THE BROAD SPECTRUM OF

AUTISM
INDIVIDUALIZING APPROACHES
ON THE ROAD TO RECOVERY

Kenneth A. Bock, MD, FAAFP, FACN, CNS

Rhinebeck Health Center
108 Montgomery Street
Rhinebeck, NY 12572
845.876.7082
kbock@rhinebeckhealth.com

www.rhinebeckhealth.com
 Subgroups of ASD / “Autisms”
Subgroups
 GI/Gut-Brain
 Allergy/Sensitivities
 Immune Deficiency/Autoimmune
 Infections
Viral/Bacterial(Strep, Anaerobic)/Fungal/Parasitic
 Metabolic
Enzyme Dysfunction
Mitochondrial Dysfunction
 Heavy Metals/Chemicals
 Inflammation

© 2009 K. Bock, MD
 Dysfunction in ASD

Neurologic/Neurotoxic
Gastrointestinal
Metabolic
Immunologic

© 2009 K. Bock, MD
Neurologic / Neurotoxic
Dysfunction
Environmental Toxins Known to Cause
Damage to Children’s Developing
Brains and Nervous Systems
Heavy Metals
 Lead
 Mercury
 Cadmium
 Arsenic
Chemicals
 PCBs
 Chlorinated dibenzofurans
 Organophosphate pesticides
 Brominated flame retardants
Woodruff et al
Pediatrics; 2004;
113(4):1133-40.
 Synergistic Toxicity

Pb and stress

Pesticides
 Paraquat and maneb - relative risk of
Parkinson’s Disease
Polybrominated diphenylethers
(PBDEs) and PCBs
Heavy metals
Cory-Slechta DA
Neurotoxicology 2005 Feb.

Eriksson et al
Toxicol Sci 2006 Dec; 94(2): 302-9.
 Oxidative Stress in Autism
Increased levels of prooxidants
 Organic toxins
Pesticides
PCBs
 Heavy metals
Mercury
Lead
 Inflammatory cytokines
Hypoperfusion
 Promotesoxidative stress
 Documented by SPECT and PET scans
Sadjel-Sulkowski et al
Am J Biochem and Biotech
4(2):73-84, 2008.
 Role of Oxidative Stress in
Neurodegenerative Disorders

ALS
Parkinson’s Disease
Alzheimer’s Disease

Autism

© 2009 K. Bock, MD
INADEQUATE DETOXIFICATION
IN AUTISM SPECTRUM DISORDERS
Impaired sulfation
 92% of autistic children (Waring et al)
Decreased activity of PST
(Phenylsulfotransferase)
Impaired methylation (James, Deth)
Decreased reduced glutathione levels (James)
Inadequate metallothionein function (Walsh)
Gastrointestinal
Dysfunction
 GI Symptoms
Chronic diarrhea
Constipation
Alternating diarrhea/constipation
Gas / bloating / abdominal
discomfort
Apparent pain after eating
Refusal to eat
Awakening at night crying
© 2009 K. Bock, MD
 Gastrointestinal Abnormalities in Children
with Autism Spectrum Disorders

Gastrointestinal abnormalities
 Impaired digestion
 Inflammation
 Increased intestinal permeability
 Altered bowel flora
Fungal overgrowth / hypersensitivity
Bacterial
Parasites
Viral
 Food allergies / sensitivities

© 2009 K. Bock, MD
 Metabolic
Dysfunction
 Methylation
Methionine
FOLATE CYCLE TRANSMETHYLATION
THF
B6
SAM Methyl acceptor

5,10-CH2-THF MS DMG
MSR
Methyl transferase
B12
Trimethylglycine Methylated Product
MTHFR
SAH (DNA, RNA, Protein,
5-CH3-THF neurotransmittors)
SAHH

Homocysteine
Adenosine
B6 CBS
Cystathionine
Cell membrane
B6
Cysteine TRANSSULFURATION
Glutathione
Reactive Oxygen Peroxide
GST M1
Species:
Peroxides GSH GSSG
NULL
Courtesy of Jill James, PhD, University of Arkansas
 A Targeted Approach to Autism Genetics:
Using the Metabolic Endophenotype as a
Guide to Candidate Genes
Methionine

THF
SAM Methyl Acceptor
DMG
5,10-CH2-THF B12 TC II Methyltransferase COMT

MTHFR Methylated Product

5-CH3-THF SAH
RFC
Homocysteine Adenosine

Cystathionine
CBS
Cysteine
GCL
Glutathione GST Am J Med Genetics, 2006
GLUTATHIONE
 Glutathione Modulation and MeHg
Induced Neurotoxicity
Maintenance of adequate GSH levels protects
against MeHg-induced oxidative stress in primary
cell cultures of neurons and astrocytes
Neurons more susceptible than astrocytes to MeHg
toxicity due to decreased concentrations of GSH
Modulation of GSH levels effectively change the
intracellular concentration of MeHg, which in turn
will alter the risk of MeHg-induced oxidative stress
Supplementation with GSH precursor (NAC)
protects against MeHg exposure in vitro
Kaur et al
Neurotoxicology
2006; 27:492-500
 The relationship between GSH function and the
systemic abnormalities associated with autism

Adapted from Kern and Jones, Journal of Toxicology and Environmental Health,
Part B. 2006;(9):493.
 MITOCHONDRIAL DYSFUNCTION

Mercury leads to:

 Uncoupling of oxidative phosphorylation
Impaired mitochondrial energy
generation
Increased oxyradical formation

© 2009 K. Bock, MD
 LAB CLUES TO MITOCHONDRIAL
DYSFUNCTION

 Chem Profile
 Decreased CO2
 Increased AST, CK (Poling et al, 2006)

 Increased serum lactate, alanine, ammonia

 Decreased free and total carnitine levels (Filipek et al, 2004)

 Decreased glutathione
 Increased lipid peroxides
 Abnormal metabolites on UOAT

 Muscle biopsy

© 2009 K. Bock, MD
Immunologic
Dysfunction
 Immune Balance
The key to normal immune system
function depends upon balanced
immune system responses.
Cellular response
T and B cells
Humoral response
 Antibodies

© 2009 K. Bock, MD
 Cytokines

Small peptides secreted by a variety of

cells which regulate both initiation and
maintenance of the immune response
through a complex network

© 2009 K. Bock, MD
IL-12 Naïve IL-4
(Macrophages) T Cell (Other T Cells)

IL-2

X X

INF-γ IL-4
TH1 TH2

IL-2 IL-4 IL-10

IL-5 IL-13
IFN- γ IL-9
 Immune Dysregulation in ASD

Deficiency / dysfunction

Hypersensitivity / allergy

Autoimmunity

Inflammation

© 2009 K. Bock, MD
 Increased Inflammation is Frequently Seen in
Children with Autism

Over-active innate inflammatory responses,

especially increased pro-inflammatory cytokines
such as TNF-α, are consistent findings.

Immune system over-activation, especially the

innate immune system (although the adaptive
immune system appears to be dysregulated as well)
with evidence of immune inflammation,
neuroinflammation and GI tract inflammation in
many of these children.

© 2009 K. Bock, MD
 PATHOGENESIS FOR PANDAS

Susceptible
Host

Immunomodulatory
Treatment
GABHS

Abnormal
Immune CNS & Clinical
Response Manifestations
Antibiotic Prophylaxis

Adapted from
SE Swedo, MD
Molecular Psychiatry 2002; 7: S24-S25
 Integrative/Functional Medicine
Approach to Chronic Inflammation and
Oxidative Stress
Deal with potential underlying
contributing factors
 Infections, Toxins (heavy metals/chemicals),
Allergens
 GI issues
Dysbiosis
Intestinal hyperpermeability
Food allergies/sensitivities
 Environmental allergies/sensitivities
 Nutritional deficiencies/imbalances
 Hormonal imbalances
 Immunological imbalances
© 2009 K. Bock, MD
 The Healing Program for Autism
Spectrum Disorders

Reduce Environmental Exposures

Dietary Modifications
Nutritional Supplementation
Detoxification
Medications

© 2009 K. Bock, MD
 First and Foremost
Reduce toxic exposures (as much as possible)
 As in chicken, pressure treated wood
 Hg in fish, emissions, vaccinations
 Pb in water, soil, dust
 Chemicals – multiple types
Treat underlying infections
 Gut
 Sinuses
 Fungal, Viral, Bacterial, Parasitic
Avoid allergens
 Foods
 Environmental controls

© 2009 K. Bock, MD
 Dietary
Modifications
 Dietary Modifications
Organic Foods
Avoid refined carbohydrates/trans fats
GF/CF
Avoid reactive foods
Food allergens/sensitivities

 High phenolic foods

Yeast-Free
Hypoglycemia
Specific carbohydrate diet (SCD)
Low oxalate diet (LOD)

© 2009 K. Bock, MD
Diet as an Anti-inflammatory Therapy

 Increased CD3(+)TNFα,CD3(+)IFNγ cells

 Fewer CD3(+)IL-10 cells
 Significantlygreater proportion of CD3(+) TNFα(+)
cells in colonic mucosa in those ASD children with
no dietary exclusion compared with those on a gluten
and/or casein free diet
 Consistentprofile of increased pro-inflammatory
cytokines and decreased regulatory activities
 Furtherevidence of a diffuse mucosal
immunopathology in some ASD children and the
potential for benefit of dietary and
immunomodulatory therapies Ashwood et al
J. Clin Immunol
2004 Nov;(6)664-73
 Nutritional
Supplements
 Nutritional Supplements

General
 Minerals
Zn, Mg, Ca, Se, Cr, Mo, Fe
 Vitamins
A, C, D, E, B6, MB12
 Amino Acids
Targeted: Taurine, Arginine, Lysine, BCAAs,
Methionine
 Essential fatty acids
EPA/DHA
GLA

© 2009 K. Bock, MD
 Nutritional Supplements

Antioxidants
Vitamin A
Vitamin C

Vitamin E

Selenium

© 2009 K. Bock, MD
 Autism and Vitamin D

Calcitrol (activated vitamin D) down-regulates

production of inflammatory cytokines in the brain
(cytokines that have been associated with autism)
Consumption of vitamin D-containing fish during
pregnancy reduces autistic symptoms in offspring
Autism is more common in:
 Areas of impaired UVB penetration
 Poleward latitudes
 Urban areas
 Areas with high pollution and high precipitation

Cannell JJ
Med Hypotheses
2008;70(4):750-9
 Immunoregulatory and Anti-
Inflammatory Effects of Ω-3 EFAs

Dietary fish oil reduces:

 MHC class II expression and antigen
presentation
 Production of pro-inflammatory cytokines
(IL1, IL6, TNF)
 The response to endotoxin and pro-
inflammatory cytokines
 Production of adhesion molecule
expression
Ann Nutr. Metab., 1997
Braz J. Med. Biol. Res., 1998
 Curcumin
Component of turmeric
Nontoxic
Antioxidant activity
Inhibits mediators of inflammation
 NFκB
 Cyclooxygenase-2 (COX-2)
 Lipoxygenase (LOX)
 Inducible nitric oxide synthase (iNOS)

Bengmark S
J Parenter Enteral Nutr
2006 Jan-Feb; 30(1):45-51
Baker, SM, James, J, Milivojevich, A.
Patterns of Thiol Chemistry
in Autistic Children
 CH3 B12

Neuroprotective effect
 Enhanced methylation
Phosphatidyl choline formation in membrane
phospholipids
 May mimic effects of nerve growth factor (NGF)
 Reduction of homocysteine concentration

 Prevention of NO toxicity

Protects neurons against NMDA receptor-mediated

glutamate toxicity
Akaike et al
Eur Jour Pharm
241 (1993) 1-6
 CH3 B12

Coenzyme in synthesizing methionine from

homocysteine via transfer of methyl group
Promotes RNA synthesis
Promotes protein synthesis
 Motoneurons
 Schwann cells

May act on both motoneurons and Schwann

cells to promote axonal regeneration

Yamazaki et al
Neuroscience Letters
170 (1994) 195-197
 Gastrointestinal Treatment Modalities

Gastrointestinal abnormalities
 Treat inflammation
 Treat dysbiosis (fungal,anaerobic)

 Restore bowel flora

 Restore and maintain intestinal wall integrity

 Digestive enzymes

© 2009 K. Bock, MD
Detoxification
 Detoxification
General
 Exogenous
Heavy metals
Chemicals
 Endogenous
Metabolites
 Bacterial/Fungal
 Ammonia
Glutamate
Gastrointestinal
 Essential to deal with constipation (if it is present)

Liver

© 2009 K. Bock, MD
 Detoxification
Methylation/Sulfation
 Zinc (picolinate, monomethionine)
 Methyl B12
 Folinic acid/Methyltetrahydrofolate
 TMG/DMG
 Reduced Glutathione
 N-Acetyl Cysteine (NAC)
 ES (Magnesium sulfate)
 Taurine
 TTFD

© 2009 K. Bock, MD
 ENHANCE GLUTATHIONE

NAC
Alpha Lipoic Acid
Vitamin C
Vitamin E
Silymarin
Curcumin
Folinic acid, TMG, Methylcobalamin
TD/Nebulized Glutathione
IV Glutathione
 Most direct and effective way
© 2009 K. Bock, MD
 Heavy Metal Detoxification:
CHELATION THERAPY
Chelators
 Bind a free metal ion into a ring structure,
thereby neutralizing its reactive state
Thiols
 Organic compounds which contain a sulfhydryl
group (-SH) attached to a carbon atom
Pharmaceutical chelators
 EDTA (Ethylenediaminetetraacetic acid)
CaEDTA
 DMSA (Dimercaptosuccinic acid)
 DMPS (Dimercaptopropane sulfonate)

© 2009 K. Bock, MD
 Heavy Metal Detoxification:
CHELATION THERAPY
 Nutritional considerations
 Mineral status
Zinc/copper
Magnesium
 ES baths/cream
Selenium
Chromium
Manganese
 Fungal dysbiosis

© 2009 K. Bock, MD
Medications
 Medications
 Behavioral  Anti-inflammatory
 Actos
 Atypical antipsychotics  Spironolactone
 SSRIs  Singulair
 GABAergic agents/mood  Asachol
stabilizers  Prednisone
 Stimulants  Immunomodulatory
 LDN
 Central-acting α-agonists
 IV IG
 Anti-infective
 Hormonal
 Antiviral  Armour Thyroid
 Antibacterial  Oxytocin
 Antifungal
 Antiparasitic

© 2009 K. Bock, MD
 IV IG in Children with Autism
IV IG is used in the treatment of immunological
diseases that affect the entire neuroaxis, including
the brain, spinal cord, peripheral nerves, muscles
and neuromuscular junction
Minimal risks
Certain subset of autistic children might benefit
 Immune deficiency
Low immunoglobulin levels
 Increased autoantibodies
Anti-MBP
Anti-thyroid
Anti-DNase B and anti-streptolysin O
Boris et al
Nutr and Environ Med
2006; 15(4):1-8
HBOT in Autism

Rossignol and Rossignol

Med. Hypotheses. 2006
Conclusions: Children with autism who received hyperbaric treatment at
1.3 atm and 24% oxygen for 40 hourly sessions had significant
improvements in overall functioning, receptive language, social
interaction, eye contact, and sensory/cognitive awareness compared to
children who received slightly pressurized room air.
THE BROAD SPECTRUM OF
AUTISM
INDIVIDUALIZING APPROACHES
ON THE ROAD TO RECOVERY

Kenneth A. Bock, MD, FAAFP, FACN, CNS

Rhinebeck Health Center
108 Montgomery Street
Rhinebeck, NY 12572
845.876.7082
kbock@rhinebeckhealth.com

www.rhinebeckhealth.com