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Diet, Nutrition and Inflammatory Bowel Disease Jason K. Hou, MD Baylor College of Medicine Houston, TX.

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Presentation on theme: "Diet, Nutrition and Inflammatory Bowel Disease Jason K. Hou, MD Baylor College of Medicine Houston, TX."— Presentation transcript:

1 Diet, Nutrition and Inflammatory Bowel Disease Jason K. Hou, MD Baylor College of Medicine Houston, TX

2 Disclosures None None

3 Objectives At the conclusion of the conference, participant should be able to: At the conclusion of the conference, participant should be able to: 1) Describe the possible role of diet in the development of IBD 1) Describe the possible role of diet in the development of IBD 2) Identify the importance of nutritional deficiencies in IBD 2) Identify the importance of nutritional deficiencies in IBD 3) Describe the potential use of diet as therapy for IBD 3) Describe the potential use of diet as therapy for IBD

4 So doc, what can I eat? Intellectual divide Intellectual divide Physicians focus on nutritional deficiencies Physicians focus on nutritional deficiencies Patients interested in diet as cause or cure of symptoms Patients interested in diet as cause or cure of symptoms

5 Malnutrition- then and now 20-85% of IBD patients with protein-energy malnutrition 20-85% of IBD patients with protein-energy malnutrition Hospital based studies (1970s) Hospital based studies (1970s) Most prevalent nutritional abnormality Most prevalent nutritional abnormality = excess body weight (2007) Sousa Guerreiro et al. Am J Gastroenterol. 2007 Nov;102(11):2551-6

6 Got milk? Food avoidance Food avoidance 65% of IBD patients report food avoidance 65% of IBD patients report food avoidance 28% of IBD patients on dairy-free diet 28% of IBD patients on dairy-free diet Lactose intolerance no more common or even less common in UC than non-IBD controls. Lactose intolerance no more common or even less common in UC than non-IBD controls. Gerasimidis et al. Aliment Pharmacol Ther. 2008 Jan 15;27(2):155-65 Bernstein et al. Am J Gastroenterol. 1994 Jun;89(6):872-7

7 Hypothesis Diet patterns may play a role in the pathogenesis/risk of development of IBD Diet patterns may play a role in the pathogenesis/risk of development of IBD Diet modification/supplementation may be a method of treatment of IBD Diet modification/supplementation may be a method of treatment of IBD

8 Diet as Etiology

9 Incidence of IBD is increasing Hou et al. Am J Gastroenterol. 2009 Aug;104(8):2100-9

10 Dietary fats Omega 3-fatty acids Omega 3-fatty acids Docosahexonenoic acid (DHA) Docosahexonenoic acid (DHA) Eicosapentaenoic acid (EPA) Eicosapentaenoic acid (EPA) Docosepentaenoic acid (DPA) Docosepentaenoic acid (DPA) Omega 6-fatty acids Omega 6-fatty acids Linoleic acid Linoleic acid

11 Dietary fats Hou et al. Therapy, Mar 2010, 7(2), 179-189

12 Dietary fats Food frequency questionnaire in newly diagnosed pediatric CD patients (130 patients) Food frequency questionnaire in newly diagnosed pediatric CD patients (130 patients) Dose dependent protective effect of omega-3 FA (EPA, DPA, DHA) for CD Dose dependent protective effect of omega-3 FA (EPA, DPA, DHA) for CD OR 0.44 (95% CI 0.19-1.00) OR 0.44 (95% CI 0.19-1.00) Ratio of omega-3 PUFA/ omega-6 PUFA Ratio of omega-3 PUFA/ omega-6 PUFA OR 0.32 (95% CI 0.14-0.71) OR 0.32 (95% CI 0.14-0.71) Amre et al. Am J Gastroenterol. 2007 Sep;102(9):2016-25

13 Dietary fats Vegetable, fruit, nut, fish, dietary fiber intake protective in dose dependent manner Vegetable, fruit, nut, fish, dietary fiber intake protective in dose dependent manner Western diet Western diet meat, fried food, fast food, snacks, dessert meat, fried food, fast food, snacks, dessert positive associated in development of CD in girls [OR 4.7 (95% CI 1.6-14.2)] positive associated in development of CD in girls [OR 4.7 (95% CI 1.6-14.2)] D'Souza et al. Inflamm Bowel Dis. 2008 Mar;14(3):367-73

14 EPIC Prospective cohort study 203,193 persons Prospective cohort study 203,193 persons Case control of 126 incident cases of UC Case control of 126 incident cases of UC Linoleic acid positively associated with development of UC in a dose dependent manner Linoleic acid positively associated with development of UC in a dose dependent manner OR 2.49 (95% CI 1.23-5.07 in highest quartile) OR 2.49 (95% CI 1.23-5.07 in highest quartile) Dose dependent protective effect of DHA for UC Dose dependent protective effect of DHA for UC OR 0.23 (95% CI 0.06-0.97) OR 0.23 (95% CI 0.06-0.97) Hart et al. Gut. 2009 Jul 23

15 EPIC-UK UK subset of EPIC UK subset of EPIC 25, 639 persons 25, 639 persons Ages 40-74 Ages 40-74 22 incident UC (median f/u 3.9 years) 22 incident UC (median f/u 3.9 years) The highest tertile of dietary oleic acid protective for UC (OR 0.11 (95% CI=0.01-0.87) The highest tertile of dietary oleic acid protective for UC (OR 0.11 (95% CI=0.01-0.87) De Silva et al. Abstract DDW 2010

16 EPIC-E3N Prospective diet survey of 67, 581 French women (disease free) Prospective diet survey of 67, 581 French women (disease free) Ages 40-65 at enrollment Ages 40-65 at enrollment Mean follow up 10.5 years Mean follow up 10.5 years 77 incident IBD cases 77 incident IBD cases Animal protein, was associated with increased risk of IBD, HR third and first tertile 3.03 and 1.45-6.34 (P trend=0.005) Animal protein, was associated with increased risk of IBD, HR third and first tertile 3.03 and 1.45-6.34 (P trend=0.005) Jantchou et a. Am J Gastroenterol. Epub 2010 May 11

17 Carbohydrates FODMAPs FODMAPs Fermentable Fermentable Oligo- Oligo- Di- Di- Mono-saccharides Mono-saccharides And And Polyols Polyols

18 FODMAPs May increase bacterial overgrowth in distal small bowel May increase bacterial overgrowth in distal small bowel Increase intestinal permeability Increase intestinal permeability Trigger CD in susceptible host Trigger CD in susceptible host No data Gibson et al. Aliment Pharmacol Ther. 2005 Jun 15;21(12):1399-409

19 Microparticles Titanium Titanium Aluminum Aluminum Silicon Silicon Observed to accumulate in Peyers patches Observed to accumulate in Peyers patches Possible activation of inflammatory response Possible activation of inflammatory response No benefit of low microparticle diet on multicenter RCT (CD) No benefit of low microparticle diet on multicenter RCT (CD) Lomer et al. Eur J Gastroenterol Hepatol. 2005 Mar;17(3):377-84

20 Nutritional Deficiencies

21 Nutritional deficiencies CD CD 32% overweight 32% overweight 8% obese 8% obese 2.6% underweight 2.6% underweight 5.3 % considered malnourished by SGA 5.3 % considered malnourished by SGA Sousa Guerreiro et al. Am J Gastroenterol. 2007 Nov;102(11):2551-6

22 Nutritional deficiencies Food avoidance 29% excluded grains 28% excluded milk 18% excluded vegetables 11% excluded fruits Sousa Guerreiro et al. Am J Gastroenterol. 2007 Nov;102(11):2551-6

23 Nutritional deficiencies Percentage of patients who reached daily recommended intake Percentage of patients who reached daily recommended intake Sousa Guerreiro et al. Am J Gastroenterol. 2007 Nov;102(11):2551-6

24 Calcium and Vitamin D 21-40% increased risk of fractures 21-40% increased risk of fractures Increased risk even after adjusting for steroid use Increased risk even after adjusting for steroid use Management Management Bisphosphonate Bisphosphonate Bernstein et al. Gastroenterology. 2003 Mar;124(3):795-841 Siffledeen et al. Clin Gastroenterol Hepatol. 2005 Feb;3(2):122-32 von Tirpitz et al. Eur J Gastroenterol Hepatol. 2000 Jan;12(1):19-24

25 AGA guidelines (2003) Who to Screen Who to Screen > 3 months steroids > 3 months steroids Low trauma fracture Low trauma fracture Postmenopausal female Postmenopausal female Male > 50 Male > 50 Hypogonadism Hypogonadism Management DEXA T score < -2.5 OR history of compression fracture Bisphosphonate -2.5 { "@context": "http://schema.org", "@type": "ImageObject", "contentUrl": "http://images.slideplayer.com/6/1623262/slides/slide_25.jpg", "name": "AGA guidelines (2003) Who to Screen Who to Screen > 3 months steroids > 3 months steroids Low trauma fracture Low trauma fracture Postmenopausal female Postmenopausal female Male > 50 Male > 50 Hypogonadism Hypogonadism Management DEXA T score < -2.5 OR history of compression fracture Bisphosphonate -2.5

26 Folate/B12 Decreased intestinal transport- sulfasalazine Decreased intestinal transport- sulfasalazine Deficiency may result in hyperhomocystinemia Deficiency may result in hyperhomocystinemia Hypercoagulable state Hypercoagulable state Folate supplementation- possible protective against colorectal cancer/dysplasia Folate supplementation- possible protective against colorectal cancer/dysplasia Lashner et al. Gastroenterology. 1989 Aug;97(2):255-9 Lashner et al. Gastroenterology. 1997 Jan;112(1):29-32

27 Micronutrients Zinc Zinc wound healing wound healing Selenium Selenium possible anti-inflammatory and anti-neoplastic properties possible anti-inflammatory and anti-neoplastic properties Antioxident vitamins Antioxident vitamins

28 Diet as Therapy

29 Possible pathways Remove toxin/antigenic stimulus (elemental diet) Remove toxin/antigenic stimulus (elemental diet) Alter bacteria flora (prebiotic) Alter bacteria flora (prebiotic) Alter intestinal fluid transport/gas production Alter intestinal fluid transport/gas production

30 Enteral therapy Elemental and non-elemental diet Elemental and non-elemental diet No differences in efficacy No differences in efficacy Limitations Limitations Palatability Palatability May require nasogastric feeding May require nasogastric feeding

31 Enteral Therapy- Cochrane review (2007) Induction of remission: 20-84% Induction of remission: 20-84% Beneficial but inferior to corticosteroids Beneficial but inferior to corticosteroids Open label RCT Open label RCT 37 pediatric new diagnosed CD 37 pediatric new diagnosed CD Remission (10 wk) Remission (10 wk) ET: 79%; 95% confidence interval (CI), 56%-92% ET: 79%; 95% confidence interval (CI), 56%-92% Steroid 67%; 95% CI, 44%-84% P =.4 Steroid 67%; 95% CI, 44%-84% P =.4 Endoscopic healing seen only in ET group Endoscopic healing seen only in ET group Zachos et al. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000542 Borrelli et al. Clin Gastroenterol Hepatol. 2006 Jun;4(6):744-53

32 Nutritional supplements Omega-3- PUFA (Fish oil) and CD Omega-3- PUFA (Fish oil) and CD EPIC-1 (quiescent disease) EPIC-1 (quiescent disease) EPIC-2 (flare, remission induction by steroids) EPIC-2 (flare, remission induction by steroids) 4 grams daily 4 grams daily Control- MCT Control- MCT Feagan et al. JAMA. 2008 Apr 9;299(14):1690-7

33 Nutritional supplements Omega-3- PUFA Omega-3- PUFA EPIC-1 EPIC-1 At 1 year 31.6 % vs. 35.7% relapse At 1 year 31.6 % vs. 35.7% relapse HR 0.82, 95% CI 0.57- 1.19 HR 0.82, 95% CI 0.57- 1.19 EPIC-2 EPIC-2 At 1 year 47.8% vs. 48.8% relapse At 1 year 47.8% vs. 48.8% relapse HR 0.90, 95% CI 0.67- 1.21 HR 0.90, 95% CI 0.67- 1.21 Feagan et al. JAMA. 2008 Apr 9;299(14):1690-7

34 Nutritional supplements Omega-3- PUFA Omega-3- PUFA Cochrane review (2009) Cochrane review (2009) Small pooled benefit Small pooled benefit RR 0.77, 95% CI 0.61-0.98 RR 0.77, 95% CI 0.61-0.98 Authors conclude likely no benefit based on EPIC Authors conclude likely no benefit based on EPIC Turner et al. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006320

35 Nutritional supplements Fiber and UC Fiber and UC Converted to short chain fatty acids (SCFA) Converted to short chain fatty acids (SCFA) Energy source for colonocytes Energy source for colonocytes Modulate local immune response Modulate local immune response (attenuate IL-6, IL-8, TNF-α, leukocyte adhesion) (attenuate IL-6, IL-8, TNF-α, leukocyte adhesion) Modify microbiota (prebiotic) Modify microbiota (prebiotic) Menzel et al. Inflamm Bowel Dis. 2004 Mar;10(2):122-8 Galvez et al. Mol Nutr Food Res. 2005 Jun;49(6):601-8

36 Nutritional supplements Butyrate (SCFA) Butyrate (SCFA) Increase in dietary fiber can increase fecal butyrate Increase in dietary fiber can increase fecal butyrate Germinated barley foodstuff (GBF) Germinated barley foodstuff (GBF) Alter colonic bacterial concentrations Alter colonic bacterial concentrations Increase in Bifidobacterium sp. and Eubacterium limosum Increase in Bifidobacterium sp. and Eubacterium limosum Hallert et al. Inflamm Bowel Dis. 2003 Mar;9(2):116-21 Kanauchi et al. J Gastroenterol. 2002 Nov;37 Suppl 14:67-72

37 Nutritional supplements Butyrate (SCFA) Butyrate (SCFA) Butyrate enemas Butyrate enemas Benefit in UC (pilot study) Benefit in UC (pilot study) Did not reach statistical significance in RCT Did not reach statistical significance in RCT Plantago ovata seeds Plantago ovata seeds Open label randomized trial (105 pts) Open label randomized trial (105 pts) Mesalamine 500 TID vs. fiber 10 gm BID Mesalamine 500 TID vs. fiber 10 gm BID Increased fecal butyrate in fiber group Increased fecal butyrate in fiber group No difference @ 1 year No difference @ 1 year Relapse 40% in fiber Relapse 40% in fiber Relapse 35% in mesalamine Relapse 35% in mesalamine Scheppach et al. Gastroenterology. 1992 Jul;103(1):51-6 Fernández-Bañares et al. Am J Gastroenterol. 1999 Feb;94(2):427-33

38 Nutritional supplements Defined diets- No data Defined diets- No data Specific Carbohydrate Diet Specific Carbohydrate Diet Breaking the Viscious Cycle Breaking the Viscious Cycle Makers diet Makers diet juicing diets juicing diets

39 Nutritional supplements- CAM Hou et al. Therapy, Mar 2010, 7(2), 179-189

40 Ongoing research BCM

41 BCM Food aversion study Hypothesis: Hypothesis: Food aversion in IBD is common. Food aversion in IBD is common. Food aversion in IBD may be related to several factors Food aversion in IBD may be related to several factors Physician Physician Patient directed education Patient directed education Patient symptom correlation Patient symptom correlation

42 BCM Food aversion study Primary aim: To define the frequency and character of dietary alterations that occur in patients with IBD Primary aim: To define the frequency and character of dietary alterations that occur in patients with IBD Secondary aims: Secondary aims: Identify the reason IBD patients initiate dietary modifications Identify the reason IBD patients initiate dietary modifications Identify if IBD patients feel dietary modifications are effective Identify if IBD patients feel dietary modifications are effective

43 Methods Prospective, controlled data acquisition Prospective, controlled data acquisition 100 IBD patients 100 IBD patients 50 CD 50 CD 50 UC 50 UC 100 healthy controls 100 healthy controls Non-IBS Non-IBS Matched for age, sex Matched for age, sex

44 BCM Food aversion study Goals Goals Establish food aversion patterns in IBD Establish food aversion patterns in IBD Identify etiology of food aversion patterns in IBD Identify etiology of food aversion patterns in IBD Create pilot data for further studies regarding dietary habits and IBD Create pilot data for further studies regarding dietary habits and IBD Establish if unnecessary food aversion result in nutritional deficiency Establish if unnecessary food aversion result in nutritional deficiency Apply educational tools to correct nutritional deficiencies Apply educational tools to correct nutritional deficiencies

45 Conclusions Diet as Etiology Diet as Etiology Fatty acids composition may play a role in pathogenesis Fatty acids composition may play a role in pathogenesis Nutritional deficiencies Nutritional deficiencies Protein-calorie malnutrition becoming less common, but Micronutrient deficiencies common Protein-calorie malnutrition becoming less common, but Micronutrient deficiencies common Diet as Therapy Diet as Therapy Fiber, enteral therapy, CAM Fiber, enteral therapy, CAM

46 Thank you for listening Special thanks to Drs. Hashem El-Serag, Joseph Sellin, and Selvi Thirumuthi

47 Calcium and Vitamin D What endpoint? What endpoint? Serum 25-hydroxyvitamin D (25-OH-D) Serum 25-hydroxyvitamin D (25-OH-D) Jahnsen et al. Jahnsen et al. 27% of CD patients 27% of CD patients 15% of UC patients 15% of UC patients Did not correlate with bone mineral density Did not correlate with bone mineral density Leslie et al. Leslie et al. 25-OH-D correlated with BMD 25-OH-D correlated with BMD Jahnsen et al. Scand J Gastroenterol. 2002 Feb;37(2):192-9 Leslie et al. Am J Gastroenterol. 2008 Jun;103(6):1451-9

48 Future studies Can diet modification prevent or treat IBD? Can diet modification prevent or treat IBD? Omega-3-PUFA/Omega-6-PUFA Omega-3-PUFA/Omega-6-PUFA Butyrate Butyrate CAM CAM The role of diet modification and microbiome The role of diet modification and microbiome

49 Enteral Therapy- Cochrane review (2007) Trend towards improved response of very low fat/very low triglyceride formulations vs. high fat formulations Trend towards improved response of very low fat/very low triglyceride formulations vs. high fat formulations OR 1.55, CI 95% 0.75-3.23 OR 1.55, CI 95% 0.75-3.23 Compared different fatty acids Compared different fatty acids Zachos et al. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000542.

50 Our research question It is also important to define the reasons for food aversions It is also important to define the reasons for food aversions Ethical/moral concerns Ethical/moral concerns Instructed by physician Instructed by physician Instructed by friend/ other information source Instructed by friend/ other information source Truly associated with symptoms Truly associated with symptoms

51 Overview Diet as etiology Diet as etiology Nutritional deficiencies Nutritional deficiencies Diet as therapy Diet as therapy Ongoing study Ongoing study

52 Our research question Very few investigations examining dietary modifications in IBD, especially patient initiated modifications Very few investigations examining dietary modifications in IBD, especially patient initiated modifications Limited number of studies systematically examining food aversions.- Lack control group Limited number of studies systematically examining food aversions.- Lack control group Control group is essential since as many as a third of healthy individuals may have food aversions. Control group is essential since as many as a third of healthy individuals may have food aversions.


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