1. Dr. Shandis Price April 21, 2012 Annual Scientific Assembly

2. Objectives To review diagnosis and pathophysiology of IBS To review diet and IBS To become aware of botanicals that may be useful in the management of IBS To review probiotics, acupuncture and mind-body treatments for IBS

3. IBS - definition A syndrome characterized by chronic abdominal pain and altered bowel habits without an organic cause Most common GI disorder More common in women and younger patients Abdominal pain usually crampy Often worse after eating and with emotional stress Often better with defecation

4. Diagnosis Rome III criteria (revised 2005) Recurrent abdominal pain or discomfort at least 3 days per month in the past 3 months onset at least 6 months prior to diagnosis associated with 2 or more of the following: improvement of pain with defecation Onset of pain associated with a change in frequency of stool Onset of pain associated with a change in the form (appearance) of stool

5. Diagnosis (contd) Supportive Sx (not part of Rome criteria) Abnormal stool frequency 3 BMs per day Abnormal stool form lumpy/hard, loose/watery Defecation straining Urgency Feeling of incomplete emptying Passing mucus up to 50% pts with IBS describe passing mucus Bloating

6. Diagnosis (contd) Subtypes of IBS Diarrhea predominant IBS Hard/lumpy stools < 25% Loose/watery stools >25% Constipation predominant IBS Loose/watery stools <25% Hard/lumpy stools >5% Mixed IBS Hard/lumpy stools >25% Loose/watery stools >25%

7. Diagnosis (contd) Alarm symptoms Rectal bleeding Nocturnal or progressive abdominal pain Weight loss Abnormal labs Age >50 FHx colon CA / IBD Should get further investigations / colonoscopy

8. Investigations Labs – CBC, lytes – should all be normal Celiac screen Meta-analysis (Ford, Archive Int Med, 2009) Celiac disease 4x more common in patients with IBS than in controls Should check celiac screen on all patients with IBS Stool cultures if diarrhea predominant IBS r/o Giardia

9. Pathophysiology Visceral hypersensitivity more sensitive to visceral stimuli Abnormal gut motility Increased/decreased gut transit time Increased motility to various stimuli compared to controls Psychosocial factors Brain-Gut interaction / neuroendocrine dysfunction Latent or potential Celiac disease Infection and inflammation Post-infectious IBS, altered gut flora

10. Pharmacologic treatments Antidepressants TCAs and SSRIs Antispasmodic agents Eg. Pinaverium – Dicetel Loperamide – (Immodium) Selective serotonin (5-HT4, 5-HT3)reuptake inhibitors Eg. alosetron, tegaserod Ischemic colitis, CV events Non-absorbable antibiotics (rifaximin)

11. Overall low patient satisfaction with pharmacologic treatments 50% of patients with IBS turn to CAM therapies

12. Diet and IBS Lactose (dairy) Lactose intolerance is common Can aggravate IBS or cause Sx that are similar to IBS Trial of 3 weeks dairy-free diet for all patients with IBS

13. Diet and IBS Gluten sensitivity (without overt celiac disease) Latent or potential celiac disease non-celiac gluten intolerance Biesiekierski et al., Am J Gastroenterol. 2011 Double-blind randomized placebo-controlled trial of 34 patients with IBS controlled on gluten-free diet Re-introduction of gluten for 6 weeks significantly worsened Sx Consider trial of gluten-free diet

14. Diet and IBS Exclusion of gas-producing foods Underlying visceral hyperalgesia Exclusion of foods that increase gas production: beans, cruciferous vegetables (broccoli, cauliflower, cabbage), celery, carrots, raisins, bananas, prunes

15. Diet and IBS Carbohydrate malabsorption – FODMAPs Fermentable Oligosaccharides Disaccharides Monosaccharides And Polyols May lead to Sx of IBS, increased intestinal permeability and possibly inflammation

16. Oligosaccharides Fructans (wheat, onions, artichokes) Galactans (legumes, cabbage, and brussel sprouts) Disaccharides Lactose (dairy) Monosaccharides Fructose (honey, watermelon, high fructose corn syrup) Polyols (sugar alcohols) Sorbitol (chewing gum) Xylitol Mannitol Some studies restricting FODMAPs have suggested benefit Consider trial of low FODMAPs diet

17. Diet and IBS Food allergies Role is unclear No reliable method of testing for food allergies

18. Diet and IBS (contd) Elimination diets Empiric trial to systematically remove certain food allergens/sensitivities Sinister 7 Cows milk, wheat, soy, corn, yeast, refined sugar, eggs Can remove all 7 from diet x 14 days then systematically re-introduce every 72 hrs Or remove one at a time and then reintroduce

19. Botanicals and IBS Several botanicals have been studied Results limited by often small sample sizes and substantial placebo response

20. Peppermint Oil Anti-spasmodic – helps with cramping Slows gut motility / transit time Mechanism of action – smooth muscle relaxation via Ca- channel blockade Useful for diarrhea- predominent IBS

21. Peppermint Oil Meta-analysis (Ford, BMJ, 2008) Peppermint oil effective in symptom relief in patients with IBS NNT=2.5 for benefit with peppermint oil 2009 American College of Gastroenterology recommendations for the treatment of IBS Peppermint oil recommended for short-term relief of abdominal pain/discomfort in IBS

22. Peppermint Oil (contd) Dose: enteric coated peppermint oil capsules 0.2mL tid S/Es: anal burning and heartburn Take peppermint oil capsules with food Worthwhile to try first in diarrhea predominant IBS

23. Botanicals – Carminatives Spices and herbs traditionally used for bloating and gas 64% of patients with IBS complain of bloating Also have other properties / secondary benefits eg. antimicrobial properties, anxiolytic properties

24. Carminatives – secondary benefits Basil – anti-inflammatory Caraway - slows GI transit time Peppermint - slows GI transit time Ginger – pro-kinetic, anti-emetic Cinnamon – insulin resistance Thyme - coughs, colds Dill – lactagogue Sage - hot flashes/sweating

25. Ginger Prokinetic and anti- emetic Useful in IBS – constipation dominant Useful for gas and bloating (carminative) Also used as an anti- inflammatory (being studied for arthritis)

26. Ginger (contd) Dose: dried powdered ginger 500mg dried ginger root – 1 tab tid before meals safe in pregnancy NOT concentrated extracts of ginger Extracts used as anti-inflammatory Can cause heartburn and GI distress at high doses and safety not confirmed in pregnancy

27. Iberogast (STW 5) Blend of 9 herbs / plant extracts Candytuft Chamomile Peppermint Caraway Licorice root Lemon balm Celandine Milk thistle Angelica Study (Madisch, 2004) – double-blind placebo RC T Showed effective in relieving IBS symptoms

28. Fiber Commonly recommended May exacerbate symptoms in some patients Fiber supplements (eg. psyllium) may be beneficial for constipation predominant IBS Main side effect is bloating and gas Take with lots of water, titrate slowly

29. Probiotics Living organisms that, upon digestion in certain numbers, exert health benefits beyond those of basic nutrition Some commonly studied probiotics Lactobacillus Bifidobacterium Saccharomyces boulardii

30. Probiotics (contd) May be a role of altered gut flora in the pathogenesis of IBS Probiotics help balance the gut flora McFarland, 2008 Meta-analysis of 23 studies showed improvement of global IBS symptoms and abdominal pain warrents further study TuZen Lactobacillus plantarum 299v

31. Acupuncture and IBS Manheimer et al., April 2012, (Am J of Gastroenterology) Systematic review and meta-analysis of Acupuncture and IBS 17 RCTs (N=1806) Acupuncture vs. sham acupuncture (5 trials) – no difference Acupuncture more effective than pharmacologic therapy (5 trials) Acupuncture equal effectiveness to bifidobacterium (2 trials) or psycotherapy (1 trial) Addition of acupuncture to standard medical care more effective than standard medical care alone (2 trials)

32. Acupuncture (contd)

33. Mind-body and IBS Dysregulation of the brain-gut axis Visceral hypersensitivity Stress plays a role in onset and ongoing IBS symptoms Mind-body approaches have been investigated in management of IBS Sx Meditation, relaxation, hypnotherapy, CBT

34. Mind-body (contd) Yoga and relaxation Useful to recommend in patients with IBS, especially if they are stressed 2 studies show benefit of yoga on IBS Sx (Kuttner 2006, Taneja 2006) CBT Shown to be effective in IBS (Drossman, 2003)

35. Mind-Body (contd) Hypnotherapy Multiple studies have shown benefit in IBS an intentional induction of the hypnotic state that is achieved by various methods including deep relaxation, mental imagery or more subtle indirect techniques Good evidence to show that hypnotherapy is effective for treatment of IBS and has long term benefits (Gonsalkorale 2002, 2003)

36. 2009 American College of Gastroenterology recommendations for the treatment of IBS Psychological therapies, including cognitive therapy, dynamic psycotherapy and hypnotherapy more effective than usual care in relieving global symptoms of IBS

37. Mind-body (contd) Placebo effect and IBS Kaptchuk et al 2010 Placebos without deception: A Randomized Controlled Trial in Irritable Bowel Syndrome - 70 patients with IBS, 3 wk RCT "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes vs. no- treatment controls with the same quality of interaction with providers Statistically significant improvement in global improvement scores, reduced symptom severity and adequate relief scores Placebos administered without deception may be an effective treatment for IBS

38. Exercise Increased physical activity may help with symptoms of IBS RCT (Johannesson, 2011)showed improved GI symptoms in patients with IBS 20-60min moderate to vigorous activity 3-5x/week Should be recommended to all patients with IBS good for general health as well

39. Summary Rule out celiac disease Trial no dairy x 3 weeks Trial gluten-free diet x 3 weeks Can try elimination diet or low FODMAPs diet if motivated Trial of peppermint oil if diarrhea-dominant or mixed Trial of probiotics Trial of acupuncture Recommend exercise to all patients Recommend trial of yoga, CBT, hypnotherapy

40. References Borrelli et al., Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomitting. Obstet Gynecol. 2005 Apr; 105(4): 849-56. Drossman et al., Cognitive-behavioral therapy versus education and desipramine vs. placebo for moderate to severe functional bowel disorder. Gastroenterology. 2003 Jul;125(1):19-31. Johannesson et al., Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011 May; 106(5):915-22. Kaptchuk et al., Placebos without deception: A Randomized controlled trial in Irritable Bowel Syndrome., PLoS One 2010 Dec 22;5(12) Kuttner et al., A randomized trial of yoga for adolescents with irritable bowel syndrome. Pain Res Manag. 2006 Winter;11(4):217-23 Manheimer et al., Acupuncture for Irritable Bowel Syndrome: Systematic Review and Meta-Analysis. Am J of Gastroenterology, 10 April 2012 Masdisch et al,. Treatment of Irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial. Ailment Pharmacol Ther., 2004 Feb 1; 19(3):271-9. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol 2008; 14(17):2650- 61. Ford et al., Effect of Fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta- analysis. BMJ. 2008 Nov 13; 337:a2313 Ford et al., Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis. Arch Intern Med. 2009;169(7):651. Gonsalkorale et al. Hypnotherapy in irritable bowel syndrome: a large-scale audit of a clinical service with examination of factors influencing responsiveness. Am J Gastroenterol. 2002 Apr;97(4):954-61. Gonsalkorale et al. Long term benefits of hypnotherapy for irritable bowel syndrome. Gut. 2003 Nov;52(11): 1623-9. Manheimer et al., Acupuncture for Irritable Bowel Syndrome: Systematic Review and Meta-Analysis. American Journal of Gastroenterology, 10 April 2012 Ryan et al., Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer. 2011 Aug 5. aneja et al., Yogic versus conventional treatment in diarrhea-predominant irritable bowel syndrome: a randomized control study. Appl Psychophysiol Biofeedback. 2004 Mar;29(1):19-33. Wu et al., Effects of ginger on gastric emptying and motility in healthy humans. Eur J Gastroenterol Hepatol. 2008 May; 20(5):436-40. University of Arizona Integrative Medicine Fellowship – Integrative Gastroenterology - Irritable Bowel Syndrome. Up To Date

41. Comments/Questions?