PATHOGENESIS AND INTEGRATIVE MANAGEMENT OF INFLAMMATORY BOWEL...
Transcript of PATHOGENESIS AND INTEGRATIVE MANAGEMENT OF INFLAMMATORY BOWEL...
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
INTERACTION OF VARIOUS FACTORS CONTRIBUTING TO CHRONIC INTESTINAL
INFLAMMATION IN A GENETICALLY SUSCEPTIBLE HOST
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
PATHOGENESIS OF IBD
Macrophage
Inflammation
IL2-R
T9 4F2
Activated Th1 Cell
Ag
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
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)
Enteral > Placebo Enteral < GCS Enteral = TPN
Polymeric = Elemental
SUMMARY: EFFECTIVENESS OF NUTRITIONAL SUPPORT FOR CROHN’S DISEASE
ENTERAL NUTRITION MECHANISMS OF ACTION?
Enteral Nutrition
Gut Permeability
Bowel Rest
Glutamine
Antigenic Load
Fat Composition
Gut Flora
POPULAR DIETS FOR IBD DIET RATIONALE PLAN EVIDENCE 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).
DIET RESEARCH: ASSOCIATIONS 2011 review article showed associations between dietary intake and risk of IBD Fats and Meats • High dietary intakes associated with an increased risk of IBD Fibre and Fruits • High dietary intakes were associated with decreased risk of CD Vegetables • High dietary intake was associated with decreased 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 of diet on current disease activity.
Hou JK, et al. Am J Gastroenterol . 2011;
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
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
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.
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
SCOPE OF PROBIOTIC PRODUCTS AND USES
Sanders M E et al. Gut 2013;62:787-796
PROBIOTICS PREVENTS UC FLARE
POTENTIAL MECHANISMS OF ACTION OF SACCHAROMYCES BOULARDII (SBC).
World J Gastroenterol. 2010 May 14; 16(18): 2202–2222.
BENEFITS OF PROBIOTICS IN IBD: MECHANISMS OF ACTION
INHIBIT PATHOGENIC BACTERIA
IMPROVE EPITHELIAL FUNCTION
IMMUNOREGULATION
pH SCFA’s IL-10, TGF
Bacteriocidal proteins Healing TNF, IL-12
Epithelia binding Mucus sIgA
Epithelial invasion Barrier Integrity NFkB
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.
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 of 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 of relapse after successful antibiotic treatment has also been successful, receiving an ‘A’ recommendation.
POSSIBLE EXPLANATIONS AND PROPOSED SOLUTIONS FOR BETTER RESULTS OF PROBIOTICS FOR IBD
Gut 2013;62:787–796. doi:10.1136/gutjnl-2012-30250
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
PREBIOTICS IN UC
AUTHOR YEAR FIBRE STUDY OUTCOME
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
“Relax, sir. The hair in your soup provides fibre.”
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
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.
PROSPECTIVE STUDIES OF SCFA FOR LEFT-SIDED ULCERATIVE COLITIS
• Extracellular matrix
formation • Cell migration • Differentiation • Immune regulation • Tissue remodeling • Regulates inflammation • Promotes healing
TGF-β
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
• The relapse rate was high after remission achieved with nutritional therapy
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.
C Hartman, et al, IMAJ, July 2008
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
FACTOR EFFECT OF OMEGA-3 FATTY 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
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.
FISH OILS & UC INDUCTION OF REMISSION
Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005986. * 72% weaned off or reduced medication dose. N=159
STUDY EPA DHA CLINICAL REMISSION
ENDOSCOPIC EVIDENCE
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
FISH OIL FOR THE MAINTENANCE OF ULCERATIVE COLITIS
Turner, D et al. Inflamm Bowel Dis. 2011 Jan;17(1):336-45
FISH OIL FOR THE MAINTENANCE OF CD
Turner, D et al. Inflamm Bowel Dis. 2011 Jan;17(1):336-45
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
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
AN ORAL SUPPLEMENT ENRICHED WITH FISH OIL, SOLUBLE FIBRE AND ANTIOXIDANTS FOR CORTICOSTEROID SPARING IN
ULCERATIVE COLITIS: A RANDOMISED, CONTROLLED TRIAL
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
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
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
Plasma phospholipid FA levels
THE EFFECTS OF AN ORAL SUPPLEMENT ENRICHED WITH FISH OIL, PREBIOTICS, AND ANTIOXIDANTS ON
NUTRITION STATUS IN CROHN’S DISEASE PATIENTS
Vitamin D and PTH levels
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
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
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
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
Gastroenterology 2012;142;3:482-489
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
PATHOGENESIS OF IBD
Macrophage
Inflammation
IL2-R
T9
4F2
Activated Th1 Cell
Ag
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, IFN-g
IL-1
+
+
CD45R CD4
Memory T Cell
Lymphokines
ROS
(-)
Nutritional
DNA
NUCLEUS
MITOCHONDRION
PEROXISOMES LYSOSOMES
ENDOPLASMIC RETICULUM
CYTOPLASM
LIPID BILAYER OF ALL CELLULAR MEMBRANES
IMPAIRED CELLULAR DEFENSE MECHANISMS IN IBD
Vitamin E
Catalase
Cu/Zn SOD
Vitamin E + Beta-Carotene Mn
SOD + Glutathione Peroxidase + GSH
Vitamin E
Vitamin C
Glutathione Peroxidase
GSH
Vitamins C and E Beta-Carotene
Beta-Carotene
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
BOTANICAL MODULATION OF ARACHIDONIC ACID CASCADE
Mullin GE, et al, Expert Review of Gastroenterology and Hepatology, April 2008
Singarelli B. CCM. 2005;33:S414-416
NF-κB probiotics
NATURAL PRODUCTS WITH ANTI-INFLAMMATORY ACTIONS
NFkB inhibitors: • Curcuminoids • 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)
Inflammatory inhibitors (NFkB-independent):
• DHA (fish oil) • ALA (flax seed oil) • White Willow Bark • Devil’s Claw
PHYTONUTRIENTS AND BOTANICALS LIKELY TO BE USEFUL IN INFLAMMATORY
CONDITIONS OF THE GI TRACT
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)
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
PROPHYLACTIC AND THERAPEUTIC EFFECTS OF POLYPHENOLS FOR COLITIS
POLYPHENOL N ROUTE, DOSE RESULTS
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
FOODS ASSOCIATED WITH A DECREASE IN INFLAMMATORY MARKERS IN HUMAN INTERVENTIONAL STUDIES
FOOD DURATION EFFECT
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
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
PLEASE PASS THE BERRIES!
J Med Food. 2007;10;2:258-265.
RED WINE COOLS COLONIC INFLAMMATION IN UC
Digestion 2011 Aug 26;84(3):238-244.
TURMERIC (CURCUMA LONGA)
Mechanism of action: • Inhibits TNF-α • Dual inhibitor of arachidonic
acid metabolism • Cortisone-like inhibitory action
on phospholipases • Antioxidant activity Note: Turmeric is a potent inhibitor of transcription factor NF-κB
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.
CURCUMIN IN ULCERATIVE COLITIS
Hanai H, et al. Clinical Gastro Hepatol. 2006;4:1502-1506.
BOSWELLIA AND IBD AUTHOR DESIGN/# DISEASE CONTROL DURATION 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
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
Aliment Pharmacol Ther. 2013 Oct;38(8):854-63. doi: 10.1111/apt.12464. Epub 2013 Aug 2
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
Alimentary Pharmacology & Therapeutics 25 AUG 2013 DOI: 10.1111/apt.12464 http://onlinelibrary.wiley.com/doi/10.1111/apt.12464/full#apt12464-fig-0001
Aliment Pharmacol Ther. 2013 Oct;38(8):854-63. doi: 10.1111/apt.12464. Epub 2013 Aug 2
FLOW DIAGRAM OF THE STUDY SELECTION PROCESS. ASA: AMINOSALICYLIC ACID
RESULTS FOR OUTCOMES INVESTIGATED FOR EACH
INCLUDED STUDY
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
RESULTS OBTAINED FROM SUB-ANALYSES BASED ON PLANT TYPE
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
INDIVIDUAL AND POOLED RELATIVE RISK (A), HETEROGENEITY INDICATORS (B) AND PUBLICATION BIAS INDICATORS (C) FOR THE OUTCOME OF “CLINICAL
REMISSION” IN THE STUDIES CONSIDERING HERBAL MEDICINES COMPARING TO PLACEBO THERAPY IN INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS.
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
INDIVIDUAL AND POOLED RELATIVE RISK (A), HETEROGENEITY INDICATORS (B) FOR THE OUTCOME OF “CLINICAL REMISSION” IN THE STUDIES CONSIDERING
HERBAL MEDICINES COMPARING TO PLACEBO THERAPY IN ULCERATIVE COLITIS (UC) PATIENTS.
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
INDIVIDUAL AND POOLED RELATIVE RISK (A), HETEROGENEITY INDICATORS (B) AND PUBLICATION BIAS INDICATORS (C) FOR THE OUTCOME OF
“CLINICAL RESPONSE” IN THE STUDIES CONSIDERING HERBAL MEDICINES COMPARING TO PLACEBO THERAPY IN IBD PATIENTS.
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
INDIVIDUAL AND POOLED RELATIVE RISK (A), HETEROGENEITY INDICATORS (B) FOR THE OUTCOME OF “CLINICAL RESPONSE” IN THE STUDIES CONSIDERING HERBAL MEDICINES COMPARING TO PLACEBO THERAPY FOR CROHN’S DISEASE CD (LEFT) AND UC (RIGHT) PATIENTS
INDIVIDUAL AND POOLED RELATIVE RISK (A), HETEROGENEITY INDICATORS (B) FOR THE OUTCOME OF “ENDOSCOPIC REMISSION” IN
THE STUDIES CONSIDERING HERBAL MEDICINES COMPARING TO PLACEBO THERAPY FOR UC PATIENTS.
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
INDIVIDUAL AND POOLED RELATIVE RISK (A), HETEROGENEITY INDICATORS (B) FOR THE OUTCOME OF
“ENDOSCOPIC REMISSION” IN THE STUDIES CONSIDERING HERBAL MEDICINES COMPARING TO
PLACEBO THERAPY FOR UC PATIENTS.
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
INDIVIDUAL AND POOLED RELATIVE RISK (A), HETEROGENEITY INDICATORS (B) AND PUBLICATION BIAS INDICATORS (C) FOR THE OUTCOME OF “ANY ADVERSE EVENTS”(LEFT)
AND “SERIOUS ADVERSE EVENTS “ (RIGHT) IN THE STUDIES CONSIDERING HERBAL MEDICINES COMPARING TO PLACEBO THERAPY IN IBD PATIENTS.
Rahimi et al. World Journal of Gastroenterology Sept 14, 2013; 19;34:5738-5749.
An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL, P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h, P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000). CONCLUSION: Silymarin as a natural supplement may be used in UC patients to maintain remission.
NUTRACEUTICALS & IBD NOT READY FOR PRIME TIME
• Alpha Lipoic Acid 500 mg 2-3/D • NAC 800 mg/D • L-Carnitine 1,000 mg/D • Vitamin E enemas 800 IU/D • Phosphatidyl choline 500 mg QID delayed
release
NUTRITIONALS SHOWING EFFICACY IN IBD
MULTIPLE STUDIES • Elemental Diet • Modulen • Prebiotics • Probiotics • Turmeric • Fish Oils • Artemesia absinthium • Triticum Aestivum
SINGLE STUDIES • Boswellia serrata • Lycopene • Aloe vera • Andrographis paniculata
extract (HMPL-004) • Ginger • Wheatgrass juice • Silymarin • UCNS • CDNS
CONCLUSION
MODALITY LEVEL OF EVIDENCE RISK
Omega-3 fatty acids B Low
Modulen (TGF-b)* B na
Curcumin B na
Probiotics A low
Butyrate enemas B na
Diet B na
A B high
Aminosalicylates A moderate
Corticosteroids A high
* Transforming growth factor
THERAPEUTIC MODALITIES FOR IBD
Azathioprine
TAKE HOME POINTS • Polyphenols, fish oils, probiotics, vitamin D,
antioxidants: downregulate inflammation to “cool the fire in the gut”
• Short chain fatty acids are colonic-specific anti-inflammatory nutrients
• SBC, arabinogalactans, MCTs, whey, raw milk, pre- and probiotics - Immune Modulators
• High ORAC foods, wild cold-water fish, etc. Think of food as medicine first!
Pt with diarrhoea, wt. loss, abd pain,
inflammatory markers
Evaluate for Inflammatory Bowel Disease
Other Diagnoses IBD Localisation, colitis vs. enteritis
Colitis
Short Chain Fatty Acid Enemas
Prebiotics, Ca Mg Butyrate
Anti-inflammatory Diet
Enteritis
Glutamine, Aloe, zinc-L-carnosine
SCD, low FODMAPs
Dysbiosis, Immune Regulators
Systemic Inflammation. Fish Oil, Curcumin, Bowsellia, Vitamin D, Elimination diet
Consider Coeliac Disease and/or other
Dx
Symptoms Persist
Serology, Radiology, WCE
“Let medicine be thy food and let food be thy medicine”
Hippocrates