Draoife.com

A sampling of targeted integrative therapies
By Aoife Earls MSc, ND
Inflammatory Bowel Diseases (IBD) such as Crohn’s of energy for colonocytes and can regenerate mucosa, as well as
disease (CD) and ulcerative colitis (UC) are chronic, having the capacity to reduce inflammation through enhancement relapsing-remitting inflammatory diseases with several of anti-inflammatory cytokines such as IFN-gamma and NF-kB hallmarks of dysfunction, including a breakdown in intestinal which are down-regulated in both Crohn’s disease and ulcerative barrier function and intestinal permeability, unchecked chronic colitis (Looijer-van Langen 2009). In a group of 19 patients with inflammation, and an exaggerated immune response characterized active UC (mild-moderate disease severity) administered inulin by imbalanced anti-inflammatory and proinflammatory cytokines. for 2 weeks in addition to the 3g/daily of mesalamine, a significant Proinflammatory cytokines such as IL-1, IL-6, IL-12, IFN-gamma reduction in calprotectin (a fecal inflammatory marker increased and TNF-alpha are increased with lowered anti-inflammatory in IBD) compared with the placebo control group was observed and regulatory cytokines like IL-10 and TGF-beta. When (Casellas 2007, Konikoff 2006). UC in general shows more diagnosed with IBD later in life, aside from regular check-ups with significant benefit from prebiotic support compared with CD. gastroenterologists between procedures and to monitor efficacy of pharmaceutical interventions, many adults have questions about Probiotic support is widely considered a gold-standard intervention their specific needs and are looking for additional support. However, in both conventional and integrative medicine for both active many patients are reluctant to seek out integrative healthcare as they and remission phases of IBD, with benefits of the most popular are concerned they will be encouraged not to take their medications investigated strains summarized in Table 1. Current research has which are helping to reduce their symptoms and provide quality of explored specific strains and their ability to influence active vs. life. Naturopathic doctors have a unique opportunity to support remission phases of IBD, as summarized in Table 2. Of research patients with IBD by using the most appropriate treatments during produced to date, administering the proper probiotic strain(s) different stages of the disease process.
is crucial to seeing rapid improvements in bowel mucosa, stool quality and frequency, as well as reducing systemic inflammation Supporting Intestinal Barrier Function and Intestinal
(Looijer-van Langen 2009). The probiotic VSL#3, which provides Permeability
a high- dose milieu of bacteria, is more appropriate in IBD disease 1.Prebiotic and Probiotic support
remission than is S. boulardi , which shows fantastic response Prebiotic supports (i.e. oligofructosaccharides and/or inulin found for diarrhea-control and initiating remission (Ewaschuk 2010). in chicory, wheat, onions, bananas) encourage growth of beneficial bacteria and have the capability of skewing directional growth of probiotic strains which confer specific host benefits (Bouhnik 2004, Langlands 2004, Looijer-van Langen 2009). Some of these host benefits include providing energy sources for intestinal bacteria to ferment into short chain fatty acids (SCFA) (Looijer-van Langen 2009). Short chain fatty acids (SCFA’s) such as butyrate are a source 62 | IHP June/July 2011 } ihpmagazine.com
A recent meta-analysis comparing multiple studies and strains 2008). Hence, screening for the proper strains by looking at disease
contrasted these conclusions for CD specifically, finding significance activity and subjective symptomatology is the most useful strategy
for E.coli and S. boulardi but not for lactobacillus strains (Rahimi in selection appropriate probiotic blends for IBD management.
Table 1: Immunological impact of probiotics in IBD
Probiotic Species
Beneficial Immune Action
VSL#3 (L. Acidophilus, L. Bulgaris, L. Casei, L. Plantarum, Improves cell barrier integrity, mucous production, reduction in TNF-alpha and INF- B. Breve, B. Infantis, B. Longum, S. thermophilus) Alters short chain fatty acids (SCFA), inhibits T-cell activation Enhances phosphorylation in tight junctions Hydrolyze prebiotic oligosaccharidesSecrete metabolites that reduces TNF-alpha Table 2: Disease- stage application of different probiotic blends (Modified from Ewaschuk 2010)
Study Group
Assists Active > Remission
Helpful in Maintaining Remission Does not prevent remission
Ulcerative Colitis (UC)
RCT, N= 187 Lactobacil us GG 18 x 10(9)/day (65 patients) vs. mesalazine 2400 mg/day (60 patients) or both L. GG + mesalazine (62 patients), no difference in relapse rate for 3 groups however lactobacil us GG > than mesalazine in relapse-free time (P < 0.05) (Zocco 2006) RCT 116 adults for 12 months, 44 patients with mesalamine and 39 with E.coli tx, mean time to remission 206 days mesalamine and 21 days E.coli equivalent (Rembacken 1999) Crohn’s Disease (CD)
32 px 1g bid for 6 mths and mesalamine 1 g twice daily and 1 g tid, RELAPSES  VS  MESALAMINEalone (Guslandi 2000) s 2#4  WEEKS N   EXCLUDED Lactobacil us rhamnosus strain GG (LGG) 6 BILLION X  CFU BID VS PLACEBO  PLACEBOREMISSION  MTHS VS ,'' 0RANTERA  s , ''  X  #&5DAY OR PLACEBO FOR months, time to relapse non-significant (12-16 wks between groups) (Schultz 2004) ihpmagazine.com { June/July 2011 IHP | 63
2. Amino Acid Supplementation
culture has demonstrated IL-10 production, reduction of IL-1B Increased intestinal permeability can be predictive of how soon activity, and further reduction of cell signaling molecules in
an individual relapses to active disease. IFN-gamma and TNF-a, inflammatory pathways (Epstein 2009).
central mediators of intestinal inflammatory diseases, induce
intestinal epithelial barrier dysfunction (MacDonald 1990, Wyatt An RCT involving 89 patients with UC in remission were exposed
2004). L-glutamine, the major feeding source for enterocytes, to either 2 g/day of curcumin with sulfasalazine or placebo with
has been suggested to have antioxidant potential by reducing sulfasalazine, with significant findings for delay of relapse in
nitrous oxide (NO) as well as restoring loose connections between patients given curcumin (4.65%) as treatment compared with
tight junctions of colonocytes (Coeffier 2010, Grozswitz 2009). placebo (20.51%; p=0.040) (Hanai 2006). Further studies need
Animal-models of IBD induced via dextran sulfate sodium or to be completed, in addition to answering questions surrounding
acetic acid show promise with reduction of proinflammatory curcumins oral bioavailability (Marczylo 2007).
cytokines (TNF-alpha and IL-8) and intestinal damage in the
presence of L-glutamine consumption (Coeffier 2010). However, Oxidative stress
when used in human studies, glutamine supplementation does Reactive oxygen species and radical nitrogen metabolites
not show the same benefits in symptomatic reduction of disease accumulate rapidly during intestinal inflammation in patients
activity through subjective scoring of the disease activity indices with IBD, of which antioxidant support can be invaluable
(CDAI) (Akobeng 2007, Den Hond 1999, Ockenga 2005). (Aghdassi 2003, Najafzadeh 2009). In addition to vitamin C,
Study designs could use some improvements both in consistency quercetin shows promise in animal models of IBD and has
of dosages administered as well as methodology of testing. been used in combination with fish oil to restore glutathione
Biopsies of inflamed gastrointestinal mucosa and measurements concentration and to reduce COX-2 more significantly than with
of cytokine levels are for the most part lacking in human trials just fish oil alone (Camuesco 2006).
post-glutamine consumption; perhaps it is in the microscopic
changes of the intestinal barrier where the impact of L- glutamine Dietary Support
supplementation will be observed (Coeffier 2005, Coeffier 2010).
As integrative healthcare providers, we concern ourselves with elimination of irritating proinflammatory foods such as dairy Reducing Chronic Inflammation
products (primarily cow’s milk), wheat gluten, peanuts, citrus A. N-3 Fish oil
fruits, fish and shellfish, synthetic and excessive sugar, and soy The inflammation-reducing capacity of high-potency n-3 fish oils products. The “Western diet” high in animal meats, dairy, and via the arachidonic acid pathways are well- publicized, acting as sugars has been implicated in the increase in prevalence of both do current pharmaceutical supports for IBD including 5-ASA UC and CD in a comparison between 1990 and 2007 of reduced (Belluzzi 2000). While patients with IBD have steatorrhea and microbes in the intestines and food consumption (Asakura 2008). fat-soluble vitamin malabsorption, fish oil supplementation should be a top priority in integrative support of IBD (Hartman Along the same vein, lactose intolerance and lactose malabsorption 2009). A selection of research groups in comparison of N-3, have a strong amount of research support with correlations to N-6 and N-9 oil usage for IBD across 10 years has been quickly worsening IBD, especially CD compared with controls (Szilagyi summarized in Table 3 to further confirm the absolute necessity 1998). Lactulose breath tests are often used to confirm this, however of n-3 fish oil for IBD support.
as most patients with IBD have imbalanced or higher than normal quantities of bowel flora, results prove to be inconsistent across B. Curcuma longa or Curcumin
many studies (Szilagyi 1998). Milk allergy and/or IgE antibodies Curcumin shows incredible promise from both preclinical models to cow’s milk proteins are not often positive, which adds to the and recent human trials in IBD. It has demonstrated the ability confusion where patients feel well avoiding dairy products but to influence the arachidonic acid pathway and downregulate blood titres do not confirm the subjective improvements (Knoflach chemokine production (Arafa 2009, Goel 2007, Jagetia 2007). 1987, Mishkin 1997). Even if and when allergy results are positive Neutrophil motility in IBD is correlated with disease severity with and patients avoid offending foods for a period of time through higher rates of neutrophil migration leading to reduced epithelial elimination, intestinal permeability may still be increased as was barrier function (Larmonier 2011); curcumin administration in demonstrated in a group of patients with IBD who avoided allergen murine models of IBD has demonstrated reduced neutrophil exposure for six months yet still had high lactulose/mannitol ratios motility as well as reduced NF-kappaB as has led to further (Wyatt 1993). Intestinal permability can be an independent issue exploration in human IBD (Salh 2003).
that is not easily solved with food avoidance. Ex vivo¸biopsies from colonic mucosa and myofibroblasts from In addition, replacement or substitution for these caloric losses children and adults with active IBD exposed to curcumin in in food avoidance is an issue as there is a need to nourish patients 64 | IHP June/July 2011 } ihpmagazine.com
with IBD. Prednisone as an anti-inflammatory support in some for such intolerances, thus taking each patient’s care as a unique
patients with active IBD leaches calcium from the bones, and situation despite general IBD trends.
vitamin D is not only essential in directing calcium to the
bones but to support proinflammatory cytokines such as IL-1 Conclusion
and TNF-alpha suppression in IBD and in colorectal cancer Integrative healthcare providers play a unique supportive role in IBD.
prevention (Raman 2011). Among patients in remission from Recognizing the current disease state (active vs remission), the extent
CD, 50% were shown to have low plasma concentrations of of inflammation, bowel flora status, and supporting processes of
vitamin C (84%), copper (84%), niacin (77%), and zinc (65%) in oxidative stress can improve quality of life for patients. Patients need
addition to malabsorption of fat and fat-soluble vitamins (Filippi the reassurance that they wil not be in a competition or battle between
2006). Exploring all options including screening for celiac their integrative healthcare provider and conventional supports (GI
disease, lactose intolerance, and multiple food allergies would specialist, MD) but that we can provide improved quality of life by
be prudent rather than strictly eliminating foods without testing XPSLJOH
BT
QBSU
PG
BO
JOUFHSBUJWF
IFBMUI
DBSF
UFBN
t
Table 3: Human trials of fish oil in IBD management
Active Disease
Remission at Study n-3 (triglyceride or ethyl
at Study Start
ester) vs. placebo
Ulcerative Colitis (UC)
significant reduction in overal steroid usage s &ISH OIL SIGNIlCANTLY IMPROVED CELL QUALITY s )NCREASED BODY WEIGHTs $ECREASED PRODUCTION OF LEUKOTRIENES INFECAL MATTER BY s )MPROVED QUALITY OF LIFEs (/7%6%2 DID NOT REDUCE AMOUNT OFsteroids consumed Crohn’s Disease (CD)
Non-significant, relapse within 360 days remained in remission for one year vs. 10 Combined IBD interventions (UC and CD patients in study)
Benefit only to UC, non-significant for CD but reduction in inflammatory mediators overall s . SIGNIlCANTLY INCREASED THE ERYTHROCYTE membrane n-3/n-6 ratio in IBD patients (0.41 ± 0.16 versus 0.70 ± 0.20; P < 0.001).
s &! CELL MEMBRANE COMPOSITION IN THE remission group (n = 145) was significantly higher than that in the relapse group (n = 85) (0.65 ± 0.28 versus 0.53 ± 0.18; P < 0.001).
ihpmagazine.com { June/July 2011 IHP | 65
Jagetia GC and Aggarwal BB. “Spicing up” of the immune system by curcumin. J Clin Immunol. Aghdassi E, Wendland BE, Steinhart AH, Wolman SL, Jeejeebhoy K, Al ard JP. Antioxidant vitamin supplementation in Crohn’s disease decreases oxidative stress: a randomized control ed trial. Am J Gastroenterol 2003; 98(2): 348-53.
Kato K,Mizuno S,Umesaki Y ,Ishi Y ,SugitaniM,Imaoka A, Otsuka M, Knoflach P, Park BH, Cunningham R, et al. Serum antibodies to cows’ milk proteins in ulcerative colitis and Crohn’s Akobeng AK, Thomas AG. Enteral nutrition for maintenance of remission in Crohn’s disease. disease. Gastroenterology 1987; 92:479-85.
Cochrane Database Syst Rev. 2007: CD005984.
Konikoff MR, Denson LA. Role of fecal calprotectin as a biomarker of intestinal inflammation Arafa HM, Hemeida RA, El-Bahrawy AL, Hamada FM (2009). Prophylactic role of curcumin in inflammatory bowel disease. Inflammatory Bowel Dis 2006; 12: 524-34.
in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model. Food Chem Toxicol ; Langlands SJ, Hopkins MJ, Coleman N, et al. Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut 2004;53:1610-1616.
Asakura et al. Is there a link between food and intestinal microbes and the occurrence of Crohn’s disease and ulcerative colitis? Journal of Gastroenterology and Hepatology. 2008; 23: 1794–1801.
Larmonier CB, Midura-Kiela MT, Ramalingam R, Laubitz D, Janikashvili N, Larmonier N, Ghishan FK, Kiela PR. Modulation of neutrophil motility by curcumin: implications for Bel uzzi A, Boschi S, Brignola C, Munarini A, Cariani G, and Miglio F. Polyunsaturated fatty inflammatory bowel disease. Inflamm Bowel Dis 2011; 17(2) 503-15.
acids and inflammatory bowel disease. Am J Clin Nutr 2000;71(suppl):339S–42S.
Loeschke K, Ueberschaer B, Pietsch A, Gruber E, Ewe K, Wiebecke B, Heldwein W, Lorenz Bel uzzi A, Brignola C, Campieri M, et al. Effect of an enteric-coated fish oil preparation on R. n-3 fatty acids only delay early relapse of ulcerative colitis in remission. Dig Dis Sci 1996; 41: relapses in Crohn’s disease. N Engl J Med 1996; 334: 1557-616.
Bibiloni R, Fedorak RN, Tannock GW, Madsen KL, Gionchetti P, Campieri M, De SC, Sartor Looijer-van Langen MAC and Dieleman LA. Prebiotics in Chronic Intestinal Inflammation. RB. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Inflamm Bowel Dis 15(3) 2009; 15: 454-462.
Lorenz R, Weber PC, Szimnau P, Heldwein W, Strasser T, Loeschke K. Supplementation with Bouhnik Y, Raskine L, Simoneau G, et al. The capacity of nondigestible carbohydrates to n-3 fatty acids from fish oil in chronic inflammatory bowel disease - a randomized, placebo- simulate fecal bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, controlled, double-blind cross-over trial. J Intern Med Suppl 1989; 225-32.
parallel-group, dose-response relation study. Am J Clin Nutr 2004, 80: 1658-1664.
MacDonald TT, Hutchings P, Choy MY, Murch S, Cooke A. Tumour necrosis factor- alpha and Camuesco D, Galvez J, Nieto A, Comalada M, Rodriguez-Cabezas ME, Concha A, Xaus interferon-gamma production measured at the single cel level in normal and inflamed human J, Zarzuelo A. Dietary olive oil supplemented with fish oil rich in EPA and DHA (n-3) intestine. Clin Exp Immunol 1990;81:301-5.
polyunsaturated fatty acids, attenuates colonic inflammation in rats with DSS-induced colitis. J Marczylo TH, Verschoyle RD, Cooke DN, et al. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol Casel as F, Borruel N, Torrrejon A, et al. Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is wel tolerated and associated with lowered faecal calprotectin. Aliment Mishkin S. Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory bowel disease. Am J Clin Nutr 1997; 65:564-7.
Coeffier M, Marion-Letel ier R, Dechelotte P. Potential for Amino Acids Supplementation During Inflammatory Bowel Diseases. Inflamm Bowel Dis 2010; 16:518-524.
Najafzadeh M, Reynolds PD, Baumgartner A, Anderson D. Flavonoids inhibit the genotoxicity of hydrogen peroxide (H2O2) and of the food mutagen 2-amino-3-methylimadazo[4,5- Coëffier M, Hecketsweiler B, Hecketsweiler P, Déchelotte P. Effect of glutamine on water and f]-quinoline (IQ) in lymphocytes from patients with inflammatory bowel disease (IBD). sodium absorption in human jejunum at baseline and during PGE-1 induced secretion. J Appl Mutagenesis vol. 24 no. 5 pp. 405–411, 2009.
Physiol. 2005 Jun;98(6):2163-8. Epub 2005 Jan 20.
Ockenga J, Borchert K, Stuber E, et al. Glutamine-enriched total parenteral nutrition in patients Den Hond E, Hiele M, Peeters M, et al. Effect of long-term oral glutamine supplements on with inflammatory bowel disease. Eur J Clin Nutr. 2005;59:1302–1309.
small intestinal permeability in patients with Crohn’s disease. JPEN 1999;23:7-11.
Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in Epstein J, Docena G, MacDonald TT, Sanderson IR. Curcumin suppresses p38 mitogen- preventing recurrence after curative resection for Crohn’s disease: a randomised control ed trial activated protein kinase activation, reduces IL-1beta and matrix metal oproteinase-3 and with Lactobacillus GG. Gut 2002; 51(3): 405-9.
enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr. Rahimi R, Nikfar S, Rahimi F, Elahi B, Derakshani S, Vafaie M, Abdol ah M. A Meta-Analysis on the Efficacy of Probiotics for Maintenance of Remission and Prevention of Clinical and Ewaschuk JB and Dieleman LA . Prebiotics and probiotics in chronic inflammatory bowel Endoscopic Relapse in Crohn’s Disease. Dig Dis Sci 2008; 53: 2524-253.
diseases. World J Gastroenterol 2006; 12(37): 5941-5950.
Raman M, Milestone AN, Walters JRF, Hart AL, and Ghosh S. Vitamin D and gastrointestinal Feagan BG, Sandborn WJ, Mittmann U, Bar-Meir S, D’Haens G, Bradette M, Cohen A, disease: inflammatory bowel disease and colorectal cancer. Ther Adv Gastroenterol 200; 4(1): 49-62.
Dal aire C, Ponich TP, McDonald JW, Hébuterne X, Paré P, Klvana P, Niv Y, Ardizzone S,Alexeeva O, Rostom A, Kiudelis G, Spleiss J, Gilgen D, Vandervoort MK, Wong CJ, Zou GY, Rembacken BJ, Snel ing AM, Hawkey PM, Chalmers DM, Axon AT. Non-pathogenic Donner A, Rutgeerts P. Omega-3 free fatty acids for the maintenance of remission in Crohn Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. disease: the EPIC Randomized Controlled Trials. JAMA. 2008 Apr 9;299(14):1690-7.
Filippi J, Al-Jaouni R, Wiroth JB, Hebuterne X, and Schneider S. Nutritional Deficiencies in Salh B, Assi K, Templeman V, Parhar K, Owen D, Gomez-Munoz A, Jacobson K. Curcumin Patients With Crohn’s Disease in Remission. Inflamm Bowel Dis 2006;12:185Y19.
attenuates DNB-induced murine colitis. Am J Physiol Gastrointest Liver Physiol 2003; 285(1): Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “curecumin”: from kitchen to clinic. Schultz M, Timmer A, Herfarth HH, Sartor RB, Vanderhoof JA, Rath HC. Lactobacil us GG in inducing and maintaining remission of Crohn’s disease. BMC Gastroenterol. 2004 Mar 15;4:5.
Groschwitz KR and Hogan SP. Intestinal Barrier Function: Molecular Function and Disease Pathogenesis. J Al ergy Clin Immunol 2009;124:3-20.
Stenson WF, Cort D, Rodgers J et al. Dietary supplementation with fish oil in ulcerative colitis. Guslandi M, Giol o P, Testoni P. A pilot trial of Saccharomyces boulardi in ulcerative colitis. Eur J Gastroenterol Hepatol 2003; 15:697-8.
Szilagyi A. Altered colonic environment, a possible predisposition to colorectal cancer and colonic inflammatory bowel disease: Rationale of dietary manipulation with emphasis on Hanai H, Lida T, Takeuchi K, Watanabe F, Maruyama Y, Andoh A et al. Curcumin maintenance disaccharides. Can J Gastroenterl 1998; 12(3): 133-146.
therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-control ed trial. Clin Gastroenterol Hepatol 2006; 4(12): 1502-6.
Uchiyama K, Nakamura M, Odahara S, Koido S, Katahira K, Shiraishi H, Ohkusa T, Fujise K, Tajiri H. N-3 polyunsaturated fatty acid diet therapy for patients with inflammatory bowel Hartman C, Eliakim R, Shamir R. Nutritional status and nutritional therapy in inflammatory disease. Inflamm Bowel Dis. 2010 Oct;16(10):1696-707.
bowel diseases. World J Gastroenterol 2009; 15(21): 2570-8.
Venturi A, Gionchetti P, Rizzel o F, Johansson R, Zucconi E, Brigidi P, Matteuzzi D, Campieri Hasunuma O, Kurihara R, Iwasaki A, Arakawa Y. Randomized placebo-control ed trial assessing M. Impact on the composition of the faecal fl ora by a new probiotic preparation: preliminary the effect of bifidobacteria-fermented milk on active ulcerative colitis. Aliment Pharmacol Ther data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999; Hawthorne AB, Daneshmend TK, Hawkey CJ et al. Treatment of ulcerative colitis with fish oil Wyatt J, Vogelsang H, Hubl W, Waldhoer T, Lochs H. Intestinal permeability and the prediction supplementation: a prospective 12 month randomized controlled trial. Gut 1992, 22;922-8.
of relapse in Crohn’s disease. Lancet 1993;341:1437-9.
Ishikawa H, Akedo I, Umesaki Y, Tanaka R, Imaoka A, Otani T. Randomized control ed trial Zocco MA, dal Verme LZ, Cremonini F, Piscaglia AC, Nista EC, Candel i M, Novi M, Rigante of the effect of bifidobacteria-fermented milk on ulcerative colitis. J Am Coll Nutr 2003; 22(1): D, Cazzato IA, Ojetti V, Armuzzi A, Gasbarrini G, Gasbarrini A. Efficacy of Lactobacil us GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1567-74.
66 | IHP June/July 2011 } ihpmagazine.com

Source: http://draoife.com/wordpress/wp-content/uploads/2011/08/Earls-issue-21-IBD.pdf