Alternative Therapies for

Inflammatory Bowel Disease

IBD• Refers to UC and CD • Affects 1-2 million Americans• Treated with amino salicylic acids, corticosteroids,

immunomodulators, and antibiotics. – help maintain remission but also have serious side effects

• Many patients are dissatisfied with the conventional treatments and therefore seek alternative therapies – most common forms used are herbal and nutritional

supplements, acupuncture, and diet modification. – Higher rate of use in IBD patients – 1/3 of patients seeking gastroenterology care are also receiving

various CAM therapies.

Pathophysiology

• characterized primarily by intestinal wall inflammation with elevated proinflammatory cytokines, oxidative stress, and leukocyte infiltration

• cell-mediated Th1 response – Includes IL-12, INF-gamma, TNF-α, IL-1, IL-2, IL-6,

and IL-8 • UC is also characterized by a high Th2 response

– elevated levels of IL-5• The exaggerated T-cell response in both

conditions leads to intestinal damage and increased permeability

Disruption of Intestinal environment

• Caused by 2 events.– increased permeability – disturbance in the intestinal micro flora. – Either mechanism leads to increased pathogenic

invasion of the intestine. • Increased mucosal permeability

– Alteration of tight junctions between intestinal epithelial cells

• allows bacteria to penetrate the mucosal barrier • Activates intestinal immune response

– The alteration of tight junctions can be mediated by inflammation, increased TNF-α, and ulcerations

Disruption of Intestinal environment

• disturbance in the intestinal micro flora.– the normal flora such as bifidobacterium and

lactobacillus are decreased– pathogenic bacterial are increased.

• stimulates inflammation – secreting enterotoxins, synthesizing immunosuppressive

proteins, and disrupting epithelial cell metabolism • The enterotoxins increase intestinal permeability and allow

for the translocation of antigens across the epithelial creating immune activation

• Since IBD patients are in a chronic state of inflammation, the micro flora ecosystem is always altered

Alternative Therapies

• target the disruptions in the intestinal tract that may predispose individuals to IBD or may exacerbate the disease

• probiotics, antioxidants, fish oil, curcumin, glutamine, short chain fatty acids, garlic, acupuncture and dietary modifications.

• Some are believed to produce the same immune modulation and suppression as conventional medications to maintain remission and relapses control.

Probiotics• Friendly bacterial in GIT

– Lactobacilli, Streptococci, Bifidobacteria, and certain E. coli subspecies • Alter intestinal microflora and restore the balance disturbed in IBD• Potential mechanisms of probiotic action include:

– inhibition of pathogenic microbial growth – modification of intestinal permeability by increasing tight junctions – regulation of intestinal immune response and immune cells – synthesis of antimicrobial metabolites – decomposition of pathogenic antigens in the lumen

• By using a combination of different probiotics such as Streptococcus, Bifidobacterium and Lactobacillus, studies have proven their ability to normalize transport function and mucosal barrier in the intestine as well as the ability to inhibit TNF-α and IFN-gamma synthesis

Antioxidants

• protect cells from the damaging effects of free radicals such as singlet, oxygen, superoxide, peroxyl radicals, hydroxyl radicals and peroxynitrite

• Protect by:– Tissue level: downregulate neutrophil or monocyte

activation which prevents formation of free radicals– Cellular level: block membrane receptors– Scavenge free radicals after formation and release

• Vit. C and E, flavonoids and glutathione increase antioxidant activity

Curcumin

• component of the spice turmeric (Curcuma longa) that has been proven to have antioxidant and anti-inflammatory properties.

• Suppresses proinflammatory cytokines IL-12, and TNF-α thru down regulation of NFқB.

Fish Oil

• Omega 3-fatty acid

• Controls inflammatory response when in an appropriate balance with omega-6

• competes with arachidonic acid to decrease prostaglandin, thromboxane and leukotriene production

Glutamine

• Essential amino acid found in abundance in the body

• In catabolic states the body’s demand exceeds its ability to synthesize it

• protects the mucosa and decreases inflammatory process.

• L-glutamine enemas where shown to be more beneficial than 5 ASA in rat studies

Short Chain fatty acids

• Primary energy source for colonocytes• butyrate, acetate, and proprionate • decrease the synthesis of inflammatory

cytokines, IL-6, IL-8, and TNF-alpha, while also playing a role in the repair and regeneration of injured colonic cells

• butyric enemas in UC resulted in equivalent remission rates as mesalamine and corticosteroids

Garlic

• Actions in IBD– suppress IL-8, up-regulate IL-10, inhibit IL-12, and act

as an antibacterial or antifungal agent

• IL-8 attracts neutrophils to site of inflammation• IL-10 is an anti-inflammatory agent• IL-12 promotes INF-gamma production• One study proved that additive therapy of garlic

extract to methylprednisone produced a greater therapeutic effect than just methylprednisone alone

Diet modifications

• diet is believed to have the ability to impact the content and metabolic activity of the human fecal flora

• High sulfur diets

• High protein diets

High Sulfur Diet

• Compromise micro flora in GIT– Increase synthesis of harmful bacteria– metabolize by sulfate-reducing bacteria (SRB) in the

colon to sulfide • Abdominal distention• Inhibition of butyrate oxidation

• Diet with low intake of sulfur would be beneficial– Limit intake of preservatives, dried fruits, dehydrated

vegetables, shellfish, white bread, alcoholic beverages, cow’s milk, cheese eggs, and cruciferous vegetables

High Protein Diet

• Protein can escape digestion in upper GIT and reach colon undigested– Fermented into ammonia, amines, phenols,

sulfide, and indoles by micro flora

• Ammonia alters mucosal cell morphology and metabolism reducing their life span.

• Phenols and indoles can act as co-carcinogens allowing the development of bowel cancer.

Conclusion

• Alternative therapies are capable of producing similar effects as conventional medicines, but without the serious side effects

• They control the over exaggerated immune response common in IBD by down regulation of pro-inflammatory cytokines, restoration of micro flora balance, and reduction in intestinal permeability.

• Therefore alternative therapies show promising use in inflammatory bowel disease either as mono adjunct therapy.

References

• Bai A, Ouyang Q. Probiotics and inflammatory bowel disease. Postgrad Med J 2006;82:376-382.• Bethesda, MD. Curcumin may be ab effective therapy for inflammatory bowel disease. Prohealth network; 2003.

http://www.prohealthnetwork.com/library/showarticle.cfm/ID/4858/e/1/T/CFIDS_FM/• Accessed on February 21, 2008. • Hart A, Stagg A, Kamm M. Use of probiotics in the treatment of inflammatory bowel disease. J Clin Gastroenterol

2003;36(2):111-119• Hawrelak J, Hons B, Myers S. The Causes of Intestinal Dysbiosis: A Review. Alternative Medicine Review

2004;9(2):181-197.• Head K, Jurenka J. Inflammatory Bowel Disease Part II: Crohn’s Disease Pathophysiology and Conventional and

Alternative Treatment Options. Alternative Medicine Review 2004; 9(4):360-401.• Head K, Jurenka J. Inflammatory Bowel Disease Part I: Ulcerative Colitis – Pathophysiology and Conventional

and Alternative Treatment Options. Alternative Medicine Review 2003; 8(3):247-283.• Heuschkel R, Afzal N et al. Complementary medicine use in children and young adults with inflammatory bowel

disease. Am J Gastroenterol 2002;97(2): 382-388.• Hodge G, Hodge S, Han P. Allium sativum (Garlic) suppresses leukocyte inflammatory cytokine production in

vitro: Potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry 2002;48:209-215.• Kanauchi o, Mitsuyama K, Araki Y, Andoh A. Modification of intestinal flora in the treatment of inflammatory

bowel disease. Curr Pharm Des 2003;9:333-346.• Langmead L, Dawson C, Hawkins C, Banna N, Loo s, Ramptom D. Antioxidant effects of herbal therapies used

by patients with inflammatory bowel disease: an in vitro study. Aliment Pharmacol Ther 2002;16:197-205.

References• Lukaczer D. The Probiotic Solution for Colitis. Nutrition Science News 2000.

http://www.chiro.org/nutrition/FULL/Probiotic_Solution_for_Colitis.shtml• accessed on 8/29/07..• Meister D, Ghosh S. Effect of fish oil enriched enteral diet on inflammatory bowel disease tissues in organ culture:

Differential effects on ulcerative colitis and Crohn’s disease. World J Gastroenterol 2005;11(47):7466-7472.• Miller A. The Pathogenesis, Clinical Implications, and Treatment of Intestinal • Hyperpermeability. Alt Med Rev 1997:2(5):330-345• Ockenga J, Borchert K, Stuber E, Lochs H, Manns MP, and Bischoff SC. Glutamine-enriched total parenteral

nutrition in patients with inflammatory bowel disease. Eur J Clin Nutr 2005;59:1302-1309.• Omega-3 fatty acids. University of Maryland medical center website. http://www.umm.edu/altmed/articles/omega-

3-000316.htm. Accessed on February 20, 2008.• Shah S. Dietary factors In the modulation of inflammatory bowel disease activity. MedGenMed 2007;9(1):60• Simopoules, A. Omega-3 Fatty Acids in inflammation and autoimmune disease. J Am Coll Nutr 2003;21(6): 495-

505.• Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das P. Curcumin, the major component of food flavour

turmeric, reduces mucosal injury in trinitribenzene sulphonic acid-induced colitis. Br J Pharmacol 2003;139:209-218.

• Wild G, Drozdowski L, Tartadlia C, Clandinin M, and Thomson A. World J Gastroenterol 2007;13(1):1-7.• Xu C, Meng S, Pan B. Drug therapy for ulcerative colitis. World J Gastroenterol 2004;10(16):2311-2317.