Causes. Etiology and Biochemical Abnormalities
of Autism
CHAPTER II
Alan Schwartz, M.D.
Medical Director: Holistic
Resource Center
29020 Agoura Road, Suite A-B
Agoura Hills, CA 91301 (818) 597- 0966
Supporting a lecture given on Sunday October 10, 2004 at Conference:
Maximizing Children’s Potential: Treating Autism, PDD and AD(H)D
CHAPTER II
The Etiology of Autism
What Causes Autism?
The Genetic Propensity
What Is Metallothionein
Dysfunction?
What are some of the other enzymatic (genetic) defects
seen in autism
and in what way do they cause the abnormalities seen in
autistic children?
Methylation Dysfunctions:
MTHFR Dysfunction:
(Methylene TetraHydroFolate
Reductase)
COMT dysfunctions
What is Dopamine’s Role?
What is Epinephrine’s Role?
What is NorEpinephrine’s Role?
G-alpha Protein Abnormalities
The Glutamate Connection
Impaired Detoxification (Sulfation) in the Liver
Gastro-Intestinal Abnormalities
The Streptococcal Connection
The Toxic Metals Connection
The Measles (and other viruses) Connection
Toxic Peptides:
“The Opioid Excess
Theory of Autism”
Toxic substances form gut organisms
The Beneficial Germs
What Causes Autism?
A great deal has been learned about the etiology of autism in recent
years. The physiological abnormalities that occur in autism appear in most
cases to be due to a combination of genetic propensity and environmental
insult.
The theory that best accounts for most of the abnormalities in autism
is that of metallothionein dysfunction, however many other biochemical
abnormalities have been found in increased frequency in autistic individuals,
and a number of these will be discussed in this chapter.
The Genetic Propensity
What Is Metallothionein
Dysfunction?
1. Metallothionein dysfunction: In February 2000 William Walsh,
Ph.D. of the Pfeiffer Treatment Center discovered that “most autistic
patients exhibit evidence of diminished metallothionein (MT) activity and
(that)…many of the classic features of autism can be explained by a
compromised metallothionein system.”
The metallothionein family of proteins is found throughout the body.
They are short, linear, S-shaped chains of amino acids and are rich in
cysteine, a toxic-metal-binding amino acid. Each metallothionein can bind up to
7 zinc ions and 13 copper ions.
They function to:
- Regulate zinc and copper levels in blood.
- Detoxify Mercury and other harmful metals.
- Regulate the development and function of the Immune System.
- Regulate the development and pruning of brain neurons.
- Prevent yeast overgrowth in the GI tract.
- Produce enzymes that break down casein and gluten (DPP IV).
- Respond appropriately to intestinal inflammation.
- Produce stomach acid.
- Regulate taste and texture discrimination on the tongue
- Normalize hippocampal function and behavior control
- Normalize the development of emotional memory and socialization.
Dr. Walsh hypothesizes that autistic children probably have a genetic
or acquired defect in the function or activity of the metallothionein proteins.
This defect by itself would not generally cause autistic symptoms to develop
were it not for an added environmental insult that disabled the metallothionein
proteins.
Examples of known biochemical factors that are able to disable
metallothionein proteins include:
1. Severe zinc depletion: Zinc is regulated by metallothioneins and
depletion inactivates these essential proteins. Zinc is an essential trace
mineral that is necessary for activating many fundamental biochemical reactions
in the body that regulate immune function, hunger, taste sensation, digestion,
metallothionein function and others.
2. Abnormalities in the Glutathione Antioxidant System
3. A deficiency in cysteine
4. Malfunction of metal regulating elements.
5. Genetic inherited modifications in the structure of the
metallothionein proteins (i.e.: mutations). It is likely that autism propensity
is not determined by a single genetic defect, but rather by several genetic
variances. The new term for these is “Single Nucleotide
Polymorphisms” or SNPs (pronounced “snips”).
6. Toxic metals like Mercury, lead and cadmium. Even excess copper, an
essential element, has been shown to temporarily disable the Metallothionein
proteins.
7. Pyrrole chemistry disorders
8. Impaired functioning of an antioxidant enzyme called super oxide
dismutase (SOD).
9. Free radicals, emotional stress, infection and inflammation may also
deplete metallothioneins.
There are four varieties of metallothionein proteins. MT-I and MT-II
are found throughout the body and function to regulate zinc and copper levels,
promote the development of neurons and synaptic connections, normalize immune
function and to detoxify heavy metals.
MT-III functions to rid the brain of excess neurons during early
infancy when the brain is overpopulated with.populations of small, densely
packed neurons. MT III eliminates the excess neurons and by so doing allows the
remaining neurons to develop normally and make appropriate synaptic
connections.
As Doctor Walsh states in his book “Metallothionein and
Autism” [p11], “An early MT-III dysfunction would be expected to
result in (a) incomplete pruning [elimination of unwanted neurons], (b) areas
of densely packed small neurons, and (c) increased brain volume and head
diameter. All of these phenomena have been observed in autism.”
MT proteins are found in high levels in the hippocampal region in the
brain, an area important in learning, memory and behavior control. MT proteins
are also found in the amygdala, a region important in the development of
socialization skills and emotional memory.
Impaired MT function in early childhood would be expected to result in
regressions in speech, behavior, socialization and cognition if the damage is
done when those particular areas of the brain are developing, generally be
before the age of three years. According to Dr. Walsh, “After the age of
3, the brain may have matured sufficiently so that environmental insults can no
longer provoke autism.” {Ibid p. 12].
MT proteins are also found to be abundant in the pineal gland, which
manufactures melatonin, a master regulating hormone, and essential for
normalizing sleep cycles. Many autistic children have sleep disturbances and
melatonin has been found in a number of studies to be helpful in this regard.
Mice with deficient MT proteins have an increased incidence of seizures
and a severely impaired immune system. MT proteins ferry zinc, an essential
element in immune functioning, to peripheral tissues including the immune cells
in the thymus and lymphoid system. If zinc is not transported in sufficient
amount the cellular immunity is weakened. This results in overproduction of a
transcription factor associated with inflammation called NF kappa-B and the
release of inflammatory mediators like Interleukin 6 (IL-6), which in turn
overstimulate the humoral antibody response.
Metallothioneins are also excellent antioxidants. Macrophages and
neutrophils are white cells that kill germs like bacteria and viruses by
releasing toxic substances including hydrogen peroxide. After an infection with
bacteria or viruses there is an increased amount of this peroxide left behind
that must be neutralized by enzymes like the metallothioneins.
Impaired metallothionein function would therefore be expected to leave
child vulnerable to the effects of vaccines and to be hypersensitive to a
variety of infectious agents.
Metallothioneins are “heavy metal magnets”. They bind these
toxic elements tightly and render them relatively harmless. Deficiencies in
metallothionein functioning would therefore be expected to lead to an increased
burden of these dangerous substances, and that, indeed, is what we find in
these children.
Metallothionein proteins are found at very high concentrations in
intestinal linings. There they “capture” any heavy metals that are
present in the gut, which discards its mucosal cells every 3-10 days. If MT
proteins are deficient in the GI tract heavy metals are more readily able to
“leak” through into the blood stream and disable important enzyme
systems. MT proteins are also found in high concentrations in the liver, kidney
and the blood-brain barrier.
Since it is impossible to avoid exposures to heavy metals, especially
in today’s toxic environment, an efficient MT system is essential for
good health. The average adult ingests 20 mcg of mercury each day (much more if
we eat certain fish) of which about 1 mcg is absorbed into the blood stream.
The metallothioneins also bind to copper and regulate its absorption
into the blood stream. Once absorbed copper is bound to ceruloplasmin, a copper
binding protein. Autistic children have increased copper in the blood stream
and decreased ceruloplasmin. This results in an excess of free copper, which
can damage organ systems and inactivate metallothionein functioning.
Excess copper has been shown to be associated with hyperactivity,
learning difficulties (short term memory failure, trouble concentrating),
anxiety and impulsive behaviors.
Metallothioneins also function in the synthesis of certain digestive
enzymes (Carboxypeptidase and aminopeptidase), which help break down food
proteins, including gluten and casein. The MT proteins donate zinc, which
activates DPP IV, a gut enzyme that breaks down gliadorphin, casomorphin and
other morphine-like toxic peptides that form when certain foods, like dairy
(casein), gluten-containing grains, and soy are ingested. Elimination of
gluten, casein and soy from the diet of most autistic children often results in
marked improvements in functioning.
Metallothioneins are found on the tongue and normalize sensations of
taste and texture. In the stomach they protect against inflammation, enhance
the production of stomach acids and activate digestive enzymes. Low stomach
acid output results in an inadequate production of secretin from the duodenum.
Secretin is a hormone that stimulates the pancreas to “dump” its
digestive enzymes into the digestive tract.
Sub-optimal hydrochloric acid production in the stomach will therefore
result in a diminished output of secretin, which in turn results in
insufficiently broken down food proteins, which may then leak through the gut
mucosa and promote food allergies. Impaired hydrochloric acid and secretin
production will also result in the insufficient digestion and assimilation of
many nutrients necessary for optimal physiological functioning.
Impaired MT function also offers us an explanation for the predominance
of autism and ADHD in males. It has been found that the “female
hormones” estrogen and progesterone induce the manufacture of
metallothioneins, so females would be expected to have higher levels of
metallothioneins than males and thus be offered some protection in this regard.
Testosterone, a “male hormone,” has been shown to enhance the toxic
effects of mercury, which again places males at a biochemical disadvantage
If the MT system isn’t functioning properly then impairment of
the brain, liver and kidneys may result along with a dysfunctional immune
system, digestive tract, and problems with learning, behavior, speech,
socialization and impaired enzyme functioning are likely to occur.
The Pfeiffer Clinic approach has been to treat autistic children with
high copper to zinc ratios with an initial supplement of zinc (“Pfeiffer
Primer III”) for 6-8 weeks followed by an amino acid supplement
(“MT Promoter II”). During the zinc loading phase amino acids,
glutathione and selenium should be withheld. A too rapid reduction in copper
sometimes causes increased stimming and irritability. Dosing the zinc in a
pulsatile manner often reduces these potential side effects.
The Pfeiffer Clinic practitioners also attempt to identify intestinal
bacterial imbalances and correct these, remove the toxic metals using chelation
or clathration protocols and supplement with appropriate nutrients and
digestive enzymes. This methodology has resulted in improved functioning in up
to 90% of autistic children, however there are some who get no benefit or who
have had side effects (increased stimming, graying of hair, etc).
What are some of the other enzymatic (genetic)
defects seen in autism and in what way do they cause the abnormalities seen in
autistic children?
B. Methylation Dysfunctions:
Impairments in
moving that darn methyl group around (biochemists call this “impaired
transmethylation”)
MTHFR Dysfunction: (Methylene TetraHydroFolate
Reductase)
This enzyme, as has been previously discussed, functions to
donate a methyl group to folic acid in order to make 5- methyl tetra hydro
folate, the active form of folic acid. 5-methyl tetrahydro folate then donates
its newly acquired methyl group to the vitamin B12 molecule turning it into
methyl B12 (AKA methyl cobalamin).
This is accomplished with assistance of yet another methyl passing
enzyme (methionine synthase), which immediately grabs the methyl group from the
B12 molecule and attaches it to homocysteine, thereby converting it into
methionine, a vitally important amino acid. The end result of these rapid
chemical reactions is an increase in methionine and a consequent decrease in
homocysteine, a potentially harmful amino acid.
When insufficient amounts of methionine, an essential amino acid, are
not being created due to dysfunctions in the MTHFR enzyme (or the methionine
synthase enzyme), a great many biochemical abnormalities may, and often do,
result.
For example, methionine is necessary in the manufacture of cysteine,
one of the amino acids found in glutathione. With insufficient cysteine, not
enough glutathione is made. SAM (S-adenosyl methionine) is also made from
methionine and is another important methyl donor.
Glutathione is an extremely vital substance that helps combat free
radical damage in the body (i.e. it is an antioxidant). It activates a variety
of enzyme systems (including the metallothioneins) and is a premier
detoxification agent in its own right (it removes mercury and other toxic
metals).
Defects in the MTHFR enzyme (that activates folic acid) cannot be
overcome by providing folic acid, however if the active form of the folic acid
is provided (5 methyl tetra hydro folate), or folinic acid is substituted, then
the mutation may be successfully bypassed
COMT dysfunctions:
As was previously
discussed, Catechol O-Methyl Transferase (COMT) aids in transferring a methyl
group (donated by SAM: s-Adenosyl Methionine) to dopamine, epinephrine and
nor-epinephrine (chemists call these substances catecholamines).
“Methylating” these neurotransmitters inactivates them.
Many children with autism or attentional disorders possess an aberrant
form of the COMT enzyme (it has several variations) and either under-methylate
(minimally inactivate) or over-methylate (over-inactivate) the catecholamine
neurotransmitters. These variances in COMT functioning cause neurotransmitter
imbalances that effect mood, attention and activity. Individuals with low
enzyme (COMT) activity will tend to have higher levels of dopamine, epinephrine
and norepinephrine Those with overactive COMT enzymes will have low levels of
these substances.
What is Dopamine’s Role?
Arvid
Carlsson won the 2000 Nobel Prize in physiology or medicine for his discovery
of dopamine’s role as a neurotransmitter.
Dopamine has many affects both in and outside of the central nervous
system. One of its main functions is to inhibit the release of the hormone
prolactin. Dopamine also helps coordinate and control our movements. The death
of dopamine-generating neurons is commonly associated with Parkinson’s
disease. In addition, Dopamine plays a vital role in memory, attention and
problem solving.
Dopamine is commonly associated with the 'pleasure system' of the
brain. It stimulates feelings of enjoyment and motivates us to do, or continue
doing, certain activities, like eating and engaging in sexual activities. Even
anticipating something pleasurable will cause the release of dopamine. It is
the neurotransmitter of desire.
Low levels of dopamine (brought about by drugs or otherwise, are
associated with a decline in desire for pleasurable activities, however if
pleasurable activities do occur they are enjoyed just as much.
A normal variant of the gene for catechol-O-methyl transferase
“has been shown to affect cognitive tasks broadly related to executive
function, such as response inhibition, abstract thought and the acquisition of
rules.”[Wikipedia, the free encyclopedia]
Dopamine also helps us prioritize which objects or events are likely to
be important in both pleasurable and potentially harmful ways. Major
disruptions in the dopamine system have been associated with psychoses,
including schizophrenia.
An interesting way to assess dopamine levels clinically is to count the
number of blinks per minute. The average number of blinks is 15-30 per minute.
The blink rate has been found to vary with the amount of dopamine present: the
more dopamine, the more the blinking rate and vice versa.
What is Epinephrine’s Role?
Epinephrine is implicated in arousal, whether this takes the form of
anxiety, excitement, or fear. Within the body, adrenaline acts in such a way as
to maintain an activated state, allowing a higher state of energy to be
produced.
What is NorEpinephrine’s Role?
Norepinephrine functions to improve memory, attention and allows us to
inhibit certain behaviors via its stimulation of certain specific neuronal
receptors (alpha 2 adrenergic receptor). It is also produced (like epinephrine)
in the adrenal glands in response to stress.
Many studies implicate nor-epinephrine neurotransmitter system
dysfunctions in causing attentional deficit disorders. It is likely that
insufficient stimulus of the norepinephrine receptor in the brain promotes
attentional deficits. This disorder may be due to inadequate production of
norepinephrine or to abnormalities in the receptor for this hormone.
3. G-alpha Protein Abnormalities - The Megson
Protocol: Vitamin A and Bethanecol (Urecholine)
In 1999 Dr. Mary
Megson of the University of Virginia presented her research findings at the
Defeat Autism Now! (DAN!) Conference. Dr. Megson discovered that G-alpha
protein receptors on the surface of cells were disrupted in autistic children
with genetic susceptibilities to this defect. G proteins are cell surface
molecules which, when activated, transmit signals to the inside of the cell
that in turn cause a variety of chemical reactions to occur.
The abnormal G-alpha protein receptors found in autistic children were
associated with defective receptors for retinoids (vitamin A and its analogs)
in the brain and intestinal tract. Vitamin A is necessary for vision, the
prevention of night blindness, sensory perception, language processing and
attention. Children of families with a history of night blindness,
pseudo-hypo-parathyroidism or adenoma (benign tumor) of the thyroid or
pituitary gland were found to be more prone to this G-alpha protein
abnormality.
Dr. Megson found a connection between the measles and pertussis
vaccinations and G-alpha protein defects. She discovered that the pertussis
toxin found in the DPT vaccine (normally injected at 2, 4, 6 and 18 months of
age) separates the G-alpha protein from retinoid (vitamin A) receptors. It also
promotes a chronic auto-immune reaction (monocytic [a type of white cell]
infiltration) of the deep layer (lamina propria) in the gut lining (mucosa).
This in turn leads to a chemical disconnect of the G-alpha protein
pathways and the regulating retinoid (Vitamin A) switch, which results in the
non-specific branch of the immune system being turned on. Unfortunately,
without the proper functioning of the retinoid switch the immune system
can’t be turned off!!
The measles virus, part of the MMR vaccination, also plays a role in
the g-alpha protein problem. Measles vaccination is associated with lower
vitamin A levels and vitamin A in its natural form (cis-vitamin A) is necessary
for activating the retinoid receptors.
The antibodies to the measles virus also disrupt the “molecular
glue” that connects one cell to another and which is so essential
cell-to-cell communication and gut mucosal integrity. The absorption of vitamin
A from the intestinal tract requires an intact gut mucosal surface, the right
acidity (pH) and the presence of bile.
Dr. Megson also found that there is an important difference between
natural (cis-retinoic acid) Vitamin A (found in fish oils) and the synthetic
vitamin A palmitate found in infant formulas and commercial vitamins. The
artificial Vitamin A palmitate binds the free G-alpha protein and by so doing
deactivates the “off switch” for multiple metabolic pathways
involved in vision, cell growth, hormonal regulation and the metabolism of
lipids (fats), proteins and glycogen, a storage form of glucose.
Fortunately, Dr. Megson was able to find a simple and inexpensive
solution for this biochemical dilemma: cod liver oil and Urocholine
(Bethanecol). This protocol has been used in over 500 patients without any side
effects. In the first phase loading with vitamin A in its natural form,
preferably from toxin-free cod liver oil) is started and continued for 2-3
months. This is followed by the introduction of Bethanecol, a parasympathetic
nervous system stimulator that promotes the utilization of vitamin A in cells.
The treatment is especially effective for those experiencing any of the
following symptoms: malabsorption, divergent gaze, speech delay, dry skin, poor
social skills, night blindness, soft stools and dry eyes.
The recommended dosage of mercury & dioxin-free cod liver oil is
as follows:
20-30 lbs 850-1250 IU
31-45 lbs 2500 IU
46-75 lbs 3750 IU
76-125 lbs 5000 IU
>125 lbs 7500 IU
Good brands of cod liver oil include Nordic Naturals, Eskimo 3,
Pharmax, Carlson’s and Kirkman’s
The bethanecol comes as thin, scored 10 mg tablets. They can be halved
or quartered or crushed and dissolved in water. Bethanecol remains stable in a
watery solution for at least 30 days. Don’t start the Bethanecol until
the child has been on the cod liver oil for at least two months. Continue the
cod liver oil while on the Bethanecol.
Suggested oral daily dosages of bethanecol are as follows:
Less Than 5 years start with 2.5 mg
5-8 years start with 5-7.5 mg
Above 8 years start with 10 mg
Maximum dosage is 12.5 mg
If the initial dosage of bethanecol doesn’t result in signs of
improved functioning then the dose may be increased by increments of 2.5 mg per
dose to maximum of 12.5 mg. A sign of too much bethanecol is constricted
pupils.
4. The Amy Yasko Hypothesis: The role of Excitotoxins, Streptococcus
bacteria and Enzyme Dysfunctions and the benefits of RNA Therapeutics
Amy Yasko, Ph.D., N.D., (etc.) has a BS in chemistry and a PhD in
Microbiology, Immunology and Infectious Diseases. In addition she is a Doctor
of Naturopathy and Natural health. She is also the co-founder of a successful
biotech company involved in RNA and DNA diagnostics and therapeutics.
Dr. Yasko got interested in the problem of autism a number of years ago
and has recently teamed up with Dr.. Gary Gordon to write a book on her
discoveries and theories.
Dr. Yasko hypothesizes, as do so many others, that autism is caused by
certain genetic predispositions aggravated by certain environmental insults. In
her research she has traced the complicated biochemical pathways leading to the
autistic state.
Dr. Yasko believes that certain natural substances, like glutamate and
aspartate (two common amino acids), which in excess are known to cause
neurological damage, represent one important cause of the dysfunctions seen in
autism. These substances are known as excitotoxins when present in excessive
amounts, because they both excite and damage neurons. There is a long list of
foods that contain excitotoxins, and these include MSG (monosodium glutamate)
and aspartame (Nutrasweet), which is a mixture of the amino acids phenylalanine
and aspartate. Gluten from wheat and other grains, casein from milk and
hydrolyzed yeast are some other sources of concentrated glutamate.
The Glutamate Connection
Glutamate (made from glutamine and one form is glutamic acid) is the
main excitatory neurotransmitter and is essential for learning, attention,
focus and memory. Interestingly, it is also the precursor of a calming
neurotransmitter called GABA.
GABA is a neurotransmitter that engenders a feeling of peaceful
satisfaction. It is also important in the acquisition of speech, as it helps us
to distinguish between the onset of a sound and background noise. This can lead
to sensory overload. Low GABA levels make seizure activity more likely.
The enzyme that converts glutamate to GABA (glutamic acid
decarboxylase) also requires vitamin B6 as a cofactor for its activity. Vitamin
B6 plays a role in many chemical reactions pertinent to reversing autism and is
one of the nutrients that has shown great success in this regard.
In autistic children there is often a failure to convert glutamate to
GABA in sufficient amounts. This results in an imbalance that results in too
much neuronal excitation (which can lead to “stimming” behaviors)
and too little GABA calming (which can lead to speech impairment).
One of the frequent findings in autistic children is the presence of a
chronic viral infection (like measles). Viral infections are known to inhibit
the conversion of glutamate to GABA. Excess copper, a common finding in 85% or
more autistic individuals, also inhibits GABA.
Excess glutamate can damage and even kill neurons. It does this by
generating free radicals in the cells that it over-excites. Glutamate also
stimulates the production of glucose, the chief energy molecule for the brain.
When glucose levels are low the brain has difficulty clearing the excess
glutamate, and excess glutamate depletes glutathione, a potent antioxidant that
protects neurons from oxidative damage and toxic metal poisoning.
One of the sic receptors that glutamate attaches to is known as the
NMDA receptor. When glutamate or other excitatory compound (like aspartate)
land on this receptor they open a channel that allows calcium into the cell.
It’s the calcium in the cell that causes the excitation in the cell.
Excessive influx of calcium damages the neuron. This can be blocked with
magnesium and zinc and both of these elements have been used successfully as
supplements for autism.
There is also a direct connection between mercury toxicity and
glutamate. Researchers have recently discovered that methyl mercury won’t
damage neurons unless glutamate is present (Aschner, et al, “Methyl
Mercury Alters Glutamate Transport in Astrocytes” NeuroChem Intl 2000;
37:199). This suggests that excess glutamate will potentiate the toxicity of
even low levels of mercury.
So, do autistic children exhibit elevated levels of these excitatory
neurotransmitters? Yes, research shows that both glutamate and aspartic acid
are elevated in individuals exhibiting autistic tendencies. There is also some
evidence indicating that autistic children also possess increased numbers of
glutamine receptors. This isn’t all bad, however, as research (Joe Tsien
of Princeton in Sept 2, 1999 Nature) has shown a link between increased numbers
of glutamine receptors in mice and a superior ability to learn and memorize.
Impaired Detoxification (Sulfation) in the Liver
The liver detoxifies huge numbers of chemical compounds by the
processes of oxidation and by attaching other molecules, like sulfate (a sulfur
atom attached to several oxygen atoms) to them. The detoxified substances are
then sent to the GI tract via the gall bladder. One of the enzymes in the liver
that transfers sulfate groups to toxic substances is PST
(phenol-sulfotransferase). This enzyme is low in almost all autistic children
and, as a result, their ability to detoxify is impaired.
Gastro-Intestinal Abnormalities
Autistic children often have impaired digestive and absorptive ability.
This is due to decreased output of stomach acid, insufficient production of
digestive enzymes and bile and insufficient production of secretin (which
stimulates the pancreas to neutralize the stomach acid and to secrete digestive
enzymes) and other hormones like CCK (which stimulates the gall bladder to
release bile) and Gastric Inhibitory Peptide, which slows the release of acid
into the digestive tract..
These digestive concerns promote the overgrowth of yeasts and other
potentially harmful microorganisms in the gut. The normal, protective and
beneficial microflora (like Lactobacilli and Bifidobacteria) are often found in
insufficient numbers. This often causes a drop in the levels of vitamin K, a
fat-soluble vitamin that is produced in the intestinal tract by the action of
beneficial bacteria on leafy green foods.
Vitamin K is well known as a factor important in the clotting system.
Less well known are its roles in building bone and in controlling
hypoglycemic-related panic attacks. Children with autism seem to be
particularly susceptible to side effects from sugar ingestion and they are
frequently dysbiotic (showing imbalanced gut organisms) and often don’t
eat green-leafy vegetables.
The Streptococcal Connection
The streptococcus germ (usually referred to as the “strep”
organism) is well known for causing infections like sore throats and impetigo.
Chronic strep carriage is not uncommon. In some populations as many as 25% of
the people will harbor strep in their throats. Some individuals experience
autoimmune reactions after a strep infection that can damage the heart
(rheumatic fever), kidneys (glomerulonephritis) or the brain (Chorea, OCD or
PANDAS).
Chorea refers to the strange and inappropriate movements that some
individuals experience after strep infections. OCD is obsessive, compulsive
disorder and PANDAS is an acronym for “pediatric autoimmune psychiatric
disorders associated with streptococcus”, and all these disorders have
been observed in certain susceptible children after a strep infection.
PANDAS can manifest as peculiar behaviors or motor disturbances. Dr.
Vojdani of Immuno Sciences Lab has found antibodies to the strep M protein as
well as autoantibodies against neuronal tissue in samples taken from autistic
children. Strep infection can promote the production of certain inflammatory
substances like tumor necrosis factor (TNF) and nuclear factor kappa B (NFK-B).
High levels of TNF are seen in those with tic disorders and in those with OCD.
Strep germs produce a number of troubling substances. These include
streptokinase, which can increase TNF and IL6, another inflammatory mediator,
and NADase, an enzyme that depletes NAD, which is necessary for recycling
glutathione. TNF and IL6 are known to decrease methylation, which would serve
to aggravate the 85% of autistic children who are undermethylated to begin
with, and methylation reactions are necessary for the proper myelination of
nerves and the “pruning” of excessive brain neurons. Autistic
children show myelination delays in the outer area of white matter of the brain
consistent with this hypothesis.
The Toxic Metals Connection
We live in a highly toxic world.. Many of us harbor elevated levels of
lead, mercury cadmium, arsenic and other poisonous metals. Autistic children
have impaired detoxification systems (low glutathione, cysteine, lipoic acid
and metallothioneins) and can’t excrete these dangerous substances well.
Dr Bradstreet found the mercury burden in autistic children to be 8 times
higher than in non-autistics. The main source of this mercury was the inclusion
of Thimerosal (which is almost 50% ethyl mercury) as the preservative in the
immunizations given to babies and children..
All practitioners serving the autistic community today believe in
removing these harmful metals from the body by processes known as chelation or
clathration. There are many chelating substances available today, like DMSA,
EDTA and DMPS.
Dr. Yasko prefers EDTA plus a unique, RNA-based process that she
believes gets out the “bound” metals that the other agents miss.
She claims that her chelating agents remove toxic metals “even with
patients who have undergone extensive parenterally administered DMPS to the
point that others have been convinced that mercury was no longer an
issue.”
Dr Yasko points out that the Thimerosal molecule may harm the body in
three ways: first by poisoning the body with mercury, second, by mimicking the
nucleic acids (which it resembles structurally) that form the building blocks
of DNA and RNA (our genetic materials), and thirdly, by interfering with the
actions of a number of enzymes
She hypothesizes that the Thimerosal gets bound to the DNA molecule and
thereby “hides” from the chelating agents. She further suggests
that viral infections induce a particular form of metallothionein that
effectively binds mercury and other toxic metals, but which gets trapped in
cells. When these toxic metals are sequestered in cells they may compromise
immune function, which sets the stage for a chronic infection with viruses or
other organisms.
She concludes by suggesting that one must eliminate the chronic viral
infection in order to fully eliminate the heavy metal burden. The best way to
do this is with chelating agents like EDTA, DMPS and DMSA, all of which also
possess anti-viral properties. She and Dr. Gary Gordon have designed an oral
RNA-based liquid product that they believe will effectively remove these toxic
substances from the body.
E. The Measles (and other viruses)
Connection
Dr. Andrew Wakefield has pretty much laid to rest the controversy
surrounding the MMR vaccine and its relationship to autism. Although
conventional medicine does not see the connection, Dr. Wakefield’s
extensive research, as well as that of many other practitioners, clearly makes
the connection between the measles virus from the MMR vaccine and the onset of
autism in susceptible individuals in a more than compelling manner.
For example:
- Measles virus RNA is found in 82% of the diseased lymphoid follicles
of those with ASD and in only 7% of controls. 99% had the MMR strain (not the
wild strain)
- Autistic children have a markedly decreased CD3 lymphocyte
production after the MMR compared to controls, and an
- Increased CD8 and CD 98 immune response, as well as
- Much higher levels of antibodies to the measles virus than do
controls
- Children in utero exposed to the measles virus are at increased risk
for autism.
- There is a known association between GI pathology-cobblestone
intestines due to lymphoid hypertrophy-in autistic children. This represents a
novel inflammatory reaction that is often associated with elevated blood
ammonia levels
- There has been an increased isolation of the measles virus after the
MMR in the CNS of autistic children (68%) compared to controls (3%).
- The severity of the autism is worse in children given two doses of
the MMR vaccine. Pus and inflammation was noted in 57% after the second MMR vs.
13% in those that received only one MMR.
- Mercury has been shown to increase the susceptibility to infection
from the MMR
- Affected children appear to have an abnormal antibody response to
the measles virus that is associated with development of autoantibodies against
myelin basic protein
- An antibiotic given around the same time as the MMR increases the
likelihood of autism developing.
Other viruses, like HHV 6, Rubella, Mumps and other herpes viruses may
be implicated in the autism picture. Chronic viral infections can activate T
cells that are specific for autoimmune reactions (to myelin basic protein for
example). If the cells are there, but inactive, they do no harm.
F. Toxic Peptides: “The Opioid Excess Theory
of Autism”
In 1979, researcher Jack Panksaap was struck by the similarity between
autistic symptoms and the effects of naturally occurring substances called
endorphins that are produced by the brain and which mimic the effects of
narcotic substances like the opiate drugs.
Inspired by Dr. Panksapp’s observations, Norwegian scientist Karl
Reichelt began his research into urinary peptides that are able to attach to
opioid receptors in the brain. He found very elevated levels of these peptides
in autistic children. Thus far he has isolated at least 8 different opioid
peptides.
Subsequent research by Paul Shattock and Robert Cade have confirmed
Reichelt’s work and have led to the theory of opioid excess as a cause of
some of the symptoms seen in autism. The theory suggests that certain breakdown
products of particular proteins from gluten, casein and soy, called peptides,
are prevented from being further digested due to abnormalities in the breakdown
of these small protein fragments. The enzyme that is supposed to function in
this regard is DPP IV (Dipeptidyl Peptidase IV), which is a metallothionein
dependent enzyme.
These toxic peptides leak through the gut wall, enter the blood stream
and affix to opioid receptors in the brain and on certain immune cells. In the
brain they may mimic the effects of narcotic drugs or of certain
neurotransmitters. They may cause a dull affect and decreases in focus and
attention. Like narcotics they may also be addictive. Some children crave these
foods (wheat products, dairy products, etc) and experience mild withdrawal
reactions when they go off the offending foods.
In the GI tract morphine and other narcotic agents tend to slow the
movement of food. This can result in constipation. Children with high levels of
these opioid peptides are also often constipated.
These peptides eventually are excreted into the urine where they can be
measured. Dr. Reichelt has been able to show that when the levels of these
peptides in the urine are high, the child’s autistic symptoms worsen, and
conversely, when the levels decline the symptoms improve.
These peptides include casomorphin from casein found in dairy products,
gliadorphin which comes from gliadin or gluten in gluten-containing grains and
dermorphin whose etiology is unclear, but which is identical to a toxin
produced by a certain South American tree frog.
A majority of children who eliminate the foods that promote the
production of these peptides will show a dramatic improvement in their
functioning.
G. Toxic substances form gut organisms
Our intestinal tract is home to tens of trillions of microorganisms.
These include bacteria, yeasts, protozoans and sometimes parasites. When the
number and kind of organisms is in balance all goes well, but when there is an
imbalance in the number or type of these microflora, then disease may result.
Dysbiosis is the term used to describe an imbalance in gut bacteria and yeasts
that causes harm.
The Beneficial Germs
Gut organisms may be helpful. Some organisms ferment fiber to make short
chain fatty acids that are the food for the large intestinal cells. Others
detoxify harmful substances, or make vitamins like vitamin K, or protect
against the overgrowth of more harmful bacteria. Some examples of “good
guy” bacteria include Lactobacilli, which protect the small intestine,
and Bifidobacteria, which protect the large intestine. A beneficial yeast,
Saccharomyces Boulardii, has also been found, and it seems to lessen the toxic
effects of certain harmful bacteria known as Clostridia.
Still, other organisms may be harmful. Some yeasts produce a variety of
potentially toxic chemicals, like arabinose and tartaric acid.
Dr. Shaw, of the Great Plains Lab, has studied two children with autism
whose autistic symptoms improved and whose arabinose levels declined whenever
they were treated with an antifungal remedy (Nystatin). He noted that whenever
the Nystatin was stopped the symptoms would worsen and the arabinose levels
would increase and when it was restarted the symptoms would decline again along
with the arabinose. He concluded that arabinose probably has some neurotoxic
effect and that it is necessary to treat autistic children for long periods of
time (often over a year) in order to prevent this toxic problem.
Gut bacteria can also produce toxic substances. Clostridia are a family
of germs that can cause diseases like tetanus and botulism. They are capable of
producing toxins that can adversely affect the brain. One of these substances
is HPHPA. Both HPHPA and arabinose, as well as other toxic substances, may be
measured by getting a urine organic acid test. The Great Plains Lab is the only
lab in the country currently able to accurately measure levels of HPHPA and
arabinose.
Dr. Sophie Rosseneu and her colleagues at the Royal London Hospital
have been studying undesirable gut organisms called aerobic gram negative
bacilli (AGNBs). These include bacteria with names like Klebsiella, Proteus,
Pseudomonas, Citrobacter, Acinetobacter, Serratia and Enterobacter. While these
may be present in small numbers in many people, they can cause harm if they are
overabundant. Biologically speaking, overabundance is considered any amount
over 100,000 organisms per ml of saliva or feces. The mechanism by which they
cause harm is via the creation of toxic substances called endotoxins.
Almost all gut bacteria produce endotoxins, but the AGNBs produce ten
times more than do other common bacteria like E. coli. The usual defense
against these “bad guy” bacteria is the vast number of anaerobic
flora that normally live in the intestinal tract. Aerobic refers to an organism
that prefers living in air and anaerobic refers to organisms that die when
exposed to air.
Dr. Rosseneu wondered if children with autism harbored more of these
harmful “gut critters” than did non-autistic children. She did a
study of 80 autistic children who were experiencing constipation, abdominal
pain and overflow diarrhea and found that 61% had abnormal AGNB overgrowth and
95% had E. coli overgrowth. Candida was not found in excess.
She found abnormalities in the intestinal lining layer in autistic
children that could explain some of their symptoms. She also showed that by
eradicating the abnormal gut flora, with a three-month antibiotic regimen, she
was able to improve both the autistic behavioral symptoms as well as the GI
abnormalities.
Back to Chapter I |
