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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:

  1. Regulate zinc and copper levels in blood.
  2. Detoxify Mercury and other harmful metals.
  3. Regulate the development and function of the Immune System.
  4. Regulate the development and pruning of brain neurons.
  5. Prevent yeast overgrowth in the GI tract.
  6. Produce enzymes that break down casein and gluten (DPP IV).
  7. Respond appropriately to intestinal inflammation.
  8. Produce stomach acid.
  9. Regulate taste and texture discrimination on the tongue
  10. Normalize hippocampal function and behavior control
  11. 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


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