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2007 Dr. Irfan Qureshi, ND 1 The Biomedical Approach to Autism: The Gut-Brain Connection Dr. Irfan Qureshi, ND Pacific Highway Natural Medicine 15245 International.

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Presentation on theme: "2007 Dr. Irfan Qureshi, ND 1 The Biomedical Approach to Autism: The Gut-Brain Connection Dr. Irfan Qureshi, ND Pacific Highway Natural Medicine 15245 International."— Presentation transcript:

1 2007 Dr. Irfan Qureshi, ND 1 The Biomedical Approach to Autism: The Gut-Brain Connection Dr. Irfan Qureshi, ND Pacific Highway Natural Medicine International Blvd., Suite 210 Seattle, Washington Phone: (206)

2 2007 Dr. Irfan Qureshi, ND 2 Naturopathic Medicine Philosophy and Scope of Practice A discipline of medicine requiring a doctorate level education similar to degree programs in allopathic medicine A holistic system of medicine encompassing diet therapy, lifestyle changes and therapeutic nutrition. In a number of states in the US, Naturopathic Physicians are licensed to practice as Primary Care Physicians Naturopathic Physicians stress treatments that are natural to help with chronic conditions, such as diet and lifestyle changes, herbal medicine and nutritional supplementation; however, they also can prescribe drugs, when necessary. Aim is to address the cause of the illness and not just treat the symptoms.

3 2007 Dr. Irfan Qureshi, ND 3 Dr. Irfan Qureshi, ND Pre-med. BSc Microbiology (University of Washington) Doctor of Naturopathic Medicine (Bastyr University) Licensed Primary Healthcare Physician, State of Washington, USA In practice since 2003 in Singapore and Washington State Special areas of interest include natural alternatives for Autism, Attention Deficit Disorder, Diabetes and other chronic diseases Specifically: Gastrointestinal health in Autism and other developmental disorders Autoimmune disorders Clinical nutrition

4 2007 Dr. Irfan Qureshi, ND 4 Objectives of the Talk To develop an understanding of the Biomedical approach to Autism (especially as it relates to gut health) How to measure progress To understand how to get started Individualized therapy How to decide if you should try it

5 2007 Dr. Irfan Qureshi, ND 5 Autism on the rise There has been a disturbing trend over the last 2 decades Incidence in the past was always cited as nearly 1 in 2000 individuals Evidence is that the incidence has increased to 1 in 200, with the incidence in some areas even higher! No one definitive cause for this condition that has been identified. An autism epidemic? No decrease in cases in sight.

6 2007 Dr. Irfan Qureshi, ND 6 Overt Signs and Symptoms of impaired digestion Gas and bloating Belching Heartburn Acid Reflux Nausea/vomiting Constipation Diarrhea

7 2007 Dr. Irfan Qureshi, ND 7 Hidden Signs and Symptoms of Gut disturbance Behavioral changes Dazed sensation Food reactions Toe Walking (a sign of constipation) Asthma Skin rashes Headaches Attention deficits History of chronic infections Impaired immune function

8 2007 Dr. Irfan Qureshi, ND 8 Evidence of poor intestinal health in Autism Food Allergies Dysbiosis (Imbalance) of bacterial flora in intestines Candida and Clostridium overgrowth in the gut Increased intestinal permeability Leaky Gut Syndrome Opioid-receptor effects of milk and wheat proteins (casein and gluten) Oxidative damage of intestinal tissues Abnormal immune function Increased levels of heavy metals Impaired detoxification…and increased toxic load

9 2007 Dr. Irfan Qureshi, ND 9 Autism: The Biomedical Approach Aims to correct the underlying abnormalities seen in Autistic patients. Treatment consists of: Dietary modification Removal of food allergens and sensitivities from the diet Decrease sugars and processed foods Targeted nutritional supplementation Determined by results of functional physiological testing of stool, blood, and urine To improve gut health Reduce toxic burden

10 2007 Dr. Irfan Qureshi, ND 10 Autism: The Biomedical Approach Treatment targets the following areas: Food Allergies Reducing Free Radical damage Improving Digestive Function Rebuilding intestinal mucosa and correcting Leaky Gut Correcting bacterial imbalances Eliminating intestinal pathogens (Candida and Clostridia) Removing toxins and improving detoxification systems Stimulating immune function

11 2007 Dr. Irfan Qureshi, ND 11 Food Allergies A number of autistic kids have been shown to have one or more significant food allergies. Dramatic improvement can be seen in many cases upon elimination of allergic foods from the diet. Lucarelli S, et al. Food allergy and infantile autism. Panminerva Med Sep;37(3): The majority of problematic food allergies are the delayed-onset type (IgG), taking hours to days to occur. Immediate reactions are easier to identify and eliminate because they have a fast onset (IgE antibody). (Skin prick testing identifies only these type, and is better for environmental sensitivities) The blood testing screens multiple foods for reactions based on both immediate and delayed onset (IgG and IgE antibody reactions). Major allergens may be dairy, wheat, soy, eggs. Other foods can also be reactive.

12 2007 Dr. Irfan Qureshi, ND 12 Gluten and Casein defined Gluten is a protein component of grains. The following grains contain gluten: Wheat (durum, semolina) Rye Barley Spelt Triticale Kamut Farina Oats (controversial) Casein is a protein derived from dairy products: Includes milk, butter, cheese, yogurt, ice cream, etc. Goats milk has casein, but it may or may not be reactive (controversial). Elliott RB, Harris DP, Hill JP, Bibby NJ, Wasmuth HE. Type I (insulin- dependent) diabetes mellitus and cow milk: casein variant consumption. Diabetologia 1999 Mar;42(3):292-6

13 2007 Dr. Irfan Qureshi, ND 13 The Role of Gluten and Casein in autism Opioid-like effects Food Allergies Free-radical damage to gut cells Leaky Gut syndrome

14 2007 Dr. Irfan Qureshi, ND 14 Opioid effects of gluten and casein These are not food allergies and are not necessarily immune-mediated reactions. Many food proteins are known to exert opioid-like effects on the brain. Teschemacher H. Opioid receptor ligands derived from food proteins. Curr Pharm Des. 2003;9(16): These proteins attach to receptors in the brain. They are nearly identical in structure to natural opioid-binding peptides. (Can have morphine-like effects) The proteins enter the blood circulation in incompletely digested forms (due to digestive enzyme deficiencies and leaky gut) and potentially cause changes in mood and brain function.

15 2007 Dr. Irfan Qureshi, ND 15 Opioid effects of gluten and casein These effects may be responsible for autistic children seemingly being dazed. Components of gluten and casein have been found in abnormally high levels in the urine of autistic patients. Reichelt, et al. Gluten, milk proteins and autism: dietary intervention effects on behavior and peptide secretion. J Appl Nutrition 1990; 42(1):1-11.; Shaw, William, Ph.D. Biological Treatments for Autism and PDD. Overland Park, KS: Studies show that elimination of gluten and casein from the diet has improved behavior in autistic children. Knivsberg AM, Reichelt KL, Hoien T, Nodland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci Sep;5(4): Important to remember that autistic children can have both allergies AND sensitivities to wheat and dairy.

16 2007 Dr. Irfan Qureshi, ND 16 Leaky Gut Syndrome The normal intestinal barrier Tight junctions between cells do not normally allow the entry of large molecules into the bloodstream. Leaky gut develops when these tight barriers between cells are compromised and loosen up due to cell injury This shriveling allows the passage of large molecules (especially food particles such as casein and gluten) into the bloodstream. These large molecules are incompletely digested food proteins (possibly due to digestive enzyme deficiencies or dysfunctions)

17 2007 Dr. Irfan Qureshi, ND 17 Leaky Gut Syndrome Causes of increased intestinal permeability include: Allergenic foods causing inflammation of cells Incompletely digested food proteins (gluten/casein, etc.) Medications such as antibiotics, steroids, aspirin (irritate lining, causing imbalance in bacterial flora) Other potential causes include heavy metals, yeast and bacterial overgrowth, and components of vaccines

18 2007 Dr. Irfan Qureshi, ND 18 Leaky Gut Syndrome Evidence of intestinal problems in Autism and ADHD Chronic nonspecific diarrhea is associated with attention deficit disorder in childhood There is a relationship between the presence of ADHD and greater severity of irritable bowel syndrome. A significant number of ADHD individuals also had IBS. Wender PH, Kalm M. Prevalence of attention deficit disorder, residual type, and other psychiatric disorders in patients with irritable colon syndrome. Am J Psychiatry Dec;140(12): There is mounting evidence of impaired intestinal permeability in autistic children showing intestinal signs such as gas, bloating, diarrhea, reflux and constipation. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood) Jun;228(6):

19 2007 Dr. Irfan Qureshi, ND 19 Leaky Gut Syndrome Evidence of Intestinal problems (contd) Abnormal intestinal permeability (or leaky gut) was even found in 43% of autistic children showing no intestinal signs or symptoms. D'Eufemia P, et al. Abnormal intestinal permeability in children with autism. Acta Paediatr Sep;85(9): % of patients with neurological dysfunction (including Autism and ADD patients) were shown to have antibodies to gluten (a component of wheat and other grains.) Lahat E, et al. Prevalence of celiac antibodies in children with neurologic disorders. Pediatr Neurol May;22(5): A unique type of enterocolitis (infection of the colon) was found in 93% of individuals with developmental disorders. Wakefield AJ, et al. Enterocolitis in children with developmental disorders. Am J Gastroenterol Sep;95(9):

20 2007 Dr. Irfan Qureshi, ND 20 Casein: A role in Pain suppression and Self-injurious behavior Many autistic individuals commonly display self-immolating behavior Self-injurious Head banging Scratching to the point of bleeding

21 2007 Dr. Irfan Qureshi, ND 21 Casein: A role in Pain suppression and SIB Casein has analgesic effects Casein is a food hormone that elicits opioid effects on opioid receptors in the brain. Teschemacher H, Koch G, Brantl V. Milk protein-derived opioid receptor ligands. Biopolymers 1997;43(2): In animals, casein was shown to greatly increase the pain threshold compared to controls. These researchers concluded that one derivative of casein showed pain- relieving activity 1000x more potent than morphine. Ruthrich HL, Grecksch G, Schmidt R, and Neubert K. Linear and cyclic beta-casomorphin analogues with high analgesic activity. Peptides 1992 May-Jun;13(3):483-5 Beta casomorphin, the casein derivative found in high quantities in cows milk, causes a decreased response to pain. This protein causes behavioral changes. Blass EM, Blom J. Beta-Casomorphin causes hypoalgesia in 10-day-old rats: evidence for central mediation. Pediatr Res 1996 Feb;39(2): Researchers studied 8 children for the presence of casein derivatives in the brain. Casein derivatives were found in 19 different functionally- relevant areas of the brain. These proteins can play a role in the regulation of many physiological processes. Pasi A, et al. Beta-Casomorphin- immunoreactivity in the brain stem of the human infant. Res Commun Chem Pathol Pharmacol 1993 Jun;80(3):

22 2007 Dr. Irfan Qureshi, ND 22 Casein: A role in Pain suppression and SIB The link to self-injurious behavior A study was conducted on 80 autistic children. Researchers concluded that there is a significant relationship between certain self-injurious behaviors and the apparent reduced pain reactivity in autistic children. Tordjman S, Antoine C, Cohen DJ, Gauvain-Piquard A, Carlier M, Roubertoux P, Ferrari P. [Study of the relationships between self-injurious behavior and pain reactivity in infantile autism]. Encephale Mar-Apr;25(2): A study was performed on autistic children with and without SIB. The results supported the idea that severe self-injurious behaviour is related to functional disturbances in the endogenous opioid system. Willemsen-Swinkels SH, Buitelaar JK, Weijnen FG, Thijssen JH, Van Engeland H. Plasma beta-endorphin concentrations in people with learning disability and self-injurious and/or autistic behaviour. Br J Psychiatry Jan;168(1): Avoidance of casein may be particularly useful in autistic children who show signs of self-injurious behavior.

23 2007 Dr. Irfan Qureshi, ND 23 Gluten: Direct harm to the intestines Components of gluten can harm the intestines through a variety of mechanisms. Studies have shown that components of gluten can cause death (apoptosis) of intestinal cells in gluten-sensitive patients. Giovannini C, Matarrese P, Scazzocchio B, Vari R, D'Archivio M, Straface E, Masella R, Malorni W, De Vincenzi M. Wheat gliadin induces apoptosis of intestinal cells via an autocrine mechanism involving Fas-Fas ligand pathway. FEBS Lett Apr 10;540(1-3): Gluten activates enzymes in the intestines that cause the breakage of tight junctions between intestinal cells. Leaky Gut. Clemente MG, De Virgiliis S, Kang JS, Macatagney R, Musu MP, Di Pierro MR, Drago S, Congia M, Fasano A. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut Feb;52(2):

24 2007 Dr. Irfan Qureshi, ND 24 Gluten: Direct harm to the intestines Gluten causes an abnormal immune response with the activation of high levels of inflammatory substances and white blood cells. Leads to active inflammation in the guts. Westerholm-Ormio M, Garioch J, Ketola I, Savilahti E. Inflammatory cytokines in small intestinal mucosa of patients with potential coeliac disease. Clin Exp Immunol Apr;128(1): Some gluten-sensitive patients have been shown to have low levels of enteropeptidase enzymes (responsible for digesting gluten protein) in their intestines. Giving digestive enzymes resulted in near normalized growth. Moroz SP, Hadorn B, Rossi TM, Haworth JC. Celiac disease in a patient with a congenital deficiency of intestinal enteropeptidase. Am J Gastroenterol Jul;96(7): Gluten causes flattening of the villi in the intestines of gluten-sensitive patients. Villi are the projections on intestinal cells that allow absorption of nutrients from foods. This results in decreased absorption and documented nutritional deficiencies. The villi return to their normal shapes after gluten removal, and the nutritional deficiencies are corrected.

25 2007 Dr. Irfan Qureshi, ND 25 The Gut-Brain Connection: The link between digestion and behavior The Gut is our second brain, also known as the enteric nervous system. Both the brain and the gut develop from the same tissue in the fetus. There is a network of nerves and neurotransmitters in the tissue lining the gut that are directly linked to the brain. The digestive organs can operate independently from the CNS. In people who are brain-dead, the stomach functions properly. Evidence suggests that emotions and feelings are intimately associated with bowel function. Example is Irritable Bowel Syndrome, where stress and emotions can cause digestive symptoms.

26 2007 Dr. Irfan Qureshi, ND 26 The Gut-Brain Connection: The link between digestion and behavior Many autistic children develop intestinal symptoms at the same time they are losing acquired skills such as language. This shows that gut health can have a major impact on development of sensory skills. Mcmillin DL, et al. The Abdominal Brain and Enteric Nervous System. J Alt and Compl Med. 1999; 6: One study looked at 12 autistic children with a history of normal development followed by a loss of acquired skills. All of them had developed diarrhea and abdominal pain. Wakefield AJ, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998; 351: The gut, like the brain, has opiate receptors. Drugs like morphine act on the brain, but also on the gut, to cause constipation by binding to the opiate receptors. ( Casein and gluten proteins can similarly bind to the gut opiate receptors, causing digestive complaints.

27 2007 Dr. Irfan Qureshi, ND 27 The Gut-Brain Connection: The link between digestion and behavior Neurological dysfunction in ADD and Autism may be explained by allergies to foods and additives (as in the case of gluten). Lahat E, et al. Prevalence of celiac antibodies in children with neurologic disorders. Pediatr Neurol May;22(5): Wheat gluten component was shown to have high opioid activity. Bound receptors as well as a dose of morphine. Huebner FR, Lieberman KW, Rubino RP, Wall JS. Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates. Peptides Nov-Dec;5(6): A group of adults with dementia were later found to be sensitive to gluten. GF diet improved cognitive activity in some patients. Collin P, Pirttila T, Nurmikko T, Somer H, Erila T, Keyrilainen O. Celiac disease, brain atrophy, and dementia. Neurology Mar;41(3): A significant number of adults with migraines may have gluten sensitivity. Gluten-free diet improved symptoms in majority of cases. Gabrielli M, Cremonini F, et al. Association between migraine and Celiac disease: results from a preliminary case-control and therapeutic study. Am J Gastroenterol Mar;98(3):625-9.

28 2007 Dr. Irfan Qureshi, ND 28 The Gut-Brain Connection: The link between digestion and behavior Study showed that gluten sensitivity can cause ataxia (problem with coordination and walking). Gluten caused inflammation and damage to the cerebellum, the spinal cord, and to peripheral nerves in a group of gluten-sensitive patients. Hadjivassiliou M, Grunewald RA, et al. Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet Nov 14;352(9140): Clinical evidence of an association between gluten and schizophrenia. Schizophrenics showed improvement on a GF diet. Ross-Smith P, Jenner FA. Diet (gluten) and schizophrenia. J Hum Nutr Apr;34(2): Interestingly, there is a subgroup of autistic children who develop schizophrenia. Petty LK, Ornitz EM, Michelman JD, Zimmerman EG. Autistic children who become schizophrenic. Arch Gen Psychiatry Feb;41(2):

29 2007 Dr. Irfan Qureshi, ND 29 Determining the need for CFGF diet Signs and symptoms- Digestive symptoms indicate the presence of one or more food sensitivities. Researchers have observed that children who exhibit autistic signs near the time of birth are more sensitive to casein. Children exhibiting signs only after the age of 2 are usually more sensitive to gluten. Self-injurious behavior and clear digestive signs and symptoms may be enough to warrant a trial on the diet. Urine Testing Detects the levels of casein and gluten in the urine. Elevated levels suggest the need to go on the diet. Eliminating gluten and casein lowers the amount of these proteins in the urine. Research has shown lowered levels correlate to behavioral improvement. Advantage of testing: May be able to determine whether gluten or casein or both are problematic. Testing is only valid prior to beginning CFGF diet!!

30 2007 Dr. Irfan Qureshi, ND 30 Urinary Test for Casein and Gluten Available from Great Plains Laboratory (USA) Relatively simple specimen collection – 5 ml. or more of first morning urine (ideally). Sample reports Patient 1: Results indicate elevated casein and gluten in urine. Patient 2: Results show elevated gluten, but normal levels of casein.

31 2007 Dr. Irfan Qureshi, ND 31 Outcomes Many researchers recommend removing one food at a time. Start by eliminating casein (dairy products) If individual is casein sensitive, results should be seen in 7 to 10 days. Continue for 3 weeks to be sure of its benefits. If beneficial, continue further. Casein is a major culprit in constipation. 50% of autistic children have constipation. Second, eliminate gluten (wheat and other grains) Gluten elimination takes longer to produce results Trial should be done for 3 months to determine effectiveness. If effective, continue the diet. ***There are some reports of benefit seen only after 6 months or longer on the diet.***

32 2007 Dr. Irfan Qureshi, ND 32 Cumulative effects of opioids The effects of gluten and casein are mediated by the concept of Total Load This means that in order for gluten and casein to have an effect on the brain, a majority of opiate receptors need to be bound simultaneously. Reducing the total body burden by eliminating these foods eliminates the opioid effects. Eliminating these foods for 4-6 months as much as possible is a good idea. Thereafter, the person may be able to have some casein and gluten-containing food (on a rotation basis, once every 4-5 days) without problems. Supplemental enzymes can help

33 2007 Dr. Irfan Qureshi, ND 33 The Bottom Line Be as strict as possible on the diet!! But you will see benefit even if not 100% compliant! A trial on the diet is certainly worth undertaking. 80% of the cases have shown benefit on the diet in research trials and in practical experience.

34 2007 Dr. Irfan Qureshi, ND 34 Cautions and Considerations Gluten and casein-containing foods are feel good foods because of their opioid effects. Withdrawal symptoms may be seen (but not in all cases), such as strong cravings for these foods. Yeast and bad bacteria (often seen as an issue in autism) thrive on these foods, and this is one reason autistic people crave these foods. Increased irritability is a common symptom. Withdrawal will last a maximum of 1 to 2 weeks and will diminish after that. Withdrawal is less severe with casein (observation) Withdrawal symptoms may be avoided by removing only one food group at a time. Beneficial side effects include improved presence of mind, concentration, behavior, diminished self-immolation, drastically improved digestive function and more!

35 2007 Dr. Irfan Qureshi, ND 35 Nutritional Deficiency with CFGF In many autistic children, wheat and dairy form a significant part of the diet. Autistic patients tend to be finicky eaters, with a limited diet. One reason may be the feel good effects of wheat and dairy products. People feel good when eating these foods. Removal of these foods can pose a problem with nutrition Dairy is the major source of Calcium in many of these children It is important to seek help from knowledgeable professionals when considering the CFGF diet Adequate supplementation may be needed to prevent vitamin and mineral deficiencies Professionals can help to properly guide the implementation of the diet. Interestingly, experience shows that when patients go on a CFGF diet, their dietary choices tend to significantly broaden. Other good sources of Calcium in the diet include green leafy vegetables, fish, seafood (beware of high levels of mercury and other heavy metals), beans, nuts and seeds.

36 2007 Dr. Irfan Qureshi, ND 36 CFGF is not the Complete Story Other Dietary factors Eliminating sugars and simple carbohydrates to control yeast and bacteria overgrowth Eating a healthy well-rounded diet high in nutrition Increasing fiber intake and water consumption to remove toxins Testing for and removing other food allergens

37 2007 Dr. Irfan Qureshi, ND 37 CFGF is not the Complete Story Correcting Leaky Gut and Digestion An integral part of the biomedical approach Intolerances to Casein and Gluten are a result of Leaky Gut and poor digestive health Research in patients on a GF diet showed that there was still an imbalance in the bacteria of the intestines. Patients still had digestive symptoms. The overgrowth of harmful bacteria and yeast persisted even months into the GF diet. Tursi A, Brandimarte G, Giorgetti G. High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal. Am J Gastroenterol Apr;98(4): Treating Leaky Gut and related issues can improve the effectiveness of the diet Reduces reactions to food allergens Dietary measures can be relaxed when the guts are healed.

38 2007 Dr. Irfan Qureshi, ND 38 Intestinal bacterial imbalance Decreased amounts of beneficial bacteria seen in autistic patients. Allows for overgrowth of harmful bacteria and yeast Can be due to chronic use of antibiotics and other medications, as well as dietary factors (high intake of refined foods, sugars) Antibiotics are frequently given for ear infections in childhood. Overuse and unnecessary use of antibiotics leads to a number of problems Autistic children tend to have a number of ear infections during childhood Physicians treat with (and parents request!) antibiotics. Earlier incidence of ear infections was correlated to the development of autism spectrum disorders. In autistic children, frequency of ear infections also correlated with severity of autism. (Konstantareas M and Homatidis S. Ear infections in autistic and normal children. J Autism and Dev Dis 17:585, 1987.) Stool tests of autistic patients frequently show no or low levels of growth of L. acidophilus and Bifidobacterium species.

39 2007 Dr. Irfan Qureshi, ND 39 Candida and Clostridium Candida overgrowth of the intestinal tract is common in autistic individuals, as shown by increased yeast byproducts in the urine. Shaw, William, Ph.D. Biological Treatments for Autism and PDD. Overland Park, KS: 2002 Antifungal treatment has also been shown to decrease the amount of these yeast byproducts and improve autistic symptoms. Chronic or frequent antibiotic usage allows Candida overgrowth of the intestines by killing off normal beneficial bacteria. Samonis G, et al. Prospective evaluation of the impact of broad-spectrum antibiotics on the yeast flora of the human gut. Eur J Clin Microbiology & Inf Dis 13:665-7, Some antibiotics have actually been shown to promote yeast growth. Kasckin P. Some aspects of the candidosis problem. Mycopathologia et Mycologia applicata. 53: , 1974.

40 2007 Dr. Irfan Qureshi, ND 40 Candida and Clostridium Intestinal overgrowth of Clostridium bacteria has also been identified in some children with autism. Many have high levels of a metabolite of Clostridium in their urine. Shaw, William, Ph.D. Biological Treatments for Autism and PDD. Overland Park, KS: 2002 Various Clostridium species cause diseases such as tetanus, gangrene, diarrhea and botulism. The DPT vaccine may cause a low level tetanus infection in autistic children. Shaw, William, Ph.D. Biological Treatments for Autism and PDD. Overland Park, KS: 2002.; Crone N and Reder A. Severe tetanus in immunized patients with high anti-tetanus titers. Neurology 42: , Decreased levels of beneficial intestinal bacteria can lead to an overgrowth of Clostridium following the use of antibiotics. Clostridium species are resistant to a number of antibiotics. Finegold S. Anaerobic infections and Clostridium difficile colitis emerging during antibacterial therapy. Scand J Inf Dis Suppl 49: , Clostridium species produce a potent neurotoxin that can lead to sensory hypersensitivity, which may help explain some traits of autistic children.

41 2007 Dr. Irfan Qureshi, ND 41 Intestinal oxidative damage Oxidative Stress is cellular injury resulting from free-radical generation that exceeds available antioxidants. The interplay of genes, nutrients and toxins determines the level of oxidative stress. Free-radicals are highly-reactive molecules which damage cells by oxidizing fats, proteins and DNA. Some free-radicals are a product of energy metabolism Environmental toxins (heavy metals such as mercury, pesticides) are either free-radicals themselves, or lead to the generation of free- radicals in the body (as do infections and food allergies).

42 2007 Dr. Irfan Qureshi, ND 42 What Increases Free-Radicals? Smoking, pollution, ozone Heavy metals Inflammatory cytokines Infections, allergies Oxidized foods, food additives Dirty foods (insecticide, herbicide) Depleted anti-oxidant defense

43 2007 Dr. Irfan Qureshi, ND 43 Antioxidants as free radical scavengers

44 2007 Dr. Irfan Qureshi, ND 44 Free Radical damage Healthy cells Delinearization of FFAs affects cellular communication and transport

45 2007 Dr. Irfan Qureshi, ND 45 Immune System abnormalities Candida interfering with immune function The immune system of Candida-infected individuals produces antibodies against Candida proteins that are involved in reproduction. Vojdani A, et al. Immunological cross-reactivity between Candida albicans and human tissue. J Clin Lab Immunol 48: 1-15, Alpha-gliadin (a part of gluten) from wheat is similar in structure to a Candida reproductive protein. Antibodies produced against yeast may be tricked into reacting against wheat. Theoretically, this may be one reason autistic individuals react to wheat. Shaw, William, Ph.D. Biological Treatments for Autism and PDD. Overland Park, KS: 2002 Increased WBCs in the colon Intestinal analysis performed in 21 autistic children showed increased numbers of white blood cells, indicating an inflammation or infection of the intestines. These white cells seem specifically targeted against the cells of the intestinal walls. This points to gut wall dysfunction in autistic individuals. Furlano RI, et al. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr Mar;138(3):

46 2007 Dr. Irfan Qureshi, ND 46 Immune System abnormalities Immune proteins (Ig) have been found to be deficient in autism. In one study, 20 % of autistic children had IgA antibody deficiency; 8% lacked it completely; none of the controls had IgA deficiency. 20% also showed deficiency of IgG. Gupta S, et al. Dysregulated immune system in children with autism. Beneficial effects of intravenous immune globulin on autistic characteristics. Autism Develop Dis 26: , Deficiencies of proteins lead to low immune function inability to fight off infections. IgA is the major class of immune globulin associated with intestinal tissue. A deficiency of IgA means low gut immunity, predisposing to local inflammation, infection and allergies.

47 2007 Dr. Irfan Qureshi, ND 47 Putting it all together: A vicious cycle? Impaired Digestion/ Enzyme deficiencies Improper breakdown of foods Food Allergies and sensitivities Sugars feed Candida/Clostridium Food allergens inflame intestines Development of Leaky Gut Release of toxins Entry of toxins Entry of opioid food proteins Impaired detoxification Ear infections/Lung Infections Antibiotics kill beneficial bacteria Allow overgrowth of yeast Promote Clostridium growth Vaccines – DPT and MMR Mercury damages gut cells Organisms produce chronic infections Binding of opioid foods, toxins to brain Behavioral changes Hypersensitivity

48 2007 Dr. Irfan Qureshi, ND 48 Relevant Laboratory Assessment CBC +Chem panel a way of determining general health status and gathering information about vitamin and mineral deficiencies, liver function, etc. Serum Homocysteine indicator of methylation status for DNA repair and detoxification indirectly assesses need for methylation cofactors such as B6, folic acid, B12 and DMG/TMG. Methylmalonic acid (MMA) Measure of vitamin B12 deficiency

49 2007 Dr. Irfan Qureshi, ND 49 Relevant laboratory assessment Food Allergy Assessment Multiple Options IgG + IgE Antibody Assessment (blood test). Identifies immediate and delayed food reactions. Intradermal Testing Food Elimination and Challenge. Intestinal Permeability Studies. Testing for leaky gut Lactulose/Mannitol urine concentrations are measured. Patient drinks a solution of two sugars and collects urine for next 6 hours Mannitol is a small molecule and is normally absorbed; Lactulose is a large molecule and is not normally absorbed. Elevated concentration of Lactulose in the urine means Leaky Gut is present.

50 2007 Dr. Irfan Qureshi, ND 50 Relevant laboratory assessment Comprehensive Digestive Stool Analysis. Assesses Microbiology, Digestion, Yeast Infection, Absorption / Malabsorption Assess gut bacterial balance. Measures levels of Lactobacillus and Bifidobacterium in the intestines. Gives us information on the presence of Candida and pathogenic bacteria and how they affect gut health. Urinary Peptide Test Checks for excretion of gluten and casein peptides in the urine Elevated levels of these proteins correlates with them having opioid- like effects in children.

51 2007 Dr. Irfan Qureshi, ND 51 Relevant laboratory assessment Organic Acid Testing (OAT panel) This tests for byproducts of yeast and bacteria. Urine collection. Good for picking up systemic infection with Candida Also useful for testing for the presence of Clostridium in the intestines Helpful for distinguishing Candida from Clostridia overgrowth, or presence of both simultaneously. Also tests for certain nutrient and vitamin deficiencies.

52 2007 Dr. Irfan Qureshi, ND 52 Relevant laboratory assessment Not all tests will be positive in all cases of autism. Tests serve as a guide towards implementation of the protocol They help to identify areas of focus for therapeutic intervention.

53 2007 Dr. Irfan Qureshi, ND 53 Therapeutic Nutritional protocol The goal is to correct underlying digestive imbalances to: Improve absorption and assimilation of nutrition Reduce food sensitivities Impact the physiology of mental function and behavior

54 2007 Dr. Irfan Qureshi, ND 54 Treatment targets and principles Dietary Modification Reducing oxidative damage Improving Digestive Function Rebuilding intestinal mucosa and correcting Leaky Gut Correcting bacterial dysbiosis Eliminating intestinal pathogens (Candida and Clostridia) Removing toxins Stimulating immune function

55 2007 Dr. Irfan Qureshi, ND 55 Dietary Modification This is assessed by Food Allergy testing and Urinary Peptide testing. Based on the above results, avoidance of potentially allergenic foods for the duration of protocol. If urinary peptide test is positive, avoidance of gluten and casein is important for the duration of protocol.

56 2007 Dr. Irfan Qureshi, ND 56 Reducing Oxidative Damage Increase dietary intake of foods rich in antioxidants Good quality, high-potency multiple vitamin and mineral formula Additional antioxidant supplements on a rotation basis A, C, E, Zinc and Selenium

57 2007 Dr. Irfan Qureshi, ND 57 Improving Digestive function Dietary avoidance of any potential food allergens as determined by testing. Acid-stable fungal-sourced digestive enzymes Hydrochloric acid (determined by CDSA) These improve the breakdown of foods and increase the absorption of nutrients.

58 2007 Dr. Irfan Qureshi, ND 58 Correcting Leaky Gut / Rebuilding intestinal tissue Nutrition for intestinal cell repair and rebuilding: L-Glutamine and other Amino Acids Gamma-oryzanol (rice bran) Phosphatidylcholine Essential fatty acids (combination product containing both omega 3 and omega 6 oils)

59 2007 Dr. Irfan Qureshi, ND 59 Correcting Intestinal Bacterial Balance Aim is to restore beneficial bacteria that normally colonize the intestines. These bacteria aid in the digestion of our foods and increase the absorption of our nutrients. Probiotics (containing Lactobacillus and Bifidobacterium species) Fructooligosaccharides (FOS) – food for the beneficial bacteria. Promotes growth of Bifidobacterium while inhibiting growth of yeast such as Candida

60 2007 Dr. Irfan Qureshi, ND 60 Eliminating Candida and Clostridia overgrowth Assessed by the CDSA test and organic acids. Can vary from individual to individual. Diet should be low in sugars, simple carbohydrates, alcohol and processed foods. These foods can feed the yeast. Various treatments based on type of pathogens Herbs/ Drugs to control Candida Products containing Caprylic acid and Oregano oil. Nystatin and other antifungals The most effective treatment for Clostridium has been the use of Probiotics. Shaw, William, Ph.D. Biological Treatments for Autism and PDD. Overland Park, KS: 2002

61 2007 Dr. Irfan Qureshi, ND 61 Removing intestinal toxins Increase all sources of dietary fiber. Candida and other pathogens release toxins in die-off reactions. These toxins can further injure the intestinal mucosa. Fiber binds the toxins in the GI tract and aids in their removal through the stools.

62 2007 Dr. Irfan Qureshi, ND 62 Improving Detoxification through Enhanced Methylation Depending on results of lab tests for homocysteine and MMA: Methyl-B12 Vitamin B6 Folic/ folinic acid Dimethylglycine / Trimethylglycine Magnesium

63 2007 Dr. Irfan Qureshi, ND 63 Monitoring of Therapy Two methods to monitor improvement Clinical/observational (Physician, parents) Monitoring of behavioral improvements throughout the treatment period and thereafter. Customized assessment questionnaires for individual children. Monitoring improvement over time of gastrointestinal signs and symptoms (reductions in gas, bloating, constipation, reflux, diarrhea, etc.) Questionnaires and food diaries ATEC (Autism Treatment Evaluation Checklist) scores (ARI website) To establish a baseline and to monitor progress Objective – To monitor improvements in physiology Initial assessment followed by reassessment of laboratory measures can be done (Food allergy, Intestinal permeability, CDSA) to determine physiological changes. Signs of improvement are reduction of intestinal permeability, improved digestive function, idealization of intestinal bacterial balance and reduced number of food allergies.

64 2007 Dr. Irfan Qureshi, ND 64 Practical issues of implementation specific to Autism Collection of test samples for laboratory assessment: blood, urine and stool. Sensitivity to taste of supplements, ability to swallow capsules. Determining correct dosages of supplements based on age and body weight.

65 2007 Dr. Irfan Qureshi, ND 65 Remarks Proper treatment of Autism using the biomedical approach entails finding the cause of the problem. Correcting digestion provides a foundation for optimizing health. Avoid using the shotgun approach to nutrition, as it may do more harm than good. Many doctors treat with this approach, rather than performing the necessary testing (out of ignorance??) The laboratory testing helps to customize therapy. The road to Health is paved with good Intestines - Unknown

66 2007 Dr. Irfan Qureshi, ND 66 How to Get Started Co-operation from families and friends Where are the sources of casein and gluten Learning how to read labels Substitutes Eating Out

67 2007 Dr. Irfan Qureshi, ND 67 Results of GFCF Survey 2002 RespondentsAverage age at diet start Average time spent on diet Average change in ATEC score Dramatic11.5% (16)3.0 years18 months-85 (82 %) Excellent29.5% (42)3.3 years13 months-54 (62 %) Good27% (37)4.7 years8 months-28 (38 %) Moderate22.6% (31)4.4 years7 months-12 (16 %) No result5% (7)5.7 years1 month0 Regression4.4% (6)5.5 years7 months+5 (16 %)

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