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Leaky Gut

 

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. Human Secretin receptor is a G-protein-coupled receptor that is functionally linked to the cAMP second messenger system by stimulation of adenylate cyclase (Ng et al, 1999). When given Secretin, there is overactivity of the pancreas. Intravenous Secretin causes a five-fold increase in the output of IGF-1 in pancreatic fluid. 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 distention. 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 (amylase) 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 amylase and lactase). None showed signs of Helicobacter Pylori infection, or of fungal or bacterial overgrowth even in the one-third with suspected fungal or bacterial overgrowth based on urine acid test results.

 

Dr. Karoly Horvath reported low levels of disaccharide/glucoamylase enzymes, and suggests that carbohydrate malabsorption may be the cause of the gastrointestinal symptoms seen, including abdominal pain, gas, bloating, and chronic diarrhea (loose stools). He also found 14 of 21 children had low lactase activity. He documented reflux esophagitis in 69.4%, chronic inflammation of the gastric mucosa in 41.7%, and chronic duodenal inflammation in 66.7%. Further, a high carbohydrate (high insulin), low fat, high glycemic diets (and stress) promote inflammation because GLA is being driven toward arachidonic acid by the activating effect of insulin in overwhelming the inhibitory effect of EPA upon the Delta-5 Desaturase enzymes. High insulin levels also lower blood testosterone in men by 10%! Remove the child from his high-glycemic, high-carbohydrate diet and supplement a good digestive enzyme such as Kirkman’s EnzymAidtm or Mannatech’s GI-ZymeR.

 

A recently discovered inhibitor of Delta-5 desaturase is Sesame lignans. It also enhances production of DGLA. When combined with fish oil, DGLA levels rise dramatically. Life extension Foundation supplies Super Omega-3 with Sesame lignans. This would greatly reduce the need for Evening Primrose to supply GLA/DGLA. Sesame lignans also inhibit production of dangerous cytokines, such as TNF and IL-6, and suppress free radicals that increased DHA creates. Sesame lignans also enhance levels of vitamin E and DHA. These kids also desperately need a digestive enzyme supplement, but may first need Bromelain, an effective anti-inflammatory enzyme shown to reduce inflammation by 60%. Even more effective would be Vitalzym™ that supplies both anti-inflammatory and digestive activities.

 

Your doctor has probably forgotten a simple, inexpensive, urine test that he can make in office that uncovers toxic bacteria. Ask for a “urinary indican” test. Indican is created when harmful bacteria in the bowel ferment the essential amino acid tryptophan. If the indican test is positive, decrease intake of sugar and high glycemic carbohydrates because eating these things encourage overgrowth of many types of unfriendly critters, including Candida. Supplement friendly flora to crowd out the nasties.

 

This inflamed gut (dubbed “Leaky Gut” because it has become porous allowing large, food particles of both partially digested protein [peptides] and undigested starch to pass unnaturally into the blood) produces a number of symptoms. Increased intestinal permeability (IP) may reflect damage to the microvilli, which can reduce levels of lactase, the enzyme needed to digest milk sugar, eventually triggering osmotic diarrhea. Once this disease process starts, small bowel mucosal damage, indicated by higher IP ratios, remains “an important factor” associated with increased acidosis, hypokalemia (lack of potassium), iron deficiency, dehydration, and parasitic infection.

 

Actually, the dehydration, often caused by excessive amounts of sugar in the form of wheat and other grains, bread, and any form of sugar including fruit juices, causes a breakdown of the mucosal surfaces leading to the leaky gut syndrome and all forms of allergies. Once dried out, there is no mucosal protection against the ever-present yeast, molds, bacteria, pollens, and various allergens. It is vital that you increase the child’s intake of water in most instances. Drinking a glass of water 30 minutes before eating increases the mucosal film significantly.

 

Sucrose (table sugar) leaks into the blood, and this abnormal sugar in the blood stream causes a host of problems. Sugar increases the amounts of calcium, oxalate, uric acid, and glycosaminoglycans in the urine. Particles [especially from milk (casein) and grains (gluten/gliadin)] called peptides pass through the “Leaky Gut”, and activate the immune system (Leukocytosis) creating many allergic symptoms, and also creating opioids in the brain that cause much of the “weird” behavior. Dermorphin, and other opioid-like peptides, can reduce stomach acid output (by inhibiting a zinc-bearing enzyme needed to make HCl), and change emptying time for the stomach, and therefore, hamper digestion. Undigested particles of undercooked grain starches pass into the blood and to the capillaries where they slow and clog blood circulation. Collateral circulation is likely enough to keep the organ functioning, but in the brain, neurons may be lost. Eating enzyme-deficient (cooked) foods also causes Leukocytosis (Paul Kautchakoff, MD). The immune system has to digest the foods! This is why digestive enzymes are so vital to break down these protein and starch particles before they reach the gut.  

 

As mentioned, Shan, et al, found that gliadin is not broken down completely by pancreatic enzymes, but a proline-rich fragment (a large molecule) is left that still causes leaky gut and adversely affects the bowel in celiac patients. Because the fragment is rich in the amino acid proline, investigators reasoned that a peptidase (an enzyme that breaks down proteins) with the ability to digest proline-rich chains might be able to break down the gliadin fragment, rendering it harmless to celiac patients. They have now shown that this is the case in test tubes and in rats. Dipeptidyl peptidase IV (DPP-IV—found in milk) digests proline-rich peptides (www.kirkmanlabs.com).

 

This abstract shows the problem with casein is the same and responds to the same solution – DPP-IV!

 

Complementary action of dipeptidyl peptidase IV and aminopeptidase M in the digestion of ß-caseinA heymann e [PubMed]  [Google Scholar], mentlein r [PubMed]  [Google Scholar], Eberhard Heymanna1 and Rolf Mentleina1. Biochemisches Institut, Fachbereich Medizin, Universität Kiel, D-2300 Kiel, FRG

 

Abstract

Purified bovine ß-casein was digested in vitro with varying mixtures of purified proteinases and peptidases including trypsin, chymotrypsin, dipeptidyl peptidase IV (DP IV), aminopeptidase M and prolidase. In digestion mixtures without DP IV the yield of free amino acids was considerably lower than in the corresponding assays with this peptidase. Especially, the release of proline increases drastically from almost zero to the theoretical amount in the presence of DP IV. Quantitative results indicated that the specificities of the two microvillar peptidases (aminopeptidase M and DP IV) optimally complemented each other. This effect elucidates the hitherto obscure physiological role of intestinal DP IV. A similar effect may also apply to other caseins and nutritional proteins. (Accepted Nov. 18, 1985)

 

Substance P is a known natural DPP-IV substrate [Journal of Pharmacology and Experimental Therapeutics 260 (1992) 1257]. That is, this enzyme acts upon Substance P (pain transmitter). Should it be deemed desirable, capsaicin also has been shown to reduce the levels of Substance P, probably by reducing the number of C-fibre nerves, or causing these nerves to be more tolerant. Additionally, Oral papain seems to protect against the toxic effect of gluten (Messer & Baume, 1976), however, it is important to eliminate gliaden from the diet where possible for it is a powerful Lectin. That’s quite a commitment, no gliadin for life. Taking “Seacure”, a white-fish protein product that is pre-digested will supply you with high-quality, digestable protein during the first aix-months of your gut healing. Other aids may be Hawthorne berry, folic acid, and vitamin B12.

 

Dipeptidyl peptidase (DPP-IV) is a protein that has multiple functions in the body. It is known under different names depending on where it is found. When DPP-IV is on the surface of the T-cell (lymphocyte), it is called CD26, and supports immune function. When this enzyme is found on and imbedded on the epithelial brush-border, mucosal membrane of the intestinal tract lining it is known as DPP-IV. The importance of DPP-IV is that it has primary function in breaking down casein and side chain activity in breaking down gluten. Thus, the use of a DPP-IV containing enzyme will support the digestion of casein-containing milk products as well as the gliadin in gluten-containing grains.

 

Mothers are often perplexed when, having been on Gf/Cf for a period, they find high levels of peptides still present. When a person goes Gf/Cf the body takes the opportunity to dump these things in the blood/urine again. That is why we see them in the urine for some time afterwards. In celiac literature, it speaks of taking seven years to totally clear the system! “Treatment of the latter (Candida) with conventional, synthetic, antifungal agents often causes impairment of liver detoxification functions, and a decrease in synthesis of phospho-sulfotransferase, 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, and increase the potential for toxicity in PST kids. Of utmost significance is the observation that those eating soy proteins or drinking soymilk may also have high peptide readings in their urine. Soy proteins are used extensively as emulsifiers, binders, and stabilizers in meat, poultry, snack foods, sausage, frozen spaghetti, and whipped toppings. Textured vegetable protein is soy-based, and many meat substitutes are soy-based. It has been found that those on soy may have high values of gliadorphin and casomorphin, presumably because of peptides from soy that are similar or identical to those in gluten or casein (Zhang XZ, Wang HY, Fu XQ, Wu XX, Xu GL. Bioactive small peptides from soybean protein. Anri NY, Acad Sci 1998 Dec 13, 864: 640-5. Additionally, hypoallergenic soy formulas contain very high levels of MSG. Never feed an infant soy formula. See www.truthinlabelingorg/formulacopy.html for further details.

 

Additionally, those on SerenAid™ or EnzymAid™ may show high peptide values in the urine. This may be because these products are interfering with the test.

 

Are the symptoms being suffered symptoms of “autism”, or of malnutrition, toxicity, and immune changes induced by that chronically inflamed, out of balance, gastrointestinal tract? Can nutritional intervention ameliorate these “autistic” symptoms?

 

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