toxicities.
Blood tests good for recent exposures, such as
when children are currently living in a home with
leaded paint dust.
Chronic or old exposures will not show in the
blood -can only be diagnosed by looking at
residues in the hair or nails, or by collecting
a urine sampleafter giving an agent that binds
the toxic metal and pulls it out the body

Metal Detox

Mobilizing heavy metals judiciously and

carefully according to established
protocols, can substantially move the
physiology toward a homeodynamically
balanced state.
In the chronically ill patients who has
compromised GI, liver, and renal function
and who is nutritionally deficient, starting
with chelation therapy can backfire unless
the other areas are dealt with first.

TREATMENT

GASTROINTESTINAL PROBLEMS
DIET DIGESTIVE ENZYMES
SPECIFIC TREATMENTS FOR TOXIC BACTERIA,
YEAST, AND/ OR PARASITES
PROBIOTICS
GROWTH ENHANCERS FOR GOOD BACTERIA
GI CONSULTATION IF WARRANTED
ANTIINFLAMMATORY AGENTS
LAXATIVES
OTHERS

NUTRITIONAL SUPPLEMENTS
USE BASIC NUTRITIONAL
SUPPLEMENTS: ZINC, CALCIUM,
MAGNESIUM, VITAMIN B6
,MELATONIN VITAMIN C, VITAMIN A
METHYLCOBALAMIN
AMINO ACID SUPPLEMENTS
EXTERNAL ENHANCEMENT OF SULFUR
(EPSOM SALT BATHS)

TREATMENT
HEAVY METALS
REMOVAL OF AMALGAM DENTAL FILLINGS
AVOIDANCE OF SEA FOODS
DETOXIFICATION/ CHELATION OF HEAVY
METALS
DMSA ORAL,
RECTAL EDTA
DMPSORAL, TD
TTFD TRANSDERMAL

TREATMENT
SUPPLEMENTATION OF
SELENIUM
REDUCED GLUTATHIONE
SULFATE

FAR INFRARED SAUNA

DETOXICATION
GET RID OF TOXIC INHIBITORS
DETOXIFICATION TRIALS, THERAPY IF
INDICATED
WE NEED TO PULL OUT THE
HEAVY METALS WITHOUT DUMPING
THEM INTO THE BODY WHERE THEY DO
EXTENSIVE DAMAGE ON THE WAY OUT
OR WORSE JUST GET REDISTRIBUTED TO
OTHER ORGAN SYSTEMS

Chelation
During chelation we need to provide
support for both the kidneys and the
liver directly but indirectly we can
take a great load off these overworked
organs by opening up an exit channel
through the skin.
Fir sauna
clay baths

FIR SAUNA
DETOX THROUGH SKIN
drawing toxic substances out of
the system via the eliminative
channels of perspiration.
clay baths and far infrared saunas
are cabable of covering a broader
range of chemicals

skin organ of detoxification

and elimination.
Sweat gets rid of water-soluble toxins, and
even helps to eliminate toxic heavy metals
such as mercury
80 to 85% of the fir sweat is water with the
nonwater portion being principly cholesterol,
fat-soluable toxins, toxic heavy metals,
sulfuric acid, sodium, ammonia and uric acid
sweat from conventional saunas is 95
to 97% water with salt making up a part of
the rest

DMSA
ORAL 10 MG/KG /DOSE MAX 30
MG/KG/ DAY
3 DAYS ON & 11 DAYS OFF
PROTOCOL
INTRAVENOUS NOT FDA APPROVED
RECTAL LIMITED EXPERIENCE 25
MG/KG 1/DAY 3 DAYS & 11 DAYS
OFF

DMSA SIDE EFFECTS

GI UPSET 12%
BODY ACHES 5%
SERUM TRANSAMINASES INCREASE
SORE THROAT/COUGH 4%
RASHES 3%
BONE MARROW SUPPRESSION 1%

DMPS
ORAL 3-5 MG/KG DAY 3DAYS / 11
DAYS OFF
INTRAVENOUS NOT SAFE WITH
CHILDREN
TRANSDERMAL- 1.5 MG/ KG
ALTERNATE DAY FOR MONTHS

TREATMENT
HYPERBARIC OXYGEN THERAPY
PROMISING NEW STUDY
RECTAL OZONE

Prevention