Nutraceuticals for Nutraceuticals for Gastrointestinal DisordersGastrointestinal Disorders

Leo Galland, M.D., F.A.C.P.Leo Galland, M.D., F.A.C.P.Foundation for Integrated Foundation for Integrated

MedicineMedicine

www.mdheal.orgwww.mdheal.org

Nutraceuticals vs Nutraceuticals vs PharmaceuticalsPharmaceuticals

Pharmaceuticals are mostly used to Pharmaceuticals are mostly used to suppress specific physiological functions:suppress specific physiological functions:

PPIs, H2 blockers, calcium blockers, PPIs, H2 blockers, calcium blockers, anticholinergic, antidopaminergic, anti-anticholinergic, antidopaminergic, anti-inflammatory, immunosuppressant.inflammatory, immunosuppressant.

Nutraceuticals may enhance physiologic Nutraceuticals may enhance physiologic function, complementing or replacing function, complementing or replacing drugs. Some may act like drugs.drugs. Some may act like drugs.

Esophageal RefluxEsophageal Reflux

Results from reflex relaxation of the LES in Results from reflex relaxation of the LES in response to gastric vagal mechanoreceptors response to gastric vagal mechanoreceptors (programmed in brainstem, unrelated to (programmed in brainstem, unrelated to swallowing or gastric pH). Post-prandial swallowing or gastric pH). Post-prandial gastric distension is a key trigger. gastric distension is a key trigger.

PPI’s and H-2 blockers convert acid reflux PPI’s and H-2 blockers convert acid reflux into non-acid reflux. Pepsin and bile present into non-acid reflux. Pepsin and bile present in gastric juice may yet act as esophageal in gastric juice may yet act as esophageal irritants. irritants.

Toxicity of Acid Lowering Toxicity of Acid Lowering Drugs Drugs

May increase development of atrophic May increase development of atrophic gastritis in H. pylori-infected individualsgastritis in H. pylori-infected individuals

Allow gastric bacterial/yeast overgrowth Allow gastric bacterial/yeast overgrowth and post-prandial intra-gastric production and post-prandial intra-gastric production of ethanol and nitrosaminesof ethanol and nitrosamines

May impair absorption of vitamin B12, folic May impair absorption of vitamin B12, folic acid, carotene, minerals and medicationacid, carotene, minerals and medication

Increase risk of hip fracture and Increase risk of hip fracture and pneumonia pneumonia

Calcium vs GERDCalcium vs GERD

With acute esophagitis, LES contraction With acute esophagitis, LES contraction becomes dependent upon extracellular Cabecomes dependent upon extracellular Ca

Sohn et al, J Pharmacol Exp Ther.Sohn et al, J Pharmacol Exp Ther. 1997;283:1293-304.1997;283:1293-304.

Intra-gastric calcium increases esophageal Intra-gastric calcium increases esophageal acid clearance and LES tone, independent acid clearance and LES tone, independent of antacid effects, in patients with GERD.of antacid effects, in patients with GERD.

Rodriguez-Stanley et al, Dig Dis Sci 2004; 49:1862-7 Rodriguez-Stanley et al, Dig Dis Sci 2004; 49:1862-7

Non-Drug Treatment of Non-Drug Treatment of GERDGERD

Small meals eaten slowly in a relaxed Small meals eaten slowly in a relaxed fashion to decrease gastric distention. fashion to decrease gastric distention. Chewing and swallowing enhance Chewing and swallowing enhance esophageal acid clearance.esophageal acid clearance.

Calcium citrate 250 mg after each mealCalcium citrate 250 mg after each meal Postprandial enzymesPostprandial enzymes Red pepper powder 800 mg t.i.d. Red pepper powder 800 mg t.i.d.

Bortolotti et al, NEJM 2002; 346: 947-8.Bortolotti et al, NEJM 2002; 346: 947-8.

Deglycyrrhizinated licorice, aloe, HCl (?)Deglycyrrhizinated licorice, aloe, HCl (?)

TJ-43, TJ-43, akaaka Rikkunshi-to, Liu-Jun- Rikkunshi-to, Liu-Jun-Zi-Tang, Six Gentleman Zi-Tang, Six Gentleman

FormulaFormula Speeds esophageal acid clearance in Speeds esophageal acid clearance in

children with GERD, without increasing LES children with GERD, without increasing LES tone. tone. Kawahara et al, Kawahara et al, Pediatr Surg Int. 2007Pediatr Surg Int. 2007

Stimulates gastric emptying in dyspeptic Stimulates gastric emptying in dyspeptic adults. adults. Tatsuta & Iishi, Aliment Pharmacol Ther. 1993Tatsuta & Iishi, Aliment Pharmacol Ther. 1993

Increases gastric NO production in rats. Increases gastric NO production in rats. Arakawa et al, Drugs Exp Clin Res. 1999Arakawa et al, Drugs Exp Clin Res. 1999

Raises plasma gastrin and somatostatin in Raises plasma gastrin and somatostatin in human volunteers. human volunteers. Naito et al. Biol Pharm Bull. 2001Naito et al. Biol Pharm Bull. 2001

TJ-43 ComponentsTJ-43 Components

Atractylodes lanceae rhizomeAtractylodes lanceae rhizome Ginseng rootGinseng root Pinellia tuberPinellia tuber HoelenHoelen Zizyphus (jujube) fruitZizyphus (jujube) fruit Aurantii nobilis pericarp (orange peel) Aurantii nobilis pericarp (orange peel) Glycyrrhizae (licorice) rootGlycyrrhizae (licorice) root Zingiberis (ginger) rhizomeZingiberis (ginger) rhizomeHesperidin and L-arginine are major Hesperidin and L-arginine are major

ingredientsingredients

STW 5 (Iberogast) RelievesSTW 5 (Iberogast) RelievesSymptoms of Functional Symptoms of Functional

DyspepsiaDyspepsia Iberis amara: prokinetic effects comparable Iberis amara: prokinetic effects comparable

to metoclopramide and cisapride without to metoclopramide and cisapride without CNS/cardiotoxicity CNS/cardiotoxicity

Spasmolytic herbal extracts: German Spasmolytic herbal extracts: German chamomile, angelica root, caraway, lemon chamomile, angelica root, caraway, lemon balm, milk thistle, celandine, licorice, balm, milk thistle, celandine, licorice, peppermint leaf.peppermint leaf.

Von Armin et al, Am J Gastroenterol. 2007 Von Armin et al, Am J Gastroenterol. 2007

Meltzer et al, Aliment Pharmacol Ther. 2004Meltzer et al, Aliment Pharmacol Ther. 2004

ASA/NSAID ASA/NSAID Gastropathy/EnteropathyGastropathy/Enteropathy

Protective supplements (human trials):Protective supplements (human trials):Vit C 500-1000 mg bidVit C 500-1000 mg bid

SAMe 500 mg/daySAMe 500 mg/day

Cayenne 20 gramsCayenne 20 grams

Deglycyrrhizinated licorice 350 mg tidDeglycyrrhizinated licorice 350 mg tid

Colostrum 125 mg tidColostrum 125 mg tid

L-glutamine 7 grams tidL-glutamine 7 grams tid

Gastroprotection: CayenneGastroprotection: Cayenne

Cayenne protects against aspirin-induced Cayenne protects against aspirin-induced gastric mucosal damage in humans at a gastric mucosal damage in humans at a dose of 20 g administered 30 minutes before dose of 20 g administered 30 minutes before 600 mg of aspirin. 600 mg of aspirin. Yeoh et al, Dig Dis Sci 1995Yeoh et al, Dig Dis Sci 1995..

Capsaicin is gastroprotective against a range Capsaicin is gastroprotective against a range of mucosal toxins in rats but may exert its of mucosal toxins in rats but may exert its effects by irritant-induced pre-conditioning, effects by irritant-induced pre-conditioning, stimulating gastric mucus secretion.stimulating gastric mucus secretion.

Patients with recurrent/chronic abdominal Patients with recurrent/chronic abdominal pain, cayenne aggravates 25-50%. pain, cayenne aggravates 25-50%. Kang et al, Kang et al, Gut 1992Gut 1992

Gastroprotection: Vitamin CGastroprotection: Vitamin C

ASA inhibits absorption of vitamin C ASA inhibits absorption of vitamin C ASA 400 mg bid for 3 days depletes ASA 400 mg bid for 3 days depletes

intragastric vitamin C, suppresses gastric intragastric vitamin C, suppresses gastric blood flow, SOD, GPx. Prevented by blood flow, SOD, GPx. Prevented by Vitamin C 480 mg b.i.d.Vitamin C 480 mg b.i.d.

Healthy volunteers:Healthy volunteers: Adding C reduced ASA-induced gastric lesionsAdding C reduced ASA-induced gastric lesions C 1000 mg b.i.d. for 3 days prevented ASA-C 1000 mg b.i.d. for 3 days prevented ASA-

induced duodenal injuryinduced duodenal injury

Gastroprotection: SAMeGastroprotection: SAMe

S-adenosylmethionine (500 mg) given with S-adenosylmethionine (500 mg) given with aspirin (1300 mg) reduced by 95% the aspirin (1300 mg) reduced by 95% the extent of aspirin-induced erosive gastritis extent of aspirin-induced erosive gastritis in a single-dose study of healthy in a single-dose study of healthy volunteers. volunteers. Laudanno et al, Acta Gastroenterol Latinoam 1984.Laudanno et al, Acta Gastroenterol Latinoam 1984.

Similar protective effects have been Similar protective effects have been demonstrated in rats.demonstrated in rats.

Yet, the most common side effect of SAMe Yet, the most common side effect of SAMe is abdominal pain.is abdominal pain.

H. Pylori Inhibition H. Pylori Inhibition in vitroin vitro

Mastic gum (P lentiscus), used for treatment Mastic gum (P lentiscus), used for treatment of dyspepsia, kills H. pylori, but failed a of dyspepsia, kills H. pylori, but failed a clinical trialclinical trial

Raw garlic and aqueous garlic extract inhibit Raw garlic and aqueous garlic extract inhibit growth (thiosulfinate, MIC of 40 mcg/ml)growth (thiosulfinate, MIC of 40 mcg/ml)

Sulforaphane (cabbage and broccoli) has MIC Sulforaphane (cabbage and broccoli) has MIC of <4 mcg/ml (cabbage juice and broccoli of <4 mcg/ml (cabbage juice and broccoli sprouts have been used to treat PUD)sprouts have been used to treat PUD)

Lactobacilli inhibit growthLactobacilli inhibit growth

Adjunctive Therapy of H. pyloriAdjunctive Therapy of H. pyloriHuman StudiesHuman Studies

Probiotics decrease treatment side effects Probiotics decrease treatment side effects with inconsistent effects on outcomewith inconsistent effects on outcome

Bovine lactoferrin 200 mg bid, may Bovine lactoferrin 200 mg bid, may increase therapeutic response and/or increase therapeutic response and/or decrease side effectsdecrease side effects

N-acetyl cysteine liquid 400 mg tid, N-acetyl cysteine liquid 400 mg tid, increased response to increased response to clarithromycin/lansozrapole.clarithromycin/lansozrapole.

Gurbuz, South Med J. 2005;98:1095-7. Gurbuz, South Med J. 2005;98:1095-7.

Irritable Bowel Syndromes:Irritable Bowel Syndromes:a moving targeta moving target

MotilityMotility Stress and anxietyStress and anxiety FloraFlora Digestion and fermentationDigestion and fermentation Allergy and specific food intoleranceAllergy and specific food intolerance Pain sensitivityPain sensitivity InflammationInflammation

IBS: TriggersIBS: Triggers

Stressful thoughts/eventsStressful thoughts/events MicrobesMicrobes

BacteriaBacteria YeastYeast ParasitesParasites

FoodFood Fiber/lack of fiberFiber/lack of fiber Carbohydrate, form and amountCarbohydrate, form and amount Specific food intolerance/allergySpecific food intolerance/allergy

CAUSES OF UPPER GI CAUSES OF UPPER GI BACTERIAL OVERGROWTHBACTERIAL OVERGROWTH

Achlorhydria/hypo-Achlorhydria/hypo-chlorhydriachlorhydria

Surgical Surgical resection/blind resection/blind loopsloops

Stasis from Stasis from abnormal motilityabnormal motility

StricturesStrictures

FistulasFistulas DiverticulosisDiverticulosis Immune Immune

deficiencydeficiency Intestinal Intestinal

giardiasisgiardiasis Tropical sprueTropical sprue MalnutritionMalnutrition

EFFECTS OF UPPER GI EFFECTS OF UPPER GI BACTERIAL OVERGROWTHBACTERIAL OVERGROWTH

Carbohydrate/fiber intolerance, Carbohydrate/fiber intolerance, bloating, altered bowel habit, bloating, altered bowel habit, fatiguefatigue

Vitamin B12 deficiencyVitamin B12 deficiency Bile salt dehydroxylationBile salt dehydroxylation

Impairs formation of micellesImpairs formation of micelles Bile salt deconjugationBile salt deconjugation

Increases colonic water secretionIncreases colonic water secretion Inhibit monosaccharide transportInhibit monosaccharide transport

BREATH TESTING FOR BREATH TESTING FOR BACTERIAL OVERGROWTHBACTERIAL OVERGROWTH

FALSE POSITIVESFALSE POSITIVES Smoking, sleeping, eatingSmoking, sleeping, eating Soluble fiber/FOSSoluble fiber/FOS Rapid intestinal transitRapid intestinal transit

FALSE NEGATIVESFALSE NEGATIVES Colonic hyperacidity (low stool pH)Colonic hyperacidity (low stool pH) Absence of appropriate floraAbsence of appropriate flora Delayed gastric emptyingDelayed gastric emptying AntibioticsAntibiotics

BACTERIAL OVERGROWTH IS BACTERIAL OVERGROWTH IS MORE COMMON THAN MORE COMMON THAN

SUSPECTEDSUSPECTED 202 patients with IBS underwent 202 patients with IBS underwent

hydrogen breath testinghydrogen breath testing 157 (78%) had SBBO and were 157 (78%) had SBBO and were

treated with antibioticstreated with antibiotics 25/47 patients had normal breath 25/47 patients had normal breath

tests at follow-uptests at follow-up Diarrhea and abdominal pain were Diarrhea and abdominal pain were

significantly improved by treatmentsignificantly improved by treatment

SBBO AND IBS: SBBO AND IBS: CONCLUSIONSCONCLUSIONS

Elimination of SBBO eliminated IBS in Elimination of SBBO eliminated IBS in 12/25 of patients:12/25 of patients:

48 % of patients with IBS and 48 % of patients with IBS and abnormal breath tests who abnormal breath tests who responded to antibiotics with normal responded to antibiotics with normal breath tests no longer met Rome breath tests no longer met Rome criteria for IBScriteria for IBS

Pimentel M et al, AM J Gastroenterol Pimentel M et al, AM J Gastroenterol 20002000

MANAGEMENT OF UGI MANAGEMENT OF UGI BACTERIAL OVERGROWTH BACTERIAL OVERGROWTH

INVOLVES DIET, ANTIBIOTICSINVOLVES DIET, ANTIBIOTICS

Low fermentation dietLow fermentation diet-restrict sugar, starch, soluble -restrict sugar, starch, soluble

fiberfiber Antimicrobials (in select cases):Antimicrobials (in select cases):

Metronidazole (anaerobes)Metronidazole (anaerobes) Tetracyclines (anaerobes)Tetracyclines (anaerobes) Ciprofloxacin (aerobes)Ciprofloxacin (aerobes) BismuthBismuth BentoniteBentonite

Low Fermentation DietLow Fermentation Diet

Basic diet: no wheat, sucrose, lactoseBasic diet: no wheat, sucrose, lactose Additional restrictionsAdditional restrictions

-no glutinous grains-no glutinous grains

-no cereal grains, potatoes-no cereal grains, potatoes

-restrict fruits, juices, honey-restrict fruits, juices, honey

-restrict fructose, fructans-restrict fructose, fructans

-avoid legumes-avoid legumes

-cook all vegetables-cook all vegetables

A Drug-Free A Drug-Free Clinical Approach to IBSClinical Approach to IBS

Avoid/reduce medications with GI side Avoid/reduce medications with GI side effects effects

Evaluate the role of infection or Evaluate the role of infection or microbial overgrowth/deficit microbial overgrowth/deficit (dysbiosis)(dysbiosis)

Individualized dietary prescriptionIndividualized dietary prescription Stress management, hypnotherapyStress management, hypnotherapy Nutraceutical decision treeNutraceutical decision tree

Supplements for IBSSupplements for IBS

ProbioticsProbiotics PrebioticsPrebiotics AntimicrobialAntimicrobial SpasmolyticSpasmolytic Motility enhancingMotility enhancing LaxativeLaxative AntidiarrhealAntidiarrheal

ProbioticsProbiotics

Lactic acid producers: Lactobacilli Lactic acid producers: Lactobacilli (acidophilus, plantarum, casei, salivarius, (acidophilus, plantarum, casei, salivarius, reuterri, sporogenes), Bifidobacteria, reuterri, sporogenes), Bifidobacteria, StreptococciStreptococci

Non-pathogenic E. coliNon-pathogenic E. coli Soil-derived organisms: Bacilli Soil-derived organisms: Bacilli

(laterosporus, subtilis)(laterosporus, subtilis) Saccharomyces boulardii (yeast against Saccharomyces boulardii (yeast against

yeast)yeast)

PrebioticsPrebiotics

Foods that support the growth of probiotics: Foods that support the growth of probiotics: bran, psyllium, resistant starch (high bran, psyllium, resistant starch (high amylose), oligofructose (FOS), inulin, amylose), oligofructose (FOS), inulin, germinated barley foodstuff (GBF), synthetic germinated barley foodstuff (GBF), synthetic oligosaccharides oligosaccharides

FOS is found in onions, garlic, rye, FOS is found in onions, garlic, rye, blueberries, bananas, chicory. Dietary intake blueberries, bananas, chicory. Dietary intake averages 2-8 gm/day. averages 2-8 gm/day.

Inulins are derived from chicory and artichokeInulins are derived from chicory and artichoke

Clinical Uses of ProbioticsClinical Uses of Probiotics

Antibiotic-induced diarrheaAntibiotic-induced diarrhea Traveler's diarrhea/acute GI Traveler's diarrhea/acute GI

infectionsinfections Irritable bowel syndromesIrritable bowel syndromes Inflammatory bowel diseaseInflammatory bowel disease DiverticulitisDiverticulitis Colon cancer preventionColon cancer prevention

LACTOBACILLI: LACTOBACILLI: BENEFICIAL EFFECTSBENEFICIAL EFFECTS

Produce organic acids: lower bowel pHProduce organic acids: lower bowel pH Produce H202Produce H202 Antagonize enteropathogenic E. Coli, Antagonize enteropathogenic E. Coli,

Salmonella, Staphylococci, Candida albicans, Salmonella, Staphylococci, Candida albicans, and Clostridia sppand Clostridia spp

Degrade N-nitrosaminesDegrade N-nitrosamines Anti-tumor glycopeptides (L. bulgaricus)Anti-tumor glycopeptides (L. bulgaricus) Stimulate balanced immune responsesStimulate balanced immune responses Decrease rate of post-op infection (L plantarum)Decrease rate of post-op infection (L plantarum)

BENEFITS OF BENEFITS OF SACCHAROMYCES SACCHAROMYCES

BOULARDIIBOULARDII

Stimulates production of sIgAStimulates production of sIgA Protects against antibiotic and Protects against antibiotic and

traveler’s diarrheatraveler’s diarrhea Helps reverse Helps reverse C difficileC difficile colitis colitis Improves acute diarrheal disease in Improves acute diarrheal disease in

childrenchildren SAIF inhibits NFkB induction of IL-8 SAIF inhibits NFkB induction of IL-8

gene expressiongene expression

Clinical uses of Prebiotics and Clinical uses of Prebiotics and FiberFiber

Irritable bowel syndromesIrritable bowel syndromes Ulcerative colitisUlcerative colitis Prevention of colon cancerPrevention of colon cancer Prevention of diverticulitisPrevention of diverticulitis

Herbs Used for IBS Herbs Used for IBS TreatmentTreatment

Aloe, various speciesAloe, 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 speciesChamomile, various species Caraway (Carum copticum)Caraway (Carum copticum) Lemon balm (Melissa officinalis)Lemon balm (Melissa officinalis) Triphala (Terminalia chebula/belerica, Emblica Triphala (Terminalia chebula/belerica, Emblica

officalis) officalis)

Peppermint Oil for IBSPeppermint Oil for IBS

Enteric coated peppermint oil is twice as effective Enteric coated peppermint oil is twice as effective as placebo for symptom relief; effect lasts after as placebo for symptom relief; effect lasts after Rx ends. Rx ends. Capello et al, Dig Liver Dis. 2007Capello et al, Dig Liver Dis. 2007

Inhibits gall bladder contraction, small bowel Inhibits gall bladder contraction, small bowel transit, colonic motility transit, colonic motility Goerg, Spilker Aliment Pharmacol Ther. Goerg, Spilker Aliment Pharmacol Ther.

2003 ; Asao et al, Gastrointest Endosc. 20012003 ; Asao et al, Gastrointest Endosc. 2001 Reduces cellular calcium influx. Reduces cellular calcium influx. Hills, Aaronson Hills, Aaronson

Gastroenterology. 1991 Gastroenterology. 1991 Decreases sulfide production by gut flora Decreases sulfide production by gut flora Ushid et al, J Ushid et al, J

Nutr Sci Vitaminol (Tokyo). 2002 Nutr Sci Vitaminol (Tokyo). 2002 Kills trophozoites of Giardia lamblia. Kills trophozoites of Giardia lamblia. Vidal et al, Exp. Vidal et al, Exp.

Parasitol. 2007Parasitol. 2007

TCM for Symptoms of IBSTCM for Symptoms of IBS

Individualized vs standard formula vs Individualized vs standard formula vs placebo: short-term benefits from placebo: short-term benefits from both formulas, post-treatment both formulas, post-treatment benefits only in the individualized benefits only in the individualized treatment group. treatment group. Bensoussan et al, JAMA 1998Bensoussan et al, JAMA 1998

Standarized formula no better than Standarized formula no better than placebo. placebo. Leung et al, Am J Gastroenterol. 2006 Leung et al, Am J Gastroenterol. 2006

Calcium and Fiber forCalcium and Fiber forChronic DiarrheaChronic Diarrhea

Combination of psyllium and calcium Combination of psyllium and calcium was more effective and better was more effective and better tolerated than loperamide for tolerated than loperamide for controlling symptoms of chronic controlling symptoms of chronic diarrhea. diarrhea. Qvitzau et al, Scand J Gastroenterol. 1988Qvitzau et al, Scand J Gastroenterol. 1988

Psyllium does not prevent calcium Psyllium does not prevent calcium absorption in humans, contrary to absorption in humans, contrary to animal data. animal data. Heaney & Weaver, J Am Geriatr Soc. 1995Heaney & Weaver, J Am Geriatr Soc. 1995

Inflammatory Bowel Disease:Inflammatory Bowel Disease:Dietary DecisionsDietary Decisions

Dietary responses may differ for Crohn’s disease Dietary responses may differ for Crohn’s disease and ulcerative colitis.and ulcerative colitis.

Avoid sucrose and symptom-provoking foods.Avoid sucrose and symptom-provoking foods. The specific carbohydrate diet (SCD), an The specific carbohydrate diet (SCD), an

exclusion diet or a defined formula diet may help exclusion diet or a defined formula diet may help relieve symptoms and may help induce or relieve symptoms and may help induce or maintain remission (Crohn’s). maintain remission (Crohn’s).

Replace vegetable oils with flaxseed oil and/or Replace vegetable oils with flaxseed oil and/or coconut oil (1 to tablespoons a day)coconut oil (1 to tablespoons a day)

Oat bran 60 grams a day for patients with mild to Oat bran 60 grams a day for patients with mild to moderate ulcerative colitismoderate ulcerative colitis

Germinated Barley Foodstuff Germinated Barley Foodstuff (GBF) and Ulcerative Colitis(GBF) and Ulcerative Colitis

GBF 20-30 gm/day helps to induce and GBF 20-30 gm/day helps to induce and maintain remission in patients with maintain remission in patients with ulcerative colitis. ulcerative colitis.

Mechanism: Increased colonic butyrate Mechanism: Increased colonic butyrate production decreases NFkB activationproduction decreases NFkB activation..

Hanai et al. Int J Mol Med. 2004 May;13(5):643-7.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. J Gastroenterol. 2003;38:134-41. Kanauchi et al, Int J Mol Med. 2003;12:701-4Kanauchi et al, Int J Mol Med. 2003;12:701-4 Kanauchi et al. J Gastroenterol. 2002; 37 Suppl 14:67-72. Kanauchi et al. J Gastroenterol. 2002; 37 Suppl 14:67-72. . .

Vitamins and IBDVitamins and IBD

Folic acid, 800 mcg/day or more, especially for patients Folic acid, 800 mcg/day or more, especially for patients with high homocysteine or taking 5-ASA derivatrivewith high homocysteine or taking 5-ASA derivatrive

Vitamin B12, 1000 mcg a month for patients with CD, Vitamin B12, 1000 mcg a month for patients with CD, those receiving folic acid or with high homocysteine those receiving folic acid or with high homocysteine

Vitamin B6, 10 to 20 mg/day, especially for patients Vitamin B6, 10 to 20 mg/day, especially for patients with high homocysteine or taking high dose folic acidwith high homocysteine or taking high dose folic acid

Vitamin D3, 1000 IU/day or more to maintain levels of Vitamin D3, 1000 IU/day or more to maintain levels of 25-OH vitamin D at 40 mcg/ml25-OH vitamin D at 40 mcg/ml

An antioxidant supplying vitamin E 400 IU/day and An antioxidant supplying vitamin E 400 IU/day and vitamin C 500 to 1000 mg/dayvitamin C 500 to 1000 mg/day

Vitamin K, optimal dose unknownVitamin K, optimal dose unknown

Minerals and IBDMinerals and IBD

Zinc, 25 to 200 mg/day, to maintain Zinc, 25 to 200 mg/day, to maintain plasma zinc above 800 mg/Lplasma zinc above 800 mg/L

Calcium 1000 mg/day for patients on Calcium 1000 mg/day for patients on steroids or with low dietary calcium.steroids or with low dietary calcium.

Selenium 200 mcg/day, especially for Selenium 200 mcg/day, especially for patients with ileal resection or on liquid patients with ileal resection or on liquid formula dietsformula diets

Magnesium citrate (150 to 900 mg/day) for Magnesium citrate (150 to 900 mg/day) for patients with urolithiasis. patients with urolithiasis.

Chromium 600 mcg/day for patients with Chromium 600 mcg/day for patients with steroid-induced hyperglycemia. steroid-induced hyperglycemia.

Biologicals and IBD-1Biologicals and IBD-1

Fish oils supplying 4000 to 5000 Fish oils supplying 4000 to 5000 mg/day of omega-3 fatty acids (EPA mg/day of omega-3 fatty acids (EPA + DHA)+ DHA)

VSL-3 (one sachet twice a day) for VSL-3 (one sachet twice a day) for patients with mild to moderate UC or patients with mild to moderate UC or pouchitis.pouchitis.

S. boulardiiS. boulardii 250 mg t.i.d. or 500 mg 250 mg t.i.d. or 500 mg b.i.d. for patients with chronic stable b.i.d. for patients with chronic stable disease or to maintain remission disease or to maintain remission

Biologicals and IBD-2Biologicals and IBD-2

DHEA 200 mg/day for patients with DHEA 200 mg/day for patients with refractory disease and low DHEA-Srefractory disease and low DHEA-S

N-acetyl glucosamine 3000 to 6000 mg/dayN-acetyl glucosamine 3000 to 6000 mg/day Boswellia serrataBoswellia serrata gum resin, 350 mg t.i.d. gum resin, 350 mg t.i.d. Aloe vera Aloe vera gel 100 ml b.i.d for patients with gel 100 ml b.i.d for patients with

ulcerative colitisulcerative colitis Mastic gum 1000 mg twice a day, tested in Mastic gum 1000 mg twice a day, tested in

Crohn’s diseaseCrohn’s disease