PATHOGENESIS AND INTEGRATIVE MANAGEMENT OF INFLAMMATORY BOWEL [PDF]

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PATHOGENESIS AND INTEGRATIVE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

Gerard E. Mullin MD Associate Professor of Medicine Johns Hopkins University School of Medicine International Congress on Natural Medicine June 9, 2014

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INTERACTION OF VARIOUS FACTORS CONTRIBUTING TO CHRONIC INTESTINAL INFLAMMATION IN A GENETICALLY SUSCEPTIBLE HOST

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PATHOGENESIS OF IBD

NSAIDs Antibiotics Infections Viral Bacterial Parasitic Luminal antigens Food antigens Bacteria Bacterial products FMLP LPS PGPS Th1/Th17 vs. Th2 Translocation of luminal contents Initiating Events Mucosal Damage Abnormal Immune Response Chronic Inflammation

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PATHOGENESIS OF IBD

Macrophage Inflammation

IL2-R

T9 4F2 Activated Th1 Cell

Ag

IL-12 Mucosal injury

IL-1 IL-6 TNF-a IL-8, MIP-1a

+ +

IL2-R

T9 4F2

TNF-a ADCC Lymphokines OH. O2

.-

IL-2, IFNg

IL-1 + +

CD45R

CD4

Memory T Cell Lymphokines

ROS

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INFLAMMATORY BOWEL DISEASE

Chronic inflammation, tissue injury
Gut repair is multimodal
Increased oxidative stress both in the gut

and systemically

Uncontrolled inflammation leads to fibrosis

in Crohn’s disease and higher risk of cancer in inflammatory bowel disease (IBD)

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Enteral > Placebo Enteral < GCS Enteral = TPN Polymeric = Elemental

SUMMARY: EFFECTIVENESS OF NUTRITIONAL SUPPORT FOR CROHN’S DISEASE

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ENTERAL NUTRITION MECHANISMS OF ACTION?

Enteral Nutrition Gut Permeability Bowel Rest Glutamine Antigenic Load Fat Composition Gut Flora

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POPULAR DIETS FOR IBD

DIE IET RAT ATIONALE PLA PLAN EVID IDENCE

Elimination Lower antigenic burden-up to 66% of CD pts. report food intolerances 1 Eliminate known and suspected provocative foods 2-4 weeks then reintroduce: 1 new food per day-process may take 2-3 months Mishkin S. Am J Clin Nutr. 1997 Feb;65(2):564-7. Giaffer MH, Cann P , Holdsworth CD. Aliment Pharmacol Ther. 1991 Apr;5(2):115-25 Specific Carbohydrate Diet Eliminate poorly digestible CHO’s to limit fermentation in small bowel. Avoid complex carbohydrates Allowed: meat, fish, eggs, vegetables, nuts, low-sugar fruits, oils, honey Avoid: starches, grains, pasta, legumes, and breads none Maker’s Diet 40 day diet and lifestyle regimen based upon “biblical principles” Focuses on four components of total health- physical, mental, spiritual, and

emotional. Consists of a phased approach.

Recommended foods are unprocessed, unrefined, and untreated with pesticides or hormones none Anti-inflammatory Diet Provide foods rich in flavonoids and phytonutrients Avoid red meat, dairy-favour vegetables, fish, olive oil, walnuts, etc. none

Brown AC, Roy M. Does evidence exist to include dietary therapy in the treatment of Crohn’s disease? Expert Rev. Gastroenterol. Hepatol.4(2),191–215 (2010).

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DIET RESEARCH: ASSOCIATIONS

2011 review article showed associations between dietary intake and risk of IBD Fa Fats and and Me Meat ats

High dietary intakes associated with an increa

eased ed risk of IBD Fib ibre re and and Fru ruit its

High dietary intakes were associated with dec

ecrea eased sed risk of CD Veg eget etables es

High dietary intake was associated with dec

ecrea eased ed risk of UC  Limitations with review (different studies, majority were retrospective).No particular foods, but component common to many foods may have a role. Studies did not explore role

f diet on current disease activity.

Hou JK, et al. Am J Gastroenterol . 2011;

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CONTROL IBD SYMPTOMS

Avoid “trigger” foods Not all IBD patients are affected by the same foods Common foods that may cause GI discomfort:

High-fibre foods (e.g., nuts, raw, leafy vegetables)
High-fat foods (e.g., greasy, fried foods)
Caffeine (e.g., coffee, tea, soda, chocolate)
Alcohol
Carbonated beverages
Dairy (lactose)
Sugar alcohols in sugar-free foods (e.g., sorbitol)
Spicy foods

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DYSBIOSIS AND IBD

Illness occurs through changes in

gut microbiota from drugs, environmental toxins and climate all stimulate or inhibit different types of microorganisms

Contributes to illness through

changes in intestinal permeability and altered gut microbiology

Stress, food, medical drugs,

environmental toxins and climate all stimulate or inhibit different types of microorganisms

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SKEWING THE MICROBIOME AND IBD

Devkota S, Wang Y, Musch MW, Leone V , Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB. Nature. 2012 Jul 5;487(7405):104-8

The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.

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MILK FAT INDUCES COLITIS IN GENETICALLY SUSCEPTIBLE HOST VIA DYSBIOSIS

Devkota S, Wang Y, Musch MW, Leone V , Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB. Nature. 2012 Jul 5;487(7405):104-8

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SCOPE OF PROBIOTIC PRODUCTS AND USES

Sanders M E et al. Gut 2013;62:787-796

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PROBIOTICS PREVENTS UC FLARE

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POTENTIAL MECHANISMS OF ACTION OF

SACCHAROMYCES BOULARDII (SBC).

World J Gastroenterol. 2010 May 14; 16(18): 2202–2222.

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BENEFITS OF PROBIOTICS IN IBD: MECHANISMS OF ACTION

INHIBI BIT P PATHO HOGENIC C BACTER ERIA IA IMPROVE VE E EPITHELI LIAL L FUNCTION ON IMMUNORE OREGULATION ON pH SCFA’s IL-10, TGF Bacteriocidal proteins Healing TNF , IL-12 Epithelia binding Mucus sIgA Epithelial invasion Barrier Integrity NFkB

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World J Gastroenterol. 2010 May 14; 16(18): 2202–2222. SBC does not prevent relapse of post-op CD Clin Gastroenterol Hepatol. 2013 Mar 1. doi:pii: S1542-3565(13)00278-4

RANDOMISED, CONTROLLED TRIALS FOR CHRONIC DISEASE CONDITIONS USING S. BOULARDII

World J Gastroenterol. 2010 May 14; 16(18): 2202–2222.

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SUMMARY OF PROBIOTICS IN IBD

No consistent effects have been noted in treating or

preventing relapse of Crohn's disease.

For ulcerative colitis, benefits have been described for a

combination

f

Lactobacillus, Bifidobacterium and Streptococcus probiotic species or for Escherichia coli Nissle in inducing and maintaining remission of disease activity in mild to moderately severe ulcerative colitis.

Primary prevention of pouchitis and reducing the likelihood
f relapse after successful antibiotic treatment has also

been successful, receiving an ‘A’ recommendation.

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POSSIBLE EXPLANATIONS AND PROPOSED SOLUTIONS FOR BETTER RESULTS OF PROBIOTICS FOR IBD

Gut 2013;62:787–796. doi:10.1136/gutjnl-2012-30250

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PROBIOTIC FOODS

Dairy-based

Yoghurt
Cheese
Acidophilus milk
Kefir
Yogurt
Cheese
Acidophilus milk
Kefir

Nondairy-based

Brined olives
Salted gherkins
Sauerkraut
Kimchi
Miso
Natto
Tempeh
Poi
Tanzania Togwa

Lin, D.C. NCP 18:497, 2003 Lipski, E. IN: Integrative Gastroenterology 2011

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PREBIOTICS IN UC

AUTHO UTHOR YEAR AR FIBRE BRE STUD TUDY OU OUTCO COME

Fernandez- Banares 1999 Plantago Ovata seed fibre 10 gm Fiber +/- Mesalamine = to Mesalamine Kanauci 2002 2003 30 gm barley Mod to active UC disease activity Hallert 2003 Oat bran 60 gm (20gm fibre) In remission abd pain Increase faecal butyrate Welters 2002 Inulin 24 gm IAPA pouch inflammation

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“Relax, sir. The hair in your soup provides fibre.”

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SHORT CHAIN FATTY ACIDS

Malabsorbed carbohydrate and nondigestible fibers are fermented by colonic bacteria into short chain fatty acids (SCFA).

SCFA primary fuel for colon
SCFA absorbed by colonic mucosa & used as energy in SBS
SCFA enhance sodium and water absorption
SCFA exert trophic effects in SB and colon
Regulates cell

Jeppesen et al. JPEN 1999;23:S101-S104 Royall D et al. Am J Gastroenterol 1992;87:751

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SCFA ENEMAS

(60-100 mmol/100ml 1-2 times/day)

Butyrate, acetate, and propionate are SCFAs, which are by-products of colonic fermentation.

Primary fuel for the colon
Trophic effects, increases sodium/water absorption
Mucosal levels are decreased in distal ulcerative

colitis

SCFA enemas are used for refractory distal

ulcerative colitis

1994;89(2):179-183. Patz J, et al. Am J Gastro. 1996;91(4):731-734. Scheppach W. Dig Dis Sci. 1996;41(11):2254-2259. Sengore AJ. Dis Col Rectum. 1992;35:923-927. Scheppach W. Gastroenterol. 1992;103;51-58.

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PROSPECTIVE STUDIES OF SCFA FOR LEFT-SIDED ULCERATIVE COLITIS

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Extrac

acell llular ar m matrix ix format ation

Ce

Cell m migr gration

Di

Diffe fferentiat atio ion

Immun

une r e regul ulation

Tissue r

remode delin ing

Regu

gula lates i infla lammat ation

Promotes h

heal aling

TGF TGF-β

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TGF-β-ENRICHED FORMULAS FOR CROHN’S DISEASE USING WHEY PROTEIN

3 cohort studies evaluated TGF-β-enriched formula in patients

with Crohn's disease

TGF-β diet for 8 weeks as sole nutrition, improvements:

– ESR and CRP levels – Serum albumin levels – Mucosal healing, Clinical Disease Activity – Serum IL-1β, IL-8, and IFN-γ

Th

The e rel elapse se rate w e was h s high a after er rem emiss ssion achieved eved w with nutritional nal t therapy py

Beattie RM, Schiffrin EJ, Donnet-Hughes A, et al. Aliment Pharmacol Ther. 1994;8:609-615. Fell JM, Paintin M, Arnaud-Battandier F , et al. Aliment Pharmacol Ther. 2000;14:281-289. Afzal NA, Van Der Zaag-Loonen HJ, et al. Aliment Pharmacol Ther. 2004;20:167-172.

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C Hartman, et al, IMAJ, July 2008

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OMEGA-3 MODULATION OF ARACHIDONIC ACID CASCADE

Cell membrane Phospholipase A2 Arachidonic 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

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FA FACTOR EFFE FFECT O OF OMEG MEGA-3 3 FATTY TTY A ACID Platelet activating factor (PAF)

↓

Platelet-derived growth factor (PDGF)

↓

Oxygen free radicals

↓

Lipid hydroperoxides

↓

IL-1, IL-6, and TNF

↓

NF-kB, PPARs adhesion molecules

↓

EFFECTS OF OMEGA-3 FATTY ACIDS ON FACTORS INVOLVED IN THE PATHOPHYSIOLOGY OF INFLAMMATION

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FISH OILS AND IBD: ANIMAL 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;103(30):11276-11281. Clin Nutr. 2006;25(3):466-476.

Nutrition. 2006;22(3):275-282.

World J Gastroenterol. 2005;11(47):7466-7472. Proc Natl Acad Sci U S A. 2005;102(21):7671-7676. Inflamm Bowel Dis. 2005;11(4):340-349.

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FISH OILS & UC INDUCTION OF REMISSION

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

STUD TUDY EPA PA DHA DHA CLINI NICA CAL REMISSIO ISSION ENDOSCOPI OPIC EVIDENCE NCE Almallah 1998 3.2 g/d 2.4 g/d p<0.05 p=0.013 Aslan 1992 2.7 g/d 1.8 g/d *p<0.05 NR Stenson 1992 3.24 g/d 2.16 g/d p=0.001 p=0.054

Level A Evidence

SLIDE 35

FISH OIL FOR THE MAINTENANCE OF ULCERATIVE COLITIS

Turner, D et al. Inflamm Bowel Dis. 2011 Jan;17(1):336-45

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FISH OIL FOR THE MAINTENANCE OF CD

Turner, D et al. Inflamm Bowel Dis. 2011 Jan;17(1):336-45

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Combined oral supplement to determine whether enteral nutrition can provide steroid sparing effect (n=121, 86 completed study) for 6 months 18 oz. of either:

Nutritionally balanced oral supplement (UCNS)
CHO-based placebo

Clin Gastro Hep. 2005;3:358-369.

AN ORAL SUPPLEMENT ENRICHED WITH FISH OIL, SOLUBLE FIBRE AND ANTIOXIDANTS FOR CORTICOSTEROID SPARING IN ULCERATIVE COLITIS: A RANDOMISED, CONTROLLED TRIAL

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UCNS FORMULA PER 8 OZ

310 kcal [16.1/49.7/6.5%

protein/CHO/lipid]

Fish oil (1.09 g EPA/0.46 g

DHA)

3.5 g EPA/DHA per day
FOS 2.9 g
Gum arabic 2.2 g
Calcium (mg)- 432
Phosphorus (mg)- 300
Magnesium (mg)- 108
β-carotene (μg)- 1185
Vitamin A (IU)- 1320
Vitamin D (IU)- 192
Vitamin E (IU)- 72
Vitamin K (μg)- 32
Vitamin C (mg)- 156
Folic acid (μg)- 456
Zn (mg)- 7
Se (µg)- 22

SLIDE 39

AN ORAL SUPPLEMENT ENRICHED WITH FISH OIL, SOLUBLE FIBRE AND ANTIOXIDANTS FOR CORTICOSTEROID SPARING IN ULCERATIVE COLITIS: A RANDOMISED, CONTROLLED TRIAL

SLIDE 40

Clin Gastro Hep. 2005;3:358-369.

AN ORAL SUPPLEMENT ENRICHED WITH FISH OIL, SOLUBLE FIBRE AND ANTIOXIDANTS FOR CORTICOSTEROID SPARING IN ULCERATIVE COLITIS: A RANDOMISED, CONTROLLED TRIAL

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CHANGE IN NUTRITION AND DISEASE MEASURES AFTER 4 MONTHS OF SUPPLEMENTATION

Wiese D M et al. Nutr Clin Pract 2011; 26:463-473

After 4 months, those patients with higher EPA levels had a significantly higher IBDQ (mean ± SD, 179.1 ± 26.6 vs 114.6 ± 35.9; P < .001) and lower CDAI (116 ± 94.5 vs 261.8 ± 86.5; P = .005) compared with those with lower levels of EPA

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Wiese D M et al. Nutr Clin Pract 2011;26:463-473

Increased fat-free and fat mass deposition,
Improved vitamin D status
Improvement in quality of life and lower

disease activity

Open label; high drop out rate; small sample

Plas asma ph a phospholi lipi pid F d FA le leve vels

THE EFFECTS OF AN ORAL SUPPLEMENT ENRICHED WITH FISH OIL, PREBIOTICS, AND ANTIOXIDANTS ON NUTRITION STATUS IN CROHN’S DISEASE PATIENTS

Vitam amin D D an and d PTH l H leve vels

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INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE (IBDQ) AND CROHN’S DISEASE ACTIVITY INDEX (CDAI) DURING TREATMENT WITH IBD NUTRITIONAL FORMULA (IBDNF) SUPPLEMENTATION IN PATIENTS WITH FINAL EICOSAPENTAENOIC ACID (EPA) >2%

Wiese D M et al. Nutr Clin Pract 2011;26:463-473

There was a significant increase in IBDQ (+41.4 [23.1, 47.0]; P = .002) and decrease in CDAI (−47.8 [−65, −37.8]; P = .05) in patients with higher EPA levels

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PREVALENCE OF VITAMIN D DEFICIENCY IN UNSELECTED COHORTS OF PATIENTS WITH IBD

V . P . Mouli and A. N. Ananthakrishnan Alimentary Pharmacology & Therapeutics Volume 39, Issue 2, Article first published online: 17 NOV 2013

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OBSERVATIONAL STUDIES OF THE ASSOCIATION BETWEEN VITAMIN D LEVELS AND OUTCOMES IN CROHN’S DISEASE AND ULCERATIVE COLITIS 1

V . P . Mouli and A. N. Ananthakrishnan Alimentary Pharmacology & TherapeuticsVolume 39, Issue 2, Article first published online: 17 NOV 2013

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Higher levels of 25 (OH)D3 predict lower risk of CD and higher use of vitamin D supplementation predicts lower risk of UC

Gastroenterology 2012;142;3:482-489

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Gastroenterology 2012;142;3:482-489

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UNANSWERED CLINICAL QUESTIONS REGARDING THE ROLE OF VITAMIN D IN INFLAMMATORY BOWEL DISEASES

V . P . Mouli and A. N. Ananthakrishnan Alimentary Pharmacology & TherapeuticsVolume 39, Issue 2, Article first published online: 17 NOV 2013

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PATHOGENESIS OF IBD

Macroph phage age Infla lammatio ion

IL IL2-R

T9 T9 4F 4F2 Activ ivated ed T Th1 C Cell ll

Ag Ag

IL IL-12 12 Mucosal in inju jury

IL IL-1 I 1 IL-6 6 TNF NF-a IL IL-8, M 8, MIP-1a 1a

+ +

IL IL2-R

T9 T9 4F 4F2

TNF TNF-a AD ADCC Lymph mphoki kines OH OH. O2

.-

IL IL-2, IF , IFN-g

IL IL-1 + +

CD45R D45R

CD CD4

Mem emory T T Cel Cell Lymph mphoki kines

ROS ROS

(-)

SLIDE 52

Nutritional

DNA NA NUCLEUS

MITOCHONDRION

PEROXIS ISOME MES

LYSOSOMES ENDOPLASMIC RETICULUM

CYTOPLASM

LIPID BILAYER OF ALL CELLULAR MEMBRANES

IMPAIRED CELLULAR DEFENSE MECHANISMS IN IBD

Vitam amin E n E Ca Cata talase Cu Cu/Zn S SOD OD Vitam amin E n E + Beta ta-Car arote tene ne

Mn Mn SO SOD + Glutathion

ne P

Perox

xidase

+ G GSH SH

Vitam amin E n E Vitam amin C n C Glutat athi hione ne Peroxi xidas dase GSH SH

Vitami tamins C C an and d E Bet eta-Car arote tene

Beta ta-Car arote tene ne

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PHARMACEUTICAL MODULATION OF THE ARACHIDONIC ACID CASCADE

Cell membrane Phospholipase A2 Arachidonic Acid Cyclooxygenase Lipoxygenase Leukotrienes SRS-A Thromboxane A2 Prostaglandin 2 series Cortisone X Indomethacin Aspirin Ibuprofen Sulfasalazine X Sulfasalazine X Colchicine X

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BOTANICAL MODULATION OF ARACHIDONIC ACID CASCADE

Mullin GE, et al, Expert Review of Gastroenterology and Hepatology, April 2008

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Singarelli B. CCM. 2005;33:S414-416

NF-κB

probiotics

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NATURAL PRODUCTS WITH ANTI-INFLAMMATORY ACTIONS

NFkB kB inhib ibit itors:

Cur

urcumi cuminoids

Ginger
Boswellia
Green Tea extract

(EGCG)

Bromelain
Rosemary (carnosol)
Grape Seed Extract
Phytolens (lentils)
VSL#3
Alpha-lipoic acid
Caffeic acid phenyl esther

(CAPE) Bee Propolis

Resveratrol
1,25-(OH)2D3
GLA (evening primrose oil)
EPA (fish oil)

Infla lammatory ry i inhib ibit itors rs (NFkB kB-inde depe pend ndent nt):

DHA (fish oil)
ALA (flax seed oil)
White Willow Bark
Devil’s Claw

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PHYTONUTRIENTS AND BOTANICALS LIKELY TO BE USEFUL IN INFLAMMATORY CONDITIONS OF THE GI TRACT

SLIDE 58

POLYPHENOLS

Phytochemicals found in food and beverages that are

derived from plants

Nonessential
Anti-inflammatory and vasculoprotective properties
Four polyphenols with anti-inflammatory properties have

been studied in human and animal models of colitis: −Curcumin (turmeric) −Resveratrol (grapes, wine) −EGCG (green tea) −Quercetin (apples, onions, leafy veggies, tea)

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POLYPHENOLS ATTENUATE INFLAMMATION AND INJURY

Mullin GE et al . Expert Review in Gastroenterology Expert Rev Gastroenterol Hepatol. 2008 Apr;2(2):261-80. doi: 10.1586/17474124.2.2.261

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PROPHYLACTIC AND THERAPEUTIC EFFECTS OF POLYPHENOLS FOR COLITIS

POLYPH PHEN ENOL N ROU ROUTE, D , DOS OSE RESULT LTS Resveratrol 2 5-10 mg/kg 2/2 IG 2/2 improvement: clinical, path, mediators, cytokines EGCG 3 5 g/L, 50 mg/kg/D 1 IP , 2 PO 3/3 improvement: clinical, path, mediators, cytokines Curcumin 6 2%, 30-300 mg/kg/D 6 PO, 1 IP 6/6, improvement: clinical, path, mediators, cytokines, markers 4/7 ↑ survival Quercetin 6 5 PO/IG, 0.25- 50 mg/kg/D, enema 10-100 mM/D Overall 3/6 showed efficacy Enema ineffective Animal Studies

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FOODS ASSOCIATED WITH A DECREASE IN INFLAMMATORY MARKERS IN HUMAN INTERVENTIONAL STUDIES

FOOD OOD DURAT ATION EFFE FFECT Extra virgin olive oil Single meal ↓ TXB2 and LTB4 Tomato juice 10 days ↓neutrophil airway influx in asthmatics Tomato drink 26 days ↓TNFalpha production by whole blood Whole tomatoes 28 days No change in CRP Walnuts Single meal ↓monocyte mRNA for TNFa & IL-6 Red wine 4 weeks Reduced CRP and fibrinogen Garlic powder 3 months No effect on CRP , TNF-a Flaxseed flour 2 weeks ↓CRP , fibronectin & serum amyloid A in obese subjects Tea, black 12 weeks 40-50% ↓ CRP in subjects w/CRP>3mg/L. Tea, black 6 weeks ↓CRP & platelet aggregation in healthy men Tea, green 4 weeks No effect on CRP in men; no significant effect on CRP in male smokers Cherries, sweet 4 weeks ↓ CRP and CCL5, no effect on IL-6 in healthy adults

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TOP FOOD ANTIOXIDANTS

Cinnamon Aronia black chokeberry Dry Small Red Bean Dry Red kidney bean Dry Pinto bean Dry Black bean Prune ½ cup Pecan 1 oz Wild blueberry Blueberry Cranberry Artichoke hearts Blackberry cultivated Raspberry Strawberry Sweet cherry

Nutrient Data Laboratory, Agriculture Research Service, US Department of Agriculture

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PLEASE PASS THE BERRIES!

J Med Food. 2007;10;2:258-265.

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RED WINE COOLS COLONIC INFLAMMATION IN UC

Digestion 2011 Aug 26;84(3):238-244.

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TURMERIC (CURCUMA LONGA)

Mechanism of action:

Inhibits TNF-α
Dual inhibitor of arachidonic

acid metabolism

Cortisone-like inhibitory action
n phospholipases
Antioxidant activity

Note: Turmeric is a potent inhibitor of transcription factor NF-κB

SLIDE 66

TURMERIC (CURCUMA LONGA): MAINTENANCE THERAPY FOR ULCERATIVE COLITIS

Randomised, multicentre, double-blind, placebo-

controlled trial from Japan

97 patients enrolled, 89 completed study
All took mesalamine/sulfasalazine
Curcumin 1 g BID vs. placebo
Clinical and endoscopic activity index (CAI, EI)

end points: −Recurrence @ 6 mo (on drug), 12 mo (off) −CAI, EI

Hanai H, et al. Clinical Gastro Hepatol. 2006;4:1502-1506.

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CURCUMIN IN ULCERATIVE COLITIS

Hanai H, et al. Clinical Gastro Hepatol. 2006;4:1502-1506.

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BOSWELLIA AND IBD

AUTH UTHOR DESI ESIGN/# DISEA SEASE SE CO CONTR NTROL DURATION ION RESU RESULTS Madisch et al 2007 DBRCT Collagenous colitis Placebo 6 wks Maintenance of remission superior with Boswellia Gupta et al 2001 Randomized IBD Sulfasalazine 6 wks Induction of remission superior with Boswellia Gupta et al 2001 Randomized UC Sulfasalazine 6 wks Induction of remission not different Gerhardt et al 2001 DBRCT CD Mesalamine 8 weeks Boswelia H15 36% Meslamine 31% remission Holtmeirer er al 2011 DBRCT CD Placebo 52 weeks Boswellia PS0201Bo 60%vs. P 55% remission at 52 wks

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The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non- inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis.

EudraCT-Number 2007-007928-18. Aliment Pharmacol Ther 2013; 38: 490–500

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Aliment Pharmacol Ther. 2013 Oct;38(8):854-63. doi: 10.1111/apt.12464. Epub 2013 Aug 2

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SYSTEMATIC REVIEW: THE EFFICACY OF HERBAL THERAPY IN INFLAMMATORY BOWEL DISEASE

Alimentary Pharmacology & Therapeutics 25 AUG 2013 DOI: 10.1111/apt.12464 http://onlinelibrary.wiley.com/doi/10.1111/apt.12464/full#apt12464-fig-0001

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Aliment ntary Pharmac acology gy & & Therape apeutics 25 AUG 2013 DOI: 10.1111/apt.12464 http://onlinelibrary.wiley.com/doi/10.1111/apt.12464/full#apt12464-fig-0001

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Aliment Pharmacol Ther. 2013 Oct;38(8):854-63. doi: 10.1111/apt.12464. Epub 2013 Aug 2

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