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Nutraceuticals for Gastrointestinal Disorders Leo Galland, M.D., F.A.C.P. Foundation for Integrated Medicine www.mdheal.org.

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Presentation on theme: "Nutraceuticals for Gastrointestinal Disorders Leo Galland, M.D., F.A.C.P. Foundation for Integrated Medicine www.mdheal.org."— Presentation transcript:

1 Nutraceuticals for Gastrointestinal Disorders Leo Galland, M.D., F.A.C.P. Foundation for Integrated Medicine

2 Nutraceuticals vs Pharmaceuticals Pharmaceuticals are mostly used to suppress specific physiological functions: Pharmaceuticals are mostly used to suppress specific physiological functions: PPIs, H2 blockers, calcium blockers, anticholinergic, antidopaminergic, anti- inflammatory, immunosuppressant.  Nutraceuticals may enhance physiologic function, complementing or replacing drugs. Some may act like drugs.

3 Esophageal Reflux Results from reflex relaxation of the LES in response to gastric vagal mechanoreceptors (programmed in brainstem, unrelated to swallowing or gastric pH). Post-prandial gastric distension is a key trigger. Results from reflex relaxation of the LES in response to gastric vagal mechanoreceptors (programmed in brainstem, unrelated to swallowing or gastric pH). Post-prandial gastric distension is a key trigger. PPI’s and H-2 blockers convert acid reflux into non-acid reflux. Pepsin and bile present in gastric juice may yet act as esophageal irritants. PPI’s and H-2 blockers convert acid reflux into non-acid reflux. Pepsin and bile present in gastric juice may yet act as esophageal irritants.

4 Toxicity of Acid Lowering Drugs May increase development of atrophic gastritis in H. pylori-infected individuals May increase development of atrophic gastritis in H. pylori-infected individuals Allow gastric bacterial/yeast overgrowth and post-prandial intra-gastric production of ethanol and nitrosamines Allow gastric bacterial/yeast overgrowth and post-prandial intra-gastric production of ethanol and nitrosamines May impair absorption of vitamin B12, folic acid, carotene, minerals and medication May impair absorption of vitamin B12, folic acid, carotene, minerals and medication Increase risk of hip fracture and pneumonia Increase risk of hip fracture and pneumonia

5 Calcium vs GERD With acute esophagitis, LES contraction becomes dependent upon extracellular Ca With acute esophagitis, LES contraction becomes dependent upon extracellular Ca Sohn et al, J Pharmacol Exp Ther. 1997;283: Intra-gastric calcium increases esophageal acid clearance and LES tone, independent of antacid effects, in patients with GERD. Intra-gastric calcium increases esophageal acid clearance and LES tone, independent of antacid effects, in patients with GERD. Rodriguez-Stanley et al, Dig Dis Sci 2004; 49:1862-7

6 Non-Drug Treatment of GERD Small meals eaten slowly in a relaxed fashion to decrease gastric distention. Chewing and swallowing enhance esophageal acid clearance. Small meals eaten slowly in a relaxed fashion to decrease gastric distention. Chewing and swallowing enhance esophageal acid clearance. Calcium citrate 250 mg after each meal Calcium citrate 250 mg after each meal Postprandial enzymes Postprandial enzymes Red pepper powder 800 mg t.i.d. Red pepper powder 800 mg t.i.d. Bortolotti et al, NEJM 2002; 346: Deglycyrrhizinated licorice, aloe, HCl (?) Deglycyrrhizinated licorice, aloe, HCl (?)

7 TJ-43, aka Rikkunshi-to, Liu-Jun-Zi- Tang, Six Gentleman Formula Speeds esophageal acid clearance in children with GERD, without increasing LES tone. Kawahara et al, Pediatr Surg Int Speeds esophageal acid clearance in children with GERD, without increasing LES tone. Kawahara et al, Pediatr Surg Int  Stimulates gastric emptying in dyspeptic adults. Tatsuta & Iishi, Aliment Pharmacol Ther  Increases gastric NO production in rats. Arakawa et al, Drugs Exp Clin Res  Raises plasma gastrin and somatostatin in human volunteers. Naito et al. Biol Pharm Bull. 2001

8 TJ-43 Components Atractylodes lanceae rhizome Atractylodes lanceae rhizome Ginseng root Ginseng root Pinellia tuber Pinellia tuber Hoelen Hoelen Zizyphus (jujube) fruit Zizyphus (jujube) fruit Aurantii nobilis pericarp (orange peel) Aurantii nobilis pericarp (orange peel) Glycyrrhizae (licorice) root Glycyrrhizae (licorice) root Zingiberis (ginger) rhizome Zingiberis (ginger) rhizome Hesperidin and L-arginine are major ingredients

9 STW 5 (Iberogast) Relieves Symptoms of Functional Dyspepsia Iberis amara: prokinetic effects comparable to metoclopramide and cisapride without CNS/cardiotoxicity Iberis amara: prokinetic effects comparable to metoclopramide and cisapride without CNS/cardiotoxicity Spasmolytic herbal extracts: German chamomile, angelica root, caraway, lemon balm, milk thistle, celandine, licorice, peppermint leaf. Spasmolytic herbal extracts: German chamomile, angelica root, caraway, lemon balm, milk thistle, celandine, licorice, peppermint leaf. Von Armin et al, Am J Gastroenterol Meltzer et al, Aliment Pharmacol Ther. 2004

10 ASA/NSAID Gastropathy/Enteropathy Protective supplements (human trials): Protective supplements (human trials): Vit C mg bid SAMe 500 mg/day Cayenne 20 grams Deglycyrrhizinated licorice 350 mg tid Colostrum 125 mg tid L-glutamine 7 grams tid L-glutamine 7 grams tid

11 Gastroprotection: Cayenne Cayenne protects against aspirin-induced gastric mucosal damage in humans at a dose of 20 g administered 30 minutes before 600 mg of aspirin. Yeoh et al, Dig Dis Sci Cayenne protects against aspirin-induced gastric mucosal damage in humans at a dose of 20 g administered 30 minutes before 600 mg of aspirin. Yeoh et al, Dig Dis Sci Capsaicin is gastroprotective against a range of mucosal toxins in rats but may exert its effects by irritant-induced pre-conditioning, stimulating gastric mucus secretion. Capsaicin is gastroprotective against a range of mucosal toxins in rats but may exert its effects by irritant-induced pre-conditioning, stimulating gastric mucus secretion. Patients with recurrent/chronic abdominal pain, cayenne aggravates 25-50%. Kang et al, Gut 1992 Patients with recurrent/chronic abdominal pain, cayenne aggravates 25-50%. Kang et al, Gut 1992

12 Gastroprotection: Vitamin C ASA inhibits absorption of vitamin C ASA inhibits absorption of vitamin C ASA 400 mg bid for 3 days depletes intragastric vitamin C, suppresses gastric blood flow, SOD, GPx. Prevented by Vitamin C 480 mg b.i.d. ASA 400 mg bid for 3 days depletes intragastric vitamin C, suppresses gastric blood flow, SOD, GPx. Prevented by Vitamin C 480 mg b.i.d. Healthy volunteers: Healthy volunteers: Adding C reduced ASA-induced gastric lesions Adding C reduced ASA-induced gastric lesions C 1000 mg b.i.d. for 3 days prevented ASA-induced duodenal injury C 1000 mg b.i.d. for 3 days prevented ASA-induced duodenal injury

13 Gastroprotection: SAMe S-adenosylmethionine (500 mg) given with aspirin (1300 mg) reduced by 95% the extent of aspirin-induced erosive gastritis in a single-dose study of healthy volunteers. Laudanno et al, Acta Gastroenterol Latinoam S-adenosylmethionine (500 mg) given with aspirin (1300 mg) reduced by 95% the extent of aspirin-induced erosive gastritis in a single-dose study of healthy volunteers. Laudanno et al, Acta Gastroenterol Latinoam Similar protective effects have been demonstrated in rats. Similar protective effects have been demonstrated in rats. Yet, the most common side effect of SAMe is abdominal pain. Yet, the most common side effect of SAMe is abdominal pain.

14 H. Pylori Inhibition in vitro Mastic gum (P lentiscus), used for treatment of dyspepsia, kills H. pylori, but failed a clinical trial Mastic gum (P lentiscus), used for treatment of dyspepsia, kills H. pylori, but failed a clinical trial Raw garlic and aqueous garlic extract inhibit growth (thiosulfinate, MIC of 40 mcg/ml) Raw garlic and aqueous garlic extract inhibit growth (thiosulfinate, MIC of 40 mcg/ml) Sulforaphane (cabbage and broccoli) has MIC of <4 mcg/ml (cabbage juice and broccoli sprouts have been used to treat PUD) Sulforaphane (cabbage and broccoli) has MIC of <4 mcg/ml (cabbage juice and broccoli sprouts have been used to treat PUD) Lactobacilli inhibit growth Lactobacilli inhibit growth

15 Adjunctive Therapy of H. pylori Human Studies Probiotics decrease treatment side effects with inconsistent effects on outcome Probiotics decrease treatment side effects with inconsistent effects on outcome Bovine lactoferrin 200 mg bid, may increase therapeutic response and/or decrease side effects Bovine lactoferrin 200 mg bid, may increase therapeutic response and/or decrease side effects N-acetyl cysteine liquid 400 mg tid, increased response to clarithromycin/lansozrapole. N-acetyl cysteine liquid 400 mg tid, increased response to clarithromycin/lansozrapole. Gurbuz, South Med J. 2005;98: Gurbuz, South Med J. 2005;98:

16 Irritable Bowel Syndromes: a moving target Motility Motility Stress and anxiety Stress and anxiety Flora Flora Digestion and fermentation Digestion and fermentation Allergy and specific food intolerance Allergy and specific food intolerance Pain sensitivity Pain sensitivity Inflammation Inflammation

17 IBS: Triggers Stressful thoughts/events Stressful thoughts/events Microbes Microbes Bacteria Bacteria Yeast Yeast Parasites Parasites Food Food Fiber/lack of fiber Fiber/lack of fiber Carbohydrate, form and amount Carbohydrate, form and amount Specific food intolerance/allergy Specific food intolerance/allergy

18 CAUSES OF UPPER GI BACTERIAL OVERGROWTH CAUSES OF UPPER GI BACTERIAL OVERGROWTH Achlorhydria/hypo- chlorhydria Achlorhydria/hypo- chlorhydria Surgical resection/blind loops Surgical resection/blind loops Stasis from abnormal motility Stasis from abnormal motility Strictures Strictures Fistulas Fistulas Diverticulosis Diverticulosis Immune deficiency Immune deficiency Intestinal giardiasis Intestinal giardiasis Tropical sprue Tropical sprue Malnutrition Malnutrition

19 EFFECTS OF UPPER GI BACTERIAL OVERGROWTH Carbohydrate/fiber intolerance, bloating, altered bowel habit, fatigue Carbohydrate/fiber intolerance, bloating, altered bowel habit, fatigue Vitamin B12 deficiency Vitamin B12 deficiency Bile salt dehydroxylation Bile salt dehydroxylation Impairs formation of micelles Impairs formation of micelles Bile salt deconjugation Bile salt deconjugation Increases colonic water secretion Increases colonic water secretion Inhibit monosaccharide transport Inhibit monosaccharide transport

20 BREATH TESTING FOR BACTERIAL OVERGROWTH FALSE POSITIVES FALSE POSITIVES Smoking, sleeping, eating Smoking, sleeping, eating Soluble fiber/FOS Soluble fiber/FOS Rapid intestinal transit Rapid intestinal transit FALSE NEGATIVES FALSE NEGATIVES Colonic hyperacidity (low stool pH) Colonic hyperacidity (low stool pH) Absence of appropriate flora Absence of appropriate flora Delayed gastric emptying Delayed gastric emptying Antibiotics Antibiotics

21 BACTERIAL OVERGROWTH IS MORE COMMON THAN SUSPECTED 202 patients with IBS underwent hydrogen breath testing 202 patients with IBS underwent hydrogen breath testing 157 (78%) had SBBO and were treated with antibiotics 157 (78%) had SBBO and were treated with antibiotics 25/47 patients had normal breath tests at follow-up 25/47 patients had normal breath tests at follow-up Diarrhea and abdominal pain were significantly improved by treatment Diarrhea and abdominal pain were significantly improved by treatment

22 SBBO AND IBS: CONCLUSIONS Elimination of SBBO eliminated IBS in 12/25 of patients: 48 % of patients with IBS and abnormal breath tests who responded to antibiotics with normal breath tests no longer met Rome criteria for IBS 48 % of patients with IBS and abnormal breath tests who responded to antibiotics with normal breath tests no longer met Rome criteria for IBS Pimentel M et al, AM J Gastroenterol 2000

23 MANAGEMENT OF UGI BACTERIAL OVERGROWTH INVOLVES DIET, ANTIBIOTICS Low fermentation diet Low fermentation diet -restrict sugar, starch, soluble fiber Antimicrobials (in select cases): Antimicrobials (in select cases): Metronidazole (anaerobes) Metronidazole (anaerobes) Tetracyclines (anaerobes) Tetracyclines (anaerobes) Ciprofloxacin (aerobes) Ciprofloxacin (aerobes) Bismuth Bismuth Bentonite Bentonite

24 Low Fermentation Diet Basic diet: no wheat, sucrose, lactose Basic diet: no wheat, sucrose, lactose Additional restrictions Additional restrictions -no glutinous grains -no cereal grains, potatoes -restrict fruits, juices, honey -restrict fructose, fructans -avoid legumes -cook all vegetables

25 A Drug-Free Clinical Approach to IBS Avoid/reduce medications with GI side effects Avoid/reduce medications with GI side effects Evaluate the role of infection or microbial overgrowth/deficit (dysbiosis) Evaluate the role of infection or microbial overgrowth/deficit (dysbiosis) Individualized dietary prescription Individualized dietary prescription Stress management, hypnotherapy Stress management, hypnotherapy Nutraceutical decision tree Nutraceutical decision tree

26 Supplements for IBS Probiotics Probiotics Prebiotics Prebiotics Antimicrobial Antimicrobial Spasmolytic Spasmolytic Motility enhancing Motility enhancing Laxative Laxative Antidiarrheal Antidiarrheal

27 Probiotics Lactic acid producers: Lactobacilli (acidophilus, plantarum, casei, salivarius, reuterri, sporogenes), Bifidobacteria, Streptococci Lactic acid producers: Lactobacilli (acidophilus, plantarum, casei, salivarius, reuterri, sporogenes), Bifidobacteria, Streptococci Non-pathogenic E. coli Non-pathogenic E. coli Soil-derived organisms: Bacilli (laterosporus, subtilis) Soil-derived organisms: Bacilli (laterosporus, subtilis) Saccharomyces boulardii (yeast against yeast) Saccharomyces boulardii (yeast against yeast)

28 Prebiotics Foods that support the growth of probiotics: bran, psyllium, resistant starch (high amylose), oligofructose (FOS), inulin, germinated barley foodstuff (GBF), synthetic oligosaccharides Foods that support the growth of probiotics: bran, psyllium, resistant starch (high amylose), oligofructose (FOS), inulin, germinated barley foodstuff (GBF), synthetic oligosaccharides FOS is found in onions, garlic, rye, blueberries, bananas, chicory. Dietary intake averages 2-8 gm/day. FOS is found in onions, garlic, rye, blueberries, bananas, chicory. Dietary intake averages 2-8 gm/day. Inulins are derived from chicory and artichoke Inulins are derived from chicory and artichoke

29 Clinical Uses of Probiotics Antibiotic-induced diarrhea Antibiotic-induced diarrhea Traveler's diarrhea/acute GI infections Traveler's diarrhea/acute GI infections Irritable bowel syndromes Irritable bowel syndromes Inflammatory bowel disease Inflammatory bowel disease Diverticulitis Diverticulitis Colon cancer prevention Colon cancer prevention

30 LACTOBACILLI: BENEFICIAL EFFECTS Produce organic acids: lower bowel pH Produce organic acids: lower bowel pH Produce H202 Produce H202 Antagonize enteropathogenic E. Coli, Salmonella, Staphylococci, Candida albicans, and Clostridia spp Antagonize enteropathogenic E. Coli, Salmonella, Staphylococci, Candida albicans, and Clostridia spp Degrade N-nitrosamines Degrade N-nitrosamines Anti-tumor glycopeptides (L. bulgaricus) Anti-tumor glycopeptides (L. bulgaricus) Stimulate balanced immune responses Stimulate balanced immune responses Decrease rate of post-op infection (L plantarum) Decrease rate of post-op infection (L plantarum)

31 BENEFITS OF SACCHAROMYCES BOULARDII Stimulates production of sIgA Stimulates production of sIgA Protects against antibiotic and traveler’s diarrhea Protects against antibiotic and traveler’s diarrhea Helps reverse C difficile colitis Helps reverse C difficile colitis Improves acute diarrheal disease in children Improves acute diarrheal disease in children SAIF inhibits NFkB induction of IL-8 gene expression SAIF inhibits NFkB induction of IL-8 gene expression

32 Clinical uses of Prebiotics and Fiber Irritable bowel syndromes Irritable bowel syndromes Ulcerative colitis Ulcerative colitis Prevention of colon cancer Prevention of colon cancer Prevention of diverticulitis Prevention of diverticulitis

33 Herbs Used for IBS Treatment Aloe, various species Aloe, various species Fennel seed (Foeniculum vulgaris) Fennel seed (Foeniculum vulgaris) Ginger (Zingiber officinalis) Ginger (Zingiber officinalis) Slippery elm bark (Ulmus rubra) Slippery elm bark (Ulmus rubra) Marshmallow root (Althea officinalis) Marshmallow root (Althea officinalis) Cumin (Curcuma longa) Cumin (Curcuma longa) Chamomile, various species Chamomile, various species Caraway (Carum copticum) Caraway (Carum copticum) Lemon balm (Melissa officinalis) Lemon balm (Melissa officinalis) Triphala (Terminalia chebula/belerica, Emblica officalis) Triphala (Terminalia chebula/belerica, Emblica officalis)

34 Peppermint Oil for IBS Enteric coated peppermint oil is twice as effective as placebo for symptom relief; effect lasts after Rx ends. Capello et al, Dig Liver Dis Enteric coated peppermint oil is twice as effective as placebo for symptom relief; effect lasts after Rx ends. Capello et al, Dig Liver Dis Inhibits gall bladder contraction, small bowel transit, colonic motility Goerg, Spilker Aliment Pharmacol Ther ; Asao et al, Gastrointest Endosc Inhibits gall bladder contraction, small bowel transit, colonic motility Goerg, Spilker Aliment Pharmacol Ther ; Asao et al, Gastrointest Endosc Reduces cellular calcium influx. Hills, Aaronson Gastroenterology Reduces cellular calcium influx. Hills, Aaronson Gastroenterology Decreases sulfide production by gut flora Ushid et al, J Nutr Sci Vitaminol (Tokyo) Decreases sulfide production by gut flora Ushid et al, J Nutr Sci Vitaminol (Tokyo) Kills trophozoites of Giardia lamblia. Vidal et al, Exp. Parasitol Kills trophozoites of Giardia lamblia. Vidal et al, Exp. Parasitol. 2007

35 TCM for Symptoms of IBS Individualized vs standard formula vs placebo: short-term benefits from both formulas, post-treatment benefits only in the individualized treatment group. Bensoussan et al, JAMA 1998 Individualized vs standard formula vs placebo: short-term benefits from both formulas, post-treatment benefits only in the individualized treatment group. Bensoussan et al, JAMA 1998 Standarized formula no better than placebo. Leung et al, Am J Gastroenterol Standarized formula no better than placebo. Leung et al, Am J Gastroenterol. 2006

36 Calcium and Fiber for Chronic Diarrhea Combination of psyllium and calcium was more effective and better tolerated than loperamide for controlling symptoms of chronic diarrhea. Qvitzau et al, Scand J Gastroenterol Combination of psyllium and calcium was more effective and better tolerated than loperamide for controlling symptoms of chronic diarrhea. Qvitzau et al, Scand J Gastroenterol Psyllium does not prevent calcium absorption in humans, contrary to animal data. Heaney & Weaver, J Am Geriatr Soc Psyllium does not prevent calcium absorption in humans, contrary to animal data. Heaney & Weaver, J Am Geriatr Soc. 1995

37 Inflammatory Bowel Disease: Dietary Decisions Dietary responses may differ for Crohn’s disease and ulcerative colitis. Dietary responses may differ for Crohn’s disease and ulcerative colitis. Avoid sucrose and symptom-provoking foods. Avoid sucrose and symptom-provoking foods. The specific carbohydrate diet (SCD), an exclusion diet or a defined formula diet may help relieve symptoms and may help induce or maintain remission (Crohn’s). The specific carbohydrate diet (SCD), an exclusion diet or a defined formula diet may help relieve symptoms and may help induce or maintain remission (Crohn’s). Replace vegetable oils with flaxseed oil and/or coconut oil (1 to tablespoons a day) Replace vegetable oils with flaxseed oil and/or coconut oil (1 to tablespoons a day) Oat bran 60 grams a day for patients with mild to moderate ulcerative colitis Oat bran 60 grams a day for patients with mild to moderate ulcerative colitis

38 Germinated Barley Foodstuff (GBF) and Ulcerative Colitis GBF gm/day helps to induce and maintain remission in patients with ulcerative colitis. GBF gm/day helps to induce and maintain remission in patients with ulcerative colitis. Mechanism: Increased colonic butyrate production decreases NFkB activation. Mechanism: Increased colonic butyrate production decreases NFkB activation. Hanai et al. Int J Mol Med May;13(5): Hanai et al. Int J Mol Med May;13(5): Kanauchi et al. J Gastroenterol. 2003;38: Kanauchi et al. J Gastroenterol. 2003;38: Kanauchi et al, Int J Mol Med. 2003;12:701-4 Kanauchi et al, Int J Mol Med. 2003;12:701-4 Kanauchi et al. J Gastroenterol. 2002; 37 Suppl 14: Kanauchi et al. J Gastroenterol. 2002; 37 Suppl 14:

39 Vitamins and IBD Folic acid, 800 mcg/day or more, especially for patients with high homocysteine or taking 5-ASA derivatrive Folic acid, 800 mcg/day or more, especially for patients with high homocysteine or taking 5-ASA derivatrive Vitamin B12, 1000 mcg a month for patients with CD, those receiving folic acid or with high homocysteine Vitamin B12, 1000 mcg a month for patients with CD, those receiving folic acid or with high homocysteine Vitamin B6, 10 to 20 mg/day, especially for patients with high homocysteine or taking high dose folic acid Vitamin B6, 10 to 20 mg/day, especially for patients with high homocysteine or taking high dose folic acid Vitamin D3, 1000 IU/day or more to maintain levels of 25-OH vitamin D at 40 mcg/ml Vitamin D3, 1000 IU/day or more to maintain levels of 25-OH vitamin D at 40 mcg/ml An antioxidant supplying vitamin E 400 IU/day and vitamin C 500 to 1000 mg/day An antioxidant supplying vitamin E 400 IU/day and vitamin C 500 to 1000 mg/day Vitamin K, optimal dose unknown Vitamin K, optimal dose unknown

40 Minerals and IBD Zinc, 25 to 200 mg/day, to maintain plasma zinc above 800 mg/L Zinc, 25 to 200 mg/day, to maintain plasma zinc above 800 mg/L Calcium 1000 mg/day for patients on steroids or with low dietary calcium. Calcium 1000 mg/day for patients on steroids or with low dietary calcium. Selenium 200 mcg/day, especially for patients with ileal resection or on liquid formula diets Selenium 200 mcg/day, especially for patients with ileal resection or on liquid formula diets Magnesium citrate (150 to 900 mg/day) for patients with urolithiasis. Magnesium citrate (150 to 900 mg/day) for patients with urolithiasis. Chromium 600 mcg/day for patients with steroid-induced hyperglycemia. Chromium 600 mcg/day for patients with steroid-induced hyperglycemia.

41 Biologicals and IBD-1 Fish oils supplying 4000 to 5000 mg/day of omega-3 fatty acids (EPA + DHA) Fish oils supplying 4000 to 5000 mg/day of omega-3 fatty acids (EPA + DHA) VSL-3 (one sachet twice a day) for patients with mild to moderate UC or pouchitis. VSL-3 (one sachet twice a day) for patients with mild to moderate UC or pouchitis. S. boulardii 250 mg t.i.d. or 500 mg b.i.d. for patients with chronic stable disease or to maintain remission S. boulardii 250 mg t.i.d. or 500 mg b.i.d. for patients with chronic stable disease or to maintain remission

42 Biologicals and IBD-2 DHEA 200 mg/day for patients with refractory disease and low DHEA-S DHEA 200 mg/day for patients with refractory disease and low DHEA-S N-acetyl glucosamine 3000 to 6000 mg/day N-acetyl glucosamine 3000 to 6000 mg/day Boswellia serrata gum resin, 350 mg t.i.d. Boswellia serrata gum resin, 350 mg t.i.d. Aloe vera gel 100 ml b.i.d for patients with ulcerative colitis Aloe vera gel 100 ml b.i.d for patients with ulcerative colitis Mastic gum 1000 mg twice a day, tested in Crohn’s disease Mastic gum 1000 mg twice a day, tested in Crohn’s disease


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