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Nutraceuticals for Gastrointestinal Disorders

Nutraceuticals for Gastrointestinal Disorders. Leo Galland, M.D., F.A.C.P. Foundation for Integrated Medicine www.mdheal.org. Nutraceuticals vs Pharmaceuticals. Pharmaceuticals are mostly used to suppress specific physiological functions:

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Nutraceuticals for Gastrointestinal Disorders

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

  2. Nutraceuticals vs Pharmaceuticals • 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. • 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 • 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 • Increase risk of hip fracture and pneumonia

  5. Calcium vs GERD • With acute esophagitis, LES contraction becomes dependent upon extracellular Ca Sohn et al, J Pharmacol Exp Ther.1997;283:1293-304. • 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. • Calcium citrate 250 mg after each meal • Postprandial enzymes • Red pepper powder 800 mg t.i.d. Bortolotti et al, NEJM 2002; 346: 947-8. • 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. 2007 • Stimulates gastric emptying in dyspeptic adults. Tatsuta & Iishi, Aliment Pharmacol Ther. 1993 • Increases gastric NO production in rats. Arakawa et al, Drugs Exp Clin Res. 1999 • Raises plasma gastrin and somatostatin in human volunteers. Naito et al. Biol Pharm Bull. 2001

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

  9. STW 5 (Iberogast) RelievesSymptoms of Functional Dyspepsia • 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. Von Armin et al, Am J Gastroenterol. 2007 Meltzer et al, Aliment Pharmacol Ther. 2004

  10. ASA/NSAID Gastropathy/Enteropathy • Protective supplements (human trials): Vit C 500-1000 mg bid SAMe 500 mg/day Cayenne 20 grams Deglycyrrhizinated licorice 350 mg tid Colostrum 125 mg 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 1995. • 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

  12. Gastroprotection: 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. • Healthy volunteers: • Adding C reduced ASA-induced gastric lesions • 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 1984. • Similar protective effects have been demonstrated in rats. • 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 • 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) • Lactobacilli inhibit growth

  15. Adjunctive Therapy of H. pyloriHuman Studies • Probiotics decrease treatment side effects with inconsistent effects on outcome • 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. Gurbuz, South Med J. 2005;98:1095-7.

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

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

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

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

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

  21. BACTERIAL OVERGROWTH IS MORE COMMON THAN SUSPECTED • 202 patients with IBS underwent hydrogen breath testing • 157 (78%) had SBBO and were treated with antibiotics • 25/47 patients had normal breath tests at follow-up • 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 Pimentel M et al, AM J Gastroenterol 2000

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

  24. Low Fermentation Diet • Basic diet: no wheat, sucrose, lactose • 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 • Evaluate the role of infection or microbial overgrowth/deficit (dysbiosis) • Individualized dietary prescription • Stress management, hypnotherapy • Nutraceutical decision tree

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

  27. Probiotics • Lactic acid producers: Lactobacilli (acidophilus, plantarum, casei, salivarius, reuterri, sporogenes), Bifidobacteria, Streptococci • Non-pathogenic E. coli • Soil-derived organisms: Bacilli (laterosporus, subtilis) • 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 • FOS is found in onions, garlic, rye, blueberries, bananas, chicory. Dietary intake averages 2-8 gm/day. • Inulins are derived from chicory and artichoke

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

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

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

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

  33. Herbs Used for IBS Treatment • Aloe, various species • Fennel seed (Foeniculum vulgaris) • Ginger (Zingiber officinalis) • Slippery elm bark (Ulmus rubra) • Marshmallow root (Althea officinalis) • Cumin (Curcuma longa) • Chamomile, various species • Caraway (Carum copticum) • Lemon balm (Melissa officinalis) • 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. 2007 • Inhibits gall bladder contraction, small bowel transit, colonic motility Goerg, Spilker Aliment Pharmacol Ther. 2003 ; Asao et al, Gastrointest Endosc. 2001 • Reduces cellular calcium influx. Hills, Aaronson Gastroenterology. 1991 • Decreases sulfide production by gut flora Ushid et al, J Nutr Sci Vitaminol (Tokyo). 2002 • 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 • Standarized formula no better than placebo. Leung et al, Am J Gastroenterol. 2006

  36. Calcium and Fiber forChronic 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. 1988 • 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. • 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). • 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

  38. Germinated Barley Foodstuff (GBF) and Ulcerative Colitis • GBF 20-30 gm/day helps to induce and maintain remission in patients with ulcerative colitis. • Mechanism: Increased colonic butyrate production decreases NFkB activation. Hanai et al. Int J Mol Med. 2004 May;13(5):643-7. Kanauchi et al. J Gastroenterol. 2003;38:134-41. Kanauchi et al, Int J Mol Med. 2003;12:701-4 Kanauchi et al. J Gastroenterol. 2002; 37 Suppl 14:67-72. .

  39. Vitamins and IBD • 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 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 • An antioxidant supplying vitamin E 400 IU/day and vitamin C 500 to 1000 mg/day • Vitamin K, optimal dose unknown

  40. Minerals and IBD • 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. • 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. • 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) • 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

  42. Biologicals and IBD-2 • DHEA 200 mg/day for patients with refractory disease and low DHEA-S • N-acetyl glucosamine 3000 to 6000 mg/day • Boswellia serrata gum resin, 350 mg t.i.d. • 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

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