Biological Treatments for Autism and PDD Online > Chapter 6
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Abnormalities of the digestive system.
by William Shaw Ph.D.
Gluten and casein sensitivity
Numerous studies by Dohan, Reichelt, Shattock, Cade and others have established elevated urinary excretion of peptides derived from certain proteins in milk and wheat in children with autism and in adults with schizophrenia (1-18). Restriction of these proteins from the diet or dialysis to remove the peptides causes improvement in the symptoms of these diseases. The major protein in milk is called casein while the major protein in wheat is called gluten. Each of these proteins is made of a combination of amino acids. There are 20 amino acids that are commonly found in proteins. A protein can be thought of as analogous to a string of pearls. The pearls may have 20 different colors. The amino acids would be individual pearls on the string. The DNA or genetic code selects which particular amino acid (which of the 20 different colored pearls) is present in each protein (string of pearls). When proteins are eaten, enzymes in the gastrointestinal tract break them down to smaller pieces called peptides and then the smaller pieces are broken down into individual amino acids. The individual amino acids are then absorbed through the intestinal lining into the bloodstream.
Historical perspective
Both cow's milk and are fairly new on the evolutionary scale to human beings and were probably first used as foods by many our ancestors in the Mideast approximately 10,000 years ago; at this time the first sickles used to harvest cereals were used in Turkey (19). Up until this time our ancestors ate a very varied diet of wild plants, fish, animals, and insects. Civilization from the Mideast spread throughout Europe as these new farmers moved into lands just vacated by retreating glaciers that covered northern Europe, Asia, and North America. The milk cow and domesticated grain seeds moved with these invaders. Many of the native people in Europe were not biochemically adapted to eating these foods, did not do well on such diets, and many died. Children who ate these foods did not do as well either and many died. As a result, the genes associated with gluten sensitivity from the population became reduced in the population. In countries such as Ireland which were invaded most recently by people subsisting on a diet high in wheat and milk, the incidence of sensitivity to wheat is higher than in any other country because the toxic wheat and milk products have not had very long to kill off the sensitive individuals in the population. Western Ireland has the highest incidence of schizophrenia in the world (20) probably because it also has the highest incidence of wheat-sensitive people. Dohan found that schizophrenia was essentially absent from primitive people in the East Indies until they adopted a Westernized diet with increased grains (2).
Effects of gluten sensitivity
What are the effects of gluten sensitivity? In the medical disorder called celiac disease, there is a reduced ability to digest wheat and there is often a direct toxic effect of gluten on the lining of the intestine called the intestinal mucosa. Symptoms may include diarrhea, failure to thrive, short stature, discolored dental enamel, depression, premature degeneration of the nervous system, seizures, arthritis, nutritional deficiencies due to malabsorption, and abdominal distension (21-24). Long eyelashes, premature balding, and clubbing of the fingers are also commonly reported in this disease. In celiac disease, there is also an increase in the blood of antibodies to wheat. It is thought that the immune system produces antibodies against the undigested wheat proteins. In celiac disease, there is an increased incidence of certain antigens on the white blood cells called HLA(human leukocyte antigen). These HLA types are most commonly used to determine suitability for tissue transplants and for paternity testing.) Patients with celiac disease have increased frequency of the HLA-B8 and HLA-Dw3 types compared to the population as a whole (25). The HLA-B8 antigen is present on the white blood cells of about 85-90% of celiac patients compared to only 20% of the general population.
Differences between wheat sensitivity in autism and celiac disease
In celiac disease the cells of the mucosa (the lining of the intestinal tract) lose their characteristic features, do not function as well, and may have impaired ability to produce hormones like secretin that stimulate the pancreas to function properly. As a consequence, the absorption of food from the intestine is impaired and there may be severe diarrhea due to this malabsorption. Severe nutritional deficiencies may also occur due to this defective absorption of nutrients. In individuals with autism and schizophrenia, the intestinal cells do not appear to be as badly damaged as in celiac disease and if a small piece of the intestinal lining is removed in a biopsy, the microscopic pattern of the tissue is not usually the same as in celiac disease.
Autism is also different from celiac disease in that patients with autism frequently have elevated antibodies against both wheat and milk. The major difficulty in both autism and schizophrenia appears to be the absorption of the incompletely digested pieces of the gluten and casein proteins called peptides. One of the reasons for the incomplete digestion may be a deficiency of enzymes that break down these small peptides. I have talked with numerous parents who had the biopsy done to test for celiac disease and none of the tests indicated the microscopic pattern of classic celiac disease even though the child improved on a gluten-restricted diet. The anti-endomysial antibody test which is positive in most people (around 95%) with celiac disease is negative in all but a small percentage of people (less than 5%) with autism.
These peptides from gluten and casein are important because they react with opiate receptors in the brain, thus mimicking the effects of opiate drugs like heroin and morphine. The peptide from wheat is called gluteomorphin (gluten + morphine) or gliadorphin and the peptide from milk is called caseomorphin (casein + morphine).
Both casomorphin and gluteomorphin start with the beginning N-terminal sequence tyr-pro (for tyrosine and proline) with additional pro residues (proline) in positions 4 and 6 of both peptides as indicated below. Similarities are indicated by bold print.
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| Casomorphin: |
tyr- |
pro- | phe- | pro- | gly- | pro- | ile |
| Gliadorphin | tyr- | pro- | gln- | pro- | gln- | pro- | phe |
The urine peptide test can be ordered from The Great Plains Laboratory.
E-mail: GPL4U@aol.com
These compounds have been shown to react with areas of the brain such as the temporal lobes, which are involved in speech and auditory integration. Furthermore, the administrations of drugs like naltrexone (see chapter by Bruce Semon MD, Ph.D.) that block the effects of opiate drugs lessen the symptoms of autism (26). Children with autism frequently improve overall after restriction of these foods. Slip-ups can be catastrophic. One mother reported to me that her teenage son with autism who was doing very well on a gluten-restricted diet severely damaged her house in a rage after eating a few wheat crackers. I have personally been informed of so many cases of improvement after gluten and casein restriction that there is no doubt in my mind that this dietary restriction should be considered for every child with autism. Conversely, I would be very cautious in changing the diet if it has been successful. Because the milk and wheat peptides function as opiates, a withdrawal reaction similar to that of a drug addict may occur when these foods are removed from the diet.
The withdrawal reaction from gluten and casein can sometimes be severe. Sidney Baker MD describes the reaction of one child with autism to the removal of gluten and casein in his book Detoxification and Healing (27). The child refused to eat, lost 15 pounds, was extremely hyperactive, barely slept, increased biting and hitting behaviors, and had to have liquids forced on him to prevent dehydration. Repeated doses of Alka-Seltzer Gold provided temporary relief from the symptoms. At the end of the six weeks, the withdrawal ended and the child was significantly improved. Alka-Seltzer Gold is bicarbonate that helps to neutralize stomach acid. Warning! Other types of Alka-Seltzer are not the same as Alka-Seltzer Gold and could cause serious side effects if given excessively.
Restriction of gluten and casein from the diet.
Lisa Lewis, Pamela Scott, and Karyn Seroussi, and Bruce Semon deal extensively with dietary therapies and I will not cover them here.
Alpha-1-antitrypsin deficiency
Alpha-1-antitrypsin is a protein produced by the liver. Deficiency of this protein is associated with chronic obstructive lung disease or emphysema, cirrhosis of the liver, and respiratory distress of the newborn. Alpha-1-antitrypsin is an inhibitor of enzymes that break down proteins (proteases). It inhibits the action of a number of naturally occurring proteases including trypsin, chymotrypsin, collagenase, white blood cell proteases, and plasmin and thrombin, which are released in inflammatory reactions of the lung. In the absence of sufficient alpha-1-antitrypsin, plasmin and thrombin may begin to digest the lung itself. Elevated values for this protein are found in patients who are genetically heterozygous deficient for alpha-1-antitrypsin, during infection, during pregnancy, in bacteria infection, following estrogen or steroid therapy, and in rheumatoid arthritis. In the gastroenterology department of a children's hospital in Australia, it was discovered (28) that 8 of 15 children with autism had abnormally low values of alpha-1-antitrypsin. In children with celiac disease, there was also an increased incidence of low values of alpha-1-antitrypsin. The authors think that the low level of alpha-1-antitrypsin might predispose children to wheat sensitivity.
Pancreatic atrophy, hypoglycemia, and antibiotics
I reviewed the results of a very interesting case, which illustrates the possible damage of yeast byproducts. (I encountered many similar cases but this child was tested over an extended time period and was extensively evaluated by many different medical specialists so that the child's biochemistry had been analyzed exhaustively.) At about 10 months of age, this normal child whom I'll call Ralph developed a Strep throat and began to be given antibiotics. The Strep throat cleared up but the conscientious parents were advised to be sure to finish giving the entire 14-day supply of antibiotics. When Ralph's mom went to check on him, she found that he was having convulsive seizures. She rushed Ralph to the emergency room at the hospital where his blood glucose (blood sugar) was near zero. Ralph would have been dead if his mother had brought him in any later. Ralph was given an infusion of glucose into his vein and began to recover.
Because of Ralph's extremely low blood sugar; the attending physician sent a urine sample to my organic acid laboratory to see if Ralph had one of the genetic disorders that caused low blood sugar. When I examined Ralph's urine organic acid profile, he had none of the abnormalities associated with any of the genetic diseases that cause hypoglycemia (low blood glucose) such as fatty acid oxidation disorders. What Ralph did have was very high levels of the sugar arabinose, indicating (to me) a severe yeast overgrowth resulting from his antibiotic treatment for Strep. I reported my findings. A new physician at the hospital was sure Ralph had one of the genetic disorders and ordered a retest. Again, the only significant abnormality was the elevation of the same yeast-related compounds that I had found in children with autism.
When Ralph returned home, his parents became concerned because he began to stagger at certain times of the day. When tested repeatedly, his blood glucose was low again, testing between 30-50 mg per dl. Normal is about 100 mg per dl. Many other endocrine tests revealed no cause for Ralph's hypoglycemia. Ralph was referred to another specialist who suspected that Ralph might have a tumor of the pancreas that was oversecreting insulin, which lowers blood sugar. However, repeated testing revealed only a slight increase in insulin at most, not a value high enough to indicate a tumor.
His parents were taught how to perform a blood sugar test and tested Ralph's blood sugar several times a day. The child's pancreas where the insulin-secreting cells are found was examined by an imaging technique called an MRI and it was found that there was a severe atrophy of the pancreas. In addition, the tail of the pancreas was completely missing. But a tumor secreting insulin was not found. Additional organic acid tests at later times revealed the same elevation of yeast byproducts. Several times I recommended the use of an antifungal drug but my suggestions were ignored.
Instead, the parents of the child were instructed to give the child multiple doses a day of a food called cornstarch, which is broken down into sugar in the intestine. The idea was that sugar derived from cornstarch would increase the child's blood sugar. However, the child's blood glucose continued to be abnormal and the parents were reprimanded for not being diligent enough in giving enough cornstarch throughout the day. More than likely, the excessive cornstarch was feeding Ralph's untreated yeast overgrowth and just made his hypoglycemia worse. Low blood sugar is prevalent in fibromyalgia (29), a disorder in which yeast overgrowth is common (30,31). Finally, at about the age of two and a half years, I learned that Ralph was being referred to a developmental pediatrics department with the diagnosis of a probable autistic-spectrum disorder. At this time, a trial of nystatin was introduced. Ralph's blood sugar returned to normal in about a week and his organic acids were normal for the first time since he had started antibiotics as an infant. There is no doubt in my mind that I had witnessed and documented over a span of about two years the transformation of a normal infant into a child with autism.
I have lost contact with the child's parents and do not know what happened to him later on. Ralph's story indicated to me that yeast overgrowth could cause severe hypoglycemia and that it might also severely damage the pancreas. The hypoglycemia could be due to the yeast byproducts. I suspect that the damage to the pancreas was due to antibodies against the yeast that cross-reacted with the pancreas in an autoimmune reaction. (See the chapter on the immune system.) It is possible that protein crosslinks of pentosidines caused by abnormally high arabinose might also be responsible for some of the damage. (See the chapter on organic acids.) The pancreatic damage probably resulted in deficient production of digestive enzymes by the severely damaged pancreas. This deficiency of digestive enzymes would also result in the incomplete digestion of wheat and milk proteins, which would then be absorbed and cause their opiate effects on the brain.
Secretin.
Secretin is a small protein called a polypeptide produced by the cells of the small intestine and is made up of 27 amino acids (32). The function of secretin is to cause the pancreas to release bicarbonate after a meal. After a meal, the stomach secretes acid. The food passing through the stomach is very acidic. The pancreas secretes digestive enzymes to digest the food arriving into the small intestine from the stomach. These enzymes will not function properly to digest food if the acid from the stomach is not neutralized by bicarbonate from the pancreas. Thus, if secretin secretion is deficient, no bicarbonate will be formed and foods will not be digested properly. Secretin is produced by certain cells in the intestine and is stimulated by the presence of stomach acid. Secretin is available as a drug from pig intestine that is used to assess the function of the pancreas. Human and pig secretin are very similar and differ in only 2 of the 27 amino acids in the molecule (33). In order to assess pancreatic function, secretin in injected into the vein and is transported by the bloodstream to the pancreas. If the pancreas is functioning properly, then the pancreas will produce bicarbonate. The production of bicarbonate can be monitored through a tube down the esophagus and stomach while the patient is sedated.
At an eastern United States medical school, a child with autism was being tested for pancreatic function at the insistence of a parent (Confidential Personal Communication) who noticed a lot of undigested food in her child's stool. When the secretin was administered to her child, the physician noticed that not only was bicarbonate being produced, the pancreatic secretion was literally gushing out. More importantly, the development of her child began to gush as well. Before the secretin infusion, the child spoke only two words, did not make eye contact, and was zoned out most of the time. Within three weeks of the infusion, he made eye contact most of the time, spoke in short sentences, and could say hundreds of words. Similar responses have now been found in other children with autism but some children have had only slight improvement (Confidential Personal Communications).
Why are these children reacting to these infusions so dramatically? (1) Children with autism are not producing secretin in sufficient amounts and their digestive process is impaired as a result. The gush of bicarbonate after secretin might be due to the fact that the pancreas has not been stimulated adequately with the body's own secretin and therefore it overacted to the external secretin administered intravenously. This explanation is the most likely explanation. Reduced secretin production may be related to gluten sensitivity or viral damage to the intestinal mucosa caused by the live virus vaccines such as the MMR. In celiac disease, the gluten damages the intestinal cells that produce secretin (32). Presumably, the same mechanism is operating in autism. (2) Children with autism are producing a defective type of secretin that is not capable of stimulating the pancreas. It is also possible that secretin has some direct beneficial effect on brain functioning. It is also possible that autoantibodies against the pancreas induced by Candida may be preventing the pancreas from responding to the normal amount of secretin produced by the child's own body.
Tests of pancreatic function
A common way to evaluate pancreatic function is to measure the concentration of pancreatic enzymes in the stool or blood. Trypsin is one of the enzymes most commonly measured and can be done by most of the large reference labs.
If the function of the pancreas is inadequate, then secretin production or digestive enzyme production might be impaired. Another simple way to assess the secretin production of the intestinal lining is to measure the acidity of the stool. If insufficient bicarbonate is being produced, then the stool will be more acidic or have what is called a low pH. A pH value less than 6 may indicate insufficient bicarbonate due to defective secretin production. The pH can be measured with simple paper called pH indicator paper which changes to different colors at different acid concentrations or pH levels. You can get pH paper from lab supply companies and do this at home or get a nearby lab to do it for you if you don't prefer to play in poop. You'll need a physician request for the lab to do the test.
Digestive enzyme supplements.
Numerous parents have reported improved functioning of their children with autism following supplementation with digestive enzymes. This improvement may be because: (1) the children are not producing enough secretin. The decreased secretin causes reduced bicarbonate. The digestive enzymes are secreted in enough quantity but function at a reduced rate because the food passing from the stomach is too acidic. (2) The pancreas is not producing enough enzymes on its own. (3) Both of the above factors are involved.
What kind of digestive enzyme supplements might be helpful? Since undigested peptides appear to be a problem, the use of peptidase supplements that would help to digest peptides would seem appropriate. A drug store in Dallas, Texas called the Apothecary supplies a product called "peptidase" that is a mixture of carboxypeptidase and aminopeptidase. The phone number of the Apothecary is 800 969-6601; a physician's prescription is required to obtain this material. These enzymes break down peptides starting at different ends of the molecule. It seems possible to me that the supplementation of sufficient peptidases might be able to resolve the problem of gluten and casein sensitivity. If these peptides were sufficiently digested to individual amino acids, these products would not be toxic. However, other digestive enzymes in addition to peptidases might also be deficient and supplementation with a variety of digestive enzymes might be better in such a case. The function of different digestive enzymes is listed in Table 1. Many other digestive enzymes from a number of plant sources are also available generally as capsules. Since animal sources of enzymes may be more subject to contamination with bacteria or viruses, it may be safer to use plant enzymes as supplements. Many children may not be able to swallow capsules.
Could children who can't swallow capsules be given these digestive enzymes in a loose form? Probably. Meat tenderizer is really just a plant digestive enzyme that breaks down meat protein fibers. People have used this product for years and I am aware of no significant health problems associated with this product. Some of these enzymes may be denatured in the very low pH of the stomach. Do not administer these products as loose powder unless you review such therapy with the supplier and your physician.
Behavior, food dyes, and inactivation of digestive enzymes
Several studies have documented adverse effects of food colors on behavior (34-36). One possible mechanism for the negative effects of food dyes may be an inhibition of digestive enzymes by the food colors. In a study done in Germany (37), it was found that the biochemical function of the digestive enzymes amylase and trypsin were significantly inhibited by many common food colors. Thus, one of the best things you might due for your child is to remove food dyes from his diet. Children who may have pancreatic damage due to autoantibodies or intestinal damage due to toxic peptides do not need the additional burden of food colors to inhibit any functional enzymes that remain active.
Table 1. Human Digestive Enzymes
Amylase-converts starches to sugar
Sucrase-converts sucrose to simple sugars
Lactase-converts milk sugar(lactose) to glucose and galactose
Nucleases-convert nucleic acids(DNA and RNA) to nucleotides
Lipase-converts fats(triglycerides) to fatty acids and glycerol
Phospholipase-converts phospholipids to fatty acids and glycerophosphate
Trypsin-converts proteins to peptides
Chymotrypsin-converts proteins to peptides
Carboxypeptidase-converts peptides to amino acids
Aminopeptidase-converts peptides to amino acids
Cholesterol esterase-converts cholesterol esters to free cholesterol
Nucleosidase-converts nucleosides to nucleic acid bases
Phosphatase-converts organic phosphates to free phosphates
References
Biological Treatments for Autism and PDD Online > Chapter 6