Willis S. Langford

Autistic children, it has been discovered, can often be helped dramatically by an infusion of the intestinal hormone secretin. The need and the beneficial response to secretin, I think, are dependent upon the amount of damage to the duodenum and upper small intestine from whatever cause, and on the stomach’s ability to produce adequate hydrochloric acid (HCl) for proper digestion. Since these two things largely determine proper digestion, it is vital that both be present. Without adequate HCl, secretin infusion can, at best, be only partially effective in restoring digestion and proper physical and mental function. With proper HCl present, secretin infusion may be totally unnecessary.

The path of autism is different for each child. Some are prone to seizures, some are not; some behave aggressively while others are overly passive. However, children with autism and with ADHD share several factors. There is a deep disturbance in their fatty acid metabolism that impairs their utilization of amino acids, and often there is an imbalance in their electrolytes. Electrolytes control what’s called membrane traffic—what goes in and out of cells. This means that providing other nutritional supplements is relatively ineffective until the electrolyte (sodium-potassium-magnesium-calcium) imbalance is corrected. The delicate balance of electrolytes also controls the electrical activity within the brain. Additionally, there is often heavy metals poisoning, their minerals and amino acids are deficient and/or imbalanced, their production of red and white blood cells is irregular; they have a dysfunctional immune system, 80% suffer mitochondrial disorders according to Dr. Colemen, George Washington University Hospital, 90% suffer some degree of hypothyroidism, despite "normal" TSH readings (Raphael Kellman, MD), 83% suffer dysfunctional Phase 1 and 2 liver enzyme function, and 85% of autistic meet criteria for malabsorption leading to a multitude of nutrient deficiencies (B. Walsh). Both the autistic and the ADHD often suffer lymphoid modular hyperplasia (measles infection in the gut).

Samplings of immune data reveal that most of these autism-spectrum disorder (ASD) children have atypical elevations of antibodies against otherwise common pathogens such as Epstein-Barr virus, Cytomegalovirus, and/or Human Herpes Virus 6 (EBV, CMV, HHV6), and in some 30%, elevated anti-measles antibodies indicative of chronic infection from measles vaccine—Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A; Department of Paediatrics, Tokyo Medical University, Japan. "Complete IgE deficiency was seen in 10% of patients. Almost 20% of the patients had either low or a complete lack of IgA, which is quite high compared to the general population (1 in 700 to 1,000). About 25% of the subjects had IgG subclass deficiency. About 25% of the patients had a deficiency of various subsets of lymphocytes (e.g., CD3, CD4, and CD8 Killer T-Cells). In fact, almost 35% of these autistic children had a deficiency in Natural Killer Cells. In general, the cytokines IL-2 and alpha-interferon are increased, while IL-1 is normal"—Dr. Sudhir Gupta. Other test results suggest that an alteration in the suppressor T-cell subset is associated with autism. Their immune system is driving with no brakes!

There are three major classes of Immune Cell types: granulocytes, monocytes, and lymphocytes. Lymphocytes are divided into three subgroups: B-Cells, T-cells, and Natural Killer Cells. T-cells are divided into helper cells, suppressor cells, and cytotoxic CD8, Killer T-cells. T-helper cells are called CD4 cells. That is, they shows the CD4 glycoprotein on their surface. All these produce cytokines, chemical messengers that tell the other cells what to do. The CD4+ lymphocyte helper cell activities are divided into Th1 (Cell-mediated immunity—defense primarily against viral, fungi, and protozoa) and Th2 (humoral immunity—helps the B-cell to produce antibodies). Th1 and Th2 represent two separate, counterbalancing, functions of the immune system, and problems occur when they are out of balance. Its most revealing to learn that the same insult given to those of different genetic makeup will cause some to have a Th1 response, whereas others will have a Th2 response! The ratio of these two is determined by the balance of adrenal steroids, notably cortisol and DHEA. Since cortisol is an antagonist of DHEA, stress-induced cortisol production shifts the number of CD4+ lymphocytes to predominantly Th2 expression. When Th1 is diminished, Th2 predominates leading to a host of chronic diseases. Conditions are pro viral, pro candida. The chronic viral infection whether measles or other cannot be cleared as long as this bias exists. Furthermore, candida can enhance Th2. This increases IgE, causing candida to really flourish. IgE is productive of numerous allergies. So, if you have high IgE or numerous allergies, suspect that candida and stress are at work. To reduce stress-produced cortisol by 49%, give the child 100 mcg of chromium each day. A 45 minute massage (back rub?) will give a like reduction.

In addition to stress-induced, immune suppression, the body’s natural defense system is also susceptible to stress-induced malnutrition. When the body begins to suffer from stress-induced malnutrition, the cells of the immune system are deprived of critical nutrients necessary for their function. In addition to the macronutrients, myraid micronutrients that include zinc, selenium, vitamins A, C, E, and B₆, the amino acids glutamine, cysteine, and arginine, and Omega-3 and Omega-6 fatty acids are known to be necessary for a functional immune system. It is vital to note that MMR vaccine, and the chronic measles infection so often following, depletes the body of vitamin A. A deficiency of vitamin A and zinc, in particular, hinders cell-mediated immunity (Th1), and "our" kids are universally lacking in these vital nutrients.

Cell-mediated immunity (CMI) in many infants is probably low, and the vaccines lower CMI further. One vaccine decreases CMI by 50%; two together by 70%. Three? Yet, repeated immunizations with 3 vaccines simultaneously from 4 weeks to 12 or 18 months are given. Repeat DPT is given at 12 months. All these triple vaccines markedly impair CMI, yet some uninformed doctors, solely for convenience and profit give 10 viruses into these struggling immune systems in one sitting! The longest safety trial of the triple vaccine (MMR, all live attenuated viruses) was three weeks!

"The repeated use of vaccinations would tend to shift the functional balance of the immune system toward the antibody-producing side (Th2), and away from the acute inflammatory discharging side (the cell-mediated side or Th1). This has been confirmed by observation especially in the case of Gulf War Illness: most vaccinations caused a shift in immune function from the Th1 side (acute inflammatory discharging response) to the Th2 side (chronic auto-immune or allergic response).

"The wise use of vaccinations would be to use them selectively, and not on a mass scale. In order for vaccinations to be helpful and not harmful, we must know beforehand in each individual to be vaccinated whether the Th1 function or the Th2 function of the immune system predominates. In individuals in whom the Th1 function predominates, causing many acute inflammations because the cellular immune system is overreactive, a vaccination could have a balancing effect on the immune system and be helpful for that individual. In individuals in whom the Th2 function predominates, causing few acute inflammations, but rather the tendency to chronic allergic or autoimmune inflammations, a vaccination would cause the Th2 function to predominate even more, aggravating the imbalance of the immune system and harming the health of that individual"—Philip F. Incao, MD.

Multiple vaccinations, in shifting this delicate balance to a predominant Th2 response, favor the development of atopy (asthma, eczema, hay fever, and food intolerances) and, perhaps, autoimmunity through vaccine-induced, polyclonal activation leading to autoantibody production. An increase in the incidence of childhood atopic diseases may be expected as a result of concurrent vaccination strategies that induce a Th2-biased immune response.

The literature shows an association between antiviral vaccination and onset of childhood asthma. We have noted that attenuation of viral target by conventional vaccine preparation does not completely remove or degrade viral nucleic acids such as double-stranded RNA (dsRNA). It is known that viral dsRNA can induce activation of a host’s antiviral protein kinase (PKR). We have shown that activation of PKR by dsRNA leads to expression of Th2-type immune responses, e.g. allergy and asthma.—Farhad Imani, M.D., David Proud, M.D.

The odds of having a history of asthma was twice as great among (DTP) vaccinated subjects than among unvaccinated subjects (adjusted odds ratio, 2.00; 95% confidence interval, 0.59 to 6.74). The odds of having had any allergy-related respiratory symptom in the past 12 months was 63% greater among vaccinated subjects than unvaccinated subjects (adjusted odds ratio, 1.63; 95% confidence interval, 1.05 to 2.54). The associations between vaccination and subsequent allergies and symptoms were greatest among children aged 5 through 10 years.—Hurwitz, E.L., Morgenstern, H; UCLA School of Public Health, Department of Epidemiology, Los Angeles, California.

One study published in the Journal of Infectious Diseases documented a long-term depressive effect on interferon production caused by the measles vaccine. Interferon is a chemical produced by lymphocytes (a type of white blood cell) that renders the host resistant to infection. Vaccination of one-year-old infants with measles vaccine caused a precipitous drop in the level of alpha-interferon produced by lymphocytes. This decline persisted for one year following vaccination, at which time the experiment was terminated. Thus, this study showed that measles vaccine produced a significant long-term immune suppression. This suppression lays the child open to all sorts of infections.

For example: a study published in the American Journal of Public Health Investigators on children who contracted polio, a total of 1,300 cases in New York City and 2,137 cases in the remainder of New York State, discovered that children with polio were twice as likely to have received a DTP vaccination in the two months preceding the onset of polio than were the control children. More recently, in a polio epidemic in Oman, DTP vaccination caused the onset of paralytic polio. The report in the British medical journal Lancet confirmed that a significantly higher percentage of these children with polio (43% compared to 28% of controls) had received a DTP shot within 30 days of the onset of polio. The DTP vaccine suppresses the body’s ability to fight off the polio virus.

Usually then, the autistic child needs to boost Th1 cells. This can be done with Omega-3 fatty acids [EPA at 1000 to 1500 mg a day (two to three teaspoons of CLO), and DHA between 1500 to 2500 mg a day (3 to 5 teaspoons of CLO or fish oil]. Extra Virgin Olive oil, that contains oleic acid: 4 tablespoons a day of fresh oil that’s been refrigerated is very supportive of Th1. Vitamin A, 25,000 IU (adults), with a lot of carotenoids, a lot of vegetables, carrots, and things like that. In addition to that, L-glutamine, 10 to 20 grams (adult) a day, will strengthen Th1. Use Lactobacillus, two or three different kinds, and Bifidus, and magnesium, zinc, and silica. Many factors can affect liver function and glutathione availability. For instance, a recent or chronic-active infection can deplete glutathione, so you will want to build or supplement glutathione. You might even want to add, after careful testing, Pregnenolone or DHEA, because the higher the levels of DHEA, within normal, the better Th1 performs. Vitamin E, vitamin B-complex, panax ginseng, garlic, digestive enzymes, Transfer Factor™, even some things called arabinogalactans and glycoproteins (AmbroStart™ by Mannatech™), all build Th1. Mannatech™ Ambrotose® and Phyt•Aloe® are without peers in modulating this function of the immune system.

Other than vaccines, candida, and stress, what causes Th2 to be elevated? Faulty digestion, a leaky gut, white sugar, over consumption of glucose (sugar) and processed foods (that weakens systemic resistance to infection), trans-fatty acids, a diet high in the Omega-6 fatty acids like linoleic acid (cut canola, use olive), all of these promote over functioning of Th2. This makes the membranes porous, and very vulnerable to infection. Adrenal exhaustion or a lack of glutathione. may promote a cytokine shift from Th1 to Th2. A Journal of Allergy and Clinical Immunology at McGill University and the Institute Pasteur in France article says, "More clues found to molecules role in asthma: A new study has found additional evidence that a chemical involved in inflammation may play a role in asthma. The study found more of the chemical known as interleukin 9 (IL-9)." IL-9 is one of those Th2 substances that gets overactive, suppresses Th1, and you wind up with asthma. They believe that if you can lower IL-9 this is going to help treat, and even prevent asthma. It says, "Interleukins have been known to play a role in regulating the immune system, and in particular to be responsible for causing the early stages of inflammation." They found that if you can lower the Th2, especially these interleukins, and boost Th1 with all the nutrients we’ve been speaking about, they’re going to help dramatically in the management of a wide range of illnesses, including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, AIDS, Chronic Fatigue, candida, multiple allergies, multiple chemical sensitivities, hepatitis, Gulf War Syndrome, cancer, and autoimmune diseases, like autism.

Cytokines (hormone messengers secreted by immune cells), actively transported into the Central Nervous System (CNS), play a key role in this immune activation. It was recently observed that cytokines activate astrocytes and microglia cells (immune system cells), that in turn produce cytokines by a feedback mechanism. Where T-cells are stimulated, they produce large numbers and amounts of cytokines that cause inflammation in the body, muscular pains, headaches, and often weight loss, and malnourishment. The free radical damage to "self" is great. Moreover, cytokines strongly influence the dopaminergic (dopamine), noradrenergic (noradrenaline), and serotonergic (serotonin) neurotransmission. There are indications that the cascade of cytokines can be activated by neuronal processes. These findings close a theoretical gap between stress and anxiety and their influence on immunity (they greatly lower natural-killer-cell function). "When we are fit and healthy it means our bodies are working properly and keeping the germs and bugs at bay. It is only because the immune system falls down that we get ill," said Michael Endecott, research director of the Institute for Complementary Medicine in London.

Gluten (from grains) and casein (from milk) have immune, as well as neurotransmitter, impacts. Therefore, they have the ability to cause immune dysregulation and neurotransmitter imbalance. Opioids decrease T-cell proliferation via the mu-receptors, and this may cause a mild, immune suppression. When an opioid molecule attaches to a receptor in which it "fits", adenylate cyclase is inactivated, leading to a decrease in intracellular Cyclic AMP (cAMP). Cyclic AMP is an important messenger system in the brain and body. When intracellular cAMP levels have been lowered because of constant (inappropriate) stimulation of opioid receptors on the cell surface, less tryptophan hydroxylase is phosphorylated, and therefore more of the enzyme is inactive. When this happens, tryptophan is not converted into serotonin, but is shunted down alternate pathways, eventually leading to urinary IAG (indolyl acryloyl glycine) and 3-indoleacetate. It is reported this affects 93% of autistic children. Opioids can increase levels of gamma interferon also. In animals, high opioid levels cause indifference to mother and others in the family.

Most autistic children are allergic to some foods (high IgG), inhaled pollens, or mold (high IgE). These allergic reactions disrupt normal immune balance and alter interleukin-2 levels exacerbating their symptoms. Yeast species like candida are known to induce immune changes, and to produce neurotoxins, and most autistic children have yeast problems. Yeast bind the B-vitamins, and in absence of Bifidus flora, create subclinical pellagra and beriberi. This lack of B-vitamins, particularly vitamin B₆ will interfere with the production of serotonin, melatonin, and other important neurotransmitters that controls behavior—so normal brain chemistry in the presence of yeast overgrowth is unlikely. Clostridia, found in approximately 20% ASD patients, and other harmful bacteria, also cause neurotoxic effects. These immunological changes (altered interleukins, cytokines, histamine, neuro-hormones, and other immune factors) affect brain chemistry, especially in the cerebellar and sensory components of the brain, and most autistic children have altered sensory perception. The possibility of each of these imbalances should be examined, and, if present, corrected.

These alterations in normal body chemistry are largely due to a damaged, chronically-irritated, gastrointestinal tract largely caused by antibiotics, resulting candida overgrowth, and by chronic viral infections. The single most effective, least expensive way to treat the cause, and not the symptom, is homeopathy. I know the principles of homeopathy offend reason and the good American Way, "more is better". With homeopathy, "less is more". There are forces we do not begin to comprehend working in this body, and homeopathy is working with one. Find a skilled homeopath, and ask him to clear the vaccine damage and resultant virus infection (you may hear the term "nosode"), and the heavy metals poisonings. When he has done that, there will be few if any allergies left. There seems to be two schools. Some will treat individual allergies. If you treat the causes (vaccine damage to the immune system, and the metal overload), and not the allergic symptoms, expensive tests and therapies for allergies will be unnecessary. You will be amazed at the simplicity and low cost, and immediate results, though there can be regression at times. This will restore the immune function to balance, and then other necessary, nutritional and behavioral interventions will be 10 times more effective. Until you have done this, other efforts will be very expensive and not fully effective.

In a test of 36 autistic children reported by Repligen Corporation, 75% had a greater than normal pancreatic response to secretin infusion, especially among those with diarrhea (whose stool improved in consistency for several weeks afterward). These children are probably producing too little secretin, and thus receptor sites have proliferated. When given secretin, there is overactivity of the pancreas. They also documented a pattern of intestinal inflammation (esophagitis, gastritis, and duodenitis that would greatly hinder absorption of nutrients) in the majority. The most frequent gastrointestinal complaints were chronic diarrhea, gaseousness, and abdominal discomfort and distension. Histologic examination in these 36 children revealed grade I or II reflux esophagitis in 25 (69.4%) with symptoms of wakefulness with irritability or crying, pressing of the lower abdomen, and diarrhea. Chronic gastritis was detected in 15, and chronic duodenitis in 24. Low intestinal carbohydrate digestive enzyme activity was reported in 21 children (58.3%), although there was no abnormality found in pancreatic function. Thirty-nine percent were deficient of the enzyme Lactase, and thus had digestive problems with milk, with bloating, gaseousness, and a loose stool (these symptoms can be alleviated with a digestive enzyme supplement containing lactase). None showed signs of Helicobacter Pylori, fungal, or bacterial overgrowth even in the one-third with suspected fungal or bacterial overgrowth based on urine acid test results. This inflamed gut (dubbed "Leaky Gut" because it has become porous allowing large, food particles to pass unnaturally into the blood) produces a number of symptoms. Sucrose (table sugar) also leaks in, and it is an abnormal sugar in the blood stream that causes a host of problems. Particles [especially from milk (casein) and grains (gluten)] called peptides pass through the "Leaky Gut", and activate the immune system creating many allergic symptoms, and also create opioids in the brain that cause much of the "weird" behavior. Dermorphin and other opioid-like peptides can reduce stomach acid output and change emptying time for the stomach, and therefore, hamper digestion. "Treatment of the latter (candida) with conventional synthetic antifungal agents often causes impairment of liver detoxification functions, and decrease in synthesis of phosphosulfotransferase, an enzyme necessary to cleave food proteins, e.g., casein, into smaller easily absorbable peptides."—Dr. Hugh Fudenberg, MD. Thus, fungicides exacerbate the opioid problem. Are the symptoms being suffered symptoms of "autism", or of malnutrition and immune changes induced by that chronically inflamed, out of balance, gastrointestinal tract? Can nutritional intervention ameliorate these "autistic" symptoms?

Digestion begins in the mouth. Here foods are to be chewed until totally fluid, thus mixing ptyalin and other enzymes necessary to digestion of starch with the food. No fluids should be taken during chewing. Furthermore, thorough mastication of food may nourish the gut by providing it with salivary Epidermal Growth Factor (EGF) that is healing to the epithelial lining of the gut. Purified Epidermal Growth Factor has been shown to heal ulceration of the small intestine. The food then passes to the stomach where it may lay for an hour while starches continue to digest. At some point, histamine acts on the H2 receptors of the stomach’s parietal cells, and causes hydrochloric acid (HCl) to be secreted into the stomach to begin the breakdown and digestion of proteins. Pepsinogen, and "intrinsic factor" necessary to utilization of vitamin B₁₂, are also released. If these things are not happening, your child may refuse meat, or will not digest it.

Complex nitrogen (protein) metabolism appears to flourish in children with seizures, developmental delay, and Autism Spectrum Disorder (ASD) involving not only Nitric Oxide (NO) but nitrogen retention as a whole (described previously as purine autism by Mary Coleman). Kids presenting with suppression of carbon dioxide (CO₂) may shun nitrogen rich foods due to the formation of ammonia leading to a state of hyperammonemia. Thus, a hyperammonemic state yields the spacy "brain fog" reaction, or in more severe instances may lead to seizures. The method of children re-breathing their own air through "masking" used at The Institutes for the Achievement of Human Potential has often been helpful with these children as they raise their CO and oxygen levels. Seizures were often brought under control by examining the electrolytic disturbance and matching them to the child’s needs. Potassium bicarbonate, sodium bicarbonate, magnesium carbonate, and the like were used. Now we began to understand why so many children responded to Buffered C (potassium bicarbonate, calcium carbonate, magnesium carbonate), and others needed a more specific buffer (in some children for example niacin was grossly depleted, and they required niacin bicarbonate). Buffers and butyrates attenuate abnormal nitrogen metabolism, however, children with ASD are unique in their presentations, and as we examine nitrogen retention/NO, electrolyte stability, catalysts, and lipid status to determine disturbances in metabolism, it requires that we act upon these aberrations in an integrative manner from a cellular perspective, not as singular interventions. (Patricia Kane) Nitrogen retention is dependent upon dietary consumption of nitrogen-rich foods, along with lipid consumption, electrolyte stability, and mineral density and balance. Those with organic acidemias or amino acidemias often exhibit this protein intolerance.

"Albumin binds organic acids and neutralizes their toxic effect to some extent. A low serum albumin is a significant risk factor that results in a more serious clinical episode in patients with organic acidemias. The administration of valproic acid (Depakene™), or salicylates, should be carefully evaluated in cases of suspected organic acidemias, since these drugs also bind to albumin, and diminish the protective effect of albumin in neutralizing toxic organic acids.

"Lactic acid may be elevated in a wide range of conditions including the pyruvate dehydrogenase, pyruvate carboxylase, 6 diphosphatase, and phosphenol-pyruvate carboxykinase, and dihydrolipoyl dehydrogenase deficiencies, glycogen storage disease type I, fructose 1, and respiratory chain deficiencies"—Wm. Shaw. Additionally, vigorous exercise, bacterial overgrowth of intestines, shock, and anemia will elevate lactic acid. A deficiency of lipoic acid results in reduced muscle mass, brain atrophy, failure to thrive and increased lactic acid accumulation. The pyruvate is broken down by an enzyme complex that contains lipoic acid, niacin, and thiamine. If pyruvate is high I would supplement thsese nutrients.

The volume of hydrochloric acid needed for digestion may be as important as its strength (acidity). It must register a pH of 3 or below for pepsinogen to be converted to pepsin—needed to dissolve proteins into polypeptides in the first step of reducing protein to amino acids that the body can use. In today’s crazy world, even children do not produce enough HCl to digest their foods properly! It seems that autistic children in particular have a preponderant number who are lacking HCl.

Conditions associated with the depressed secretion of hydrochloric acid include infancy, aging, elevated levels of prostaglandin E2, cannabis use, billiard disease, allergies, autoimmune phenomenon, disorders in calcium metabolism, Vitiligo, and the signs and symptoms associated with fat-soluble vitamin deficiencies (A, E, D, K, Fas). Fatigue, vague epigastric distresses after meals, reflux, chronic excessive intestinal gas, constipation, belching, abdominal distention, coated tongue, nausea, vomiting, morning diarrhea, and frequent appearance of undigested food in stools all signal that HCl secretion may be impaired.

When the chyme leaving the stomach is sufficiently acid, it triggers the release of secretin from the duodenum walls into the blood. HCl is the only known stimulus of secretin. The amount of secretin released is dependent on the volume and pH of the chyme. This release of secretin does three things immediately. 1) It signals the stomach to shut down HCl production (indicating that infusions should not be administered immediately after a meal, and that signs of an acid stomach after the stomach is empty may be due to a lack of secretin output), 2) to release bicarbonate of soda in precisely the right amounts to neutralize the acid, and 3) to release pancreatic enzymes to continue the digestion of the food. The secretin then passes throughout the system, even into the brain, where it affects many body functions. Slowed emptying time of the stomach, reduced gastrointestinal symptoms, and—in many—dramatic improvements in behavior, as manifested in improved eye contact, alertness, and expansion of expressive language, is documented in many of those receiving infusions.

Secondarily, secretin generates a signal to the gall bladder to send down appropriate amounts of bile to aid the digestion of the sensed amount of fat present. The body has many "backup" or secondary systems to function under varied conditions. When fat and protein enter the duodenum, apparently even in the absence of sufficient acid to trigger secretin production, cholecystokinin (CCK) is secreted from the walls of the duodenum which signals both the pancreas and the gall bladder to do their thing. That is why we can exist without HCl, but not well, for the protein has not been broken down by HCl/pepsin in the stomach, and vitamin B₁₂ is not being assimilated. Similarly, if food is not thoroughly chewed, some carbohydrate digestion will still take place in the small intestine due to the pancreatic enzyme Amylase (that is often deficient in Autism).

CCK is dependent upon an adequate supply of the amino acid phenylalanine. Secretin and other hormones are also dependent upon adequate amino acid substrates. Due to poor digestion, and the poor eating habits of these children, amino acid concentrates must be supplemented. Lewis Laboratories’ Brewer’s yeast, or desiccated liver, or pure amino acid supplements must be supplied. SeaCure™ , a specially predigested concentrate of white fish, is a good way to go.

If the fat is not digested because of insufficient bile or a lack of the pancreatic enzyme lipase, or there is a deficiency of lipotrophic agents (primarily vitamin B-complex) there will develop a fatty acid deficiency, and a deficiency of the fat soluble vitamins A, D, E, and K contributing to many of the "autistic" symptoms. The already dysfunctional immune system will be further compromised. If the stool floats, is light tan or gray in color, bulky, shiny, and foul smelling, then fat is not being digested and a supplement of ox bile or bile salts is needed.. I’ll say more on that later.

As with secretin, CCK does many things throughout the body. There are two receptors identified: CCKA found abundantly in the pancreatic acinar cells, and CCKB, that functions also as gastrin receptors. That is the predominant form found in the brain where CCK produces satiety. Both secretin and CCK have a direct gut/brain connection. It would appear that gastrin, a hormone produced by the G-cells of the stomach, but secreted not into the stomach but into the blood stream, may have widespread effects also as it uses CCKB receptors.

"Many forms of CCK are active but the octapeptide form of CCK, which is a chain of eight amino acids, is able to promote the same degree of signal at the CCKB receptor regardless of whether sulfate has attached to it or not. On the other hand, the CCKA receptor is a thousand times more responsive to sulfated octapeptide than it is to the octapeptide’s unsulfated form In a condition of low sulfate, CCK’s maturation might be affected, and the delivery of its signal at the CCKA receptor would be unreliable. When one looks at the function of the CCKA receptor, the possible relevance to autism begins to become clear. Though it is clear there are some regions where the CCKA receptor does not regulate the production of the neurotransmitter serotonin, it clearly does have effects in the hypothalamus, and it is also clear that CCK has very powerful effects on serotonin in other regions where the receptor has not been differentiated. It may consequently have effects on serotonin’s metabolite, melatonin, in the pineal gland. (Serotonin, through its effect on CCKB, produces satiety.—WSL) The CCKA receptor powerfully regulates another neurotransmitter dopamine, and also intrinsic factor, a substance in the digestive system that allows the body to absorb B₁₂. When B₁₂ is lacking it will result in elevations in methylmalonic acid in the urine, which was found to be consistently elevated in the children in Wakefield’s recent study...The CCKA receptor also governs the release of and regulates the release of the hormones oxytocin, dubbed the 'social hormone',....CCK also helps to regulate another hormone: motilin"—Susan Owens. Thus, a lack of sulfation will greatly diminish available pancreatic enzymes necessary to digestion, and adversely affect all these neurotransmitter functions (see the information on sulfation deficit, and PST below). Opioid peptides inhibit oxytocin release, and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Both neuromodulators and neurohormones coexist in the same neuron.

"The digestive actions (of motilin—WSL) can be suppressed...when there is a high level of histamine from an allergic reaction or from an immune attack against parasites, and...when there are low levels of serotonin in the gut. Lowered gut levels of serotonin might occur if bacteria were squandering available tryptophan in order to produce the precursor to indolyl acryloyl glycine (IAG). IAG is very often extremely elevated in urinary profiles of those with autism. (It usually returns to normal when the lactobacillus acidophilus is restored to the gut—Wm. Shaw). Motilin also appears to be very influenced by opiates. This regulatory influence could have significance in a syndrome in which excess opiates from dietary sources (gluten and casein) have been frequently described; and in which inflammation is frequently seen, because inflammation would induce the expression of endogenous opiates, such as interferon-alpha. These influences upon motilin’s digestive activity may account for the variable digestive difficulties that are commonly described in autism"—Susan Owens.

Motilin is reported to be elevated in the plasma of some autistics. "Motilin has similar effects to morphine on the reflex involved with urination", and may cause difficulty in potty training. "Acute elevations in plasma motilin seem to follow on the heels of immune activation in the gut and in other GAG-rich areas such as the lungs. It could become elevated in plasma due to a regulatory effect of low bicarbonate released from the pancreas. This could happen if secretin levels were unusually low, or when CCK is not fully sulfated. Since secretin seems to stimulate the release of sulfated glucosaminoglycans (GAGs) from some epithelial tissue, these interplays of intestinal hormones may furnish more reasons why secretin has recently been found beneficial to those with autism. Motilin is also an important neurotransmitter found in abundance in the areas of the brain suspected of having problems in autism. It is a major neurotransmitter in Purkinje cells in the cerebellum, where the most conspicuous problems in brain morphology in autism have been described"—Susan Owens. Colostrum is very high in motilin, and may be helpful in this respect as well as in its antibacterial properties. It is, however, at least in mother’s milk, high in casein, so those on casein-free diets should verify there is none in the commercial colostrum of cow’s milk. In one independent testing of several brands, only Kirkman Labs’ Colostrum Gold™ was casein free.

The pancreas secretes many enzymes, including amylase (starch digesting) lipase (fat digesting), protease (protein digesting) lactase (milk digesting), and peptidase. The peptidases will breakdown the peptides of milk and gluten that, if undigested, may pass through a damaged "Leaky Gut", and become responsible for many of the problems seen in the autistic. Mercury, however, inhibits the peptidase—dipeptidyl peptidase IV—which cleaves, among other substances, casomorphin during the digestive process (Puschel et al, 1982). Mercury then is a major contributor to the opioid problem. Curiously, gelatins in that favorite of kids, Jell-O™, is now said to inhibit this enzyme, and should be eliminated from the diet. Candida, antibiotics, vaccines, and pesticides all deactivate DPP-IV—Dr. Wm. Shaw. The allergic response these opioid-forming peptides cause makes the gut all the more permeable. One study of delinquent boys (Schauss, 1980) found that they drank an average of 64 ounces of milk daily! This is an allergic addiction. The control group of non-delinquent boys drank less than half that amount. Milk doesn’t always "do the body good".

The rapid turnover of the epithelial cells of the gut (3 to 6 days) demands high nutritional levels, especially of the sulfates, that are not being supplied,. A low level dysfunction called "dysbiosis" develops within the gut. Ordinarily unvirulent organisms (yeasts, fungi, and bacteria) begin to alter the metabolic and immune responses of the body. The immune system may react to and destroy normal gut flora. Contributing to this may be a low grade, measles infection in the gut from vaccines, and chronic infection from common pathogens such as Epstein-Barr virus, Cytomegalovirus, and/or Human Herpes Virus 6. The liver is overburdened, creating a flood of free radicals that damage the liver and create toxic bile that can damage the pancreas.

It has been observed that those children whose autism appears at or around the time of birth may have a problem with casein and show diarrhea, eczema, and ear infection from an early age. These have 10 times normal IAG and high peptides; whereas those who show regression into autism at about two years of age following MMR and introduction to a wheat-based diet, have particular difficulties with gluten. These would likely not have high IAG, but do have high peptides. Both gluten and casein may need to be removed, but this may give priority in beginning the program.

One way to temporarily address that undigested peptide/leaky gut problem is to remove the casein or gluten, and the allergens from the diet. I urge you to undertake that as early as possible (See www.gfcfdiet.com). Food sensitivities that express themselves in severe symptoms, such as would be the case for autism, rarely are limited only to a relative few food categories, such as gluten and casein. I strongly encourage you to determine the full extent of relief and improvement your child can achieve through dietary intervention. It is essential to avoid not only gluten and casein containing foods, but every other problem food in your child’s diet. It has been shown that these opioids permanently increase the permeability of the blood-brain barrier opening the brain to heavy metal poisoning and other toxic damage. Antibodies to gluten of the IgA type have been observed to lead to cerebrellar degeneration. It is especially important to have the child gluten-casein free during the teen years when his brain is being pruned of one-third of brains cells and synapses in the maturing of the brain. The opioids hinder this vital phase of development. Epilepsy often ceases when the child is placed on a gluten-casein free diet. In instituting a casein free diet, one must supplement calcium (500-1000 mg). Testing has found 2/3 of these children receiving less than the RDI.

Have you been aware of food-related problems in your child? This would include, but would not be limited to, food allergies such as food-related asthma or rashes, food intolerance, food addictions, food sensitivities, food aversions such as being a very picky eater, or experiencing moderate to severe dietary limitations that are self-imposed. If your answer is ‘yes’ to one or more of these questions, then food allergies, intolerances or sensitivities are more likely to be an underlying cause of the autism-related symptoms in your child. However, avoiding the foods that trigger your child’s symptoms is a very difficult, expensive stopgap unless the improved condition it brings is used to heal the digestion and the inflamed, leaky gut.

When the duodenum or upper intestine is damaged, as in celiac disease, secretin production may be diminished or lacking. That may require administering secretin even when adequate HCl is present, as well as going on a gluten-free diet, at least until the damaged gut is healed. I think that frequent transdermal application is more natural if secretin is to be used. This would avoid the trauma of infusion, and the possibility of seizures following infusion that have been reported in rare instances. To administer secretin without first testing for pancreatic enzymes in the stool would be counterproductive. "We have been measuring pancreatic enzymes in the stool for 8 years: chymotrypsin directly and amylase and lipase indirectly. About 15% of autistic spectrum patients were deficient therein; they were given capsules containing these 3 enzymes, plus 2 additional ones (bromelain and papain) in a neutral solution. This group improved initially and continued to do so as normal enzyme levels were attained."—Dr. Hugh Fudenberg, MD.

"Autism" is of unknown cause, and has no effective treatment, however this failure of digestion, whether from HCl or secretin deficiency, or a damaged gut, causes most of their mental and physical symptoms! These symptoms of malnutrition can be ameliorated by nutritional intervention. As the nutritional status is improved, the immune function will be able to deal with the pathogens, especially if given the benefit of Ambrotose® and Phyt•Aloe® by Mannatech™ in modulating and strengthening the immune function. See the statistics of malabsorption and other biochemical malfunction at end of this paper. Clinical studies available on request.

Serotonin (5-HT) content of blood platelets is variously reported to be excessive in 30% to 50% of autistic due to an errant peptide or to a variant gene (note that those with more than one autistic offspring are apt to fall into this category). A high, blood level of serotonin is surprising in view of the limited protein intake of most autistic. McBride and colleagues recently presented results of a study that confirmed the importance of controlling for race and ethnicity in studies of platelet 5-HT. African-American and Hispanic-American subjects had higher levels of platelet serotonin when compared to Caucasian-American subjects. Interestingly, subjects with autism, who had a sibling with autism, had higher platelet 5-HT levels than subjects without a sibling with autism. Platelet 5-HT levels have been demonstrated to be stable after the age of 9 years, supporting the hypothesis that platelet 5-HT levels are under genetic regulation. Pharmacological evidence suggests more than 50% of patients with autism may have an abnormality in serotonergic neurotransmission; however, no consistent pattern of behavior or of symptoms have been identified that relate to this high platelet level of serotonin.

"For nonautistic children, serotonin synthesis capacity (of the brain) was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference."—Developmental Changes in Brain Serotonin Synthesis Capacity in Autistic and Nonautistic Children. Chugani DC, Muzik O, Behen M, Rothermel R, Janisse JJ, Lee J, Chugani HT, Department of Pediatrics, Children's Hospital of Michigan, Detroit 48201, USA.

This imbalance in allocation of available serotonin, a tryptophan deficiency, a vitamin B₆ deficiency, or a deficiency of the enzyme tryptophan hydroxylase, or some combination, leaves a deficit for the brain. Evidence of serotonin deficiency in autism comes from a pharmacological study using tryptophan depletion. Tryptophan depletion leads to reduced serotonin synthesis, release, and neurotransmission. McDougle and colleagues found exacerbation of behaviors such as whirling, flapping, pacing, banging and hitting self, rocking, toe walking, and anxiety in more than 50% of adults with autism after tryptophan depletion. This study is consistent with the finding of decreased ratio of serum tryptophan to large neutral amino acids in idiopathic infantile autism relative to controls, which would lead to a lower basal level of serotonin synthesis, vulnerability to tryptophan depletion, and response to pharmacological manipulations which increase 5-HT neurotransmission. Drugs that inhibit transport of serotonin: the tricyclic antidepressants, and the Selective Serotonin Reuptake Inhibitors (SSRI), and Monoamine Oxidase Inhibitors (MAOI)] that hold more serotonin in the synapse between brain cells longer greatly reduce the above symptoms. Normally, the enzyme MAO destroys some serotonin in the synapse while a major part is sucked back into the neuron that created it (reuptake). In the autistic with the above behaviors, there needs to be more serotonin available in the synapse. That can best be ensured by increasing the supply in the neuron—naturally—by increasing the precursor it needs to make serotonin. This is accomplished by supplementing 5-HTP, and by conserving it from destruction in the synapse by supplementing magnesium and vitamin B₆.

For those on anti-seizure medications, it should be noted that behavioral side effects of the barbiturate-related agents, Phenobarbital and phenytoin (Dilantin™), may include irritability and depression as well as aggressive behaviors such as biting, pinching, and kicking.

The anxiety produced by a lack of serotonin creates another problem. When the environment is not perceived as "safe", the nervous system will function adaptively to facilitate fight-flight behaviors. Fear and stress tend to produce illness, but fear, stress, and illness result in a retraction of the voluntary "social engagement system", leading to compromised social abilities. Depressing this neural system has several behavioral consequences including flat affect, aprosody (can’t pay attention), difficulty in phoneme recognition, articulation problems, hypersensitivity to sounds, and behavioral state regulation issues. Stress also has observable effects on intestinal micro biota. Release of ACTH from fear and anger leads to increased jejunal E. coli, loss of Bifidobacteria and Lactobacillus from fecal samples, and increased levels of the pathogenic Bacteroides fragilis. Although these symptoms are nonspecific regarding differential psychiatric or behavioral diagnosis, they are shared by many children with developmental disorders. This type of high level stress these children suffer must be countered by a variety of antioxidants (Vitamin C, E, selenium) to avoid systemic damage.

Dr. Felix Sulman began his research on those who suffer from high serotonin levels because of an inability to metabolize serotonin. He found that serotonin is a stress neuro-hormone leading even rabbits, the most docile of creatures, to be aggressive. He coined the term "Serotonin Irritation Syndrome." He found that those who were unable to break down serotonin (PST kids) would have the levels increase. An increase in serotonin in turn increases noradrenaline. They "were in effect being poisoned by the serotonin produced by their own bodies. The irritation victims suffered from migraines, hot flashes, irritability, sleeplessness, pains around the heart, difficulty in breathing, a worsening of bronchial complaints, irrational tension and anxiety, with horrifying nightmares. It also caused his volunteers to sleep badly—that is, always on the edge of consciousness so that they were not properly rested—and to wake after only a few hours of sleep." He also found it caused pregnant women to abort—October, 1977: Slater, et.al., Inhibition of REM Sleep by Fluoxetine, a Specific Inhibitor of Serotonin Uptake, October 1977, at p. 385. Children so often get coughs and colds, yet using a cough or cold medication with dextromethorphan could cause the serotonin syndrome, a very serious and potentially fatal adverse reaction and/or produce PCP reactions. This being the case, neither Prozac™ type SSRIs nor 5-HTP should be used by PST kids.

Marked disturbances of uptake of deuterated phenylalanine and tryptophan from intestine into blood were found in a portion of autistic patients (group A). In another group of the patients, a remarkable decrease in turnover of tyrosine in blood was found (group B)....These findings might suggest that the supply of tyrosine (from phenylalanine metabolism) and free tryptophan to the brain (in group A), or supply of tyrosine to the brain (group B) might be decreased. We postulated that in some of autistic patients there might exist decreases in synthesis of catecholamine or serotonin. Based on the hypothesis, we started a new treatment with L-DOPA and 5-HTP in small doses, and found significant effects in some patients. However, in some, the amino acids caused marked aggravation of the symptoms— Naruse H; Hayashi T; Takesada M; Nakane A; Yamazaki K; Source: No To Hattatsu, 1989 Mar, 21:2, 181-9.

Due to the possible negative effect of 5-HTP in PST kids, I suggest use of DMG or TMG, which has similar improvements reported, often within hours. Each child responds at a different level of intake, usually 1 to 4, 125 mg tablets of DMG, daily; so begin with one and slowly increase the amount. 1 to 4 DMG is the equivalent of 1 to 2 TMG 500 mg.

"Using TMG is an attempt to force methionine resynthesis pathway from homocysteine by an alternative pathway to the 5-methylfolate-B₁₂-methionine synthase before Cystathionine Beta Synthase (CBS) can convert homocysteine to cysteine. The byproduct is DMG. The purpose of this addition is to try to keep homocysteine in the form of methionine in order to rob CBS of substrate for overproduction of cysteine (which would be toxic—WSL). This is essentially a backup pathway, and is meant to complement the folate route for remethylation rather than supplant it. It does not interfere with the folate route"—David H Swenson Ph.D. Nevertheless, to avoid hyperactivity, and to effect the conversion in those who are cystathionine Beta-synthase deficient, one must supplement folic acid and vitamin B₁₂ when supplementing TMG/DMG. The effect of TMG is to reduce homocysteine (which sometimes builds excessively due to a cystathionine beta-synthase deficiency, and is instrumental in heart problems), while controlling cysteine production, where overproduction may be toxic to PST types.

DMG greatest benefit has received little publicity. Studies show it can have a dramatic effect on the immune system. A study at the University of South Carolina showed that when the immune system was challenged with a vaccine, those taking DMG had 400% more antibody production than controls. Before administering any vaccines, you may want to discuss the benefit this could be with your doctor. Additionally, the lymphocytes’ T-cell response was increased—J Infect Dis 81:143(1):101-104. It has been shown to increase interferon levels indicating possible antiviral activity. Since many autistic kids have elevated T-cell activity indicative of autoimmunity, this may be contraindicated for them—another thing to discuss with your doctor, and to have him monitor.

There is a newly available substance that works in this same circuit with DMG/TMG, S-adenosylmethionine (SAM), that, additionally, helps neurotransmitters bind to receptor sites. This makes the neurotransmitters more active. This would seem safer than trying to increase production of serotonin or other neurotransmitters. It has been proven more effective than the tricyclic antidepressants, helping the severely depressed who did not respond to other antidepressants, and it is without the significant side effects of those drugs, though therapeutic intake may include a dry mouth, agitation, and gastrointestinal problems. It is faster acting with no withdrawal period. I would urge its use, possibly along with small amounts of 5-HTP, to control the above listed "autistic" behaviors.

It should be possible, then, to reduce these behaviors by increasing serotonin production, or if drugs are to be used, by use of transport inhibitors rather than unnaturally interfering with serotonin reuptake by SSRIs (that typically depletes the already reduced supply still further, loads the system with fluoride, and inhibits Phase 1 liver enzyme function). If one determines that the child may respond to more serotonin in the synapse, the best way to meet the need is by supplementing SAMe and small amounts of 5-Hydroxy-Tryptophan (5-HTP), a metabolite of tryptophan that easily translates into increased serotonin and melatonin. It is of interest to note that Michael Murray, ND, says that only 3% of oral tryptophan is converted to serotonin, but 70% of 5-HTP is converted. Keep the servings small. 5-HTP and SAMe are available at any health food store.

To ensure proper conversion to serotonin, supplement vitamin B₆. A good choice would be Super Nu Thera™, by Kirkman Laboratories. It is specifically formulated to help autistic children. They presently have one without vitamin A, so you can use cod-liver oil as your source of cis vitamin A. Some have had difficulty in getting their child to take Super Nu Thera because of a "not so great" taste. One "trick" that has worked for some is to place 1/8 - 1/4 of a teaspoon of plain ascorbic acid (vitamin C) into water with the Super Nu Thera. The taste and look is almost like orange juice.

Some are fearful of the higher amounts of vitamin B₆ and magnesium in SNT. Dr. Bernard Rimland says that every child is different, but he has found the average amount of vitamin B₆ that is beneficial is around eight mg per pound of body weight per day. The French found virtually the same 17/kg/day. That is 500 mg per 60 pound child. His adult child has taken 1000 mg for longer than twelve years. He suggests starting with 1/4 the target amount and increasing slowly over a 10-14 day period. The amount of magnesium necessary with the vitamin B₆ is 3-4 mg per pound of body weight. That would be up to 240 mg for that 60 pound child. He further states that in thirty years he has heard of only four cases of autistic children suffering neuropathy. He says further that if no benefit is seen in six weeks, stop giving the high amounts. It is imperative that these higher amounts of vitamin B₆ and magnesium be taken with the underpinning of a good multivitamin/mineral supplement to avoid induced deficiencies that probably account for every reported case of neuropathy. Some don’t convert vitamin B₆ to its necessary metabolite pyridoxal 5`-phosphate (P5P), so taking that coenzyme form of the vitamin may be more effective. Remember, these two nutrients are necessary to normalize the metabolism of, and to conserve the neurotransmitter serotonin. Benefits reported are, variously, improved use of words, improved sleep, decrease in hyperactivity and irritability, better attention span, increased interest in learning, and reduced self-injurious or aggressive behavior.

Since there is no indication that the ones with these problems of hyperactivity and aggressiveness are necessarily the ones with excess serotonin, platelet saturation, and no symptoms have been associated with that condition, I believe, where these behaviors are a problem, it warrants introducing SAMe and 5-HTP in small, increasing amounts while carefully observing behavior. If present symptoms worsen, reduce or discontinue the 5-HTP. As always, make such a potentially serious change only in consultation with your medical professional. First, make sure the child eats protein at every meal. Disguise it, supplement amino acid powders or SeaCure™ (a predigested concentrate of white fish), whatever, get it down him. This is absolutely necessary for growth and development, and "normal" behavior. For sleep problems primarily, take 5-HTP (100 mg) two to four hours before bedtime (each child may vary in how long it takes to work). This has solved the sleep problem for many. For the behavioral problems take 25 to 50 mg several times through the day. It could be a problem for school if the child is made to be drowsy, in that case reduce the amount or give it later in the day.

Sleep can be poor because of sugar problems. When blood sugar drops in the middle of the night, the child will awake. If this be the case, 5-HTP may not work until you remove the offending sugars and high glycemic foods from the diet, especially from the evening meals or snacks. Feed him at least 30% protein with each meal. Remember, sugar promotes candida, with its multiple problems, and sugar can actually make the child drunk! Sugar tends to destroy the beneficial flora in the gut depriving the vital B-vitamins they manufacture and the fatty acids they give off to nourish the cells of the gut lining. It is this loss of B-vitamins needed to process lipids (fats), coupled with a high glycemic, processed food diet, that creates the fatty acid deficiencies and imbalances. Vitamin B₁₂ therapy is based in part upon the role of vitamin B₁₂ in synthesizing essential fatty acids. Experiments designed to test the biotin-yeast hypothesis have demonstrated that the concentration of simple sugars in the culture medium is the only reliable variable to directly determine the form candida cells will take. Below a certain sugar concentration the yeast remain single-celled, and stay in the gut. When sugar concentration rises above a certain threshold, the organism becomes fungal, and tends to enter the blood and thrive in moist warm areas including the brain. Sugar is a deadly poison to these beautiful children. You wouldn’t give them arsenic would you?

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To heal the digestion and the leaky gut, basically seven things are needed—supplement the following divided into 2 or more servings:

1. The amino acid L-glutamine (1500 mg/day) which also reduces blood and brain ammonia levels. Experiments with various animal models have demonstrated that the provision of glutamine can result in better nitrogen homeostasis, with conservation of skeletal muscle. There is also considerable evidence that glutamine can enhance the barrier function of the gut. Furthermore, it is now known that the gut produces large amounts of a vital antioxidant, glutathione, when adequate glutamine is present.

Glutamine is the principal metabolic fuel for small intestine enterocytes, lymphocytes, macrophages, and fibroblasts (major players in the immune function). Supplemental use of glutamine increases intestinal villus height, stimulates gut mucosal cellular proliferation, and maintains mucosal integrity. It also prevents intestinal hyperpermeability and bacterial translocation, which may be involved in sepsis and the development of multiple organ failure.—Miller AL, Altern Med Rev, 1999 Aug, 4:4, 239-48

2. Bromelain (200 mg/day), a digestive aid and anti-inflammatory available usually in item 3.

3. A digestive aid of pancreatic enzymes, including lactase, cellulase, and peptidase, (with ox bile if there is evidence of indigestion of fat). Use enough to correct all observed stomach or bowel irregularities. A good one is Spectrazyme™ by Metagenics™ available from www.randallnutritioncenter.com/rcnc2000/spectrazyme.html, but it doesn’t contain ox bile. There is only a couple of possible downsides. If you are taking large, regular doses of aspirin or NSAIDS, these will make your stomach so raw, and your gut so leaky, that the protease could eat on your stomach or gut. To give the stomach full protection against HCl and protease, drink a large glass of water one-half hour before eating (this will hydrate the mucus lining of the stomach), and take the enzymes in the middle of your meal (mix it with the food of children). So, if taking lots of pain pills, or if you have an ulcer, or severe gastritis, find an enzyme supplement without protease. RGardens, International, "Gamma-Zyme", 200 capsules for $30.00 is the only one I know of. Phone #800-700-7767. Remember too, that aspirin or aspirin-containing compounds or anti-inflammatory drugs such as indocin, butazolidin, or cortisone should never be taken when hydrochloric acid is being supplemented. This combination increases the risk of ulcer. Two enzyme tablets at bedtime is reported to usually desensitize you to pollens and things that cause hayfever—and perhaps other allergies. Enzymes introduced in large amounts too quickly can affect the bowel: usually diarrhea, intestinal bloating, peculiar acrid smell of the stool, and, in some cases, itching of the perianal area. Work up to dose slowly, back off if these symptoms persist.

4. Probiotics: Lactobacillus Acidophilus, Bifido Bifidus—these produce most of the available vitamins B–complex and K, and the fatty acids that the cells in the lining of the gut depend on for their nutrition, and they keep candida yeast from becoming a problem. Take these on an empty stomach for best results, possibly with a little soda water to help them survive the journey.

5. Supplement vitamin A and D [preferably as cod-liver oil to (5000 to 10,000 IU vitamin A, 500 to 1000 IU vitamin D)], and the mineral zinc (15-30 mg/day) and copper (in a 1 to 10 copper/zinc ratio, unless testing shows there is high copper already—as it probably will in autism] in addition to a broad-based, multi-vitamin/mineral supplement Nutrilite™ Food Supplement by Amway™ or, preferably, Profile by Mannatech™.

Dr. Woody McGinnis, MD, Tucson, Arizona, USA has this to say about copper: "I think a lot of our behavioral kids are intolerant of even a milligram or two of extra copper, even in the face of high Zinc supplementation. This is contrary to the usual proportional balance we like to strike. I get a serum Copper and a plasma Zinc, and try to keep the ratio less than 1:1."

6. Aloe (preferably Manapol™, or Ambrotose^® by Mannatech™ that contains Manapol™ and many other saccharides for even better results, for they are the only stabilized, standardized, aloe products available).

7. Fiber, preferably fructooligosaccharide to provide an environment for the "good guys" to overcome yeast and other "bad guys", or other non-gluten fiber.

8. Restore adequate sulfate to the body as outlined in the section Phenol-sulfotransferase below.

When the gut is healed and the digestion restored, bizarre eating habits will cease and a more balanced dietary will be possible. There are three things to know about glutamine:

1. It can cause a buzz like excess caffeine—the kid will be hyper, in that case reduce the amount until this disappears. The amount recommended is not likely to do this.

2. High glutamine readings are seen in subclinical ammonia toxicity. This could be due to a weak detoxification, or to excess protein intake. In the latter case, other amino acids will be high.

3. Glutamine and arginine are the precursors that, with the help of vitamin B₆, produces the amino acid GABA. GABA is an inhibitory transmitter that exerts a calming action.

Recent research by Ed Cook and associates at the University of Chicago established that there is one or more genes on chromosome 15 that manifest in autism. The chromosome 15 children studied so far showed regression. Between 12 and 24 months of age they lost skills. These children displayed low muscle tone. "They walked on time," Cook says, "and they can eat OK; it’s not severe. They may have had a little trouble holding their heads up as infants, and show a history of low tone in other ways. Most kids with autism aren’t like that, so the floppy ones stand out a bit. A lot of them visually look like Fragile X, with hyper-extensibility of the joints, double-jointedness, and ears that may be a bit longer than normal, and incorrectly ‘rotated’ backward."

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 anxiety. Alcohol, anticonvulsants like Gabapentrin™ (Neurontin™) and Vigabatrin™, and anti-anxiety medications like Xanax™ and Valium™ all work by attaching to the GABA receptor. GABA is an "inhibitory" neurotransmitter; it prevents cells from firing. Some call it the brain’s "braking system."

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, and studies of autistic individuals have detected markedly elevated levels of the phenolic metabolite of tyrosine, DHPPA. ["After 5 years of research, the identity of DHPPA analog finally is established. The compound called DHPPA analog on the organic acid test has now been positively identified as 3-(3-hydroxyphenyl) - 3 hydroxypropionic acid (HPHPA), and after the revision of the organic acid test profile in the beginning of the year 2000, the name on the organic acid test report will be HPHPA instead of DHPPA analog"—William Shaw PhD, Great Plains Laboratory.] Several autistic children with high DHPPA (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. The children treated for clostridia became more sociable, spoke more, improved their eye contact, and were less hyperactive and hypersensitive. 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. The use of ORGANIC ACID TESTING 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.

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.

Although GABA supplementation is used widely for a calming, sedative effect, there is mixed data indicating that GABA taken orally has much clinical effect. Glutamine, a precursor of GABA, readily passes through the blood-brain barrier and is, therefore, a better supplement to take if one wants to increase brain levels of GABA, since Glutamine, once it is in the brain, converts into GABA. The question of GABA’s clinical usefulness may be a function of its dosage. That is, it appears that only mega doses of GABA have clinical effects. GABA activity is found in glands controlled by the sympathetic nervous system, namely: the pancreas and thymus. A deficiency is seen in seizure disorders.

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." It should be noted, Gabapentin™ has been associated with a worsening of hyperactivity in some cases. The type 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 or GABA, or even Bethanecol, before Pepcid™? And once again, strengthen the immune function by following the suggestions herein.

Pasteur and others found that lethal strains of bacteria could be rendered harmless if other benign bacteria were given simultaneously. High intake of Lactobacillus Acidophilus GG [20 billion count, as supplied by Culturelle™ (Klaire Laboratories), available from VRP at 775-884-1300, but said to contain casein], or Kirkman Labs new acidophilus, guaranteed casein free, is the only effective way to replace these, and can be one means of controlling the Clostridia family of bacteria (as well as the yeast), some of which are unaffected by broad spectrum antibiotics! Taking these on an empty stomach, with a little bicarbonate of soda water, will help them make the journey safely. The Bifido Bifidus should also be supplemented when concerned with candida. Next time Flagyl™ is suggested, use L. Acidophilus, and skip the fluoride and the side effects. The antibiotic would likely exchange a Clostridium overgrowth for a candida overgrowth.

The stomach does not produce enough hydrochloric acid (HCl) and pepsin to breakdown the proteins in the stomach. Additionally, reduced HCl cannot activate the enzyme protease that is necessary to complete protein digestion. Other stomach hormones are reduced or lacking, and harmful bacteria are allowed to enter the gut with the food. The chyme leaving the stomach is not acid enough to trigger the secretin release. Digestion is greatly hindered for want of pancreatic enzymes (including peptidase), and the person so afflicted lacks the nutrients of protein, vitamins A, C, E, B-complex, and most of the minerals, all of which depend on HCl to be digested and assimilated effectively. One symptom may be Vitiligo. The lack of pancreatic enzymes, including peptidase, leads to peptides of casein and gluten passing into the blood stream and to the brain, creating many of the autistic symptoms, including a 30% incidence of epilepsy. A small help is to choose supplements as calcium citrate or aspartate that will be utilized even in absence of HCl.

Additionally, aspartate will breakdown the ammonia that is sometimes a problem with autistic children. It is also vital to the synthesis of glycoprotein that is essential to cell to cell communication and proper immune function. Being one of two main excitatory amino acids, an excess is found in Epilepsy and ALS (Lou Gehrig’s disease). It enhances immunoglobulin production and antibody formation. A deficiency is seen in calcium and magnesium shortages.

The lack of HCl causes the environment of the gut is greatly changed, inviting overgrowth of candida yeast that produces a multitude of adverse symptoms. One of the characteristics of some severe fungal infections is that the patient never gets a cold. We hear, "He is the healthiest person in the family." We know fungi provide protection from bacterial infections; however, when yeast is killed off without reestablishing proper flora, bacterial infestations are quick to take over. Bacterial overgrowth, such as citrobacter fruendii (that destroys the mucus lining of the gut), is also a result of this lack of HCl. Another nearly impossible to kill bacteria is Klebsiella Pneumoniae. Here is one successful way to beat them. Dr. Amy Holmes, Baton Rouge, Louisiana says, "I finally was able to completely rid Mikey of the ever-present Klebsiella Pneumoniae. It had been 4-plus in each and every stool culture for at least the last 3 years, despite throwing everything reasonable, both antibiotics and natural substances, at it. I finally realized that nothing was able to get at this bug because of its heavy LPS coat, so I ‘uncoated’ it with bismuth subsalicylate, and killed it with PO Neomycin. I used Neomycin 250 mg/bismuth subsalicylate 50 mg capsules—these must be made by a compounding pharmacist. It can be made as an oral suspension too. The dose is 1 capsule three times a day for 10 days. We are celebrating its defeat. Mike went through a period of apparent die-off for about a week, but has now gotten over that. His progress has been astounding lately." See my Electronic Book "Self-help to Good Health", Chapter "Candidiasis".

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Great Smokies Diagnostic Labs does a stool test to determine what bacteria are present, and the natural substance to which they are susceptible. These are the substances that may overcome these "bugs": Berberine, amphotericin B, Oil of Oregano, Plant Tannins, Uva-Ursi, and Tanalbit (3 caps per meal). [Intensive Nutrition Products, 1-510-632-2370, Oil of Oregano (1 cap AM meal/1 cap PM meal—capsules need to be made—8 drops per cap)]. Amphotericin B™ is more effective and less allergenic than Oregano, and all aromatic oils place an extra demand on Phase 1 liver enzymes that is undesirable for most autistic. Nystatin™ and Amphotericin B™ seem to work well in combination. Oral Amphotericin B™ is safe, and about four times as effective as Nystatin™, injections, however, come with a long list of possible side effects that would indicate it is preferable to use it orally, or to use the natural things first.

Almost all remedies lose effectiveness in time and must be alternated, however goat yogurt and hydrogen peroxide therapy (H2O2) seem to continue effective. Perhaps an easier way is to periodically use colostrum (Kirkman Labs’ Colostrum Gold™ is casein free—others may not be), or whey, if you can tolerate it. (These must be undenatured. There are two I know of, Immunocal™ that may not be readily available, and is very expensive, and "The Ultimate Whey™" by Next Nutrition, Inc., www.designerprotein.com, that is available at most health food stores, or may be ordered from Nutrition Express 800-338-7979.) These provide lactoferrin that deprives these bacteria of the iron they need to replicate, and it contains a peptide, lactoferricin, that is bactericidal against E.coli, klebsiella, pseudomonas, Proteus, Yersinia, Staphylococcus, Listeria, and other bacterial species. Lactoferrin also kills viruses, fungi, and certain tumor cells. In any case, use of these natural aids will protect the "good guys" unlike antibiotics that destroy everything including the gut. Whey, because of its cystine content, may be undesirable where there is a sulfoxidation problem.

Uva-Ursi is normally used for lower urinary tract infections (bladder and urethra), and as a mild diuretic. Some are using it for dysbiosis. It probably should not be used by children for it may damage the liver, nor should it be used for prolong periods, or in high doses. Use it only under a doctor’s supervision. The above named remedies do not treat systemic candida, however, and it may require Diflucan™, Sporanox™ or Lamisil™ for that purpose. Please note that Diflucan™ is fluoride based, and it is best to avoid it.

These medicines prescribed should all be anti-fungal, i.e., nor-nicotine and nicotine (very limited usage), along with the nutrients vitamins B₁ through B₆ (especially nicotinic acid, that is strongly antifungal), potassium and lithium, iodine, sulfates and sulfur (MSM, Epsom salts), and iron. Soda breads (pancakes, waffles, crackers, and biscuits) are said to be helpful, but you must not use sugars with them. Some of the vitamins, especially vitamin B₁₂, are best supplemented by sublingual tablets. Unfortunately, these often contain dyes and sweeteners you may find unsuitable. There are liquid vitamins that can be sprayed into the mouth and held there. You may want to check their suitability. Using these sublingually will supply the needed help regardless of the digestive problems.

Remove all yeast and raw vegetables from the diet, and boil all vegetables in salt (NaCl) water—drain, and cook normally. This will remove all bacteria and fungi the child’s body is not yet able to handle. Supplement HCl, as suggested elsewhere, to provide an additional barrier and enhance digestion. Also avoid the strongly pro-fungal pill binder, lactose (milk sugar), and milk products, and the chlorophylls. All forms of stress must be avoided for that produces cortisol and other steroids that feed the fungi. Heavy or even modest physical workouts must be avoided because they generate lactic acids at a rate that the body cannot handle. If this cannot be avoided, then Mannatech’s Sport and Em•Pact™ have been shown to give rapid recovery from lactic acid overload.

A most appealing way to rid the body of candida is the use of an inexpensive, transient, spore-forming, soil bacteria that is nontoxic, nonpathogenic, and has an extremely antagonistic effect on Candida Albicans. It is believed to actually "feed" selectively on candida, coexisting with bifido-bacteria that the formula also supplies. It is called "Bacillus Laterosporus BOD", and can be obtained as Yeast Avenger™ from www.cfsn.com. You may be able to control the rate of die off by how much you take, and can avoid reinfestation immediately, as often occurs when quitting drugs, by continuing a small amount periodically. An interesting idea is to use this bacteria as a challenge test. If you experience no die-off symptoms, then you likely do not have candida overgrowth. This should be coupled with Culturelle™, or other high count L. Acidophilus.

Die-off can produce severe regression in all autistic symptoms, explosive diarrhea, severe yeast diaper rash, lethargy, fever, bloating, nausea, vomiting, eczema, aching, headache, stuffiness, seizures, and an intense craving for sweets. This is a quote from Dr. Shaw’s book "Biological Treatments for Autism and PDD": "Many of the yeast byproducts are acids and release of the acids which are absorbed into the body may cause a condition called metabolic acidosis. An extremely simple therapy used by physicians who treat autism is to supply a mild antidote that neutralizes the excess acids. The most convenient product is a nonprescription drug called AlkaSelzer Gold™. Do not use any other kind of AlkaSelzer™. AlkaSelzer Gold™ is simply a very safe product called bicarbonate that helps to neutralize excess acids of any kind. The dose for children is on the label. Do not exceed the number of recommended doses." One mother wrote, "It worked so well for both of my children that the die-off was an uneventful experience, even though they both had very high levels of yeast." The restoring of acid/alkaline balance also relieves many allergies.

"These children also had grave disturbances in electrolyte chemistry, and tended to be acidotic (low CO). The data that unfolded was fascinating and clearly earmarked the acidosis and hypoxic state (low serum bicarbonate = low O2 levels). Potassium bicarbonate, sodium bicarbonate, magnesium carbonate and the like were used. Now we began to understand why so many children responded to Buffered C (potassium bicarbonate, calcium carbonate, magnesium carbonate), and others needed a more specific buffer (in some children for example niacin was grossly depleted and they required niacin bicarbonate)"—Patricia Kane. In any case, it should take no longer than six months to rid the body of all parasites. If it has been longer, you are probably not being aggressive enough, or you are not using a proper protocol. It is imperative you take aggressive action to rid the body of parasites and heavy metals. With them will go many "autism" symptoms.

This additional information from Dr. Shaw: Most of the abnormal microbial products found in urine testing are almost surely from yeast and/or fungi in the gastrointestinal tract, since they decline following the use of an antifungal drug, Nystatin™. Many autistic children have a background of frequent infections (especially middle ear infection), which are treated with broad spectrum antibiotics (even though the ear infections are usually of viral origin—WSL). Some children may have elevated yeast metabolites after only a singular antibiotic exposure. Over 700 articles in the medical literature document antibiotic stimulation of yeast growth. Since both early onset and high frequency of ear infection are associated with greater severity of autism, a yeast connection seems worthwhile to evaluate. Autism is usually a regression. This regression is often associated with thrush and/or frequent antibiotic use.

Dr. Shaw’s laboratory has biochemically documented the "yeast die off" or Herxheimer reaction which follows the initial use of antifungal drugs. During the first three days of antifungal use, values for these microbial metabolites increase dramatically, and begin to normalize near day four.

"All the mainstream medical textbooks talk about how people with hormone imbalances due to pituitary problems get yeast. Mercury causes pituitary problems. (In fact, heavy metals like lead, mercury, and cadmium as well as pesticides and chemicals in plastics we daily use are hormone disruptors—WSL.) As if that isn’t enough, yeast is controlled by neutrophils generating oxygen radicals, and mercury prevents your neutrophils from generating oxygen radicals. So it seems reasonable that mercury toxicity causes yeast problems. The fact that lots of adults with intractable yeast problems have them suddenly go away without special treatment once they started mercury detox supports the view that mercury causes yeast. So, if you are mercury toxic, you have a high chance of having a yeast problem, and the yeast will cause its own symptoms. You can reduce those symptoms modestly if you treat the yeast, but you will never really get better until you treat the mercury—and once you do that, you can stop treating the yeast because your body will be able to keep it in check"—Andy Cutler.

As indicated, bovine colostrum is very effective is helping the immune system destroy bacterial, viral, and fungal infections (including candida) in that it boosts natural killer cell function and glutathione production too, when sufficient substrates (the amino acids cysteine, glycine, and glutamine) are available. It has been used effectively in reducing inflammation in autoimmune conditions. It also increases Growth Hormone (hGH) that benefits the transport of amino acids into cells, and elevates the uptake of blood glucose, and causes greater utilization of fat for energy. It (hGH) also tends to increase muscle mass. Increased production of growth hormone greatly increases the need for EFAs. There is a product called "Transfer Factor" (TF) derived from colostrum in which the factor or factors that boost the immune system’s ability to recognize antigens (invading bugs), it has never been exposed to, and destroy them is concentrated to about 100 to 1. This "messenger molecule" is not destroyed in the stomach as a protein antibody would be. Thus, the immunity of the cow, which contains many of the antibodies of the human, is transferred to the human. There is a general "Transfer Factor", and there are specific "Transfer Factor" products, (e.g., one where the cow was infected with HIV should be effective for AIDS). The general one is a relatively inexpensive food supplement available for all ages, but the specific one is a drug, and must be administered by a doctor. These TF products are protected by patent, and so there is only one legitimate product. You may learn more about it, and purchase it at: www.supercolostrum.com/colostrum/Information/information2.htm. The need and benefit of such a product is easy to understand when one recognizes most of these children are suffering with one or more low grade, chronic infections, and their immune system either does not recognize it, or does not have the antibodies sufficient to destroy it. Dr. Hugh H. Fudenberg has done the definitive work with TF in autism. An abstract of a study with autistic youngsters follows:

Fudenberg, H. H. Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot study. Biotherapy 1996;9(1-3):143-7. Immuno Therapeutics Research Foundation, Spartanburg, S.C., USA. Abstract: 40 infantile autistic patients were studied. They ranged from 6 years to 15 years of age at entry. Twenty-two were cases of classical infantile autism; whereas 18 lacked one or more clinical defects associated with infantile autism—dubbed "pseudo-autism". Of the 22 with classic autism, 21 responded to transfer factor (TF) treatment by gaining at least 2 points in symptom severity score average (SSSA); and 10 became normal in that they were mainstreamed in school, and clinical characteristics were fully normalized. Of the 18 remaining, 4 responded to TF, some to other therapies. After cessation of TF therapy, 5 in the autistic group and 3 of the pseudo-autistic group regressed, but they did not drop as low as baseline levels. PMID: 8993773, UI: 97146917.

Let’s stop and think what secretin does to lipid (fat) metabolism. Autistic kids are universally deficient in the fatty acids. Secretin is a pro-oxidant hormone. The metabolic impact of Secretin is that it stimulates the arachidonic acid cascade (contraindicated in seizure disorders) and bicarbonate production, oxidizes or burns off (beta oxidizes) fatty acids (including both essential fats, insulating fatty acids, and very long-chain, fatty acids), increases the metabolism of bile acids, and, theoretically, may stimulate Cholecystokinin-B (CCK-B) that plays a neuromodulatory role in the regulation of GABAergic neuronal activity perhaps (theoretically) stimulating speech. When a child receives secretin over and over again without replenishing the lipids (fatty acids) and catalysts (vitamins and minerals), then the impact could ultimately be quite negative. On the other hand, children with autistic spectrum disorder tend to have a buildup of very long-chain, fatty acids (VLCFA) indicative of suppressed, peroxisomal, beta oxidation, and the use of secretin stimulates the burning off of these aberrant lipids that irritate the brain (and many other systems of the body); thus, in that degree, it is of immediate benefit. The administration of secretin, DHEA, pregnenolone, or thyroid hormone stimulates the beta-oxidation of VLCFAs as would pro-oxidant nutrients and oxidative therapies. Stimulating beta oxidation, however, concurrently stimulates the burning off of essential fatty acids (EFAs) as we said. Children with ASD most often present with acidosis, low CO₂/Bicarbonate, and low oxygen. (Dr. Patricia Kane, Ph.D.). The spacy, dreamy, lack of clarity state you observe in most autistic children is often associated with a low bicarbonate and disturbed electrolyte status. Insufficient oxygen in the brain can lead to a spacy, confused, non alert quality also. Infusions of Secretin will correct the acidosis that most children with ASD present, ultimately impacting their hyperammonemic states that may be stabilized with the increased bicarbonate production (bicarbonate released from the pancreas plus ammonia yields urea that can be excreted). Excess ammonia in the blood is associated with excess lysine.

Peroxisomes are organelles within cells that are pivotal in the biotransformation of endogenous compounds in lipid metabolism such as fatty acids, steroids, prostaglandins, the formation of myelin, neurotransmission, detoxification of exogenous compounds and xenobiotics (phenols and other compounds discussed under the section PST). VLCFAs are fatty acids with 22 or more carbons. Normally, these are oxidized down to C20 or less by p450 oxidase enzymes in the oxisome organelles in the liver. Normally, the C20s are then shuttled by carnitine to the mitochondria for further metabolism. However, mitochondria cannot metabolize VLCFAs so they then accumulate in the nerve cells where they have toxic effects. This is almost universally true in autistic children, but is also seen in Alzheimer patients, chronic fatigue, and cardiovascular disease. The accumulation of VLCFAs (Docosahexaenoic, Docosapentaenoic w3, Behenic, Lignoceric, and Nervonicinside) inside the cell membrane represents defects in peroxisomal, beta oxidation rather than a mitochondrial disturbance. This accumulation may be used to profile the deleterious effects upon the brain, endocrine, gastrointestinal, and immune systems, as well as the cytochrome P450 liver enzyme derangement involving nitric oxide synthase (NOS) characteristic in autistic spectrum disorder due to autoimmune presentation. Therefore the toxic aspect so often described in autism may be defined clearly through examination of Red Blood Cell lipids with elevation of VLCFAs being a reflection of blocked detoxification mechanisms. (Patricia Kane)

This failure to metabolize VLCFAs to shorter ones to be burned in the mitochondria is a failure of the Phase 1 liver detox enzymes. Correct cytochrome p450 function, and you correct fatty acids. Correct fatty acids, you correct protein metabolism. To do that, you have to support the liver. Herbs that enhance Phase 1 detoxification, like milk thistle, and the lipotrophic vitamins of the B-complex will be valuable here. Get a copy of "The Liver Cleansing Diet; Love Your Liver Live Longer" by Dr. Sandra Cabot, MD, (www.liverdoctor.com), and eat a liver-friendly diet.

Autism is said to often involve a demyelination of the myelin sheath of nerves, disrupting nerve transmission. Brain autoantibodies to myelin basic protein and neuron-axon filament protein have been found in autistic children. Some have found Sphingolin™ most helpful. It benefits the myelin sheath, increasing perception and response. Dr. Jeff Bradstreet, however, reports that children who took oral myelin basic protein (Sphingolin™) seemed worse when they were infused with secretin. The secretin burned off the fats (needed to make myelin and prostaglandins, both the insulating fats and the very long chain fats). It is a big "no no" to stimulate with peptides (secretin) with Sphingolin™ without fats! (Patricia Kane) If you choose to infuse, you must supplement generously with Evening Primrose oil (EPO); and always with fatty acids, you must supplement with the antioxidants vitamin C and vitamin E with selenium, preferably before beginning the EPO. Additionally, Dr. Woody McGinnis, MD, of Tucson, Arizona, USA, has reported investigating two seizures that occurred during or immediately following infusion. One was near fatal. Make sure the one infusing is ready for any emergency. It is probably inadvisable to infuse one who is subject to seizures. Dr. McGinnis tells of a doctor whose son started having seizures (not immediately, but delayed) after secretin. She found the urinary pH really alkolotic, gave him generous unbuffered vitamin C, and says the seizures abated. Perhaps, before infusion, one should check for an overly alkaline urine, and do so again after the infusion to anticipate and forestall any possible seizures.

In the case of inadequate HCl production, infusion or transdermal supply of secretin may indeed help, but it does not fully address the most basic need—that of necessary digestion and utilization of food. The proper course for many seems not to be secretin infusion, but a supplementing of hydrochloric acid to the degree necessary to trigger release of the secretin so vital to proper digestion and hormonal response. In at least a minority of these children, the gut will be able to release adequate secretin. The supply of adequate acidity to the chyme would then "Kick Start" secretin production. One mother reports, "Since I followed your suggestion, and supplemented HCl, my son has the same responses he had to his secretin infusion!"

In view of the above, I think it better to address the need for HCl first. Low HCl production is associated with many problems. Iron deficiency anemia, owing to poor iron absorption, or to lead or cadmium poisoning, and osteoporosis, resulting in part from decreased calcium absorption, are two important problems. General allergies and, specifically, food allergies are correlated with low HCl. Poor food breakdown and the "leaky gut" syndrome are associated with food allergies. More than half the people with gallstones show decreased HCl secretion compared with gallstone-free patients. Diabetics have lower HCl output, as do people with eczema, psoriasis, seborrheic dermatitis, Vitiligo, and tooth, and periodontal disease. With low stomach acid levels, there can be an increase in bacteria, yeasts, and parasites growing in the intestines. You may obtain Betaine Hydrochloride or Glutamic Hydrochloride, 10-grain capsules from the health food store. If allergic to beets, choose Glutamic Hydrochloride. If sensitive to sulfites [MSG—Chinese restaurant syndrome, or diagnosed as suffering from phenol-sulfotransferase deficiency (PST)], choose Betaine Hydrochloride. Glutamic acid hydrochloride is only mildly acidic, and does not work as well as betaine hydrochloride. Betaine may be used alone, in supplements, or along with pepsin or other digestive agents. A child should get good results with one to five, 10-grain capsules, adults with five to ten (a predominantly pasta meal would need less than a high protein one). Start with one, and increase gradually. For children who will not swallow a capsule, it may be mixed with the food, or mixed in a small amount of drink that will be consumed completely. Woodlands Healing Research Center reports an older autistic boy showed marked improvement in digestive function, and a dramatic reduction in agitation when the mother began mixing betaine hydrochloride with pepsin into meat, poultry or other protein foods before meals.

Low stomach acid can be corrected by eating a balanced diet of wholesome foods, and by reducing our daily levels of stress. Niacin stimulates HCl production. This can be taken before meals, as can magnesium chloride and pyridoxal-5-phosphate (the active form of vitamin B6) to help stimulate the body’s own HCl output. Zinc is essential to HCl production. Drinking the juice of half a lemon squeezed in water or a teaspoon of apple cider vinegar in a glass of warm water 30 minutes before meals helps, and supplements taken during or after meals should be swallowed using the lemon or vinegar treated water. Use of Swedish Bitters or gentian has been helpful in improving digestion.

We are talking acid here. One 10-grain tablet of HCl in 1-1/2 ounces of water will have a pH of about three. This is not nearly as strong as what you may have experienced when you burped, and the acid really burned your throat; but, when HCl is mixed with food, it must be swallowed right down without chewing. Do not leave this food in the mouth. It could damage the enamel on the teeth. Additional food should be eaten immediately to clear the throat. If mixed with a drink, drink it with a straw to protect the teeth. Rinse the mouth, and swallow to clear the throat. Try it yourself, Mama. As with all such matters pertaining to your child’s health, consult with your medical professional.

If the hydrochloric acid is sufficiently strong, and the gut is able to release secretin, and the pancreas is functioning, the use of an enteric-coated, alkaline tablet will not be needed to neutralize the acid in the intestine. The pancreas will normally release enough bicarbonate based on the strength of the secretin signal. The amount of secretin released is dependent on the amount of hydrochloric acid in the chyme entering the gut.

Where HCl is adequate, but secretin is not being adequately produced, or the pancreas is not functioning well, the proteolytic enzymes may not be released; or, because of a lack of bicarbonate of soda, they will be destroyed by the acidity of the chyme. This can result in incomplete breakdown of proteins. These "foreign" protein molecules may be absorbed into the bloodstream, and circulated throughout the body. These "peptides" can cause all types of allergic (autoimmune responses) or toxic reactions, in particular those relating to breathing and skin irritation. Taking an alkalizing substance (an enteric coated pill) in that case, will neutralize the stomach acid in the gut, prevent the destruction of the proteolytic enzymes if any are available, and maintain an environment for the flora of the gut. If a tablet is not available, taking 1/2 teaspoon of bicarbonate of soda in a glass of water after the stomach begins emptying (about 2-1/2 hours after eating) can be just as effective. Without sodium being present glucose cannot be absorbed. Picture a revolving door in the wall of the gut with two segments. Without these two substances filling the segments, the door won’t turn. Mercury causes excessive sodium excretion, as shown in studies of dental amalgam placed in monkeys and sheep (Lorscheider et al, 1995).

Do not take any water, tea, or other nonfood drink with a meal or within two hours as that will dilute the HCl and hinder digestion. If you must drink water to take pills, put a tablespoon or more of lemon juice or apple cider vinegar in the water to help preserve stomach acidity.

As to the amount of acid in the capsules, you will not begin to administer as much as a normal stomach produces for an average adult meal (estimated to be equivalent to 30 capsules). It is the quantity as well as the degree of acidity that is important. Normal pH must be below three (preferably two) to convert pepsinogen into pepsin (needed to digest protein). It is often as low as one (the strongest acid).

If there is burning or pain, or if the digestive distress experienced previously (bloating, belching, heartburn, reflux) becomes worse, discontinue the use of the hydrochloric acid. Sensitivity of the stomach to acid (especially a burning pain just below the sternum) may indicate an ulcer. However, it likely indicates the person is dehydrated, or using aspirin or NSAID for pain. Everyone should drink a large glass of water 30 minutes before eating. That will rehydrate the mucus lining of the stomach, and protect the stomach from the acid. If there seems to be adverse reactions other than pain or burning, an allergy to Betaine (beets) Hydrochloride may be the cause. Try Glutamic Hydrochloride instead.

HCl production is controlled by the enzyme carbonic anhydrase. Toxins of bacterial overgrowth, gluten-casein peptides, metabolic acidosis, and lack of zinc all depress this enzyme. An inflamed, irritated gut present in autism will not absorb zinc well. You must supplement zinc, and balance your zinc-copper ratio, and restore the proper body pH to restore HCl production. This pH can be improved by supplementing ionic calcium—that autistics are universally lacking. When there is adequate calcium, the saliva will be near pH 7.0 between meals, anything less than pH 6.5 is cause for concern.

Common features in those with autism include: raised blood or serum lactate, regional disturbances in glucose uptake in the brain, particularly in the cortex, and reduced brain levels of high energy phosphate compounds.

These observations would suggest a mitochondrial energy disorder in the brain. Mitochondrial dysfunction may result from any of the following:

1. Impairment of mitochondrial fatty acid oxidation due to carnitine deficiency. Carnitine pumps fatty acids into the mitochondria. With the help of vitamins B₆,C, and niacin, the body produces carnitine from the amino acids lysine and methionine found in high quality protein. Adequate amounts are not thus formed so some carnitine must come from muscle and organ meats in the diet for it is not found in vegetables. Obviously, a low protein or vegetarian diet would likely create a deficiency of this vital nutrient, and impair mitochondrial function causing a loss of energy and a build up of triglycerides and fatty acids in the blood and cells.

The Cincinnati Children’s Hospital Medical Center’s Department of Enzymology has identified two patients with the "carbohydrate deficient glycoprotein syndrome" through alpha-1-antitrypsin phenotyping. The carbohydrate deficient glycoprotein in the serum of these patients produces a band on polyacrylamide gel isoelectric focusing that moves cathodally of the Z-band. In the area of carnitine deficiency, there is, for example, less than 5% of normal muscle carnitine concentration. After carnitine supplementation, patients unable to talk or walk, with hypotonic musculature and symptoms of autism, became able to walk with the help of a walker. They could stand alone for short periods, and they acquired an interest in their surroundings. The common findings of carnitine deficiency were an impaired ability to walk, muscular hypotonia, reduced muscle carnitine concentration and an improvement in locomotion while on carnitine. A supplement seems essential.

It should be noted that not only fatty acids are needed, but glucose must be able to enter the cell to produce energy needed by the cell and by the muscles. Just as L-carnitine pumps in fatty acids, Alpha Lipoic Acid pumps in glucose. It’s supplementation tends to overcome syndrome X, where the cells are resistant to glucose. This resistance produces unnaturally high blood levels of insulin.

Since the amino acid L–carnitine is frequently lacking in the autistic, this could predispose to heart problems and a lack of energy. Carnitine carries the fatty acids into the mitochondrial furnace to fuel ATP (the energy molecule). A deficiency can be indicated by high triglyceride and cholesterol readings.

The primary function of carnitine is to escort fatty acids into the mitochondria where the fat is burned for energy, in this action it reduces blood levels of triglycerides and cholesterol dramatically, and aids weight loss. It boosts energy levels for those suffering from elevated blood sugar levels and kidney insufficiency. This reduces fatigue. Tests by Dr. Carl Pepine at the University of Florida showed that carnitine increases blood flow in the heart by 60%, and reduced vascular resistance 25%. It reduces heart arrhythmias by 58% to 90% in patients with chronic heart problems. He reported that patients were enabled to walk 80% farther before discomfort set in. Dr. A. Feller (1988) reported in the Journal of Nutrition that arrhythmia’s are usually a result of a carnitine deficiency. The heart is enabled to pump more blood, with fewer beats, and with less tendency toward oxygen deprivation. Vitamin E would be its ally in this for it enables muscles to function on 40% less oxygen. This would relieve angina and reduce risk of heart attack. A deficiency may result in chronic tiredness, fatigue, nausea, dizziness and anemia. Lysine is converted to carnitine, and carnitine increases acetylcholine an important neurotransmitter. Autonomic system abnormalities can be caused by disturbances in acetylcholine levels, known to be deficient in both autism and mercury poisoning.

L-carnitine (500 mg capsules taken twice daily on an empty stomach, or with a carbohydrate snack) will reduce ketone, triglyceride (up to 40%), and cholesterol levels (up to 21%), and increase HDL levels (up to 15%). It will conserve calcium, magnesium, and potassium, and may reduce heart arrhythmias and fatigue—which will reduce risk of heart attack.

Due to increased fat burning, carnitine supplementation creates a significant need for caloric increase. If none is supplied there will likely be weight loss. Additionally, lower than normal levels of certain essential fatty acids, such as cholesterol (needed as the precursor to many hormones) and triglycerides (a large proportion of the blood’s fatty substances) can be exacerbated by supplemental carnitine. One Mother says, "We lost our seizure control and did not regain it until calories had been upped significantly...Please, everyone, let’s consider very carefully the premise that carnitine supplementation creates a significant need for caloric increase." The level of fatty acids in the autistic child is an important factor because the endocrine system and its hormones, the brain and its neurotransmitters, the myelin sheath, and all the immune system components are derived from lipids (fats).

However, mitochondria cannot metabolize Very Long Chain Fatty Acids which many autistic have accumulated; so, if carnitine pumps additional ones into the cell, they can accumulate in the cells where they have toxic effects. This is almost universally true in autistic children, but is also seen in Alzheimer patients, chronic fatigue, and cardiovascular disease. The accumulation of VLCFAs inside the cell membrane represents defects in peroxisomal, beta oxidation that is likely the result of hypothyroidism. Therefore, the toxic aspect so often described in autism may be defined clearly through examination of Red Blood Cell lipids with elevation of VLCFAs being a reflection of blocked detoxification mechanisms.

Carnitine supplementation holds great promise, and it must be supplemented when Depakote™ is being used, but I think there are some things we must guard against. Additional carnitine will pump more fatty acids into the mitochondria to produce additional energy. It would help to know from a previous blood test that the triglycerides and cholesterol were normal or elevated. When using carnitine, to avoid creating a deficiency in fatty acids, we must supplement with Evening Primrose and cod-liver oils as outlined elsewhere in this paper, and ensure the child is getting enough calories for his size and activity. The wild card is the VLCFAs. To determine their status run the Red Blood Cell Lipid test. Symptoms of fatty acid deficiency would tend to be thirst, dry skin and hair, brittle nails, excess urination, dandruff, and rough skin. If these symptoms, or low triglyceride/cholesterol levels, or excess VLCFAs are present, I would not supplement carnitine, until these problems were being corrected. As I understand it, carnitine could lower the fatty acids and blood fats adversely, and could overload the cell with VLCFAs that it cannot burn.

2. A second cause of mitochondrial energy disorder is inflammation associated with the release of excess nitric oxide. Excess nitric oxide can cause uncoupling of oxidative phosphorylation as well as inhibiting the Kreb’s cycle enzyme, aconitase. This will result in organic acidemias, and low mitochondrial energy production. Lactic acidosis and carnitine deficiency in autistic patients suggests excessive nitric oxide production in mitochondria (Lombard, 1998; Chugani et al, 1999), and mercury may be a participant. Methylmercury accumulates in mitochondria, where it inhibits several mitochondrial enzymes, reduces ATP production and Ca2+ (calcium) buffering capacity, and disrupts mitochondrial respiration and oxidative phosphorylation (Atchison & Hare, 1994; Rajanna and Hobson, 1985; Faro et al, 1998). The herb Ginkgo Biloba selectively increases the release of nitric oxide synthase, the enzyme that reacts with arginine to produce nitric oxide. It should be avoided in this instance.

Neurological problems are among the most common and serious of mercury poisoning, and include memory loss, moodiness, depression, anger and sudden bursts of anger/rage, self-effacement, suicidal thoughts, lack of strength/force to resolve doubts or resist obsessions or compulsions, etc. Mercury causes decreased lithium levels, which is a factor in neurological diseases such as depression and Alzheimer’s. Lithium protects brain cells against excess glutamate induced excitability and calcium influx, and low levels cause abnormal brain cell balance and neurological disturbances. Medical texts on neurology point out that chronic mercurialism is often misdiagnosed as dementia or neurosis or functional psychosis.

Mercury at extremely low levels interferes with formation of tubulin producing neurofibrillary tangles in the brain similar to those observed in Alzheimer’s patients with high levels of mercury in the brain. Mercury and the induced neurofibrillary tangles appear to produce a functional zinc deficiency in the AD sufferers, as well as causing reduced lithium levels. Mercury binds with cell membranes interfering with sodium and potassium enzyme functions, causing excess membrane permeability, especially in terms of the blood-brain barrier. Less than 1ppm mercury in the blood stream can impair the blood-brain barrier. Mercury also blocks the immune function of magnesium and zinc. Exposure to mercury vapor causes decreased zinc and methionine availability, depresses rates of methylation, and increases free radicals—all factors in increased susceptibility chronic disease and to cancer.

A recent study demonstrates that oral administration of N-acetylcysteine (NAC), a widely available and largely nontoxic amino acid derivative, produces a profound acceleration of urinary methyl mercury excretion in mice. Mice that received NAC in the drinking water (10 mg/ml) starting at 48 hr after methyl mercury administration excreted from 47 to 54% of the 203 Hg in urine over the subsequent 48 hr, as compared to 4-10% excretion in control animals. When NAC was given from the time of methyl mercury administration, it was even more effective at enhancing urinary methyl mercury excretion, and at lowering tissue mercury levels. In contrast, excretion of inorganic mercury was not affected by oral NAC administration.

3. Defects in respiratory chain enzymes. Pyrurate Dehydrogenase or mitochondrial respiratory chain defects, that is, NAD, NADH, CoEnzyme Q10, and cytochrome oxidase deficiency. Although we find a variety of autistic phenotypes to have associated mitochondrial abnormalities, the most common is nonspecific PDD, typically of a form that manifests language and cognitive regression or stagnation during the second year. Most surprising among multiplex families is that the biochemical and clinical markers of mitochondrial disease often segregate in an autosomal dominant manner (that is, genetically induced). Although no molecular lesion has yet been found in the autosomal dominant families, the biochemical findings are most consistent with abnormal mitochondrial complex I activity (that is NAD/NADH activity—WSL). Early and careful evaluation of autistic children for these more subtle mitochondrial disturbances may rescue them from more severe brain injury (Kelley, Richard, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD). Note that the acetylaldehyde toxin given off by candida yeast inhibits the NAD/NADH exchange.

4. Excess glutamate exposure, a common and increasing source being MSG. Generally, autistic children show low glutamine, high glutamate. Plasma levels of glutamic acid and aspartic acid are elevated even as levels of glutamine and asparagine were low (Moreno-Fuenmayor et al, 1996). Mercury inhibits the uptake of glutamate, with consequent elevation of glutamate levels in the extracellular space (O’Carroll et al, 1995). Thimerosal enhances extracellular free arachidonate and reduces glutamate uptake (Volterra et al, 1992). Excessive glutamate is implicated in epileptiform activities (Scheyer, 1998; Chapman et al, 1996). Cells that are without oxygen may release excessive glutamate. Low oxygen is common in autistics. Children’s forming brains are four times more sensitive to neuro-excitotoxins. The lower the energy production of the cell, the more susceptible it is to excitotoxicity. Low magnesium levels (common in "our" children) can double free radical production and magnify their toxicity! The generation of increased levels of free radicals within the cell can activate the p53 tumor-suppressor gene triggering apoptosis (cell suicide). Excess glutamate can kill neurons by necrosis (by its allowing excess calcium into the cells) as well. Magnesium is the calcium regulator. Elevated plasma glutamate lowers cellular GSH by inhibiting cystine uptake.

Additionally, high levels of insulin inhibit an enzyme in the cell wall responsible for helping to regulate proper intracellular calcium balance. Since the interstitial fluid outside the cell usually contains a thousand times higher concentration of calcium than is normally present within the cell, this excess insulin response to our improper (high carbohydrate) diet simply opens the calcium floodgates into the cell by inhibiting this membrane enzyme. Excessive calcium will enter the cells, impairing metabolism, producing cross-lnkages and premature aging, and eventually producing excessive arterial spasm. Manganese is a natural chelating agent when taken in the food supply or as a supplement. It will do everything a calcium channel blocker will do, but more naturally and effectively. There will be no intracellular infiltration by calcium transporting through the cell membrane as long as manganese is present as a substitute. It works in a similar way to magnesium’s characteristic of displacing calcium ions. One of the keys to mercury’s effects on health may be its ability to block the functioning of manganese, a key mineral required for physiological reactions. New studies in humans and in the laboratory show that PCBs and mercury interact to cause harm at lower thresholds than either substance acting alone.

Though forced to remove MSG, baby formula today frequently utilizes caseinate that contains a high enough level of glutamate to endanger a newborn’s brain! These excitotoxin additives are hidden under the terms hydrolyzed vegetable protein, protein isolate, protein extracts, caseinate, and natural flavorings! Another damaging excitotoxin is Aspartame™ that has increased exponentially in all our foods. Others include fluoride, aluminum, iron overload, and organophosphate pesticides and herbicides.

It would appear that the pathology of autism is one of immune dysregulation, with associated food intolerance, and opportunistic infection that triggers excessive production of the inflammatory cytokines and nitric oxide leading eventually to neural mitochondrial inhibition.

Nutrients that may improve mitochondrial function include, magnesium, CoEnzyme Q10, N-acetylcarnitine, N-acetyl cysteine, vitamins B₁, B₂, niacin, folic acid, NAD (Nicotinamide Adenine Dinucleotide), alpha-keto-glutarate, and antioxidants such as vitamin E, C, alpha lipoic acid, manganese, and selenium. Supplementation of glutathione has improved skill with numbers and fine motor skills. Glutathione is expensive, and not well assimilated. If you use it, take it with some vitamin C which will improve its assimilation by up to 20%. Where possible, help the body produce its own supply.

Olfactory and gustatory symptoms of psychiatric patients ameliorated completely or partially by zinc supplementation, that is, their sense of smell and taste are improved so they tend to eat better. In a small study (Am J Clin Nutr 53:16, 1991), 30 mg zinc per day intake increased the short term recall of visual images. Since it is known that essential fatty acid metabolites stimulate intestinal zinc, supplementing fatty acids with zinc is clearly warranted. Zinc is known to help in the healing of gastric and peptic ulcers. This is probably because zinc is required for the synthesis of gastric mucosa. Zinc, and vitamins B₃, B₆, and C are necessary for the conversion of essential fatty acids to PgE1 (prostaglandin E1) that is protective from the excessive gastric secretion. Zinc controls over 200 enzymes, one of which is necessary for the stomach to produce hydrochloric acid. Note this quote: "We took hair samples from 31 boys and 15 girls, and had them analyzed by Dr. P. J. Barrow of the Dept of Environmental Health, University of Aston, Birmingham. Twenty-four of the boys and seven of the girls had zinc values below the normal range."—from 1979 survey of hyperactive children belonging to the H.A.C.S.G. Our May 1981 research paper: "A Lack of Essential Fatty Acids as a possible cause of Hyperactivity in Children" was based on these findings.

Children that are unsettled, frequently demanding attention, upset much of the time, and those whose sleep is regularly broken during the night can be very wearying on parents to say the least. Additionally, recent studies show that in sleep-deprived people the part of the brain responsible for language slowed down tremendously. Furthermore, after a sleepless night a person will do only half as well on memory tests as when well rested. Sleep deprivation produces more insulin and cortisol, both damaging to health and well being. Dr. Joseph T. Hart, a pediatrician of Portland, Oregon, has found that by supplementing zinc you may be able to eliminate the problem of sleeplessness. He has supplied zinc drops to hundreds of children, and in the majority of the cases the chronic sleeplessness has disappeared! Additionally, copper, iron, and magnesium deficiencies will adversely affect sleep. Dr. K. M. Hambridge of Denver, Colorado, observed that zinc-fed babies were much less irritable. Hart reports that zinc supplementation also produces improvement in appetite, and reduces daytime irritability, diarrhea, skin rashes, and pallor. In older children, whose wakefulness was followed by climbing out of bed and getting in with their parents, the habit was lost.

Zinc also helps get rid of the terrible two’s. Within a week you can often see a definite settling down, and reduction of tantrums and of the terrorizing of the poor mother! Zinc is being successfully used for learning disabled children, for children with seizures, skin lesions, and histories of infections. Zinc is essential for new tissue formation. It is essential for white blood cell and antibody formation. It helps neutralize toxic minerals in the bo