This document is copyrighted © 2003 by Bryan Jepson MD, PC. Dr. Jepson developed this
document as the basis for the treatment offered by the Children’s Biomedical Center of Utah.
The information protocol contained in this document is based on Dr. Jepson’s effort to compile
information available from varied credible sources on the topic of Autism and reports published
by the Autism Research Institute and the Defeat Autism Now! (DAN!) Association as well as
personal experience in treating autistic children.
Disclaimer
This document is not a recommendation for diagnosis or treatment of Autism Spectrum Disorder
independent of the supervision of a qualified physician. The intent of this document is to inform
and provide treatment options to those families attending the Children’s Biomedical Center of
Utah.
Acknowledgements
Dr. Jepson acknowledges the work and materials published by the Autism Research Institute and
the many physicians and researchers who have collaborated within the DAN! Association.
Particular thanks are given to Dr. Amy Holmes for her advice and counsel during the initial
establishment of the Children’s Biomedical Center of Utah.
I. INTRODUCTION
Autism Spectrum Disorder (ASD) is a group of diseases that is characterized by a delay in
language development, impairment of social interaction, and the use of restrictive, stereotyped
behavior patterns. It was first described in 1944, but great strides in research and understanding
of the disorder have been made only recently. It was initially felt to be a fairly rare illness (less
than 5 in 10,000) but over the last twenty years there has been an explosive increase in incidence,
growing on average around 25% per year and up to 100% per year in some areas. In the United
States, it is currently believed to affect 1 out of every 250 individuals on average (up to 1 in 150
in some areas) with a 4 to 1 male predominance. Thanks to the dedication of many researchers,
physicians and parents, we are rapidly learning much more about the biochemistry and origins of
this illness. Concurrently, many treatments are being developed and are in use across the
country with promising results. Many children who are receiving these treatments are
improving, some to the point of total or, at least, functional recovery. It must be accepted,
however, that the clinical research behind these treatments is in the early stages and as time goes
on and our understanding is improved, the treatment protocols are likely to be modified. The
treatment protocol that your child will be receiving is currently recognized as consensus among a
group of physicians who refer to themselves as DAN! (Defeat Autism Now!) practitioners and
has been implemented in thousands of children without significant danger or adverse effects.
The DAN! movement arose out of an organization called the Autism Research Institute, which
has been in the forefront of autism research for the last 40 years. The DAN! philosophy is that
we can no longer afford to wait for all of the research to be completed and mainstreamed before
we start trying things that have biological plausibility, are safe and may help. We understand the
motivation of parents to do all that they can to help their own children with autism. In fact,
many of us are parents of autistic children ourselves. Our goal is to help as many children as
possible by aggressive early intervention.
We believe that autism is caused when a child with the appropriate genetic susceptibility is
exposed to a number of environmental insults resulting in a complex series of interactions in
several body systems, primarily the central nervous system (brain), the gastrointestinal system
(the gut), and the immunological system (body defense). Understanding the biomedical model
of autism requires recognizing that your child’s body functions as a unit and that treatment
requires an integrated approach. Treatments are based on priorities and should progress in a
fairly logical and step-wise fashion. I will try to explain things with sufficient detail to help you
understand the reasoning behind the intervention but without requiring you to have a degree in
biochemistry. Try not to be overwhelmed by the amount of information contained in this packet.
It is intended for reference. You certainly will not be asked to begin these treatments all at once
or continue them all indefinitely. This is merely an explanation of the currently available
treatments and the reasoning behind them. Remember that each child with autism is a unique
individual and has unique biochemistry that has somehow become disordered. Our job is to help
you find which treatments are most effective for your child. The treatments can be time
consuming, expensive and may require a dramatic change in lifestyle but I believe you will find
that it is all worth it when you see the strides that your child is making!
II. GENETIC SUSCEPTIBILITY A. Metallothionein dysfunction
This hypothesis was proposed by William Walsh, PhD, who heads the Pfeiffer
Research Center in Illinois. He took extensive biochemical analyses of over 500
autistic patients that are treated at his clinic and discovered that almost universally,
these children have abnormal copper/zinc ratios with high body copper and low body
zinc. Extrapolating backwards, he discovered that the body’s control mechanism for
copper and zinc is a function of a family of proteins called metallothionein (MT).
Other functions of MT in the body include development of brain neurons,
detoxification of heavy metals, maturation of the GI tract, anti-oxidation, boosting
immune function and delivery of zinc to cells. MT dysfunction would result, then, in
many of the issues that we see with autistic children such as the leaky gut syndrome,
incomplete breakdown of casein/gluten protein by zinc dependent enzymes, disrupted
ability to combat yeast, reduced production of stomach acid and impaired stimulation
of the pancreas by secretin. It would also lead to inability to clear the body of heavy
metals, a disordered immune system and ultimately to the neurological changes seen
in autism. It would also explain the male sex predominance (4:1) seen in autism
because MT synthesis is enhanced by estrogen and progesterone. MT dysfunction
could be caused by a genetic MT defect, a genetic disorder that disables MT, or an
environmental insult that disables MT. Theoretically, if we could find a way to detect
the MT abnormality early on, autism could be prevented through avoiding environmental insults and supplementing with MT promotional agents (zinc,
glutathione, N-acetyl cysteine, selenium, pyridoxal-5-phosphate, vitamins A,C,D,E,
others.)
B. Other genetic factors
Much research is currently being done in an effort to discover the genetic basis of
autism. It is beyond the scope of this document to describe in detail the genetic
research in this area. As yet, no single gene has been isolated as the culprit and in
fact, autism, with its wide spectrum of presentations and severity is unlikely to be
caused by a single gene defect. Clearly, autism and autism-related illnesses tends to
have a higher incidence in some families. There is also an increased incidence of
other auto-immune diseases such as rheumatoid arthritis, diabetes and inflammatory
bowel disease in the families of autistic children. I think that this indicates an
underlying weakness in the immune system in these families. However, the overall
rate of rise in the incidence of autism cannot be completely explained by genetics
alone. Autism has risen over 1000% in the last 20 years which is not possible if
genetic mutation is the only cause. There must be an environmental component that
is inducing these susceptible children to become autistic.
III. ENVIRONMENTAL INSULTS
I have included below several environmental factors that I believe are playing a role in the rising
incidence of autism. It is important to note that it is unlikely that any of these factors cause
autism in isolation. I believe that it is a combination of these factors and probably many others
that is creating a toxic overload in these children who have abnormal metabolism probably based
on their genetic make-up. The worse their genetics, the fewer environmental insults it will take
to induce the abnormalities and the severity of their deficits will likely be worse and evident at
an earlier age. It is interesting to note that the regressive forms of autism (where the children
seem to regress after a period of normal development) is rising at a much higher rate than the
classic forms of autism which are evident from birth. This makes sense to me since these
children are those whom I believe have less severe deficits genetically and so the rise in
environmental exposure is starting the autism cascade, where 20 years ago, they may have
avoided it.
A. Mercury Toxicity
In April 2000, Sally Bernard, a parent of an autistic child, and several other
investigators published an article suggesting that autism is a form of mercury
poisoning. They meticulously compared signs and symptoms of mercury poisoning
with those of autism and found that there is striking similarity in almost every aspect.
They cited examples of other historically-significant disease epidemics as evidence of
autism-like illnesses created by environmental exposure to mercury. These diseases
also presented with large range of variability and susceptibility among individuals in
the population and were eradicated when the source of the exposure was eliminated.
These illnesses are acrodynia or Pink’s disease (teething powders), Mad Hatter’s disease (occupational exposure) and Minamata’s disease (consumption of
contaminated fish.)
Physiologically, mercury has been shown to have many harmful effects. It can bind
to sulfhydryl groups on many proteins resulting in decreased enzyme function and
loss of structural integrity. This may be contributing to or causing a “leaky gut” by
damaging intestinal lining (mucosa). Mercury can impair cell-mediated immunity
resulting in decreased ability to clear viral and yeast infections. It induces
autoimmunity (the body attacks itself) resulting in the production of anti-brain
antibodies. It can cause or worsen zinc deficiency and inactivate DPPIV (the enzyme
that breaks down casein and gluten.) It alters the brain’s ability to clear unwanted
brain cells or neurons (apoptosis), a process that is a normal and integral part of brain
development. It affects the body’s anti-oxidation ability by depleting intracellular
glutathione (a protein important in clearing toxins from the body.) The clinical effect
on the CNS includes impaired motor planning, decreased facial recognition, blurred
vision and constricted visual fields, insomnia, irritability, tantrums, excitability, social
withdrawal, anxiety, difficulty verbalizing, altered taste, impaired short-term
memory, slowed reaction time and difficulty with concentration. It has been shown
to be the most toxic to infants and males. So how are our kids being poisoned by mercury? Mercury is not uncommon in our
environment. Fish in our diet and dental amalgams in our mouths are common
sources, but by far the largest exposure to our infants are from vaccinations!
Thimerosal is a preservative that is included in many vaccines to prevent bacterial
contamination and thus, prolonging shelf-life and facilitating multi-use vials. It
consists of approximately 50% ethylmercury. As noted above, mercury can be highly
toxic, even in small doses. Some infants receive up to 100 times the EPA
recommended safe level of oral exposure to mercury based on adult weights, in one
day. Injecting it into their muscle also bypasses one of the main first-line defense
mechanisms, the GI tract. We now begin immunizing newborns with hepatitis B
vaccines as early as the day of birth. It doesn’t seem like much of a stretch in logic to
think that these infants’ immune systems and neurological systems are too immature
to handle such a toxic load. Fact is, most children seem to be able to tolerate it just
fine, but we believe that many children, who are genetically predisposed, are being
adversely affected. Several databases have reported an alarming increase in the
incidence of autism in the last 20-year period (over 1000% increase was reported in
California.) It is also interesting to note that in that same period, the number of
immunizations that a child receives before the age of two has increased from 8 in
1980 up to 33 in the year 2001, and more are being developed. When the Hepatitis B
and the HIB vaccine were added to the schedule in the early 1990s the load of
mercury to our children more than doubled. Largely as a result of the effort of many
DAN!-affiliated practioners and parents in 1998, the FDA has required that vaccine
manufactures remove thimerosal from their vaccines, but fell short of demanding a
recall of the existing thimerosal-containing product. This remains a hotly debated
issue among the medical and parent community. The Institute of Medicine convened in 2001 to research this issue in more detail and concluded that there is not enough
evidence currently to prove or disprove the association between vaccines and autism
but conceded that there is biological plausibility for the interaction. They called for
more research into this issue.
Thimerosal has also been present in other commercial products such as contact lens
solution (removed in 1998), eardrops and various nasal preparations. It is interesting
that thimerosal was taken out of animal vaccines a decade ago because it was felt to
be unsafe. There is ample evidence that manufacturers of vaccines new about the
dangers of thimerosal as early as 30 years ago.
B. Heavy viral antigen loading
Mercury may not be the only way that vaccines may be harming some children. A
British researcher, Andy Wakefield, has studied the relationship between autism and
enterocolitis (an inflammatory bowel disorder). As will be discussed later, the
majority of children with autism have some abnormalities of their gastrointestinal
functioning. He did colonoscopies on a group of autistic children with
gastrointestinal problems and found a significant degree of lymph node hyperplasia
(enlargement) in the mucosa of the ileum (the last portion of the small bowel). On
biopsy, he discovered that these nodules were full of vaccine-strain measles virus. He
hypothesizes that the combination MMR vaccine overloads the autistic immune system with too extensive of a viral load at one time. These children are unable to
clear the virus resulting in a chronic sub-clinical infection. These initial findings have
recently been replicated in other labs. Others have found evidence of measles virus in
the cerebral spinal fluid of autistic children at rates that are significantly higher than
normal children. It may be that combination vaccinations such as the MMR and the
DPaT may also overstimulate these children’s immune systems. Many autistic
children show a hyperactive response when vaccine titers (especially measles) are
tested. Whether this reaction to viruses is a cause or merely a reflection of the
underlying immune system abnormalities is uncertain. Many epidemiological studies
have been done that have looked at this connection without finding an association.
However, these types of studies are unable to answer the question conclusively
because they cannot limit the variables that may be involved. Clinical research on
autistic children themselves is much more likely to resolve this issue. It certainly is
plausible that the MMR and exposure to other viruses (including native infections)
can be contributing to the severity of their symptoms but it is unlikely to be the sole
causative factor.
Among the problems with the autistic child’s immune system is an imbalance
between the TH1 (responsible for viral and fungal infections) and the TH2
(responsible for antibody formation and allergies) subtype lymphocytes. Autistic
children are shifted towards TH2 and away from TH1 making them less able to
defend against and rid their system of viral and fungal infections. This shift also
makes them more likely to form antibodies (resulting in multiple allergies) and
autoimmune reactions. These persistent infections and antigens result in chronic
inflammation that can lead to increased gut permeability and abnormal bowel flora.
Many autistic children also have recurrent and prolonged viral infections (upper
respiratory infections, gastroenteritis, bronchitis, etc.)
C. Antibiotic overuse
The over-prescription of antibiotics is a problem not isolated to autism and has led to
the emergence of many antibiotic-resistant organisms that have become very difficult
to eradicate. Autistic children have a particular problem with this because of the
above discussion about their low TH1 lymphocyte activity. Antibiotics are generally
broad-spectrum, meaning they wipe out all the bacteria that they come in contact
with. Our bodies harbor a microscopic ecosystem of bacteria and fungi, some
beneficial and some harmful. When we take an antibiotic, it clears our system of both
kinds, good and bad, and provides the harmful resistant organisms an opportunity to
take over. This is referred to as intestinal dysbiosis. Because autistic children have
depressed TH1 function, they have less ability to clear these harmful organisms and
to restore the normal balance of intestinal flora. This can result in yeast overgrowth
and persistent bacterial and parasitic infections of their gut. These organisms can
interfere with normal digestion and can emit harmful metabolites (break-down
products) that can affect autistic behavior.
D. Other infections
Because of their diminished immune function and poor nutritional status, many
autistic children are prone to other infections such as recurrent ear infections, reactive
airway disease, eczema and sinusitis. This certainly exacerbates the problem with
antibiotic overuse, as described above, since much of the time, antibiotics are
prescribed to treat these illnesses. At times, other children, who seem to be
developing normally, seem to regress after a more serious infection and develop
symptoms of autism. This suggests that this infection may have been the triggering
event that started their autistic biomedical cascade.
IV. BIOMEDICAL DYSFUNCTIONS OF AUTISM
A. Poor nutrition/vitamin and mineral deficiencies
Autistic children are known to be very picky eaters. For reasons that we will discuss
as part of the casein/gluten diet section, they tend to crave carbohydrates and become
addicted to certain foods, and thus, narrowly self-limit their diet. This diet typically
does not provide them with the essential vitamins and minerals that they need for
healthy body functioning. Couple this with the fact that they have abnormal
gastrointestinal systems that prevent absorption and proper utilization of the nutrients
that are taken in. And, as mentioned in previous discussions, their body’s system to
regulate these essential nutrients is dysfunctional. For all of these reasons, children
with autism almost universally are deficient in certain vitamins and minerals. These
nutrients act as anti-oxidants and cofactors for many enzymatic pathways and are
needed in the development of healthy gastrointestinal, immunological and
neurological systems. They are also critical in detoxification. Common mineral
deficiencies include zinc, selenium, magnesium, molybdenum, manganese, vanadium
and chromium. They are deficient in vitamin C, vitamin B6 (pyridoxine or pyridoxal-
5-phospahte), vitamin B12, vitamin A, vitamin E, folate and niacin.
B. The Leaky Gut Syndrome
As mentioned earlier, autistic children have abnormal gastrointestinal systems. The
reasons for this are varied but include abnormal mucosal barriers from dysfunctional
intestinal metallothionein, depleted sulfate which prevents normal healing of the
mucosal layer, chronic inflammation from persistent viral infections and autoimmune
reactions, injury to the mucosa from abnormal bowel flora and abnormal pancreatic
digestive function. This leads to incomplete breakdown of proteins resulting in
partially undigested chains of amino acids called peptides, which are usually several
amino acids in length. These peptides, which would normally be broken down
further or passed through the stool, are absorbed through the damaged and overly-
porous mucosal lining. It has been shown that the peptides that most often are at fault
are from casein (milk) and gluten (wheat, barley, oats, rye). These children have
diminished functioning of an enzyme called DDPIV that is responsible for breaking
down these particular peptides. The peptides are absorbed through the intestinal tract
into the blood stream and from there are carried to the various body tissues including
the brain. These peptides have basically the same structure of a group of hormones
called opiates. There are opiate receptors throughout the body but a particularly high
concentration exists in the brain. When activated they cause euphoria and decreased
pain response. These are the same receptors that bind opioid-like drugs including
morphine and heroin. It is hypothesized that the gluten and casein proteins are
binding to these receptors and effectively causing an opioid intoxication. That may
be why these autistic children seem to crave foods rich in gluten and casein. They
frequently will have severe tantrums when these foods are first eliminated or become
unavailable. They are potentially going through an opiate withdrawal that often
results in and is relieved by binging on these foods. All they know is that eating these
foods seem to make them feel much better, which in turn causes them to limit their
diet to these specific foods. Unfortunately, chronic opioid toxicity affects learning,
social interaction and motor/sensory neurological function. Most autistic children
have also shown to have an abnormal immune system response to gluten, casein and
soy.
other? you can call me : heri_stm@yahoo.com
