1. Diet and IBS, Fibromyalgia, and Migraine

2. What Is Irritable Bowel Syndrome? Symptom Based Diagnosis of Exclusion Symptom Based Diagnosis of Exclusion Diarrhea Predominant IBS Diarrhea Predominant IBS Constipation Predominant IBS Constipation Predominant IBS Cyclic IBS Cyclic IBS

3. Rome II Criteria for IBS Relief after defecation Relief after defecation Onset associated with a change in stool consistency Onset associated with a change in stool consistency Onset associated with a change in stool frequency Onset associated with a change in stool frequency

4. Rome II Continued Other symptoms that are not essential but support the diagnosis of IBS: Other symptoms that are not essential but support the diagnosis of IBS: Abnormal stool frequency Abnormal stool frequency –greater than 3 bowel movements/day – less than 3 bowel movements/week Abnormal stool form Abnormal stool form – lumpy/hard – loose/watery stool Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation) Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation) Passage of mucus Passage of mucus Bloating or feeling of abdominal distension. Bloating or feeling of abdominal distension. Source: International Foundation of Functional Gastrointestinal Disorders

5. When You Should Ask The Doctor to Double-Check IBS Diagnosis: Profound weight loss, anemia or blood/occult in stool Profound weight loss, anemia or blood/occult in stool Travel to places with parasitic endemics Travel to places with parasitic endemics Hx of colon cancer Hx of colon cancer Skin abnormalities Skin abnormalities Signs of malabsorption Signs of malabsorption Thyroid dysfunction Thyroid dysfunction This list is not exhaustive, but is helpful…

6. Consequences of IBS Patients with IBS averaged 15 of 30 days with poor physical or mental health. Patients with IBS averaged 15 of 30 days with poor physical or mental health. These average overall unhealthy days exceeded those of respondents with arthritis, diabetes, heart disease/stroke, cancer, and class III obesity (body mass index > or =40 kg/m2) from the U.S. survey. These average overall unhealthy days exceeded those of respondents with arthritis, diabetes, heart disease/stroke, cancer, and class III obesity (body mass index > or =40 kg/m2) from the U.S. survey.

7. Traditional Therapies Medication Side Effects Side Effects Band-Aid solution- only addresses symptom of diarrhea, not underlying problems so other problems continue. Band-Aid solution- only addresses symptom of diarrhea, not underlying problems so other problems continue.

8. IBS is not a distinct entity but a collection of disorders Food intolerance represents an important proportion of conditions which together make up IBS Food intolerance represents an important proportion of conditions which together make up IBS John Hunter, MD, FCRP Director or Gastroenterology Food Allergies and Food Intolerance Brostoff & Challacombe, Second Edition, 2002

9. IBS not only symptom Lancet 2000 Jul 29;356(9227):400-1 We found that food provocation in food intolerant patients was characterized by a general and systemic immune activation accompanied by an increase in systemic symptoms… important for the understanding of the mechanisms involved in the pathogenesis of food intolerance. Food sensitivities ushered in by IBS lead to feeling bad all over…

10. FOOD INTOLERANCE CAUSES FOOD INTOLERANCE CAUSES IBS SYMPTOMS IN CERTAIN PATIENTS IBS SYMPTOMS IN CERTAIN PATIENTS Merck Manual pg 1051 Food Intolerance was found to be responsible for symptoms of some patients with the IRRITABLE BOWEL SYNDROME

11. Trial and Error as a Therapy But through Trial and Error many people find they feel better when they stop eating certain foods. These foods cause the intestines to contract, which can aggravate IBS in people who have diarrhea as their main symptom. Nicholas Talley, MD., Patrice Burgess, MD Controlling I.B.S. With Diet Healthwise Information Library But meanwhile, life goes on….. Without remission….

12. The IBS Employees Average Combined Work Time Lost to Absenteeism and Work Cut Backs due to IBS Symptoms was found to average ONE WEEK per MONTH, for a total of 12 WEEKS per YEAR of lost productivity. This represents a loss of nearly 25% of productivity PLUS the costs of accompanying sick leave pay.*

13. American Gastroenterological Association Position Statement Education and Reassurance Education and Reassurance Dietary and Lifestyle Modifications Dietary and Lifestyle Modifications Symptom Monitoring Symptom Monitoring Symptom-Directed Medication PRN Symptom-Directed Medication PRN Psychological Treatment Psychological Treatment

14. Dietary Trial and Error Dietary Trial and Error Caffeinated drinks Caffeinated drinks Tyramine and phenylethylamine- pressor amines Tyramine and phenylethylamine- pressor amines Histamine Histamine Solanine: naturally occurring toxicant in the nightshade plant family Solanine: naturally occurring toxicant in the nightshade plant family Nitrates and Nitrites Nitrates and Nitrites Benzoic Acid: also benzoin, gum benzoin, benzoate and naturally occurring diet. Benzoic Acid: also benzoin, gum benzoin, benzoate and naturally occurring diet. Sorbitol Family: sorbitol, sorbitan, polysorbate 80, polysorbate 60 Lectins (in beans, lentils, peas, peanuts, snails, wheat). Peptides: small protein-like molecules Proteolytic Enzymes (raw pineapple, raw papaya most common Eating Habits Scrutinized : Too much at one time and too high fat content too much stress especially when you eat

15. 15 IF food Intolerance IS important to IBS symptoms, WHY do most Diets fail to make much difference? Unlike allergies, food sensitivity reactions are: 1. 1.Dose Dependent 2. 2.Delayed Onset (up to 72 hours post ingestion) 3. 3.Multiple foods can cause symptoms (single elimination trials are useless) 4. 4. NO Universal Bad Food- Very patient specific Until now, it was just hard to find those triggers

16. Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms. Bengtsson U, Nilsson-Balknas U, Hanson LA, Ahlstedt S Allergy Centre, University of Goteborg, Sweden Gut. 1996 Jul;39(1):130-5. no indications of IgE In adult patients with staple food induced gastrointestinal symptoms, objectively verified by DBPCFC, there were no indications of IgE mediated allergy to the relevant foods, suggesting other mechanisms in adults than in children. Should we test for allergies (IgE)?

17. Intestinal Perfusion Studies Balloon Jejunum Stomach Catheter Knutson et al, J. of Allergy and Clin. Immunology 93; 91(2): 553-9

18. Intestinal Perfusion Studies Segment of jejunum is endoscopically isolated by placement of two balloons Segment of jejunum is endoscopically isolated by placement of two balloons Segment of jejunum between balloons is perfused with potential food allergen and then jejunal contents are collected Segment of jejunum between balloons is perfused with potential food allergen and then jejunal contents are collected Knutson et al, J. of Allergy and Clin. Immunology 93; 91(2): 553-9 Anatomy of a Food Sensitivity

19. Intestinal Perfusion Studies Patients with known sensitivity to the food had increased production of cytokines found in the washings after positive challenge. Patients with known sensitivity to the food had increased production of cytokines found in the washings after positive challenge. No increased cytokines seen in controls No increased cytokines seen in controls Found no IgE to specific offending foods in sensitive patient group Found no IgE to specific offending foods in sensitive patient group Knutson et al, J. of Allergy and Clin. Immunology 93; 91(2): 553-9 Anatomy of a Food Sensitivity

20. To summarize: No physical evidence of damage in the jejunum No physical evidence of damage in the jejunum No evidence of an allergy: No IgE in the aspirated contents of the jejunum No evidence of an allergy: No IgE in the aspirated contents of the jejunumBUT Evidence of an immune reaction, Evidence of an immune reaction, i.e., presence of cytokines.

21. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. 150 outpatients with IBS 150 outpatients with IBS Randomized X 3 months Randomized X 3 months Test: diet excluding all foods which raised IgG Test: diet excluding all foods which raised IgG Control: sham diet excluding the same number of foods but not those to which they had antibodies. Control: sham diet excluding the same number of foods but not those to which they had antibodies. Outcome measured: IBS and global symptoms Outcome measured: IBS and global symptoms Gut. 2004 Oct;53(10):1459-64. What about IgG testing?

22. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. In 12 weeks In 12 weeks Elimination diet resulted in a 10% greater reduction in symptom score than the sham diet Elimination diet resulted in a 10% greater reduction in symptom score than the sham diet CONCLUSION: Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research. Gut. 2004 Oct;53(10):1459-64. What about IgG Testing? p2

23. IgG –Based Elimination Well, yes, statistically significant but Only 10% improvement in 12 weeks? Can we do better if we get a broader picture….. Did they miss something?

24. Types of Adverse Food Reactions Allergy -IgE Sensitivity -Non-IgE Intolerance What Is It? Immediate Immune reactions Delayed immune reaction Enzyme Deficiency Unique Characteristics: Usually about 30 minutes to first reaction EASY to detect Dose-related, time delayed Cause-effect confusing without helpful testing. Treated With Digestive Enzymes Target Organs Affected: Skin, Airways, Digestive Tract Any Organ System Can Be Affected Gastrointestinal Tract Cells Involved: IgE Measure IgE! IgG, IgM,C3, C4, Platelets, and more (about 90 different cells) Direct Cellular Reactions Toxins None EASY to treat # of Reactive 1 - 410 - 201 Involved in IBS? Co-morbid 8- 10% Estimated 30-40%?

25. Other symptoms…. 15% identified muscle and joint pain, not IBS symptoms, as the major cause of their activity limitation. Psychosom Med. 2006 Mar-Apr;68(2):312-20.

26. Comorbid to IBS Migraine Migraine Fibromyalgia Fibromyalgia Sinusitis Sinusitis Rheumatoid Arthritis Rheumatoid Arthritis GERD GERD Some of these symptoms persist long after IBS-D remits if food sensitivity not treated.

27. Why measure mediators? Because they are agents of chemical warfare released by cells to fight off invaders or perceived invaders Because they can cause collateral damage –Smooth muscle contraction (evacuation) –Inflammation (leak WBC to point of infection) –Fever (in total flu-like symptoms) Cells sometimes attack otherwise benign substances like foods and additives

28. Measuring Mediators MRT Tested- 123 foods and 27 chemicals MRT Tested- 123 foods and 27 chemicals Plasma to solids ratio (indirect measure of mediator release) is measured on all tested foods to give a ratio. Plasma to solids ratio (indirect measure of mediator release) is measured on all tested foods to give a ratio. If the volume of the plasma increases dramatically, that's considered a 'highly' reactive food. If there's no or very little volume change, that food is considered 'non-reactive. If the volume of the plasma increases dramatically, that's considered a 'highly' reactive food. If there's no or very little volume change, that food is considered 'non-reactive.

29. Formation of the Diet Results put in graphical and diet form Results put in graphical and diet form Diet book sent to patient Diet book sent to patient Results and pt history sent to dietitian Results and pt history sent to dietitian

30. Short Term Data-Driven Protocols Symptom Survey Symptom Survey –Did we address the chief complaints? –Did the symptoms that respond best to elimination disappear with good compliance?

31. Long-Term Data-Driven Protocols SF-36 SF-36 –Does the person have better functioning? –Can the person have a life? –Is the person happier?

32. 39 y.o. male IBS, GERD, and intestinal parasites Extreme stomach pains, cramps, intestinal pain, constipation, gas, diarrhea, and nausea for a period of 8 months. Unable to go to work, suffered constant pain, and was demoted once. His job was in jeopardy. He scored 68 on the symptom survey. Consuming 20 medications and supplements per day. No relief of IBS attacks, gas which he described as so bad that his abdomen was rock hard with bloating. He had difficulty sleeping, always feeling fatigued and miserable. LEAP Case Study- IBS

33. The dietitian asked the patient if he had ever experienced remission of symptoms during these 8 months. He replied that he had once felt ok for ½ of one day. According to LEAP protocol, the patient eliminated all supplements and medications except those to ease GERD and treat intestinal parasites. Within 1 week, his symptoms had decreased dramatically, with complete remission of diarrhea and bloating (his symptom score was down from a 68 to an 11) and he was able to go back to work. Able to identify isolated foods which seemed to still trigger GERD episodes. By the time he reached 2 ½ months his GERD also dissipated. Able to go off of all medication at that point. Pt was successfully discharged LEAP Case Study- IBS pg 2

34. LEAP Case Study- Migraine 54 y.o. female with migraine headaches, tension headaches, controlled hypertension, fatigue, fibromyalgia, lack of sleep, confusion, lactose intolerance, colitis. Patient worked as a consulting psychologist. Treatment, to date, included Toprol, Flexeril, Maxalt, Xanax and Ambien, daily, Tylenol or Excedrine PRN. Supplements included Centrum, Calcium, Magnesium Glyconate, Her height was 50 and weight was 94#. Blood pressure was 130/80. Significant effects to lifestyle included inability to hold a thought, difficulty doing work, difficulty enjoying vacations. The patient said that migraine headaches would last several days at a time and occur more than 4 times per month. The patient was very distressed, having difficulty waiting for her referring physician to release the results of the test, becoming agitated. She threated suicide

35. The dietitian checked with the referring physician to see if this threat was authentic. The physician said the patient made this statement frequently. Still, the dietitian scheduled this highly agitated patient ASAP. According to LEAP protocol, the patient suspended all supplements to be tested in later phases. She was started in Phase 1, of her personalized elimination diet. Within 8 days, her symptoms had decreased dramatically (his symptom score was down from a 59 to 13) and she was migraine- free, with no GI problems, reduced joint stiffness and muscle pain, able to sleep and was no longer taking PRN sleeping medication. LEAP Case Study- Migraine pg 2

36. Husband got on the phone and thanked the dietitian Dietitian made suggestions for menu selection and ordering at her favorite restaurants. The patient would try to occasionally eat small amounts of reactive foods, but since they caused migraines, the patient quickly returned to her diet. Pt was successfully discharged from the LEAP program and said that she would like to make this test available to her relatives in Mexico (currently LEAP testing is available in the United States and Europe) LEAP Case Study- Migraine pg 3

37. LEAP Case Study- Fibromyalgia 52 y.o. female with fibromyalgia pain in shoulders, neck knees, hips, ankles, s/p cholecystectomy, s/p appendectomy, c-section, vaginal cyst, vaginal hysterectomy, diverticulitis, asthma and chronic rhinits. Patient smokes cigarettes and uses oxygen at night to treat COPD. Her treatment, to date, included Q Dall, Clonazipam, Duoneb, Advair and Ibuprophen. Her height was 51/2 and weight was 185#. Significant effects to lifestyle included inability to get out of bed in the morning upon awakening, constant pain and self- recrimination for weight gain. Works in a job as cashier.

38. According to LEAP protocol, the patient suspended all supplements to be tested in later phases. She was started in Phase 1, of her personalized elimination diet. Within 8 days, her symptoms had decreased dramatically (his symptom score was down from a 105 to 36), she had lost 8 #, with reduction in muscle and joint pain, gastrointestinal symptoms, and nasal symptoms. At the third follow-up, she declared that she was pain free with her symptom scores decreasing another 16 points to a score of 36. At the fourth follow-up, her chest congestion was completely gone and patient was functioning at a much higher level. Her daughter- who gave birth to a premature baby was assisted by a more energetic mom At the fifth follow-up, patient related that she got a new job as a manager and got double her previous pay. A t t h e t h i r d f o l l o w - u p, s h e d e c l a r e d t h a t s h e w a s p a i n f r e e w i t h h e r s y m p t o m s c o r e s d e c r e a s i n g a n o t h e r 1 6 p o i n t s t o a s c o r e o f 3 6. A t t h e f o u r t h f o l l o w - u p, h e r c h e s t c o n g e s t i o n w a s c o m p l e t e l y g o n e a n d p a t i e n t w a s f u n c t i o n i n g a t a m u c h h i g h e r l e v e l. H e r d a u g h t e r - w h o g a v e b i r t h t o a p r e m a t u r e b a b y w a s a s s i s t e d b y a m o r e e n e r g e t i c m o m. A t t h e f i f t h f o l l o w - u p, p a t i e n t r e l a t e d t h a t s h e g o t a n e w j o b a s a m a n a g e r a n d g o t d o u b l e h e r p r e v i o u s p a y. LEAP Case Study- Fibromyalgia- pg 2

39. Stats on 127 Patients In therapy for 1 month In therapy for 1 month One baseline survey and two follow-up on schedule, to provide us an overall symptom score One baseline survey and two follow-up on schedule, to provide us an overall symptom score Fit our patient selection criteria Fit our patient selection criteria (IBS, Fibromyalgia, Migraine) (IBS, Fibromyalgia, Migraine)

40. RESULTS 10 day 54.89 % Average Symptom Reduction 1 mo. 74.82 % Average Symptom Reduction