Role of Nutrition in IBD

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Madeleine on Jun 12, 2011 Says :

very informative and interesting.

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Nutritional Guidance for your IBD Patient Gerard Mullin, M.D.

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Objectives To discuss the prevalence of malnutrition in IBD To describe the nutritional complications of IBD To weigh the pro’s and con’s of specialized nutrition support for IBD patients To discuss the role of dietary therapy for IBD

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Disclosures

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Malnutrition in CD Patients Up to 75% hospitalized CD patients are malnourished* Multiple factors contribute to malnutrition: Reduced absorption Increased nutrient loss Increased metabolic requirements Reduced Intake Medications Loss of visceral protein mass occurs when the appropriate nutritional support is not provided. * GI Clinics of North America 1989;18:129-155.

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Medications and Nutrient Lossin IBD Sulfasalazine produces folate malabsorption by competitive inhibition of the jejunal folate conjugate enzyme. Corticosteroids suppress small intestinal calcium absorption and increase urinary calcium excretion. Cholestyramine produces fat, calcium, and fat-soluble vitamin deficiencies. Sulfasalazine, 5-aminosalicylic acid, or metronidazole may cause nausea, vomiting, and dyspepsia curtailing nutrient intake.

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MALNUTRITION IN IBD

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Categories ofNutritional Therapy in CD Specialized nutrition support (TPN, enteral nutrition) Alteration of gut flora (probiotics. prebiotics). Enterocyte nutrition (glutamine and SCFA). Presence of growth factors (TGF-ß, EGF) Antiinflammatory (omega 3 fatty acids) Fell JM et al. J Pediatr Gastroenterol Nutr.1997;24:474.

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TPN as primary therapy

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META-ANALYSIS OF ENTERAL NUTRITION AS A PRIMARY TREATMENT OF ACTIVE CROHN’S DISEASE

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Enteral Nutrition Pooled results from 12 randomized, controlled trials1 Patients entering remission: Enteral diet 113/159 (71%) Steroid 47/55 (85%) Benefits: induce remission, correct nutrient deficiencies, and spare corticosteroids Limitations: failure to maintain remission,high cost, and poor compliance 1Han PD et al. Gastroenterol Clin North Am. 1999;28:423.

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ROLE OF NUTRITION SUPPORT IN CD

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ROLE OF NUTRITION SUPPORT IN CD

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ROLE OF NUTRITION SUPPORT IN CD

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ROLE OF NUTRITION SUPPORT IN UC

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Enteral > placebo Enteral < GCS Enteral = TPN Polymeric = elemental NO DATA ON NUTRITON PLUS MEDICATIONS!! Effectiveness of Nutritional Support for Crohn’s Disease

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No immune activation Macrophage and TH1 immune activation No colitis Colitis Resident bacteria No bacteria Mice IL-2KO IL-10KO TCRaKO CD3E26TG SAMP1/Yit DSS CD45RBhi SCID Rats HLA-B27 TG Indomethacin Guinea pigs Carrageenan Nonhuman primate Cotton-top tamarin IBD: Pathogenesis animal modelsintimate relationship with bacteria ?

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IBD Animal Model

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Probiotics:rationale Biblical references to “sour milk” longevity of Abraham Metchnikoff (1874-1961) Increase longevity Rapidly expanding literature on the role of Probiotics and GI Disease Human and animal studies: Immune regulation (Th1/Th2) Anti-inflammatory effects Prevents and treats intestinal disease

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Prevent infections (systemic and GI) Regulate local and systemic immune function Metabolic pathway nutrients: glycemic control, cholesterol, amino acids Enhance nutrient utilization Regulate bowel motility Regulate appetite (leptin, ghrelin) Regulate Inflammation, local and systemic Prevent neoplastic changes Support mucosal barrier Probiotics and Prebiotics: Exploring the Mutually Beneficial Effects of Bacteria and Their Substrates in the Human Host Prebiotics and Probiotics

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Setting the Immune Response Th1 Th2 Th3 Microbes Inflamatory Regulation Down Tolerance Cellular Humoral Dendritic Macrophage Th0 CD4 Helper T Cell Lymphocytes

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Benefits of Probiotics in IBD mechanisms of action Immunomodulator Upregulate IL-10 Downregulate Th1 cytokines (IL-12) Inhibit IFNg by T cells Inhibit NFkB Stabilize IkB levels Induce T-regs Local effects Increased mucin production Inhibition of epithelial IL-8 production by TNF-a Maintain tight junctions and epithelial integrity Diminish visceral hypersensitivity in animal models Diminish Intestinal muscle inflammation and restoring function with Trichinella spiralis infection Hart AL, et. Al. Gut 2004;53:1602-9

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Probiotics in Ulcerative Colitis

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Benefits of Probiotic VSL#3 in UC VSL#3 VSL#3 VSL#3 VSL#3/Balasalazide VSL3# DNA Pouchitis post-op prevention and maintenance UC Induction of remission UC Maintenance UC induction of remission vs. balsalazide alone *Ameriorates colitis in DDS-induced colitis in mice *Rachmilewitz D, et. Al. Gastroenterol 2004;126:520-8

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Prebiotics Three Necessary Criteria of Ingredient Must be non-digestible by host enzymes Must be fermented in the GI tract by anaerobic endogenous bacteria in colon Must be selective in the stimulation of intestinal flora/metabolic activity Examples: Inulin, fructooligosaccharides (FOS), galactooligosaccharides (GOS), lactulose Foods:asparagus, onion, leek, Jerusalem artichoke

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Prebiotics in UC

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Prospective Studies of SCFA for left-sided UC

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Cell membrane Phospholipase A2 Arachnidonic Acid Cyclooxygenase Lipooxygenase Leukotrienes SRS-A Thromboxane A2 Prostaglandin 2 series EPA/DHA EPA/DHA LTB 5 PGE3 DHLA X X W-6 FA W-6 FA W-3 FA W-3 FA Omega-3 Modulation of Arachidnonic Acid Cascade

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Omega 3 Fatty Acids Fish Walnuts Flax Canola oil Omega 6 Fatty Acids Corn Primrose Safflower oil Red meat Omega-3,6 Modulation of Arachidnonic Acid Cascade

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Effects of Omega-3 Fatty Acids on Factors Involved in the Pathophysiology of Inflammation

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Effects of Omega-3 Fatty Acids on Factors Involved in the Pathophysiology of Inflammation

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A schematic of the biosynthetic routes for lipoxins, resolvins and protectins

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World-Wide Prevalence of Autoimmune Disease

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Pathogenesis of IBD Macrophage Inflammation Ag Ag IL-12 Mucosal injury IL-1 IL-6 TNF-a IL-8, MIP-1a + + TNF-a ADCC Lymphokines OH. O2.- IL-2, IFNg IL-1 + + CD45R CD4 Memory T Cell Lymphokines ROS (-)

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Fish Oils & IBDAnimal Studies 6/6 Mice models of ulcerative colitis showed protection from injury and healing with omega-3 fatty acids. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11276-81. Clin Nutr. 2006 Jun;25(3):466-76. Epub 2006 May 15 Nutrition. 2006 Mar;22(3):275-82 World J Gastroenterol. 2005 Dec 21;11(47):7466-72 Proc Natl Acad Sci U S A. 2005 May 24;102(21):7671-6. Inflamm Bowel Dis. 2005 Apr;11(4):340-9

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Fish Oils & UCInduction of Remission Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005986. * 72% weaned off or reduced medication dose. N=159

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Fish Oils & Crohn’s Disease Turner D, Zlotkin SH, Shah PS, Griffiths AM. Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. N=301

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Omega 3 Fatty Acids For Maintenance Of Remission in Crohn’s Disease

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Omega 3 Fatty Acids For Maintenance Of Remission in Crohn’s Disease Enteric-Coated Studies

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Prebiotics in UC

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Potential Role of Vitamin D in IBD

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Combined oral supplement to determine if enteral nutrition can provide steroid sparing effect (n=121, 86 completed study) for 6 months Nutritionally balanced oral supplement (UCNS) 1.3 kcal/mL, 310 kcal [16.1/49.7/6.5% Protein/CHO/Lipid] vs. CHO-based placebo (18 oz) Fish Oil (1.09 g EPA/0.46 g DHA) per 8 oz FOS 2.9 gm Gum arabic 2.2 gm Vitamin E 72 IU, Vitamin C 156 mg Clin Gastro Hep 2005;3:358-369

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Clin Gastro Hep 2005;3:358-369

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Clin Gastro Hep 2005;3:358-369

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Case Presentation 43 year old Greek male with 5 year of UC is interested in nutritional counseling. He is asking for advice on dietary therapy. He is otherwise healthy and takes Asacol 3.6 g/D. Exam is unremarkable. Laboratories show vitamin 25-OH-D (16 ng/mL) What dietary recommendations are appropriate?

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Recommendations Possible nutraceuticals to consider: Pre/Probiotics (VSL#3, FOS) Fish oils (3 gm EPA/DHA daily) Calcium (DRI 1000 mg/D) Vitamin D (DRI 400-800 I.U./D) Diet FOS containing foods: Asparagus, Jerusalem artichokes, onions, leeks Cruciferous vegetables vs. Indole-3-Carbinol Mediterranean diet: Rich in green leafy vegetables Whole grains High in fish, poultry-low in red meat Olive oil as essential fatty acid base

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www.cmbm.org

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Thank You

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QUESTIONS?

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