Recent research by Ed Cook and associates at the
Some had speech delay, lack of social skills, and “stereotyped” or repetitive behaviors. In addition, these children had seizures and hypotonia, or low muscle tone, characteristics that are not normally associated with autism. These children all had a duplication of part of chromosome 15.
The prospects for knowledge of chromosome 15 leading to a biomedical treatment for autism are high. This is so because the affected region on chromosome 15 contains three genes that code for the neurotransmitter gamma-amino butyric acid (GABA), This is the neurotransmitter involved in preventing anxiety and is essential to integrating motor and mental functions. It is used as an aid to restoring speech following stroke. Lou Gehrig’s disease (ALS) and other neurological conditions result from altered metabolism of the neurotransmitter glutamate, needed to form GABA, which leads (in ALS) to motor-neuron degeneration and loss of motor function. Excess copper suppresses GABA and also suppresses thyroid function. Those suffering ALS actually have twice as much serum glutamate as normal, apparently from a lack of glutamate transporter protein that normally removes excess glutamate (this defect has only been seen in ALS), storing it in the Astrocytes. Aspartate levels were also elevated while other amino acid levels were normal! Glutamate and Aspartate are excitotoxins when in excess at the neuron, and cause death of the neurons. It has been shown that exposure to high concentrations of excitotoxins in short term most often produces ALS and Parkinson’s, while long term, chronic exposure produces dementia. There is increased risk of stroke and seizures. These excitotoxins are a distinct problem with autistic and other children due to the large amounts of flavor enhancers and aspartame being consumed by many.
Excessive glutamatergic stimulation is associated with epileptiform activity, which is common in autistic subjects. This excessive stimulation, with its potential loss of neurons, is greatly increased when brain energy supplies are reduced as in hypoglycemia and uncontrolled seizures (which use enormous amounts of energy). When a seizure occurs, the brain undergoes some drastic biochemical changes. It’s metabolic rate increases enormously, and glucose and oxygen consumption increases to supply the needed energy. Unfortunately, the oxygen delivery system is unable to keep up with the enormous demands. The brain becomes oxygen starved, and must shift its metabolism to a much less efficient energy producing system called glycolysis. A lactic acid buildup occurs in the brain, and if the seizure is not stopped, neurons begin to die. Glutamate levels are elevated in absence of adequate energy. High extra-cellular levels of glutamate cause extrusion of intracellular cysteine resulting in glutathione depletion. Low levels of magnesium also result in decreased levels of Glutathione, as does infection or inflammation that causes elevations in TNF (a). A supplement of vitamins C, E, K, and B6, the amino acids Theanine (precursor to GABA), taurine, glycine, and acetyl-L-carnitine, the minerals magnesium, manganese, zinc, and lithium, oral or transdermal glutathione, melatonin, and large amounts of L-leucine (induces Glutamate Dehydrogenase) greatly reduce the excitotoxic effects and significantly improves neurological function.
Alcohol, anticonvulsants like Gabapentin (Neurontin™) (sic), and anti-anxiety medications like benzodiazepine, Xanax™, and Valium™ all work by attaching to the GABA receptor. Vigabatrin™ binds to enzymes that inactivate GABA, knocking them out of commission. This ensures that GABA stays at a level that will keep the message delivery system working properly. GABA is an “inhibitory” neurotransmitter; it prevents cells from firing. Some call it the brain’s “braking system”. Taking 750 mg of GABA, divided into 3 doses daily (Adult) is very effective even in acute anxiety, and may reduce nighttime urination. Taurine is a second calming neurotransmitter that proves very effective in conjunction with GABA. It is known that vitamin B12 may be important for many conditions including anxiety, depression, mood swings, and memory loss, so it should be supplemented also (serum B12 is not necessarily an accurate way of measuring B12 status).
The above statement is in error as far as GABApentin
(Neurontin™) is concerned. Here from the PDR (
This brings us to another line of converging evidence: in the cerebellum, the Purkinje cells (that Margaret Bauman has found to be diminished in the autistic brain) release GABA.
Bolte notes that tetanus infection of the intestines leads to the formation of toxic compounds called phenols. As a corrosive substance, phenol (carbolic acid) denatures proteins and generally acts as a protoplasmic poison. Studies of autistic individuals have detected markedly elevated levels of the phenolic metabolite of tyrosine called 3-(3-hydroxyphenyl) - 3-hydroxypropionic acid (HPHPA). Several autistic children with high HPHPA levels, “…have shown a significant reduction in stereotyped behaviors when treated with antimicrobials effective against intestinal Clostridia”—a genus of bacteria that includes tetanus. “When certain bacteria of the CLOSTIRIDUM family (genus) are present in high numbers, phenylpropionic acid or 3-hydroxytrosine may be formed in the intestinal tract. Either of these compounds may then be converted to 3-hydroxphenyl-propionic acid that is, in turn, converted to HPHPA by the enzymes in the human mitochondria that break down fatty acids”—William Shaw, Great Plains Laboratory. This could be a major contributor to the phenol toxicity of the PST child.
These phenolics prolong the life of and intensify cellular responses to catecholamines (epinephrine, norepinephrine, etc.). They each act as cardiac stimulants, which accounts for the accelerated pulse that Dr. Arthur F. Coca so wisely deduced was symptomatic of an allergenic response. Nicotine was observed to have a pronounced effect on biological membranes, that is, it increases the permeability of these membranes to certain pharmacologically active substances, such as norepinephrine, epinephrine, and dopamine. Peristalsis is increased in the intestine and distribution of blood is altered by these phenolics because of the sensitizing of smooth muscles to epinephrine, norepinephrine, and other physiological stimulants. There is evidence for increased entry of potassium ions into the cell under the influence of epinephrine. This could account for the electrolyte imbalances and water retention (edema) noted in allergies.
“We have noticed that the molar ratio of the urinary concentration of the dopamine metabolite homovanillic acid (HVA) to that of the epinephrine/norepinephrine (adrenaline/noradrenaline) metabolite vanillylmandelic acid (VMA) is commonly elevated when HPHPA is elevated. This appears to indicate that a by-product involved in the formation of HPHPA likely inhibits the conversion of dopamine to norepinephrine leading to relative dopamine excess. Animal studies indicate that dopamine neurons mediate behaviors such as hyperactivity and stereotypical behaviors common in autism. Of course, the drugs such as the phenothiazines and Haloperidol (and Risperdal™), commonly used to treat autism and schizophrenia, are well known to block the action of excessive dopamine at the receptor level”—Biological Treatments for Autism and PDD, Wm. Shaw. It is noted that excess dopamine contributes to sleep disorders, tics, OCD, and Exposure Anxiety that keeps the autistic child in constant fight-or-flight mode. It would seem that a test for and treatment of Clostridia could be very well indicated. Additionally, supplements of magnesium and potassium will tend to balance the Autonomic Nervous System, calming the child. Choline (Lecithin) is antidopaminergic, as is anything that will build acetylcholine. Vitamin B6 and zinc deficiency tends to excess dopamine and a relative lowering of acetylcholine needed for cognition.
Now, the $64.00 question is, what raises HPHPA and interferes with the neurotransmitters? That is a well-known answer. It is from Clostridia acting on the amino acid phenylalanine! Now, why would this essential amino acid be a problem? Two reasons: 1) you inherited a problem with metabolizing it called Phenylketonuria (PKU). This is a condition tested for at birth, and if found, a diet free of phenylalanine is prescribed, but it is notorious that the guideline in USA for treating what I will call subclinical phenylketonuria is allowing many to have the problem without being treated. Disruption in tyrosine production in hepatic cells, arising from this genetic condition, also results in autism (Gillberg & Coleman, 1992, p.203). PKU babies are born with pale-colored eyes, pale skin (lack of melanin), and are born with or quickly developed blond hair (90% have blond hair, others are significantly lighter than their family). As retardation develops, there are behavior problems: irritability, hyperactivity, impulsivity, and destructive outbursts. They have a predisposition for eczema, and are recognized by their peculiar body odor. The high phenylalanine level is due to a genetic lack of phenylalanine hydroxylase, which converts phenylalanine to tyrosine. It is possible that mercury, cadmium, lead, and arsenic could depress this enzyme producing hyperphenylalanine. Subclinical PKU creates many symptoms associated with autism. Nevertheless, Great Plains Laboratory found only one case of PKU in 10,000 tests. 2) Clostridia overgrowth: When these are present in high numbers, the phenylpropionic acid or 3-hydroxytyrosine may be formed by these bacteria from phenylalanine in the intestinal tract. These are then converted to HPHPA in the mitochondria. What is the chance you have Clostridia? You might want to have an OAT and a stool test by Great Plains Laboratory to determine if you have the Clostridia problem creating an excess of dopamine, or if you have PKU creating many autistic symptoms. If formation of these phenols proves to be the cause of high dopamine, then you are drug free! If your PKU test shows a value five or higher, then treat for PKU (restrict phenylalanine). Kill off any Clostridia found.
The children treated for clostridia (usually with Flagyl™) become more sociable, speak more, improve their eye contact, and are less hyperactive and hypersensitive. It should be noted that very high doses of L. Acidophilus GG is usually equally effective as metronidazole (Flagyl™) except for systemic overgrowth. Additionally, Flagyl™ has a lot of side effects (including disabling the biochemical paths of energy generation, producing symmetrical brainstem damage), and can upset the ecological balance in the gastrointestinal tract leading to a yeast overgrowth. Dr. Shaw warns that the die-off effect can be even more severe than that of Candida. Some combination of Alka-Seltzer Gold™, bentonite clay, and charcoal should be used to minimize the die-off effect and protect from damage. Supplemental Alpha Lipoic Acid and N-acetylcysteine (NAC) detoxify this poison also.
Bolte adds, “Parents also noted that regression occurred very quickly” after treatment was discontinued. Given these findings, Bolte says, “Parents, doctors, and researchers must combine efforts to determine if some people diagnosed as autistic are actually suffering from unrecognized forms of sub-acute tetanus.” This is very significant to that large block of children who do not handle phenol well (PST). The use of Organic Acid Testing (OAT) can provide a valuable tool guiding therapy so that harmful microorganisms may be eliminated before treatments with amino acids like phenylalanine that might actually cause neuropsyciatric symptoms to worsen. It is most interesting to note that phenol poisoning, as suffered by the PST child, deadens the nerves endings much as does aspirin (a phenol), thereby masking pain.
In addition, she notes, inhibitory neurons that release the neurotransmitter GABA are a preferred target for tetanus neurotoxins—and the Purkinje cells of the cerebellum, that often appear highly abnormal in autistic individuals, are inhibitory neurons that release GABA. Additionally, GABA is reported to stimulate the brain to release human growth hormone (HGH), and to stimulate the anterior pituitary function.
Glutamine, a precursor of GABA, readily passes through the blood-brain barrier and is a good supplement to take if one wants to increase brain levels of GABA, since glutamine, once it is in the brain, converts into GABA, however, excess glutamine can become excitotoxic. Due to that possibility, GABA may be the preferred supplement. GABA activity is found in glands controlled by the sympathetic nervous system, namely: the pancreas and thymus. If the pancreas is not healthy, the result can be high glutamate, low GABA levels, decreased Secretin and CCK levels, and decreased vitamin K, among other imbalances. It is estimated that 30–40% of all CNS neurons utilize GABA as their primary neurotransmitter! Glutamic acid decarboxylase (GAD), the active enzyme capable of decarboxylating glutamate to GABA, requires pyridoxal 5-phosphate (P5P) as cofactor.
Nevertheless, magnesium will not suppress the immune function, as does Dilantin: Evidence is accumulating that this anti-seizure medication may have significant immunosuppressive effects (Hadden 1986). National Toxicology Program studies in mice exposed to diphenylhydantoin demonstrated a selective effect on immune function resulting in depressed serum IgA levels and altered bone marrow function. Researchers are trying to correlate these findings with the IgA deficiency and increased sinuopulmonary infection that occurs in humans on long-term diphenylhydantoin treatment (NTP 1984).
GABA”B” receptors are metabotropic receptors that are coupled to G-proteins and thereby indirectly alter membrane ion permeability and neuronal excitability. Activation of GABA-B receptors in many brain regions results in an increase in K+ (potassium) channel conductance with a resultant hyperpolarization of the neuronal membrane. This increase in K+ conductance is often blocked by pretreatment with pertussis toxin (pertussis toxin uncouples Gi-protein from receptors), indicating that many postsynaptic GABA-B receptors are indirectly coupled to K+ channels through an intervening G-protein. There is considerable evidence that a large proportion of GABA-B receptors are coupled to G-proteins, but there is also evidence that some presynaptic GABA-B receptors may be directly linked to K+ channels. The fact that GABA-B receptors are coupled to G-proteins may also explain, in part, the reported effects of GABA-B receptor agonists on calcium (Ca2+) conductance and secondarily neurotransmitter release.
One mother has noted increased verbal capacity after supplementing the amino acid GABA! An adult, Polly Hattemer, says, “I tried GABA. It made me regress intellectually. I could hardly recall any nouns. GABApentin was helpful.” The usual effect of too much GABA is lethargy (fatigue). It should be noted; GABApentin has been associated with a worsening of hyperactivity in some cases. The types apt to respond to GABA are the clearly identified “chromosome 15” kids, and those with high phenol levels (See PST below). That encompasses about everybody! Methinks, maybe we should try glutamine with vitamin B6 (P5P), or GABA, or even Bethanechol, before Pepcid™? Once again, strengthen the immune function by following the suggestions herein.
There is a growing interest in an amino acid Theanine (not Threonine) that induces a very relaxed frame. L-theanine is a natural antagonist to the structurally similar amino acid, glutamate. The similarity enables L-theanine to physically block glutamate. Although researchers aren’t positive how theanine works yet, they theorize that it blocks the NMDA receptor which is the doorway that glutamate uses to affect cells. Because of the similar structure, theanine can also fit in this doorway keyhole, blocking access to glutamate. Although it can fit in the keyhole, theanine does not have the same effect on the cell as glutamate does (i.e., opens the calcium channel). Rather than causing damage, theanine acts like a shield against damage by acting as a Calcium Channel Blocker along with magnesium, manganese, and zinc. Together, they should reduce excitotoxic excitation of neurons and cells, preventing hyperexcitability and lowering blood pressure. Theanine is a precursor known to increase GABA, an important inhibitory neurotransmitter. You might like to use this instead of GABA. Theanine has also been found to have beneficial effects by raising the levels of serotonin and/or dopamine in various important brain regions, particularly the hypothalamus, hippocampus (memory center), and striatum. Theanine reduces norepinephrine and epinephrine activity, turnover, and urinary excretion. Adult dosage is reported to be 100 mg 1 to 4 times per day.
Additionally, Bukowski explained that L-theanine (found in tea) is broken down in the liver to ethylamine, a molecule that primes the response of an immune-system element called the gamma-delta T-cell. That’s the T-cell that prompts the secretion of interferon, which is an important way our bodies fight infection. “We know from other studies that these gamma-delta T-cells in the blood are the first line of defense against many types of bacteria, viral, fungal, and parasitic infections. They even have some anti-tumor activity.”
Some additional thoughts on the importance of supporting the thymus: Thymus glandulars taken orally with a multiple-vitamin/mineral supplement have been proven to be modulators of the immune system, normalizing the ratio of T-helper cells to suppresser cells whether the ratio is low as in AIDS, chronic infections, and cancer; or high as in allergies, migraine headaches, and autoimmune diseases. Thymus glandulars can be dramatically effective in children suffering chronic infections. In autoimmune diseases, a high ratio of T-helper cells to suppresser cells causes a higher than normal number of antibodies to be produced which can damage body structures. A robust thymus will normalize this ratio and suppress “immune complexes”. Who needs to rebuild the thymus? Typically thymic hormone levels are very low in the elderly, in those prone to infection, in cancer and AIDS sufferers, and in those undergoing chronic stress. Specifically, those with multiple sclerosis (MS), diabetes, hepatitis, allergies and other autoimmune diseases, the nutrient deficient (that is, those eating quantities of white sugar and refined foods), those with high cholesterol levels, and all children who never had a mother’s milk for at least four months. Did I miss anyone? Support the thymus by using a Thymus Glandular and a multivitamin/mineral supplement!
When the thymus gland dries up, no one treats that as a medical condition even though every doctor and nurse is taught that the thymus gland controls the immune system. It controls the immune system in two ways. First, it is a source of T (thymus)-cells or T-lymphocytes. It is these T-cells that fight the battle against viruses, bacteria, yeast, and other foreign invaders that attack the body’s immune system. The thymus gland seeds the bone marrow with immature T-cells that multiply and mature. Second, the thymus gland produces a variety of hormones that stimulate the maturation of T-cells and increase production of other hormones, such as interferon and the immune globulins. Several hormones have been isolated from the thymus, but the one receiving the most attention in medical studies right now is Alpha 1. Supplementation as recommended has been shown to increase Alpha 1 from 300% to 700% depending on the dosage—My Experience Treating Immune System Disorders with Glandular and Vitamin Supplements, by Dr. Carson G. Burgstiner, MD, PC. Zinc is specific to the improved function of the thymus. Except for nursing infants, 15 mg zinc daily is safe, however, when taking zinc and high amounts of vitamin C one must check copper status or run the risk of depleting copper and creating a copper anemia. So, to support the thymus, supplement zinc, arginine, vitamin A and pantothenic acid with a good multivitamin/mineral.
Dr. Burgsteiner speaks of Thymus extract and a good multivitamin/mineral healing his Hepatitis C. Dr. Jonathan Wright, MD, recommends a protocol developed by Dr. Burton Berkson, MD, that emphasizes Lipoic acid (600 mg), Silymarin (Milk Thistle, 900 mg), and selenium (400 mcg), adult amounts. Selenium, according to Dr. Wright, slows the replication of the virus. Lipoic Acid significantly alters thiol [a compound that contains the functional group composed of a sulfur-hydrogen bond (-SH)]. Being the sulfur analogue of an alcohol group –OH, this functional group is referred to either as a thiol group or a sulfhydryl group. More traditionally, thiols are often referred to as mercaptans. Lipoic Acid significantly alters thiol metabolism, excretion, and distribution - significantly increasing plasma cysteine levels and bile excretion of glutathione resulting in depletion of the liver stores of glutathione – actually decreasing bile output according to one source. These side effects contradict the proposal for a sustained megadosing of LA. Ambrotose®, by Mannatech, Inc. has been successful in restoring liver function and energy output. Be mindful of my concerns, mentioned elsewhere in this paper, about Milk Thistle and high amounts of Lipoic Acid.