Notes on Paul Shattock Lecture

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Notes on Paul Shattock Lecture
Environmental Factors in the Causation of
Autism implications for therapy and treatment.
Newquay, Cornwall 7th Sept. 2004
Exeter, Devon, 8th Sept. 2004
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A presentation divided into three sections-
1. Prevalence Increases?
2. What environmental Factors?
3. So what can we do about it? A Practical Guide
to biomedical interventions.
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The brain is part of an entire body.
It is not a totally separate entity which functi
ons
independently.
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Waltz M., Shattock P., (2004) Autistic Disorder
in nineteenth century London three case
reports. Autism 8 (1) 7-20
TREATMENTS
a) Hydrotherapy (water plus mineral salts)?
b) Various bromide salts (anticonvulsant
and sedative)
c) Herbal remedies?
d) Treatment of bowel symptoms (Senna Calomel,
Cod Liver Oil)
TREATED VERY MUCH AS AN ORGANIC DISORDER NOT
PSYCHOGENIC
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California epidemiological study (1999)
No. of Persons with Autism (UK)
No. of Persons with Autism (US)
UK epidemiological study (1999)
Year of Birth
Patterns of autism in US and UK
Birth Year of People with Autism
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Shattock Paul, Whiteley Paul, Todd Lynda.
Is there an Increasing Incidence of Autism?
evidence and possible explanations.
Consensus in Child Neurology (Supplement of
Journal of Child Neurology) November 2002 29-34
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Chakrabarti S., Fombonne E. JAMA 285 3093-3099
(June 2001) Pervasive Developmental Disorders in
Pre-School Children
Children aged 2.5-6.5 years in West Midlands U
Autism Rate of 16.6 per 10,000 1600
Total PDD 62.6 per 10,000 1160
Our results suggest that the rates of PDD are
higher than previously reported. Methodological
limitations in existing investigations preclude
interpretation of recent high rates as indicative
of increased incidence of these disorders
although this hypothesis requires further
rigorous testing.
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Autism Spectrum Disorders Epidemiology
Similar reports from around the world-
Each State in the United States of America
Local Authorities in all the United Kingdom
Ireland, Saudi Arabia, Kuwait, Canada Denmark
Norway Australia New Zealand Canada
Malaysia? Indonesia? etc. etc.
Suggestive of a Pandemic.
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Brick Township, New Jersey USA 1 in
151 Children
Granite Bay, California, USA
1 in 131 Children
Local Authorities in UK
(Wakefield and Kingston on Thames)
1 in 138 Children
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ONE in 138 CHILDREN is equivalent to ONE in
86 BOYS

Aged 2-3 Not Asperger Syndrome
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Genetic Fragility
Environmental Stressors - Cumulative.
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Some conditions which are accepted as having
increased in incidence
Asthma Allergies including Hay Fever
Cancers (especially of childhood)
Meningitis Peanut and other nut allergies Diab
etes (especially of childhood)
Cardiac Disease New Variant CJD - (Mad Cow Disea
se) ME(CFS)? Gulf War Syndrome Cot Death.
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Some Conditions which are suspected as having
increased in incidence
Autism Asperger Syndrome Attention Deficit Dis
orders Hyperactivity Dyslexia Dyspraxia? Dys
phasia?
Naughty Children?
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Some Environmental Triggers
Infections - Acquired naturally
- Acquired via
inoculation.
Pesticides v insects, fungi, weeds.
Dietary Changes - specific toxicity
- specific allergy.
Dysbioses - Bacteria, fungi, parasite.
Heavy Metals - food, vaccines.
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Some Environmental Triggers
Plasticizers - Soft drink bottles.

Toxic Fumes - computers, TV, traffic.
Food Additive - colour, preservative -
Flavours (Aspartame, MSG).
Very toxic agents - Dioxins, PCBs.
Drug residues - hormone, b-blockers
Culture Peter Andre and Jordan.
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What is Beta-Endorphin?
A peptide with morphine-like activity which
occurs naturally in certain brain areas
(endogenous morphine endorphin)
Some reported effects of beta-endorphin
1. Altered Pain Sensitivity - (Antinociceptive
Effect) Particularly at times of stress.
2. Altered EEG patterns - involvement with
epilepsy
3. Modification of sleep patterns
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Some reported effects of beta-endorphin (cont)
4. Effects on Memory and Learning - Reward
leading to reinforcement and motivation
5. Decrease in Sociability
6. Involvement in Stereotypy/hyperactivity
7. Modification of Intake of Food and Drink
8. Constipation - Abnormal Poo
9. Regulation of Body Temperature
There are many other effects. This list is by
no means exhaustive
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Hypotheses
1. Peptides interfere with neurotransmission in
all the major systems of the C.N.S.
2. These peptides are derived from the
incomplete digestion of food, principally glut
en and casein,
in the Gastro-Intestinal Tract.
3. These peptides cross into the bloodstream
and can enter the C.N.S. to exert their effect
s.
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What are these biologically active compounds?
PEPTIDES
PROTEINS are made up of very long chains of
AMINO-ACIDS. During digestion, proteins are bro
ken down into short chains called PEPTIDES. Typ
ically, peptides contain 2-8 amino-acids,
but may be much larger (e.g. beta-endorphin)
Leu-ENKEPHALIN (A naturally occurring ne
uropeptide) Tyr-Gly-Gly-Phe-Leu
Beta-CASOMORPHIN Human Tyr-Pro-Phe-Val-Glu-Pr
o-Ile Bovine Tyr-Pro-Phe-Pro-Gly-Pro-I
le
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These Peptides will affect transmission in the
C.N.S. and may therefore affect- Perception
(Vision, Hearing, Taste, etc) Cognition Behavi
ours (e.g. Stereotypies) Mood Emotions C.N.S
. development (pruning of CNS)
(Immune System) (Gastro Intestinal Tract)
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Standard urine sample for person with ASD
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trans indolyl-3-acryloylglycine IAG
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Anderson RJ, Bendell DJ, Garnett I, Groundwater
PW, Lough WJ, Mills MI, Savery D, Shattock PEG.
Identification of Indoly-3-Acryloyl Glycine in
the urine of people with autism. Journal of
Pharmacy and Pharmacology 54 (2) 295-298 (2002)
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Bull G., Shattock P., Whiteley P., Anderson R.,
Groundwater P., Lough JW., Lees G. Med. Sci.
Monit. 9 (10) (2003) pp
Indolyl-3-acryloylglycine (IAG) is a putative
diagnostic urinary marker for autism spectrum
disorders.
Our results strongly suggest that urinary titres
of IAG may constitute an objective diagnostic
indicator for ASD. Mechanisms for the involvement
of IAG in ASD are discussed together with future
strategies to address its specificity.
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Alcorn A., Berney T., Bretherton K., Mills M.,
Savery D., Shattock P.
Urinary Compounds in Autism
Journal of Intellectual Disability Research 48
(Part 3) 274-278 (March 2004)
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LC-MS 1
DERMORPHIN Tyr - D - ALA - Phe - Gly - Tyr - Pro
- Ser - NH2

• Very difficult compound for the
• body to break down
• 700x more potent than beta-casomorphin

Previously only found on my skin!
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Reichelt KL et al. Presence of peptides with
selective serotonin uptake stimulating properties
in the
urine of children with autism.
Only known source - REELIN protein
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SULPHATION IN AUTISM
Symptoms made worse by the same foods which
acted as triggers for migraine (cheese, chocol
ate, banana)
PARACETAMOL SULPHATE
PARACETAMOL
AUTISM
PARACETAMOL GLUCURONIDE
PARACETAMOL SULPHATE ----------------------------
------------
PARACETAMOL GLUCURONIDE
RATIO
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WARING, R.H., NGONG, J., KLOVRZA, L.
University of Birmingham, School of Biochemistry,
UK
MEAN RATIO OF SULPHATE / GLUCURONIDE
AUTISM 0.87 /- 0.67 (n 46) CO
NTROL 2.09 /- 0.65 (n 46) p PLASMA SULPHATE LEVELS AUTISM 1.51
/- 2.75 (n 14) CONTROL 8.30 /- 5.40
(n 14) p
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Alberti A., Pirone P., Elia M., Waring R., Romano
C. A sulphation deficit in autistic children a
pilot study. Biological Psychiatry 8 420-424 (
1999)
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Sulphur Metabolism in Autism Waring Klovrza (20
00) Journal of Nutritional and Environmental Medi
cine 10, pp25-32
Results Autism (n232) Controls (n68) Age
7.6 2.4 8.5 3.7 Sulphite 106.9 162.9
2.1 6.3 Sulphate 6819.0 6712.3 3030.8 14
61.0
Protein 103.2 89.9 64.5 27.5
Thiosulphate 130.8 148.1 18.6
25.0 Thiocyanate 6.4 16.9
44.0 101.0
Anion excretion in nmol/ml. Mean SD p(Wilcoxon rank sum test)
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Effects of lack of sulphating ability-
1. Neurotransmitters not removed from system
2. Toxic substances not removed from system - OP
pesticides? Metals? Bile pigments Phenolics.
3. Mucus lining of GI tract becomes patchy
-increases permeability of intestines
4. GAGs of GI wall less sulphated - increases
permeability of intestinal wall
5. Loss of activity of certain hormones (CCK and
Gastrin?) and resulting malabsorptions
6. Easing of access for Yeasts.
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A
B
GUT
GUT
BLOOD
BLOOD
BRAIN
BRAIN
C
D
GUT
GUT
BLOOD
BLOOD
BRAIN
BRAIN
GUT PERMEABILITY ?
GUT PERMEABILITY ?
BLOOD-BRAIN- BARRIER PERMEABILITY ?
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IF (as current research indicates) ASDs are
occurring at a rate of 1 in 150 births
and the UK parents are telling the truth - 10 of
ASDs are triggered by MMR
ONE BRITISH CHILD IN 1,500 WILL BE RENDERED
AUTISTIC BY MMR VACCINE
IF the US parents are telling the truth and 50
of ASDs are triggered by MMR
ONE American child in 300 will be rendered
autistic by MMR vaccination.
ONE AMERICAN BOY IN 172 WILL BE AUTISTIC BY MMR
VACCINATION
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Metabolism of phenylalanine in states
of hyperphenylalaninaemia
COOH
COOH
X
Tyrosine
CH
CH2 CH
CH2
CH2COOH
Phenylketonuria
NH2
NH COCH3
Phenylalanine
N-acetylphenylalanine other metaboiites
dopa decarboxylase
OH
p-hydroxyphenol
pyruvate oxidase
dopamine beta-hydroxylase
transaminase
o-hydroxyphenol- acetate
OH
CH2 CO COOH
CH2 CH2 NH2
CH2 CH2 NH2
aromatic alpha-ketoacid reductase
Phenylpyruvate
Phenylethylamine
Phenylethanolamine
OH
MAO
MAO
CH2 CH COOH
Phenylacetyl - CoA
(Aldehyde)
(Aldehyde)
Phenyllactate
OH
CH2 CO NH
CH2 COOH
CH CH2 CH2 CO NH2
CH COOH
Phenylacetate
COOH
Mandelate
Phenylacetylglutamine
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Some elements of the Metabolism of Tryptophan
3-Indole Acetic Acid (3-IAA)
Indole and Indican
3-Indole Propionic Acid
Kynurenine and derivatives
3-Indole Pyruvic Acid
TRYPTOPHAN
(tryptophan hydroxylase)
3-Indole Acrylic Acid (IAcrA)
5-Hydroxy Tryptophan
(5-Hydroxytryptophan decarboxylase)
3-Indolyl Acryloyl Glycine (IAG)
Melatonin
5-Hydroxy Tryptamine (5-HT Serotonin)
Bufotenin
5-Hydroxy Indole Acetic Acid (5-HIAA)
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Indole Acrylic Acid

• IAcrGly may be considered to be a detoxified
  version of a parent acid compound
  (indole-3-acrylic acid, IAcrA).
  
• Suggested formation through the Tryptophan and
  kynurenine metabolic pathways.
  
• Due to the reactivity and flat planar geometry of
  IAcrA, it has been suggested that this compound
  may contribute to an increase in the permeability
  of certain membranes throughout the body.

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THE SUNDERLAND PROTOCOL (Shattock Whiteley, 20
00)
CEASEFIRE - Remove source of bullets
1. CASEIN - 3 weeks
2. GLUTEN - 3 months
PRELIMINARY AGREEMENT
3. OTHER FOODS - Food diary (Corn Soya
Tomatoes Avocado Beef et al)
4. TESTING - Vitamins, Minerals, Amino Acids,
Allergies (IgG, IgE) Supplement as appropriat
e Zn, Ca, Mg, Mb, A, C, B1, B3, B6 5. PAR
ASITIC ORGANISMS - Yeasts, Others
ACTIVE RECONSTRUCTION
6. SULPHATION ISSUES - Epsom Salts
(Internal/External), MSM 7. ENZYME ACTIVITY -
Betaine Hydrochloride 8. FATTY ACIDS - Evenin
g Primrose Oil, Fish Oils,Cod Liver Oil (Vit. A),
Flax Seed 9. L-GLUTAMINE - Correct Imbalance
, Intestinal Nutrient 10. ENZYME SUPPLEMENTATION
- Bromelain, Seren-Aid, EnZymAid.
______________________________________________
_________________________ 11. 5-HYDROXY TRYPTOPH
AN (5-HTP) 14. MEGADOSE B6 Mg
12. PIGMENT-FREE 15. DIMETHYLGLYCINE (DMG)
13. SALICYLATE-FREE 16. SECRETIN
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The Sunderland Protocol
A logical system for the implementation of
biomedical interventions for people with autism
and related disorders.
The protocol is divided into three sections and
is based loosely upon the Northern Ireland Peace
Process 1. The Ceasefire - removal of guns and b
ullets 2. The Preliminary Agreement

- and analysis of underlying
problems 3. Active Reconstruction - permanent re
solution.
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Before you start.
1. Read and understand
2. Obtain professional support
3. Consider known conditions - Coeliac Disease
and amino-acids
4. Take a good, balanced,(GF/CF) vitamin and
mineral supplement.
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Each therapy must be seen as a part of an overall
treatment programme. These biomedical interventio
ns are not alternatives to an educational
programme - they are complementary.
Each intervention must be seen as a time limited
experiment for that person. Only if the benefits
outweigh the problems - continue. If not - stop
it.
Be prepared to revisit failed interventions.
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THE CEASEFIRE
1. Remove Casein Derivatives three weeks and as
sess situation.

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Lucarelli et al (1995) - Effect of casein-free d
iet (alone) (n36 age 8-13 yrs)
control group (n20) - Blind casein-chal
lenge (placebo vs. casein capsules)
- IgE, IgA, IgM, IgG antibodies to food antigen
s (pre-diet) - Behaviour Summarised Evaluatio
n (BSE)
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Results Significantly elevated levels of - I
gA specific antibodies to casein,
ß-lactoglobulin - IgM IgG antibodies to casein
- IgM to lactalbumin Significantly changes
to BSE after 8 wks of diet (autistic isolation,
verbal communication, cognition)
Changes to BSE following casein-challenge
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Food aint what it used to be.
Milk
1) Different Breeds (species)
2) Pasteurized homogenized
3) Days old (at best)
4) Cows fed on different food different fatty
acid component
5) US only (packed with hormones and antibiotics).
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THE CEASEFIRE
1. Remove Casein Derivatives three weeks and as
sess situation.
2. Remove Gluten and derivatives
three months (at least) - assess.
Separate elements to minimise side effects
Preliminary stage - remove obvious bullets.
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Some transient negative effects following the
removal of gluten and/or casein from the diet of
people with autism These effects are variable in
extent but experience suggests
that they may be more apparent in younger and
smaller children - Anxiety - Clinginess -
Crying and general whinginess - Staring into spa
ce - Marked decrease in movement / dizziness -
Increased frequency in urination / defaecation
- Flu-type symptoms
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Mercury - a risk factor?
From Vaccines? Food (some sources of fish)?
Dental amalgams? Environment?
Evident only after challenge.
Use of chelating agent such as DMSA
(Di-Mercapto-Succinic Acid) DAN?
DMSA - Chelation or Sulphation????
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PRELIMINARY AGREEMENT
3. Keep a food diary - Idiosyncratic effects
(Corn soya eggs beef tomato avocado.)
4. Testing - vitamins and minerals
- allergies (IgE IgG others?)
supplement or remove as appropriate.
5. Parasitic organisms - consider yea
sts protozoa worms.
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ACTIVE RECONSTRUCTION PROCESS
ACTIVE RECONSTRUCTION PROCESS
6. Sulphation Issues - Epsom salts MSM.
7. Enzyme activity - Betaine Hydrochloride.
8. Fatty Acids - a) evening primrose, b) fish
oils c) cod liver oil (Vit A) d) flax oil.
9. L-Glutamine correct imbalance nourish intes
tines.
10. Enzyme supplementation - bromelain SerenAid
EnzymeAid
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ACTIVE RECONSTRUCTION PROCESS
11. 5-Hydroxy Tryptophan (5HTP)
- to bridge the missing stage.
12. Pigment-free diet (sulphation issues).
13. Salicylate-free diet - prostaglandin inhibi
tion.
14. Megadose B6.
15. DiMethyl Glycine (DMG).
16. Secretin.
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..To Be Decided.
A) Heavy metal removal - chelation?
B) Introduction of Organic Diet?
C Removal of environmental pollutants Britney
Spears Ricky Martin.
D) many others. - hyperbaric? - crani
al osteopathy?
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Paul Shattock Autism Research Unit, School of
Health Sciences, University of Sunderland, SUNDE
RLAND SR2 7EE Tel [phone] Fax [phone]
0420 autism.unit_at_sunderland.ac.uk http//osiris.
sunderland.ac.uk/autism/