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Bio Medical Approach to Autism

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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 Blvd., Suite 210Seattle, Washington 98188

    Phone: (206) 923-7600

    Email:[email protected]

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    2007 Dr. Irfan Qureshi, ND 2

    Naturopathic Medicine Philosophy and Scope of Practice

    A discipline of medicine requiring a doctorate level educationsimilar 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 arelicensed to practice as Primary Care Physicians

    Naturopathic Physicians stress treatments that are natural tohelp with chronic conditions, such as diet and lifestylechanges, 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 thesymptoms.

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    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

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    2007 Dr. Irfan Qureshi, ND 4

    Objectives of the Talk

    To develop an understanding of the

    Biomedical approach to Autism (especiallyas 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

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    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 in2000 individuals

    Evidence is that the incidence has increased to 1 in200, with the incidence in some areas even higher!

    No one definitive cause for this condition that hasbeen identified.

    An autism epidemic? No decrease in cases in sight.

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    2007 Dr. Irfan Qureshi, ND 6

    Overt Signs and Symptoms of

    impaired digestion

    Gas and bloating

    Belching Heartburn

    Acid Reflux

    Nausea/vomiting Constipation

    Diarrhea

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    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

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    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 detoxificationand increased toxic load

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    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

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    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

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    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 eliminationof allergic foods from the diet. Lucarelli S, et al. Food allergy and infantile autism.Panminerva Med. 1995 Sep;37(3):137-41.

    The majority of problematic food allergies are the delayed-onsettype (IgG), taking hours to days to occur.

    Immediate reactions are easier to identify and eliminate becausethey have a fast onset (IgE antibody). (Skin prick testing identifiesonly these type, and is better for environmental sensitivities)

    The blood testing screens multiple foods for reactions based on bothimmediate and delayed onset (IgG and IgE antibody reactions).

    Major allergens may be dairy, wheat, soy, eggs. Other foods canalso be reactive.

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    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 1999Mar;42(3):292-6

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    2007 Dr. Irfan Qureshi, ND 13

    The Role of Gluten and Casein inautism

    Opioid-like effects

    Food Allergies

    Free-radical damage to gut cells

    Leaky Gut syndrome

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    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. CurrPharm Des. 2003;9(16):1331-44.

    These proteins attach to receptors in the brain.They are nearly identical in structure tonatural opioid-binding peptides. (Can have

    morphine-like effects) The proteins enter the blood circulation in

    incompletely digested forms (due to digestiveenzyme deficiencies and leaky gut) and

    potentially cause changes in mood and brainfunction.

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    2007 Dr. Irfan Qureshi, ND 15

    Opioid effects of gluten and casein

    These effects may be responsible for autistic childrenseemingly 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 effectson 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: 2002.

    Studies show that elimination of gluten and caseinfrom the diet has improved behavior in autisticchildren.Knivsberg AM, Reichelt KL, Hoien T, Nodland M. Arandomised, controlled study of dietary intervention in autistic syndromes.

    Nutr Neurosci. 2002 Sep;5(4):251-61.

    Important to remember that autistic children can haveboth allergies AND sensitivities to wheat and dairy.

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    2007 Dr. Irfan Qureshi, ND 16

    Leaky Gut Syndrome The normal intestinal barrier

    Tight junctions between cells do notnormally allow the entry of large

    molecules into the bloodstream. Leaky gut develops when these tight

    barriers between cells are compromisedand loosen up due to cell injury

    This shriveling allows the passage oflarge molecules (especially food

    particles such as casein and gluten)into the bloodstream.

    These large molecules are incompletelydigested food proteins (possibly due todigestive enzyme deficiencies ordysfunctions)

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    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 bacterialflora)

    Other potential causes includeheavy metals, yeast and bacterialovergrowth, and components ofvaccines

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    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 ofADHD and greater severity of irritable bowelsyndrome. A significant number of ADHDindividuals also had IBS. Wender PH, Kalm M.

    Prevalence of attention deficit disorder, residual type, and otherpsychiatric disorders in patients with irritable colon syndrome. AmJ Psychiatry. 1983 Dec;140(12):1579-82.

    There is mounting evidence of impaired

    intestinal permeability in autistic childrenshowing intestinal signs such as gas, bloating,diarrhea, reflux and constipation. White JF. Intestinalpathophysiology in autism. Exp Biol Med (Maywood). 2003

    Jun;228(6):639-49.

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    2007 Dr. Irfan Qureshi, ND 19

    Leaky Gut SyndromeEvidence of Intestinal problems (contd) Abnormal intestinal permeability (or leaky

    gut) was even found in 43% of autisticchildren showing no intestinal signs orsymptoms. D'Eufemia P, et al. Abnormal intestinal

    permeability in children with autism. Acta Paediatr. 1996

    Sep;85(9):1076-9.

    57% of patients with neurological dysfunction(including Autism and ADD patients) wereshown to have antibodies to gluten (acomponent of wheat and other grains.) LahatE, etal. Prevalence of celiac antibodies in children with neurologic

    disorders. Pediatr Neurol. 2000 May;22(5):393-6.

    A unique type of enterocolitis (infection of thecolon) was found in 93% of individuals withdevelopmental disorders. Wakefield AJ, et al.Enterocolitis in children with developmental disorders. Am JGastroenterol. 2000 Sep;95(9):2285-95.

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    Casein:

    A role in Pain suppression and

    Self-injurious behavior

    Many autistic individuals commonly displayself-immolating behavior

    Self-injurious

    Head banging Scratching to the point of bleeding

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    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 opioidreceptors in the brain. Teschemacher H, Koch G, Brantl V. Milk protein-derived opioid receptorligands. Biopolymers 1997;43(2):99-117

    In animals, casein was shown to greatly increase the pain thresholdcompared 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 incows milk, causes a decreased response to pain. This protein causes

    behavioral changes. BlassE

    M, Blom J. Beta-Casomorphin causes hypoalgesia in 10-day-old rats:evidence for central mediation. Pediatr Res 1996 Feb;39(2):199-203

    Researchers studied 8 children for the presence of casein derivatives inthe brain. Casein derivatives were found in 19 different functionally-relevant areas of the brain. These proteins can play a role in theregulation 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):305-22.

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    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 causedeath (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 anautocrine mechanism involving Fas-Fas ligand pathway. FEBSLett. 2003 Apr 10;540(1-3):117-24.

    Gluten activates enzymes in the intestines that cause thebreakage 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 intracellularsignalling involved in intestinal barrier function. Gut. 2003 Feb;52(2):218-23.

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    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 theguts. Westerholm-Ormio M, Garioch J, Ketola I, Savilahti E. Inflammatory cytokines in small intestinal mucosa of patientswith potential coeliac disease. Clin Exp Immunol. 2002 Apr;128(1):94-101.

    Some gluten-sensitive patients have been shown to have low levels of enteropeptidaseenzymes (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 JGastroenterol. 2001 Jul;96(7):2251-4.

    Gluten causes flattening of the villi in the intestines of gluten-sensitivepatients.

    Villi are the projections on intestinal cells that allow absorption of nutrientsfrom foods.

    This results in decreased absorption and documented nutritional deficiencies.

    The villi return to their normal shapes after gluten removal, and the nutritionaldeficiencies are corrected.

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    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 theenteric 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 thebrain.

    The digestive organs can operate independently fromthe CNS. In people who are brain-dead, the stomach

    functions properly. Evidence suggests that emotions and feelings are

    intimately associated with bowel function. Exampleis Irritable Bowel Syndrome, where stress andemotions can cause digestive symptoms.

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    2007 Dr. Irfan Qureshi, ND 26

    The Gut-Brain Connection:The link between digestion and behavior

    Many autistic children develop intestinal symptoms at thesame time they are losing acquired skills such as language.This shows that gut health can have a major impact ondevelopment of sensory skills. Mcmillin DL, et al. The Abdominal Brain andEnteric Nervous System. J Alt and Compl Med. 1999; 6:575-586.

    One study looked at 12 autistic children with a history ofnormal development followed by a loss of acquired skills. Allof them had developed diarrhea and abdominal pain. Wakefield AJ,et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmentaldisorder in children. Lancet 1998; 351:637-641.

    The gut, like the brain, has opiate receptors. Drugs likemorphine act on the brain, but also on the gut, to cause

    constipation by binding to the opiate receptors.(http://immune.altmedangel.com/gutbrain.htm) Casein and gluten proteins can similarly bind to the gut opiate

    receptors, causing digestive complaints.

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    2007 Dr. Irfan Qureshi, ND 27

    The Gut-Brain Connection:The link between digestion and behavior

    Neurological dysfunction in ADD and Autism may be explainedby allergies to foods and additives (as in the case of gluten). LahatE, etal. Prevalence of celiac antibodies in children with neurologic disorders. Pediatr Neurol. 2000May;22(5):393-6.

    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. 1984 Nov-Dec;5(6):1139-47.

    A group of adults with dementia were later found to be sensitive togluten. GF diet improved cognitive activity in some patients. CollinP, Pirttila T, Nurmikko T, Somer H, Erila T, Keyrilainen O. Celiac disease, brain atrophy, and dementia.Neurology. 1991 Mar;41(3):372-5.

    A significant number of adults with migraines may have glutensensitivity. Gluten-free diet improved symptoms in majority ofcases. Gabrielli M, Cremonini F, et al. Association between migraine and Celiac disease: results from apreliminary case-control and therapeutic study. Am J Gastroenterol. 2003 Mar;98(3):625-9.

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    The Gut-Brain Connection:The link between digestion and behavior

    Study showed that gluten sensitivity can causeataxia (problem with coordination and walking) . Gluten caused inflammation and damage to the

    cerebellum, the spinal cord, and to peripheral nerves in agroup of gluten-sensitive patients.Hadjivassiliou M, Grunewald RA, et al.Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet. 1998Nov 14;352(9140):1582-5.

    Clinical evidence of an association between glutenand schizophrenia. Schizophrenics showedimprovement on a GF diet.Ross-Smith P, Jenner FA. Diet (gluten)and schizophrenia. J Hum Nutr. 1980 Apr;34(2):107-12.

    Interestingly, there is a subgroup of autistic children whodevelop schizophrenia.Petty LK, Ornitz EM, Michelman JD, ZimmermanEG. Autistic children who become schizophrenic. Arch Gen Psychiatry. 1984Feb;41(2):129-35.

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    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 moresensitive to gluten.

    Self-injurious behavior and clear digestive signs and symptoms maybe 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 andcasein 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 areproblematic.

    Testing is only valid prior to beginning CFGF diet!!

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    Urinary Test for Casein and Gluten Available from Great Plains Laboratory (USA)

    Relatively simple specimen collection 5 ml. or more of firstmorning 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.

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    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. Ifeffective, continue the diet.

    ***There are some reports of benefit seen only after 6months or longer on the diet.***

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    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 ofopiate receptors need to be boundsimultaneously.

    Reducing the total body burden by eliminatingthese foods eliminates the opioid effects.

    Eliminating these foods for 4-6 months as muchas possible is a good idea.

    Thereafter, the person maybe able to have somecasein and gluten-containing food (on a rotation

    basis, once every 4-5 days) without problems.Supplemental enzymes can help

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    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 worthundertaking.

    80% of the cases have shown benefit onthe diet in research trials and in practicalexperience.

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    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), suchas 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 diminishafter that. Withdrawal is less severe with casein (observation)

    Withdrawal symptoms may be avoided by removing only one foodgroup at a time.

    Beneficial side effects include improved presence of mind,concentration, behavior, diminished self-immolation, drasticallyimproved digestive function and more!

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    Nutritional Deficiency with CFGF In many autistic children, wheat and dairy form a significantpart 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 dairyproducts. 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 whenconsidering the CFGF diet

    Adequate supplementation may be needed to prevent vitamin andmineral deficiencies

    Professionals can help to properly guide the implementation of the diet.

    Interestingly, experience shows that when patients go on aCFGF 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 otherheavy metals), beans, nuts and seeds.

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    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

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    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 LeakyGutand poor digestive health

    Research in patients on a GF diet showed that there wasstill an imbalance in the bacteria of the intestines. Patientsstill 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 ofsmall intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal

    symptoms after gluten withdrawal. Am J Gastroenterol. 2003 Apr;98(4):839-43.

    Treating Leaky Gut and related issues can improve theeffectiveness of the diet Reduces reactions to food allergens

    Dietary measures can be relaxed when the guts are healed.

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    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 inchildhood. Overuse and unnecessary use of antibiotics leadsto a number of problems

    Autistic children tend to have a number of ear infectionsduring childhood Physicians treat with (and parentsrequest!) antibiotics.

    Earlier incidence of ear infections was correlated to thedevelopment of autism spectrum disorders. In autisticchildren, frequency of ear infections also correlated withseverity of autism. (Konstantareas M and Homatidis S. Ear infections inautistic and normal children. J Autism and Dev Dis 17:585, 1987.)

    Stool tests of autistic patients frequently show no or lowlevels of growth of L. acidophilus and Bifidobacterium

    species.

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    Candida and Clostridium Candida overgrowth of the intestinal tract iscommon in autistic individuals, as shown byincreased 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 todecrease the amount of these yeast byproductsand improve autistic symptoms.

    Chronic or frequent antibiotic usage allowsCandida overgrowth of the intestines by killingoff normal beneficial bacteria. Samonis G, et al. Prospective

    evaluation of the impact of broad-spectrum antibiotics on the yeast flora of thehuman gut. Eur J Clin Microbiology & Inf Dis 13:665-7, 1994.

    Some antibiotics have actually been shown topromote yeast growth. Kasckin P. Some aspects of the candidosisproblem. Mycopathologia et Mycologia applicata. 53:173-181, 1974.

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    Candida and Clostridium Intestinal overgrowth of Clostridium bacteria has also been

    identified in some children with autism. Many have highlevels 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 inautistic children. Shaw, William, Ph.D. Biological Treatments for Autism andPDD. Overland Park, KS: 2002.; Crone N and Reder A. Severe tetanus in immunizedpatients with high anti-tetanus titers. Neurology 42: 761-764, 1992.

    Decreased levels of beneficial intestinal bacteria can lead toan overgrowth of Clostridium following the use ofantibiotics. Clostridium species are resistant to a number of

    antibiotics. Finegold S. Anaerobic infections and Clostridium difficile colitisemerging during antibacterial therapy. Scand J Inf Dis Suppl 49: 160-164, 1986. Clostridium species produce a potent neurotoxin that can lead

    to sensory hypersensitivity, which may help explain sometraits of autistic children.

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    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-radicalsthemselves, or lead to the generation of free-radicals in the body (as do infections and foodallergies).

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    What Increases Free-Radicals?Smoking, pollution, ozone

    Heavy metals

    Inflammatory cytokinesInfections, allergies

    Oxidized foods, food additives

    Dirty foods (insecticide, herbicide)

    Depleted anti-oxidant defense

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    Antioxidants as free radical scavengers

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    Free Radical damageHealthy cells

    Delinearization of FFAs affects

    cellular communication and transport

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    Immune System abnormalities Candida interfering with immune function

    The immune system of Candida-infected individuals producesantibodies against Candida proteins that are involved in reproduction.Vojdani A, et al. Immunological cross-reactivity between Candida albicans and human tissue. J ClinLab Immunol 48: 1-15, 1996.

    Alpha-gliadin (a part of gluten) from wheat is similar in structure to aCandida reproductive protein. Antibodies produced against yeast may

    be tricked into reacting against wheat. Theoretically, this may be onereason autistic individuals react to wheat. Shaw, William, Ph.D. BiologicalTreatments 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 infectionof the intestines. These white cells seem specifically targeted againstthe cells of the intestinal walls. This points to gut wall dysfunction inautistic individuals. Furlano RI, et al. Colonic CD8 and gamma delta T-cell infiltration withepithelial damage in children with autism. J Pediatr. 2001 Mar;138(3):366-72.

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    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 controlshad IgA deficiency. 20% also showed deficiency of IgG.Gupta S, et al. Dysregulated immune system in children with autism. Beneficial effects of intravenous immuneglobulin on autistic characteristics. Autism Develop Dis 26: 439-452, 1996.

    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 gutimmunity, predisposing to local inflammation, infection andallergies.

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    Putting it all together: A vicious cycle?

    Ear infections/Lung Infections

    Antibiotics kill beneficial bacteria

    Allow overgrowth of yeast

    Promote Clostridium growth

    Development of Leaky Gut

    Release of toxins

    Entry of toxins

    Entry of opioid food proteins

    Impaired detoxification

    Food Allergies and sensitivities

    Sugars feed Candida/Clostridium

    Food allergens inflame intestines

    Impaired Digestion/

    Enzyme deficiencies

    Improper breakdown of foods

    Vaccines DPT and MMR

    Mercury damages gut cells

    Organisms produce chronic infections

    Binding of opioid foods, toxins to brain

    Behavioral changes

    Hypersensitivity

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    Relevant Laboratory Assessment CBC +Chem panel

    a way of determining general health status andgathering information about vitamin and mineraldeficiencies, liver function, etc.

    Serum Homocysteine indicator of methylation status for DNA repair and

    detoxification indirectly assesses need formethylation cofactors such as B6, folic acid, B12 andDMG/TMG.

    Methylmalonic acid (MMA) Measure of vitamin B12 deficiency

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    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.

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    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 theintestines.

    Gives us information on the presence of Candida and pathogenicbacteria 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.

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    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 Clostridiumin the intestines

    Helpful for distinguishing Candida from Clostridia

    overgrowth, or presence of both simultaneously. Also tests for certain nutrient and vitamin deficiencies.

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    Relevant laboratory assessmentNot 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.

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    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

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    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

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    Dietary Modification This is assessed by Food Allergy testing

    and Urinary Peptide testing.

    Based on the above results, avoidance ofpotentially allergenic foods for the durationof protocol.

    If urinary peptide test is positive, avoidanceof gluten and casein is important for theduration of protocol.

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    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

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    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.

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    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)

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    Correcting Intestinal Bacterial

    BalanceAim is to restore beneficial bacteria that normally

    colonize the intestines. These bacteria aid in thedigestion of our foods and increase the absorption ofour nutrients.

    Probiotics (containing Lactobacillus andBifidobacterium species)

    Fructooligosaccharides (FOS) food for the

    beneficial bacteria. Promotes growth ofBifidobacterium while inhibiting growth of yeastsuch as Candida

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    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 feedthe yeast.

    Various treatments based on type of pathogens

    Herbs/ Drugs to control Candida

    Products containing Caprylic acidand Oregano oil. Nystatin and other antifungals

    The most effective treatment forClostridium hasbeen the use ofProbiotics. Shaw, William, Ph.D. Biological Treatmentsfor Autism and PDD. Overland Park, KS: 2002

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    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.

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    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

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    Monitoring of Therapy Two methods to monitor improvement Clinical/observational (Physician, parents)

    Monitoring of behavioral improvements throughout the treatment periodand thereafter.

    Customized assessment questionnaires for individual children.

    Monitoring improvement over time of gastrointestinal signs andsymptoms (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 canbe done (Food allergy, Intestinal permeability, CDSA) to determinephysiological changes.

    Signs of improvement are reduction of intestinal permeability, improveddigestive function, idealization of intestinal bacterial balance andreduced number of food allergies.

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    Practical issues of implementation

    specific to Autism

    Collection of test samples for laboratory

    assessment: blood, urine and stool.

    Sensitivity to taste of supplements, ability toswallow capsules.

    Determining correct dosages of supplements

    based on age and body weight.

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    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 toHealth is paved with goodIntestines -Unknown

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    Results of GFCF Survey 2002Respondents Average age at

    diet start

    Average time spent

    on diet

    Average change in

    ATEC score

    Dramatic 11.5% (16) 3.0 years 18 months -85 (82 %)

    Excellent 29.5% (42) 3.3 years 13 months -54 (62 %)

    Good 27% (37) 4.7 years 8 months -28 (38 %)

    Moderate 22.6% (31) 4.4 years 7 months -12 (16 %)

    No result 5% (7) 5.7 years 1 month 0

    Regression 4.4% (6) 5.5 years 7 months +5 (16 %)