ESPEN Congress Lisbon 2004

Report from ESPEN working group

Effects and Benefits of Fibre in Clinical Practice: A Consensus

recommendations

Remy Meier

EffectsEffects and and BenefitsBenefits of of FibreFibre in in ClinicalClinical PracticePractice

Consensus Consensus ConferenceConferenceBarcelona, 2.Barcelona, 2.--3. Oktober 20033. Oktober 2003

ESPEN, Lisabon, 2004ESPEN, Lisabon, 2004

R. Meier, M.D.R. Meier, M.D.University HospitalUniversity HospitalLiestal, Liestal, SwitzerlandSwitzerland

BackgroundBackground•• A A largelarge number of articles on fibre were number of articles on fibre were

published in different areas of diseases published in different areas of diseases butbut the benefits are still widely discussedthe benefits are still widely discussed

•• Different definitions are used which Different definitions are used which makes the interpretations often difficultmakes the interpretations often difficult

-- physiologicallyphysiologically-- chemicallychemically-- solubilitysolubility-- dietary fibre / functional dietary fibre / functional fibrefibre

•• ThereThere isis a lack of well a lack of well perfomedperfomed and and sizedsizedclinicalclinical studiesstudies

AimsAims

•• CriticalCritical evaluationevaluation of of thethe propertiesproperties and and physiologicalphysiological effectseffects of different of different fibresfibres

•• AssessmentAssessment of of thethe evidenceevidence--basedbasedclinicalclinical benefitsbenefits of of fibrefibre

•• DefiningDefining of evidenceof evidence--basedbasedrecommendationsrecommendations forfor thethe useuse of of fibrefibre in in clinicalclinical practicepractice

•• IdentifyingIdentifying areasareas withwith lackinglacking evidenceevidence forforfuturefuture researchresearch

InterestsInterests of of thethe Consensus Consensus ConferenceConferenceI.I. General General aspectsaspects of of fibrefibre

↘↘ John John CummingsCummings (UK), Glenn Gibson (UK)(UK), Glenn Gibson (UK)II.II. InflammatoryInflammatory bowelbowel diseasedisease

↘↘ John Rombeau (US)John Rombeau (US)III.III. ConstipationConstipation, , diarrhoeadiarrhoea, IBS, IBS

↘↘ Ingvar Ingvar BosaeusBosaeus (S)(S)IV.IV. PreventionPrevention of CRCof CRC

↘↘Wolfgang Wolfgang ScheppachScheppach (G)(G)V.V. TheThe useuse of of fibrefibre in in enteralenteral nutritionnutrition

↘↘ Eduard Eduard CabrCabréé (SP), Heinz Homann (G)(SP), Heinz Homann (G)VI.VI. MetabolicMetabolic effectseffects

↘↘David Jenkins (David Jenkins (CanCan))

ProceedingsProceedings of Consensus of Consensus ConferenceConference•• SummarySummary lecturelecture and and plenumplenum discussionsdiscussions

withwith a a groupgroup of international of international expertsexperts in in thethefieldfield (N = 18)(N = 18)

•• DiscussionDiscussion of of fivefive mainmain topicstopics in in fivefive groupsgroups↘↘ SummarizingSummarizing thethe rationales and rationales and evidencesevidences

of of thethe topictopic•• Plenum Plenum discussiondiscussion and defining and defining thethe

recommendationrecommendation levellevel•• CirculatingCirculating thethe consensusconsensus recommendationsrecommendations

byby ee--mailmail untiluntil all all thethe participantsparticipants (N = 28) (N = 28) agreedagreed

Levels of Levels of evidenceevidence and grades of and grades of recommendationsrecommendationsLevel of Level of evidenceevidence Grade of Grade of recommendationrecommendation

Level I:Level I: RandomizedRandomized trialtrial oror metameta--analysisanalysis withwith lowlow riskrisk of of errorerror

Grade A:Grade A: SupportedSupported byby Level ofLevel ofevidenceevidence II

Level II:Level II: RandomizedRandomized trialtrial orormetameta--analysisanalysis withwith high high riskrisk of of errorerror

Grade B:Grade B: SupportedSupported byby at least at least oneone Level II Level II studystudy

Level III:Level III: NonNon--randomizedrandomized trialtrial ororrandomizedrandomized trialtrial of of patientspatients otherotherthatthat populationpopulation of of interestinterest ororrandomizedrandomized trialtrial of of measuringmeasuringsurrogatesurrogate outcomesoutcomes

Grade C:Grade C: No No supportsupport fromfrom Level I Level I oror II II studiesstudies

Level IV:Level IV: NonNon--randomizedrandomized trialtrial in in patientspatients otherother thanthan populationpopulation of of interestinterest oror animalanimal studiesstudies forforbiologicalbiological rationalerationale

No No recommendationrecommendation

Adapted from Heyland and Novak, JPEN, 2001, Sackett, Chest, 1989

SelectedSelected 5 5 topicstopics

•• InflammatoryInflammatory bowelbowel diseasedisease•• ConstipationConstipation, , diarrhoeadiarrhoea, , irritableirritable

bowelbowel syndromsyndrom•• PreventionPrevention of CRCof CRC•• TheThe useuse of of fibrefibre in in enteralenteral nutritionnutrition•• MetabolicMetabolic effectseffects

IaIa. Consensus on . Consensus on inflammatoryinflammatorybowelbowel diseasedisease forfor ulcerativeulcerative colitiscolitis

•• RationaleRationale-- OligoOligo--polysaccharidepolysaccharide componentscomponents of of fibrefibre arearefermentedfermented in in thethe coloncolon

↓↓•• pHpH ↓↓•• SCFASCFA‘‘ss ↑↑

-- ButyrateButyrate inhibitsinhibits thethe activationactivation of of thethe NFNF--kBkB↓↓

propro--inflammatoryinflammatory cytokinescytokines ↓↓(TNF(TNFαα, IL, IL11, IL, IL66))

-- ButyrateButyrate increasesincreases thethe antianti--inflammatoryinflammatory cytokinecytokineILIL1010

-- ButyrateButyrate oxidationoxidation isis decreaseddecreased in in ulcerativeulcerativecolitiscolitis

•• EvidenceEvidence

OnlyOnly 4 4 studiesstudies areare availableavailable usingusing orallyorallyadministeredadministered fibrefibre--polysaccharidespolysaccharides

-- InulinInulin in in aucteaucte pouchitispouchitis LE IILE II• Welters et al, Dis Colon Rectum, 2002

-- PlantagoPlantago ovataovata seedsseeds forfor maintainingmaintainingremissionremission in in ulcerativeulcerative colitiscolitis LE IILE II• Fernandez-Banares et al, Am J Gastroenterol 1999

-- FermentedFermented barleybarley in mild to moderate in mild to moderate activeactiveulcerativeulcerative colitiscolitis• Mitsuyama et al, Aliment Pharmacol Ther, 1998• Kanauchi et al, J Gastroenterol, 2002

•• RecommendationRecommendation●● UlcerativeUlcerative colitiscolitis

-- FermentedFermented barleybarley forfor activeactive mild to mild to moderate moderate ulcerativeulcerative colitiscolitis

-- InulinInulin in in pouchitispouchitis-- PlantagoPlantago ovataovata forfor maintainingmaintaining remissionremissionareare attractiveattractive RBRB

These These treatmentstreatments needneed furtherfurtherconfirmationsconfirmations

Ib. Consensus on Ib. Consensus on inflammatoryinflammatory bowelboweldiseasedisease forfor Crohn‘sCrohn‘s diseasedisease

•• ThereThere isis no no evidenceevidence thatthat fibrefibre has has anyanypositive positive effectseffects in in Crohn‘sCrohn‘s diseasedisease

II. Consensus on II. Consensus on ConstipationConstipation,,DiarrheaDiarrhea and and IrritableIrritable BowelBowelSyndromeSyndrome

•• RationaleRationale

-- SomeSome fibrefibre havehave bulkingbulking effectseffects-- SomeSome fibrefibre areare fermentedfermented↘↘ SCFASCFA‘‘ss ↑↑, , biomassbiomass ↑↑

↘↘ sodiumsodium and and waterwater absorptionabsorption ↑↑

•• EvidenceEvidence

IncreasesIncreases of of stoolstool weightweight

-- ResistantResistant starchstarch ∼∼ 1.5 g/g 1.5 g/g fedfed

-- FruitsFruits and and vegetablesvegetables ∼∼ 5,0 g/g 5,0 g/g fedfed

-- BranBran ∼∼ 7.2 g/g 7.2 g/g fedfed LELE II

•• RecommendationRecommendation

●● ConstipationConstipation

- FibreFibre resultsresults in a in a modestmodest increaseincrease in in bowelbowelmovementmovement frequencyfrequency (1.4(1.4--1.5 1.5 bmbm//weekweek) ) RARATramonte et al, J Gen Intern Med, 1997

-- FibreFibre improveimprove symptomssymptoms ((painpain, , stoolstoolconsistencyconsistency) ) butbut therethere areare no no longlong--termterm datadataavailableavailable

-- DietaryDietary fibrefibre ((rawraw branbran, , fruitfruit and and vegetablesvegetables) ) areareof of benefitbenefit in in somesome patientspatients, , butbut therethere isis notnotenoughenough evidenceevidence in RCT in RCT forfor recommendationrecommendation

●● DiarrheaDiarrhea

-- PartiallyPartially hydrolizedhydrolized guarguar gumgum in ORS in ORS reducesreducesdiarrheadiarrhea in in childrenchildren in in acuteacute and and persistentpersistent

-- diarrheadiarrheaAlam et al, J Pediatr Gastroenterol Nutr, 2000Alam et al, Arch Childhood Disease, 2004

-- ResistantResistant starchstarch in ORS in ORS reducesreduces diarrheadiarrhea in in adultsadultswithwith choleracholera RARARamakrishna et al, N Engl J Med, 2000

RARA

●● IBSIBS

-- FibreFibre (high (high fibrefibre dietdiet, , wheatwheat branbran, , bulkbulk laxativeslaxatives isisgenerallygenerally recommendedrecommended in IBS in IBS butbut therethere isis littlelittleevidenceevidence to to supportsupport itsits useuseJailwala et al, Ann Intern Med, 2000

-- PatientsPatients withwith predominantpredominant constipationconstipation maymay havehavea a betterbetter benefitbenefit mostlymostly on on bowelbowel frequencyfrequency butbutnotnot on on bloatingbloating and and painpainThereThere isis a lack of a lack of longlong--termterm datadata

-- PHGG PHGG maymay bebe betterbetter toleratedtolerated thanthan othersothers, , butbutthethe datadata areare insufficientinsufficientParisi et al, Dig Dis Sci, 2002

III. Consensus on III. Consensus on PreventionPreventionof CRCof CRC

•• RationaleRationale•• FibreFibre increaseincrease stoolstool mass and mass and decreasesdecreases

transittransit timetime↘↘ DilutionDilution of of carcinogenescarcinogenes

•• Fermentation Fermentation decreasesdecreases stoolstool pHpH andandproducesproduces SCFASCFA‘‘ss↘↘ -- ButyrateButyrate modulatesmodulates suppressorsuppressor genesgenes

-- inhibitsinhibits NFNF--kBkB-- influencesinfluences apoptosisapoptosis

•• EvidenceEvidence

-- MetaMeta--analysisanalysis of 13 of 13 casecase--controlcontrol studiesstudiesshowedshowed an an inverseinverse correlationcorrelation of of thethe CRCCRCriskrisk (13 g/d (13 g/d →→ 31% 31% reductionreduction) LE I) LE IHowe et al, J Natl Cancer Inst, 1992

-- EPICEPIC--StudyStudy: : dietarydietary fibrefibre in food in food areareinverselyinversely correlatedcorrelated to to thethe incidenceincidence of CRCof CRC

LE ILE IBingham et al, Lancet 2003

- No No effecteffect in in polyppolyp--recurrencerecurrence studiesstudies overover33--4 4 yearsyearsSchatzkin et al, N Engl J Med 2000Alberts et al, N Engl J Med, 2000

• RecommendationsRecommendations

•• TheThe rolerole of of dietarydietary fibrefibre asas an an antianti--carcinogeniccarcinogenic agentsagents isis, at best , at best equivocalequivocaltodaytoday butbut thethe intakeintake of a high of a high fibrefibre dietdiet((fruitfruit, , vegetablesvegetables, , wholewhole grainsgrains) ) isisrecommendedrecommended fromfrom childhoodchildhood onwardsonwards in in thethe generalgeneral populationpopulation RARA

IV. Consensus on IV. Consensus on usingusing fibrefibre ininenteralenteral nutritionnutrition

•• RationaleRationale

- FermentableFermentable fibrefibre increaseincrease sodiumsodium andandwaterwater absorptionabsorption↘↘ PreventionPrevention of of diarrhoeadiarrhoea in in acuteacute diseasedisease

-- BulkingBulking fibrefibre maymay maintainmaintain normal normal bowelbowelfunctionfunction↘↘ PreventionPrevention of of constipationconstipation in in longlong--termterm

enteralenteral nutritionnutrition

•• EvidenceEvidence

-- PHGG PHGG reducesreduces enteralenteral nutritionnutrition associatedassociateddiarrhoeadiarrhoea in in patientspatients afterafter surgerysurgery and in and in criticallycritically illill LE ILE I• Homann et al, JPEN, 1994• Spapen et al, Clin Nutr, 2001

-- SoySoy polysaccharidespolysaccharides combinedcombined withwith oatoat fibrefibreincreaseincrease dailydaily stoolstool weightweight and and frequencyfrequencysmallsmall groupgroup of of patientspatients, , shortshort periodsperiods)) LE IILE II

• Zar Ling et al, J Am Coll Nutr 1994-- SoySoy polysaccharidespolysaccharides showedshowed an an increaseincrease inin

stoolstool weight duringweight during oneone yearyear ((onlyonly 11 11 patientspatients))• Liebl et al, JPEN, 1990

LE IIILE III

•• RecommendationRecommendation

-- PreventionPrevention of of diarrhoeadiarrhoea in post in post surgicalsurgical and and criticallycritically illill patientspatients supplementingsupplementing enteralenteralnutritionnutrition withwith PHGG PHGG isis effectiveeffective RARA

-- Short Short termterm studiesstudies showedshowed thatthat soysoy polypoly--saccharidessaccharides combinedcombined withwith oatoat fibrefibre increaseincreasedailydaily stoolstool weightweight and and frequencyfrequency RCRC

V. Consensus on metabolicV. Consensus on metaboliceffectseffects

•• RationaleRationale

-- Viscous fibre (guar gum, pectin,Viscous fibre (guar gum, pectin,psyllium) lower cholesterol levels inpsyllium) lower cholesterol levels inhealthy and hyperlipidaemic subjects healthy and hyperlipidaemic subjects

-- Insoluble fibre has no effectInsoluble fibre has no effect-- Soluble fibre reduce blood glucose levelsSoluble fibre reduce blood glucose levels

and insulin releaseand insulin release

•• EvidenceEvidence•• 1g soluble fibre reduce cholesterol by 0.045 and LDL by 0.057 1g soluble fibre reduce cholesterol by 0.045 and LDL by 0.057

mmol/lmmol/l• Jenkins et al, Metabolism, 2001 LE ILE I

•• MetaMeta--analysis of observational studies suggest a protective analysis of observational studies suggest a protective effect of dietary fibre and /or whole grain cereals against CHDeffect of dietary fibre and /or whole grain cereals against CHD• Anderson et al, Proc Nutr Cardiol, 2003

• Liu et al, J Am Coll Cardiol, 2002 LE IIILE III•• Guar gum reduce blood glucose levels by 44%, pectin and Guar gum reduce blood glucose levels by 44%, pectin and

psyllium by 29%psyllium by 29%• Berger et al, 1992

• Wolover et al, CRC Press, 1993 LE ILE I•• Pooled data suggest that dietary fibre Pooled data suggest that dietary fibre and /or whole grain cereals and /or whole grain cereals

may have a protective effect against type II diabetesmay have a protective effect against type II diabetes• Salmeron et al, Diab Care, 1997 LE IIILE III

•• RecommendationRecommendation

•• Regular intake of viscous fibre or psyllium Regular intake of viscous fibre or psyllium shows beneficial effects on blood cholesterol, shows beneficial effects on blood cholesterol, LDLLDL--cholesterol and reduces postprandial cholesterol and reduces postprandial glucose levels and insulin response glucose levels and insulin response RARAbutbut there are no data from RCT with hard end there are no data from RCT with hard end points to indicate a clear benefit in terms of points to indicate a clear benefit in terms of prevention of CHD and diabetes prevention of CHD and diabetes

•• Fibre has beneficial effects on CHD Fibre has beneficial effects on CHD butbut fibre is fibre is only factor of dietary components which affect only factor of dietary components which affect the risk the risk RARA

ConclusionConclusion

•• TheThe useuse of of fibrefibre in in GIGI--diseasesdiseases isisfascinatingfascinating duedue to to thethe different different actionsactions of of different different fibrefibre

•• AlthoughAlthough numerousnumerous studiesstudies areare availableavailable, , therethere areare onlyonly fewfew clearclear benefitsbenefitsdemonstrateddemonstrated duedue to to thethe lack of well lack of well designeddesigned studiesstudies

•• May May bebe in in thethe futurefuture a a combinationcombination of of different different fibrefibre, , prebioticsprebiotics and and probioticsprobioticswill will changechange thethe situationsituation