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2007 Dr. Irfan Qureshi, N D 1 The Biomedical Approach to Autism: The Gut-Brain Connection Dr. Irfan Qureshi, ND Pacific Highway Natural Medicine 15245 International Blvd., Suite 210 Seattle, Washington 98188 Phone: (206) 923-7600 Email: [email protected]
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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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Page 1: 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.

2007 Dr. Irfan Qureshi, ND 1

The Biomedical Approach to Autism:

The Gut-Brain Connection

Dr. Irfan Qureshi, NDPacific Highway Natural Medicine15245 International Blvd., Suite 210Seattle, Washington 98188Phone: (206) 923-7600Email: [email protected]

Page 2: 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.

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.

Page 3: 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.

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 (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

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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 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.

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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 detoxification…and 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

Page 10: 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.

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 elimination

of 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-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.

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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. Goat’s 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

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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

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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):1331-44.

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.

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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: 2002.

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

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

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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)

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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 bacterial flora)

Other potential causes include heavy metals, yeast and bacterial overgrowth, and components of vaccines

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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 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. 1983 Dec;140(12):1579-82.

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). 2003 Jun;228(6):639-49.

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Leaky Gut SyndromeEvidence of Intestinal problems (cont’d) 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. 1996 Sep;85(9):1076-9.

57% 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. 2000 May;22(5):393-6.

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. 2000 Sep;95(9):2285-95.

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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

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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):99-117

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

cow’s 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):199-203

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):305-22.

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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. 1999 Mar-Apr;25(2):122-34.

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. 1996 Jan;168(1):105-9.

Avoidance of casein may be particularly useful in autistic children who show signs of self-injurious behavior.

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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. 2003 Apr 10;540(1-3):117-24.

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. 2003 Feb;52(2):218-23.

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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. 2002 Apr;128(1):94-101.

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. 2001 Jul;96(7):2251-4.

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.

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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.

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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; 6:575-586.

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; 351:637-641.

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. (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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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. 2000 May;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 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. 1991 Mar;41(3):372-5.

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. 2003 Mar;98(3):625-9.

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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. 1998 Nov 14;352(9140):1582-5.

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. 1980 Apr;34(2):107-12.

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. 1984 Feb;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 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!!

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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 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.

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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. If

effective, continue the diet. ***There are some reports of benefit seen only after 6

months or longer on the diet.***

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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

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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 worth

undertaking. 80% of the cases have shown benefit on

the diet in research trials and in practical experience.

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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!

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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.

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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 overgrowthEating 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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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. 2003 Apr;98(4):839-43.

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.

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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 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.

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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, 1994.

Some antibiotics have actually been shown to promote yeast growth. Kasckin P. Some aspects of the candidosis problem. 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 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: 761-764, 1992.

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: 160-164, 1986.

Clostridium species produce a potent neurotoxin that can lead to sensory hypersensitivity, which may help explain some traits of autistic children.

Page 41: 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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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).

Page 42: 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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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

Page 43: 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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Antioxidants as free radical scavengers

Page 44: 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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Free Radical damageHealthy cells

Delinearization of FFA’s affects cellular communication and transport

Page 45: 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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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, 1996.

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 WBC’s 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. 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 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: 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 gut immunity, predisposing to local inflammation, infection and allergies.

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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

Page 48: 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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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

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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 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.

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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 Clostridium

in the intestines Helpful for distinguishing Candida from Clostridia

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

Page 52: 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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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.

Page 53: 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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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

Page 54: 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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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

Page 55: 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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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.

Page 56: 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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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

Page 57: 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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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.

Page 58: 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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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)

Page 59: 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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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

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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 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

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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.

Page 62: 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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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

Page 63: 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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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.

Page 64: 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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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.

Page 65: 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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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

Page 66: 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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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

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Results of GFCF Survey 2002 Respondents 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 %)