IBS - Management of Irritable_Bowel

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Volume 16, Number 2 Alternative Medicine Review 134Copyright 2011 Alternative Medicine Review, LLC. All Rights Reserved. No Reprint Without Written Permission.

Review Article

AbstractIrritable bowel syndrome (IBS) is a chronic gastrointestinaldisorder with a range of symptoms that signicantly affectquality of life for patients. The difficulty of differentialdiagnosis and its treatment may signicantly delay initiationof optimal therapy. Hence, persons with IBS often self-treatsymptoms with non-prescribed pharmacological regimensand/or complementary and alternative medicines (CAM) andby modifying diet and daily activities. In addition, mostcommon pharmacological approaches target IBS symptommanagement rather than treatment, and prescribedmedications often result in signicant side effects. Thepurposes of this review article are to: (1) address currentissues related to IBS, including symptom presentation,

diagnosis, and current treatment options; (2) summarizebenets and side effects of currently available pharmacologi-cal regimens and other symptom management strategies,with an emphasis on commonly used CAM therapies and dietmodication; and (3) outline recommendations and futuredirections of IBS management based on systematic reviews,meta-analyses, and research ndings.( Altern Med Rev 2011;16(2):134-151)

IntroductionIBS is dened as abdominal pain or discomfort

that occurs in association with altered bowel habitsover a period of at least three months. 1 Symptomsof IBS include abdominal pain, change in bowelhabits (diarrhea or constipation), bloating, andincomplete defecation. 2 However, symptompresentation and severity vary. 3 Since currentdiagnostic criteria are based on symptoms, 1 denitive diagnosis of IBS presents challenges dueto overlap in symptom presentations with otherdiseases or associated conditions (e.g., lactoseintolerance, inammatory bowel disease, celiacsprue, small intestinal bacterial overgrowth). Morethan 75 percent of patients suffering from IBS in

the United States go undiagnosed; 75 percent ofthose diagnosed suffered at least two years or more,and one-third of these suffered for over 10 yearsprior to diagnosis. 4,5 Lack of denitive diagnosisand treatment and the chronic, debilitating natureof IBS often compel patients to change or limittheir diets, 2 seek non-prescribed pharmacologicalregimens (complementary and alternative medi-cine [CAM] therapies in particular), 6,7 and modifyroutine daily activities 8-10 in order to managesymptoms.

Te purposes of this review article are to: (1)address current issues related to IBS includingsymptom presentation, diagnosis, and current

treatment guidelines; (2) summarize benets andside effects of currently available pharmacologicalregimens and other symptom managementstrategies, with an emphasis on commonly usedCAM therapies and diet modication; and (3)recommend future directions of IBS managementbased on systematic reviews, meta-analyses, andresearch ndings.

IBS: Prevalence and DiagnosisDepending on how IBS criteria are dened,

overall prevalence rates range from 2.1-22 percent.Women are about 1.5-2 times more likely todevelop IBS than men. 1,5,11,12 Although it is presentin all age groups, prevalence of IBS seems todecline with advanced age. 5 According to Rome IIIcriteria, an IBS diagnosis can be made if recurrentabdominal pain has been present for at least threedays per month during the preceding three months,accompanied by two of the following three symp-toms: relief with defecation, onset of symptomswith a change of stool consistency, and stoolfrequency without any obvious biochemicalabnormalities or morphological changes. 13 Since

Saunjoo L. Yoon, PhD, RN Associate Professor, Collegeof Nursing, Department ofAdult and Elderly, Universityof Florida, GainesvilleCorrespondence address:Department of Adult andElderly, University of FloridaCollege of Nursing, HPNPComplex, P.O. Box 100187,Gainesville, FL 32610Email: [email protected]

Oliver Grundmann, PhD Assistant Professor, College

of Pharmacy, Department ofMedicinal Chemistry, Univer-sity of Florida, Gainesville

Laura Koepp, BSN, RN Virginia Mason MedicalCenter, Seattle, WA

Lana Farrell, BSN, RN PalmBeach Gardens MedicalCenter, Juno Beach, FL

Management of Irritable Bowel Syndrome(IBS) in Adults: Conventional andComplementary/Alternative ApproachesSaunjoo L. Yoon, PhD, RN; Oliver Grundmann, PhD; Laura Koepp, BSN, RN; Lana F


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135 Alternative Medicine Review Volume 16, Number 2 Copyright 2011 Alternative Medicine Review, LLC. All Rights Reserved. No Reprint Withou

Review Article

Key words:IBS, irritablebowel, GI, gastrointestinal,iberogast, padma lax,peppermint, TCM,probiotics, yoga, hypnosis,TXYF, curcuma, herbal,turmeric, curcumin, artichoke,cynara, food allergy, turmeric,menthe,bidobacterium,lactobacillus, B. coagulans, S. boulardii

current differential diagnosis of IBS is not based onmorphological changes or characterized by bio-chemical dysregulation, the only way to differenti-ate IBS from other functional bowel disorders

(FBD) is by exclusion. Despite the advocated use ofRome II and III criteria to diagnose IBS ( able 1), arecent systematic review published by the

American College of Gastroenterology (ACG) askForce reported that the accuracy of this criteria hasnot been well established. 1 Tis has been reectedin this review by referring to IBS as a symptomcomplex, where individual symptoms have limiteddiagnostic accuracy.

Impact on Quality of Life (QOL)Te most frequently reported symptoms

negatively impacting QOL in persons with IBS areabdominal pain, bowel difficulties, bloating, and

limitations in eating/diet restrictions.4,14

Whileconstipation-predominant IBS and diarrhea-pre-dominant IBS similarly impact QOL, 2,14 bloatingand diarrhea have the most negative impact onpatient self-condence and often lead to avoidanceof social settings. 15 IBS affects daily functioning,work and lifestyle, 4 and interrupts sleep, whichleads to increased fatigue. 16 For example, manypersons with IBS are forced to stay close to a toilet(>50%), are distressed by symptoms (69%),

experience lack of control over theirlives (57%), and are emotionallydisturbed (upset, depressed, less

condent, or worried). Te degree ofinterruption of daily life is alsorelated to co-existing or co-occurringconditions such as depression andanxiety. Relationships betweenstress and IBS have been reported byresearchers, 17-21 and most patientssuffering from IBS identify stressand anxiety as symptom aggrava-tors. 2 Psychological stress canincrease severity of IBS symptoms, 17 and a correlation between slow onsetof IBS symptoms and common stressdisorders such as depression andanxiety was noted by Mayer et al. 21 Itis therefore important to considereach individuals lifestyle, medicalhistory, and co-existing conditions(e.g., diet, physical activity, recentbowel infection, family history ofcolon cancer) when diagnosingpatients. 22,23

Health Care CostsAssociated with IBS

Te direct and indirect costsassociated with IBS are estimated at$200 billion worldwide. 24 Tis isrelated to the high incidence(approximately 250-300 cases of IBSdiagnosed per 100,000 people) andprevalence of IBS compared to otherFBDs, such as inammatory boweldisease (IBD). Moreover, the costs ofIBS in the United States havesignicantly increased during recent

Table 1. Rome II and III IBS Diagnostic Criteria

Diagnostic criterionRecurrent abdominal pain or discomfort atleast three days/month in last three monthsassociated with two or more of thefollowing:

1. Improvement with defecation.2. Onset associated with a change infrequency of stool.

3. Onset associated with a change in form(appearance) of stool.

In pathophysiology research and clinicaltrials, a pain/discomfort frequency of atleast two days a week during the screeningevaluation is recommended for subjecteligibility.

At least 12 weeks of abdominal discomfort or painthat has two out of three features, which need notbe consecutive, in the preceding 12 months:

1. Relieved with defecation; and/or2. Onset associated with a change in frequency ofstool; and/or

3. Onset associated with a change in form(appearance) of stool.

Symptoms that cumulatively support thediagnosis of IBS: Abnormal stool frequency (for researchpurposes abnormal may be dened asgreater than three bowel movements per day andless than three bowel movements per week); Abnormal stool form (lumpy/hard orloose/watery stool); Abnormal stool passage (straining, urgency, orfeeling of incomplete evacuation); Passage of mucus; Bloating or feeling of abdominal distension.

Criterion fullled for the last three months with symptom onset at least six months prior to diagnosis. Discomfort means an uncomfortable sensation not described as pain.

Adapted from: Drossman DA, Douglas A, eds.Rome III: The Functional Gastrointestinal Disorder . 3rd edition ed:Degnon Associates; 2006.

Rome III criteria Rome II criteria


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years. In 1998, direct costs (e.g., medical services,hospitalizations) were estimated to be $1.4 billion.Indirect costs (e.g., loss of work hours/productivitydue to time spent in medical services/treatment,

lost future earnings if job was lost) were estimatedto be $205 million, adding up to a total cost burdenof $1.6 billion. By 2000, this number increased to$1.8 billion. 25

Pathogenesis and PathophysiologyTe pathophysiology of IBS is distinguishable

from celiac disease and inammatory boweldiseases (e.g., ulcerative colitis, Crohns disease)since IBS does not present with gross organic orbiochemical abnormalities. 26-28

Although the pathogenesis of IBS isnot known, a multi-factorial involve-

ment of diet, gene mutations,psychosocial factors, and immune-mediated processes is hypoth-esized. 29 Te contribution of thesefactors varies and in many cases nosingle cause can be determined.

One theory regarding the patho-physiology of IBS involves interfer-ence of neurotransmission betweenthe central nervous system (CNS)and the intestines. A number ofstructures in the CNS are connectedwith the gut via serotonergic andcholinergic nerves referred to asthe enteric nervous system(ENS).30,31 Independent of theafferent connections, the intestineuses serotonin itself to regulate gutmotility. Serotonin binds to 5-H 4 and 5-H 3 receptors, and its signal-ing activity is terminated by bindingto the specic serotonin reuptaketransporter. 32,33 It has been shownthat the activity of this transporteris reduced in several GI disorders

(including IBS) that present withcommon symptoms of dysregulatedintestinal motility caused by persis-tent serotonin release at its respec-tive receptors. 33 Based on this theory,a variety of treatment approacheshave been suggested that temporar-ily treat the symptoms rather thanthe cause of IBS, since there is stillconsiderable lack of knowledge aboutIBS pathogenesis andpathophysiology.

Conventional PharmacologicalTreatments

IBS can be classied as either diarrhea predomi-nant (IBS-D), constipation predominant (IBS-C), or

a mixed form (IBS-M).22

Te diagnosis leads totreatment recommendations with limited effective-ness for IBS management. Due to the wide range ofsymptoms that may be experienced, the availablepharmacological treatments are mainly targeted atsymptom reduction. In addition, some patientsmay have coexisting conditions that contribute tothe severity of IBS symptoms, requiring furtherconsideration when choosing treatmentoptions. 34,35 Based on predominant GI motility

Table 2. Conventional Pharmacological Treatments for IBS

Indication

IBS-M

IBS-D

IBS-C

Drug Target

serotonergic and adrenergicreceptors

intestinal ora

cholinergic receptorantagonists

5-HT receptor antagonists

selective M receptorantagonists

agonist

-opioid receptor agonist

chloride channel modulator

5-HT agonists

Physiological Effect

compliance, motility

motility, bloating, pain

intestinal motility, pain

intestinal motility, pain

intestinal motility

intestinal motility, pain sensation

intestinal motility, peripheral pain

intestinal motility, water secretion

intestinal motility, water secretion

Drugs/CompoundsExamples

venlafaxine, uoxetine

probiotics

cimetropium, pinave-rium, hyoscine,otilonium, mebeverine

ondansetron, alosetron,cilansetron

zamifenacin, darifenacin

clonidine

loperamide

lubiprostone

tegaserod,metoclopramide,domperidone, cisapride


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dysfunction, loperamide and codeine for thetreatment of diarrhea in IBS-D, laxatives andprokinetics for the treatment of constipation inIBS-C, and antispasmodics for all types of IBS have

been used extensively to reduce the respectivesymptoms. Current pharmacological treatmentsare summarized in able 2.

IBS-D TreatmentsLoperamide is an opioid receptor agonist that is

not absorbed from the GI tract after oral adminis-tration, acting locally to reduce GI motility andspasms. 36 Similar to loperamide, codeine canreduce abdominal and visceral pain 37 as well as GImotility, but may affect the CNS, causing sedationand potential drug abuse. 38 Many patients withIBS-D also suffer from nausea and vomiting due to

serotonin stimulation of 5-H 3 receptors in theintestines. Tere are a number of 5-H 3 antago-nists that were originally prescribed for thetreatment of chemotherapy-related nausea, but arenow often used to reduce symptoms of IBS-D. 39 Forinstance, ondansetron, granisetron, alosetron, andcilansetron are all specic 5-H 3 receptor antago-nists that reduce nausea and vomiting and act asvisceral analgesics in IBS-D. 40

IBS-C and IBS-M Treatments Although it was more effective than a placebo,

the use of the prokinetic tegaserod in IBS-C andIBS-M has been limited due to adverse ischemiccardiovascular events. 1,41 Several other prokineticssuch as metoclopramide, domperidone, andcisapride are used off-label, even without a specicindication for IBS treatment. 42 Lubiprostone isanother recently approved prokinetic drug thatacts on chloride channels to increase water secre-tion into the intestines. Prokinetics increase GImotility and provide visceral analgesia by acting asdopamine antagonists, serotonin antagonists atthe 5-H 3 receptor, and serotonin agonists at the5-H 4 receptor.

43,44

Increasing dietary ber intake is an importanttreatment option that should be considered beforeprescribing tegaserod or lubiprostone for patientswith IBS-C. Fiber stimulates GI motility andloosens stool consistency. 45 Laxatives may also beconsidered as initial treatment if ber intake alonedoes not alleviate constipation. Use of laxativessuch as polyethylene glycol, or the stool softenerdocusate, should be monitored with care sinceelectrolyte imbalances may occur. Overall, theeffectiveness of laxatives and stool softeners in thetreatment of IBS-C is limited. 46

Antispasmodics for Various Forms of IBS Antispasmodics are the most common class of

pharmacological drugs used for managing variousforms of IBS. Antispasmodics predominantly act as

antagonists at cholinergic receptors and therebyreduce contraction of the GI tract. Commonly usedantispasmodics that have proven to be effective inthe treatment of IBS spasms are cimetropium,pinaverium, hyoscine, and otilonium. 47 Dependingon the symptoms, antispasmodics are adminis-tered up to three times daily in conjunction withprokinetics or laxatives to normalize GI motilitywithout causing constipation.

Effect of Antidepressants on IBS SymptomsIn addition to normalization of GI motility with

antispasmodics, tricyclic antidepressants ( CAs)

and selective serotonin reuptake inhibitors (SSRIs)have become a mainstay of supportive treatmentfor IBS.48 Both drug classes were initially used totreat co-existing mental disorders such as depres-sion and anxiety in patients with IBS, but clinicaltrials have shown that IBS patients without adepressive disorder can benet from low-dose CAtherapy. 49 Surprisingly, both CAs and SSRIs donot interfere with serotonin concentrations in theintestines, which would otherwise further increaseIBS symptoms. Instead, they appear to normalizeGI motility and reduce visceral pain. 50,51 Long-termoutcomes of these therapies are, however, not wellunderstood and require more research. 1 In spite ofcurrently available pharmacological treatments toreduce symptoms of IBS and improve QOL, thesearch for more effective therapies with fewer sideeffects continues. 1

Use of CAM for IBSCAM is often used for chronic medical condi-

tions, health promotion, and/or disease preven-tion. 52-55 Currently available systematic reviewsprovide conicting ndings about the effectivenessof CAM therapies for IBS. Te American College of

Gastroenterology ask Force on IBS 1 reported thatCAM therapies have not demonstrated any strongevidence-based support for positive outcomes.Other systematic reviews, however, indicateevidence of effectiveness. 6,56,57

In recent studies, up to 50 percent of individualssuffering from IBS reported using CAM, 6,7 which isnot surprising considering currently availablepharmacological treatments for IBS have shownlimited benet and signicant side effects. About50 percent of self-prescribed herbal supplementusers perceived benets of using herbal


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supplements for IBS, while the other half reportedequivocal effects. 7 Considering the chronic butvariable nature of IBS, it is not surprising thatmany IBS patients using CAM are unsure of its

effectiveness. Among various types of CAM, herbalproducts including Chinese herbal mixtures,hypnosis, relaxation technique, acupuncture,dietary changes, probiotics, and exercise have beenstudied for their potential benets. 6

Herbal Therapies Although a limited number of well-designed

studies are available, various herbal remedies havebeen tested for managing IBS, either as a singleherb or herbal combination. Single herbs that havebeen studied include peppermint oil, turmeric

extract, and artichoke leaf. Common combinationsof multiple herbs used for IBS include a variety ofChinese herbal formulas, the ibetan herbalmixture Padma Lax, and a combination of nine

herbs referred to as S W 5, marketed under thetrade name Iberogast. 58

Enteric-coated Peppermint Steam distillation oil extracts from the pepper-

mint plant ( Mentha piperita , Lamiaceae) are amongthe oldest remedies for treatment of GI problems.Tese extracts are believed to improve IBS symp-toms by exerting a spasmolytic effect on thesmooth muscles in the digestive tract. 59 In additionto a number of case reports and small, uncon-trolled studies, 60-64 two randomized, double-blind,

Table 3. Single Herbal Medicines for IBS

Reference

Capello et al (2007)

Merat et al (2010)

Bundy et al (2004)

Walker et al (2001)

Bundy et al (2004)

Samplesize

57

90

207

279

208

Samplecharacteristics

All IBS forms, IBSdetermined byRome II criteria

All IBS forms, IBS

determined byRome II criteria


All IBS forms,

meeting at least3 out of 5 RomeII criteria

All IBS forms,meeting at least3 out of 5 RomeII criteria

Studydesign

R,D,P

R,D,P

R,non-D,non-P

R,

non-D,non-P

R,non-D,non-P

Dose of active

225 mg peppermint oil percap; 2 caps bid

187 mg peppermint oil tid,

30 min before meals

2 doses, 72 mg (1 tablet)or 144 mg (2 tablets) daily

320 mg artichoke leaf

extract per cap; 2 caps tidw/ meals

320 mg (1 capsule) or 640mg (2 capsules) of 1:5artichoke leaf extract daily

Duration

4 weeks rx; 4weeks follow-up

8 weeks

8 weeks

6 weeks

8 weeks

Outcome

Signicant reduction in IBSsymptoms after 4 weeks inpeppermint oil group vs.placebo group

Signicant reduction in

abdominal pain and severityin peppermint oil group vs.placebo, signicant increase inQOL in peppermint oil groupvs. placebo

Signicant improvement inIBS QOL at end of trialcompared to baseline for bothtreatment groups

Signicant reduction of

IBS-related symptomsevaluated on a Likert scale atend of study compared tobaseline

Signicant reduction in NDIQOL score at end of trialcompared to baseline

Turmeric extract (standardized)

Artichoke leaf extract

Enteric-coated peppermint oil capsules

R: Randomized, D: Double-blind, P: Placebo-controlledNDI=Nepean Dyspepsia Index


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placebo-controlled trials report a benecial effectof peppermint oil for the treatment of IBSsymptoms. 65,66

In one study, after four weeks of treatment, a

group receiving two enteric-coated capsulescontaining 225 mg of peppermint oil twice daily(n=28) showed a statistically signicant improve-ment in overall IBS symptoms compared with aplacebo group (n=29). Te peppermint oil waseffective in alleviating constipation, bloating,diarrhea, abdominal pain, passage of gas or mucus,urgency at defecation, pain during evacuation, andfeelings of incomplete evacuation. Efficacy wasevaluated via intensity and frequency score using aLikert scale (0-4) for each symptom. 65

A randomized, double-blind clinical trial with 90IBS patients (45 subjects in each group) conrmed

that both pain severity and general healthimproved after eight weeks of administration withan enteric-coated product (Colpermin, containing187 mg peppermint oil) three times daily comparedto placebo. Outcomes were measured using theSF-36 questionnaire as well as an intensity andfrequency score with a Likert scale (0-3). 66

Te use of peppermint oil for the treatment ofIBS in children has also received a positive

evaluation by the American Academy of Pediatrics,but with cautions due to potential side effects ofheartburn or respiratory depression and lack ofavailability of standardized dosages. It is suggested

to give 0.1-0.2 mL three times daily for no longerthan two weeks under the guidance of a health carepractitioner. 67

Turmeric urmeric ( Curcuma longa, Zingiberaceae) has

been traditionally used for managing abdominalpain, indigestion, and abdominal bloating.Effectiveness of turmeric on improvement of IBSsymptoms and QOL was investigated in 207 IBSpatients. Statistically signicant improvementsbased on symptoms and quality of life (IBS-QOLquestionnaire) were found after eight weeks of

turmeric intervention at a dose of 72 or 144 mgdaily, compared to screening and baseline phases(but no placebo group). Tere were no differencesbetween the two groups, indicating a dose-inde-pendent or threshold effect. 68

Artichoke Leaf Extract wo studies on artichoke ( Cynara scolymus,

Asteraceae) leaf extract (ALE) indicated IBSsymptom improvement. According to a post-mar-keting surveillance study of 279 subjects, twocapsules ALE three times daily with meals (320 mg

ALE per capsule) relieved abdominal pain, cramps,bloating, atulence, and constipation in subjectswith dyspepsia and at least three of ve commonlyobserved IBS symptoms (evaluated by physiciansand patients using a Likert scale). 69

In another open, post-marketing study involving208 subjects, the Nepean Dyspepsia Index (NDI)indicated that there was a signicant decrease inoverall IBS symptoms, including abdominal pain,diarrhea and/or constipation, urgency, straining,feeling of incomplete passage, and passage ofmucus after two months of intervention with 320mg or 640 mg ALE daily. In addition to normaliza-

tion of bowel movements, an increased QOL wasreported with use of ALE. 70

Although the two ALE studies were conducted bysome of the same researchers with the sameartichoke extract, it is not clear why the dosage wasso different between the two studies 69,70 (assumingthe correct dosages were provided by the studyauthors).

Table 4. Herbs in Iberogast

Plant (Latin name)

Bitter candytuft(Iberis amara)

Angelica root(Angelica archangelica)

Chamomile owers(Matricaria recutita)

Caraway fruits(Carum carvi)

Milk thistle fruits(Silybum marianum)

Lemon balm leaves(Melissa officinalis)Peppermint leaves(Mentha x piperita)

Celandine (Chelidonium majus)

Licorice root extract(Glycyrrhiza glabra)

Herb-Extract ratio(alcoholic extracts)

1:1.5-2.5

1:2.5-3.5

1:2.5-4.0

1:2.5-3.5

1:2.5-3.5

1:2.5-3.51:2.5-3.5

1:2.5-3.5

1:2.5-3.5

In 100 mLIberogast

15.0 mL

10.0 mL

20.0 mL

10.0 mL

10.0 mL

10.0 mL5.0 mL

10.0 mL

10.0 mL

Adapted from: Vinson B. Development of Iberogast: Clinical evidence for multicomponentherbal mixtures. In: R. Cooper and F. Kronenberg, eds.Botanical Medicine:From Bench toBedside. Mary Ann Liebert Inc. 2009.


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Combination Herbal FormulasMultiple herbal preparations

such as Iberogast, Padma Lax,and ong Xie Yao Fang ( XYF)

have shown promising out-comes for managing IBS.Iberogast, a combination of

nine herbal extracts ( able 4),was shown in several clinicaltrials to improve symptoms offunctional dyspepsia at a doseof 20 drops three timesdaily. 71-73 While symptoms offunctional dyspepsia are oftensimilar to IBS in terms ofgastrointestinal disturbances,pain, and reduced quality of life,

only limited clinical data areavailable regarding its effective-ness for specic IBS symptoms.Te symptoms of functionaldyspepsia are often predomi-nantly related to food consump-tion, with resulting gastric acidsecretion leading to gastroin-testinal symptoms withoutdetectable functional problems.Iberogast has been shown to interact with severalreceptors in the GI tract that play an importantrole in regulation of motility and pain perception,including serotonin, muscarine, and opioidreceptors. For example, the different extracts inIberogast bind to the 5-H 3 serotonin receptor asagonists, while antagonizing the 5-H 4 andmuscarine M 3 receptor in a similar manner tocurrent synthetic drugs. Overall, the pharmacologi-cal effects of Iberogast are complex in nature,affecting acid secretion, inammation, oxidativeprocesses, as well as both hyper- and hypomotilityto varying degrees ( able 5). 74

Although some case reports provide evidence foreffectiveness of Iberogast in alleviating abdominal

pain and normalizing gut motility, 75 only oneclinical trial with a double-blind, placebo-controlleddesign has been conducted in 208 patients withIBS.76 In this study, patients were randomlyassigned to commercially available Iberogast (S W5; n=51), a research preparation of some of theherbs in Iberogast (bitter candytuft, chamomileower, peppermint leaves, caraway fruit, licoriceroot, and lemon balm leaves referred to as S W5-II; n=52), bitter candytuft alone (n=53), or

placebo (n=52) (20 drops three times daily for fourweeks). Both S W 5 and S W 5-II were found to beeffective in reducing abdominal pain severity

(evaluated via abdominal pain scale) and improvingoverall symptoms (using the IBS symptom scale)compared to placebo or bitter candytuft alone.

Te complex ibetan preparation, Padma Lax(herbs in formula are listed in able 6), has beenshown to be effective in alleviating symptoms ofIBS-C.77 In a three-month, double-blind, random-ized observational trial, 482 mg twice daily (oncedaily in seven patients who got loose stool fromthe twice-daily dosage) was superior to a placebofor reducing constipation, abdominal pain, andatulence. 78 Furthermore, rat studies demonstratePadma Lax exerts part of its activity throughcholinergic receptors by reducing contractility ofsmooth muscles in the colon as well as procontrac-tile stimulation. 79

raditional Chinese medicine ( CM), in the formof standardized combinations or formulas tailoredspecically to the individual symptom presenta-tions, improved common IBS symptoms comparedto placebo as evaluated in a double-blind, placebo-controlled, randomized study. 56 Te study wasconducted on 116 patients who received placebo, a

Table 5. The Pharmacological Effects of Iberogast

Symptoms / Botanical

Peppermint leaf extract

Chamomile ower extract

Licorice root extract

Angelica root extract

Caraway fruit extract

Milk thistle fruit extract

Melissa leaf extract

Celandine herb extract

Bitter candytuft extract

Acidsecretion

W

S

W

M

M

M

M N

M

Inammation

S

W

S

W

S

M

MM

S

Oxidativeprocesses

S

M

W

M

W

M

SM

W

Hypomotility

N

M

N

N

N

N

NM

M

Hypermotility

M

S

M

S

W

M

WN

W

N=No effect, W=Weak effect, M=Moderate effect, S=Strong effectFrom: Wagner H. Multitarget therapy the future of treatment for more than just functional dyspepsia.Phytomedicine2006;13 suppl 5:122-129.


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standard mixture of 33 herbs, or an individualizedmixture of herbs selected by a CM specialist froma list of 81 herbs. After 16 weeks, patients in theactive treatment groups showed signicant

improvements in bowel symptom scores (asevaluated by visual analog scales) and increasedQOL compared to placebo.

A specic CM herbal mixture, Shugan Jianpi,was found to reduce the number of serotonin-positive cells compared to a placebo in patientswith IBS.80 Te 24 patients received standard carethat included cognitive-behavioral therapy and awhey protein (lactein). Te placebo group did notreceive any additional medication, while theShugan Jianpi groups took 24 g of the herbalmixture three times daily or 24 g of the herbalmixture plus 15 g Smecta (a high viscosity

muco-protective agent) three times daily for twoweeks prior to biopsy to measure number ofserotonin-positive cells. Te authors did notevaluate any subjective or other objective clinicalparameters. 80

ong Xie Yao Fang ( XYF), a Chinese herbalpreparation and a variation ( XYF-A) have thepotential to improve global symptoms in IBS-D. 57,81

Although a systematic review of XYF-A indicatedits potential effectiveness for reducing IBS symp-toms, more studies with rigorous designs arewarranted. 82 Te standard preparation of XYF iscomposed of four traditional herbs Cang zhu( Atractylodes chinensis), Bai shao (Paeonia lactiora ),mandarin orange ( Citrus reticulata ), and Fang feng(Saposhnikovia divaricata ). Based on the individualsymptoms, additional herbs may be added to themixture, with the resultant formula referred to as

XYF-A. Te review evaluated 12 randomizedstudies with 1,125 participants for the short- andlong-term effects of XYF-A in reducing clinicalIBS symptoms. Te heterogeneity of the studydesign and duration of the studies complicated thedenition of end points. Overall, the preparationsimproved various IBS symptoms, including

abdominal pain, distension, atulence, anddiarrhea for as long as six months after theintervention ended.

Leung and colleagues 83 compared a preparationof 11 herbal extracts ( able 7) comprising amodication of the traditional XYF formula(n=60) with a placebo (n=59) in a controlled,randomized, blinded design. Tey found that globalassessment scales and QOL did not differ betweenthe CM herbal preparation and placebo after eightweeks of treatment. Based on this study, CMherbal preparations may not be benecial to all IBS

Table 6. Botanicals in Padma Lax

Plant part (Latin name)

Ginger rhizome(Zingiber officinalis)

Chinese rhubarb root(Rheum officinale)

Frangula bark(Rhamnus rubra)

Cascara sagrada bark(Rhamnus purshiana)

Gentian root(Gentiana lutea)

Chebulic myrobalan fruit(Terminalia chebula)

Elecampane rhizome(Inula helenium)

Aloe extract(Aloe veraand/or Aloe ferox)

Calumba root(Jateorhiza calumba)

Condurango bark(Gonolobus condurango)

Long pepper fruit(Piper longum)

Nux vomica seed(Strychnos nux vomica)

(From http://www.naturalhealthconsult.com/Monographs/padmaLax.html)

Table 7. Modied TXYF FormulaChinese name

Bai zhu

Huang qui

Bai shao

Cang zhu

Chai hu

Chen pi

Fang feng

Jiu li xiang

Shi liu pi

Ma chi xian

Huang lian

Plant part (Latin name)

Rhizome(Atractylodes macrocephala)

Root(Astragalus membranaceous)

Peeled root (Paeonia lactiora)

Rhizome (Atractylodes chinensis)

Root(Bupleurum chinense)

Peel(Citrus reticulata)

Root(Saposhnikovia divaricata)

Twigs(Murraya paniculata)

Rind(Punica grantum)

Aerial parts (Portulaca oleracea)

Rhizome (Coptis chinensis)

Dosage (g/day)

15

15

15

12

9

9

9

9

9

30

6


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patients but may show promise for specic IBSsymptoms. More clinical data utilizing rigorousclinical trial designs are required to further supporttheir use.

In summary, a number of single herbal remediesor herbal combinations ( able 8) are reportedlyeffective for relieving IBS symptoms. Furtherstudies investigating the potential mechanisms ofpharmacological action and symptom management

in rigorous clinical trial designs are warranted toconrm the observed treatment effects.

Mind-Body Therapies Among mind-body therapies, hypnotherapy and

cognitive-behavioral therapy (CB ) seem to be themost widely accepted by IBS patients.

Table 8. Summary of Studies on Herbal Combinations for IBS



IBS-C, IBSdetermined byRome I criteria

All IBS forms,determined byRome criteria(not specied)

All IBS forms,evaluation not

specied

IBS-D, IBSdetermined byRome II criteria

Outcome

Signicant reduction ofIBS symptoms andabdominal pain inIberogast and researchsolution compared toplacebo

Signicant reduction insymptom severity scoresand abdominal pain inPadma Lax compared toplacebo

Signicant reduction inbowel symptom scoresand increase in QOL forindividual preparationand standard TCMcompared to placebo

Signicant reduction inserotonin positive cells in

both Shugan Jianpigroups compared tostandard care

No signicant improve-ment in SF-36 or globalsymptoms compared toplacebo

Duration

4 weeks

12 weeks

16 weeks

2 weeks

8 weeks

Dose

STW 5, STW 5-II, orbitter candytuft extract,20 drops tid

482 mg Padma Lax(n=34) or placebo(n=27), bid (once dailyin subjects w/ loosestool)

Standard TCM mixture of33 herbs (n=43),individualized formula(n=38), or placebo(n=35), 5 capsules tid

24 g Shugan Jianpigranules tid, 24 g

Shugan Jianpi granulesplus 15 g Smecta tid, orcognitive therapy andlactein treatment asstandard care

See Table 7 for dailydose of each herb(n=60) or placebo(n=59)

Studydesign

R,D,P

R,D,P

R,D,P

R,non-D,P

R,D,P

Samplesize

203

61

116

24

119

Reference

Madisch et al(2004)

Sallon et al (2002)

Bensoussan et al(1998)

Wang et al (2008)

Leung et al (2006)

Iberogast

Padma Lax

Traditional Chinese Herbal Medicine

R: Randomized, D: Double-blind, P: Placebo-controlled


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Hypnotherapy According to several clinical trials hypnotherapy

has the potential to be effective in managing IBSsymptoms ( able 9). 84-86 Hypnotherapy was

effective in improving health-related QOL andanxiety, tiredness, and physical symptoms, but notdepression, after 12 weeks of intervention withoutrandomization, 86 while three systematic reviews 87-89 reported that hypnotherapy can be used to treatabdominal pain and improve QOL, as well asreduce anxiety and depression. A nonsignicantreduction in depression scores was seen in theaforementioned study, 86 while systematic reviewsof hypnotherapy for IBS provide evidence for areduction in depressive symptoms. 87-89 Tisdifference in outcomes may be due to heterogene-ity of study designs.

Although the precise mechanisms of action forhypnotherapy are not known, several psychologicaland physiological changes have been observed inmany of the studies, including improvement incognitive function, reductions in anxiety anddepression scores, decreased colonic contractions,

and improvement in visceral sensations. 90 It hastherefore been proposed that GI symptomimprovement is a result of central effects thatmodulate cortical brain circuits involved with pain

and vigilance modulation.91

However, furtherwell-designed studies should be conducted toconclusively establish efficacy of hypnotherapy as asupportive treatment for IBS.

Cognitive-Behavioral Therapy Cognitive-behavioral therapy is another poten-

tial alternative approach to managing IBS,although according to a recent Cochrane databasereview there does not seem to be concrete, reliableevidence to prove its efficacy. 92 A primary concernwith psychotherapeutic interventions is theinuence of psychological factors on a patients

perception of IBS symptoms. 93 Since IBS is diag-nosed based on exclusion criteria and is associatedwith signicant psychosomatic relations, patientswho reject psychological interventions or whosesymptoms are not severe enough are not consid-ered potential candidates for CB . In many cases, a

Table 9. Studies of Hypnotherapy for IBS


All IBS forms, IBSdetermined byRome I criteria

All IBS forms, IBSdetermined byRome I criteria


Outcome

Signicant improvementsin HADS scores and IBSsymptoms compared tobaseline

Signicant reduction inIBS symptoms and HADSscores as well asreduction in medicationuse in hypnotherapy-responsive patientscompared tonon-responsive patients

Signicant improvementin IBSQOL scores,abdominal pain anddistension, and anxiety

compared to baseline

Duration

12 weeks

12 weeks

Numberof sessions

12 hypnotherapysessions followed byself-study

Retrospective analysis ofIBS symptoms one yearafter hypnotherapy

5-7 hypnotherapysessions over threemonths with follow-up

Studydesign

non-R,non-D,non-P

non-R,non-D,non-P

non-R,non-D,non-P

Samplesize

250

204

75

Reference

Gonsakorale et al(2002)

Gonsakorale et al(2003)

Smith (2006)

R: Randomized, D: Double-blind, P: Placebo-controlled


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combination of CB with pharmacological treat-ment provides the best outcome. 1 According to VanDulmen and colleagues, 94 eight two-hour sessionsof CB intervention over a period of three months

was effective in signicantly decreasing abdominaldiscomfort, enhancing coping strategies, anddiminishing avoidance behavior (impacting QOL)in IBS patients. Te patients were asked to keep adaily record of the activities they avoided becauseof their IBS symptoms. 94

In a randomized, controlled trial with three arms(CB , relaxation therapy [R ], or routine clinicalcare [RCC]) involving 105 subjects, individualswere treated weekly over an eight-week period withfollow-up at 26 and 52 weeks. Although resultsshowed signicant improvement after eight weekswith all three interventions compared to baseline

in all parameters measured, there were no signi-cant differences among the three treatment groupsduring the follow-up period. It was concluded thatRCC was as effective as CB or R .95

A number of additional clinical trials andmeta-analyses found similar results; CB was aseffective as current standard pharmacologicaltreatments for IBS. A combination of both mayprovide additive symptom relief to patients. 96-100 Te ACG ask Force on Irritable Bowel Syndromesupports the use of CB for the treatment ofcertain forms of IBS. 1

Relaxation TechniquesRelaxation techniques have been studied for

their potential role in alleviating IBS symptoms.Multiple studies have indicated positive correla-tions among psychological distress, daily stress,and GI symptom aggravation 17-20,101 that triggeredIBS symptoms. 2,102 Women with IBS tend to reporta higher amount of psychological distress andlifetime psychopathology than those with no GIsymptoms. 103 Relaxation training may be benecialfor symptom improvement and appears to be atleast as effective as standard pharmacological

treatment. Te relaxation techniques used in thisstudy included progressive muscle relaxation,release-only, cue-controlled, and applied relaxation,in addition to standard clinical care. 95 Inclusion ofautogenic training, a relaxation technique thatserves to increase self-directed awareness tensionthrough conscious breathing, slowing of theheartbeat, and muscle relaxation, and otherrelaxation techniques improve IBS-related GIsymptoms as well as QOL and increase symptom-free days compared to standard pharmacological

treatment. 102,104-106 In addition, the self-administra-tion of relaxation techniques provided long-termrelief of most IBS symptoms as assessed by aone-year follow-up study. 104 Te retrospective

study reviewed 10 patients with IBS, who initiallyparticipated in a three-month study on the use ofrelaxation response meditation. After one year,participants were evaluated for abdominal pain,diarrhea, distension, and atulence all of whichpresented with signicant reductions compared tobaseline. 104

Acupuncture and Moxibustion Acupuncture can cause physiological changes

that affect various endogenous neurotransmittersystems. Of specic interest to the treatment ofIBS is the inuence of acupuncture and moxibus-

tion on the serotonergic and cholinergic neuro-transmission of the brain-gut axis. Both animaland human trials indicate specic targets foracupuncture on serotonergic, cholinergic, andglutamatergic pathways as well as reductions inblood cortisol levels. 107-110

In a controlled, randomized pilot study, 30subjects received routine clinical care or acupunc-ture for IBS. After three months of treatment,outcomes of acupuncture intervention revealedstatistically and clinically signicant improvementsin symptom severity, including pain, distension,bowel habits, and QOL compared to usual care only.In this study, however, the type of IBS was notdened for the sample population. 111

In a large, randomized, controlled study, 230subjects with IBS were assigned to one of threegroups. Te two intervention groups were eitherthree weeks of true or sham acupuncture followinga three-week run-in period of sham acupuncturetherapy with a limited (friendly, interactive)patient-practitioner relationship, while the thirdarm was a waitlist control group. Findings indi-cated no signicant difference in global outcomemeasurements between real and sham acupuncture,

but both interventions showed signicantimprovement over the waitlist control group. 112

In another similar study, Schneider and col-leagues randomized 43 subjects to receive eitheracupuncture or sham acupuncture for 10 sessions(an average of two per week). 113 Although theFunctional Diseases QOL questionnaire (FDDQL)in this study revealed that both groups improvedsignicantly in overall QOL, there was no differencebetween the two groups, suggesting that the effectof acupuncture was primarily a placebo response.


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According to Anastasi and colleagues, a combina-tion of acupuncture and moxibustion (acu/moxa)can be highly effective in IBS treatment. wenty-nine subjects who met Rome II criteria were

randomized into either individualized acu/moxatreatments or sham/placebo acu/moxa treatments.Results indicated that acu/moxa reduced abdomi-nal pain, signicantly reduced gas and bloating,and improved stool consistency over a four-week,eight-session intervention period. 114 A Cochranemeta-analysis suggests larger-scale studies arewarranted to conrm the benets of acu/moxa inalleviating IBS symptoms. 115

Diet Modication A primary goal of all IBS interventions is to

provide the patient with relief of symptoms and

improve the quality of life. Although the data fromclinical trials may in some cases not provide strongevidence for benets of dietary modication, itremains the primary non-pharmacological clinicalintervention for IBS patients; exclusion diets aresuccessfully used by many clinical practitioners. 1

Food intolerances or allergies are strong con-tributors to the exacerbation of IBS symptoms.Individuals with IBS often discover that certainfoods aggravate symptoms, 2,116-118 while others havefound relief from IBS symptoms by modifying theirdaily diet and increasing exercise activities. 2,8-10

Symptoms of IBS may be associated with visceralhyperactivity, GI motility disturbances, sugarmalabsorption, gas-handling disturbances, andabnormal intestinal permeability. 13,22,119 Eliminationdiets are often employed that remove the mostcommon allergens from the diet. 120 Although somepatients reported that removing wheat, dairyproducts, eggs, coffee, yeast, potatoes, and citrusfruits from their diets is helpful, such restrictionsmay be difficult to follow. 118 Dietary restrictionsmay provide patients with relief of IBS symptomsover time, while entirely skipping meals has beenfound to worsen IBS symptoms. 118,121

Macronutrients: Fat, Sugar, and Sugar AlcoholsIBS studies indicate a positive relationship

between fat intake and increased stool number anddiarrhea. 9,121 Intake of carbohydrates can alsoaggravate IBS symptoms. 118 Offending carbohy-drates include fructose and fructose-containingproducts such as soft drinks, cereals, and packaged/baked goods. Sorbitol and other sugar-alcoholsfound in most sugar-free or reduced-sugar prod-ucts are poorly absorbed in the GI tract and maycause increased atulence, abdominal discomfort,

and diarrhea, thus exacerbating IBS symptoms. 117 Other types of sugar-alcohols proposed to aggra-vate IBS symptoms include mannitol, xylitol,erythritol, lactitol, maltitol, and isomalt. 117 Due to

the multitude of variables related to IBS symptoms,study results are difficult to validate and challeng-ing to interpret.

Fiber Fiber intake from fruits and vegetables is

inversely correlated to bloating. 9 Te addition ofpsyllium ber, especially for persons with IBS-C,reduced IBS symptoms in some people, 117,122,123 while either wheat bran or a low-ber diet wasfound to be an ineffective management measure asevaluated by two meta-analyses of a total of 30studies. 123 Because most of the evaluated studies

had small sample sizes, the results are highlyvariable. Other widely variable factors included theamount of soluble (5-30 g) and insoluble (4.1-36 g)ber added to the diet and the duration of studyintervention (3-16 weeks). Overall, consumptionof soluble ber resulted in a decrease in global IBSsymptoms and constipation, whereas insolubleber demonstrated a less signicant effect. Neitherintervention, however, decreased abdominal painin IBS patients. Due to its moderate effectiveness,additional intake of soluble ber maybe recom-mended for IBS-C patients. Studies also revealedthat pain relief was not associated with increasedber intake and that the addition of insoluble bersuch as nuts or whole grains to the diet had eitherno effect or exacerbated IBS symptoms. 122

Lactose IntolerancePatients with IBS were found to have signi-

cantly more subjective lactose intolerance com-plaints (bloating, distention, and diarrhea) thanthose without IBS and to have increased likelihoodof lactose malabsorption than the general popula-tion. 124 Tus, decreased intake of lactose canbenet some IBS patients. 125 It is hypothesized

that, following ingestion of lactose, hydrogen gas isproduced and gut distention is promoted due tobacterial fermentation of the unabsorbed lactose.Interestingly, the majority of IBS sufferers, how-ever, failed to test positive for hydrogen breathtests that indicate lactose intolerance. 125

ProbioticsProbiotics have been extensively studied for the

treatment of IBS. A thorough review of the researchis beyond the scope of this article. A number ofstudies have examined the effect of single


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organisms on IBS symptoms and/or quality of life.Most studies used various species of Lactobacillus,Bidobacterium, and Streptococcus strains given inconcentrations of 10 8-1010 colony forming units per

day (cfu/day). Te primary endpoints of manystudies are reductions in bloating, abdominal pain,and atulence, as well as evaluation of globalsymptoms using the IBS severity scoring system.

In a randomized, controlled trial, 44 IBS patientswere given either Bacillus coagulans strain GBI-30,6086 or placebo for eight weeks. B. coagulans resulted in signicant relief of abdominal pain andbloating from baseline during each of sevenevaluation weeks; the placebo group experiencedonly signicant relief in abdominal pain at thesixth and eighth week. 126 In another study, 52patients with IBS-D were randomized to receive

either this same strain of B. coagulans or placeboonce daily for eight weeks. Te average number ofbowel movements daily signicantly decreased inthe treatment group compared to placebo. 127

Tere was a slight but statistically signicantreduction in symptom severity observed in 60patients with mild IBS randomly assigned toLactobacillus plantarum in a rosehip tea or rosehiptea alone for four weeks. L. plantarum strain DSM9843 at a dose of 2x10 10 cfu/day was found todecrease pain and atulence compared to thosetaking only rosehips. 128

At least two studies have evaluated the effects of Bidobacterium infantis 35624. One randomized,controlled trial (n=362 women with IBS of alltypes) found a dose of 10 8 cfu/day for four weeks(but not 10 6 or 10 10) was effective in reducedbloating, abdominal pain, and atulence, as well asglobal IBS symptoms compared to placebo. 129 Inthe second study, 77 IBS patients were randomlyassigned to B. infantis 35624, Lactobacillus sali-varius UCC4331, each (10 10 cfu/day), or placebo foreight weeks. B. infantis resulted in signicantreduction in symptom scores and inammatorycytokines compared to either L. salivarius or

placebo. 130 A benecial yeast Saccharomyces boulardii has also

been tested for IBS treatment. Subjects receivedeither S. boulardii (n=34) or placebo (n=33) for fourweeks. Te S. boulardii group experienced signi-cant improvement in IBS-QOL but not individualsymptom scores compared to placebo. 131

In addition to these individual organisms, morethan a dozen studies, just in the last ve years,have examined the effect of multiple probioticstrains on IBS.

ExerciseExercise can help maintain GI function and

reduce stress, which can help relieve some IBSsymptoms. Studies of IBS indicate positive rela-

tionships between physical activity and symptomrelief.10,121,132 Physical activity, such as pedaling abicycle, protects against GI symptom aggravationand alleviates gas in several studies. 10,121,132

Although one study revealed an inverse relation-ship between exercise and all GI symptoms exceptconstipation, 9 another study reported constipationimproved with mild exercise, therefore, potentiallybeneting IBS-C patients. 8

Te practice of yoga has also demonstratedreduction of IBS symptoms in both adult andadolescent populations. 133,134 Pranayama yoga hasbeen identied as an exercise regimen that

increases sympathetic tone, which is decreased inIBS-D patients. 135 In a two-month study, a yogaintervention group practiced twice daily, while theconventional treatment group received 2-6 mgloperamide daily. Results indicated that yogademonstrated improvement of IBS symptomsequivalent to conventional treatment. 135

SummaryTe goal of current standard pharmacological

treatment is to alleviate clinical symptoms of IBS.Because conventional treatments typically do notget to the root of the problem or provide anythingbut symptomatic relief, patients often seek CAMtherapies, including cognitive-behavioral therapy,herbal therapies, probiotics, mind-body therapies,acupuncture, dietary changes, and exercise.

Although most CAM therapies reviewed in thisarticle seem to provide some benet in alleviatingIBS, it is apparent that the duration, dosages, andspecics of the intervention greatly affect theoutcomes. More studies need to be conducted toestablish the subtle nuances associated with thesetreatments (e.g., specic probiotics, standardiza-tion of herbal extracts, yoga style, etc.) to provide

the most signicant benet for IBS.

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70. Bundy R, Walker AF, Middleton RW, etal. Artichoke leaf extract reducessymptoms of irritable bowel syndromeand improves quality of life in otherwise

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Appl Psychophysiol Biofeedback 2004;29:19-33.

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