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What is Autism? – Autism and Systemic Enzymes

The rigidity of the lifestyle changes necessary to manage autism has led to an increasing use of digestive enzymes as a means to alleviate symptoms and improve quality of life. Certain proteolytic (protein digesting) enzymes have been identified to have extremely beneficial actions when applied to this condition. Digestive enzymes, taken with each meal, enter into the small intestine. Enzymes can then assist in the proper break down of food into nutrients and waste.

Contained within the cells that line the villi of the small intestine is a very important proteolytic enzyme, dipeptidyl dipeptidase IV (DPP IV). Autism research has included the investigation of the role of DPP IV in the digestion of the portion of the proteins gluten and casein that are recognized as an “offender” by the immune system, also called an epitope, and can trigger an autoimmune response. These epitopes have also demonstrated the ability to pass, or permeate, through the lining of the intestines and travel through the blood to the brain where they interfere with normal cognitive processing.1

Eliminating gluten and casein has shown to be effective in reducing some of the behavioral symptoms of autism. One study looking at the neurological effects of the dietary gluten fraction gliadin in autistic children who had reported gastrointestinal problems showed that when the children were exposed to an oral dose (1 g) of gliadin, frontal nerve impulses were significantly inhibited.2 In two separate studies involving a large group of autistic patients, it was noted that an improvement of social, cognitive, and communication skills occurred when they were placed on a diet free of gluten and cow’s milk or a diet free of cow’s milk alone.3,4

The particular epitopes of concern in gluten and casein are rich in the amino acid proline. Studies show that endopeptidases, or enzymes that break protein bonds from within the molecule rather than at the ends, that are normally released by the pancreas do not effectively digest the epitopes. This suggests that DPP IV digestion in the small intestine is critical. Research has also found that DPP IV activity in patients with autism is low and that they may not have the capacity to digest the protein after a gluten or casein-rich meal, contributing to the development of symptoms.2,5 One study on this enzyme compared two populations of rats, one with the intestinal DPP IV and one which genetically lacked the enzyme. The rats were fed diets high in proline-containing peptides for 4 weeks. The control group (with DPP IV) maintained body weight after 4 weeks on the diet, while the group lacking DPP IV experienced significant weight loss.  Evidence showed that the difference in the proteolytic activities between the two groups of rats was solely due to the absence of the DPP IV enzyme.6

At this time, clinical studies relevant to gluten and casein functions in autism are limited to the removal of these factors from the diet rather than DPP IV supplementation to break them down. Proper maintenance of a gluten-free/casein-free diet is difficult, however, because many everyday foods and items are hidden sources. Researchers looked at supplementing with DPP IV, as well as other prolyl (proline-specific) endopeptidases in celiac disease – a condition characterized by an autoimmune reaction to gluten in the intestines. They found that supplementing with DPP IV can compensate for the slow protein digestion, and that supplementing with additional proteases like prolyl endopeptidase (PEP), in combination with DPP IV, may be useful in reducing or even eliminating the inflammatory response related to gluten.7,8

Additionally, there is more evidence suggesting that taking a combination of proteases for gluten digestion is more beneficial than a single enzyme. In one study, activity of X-prolyl dipeptidyl aminopeptidase (X-PDAP), a non-specific DPP enzyme, was measured alone and in combination with another enzyme, non-specific monoanimopeptidase (AP). When AP was combined with subtilisin (a serine-specific endopeptidase), gluten digestion was measured at 47%. Upon adding X-PDAP, activity increased to 64%, suggesting a synergism in breaking down proteins when these enzymes are taken as a complex.9 Another study looked at the possibilities of a combination enzyme therapy in treating celiac disease. In vivo and in vitro (rat) experimental digestive systems were used and were treated with a glutamine-specific endoprotease (EP-B2) and a prolyl endopeptidase (SC PEP) enzyme product. The analysis revealed that EP-B2 extensively breaks down complex gluten proteins in bread, and SC PEP rapidly detoxifies the residual protein products of EP-B2 digestion. Researchers concluded that by combining 2 enzymes with normal digestive activity it should be possible to increase the safe threshold of ingested gluten, reducing the need for a highly restricted diet.10

1. Hemmins WA. The entry into the brain of large molecules derived from dietary protein. Proc Roy Soc London Ser B. 1978; 200:175-192.
2. Goodwin MS, Cowen MA, Goodwin TC. Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children. J Autism Child Schizophrenia. 1971; 1:48-62.
3. Lucarelli S, Frediani T, ZIngoni AM, et al. Food allergy and infantile autism. Panminerva Med. 1995; 37:137-141.
4. Knivsberg A, Reichelt KL, Nodland N, Hoien T. Autistic syndromes and diet: a follow-up study. Scand J Edu Res. 1995; 39:223-36.
5. Israngkun PP, Newman HA, Patel ST, et al. Potential biochemical markers for infantile autism. Neurochem Pathol. 1986; 5:51-70.
6. Tiruppathi C, Miyamoto Y, Ganapathy V, Leiback FH. Genetic evidence for role of DPP IV in intestinal hydrolysis and assimilation of prolyl peptides. Am J Physiol. 1993; 265(1 pt 1):G81-9.
7. Marti T, Molberg O, Li Q, et al. Prolyl Endopeptidase-Mediated Destruction of T Cell Epitopes in Whole Gluten: Chemical and Immunological Characterization. J Pharmacol Exp Ther. 2005; 312(1):19-26.
8. Hausch F, Shan L, Santiago NA, et al. Intestinal digestive resistance of immunodominant gliadin peptides.  Am J Physiol Gastrointest Liver Physiol. 2002; 283(4):G996-G1003.
8. Byun T, Kofod L, Blinkovsky A.Synergistic Action of an X-Prolyl Dipeptidyl Aminopeptidase and a Non-Specific Aminopeptidase in Protein Hydrolysis. J Agric Food Chem. 2001; 49(4):2061-3.
9. Gass J, Bethune MT, Siegel M, et al. Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue. Gastroent. 2007; 133(2):472-80.
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