8/22/2017. Irritable Bowel Syndrome: Addressing the Role of Food, Probiotics and Medication. Learning Outcomes. Irritable Bowel Syndrome (IBS)

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1 : Addressing the Role of, Probiotics and Medication Lenore Lamanna Ed.D., ANP BC Learning Outcomes Discuss the epidemiology of Discuss the criteria for the diagnosis of as it relates to Rome IV Compare ROME III criteria to ROME IV Review the signs and symptoms of Discuss the role of and Review low FODMAP diet Discuss the role of Probiotics and Review Evidence Based Guidelines related to Medications and Irritable Bowel Syndrome (IBS) Depending on the diagnostic criteria employed, IBS affects around 11% of the population globally. Around 30% of people who experience the symptoms of IBS will consult physicians for their IBS symptoms. Women more frequently affected Impact on patients lives 69% consider it to impair their academic or occupational performance Relevant cause of absenteeism in severe cases Pathophysiology is diverse and not well understood At one time was classified as a psychiatric disorder due to very high incidence of psychological distress in these patients 1994 first diagnostic criteria of IBS published 1

2 ROME III Recurrent abdominal pain or discomfort with onset at least 6 months prior to diagnosis associated with 2 or more of the following at least 3 days per month in the last 3 months Improvement with defecation Onset associated with change in frequency of stool Onset associated with change in form (appearance) of stool Subtypes based on proportion of total stools based on Bristol Stool Chart IBS with predominant diarrhea >25%loose/watery, <25% Hard/lumpy IBS with predominant constipation >25% hard/lumpy,<25% loose watery Mixed type >25% hard/lumpy,>25% loose watery Unclassified <25% hard/lumpy,< 25% loose watery ROME IV Recent abdominal pain, on average at least 1 day per week in the last 3 months, associated with 2 or more of the following criteria: Pain is associated with defecation; either just before, during or soon after defecation Associated with a change in the frequency of stool Associated with a change in form (appearance) of stool Symptom onset at least 6 months before diagnosis Subtyping is based on patients report of the frequency of types on Bristol stool scale ROME IV Criteria Diagnostic Criteria Predominant bowel habits are based on stool form on days with at least one abnormal bowel movement IBS subtypes can be established when the patient is evaluated off medications that are used to treat bowel habit abnormalities ROME IV changes from ROME III Shift away from the term functional bowel disorder Newer term Disorder of gut brain interaction Discomfort has been removed pain Pain relief after defecation was removed ROME IV; pain related to defecation Subtyping is not dependent on specific numerical percentages of specific stool types ROME IV subtyping is based on patients report of the frequency of types on Bristol stool scale 2

ROME IV Criteria Multifactorial etiology Motility Disturbance strong emotion or stress via brain gut axis can lead to dysmotility Visceral hypersensitivity lower pain threshold or increased

3 ROME IV Criteria Multifactorial etiology Motility Disturbance strong emotion or stress via brain gut axis can lead to dysmotility Visceral hypersensitivity lower pain threshold or increased sensitivity Altered Gut Microbiota Small bowel bacterial overgrowth Microscopic inflammation Stress: psychosocial development; susceptibility to stress, cognitive and coping skills Genetics more frequent occurrence in identical twins Family history of IBS found in more than 33% of pts. as compared to 2% in control group Common symptoms include bloating, abdominal pain, excessive flatus, constipation, diarrhea or alternating bowel habit. 3

Differential Diagnoses Celiac Disease Inflammatory Bowel Disease Colon cancer Lactose Intolerance Acute or chronic diarrhea due to protozoa or bacteria Small intestinal bacterial overgrowth (SIBO)

4 Differential Diagnoses Celiac Disease Inflammatory Bowel Disease Colon cancer Lactose Intolerance Acute or chronic diarrhea due to protozoa or bacteria Small intestinal bacterial overgrowth (SIBO) Diverticulitis Endometriosis Pelvic Inflammatory Disease Ovarian Cancer Proposed factors to explain the relationship with food and IBS symptoms: hypersensitivity Luminal distention Cognitive factors such as anticipating symptoms due to previous experience IBS pts. relate their symptoms to a specific type of meal 63% know what to avoid Benefits of limiting specific food products varies among individual pts. 4

Lipids/Fatty s Avoidance especially useful for those with gas related symptoms and diarrhea Limited

Caffeine Stimulates gastric acid secretion and colonic motor activity May be worse for IBS with

mucosal damage, studies inconclusive Drinking > 4 alcoholic drinks on 1 occasion associated with

5 Lipids/Fatty s Avoidance especially useful for those with gas related symptoms and diarrhea Limited evidence related to dietary fat intake and IBS IBS symptom severity is associated with increased BMI Caffeine Stimulates gastric acid secretion and colonic motor activity May be worse for IBS with diarrhea Monitor soft drinks, coffee, dark chocolate, cocoa and OTC analgesics Alcohol May lead to mucosal damage, studies inconclusive Drinking > 4 alcoholic drinks on 1 occasion associated with diarrhea and abdominal pain among females with IBS Consider patients may misuse alcohol for stress reduction for IBS symptoms 5

Definition Fermentation: Process in which a microorganism transforms food into other products, usually through the production of lactic acid, ethanol, and other metabolic end products.

6 Definition Fermentation: Process in which a microorganism transforms food into other products, usually through the production of lactic acid, ethanol, and other metabolic end products. Fiber IBS constipation; consider soluble fibers, particularly with slow fermentability which help to avoid increased gas and cramping psyllium (Metamucil) IBS diarrhea or IBS mixed symptoms; stool consistency improved with soluble viscous fiber with limited fermentability methylcellulose (Citrucel) calcium polycarbophil (Fibercon) psyllium (Metamucil) Soluble Fiber Rich s Grains: oat & barley Nuts Seeds: flaxseed, sunflower, chia Beans: legumes Vegetables: carrots Fruits: oranges, grapefruits 6

Additives No studies investigated Intolerance/hypersensitivity to additives in processed foods Preservatives Emulsifiers Artificial flavorings/colors Low Gluten Diet Gluten is a general name for the

7 Additives No studies investigated Intolerance/hypersensitivity to additives in processed foods Preservatives Emulsifiers Artificial flavorings/colors Low Gluten Diet Gluten is a general name for the proteins found in wheat (wheatberries, durum, emmer, semolina, spelt, farina, farro, graham, rye, barley and triticale a cross between wheat and rye. Gluten helps foods maintain their shape, acting as a glue that holds food together. Non celiac wheat sensitivity Patients avoiding gluten should be aware of nutritional deficiencies Processed gluten free products are not always healthy! Low Fructose Diet Fructose is a monosaccharide found naturally in small amounts in fruits & vegetables Larger quantities found in manufactured sweets with added sugars Fructose malabsorption leads to osmotic diarrhea, gas and bloating due to fermentation Several studies found an improvement in IBS D symptoms in those who followed a low fructose diet Choose whole foods Avoid highly processed foods (soda) and industrially processed products full of fructose Fruits with a higher fructose vs glucose concentration: include star fruit, pear, papaya, mango, guava, honeydew, watermelon and apples. 7

8 Fermentable Oligosaccharides Disaccharides Monosaccharides And Polyols Low FODMAP Diet Low FODMAP Diet FODMAPS are osmotically active; not easily absorbed; and stimulate fermentation in the colon, luminal gas production and distention. Best initiated with a dietician Restrictive phase should be followed no longer than 6 weeks Long term goal is to reintroduce high FODMAP foods to personal tolerance RCT s suggest that a low FODMAP diet should be a first line therapy for IBS FODMAPS are prebiotic long term may have a negative impact on intestinal microbiome Oligosaccharides Fructans and Galacto oligosaccharide (GOS) No human enzyme capable of breaking down mal absorbed in everyone Highly fermentable Significant contributor to bloating, abdominal pain and excessive flatus Naturally found in wheat and rye products, legumes, nuts, artichokes, onion and garlic. 8

9 Disaccharide Lactose Sugar found in milk products that requires lactase to break it down for absorption Reduced in some ethic backgrounds, i.e. Asian, Mediterranean Many individuals do not have to restrict lactose as part of a low FODMAP diet; have adequate lactase production Monosaccharide Fructose Single sugar found in apples, pears, watermelon, mango, honey, sugar snap peas Used a commercial sweetener as fructose or high fructose corn syrup Slowly absorbed causes osmotic effect Polyols Most common; Mannitol, Sorbitol, Xylitol, Isomalt, Found in apples, pears, cauliflower, mushrooms, snow peas, sugar free gum & mints Likely to produce an osmotic effect regardless of whether absorption is complete or not 9

10 Low FODMAP Diet What can I eat? Green beans, bell peppers, carrots, celery, eggplant, zucchini, tomatoes, lettuce, kale, bok choy, bean sprouts, spinach, squash, turnips Banana, blueberries, cantaloupe, oranges, strawberries, grapes, kiwi, raspberries Lactose free milk, yogurt & hard cheese Meats, fish, chicken, eggs, tofu Gluten free bread & pasta, oats, rice, quinoa Almonds, hazelnuts, walnuts, peanuts, pine nuts, pecans, macadamia & pumpkin Jelly, marmalade, butter, mustard, mayonnaise, olives, cocoa powder, vinegar, soy sauce, cooking oils Low FODMAP Diet tro/fodmap/docs/user guide.pdf Probiotics definitions Prebiotic: Selectively fermented ingredients that result in specific changes in the composition and/or activity of the GI microbiota, providing benefit to the host health Probiotics: Live microorganisms that offer a health benefit to the host when administered in adequate amounts Synbiotics: Products that contain probiotics and prebiotics Fermentation: Process in which a microorganism transforms food into other products, usually through the production of lactic acid, ethanol, and other metabolic end products. 10

11 Probiotics Minimal criteria Should be specified by genus and strain nomenclature current with scientifically recognized names Strain designation Viable counts of each strain at the end of shelf life Recommend storage conditions Safe for intended use Accurate description of the physiological effect as allowed by law Post market surveillance contact information Quality of the probiotic depends on the manufacturer Most not made to pharmaceutical standards therefore, regulatory authorities may not oversee to quality standards Probiotics Specific probiotics will have different effects in different patients A probiotic that doesn t work in one indication, may have evidence of a beneficial effect for a different indication Must be taken in adequate dosage on a regular basis Should be taken for at least one month just before a meal Factors that determine the response to treatment may include: Probiotic strain Dose and concomitant medications Probiotics Available as dairy products Probiotic fortified foods Tablets Capsules Sachets containing bacteria in freeze dried form 11

12 Strain Lactobacilli Casei 19 Plantarum 299V Acidophilus NCFM, LA 5 Reuteri DSM Bifidobacteria Infantis Animalis DN Enterococcus LAB SF 68 Escerichia coli Nissle 1917 Mixture One strain of Streptococcus thermophilis, four Lactobacillis spp., & three Bifidobacterium spp. Strains Cultura Goodbelly, Proviva L.reuteri Protectis Align Activia Bioflorin Mutaflor VSL #3 Brand Name Probiotics Systematic Review evaluated 37 studies on the role of specified probiotics in managing particular lower GI symptoms/problems 32 different probiotics were investigated at doses of 1 x 10 (6) 4.5 x 10 (11)CFU given once, twice or three times daily Adults only included in the study Most of the studies focused on IBS Included all IBS subtypes: 2 studies IBS C; 3 studies IBS D Abdominal pain Bloating/distention Flatus Constipation Bowel habit/consistency of bowel movements Diarrhea Health related quality of life Probiotic Study Level of Evidence Symptom Probiotic Brand Name High Overall symptoms of IBS B. infantis Bifido bifdum MIMBb75 E. coli DSM Align Kijimea Symbioflor 2 Low Overall symptoms burden of IBS C B. lactis DN 173 Activia Moderate Overall symptoms burden of IBS D B. infantis strains of LAB sachet High Decreasing abdominal pain Bacillus coagulans GBI 30, 6086 B. infantis E. coli DSM B. lactis DN 173 Moderate Decreasing bloating/distention B. lactis DN 173 E. coli DSM B. infantis Moderate Help improve frequency &/or consistency of BM B. animalalis susp. Lactis Bb 12 B. lactis DN 173 B. infantis B. lactis DR 10 E. coli DSM Align Duolac 7 Digestive Advantage Gas form. Align Symbioflor 2 Activia Activia Symbioflor 2 Align Yosa Activia Align HOWARU/DR 10 Symbioflor 2 12

13 Slide 36 LL1 Lenore Lamanna, 3/19/2017

14 : Medications Overall symptoms of IBS Antispasmodics Dicyclomine (Bentyl) Hyoscyamine Anaspaz Levsin Levsin SL Levbid Extended release Used for decades Based on the assumption that gut, especially colonic smooth muscle spasm contributes to IBS symptoms Studies suggest using antispasmodics in pts with IBS 22 RCT s significant improvement in global symptoms modest improvement in abdominal pain Based on continuous use not as needed use Overall quality of evidence low due to lack of heterogeneity, methodological limitations and publication bias : Medications Overall symptoms of IBS Selective Serotonin Reuptake Inhibitors (SSRIs) Studies recommend against using SSRI s (low quality of evidence) 5 RCT s for 6 12 weeks showed no improvement in global symptoms paroxetine (Paxil) citalopram (Celexa) fluoxetine (Prozac) : Medications Overall Symptoms of IBS Tricyclic Antidepressants (TCAs) Studies suggest using TCA s (over no drug treatment) Low quality of evidence Multiple RCT s 6 12 weeks modest improvement in global relief Use with caution in pts at risk for prolongation of the QT interval amitriptyline (Elavil) desipramine (Norpramin) nortriptyline (Pamelor) 13

15 : Medications IBS Diarrhea Antibiotic rifaximin (Xifaxan) Studies suggest using rifaximin (over no drug treatment) Moderate quality evidence Evidence suggests that gut flora plays an important role in the pathophysiology of IBS manipulation of gut microbiome TARGET 1,2,3 trials 2 week treatment provided significant improvement of bloating, abdominal pain and loose, watery stools Recommend dosage is 550 mg orally three times a day for 14 days Can be retreated up to two times for recurrence of symptoms : Medications IBS Diarrhea Mu Opioid Receptor Agonist eluxadoline (Viberzi) Slows motility, decreases visceral sensation and inhibits secretion; possibly also reduces excessive slowing of motility recommended dosage is 100 mg twice daily with food Symptoms of pancreatitis reported after 1 2 doses of 75 mg in pts without a gallbladder (originally recommended dose for those without a gallbladder) Do not administer to the following patients: Patients without a gallbladder Have or may have had a blockage of the gallbladder or sphincter of Oddi History of pancreatitis or other problems of the pancreas History of severe hepatic impairment History of severe or chronic constipation Have or may have had intestinal obstruction History of alcohol abuse, addiction or drinks more than 3 alcoholic beverages a day : Medications IBS Diarrhea 5 HT Modulators alosetron (Lotronex) Effective in females with IBS D (Quality of evidence moderate) Decreases painful sensations from the gut and slows intestinal transit Was withdrawn from the market by the FDA for instances of severe constipation and ischemic colitis Reintroduced by the FDA in a restricted manner in 2010 for women with disabling IBS D Prescribed only in the context of a carefully risk management program 14

16 ACG /22/2017 Medications IBS Constipation Chloride Channel Activator lubiprostone (Amitiza) Superior to placebo for treatment of IBS C (moderate quality of evidence) Causes chloride and water flux into the intestinal lumen resulting in faster transit through the small and large intestine Nausea, diarrhea can occur Medications IBS Constipation Guanylate Cyclase C Receptor Agonist linaclotide (Linzess) Superior to placebo for the treatment of IBS C (Quality of evidence high) Causes secretion of bicarbonate and chloride into the intestinal lumen followed by sodium and water; also acts as a modulator of pain afferent sensors Flatulence, diarrhea can occur Other Treatments IBS Constipation Fiber Fiber provides overall symptom relief in IBS (quality of evidence Moderate) Soluble fiber (psyllium) (quality of evidence Moderate) Give 10 grams of soluble fiber once daily polyethylene glycol (PEG) (Miralax) Large polymer that acts as an osmotic laxative No evidence PEG improves overall symptoms and pain in IBS (quality of evidence very low) One RCT showed an improvement in spontaneous bowel movements (more than four movements per week with an increase of two or more over baseline) but no improvement with pain response 15

17 Other Treatments IBS Diarrhea loperamide (Imodium) Studies suggest using (over no drug treatments) in pts with IBS D (very low quality of evidence data very limited Large body of indirect evidence shows efficacy of loperamide in decreasing stool frequency Low cost, wide availability and minimal adverse effects useful adjunct to other therapies Other Treatments IBS Diarrhea peppermint oil Pepogest Ibgard Superior to placebo in improving IBS symptoms (quality of evidencemoderate) RCT s enteric coated preparation used in doses from mg TID In specific formulations, peppermint oil is effective in IBS Nonpharmacological therapies Let patients tell their story Identify and listen to patient s concerns Discuss patient anxieties as they relate to their symptoms and possible diagnosis Appreciate the patient s symptoms Help to reduce their stress discuss methods of stress reduction 16

Nonpharmacological Treatments Psychological Counseling Variety of psychological interventions effective in improving IBS symptoms (quality of evidence very low) Nonpharmacological Treatments Limited

18 Nonpharmacological Treatments Psychological Counseling Variety of psychological interventions effective in improving IBS symptoms (quality of evidence very low) Nonpharmacological Treatments Limited availability of skilled therapists experienced with managing IBS limits their use RCT s evaluated 10 different psychological therapies Benefits demonstrated for: Cognitive behavioral therapy Hypnotherapy Multi component psychological therapy Multi component psychological therapy via telephone Dynamic psychotherapy Nonpharmacological Treatments No significant effects: Relaxation therapy Self administered cognitive behavioral therapy Behavioral therapy via the internet Stress management Mindfulness meditation training 17

19 Nonpharmacological Treatments Biofeedback anorectal Retraining technique for dyssynergic defecation Physiological activity of the anus and rectum is monitored Results are shown to patient who is then trained to correct undesired patterns Systematic Review Biofeedback compared to laxatives, diazepam or standard management is superior in improving constipation symptoms Abdominal pain one study found benefits over laxatives No studies done on abdominal distention Thank you! Questions?? 18

Irritable Bowel Syndrome Now. George M. Logan, MD Friday, May 5, :35 4:05 PM

Irritable Bowel Syndrome Now. George M. Logan, MD Friday, May 5, :35 4:05 PM Irritable Bowel Syndrome Now George M. Logan, MD Friday, May 5, 2017 3:35 4:05 PM Dr. Logan indicated no potential conflict of interest to this presentation. He does not intend to discuss any unapproved/investigative