- Digestion -

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. This dislike for meat, or a taste loss, could indicate cellular distress and possibly cancer, or a lack of hydrochloric acid, or a zinc deficiency, for zinc controls the enzyme that makes HCl. Because there is a strong association between protein and zinc content in virtually all types of foods, insufficient protein intake may often be the cause of zinc deficiency.

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. (Dr. Robert Fried found that hyperventilation precedes seizures which result in arterial constriction and spasms. He concluded that the abnormal electrical activity picked up on EEGs is the result of seizures, not the cause, nor the seizure itself-WSL.) 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). (Calcium carbonate tends to constipate, and may be useful in controlling diarrhea, or when magnesium is tending to loose bowels-WSL.) Buffers and butyrates attenuate (lessens the effects of) 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.

ButyrEn™ by Allergy Research Group/Nutricology, Inc (800-782-4274) is a dietary supplement in the form of an enteric-coated formulation of calcium and magnesium salts of butyric acid, a short-chain, fatty acid. It supports the integrity of colonic mucosa by acting as primary fuel for the colonic epithelium. It is normally produced by colonic bacteria, but when these bacteria are disrupted this supplement will support colon health as you rebuild colon flora. This has been shown to modulate local electrolyte flux, thereby mediating diarrhea.

As indicated, the undigested protein turns into ammonia and goes to the brain. Kane recommends that one hour after every meal, when the body is supposed to be producing its own CO2, the carbonate buffers be given, along with a big glass of carbonated water. I feel this is too soon for it will stop protein digestion and defeat the purpose of intervention. It seems to me that 3 hours after eating would coincide with dumping time, and serve the purpose better. A child with these problems consumes mostly carbohydrates. All those carbs cause high glucose which produces more insulin than is healthful, and that interferes with fatty acid metabolism, and protein utilization, and produces insulin resistant cells, tending to overweight and diabetes. Overweight children with high levels of insulin in their blood are also likely to have high levels of homocysteine, a substance that appears to raise the risk of heart disease, stroke, and birth defects, as well as possibly other adverse effects as well. In addition, these children and adolescents appear to have lower levels of folate, a vitamin that can lower homocysteine levels-Dr. Mercola. These children may have high albumin-which is the substance that transports toxins out of the body. High albumin means high toxins are present.

These carbonate buffers can be used when you recognize a child is having a severe allergic reaction to stop the reaction. If you think someone's having an allergic reaction, and you don't have the carbonate buffers, you can try half a teaspoon or a teaspoon of baking soda in a half-glass of water. Sometimes that will stop a reaction within 10 to 15 minutes. Three commercial products AlkaAid™, AlkaSeltzer Gold™, and AlkaLime™, or alkali salts (from health food stores, usually a combination of sodium and potassium and sometimes calcium carbonate) can be used. This is very effective in not only stopping reactions, but if you take it before you eat a food to which you are sensitive, you can sometimes prevent a reaction. If you're going to a smorgasbord or to somebody's house for dinner, and you're not quite sure what they're going to serve, you certainly should try to take that in advance.

"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 these nutrients. Supporting the thyroid will increase carbon dioxide production. Anytime you are taking Valproic Acid, you must supplement L-Carnitine (Carnitor™) to avoid deadly consequences of its deficiency.

When the mitochondrial respiratory chain is blocked, metabolites that are normally processed by its enzymes may build up in the cells and cause problems. For example, pyruvate is a chemical derived from glucose that's normally shipped into the mitochondria, and then processed further so that its potential energy can be harvested by the respiratory chain. However, when the respiratory chain is blocked, pyruvate accumulates outside the mitochondria, and when too much pyruvate has accumulated, the cells start to convert it to lactic acid. "Many patients with mitochondrial disease have lactic acidosis-lactate in the blood," neuroscientist Eric Schon of Columbia University in New York says. "And there's decent evidence that the lactate isn't just a sign of faulty mitochondria, but that the lactate itself is bad-especially in the brain, but probably also in the muscle. If this is true, then holding that lactate down would help the patient." Sport by Mannatech™ can aid in removing excess lactic acid, whether in sports, or in autism; however, supplementing small amounts of alpha lipoic acid, NADH, and CoQ10 may enable the mitochondria to use it.

Cellular energy production itself produces free radicals that can damage cell structures, including the mitochondria, and ultimately lead to various diseases if the body's natural antioxidant capacity is inadequate. Acetyl l-carnitine and lipoic acid are both endogenous (naturally present in the body) antioxidants that have been shown to restore mitochondrial function and reduce free radical damage. (Hagen TM et al., 1998; Lyckesfeldt J et al., 1998). Together with NADH and coenzyme Q10, they work to maintain the function of the mitochondria.

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. Zinc appears to influence the bioavailability of secretin as well as availability of HCl. 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 L-taurine, and L-glycine are needed. If these do not correct the problem soon, then a supplement of ox bile or of 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"-Susan Owens.

Pancreatic function was significantly reduced in patients with hypothyroidism compared with healthy subjects. Treatment with thyroxine restored pancreatic function to normal. In two additional hypothyroid patients studied by means of duodenal intubation, pancreatic secretion of both bicarbonate and enzymes was found to be significantly decreased. It was concluded that the thyroid gland plays an essential role in maintaining the functional integrity of the exocrine pancreas in humans (Gullo et al, 1991). A new study published in the July issue of the American Journal of Gastroenterology by Dr. Vincenzo Toscano and colleagues at the Universita La Sapienza in Rome indicates that adolescent patients with celiac disease have elevated levels of anti-thyroid and anti-pancreatic autoantibodies.

It was shown in an in vivo experiment that treatment of rats with thyroid hormone increased hypothalamic oxytocin (OT) mRNA levels, the pituitary OT content, as well as OT levels in blood. The results reveal thyroid hormone as a physiological regulator of OT gene expression, which stimulates OT promoter activity directly through interaction with a thyroid hormone-response element in the OT gene. (Adan et al, 1992) Thyroid hormones affect oxytocin gene expression in hypothalamic neurons.(Dellovade et al, 1999).

Researchers observed that there was a remarkable family resemblance between social bonding and narcotic addiction-from the initial attachment-dependence phase to the eventual tolerance-withdrawal phases. It rapidly became clear that when animals were given very tiny doses of opiates, they were not distressed by social isolation, and they became comparatively unsocial (even though they could exhibit increases in certain social activities such as rough-and-tumble play). When given opiate antagonists, such as naltrexone, they were more disturbed by social isolation, and they became more eager for gentle and friendly social contact. It's not a far step to imagine that these opiate effects on social behavior might reflect something that is happening in childhood disorders such as autism. "When we focused on the data, it was clear that only the animals given opiates became unsocial and less pain sensitive." researchers said. Thus, it seemed more compelling to suggest that some kids with autism might also have too much opioid activity in their brain. This was especially attractive since there were experimental drugs, such as naltrexone, that could reduce such brain activities. Still, some of the kids, perhaps the insecure/anxious ones, may have too little opioid activity.

"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. Restoring the beneficial bacteria that line the intestinal tract may help to prevent the body's immune system from causing inflammation in the gut. Researchers found that these bacteria are actually able to control the immune system of the host.

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.

It is worthy of note that over 80% of children with acute otitis media improve without antibiotic therapy within a week. That compares with 93% recovery during the first week with antibiotic treatment, according to a study released by the Agency for Healthcare Research and Quality (AHRQ). "Watchful waiting" is suggested as preferred treatment. This will prevent the damage to the gut, candida overgrowth, and if made accepted practice, it will greatly reduce bacterial resistance to antibiotics.

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.

A deficiency of calcium in the serum may also be caused by hypoparathyroidism, vitamin D deficiency, kidney failure, acute pancreatitis, or inadequate amounts of plasma magnesium and protein. Mild hypocalcemia is asymptomatic (or shows as nocturnal cramps-WSL). Severe hypocalcemia is characterized by cardiac arrhythmias and tetany with hyperparesthesia (tingling as if "asleep") of the hands, feet, lips, and tongue. The underlying disorder is diagnosed, and calcium is given by mouth or intravenous infusion. Hypocalcemia is also seen in dysmature newborns, in infants born of mothers with diabetes, or in normal babies of normal mothers delivered after a long or stressful labor and delivery. The condition is signaled by vomiting, twitching of extremities, poor muscle tone, high-pitched crying, and difficulty in breathing-1998 Mosby-yearbook, Inc.

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 PhytoAloe® 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.

Willis Langford

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