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

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:
PPIs, H2 blockers, calcium blockers,
anticholinergic, antidopaminergic, antiinflammatory, immunosuppressant.
 Nutraceuticals may enhance physiologic
function, complementing or replacing
drugs. Some may act like drugs.
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Esophageal Reflux
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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.
Toxicity of Acid Lowering Drugs
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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
Calcium vs GERD
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With acute esophagitis, LES contraction
becomes dependent upon extracellular Ca
Sohn et al, J Pharmacol Exp Ther. 1997;283:1293-304.
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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
Non-Drug Treatment of GERD
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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.
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Deglycyrrhizinated licorice, aloe, HCl (?)
TJ-43, aka Rikkunshi-to, Liu-Jun-ZiTang, Six Gentleman Formula
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Speeds esophageal acid clearance in children
with GERD, without increasing LES tone. Kawahara
et al, Pediatr Surg Int. 2007
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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
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
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STW 5 (Iberogast) Relieves
Symptoms of Functional Dyspepsia
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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
ASA/NSAID
Gastropathy/Enteropathy
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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
Gastroprotection: Cayenne
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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
Gastroprotection: Vitamin C
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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:
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Adding C reduced ASA-induced gastric lesions
C 1000 mg b.i.d. for 3 days prevented ASA-induced
duodenal injury
Gastroprotection: SAMe
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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.
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Similar protective effects have been
demonstrated in rats.
Yet, the most common side effect of SAMe is
abdominal pain.
H. Pylori Inhibition in vitro
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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
Adjunctive Therapy of H. pylori
Human Studies
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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.
Irritable Bowel Syndromes:
a moving target
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Motility
Stress and anxiety
Flora
Digestion and fermentation
Allergy and specific food intolerance
Pain sensitivity
Inflammation
IBS: Triggers
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Stressful thoughts/events
Microbes
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Bacteria
Yeast
Parasites
Food
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Fiber/lack of fiber
Carbohydrate, form and amount
Specific food intolerance/allergy
CAUSES OF UPPER GI
BACTERIAL OVERGROWTH
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Achlorhydria/hypochlorhydria
Surgical
resection/blind loops
Stasis from abnormal
motility
Strictures
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Fistulas
Diverticulosis
Immune deficiency
Intestinal
giardiasis
Tropical sprue
Malnutrition
EFFECTS OF UPPER GI
BACTERIAL OVERGROWTH
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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
BREATH TESTING FOR
BACTERIAL OVERGROWTH
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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
BACTERIAL OVERGROWTH IS
MORE COMMON THAN SUSPECTED
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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
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
MANAGEMENT OF UGI BACTERIAL
OVERGROWTH INVOLVES DIET,
ANTIBIOTICS
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Low fermentation diet
-restrict sugar, starch, soluble fiber
Antimicrobials (in select cases):
 Metronidazole (anaerobes)
 Tetracyclines (anaerobes)
 Ciprofloxacin (aerobes)
 Bismuth
 Bentonite
Low Fermentation Diet
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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
A Drug-Free
Clinical Approach to IBS
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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
Supplements for IBS
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Probiotics
Prebiotics
Antimicrobial
Spasmolytic
Motility enhancing
Laxative
Antidiarrheal
Probiotics
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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)
Prebiotics
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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
Clinical Uses of Probiotics
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Antibiotic-induced diarrhea
Traveler's diarrhea/acute GI infections
Irritable bowel syndromes
Inflammatory bowel disease
Diverticulitis
Colon cancer prevention
LACTOBACILLI:
BENEFICIAL EFFECTS
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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)
BENEFITS OF
SACCHAROMYCES
BOULARDII
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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
Clinical uses of Prebiotics and Fiber
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Irritable bowel syndromes
Ulcerative colitis
Prevention of colon cancer
Prevention of diverticulitis
Herbs Used for IBS Treatment
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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)
Peppermint Oil for IBS
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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
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Inhibits gall bladder contraction, small bowel transit,
colonic motility Goerg, Spilker Aliment Pharmacol Ther. 2003 ; Asao et al,
Gastrointest Endosc. 2001
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Reduces cellular calcium influx. Hills, Aaronson Gastroenterology.
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Decreases sulfide production by gut flora Ushid et al, J Nutr Sci
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Kills trophozoites of Giardia lamblia.
1991
Vitaminol (Tokyo). 2002
Vidal et al, Exp. Parasitol. 2007
TCM for Symptoms of IBS
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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
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Standarized formula no better than
placebo. Leung et al, Am J Gastroenterol. 2006
Calcium and Fiber for
Chronic Diarrhea
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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
Inflammatory Bowel Disease:
Dietary Decisions
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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
Germinated Barley Foodstuff (GBF)
and Ulcerative Colitis
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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.
Vitamins and IBD
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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
Minerals and IBD
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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.
Biologicals and IBD-1
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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
Biologicals and IBD-2
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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