zinc and vitamin c supplementation in the treatment of ...€¦ · background: pressure ulcers...

ZincandvitaminCsupplementationinthetreatmentofpressureulcers

EVIDENCED-BASEDRESEARCHPRESENTATION

P R E S E N T E D B Y S A R I B O R N S T E I N

A U G U S T 2 0 1 5

OverviewIS S UPP LEMENTAL Z I N C AND V I TAM IN C E S S ENT I A L TO

THE TREATMENT O F P RE S SURE U L CER S ?

•  Preliminarycasestudy•  BackgroundinformaIononPUs•  Researchfromthreerecentstudies•  Comparisonofresults•  Currentguidelines•  Discussion•  Conclusion

objectiveso ReviewtheroleofzincandvitaminCinwoundhealing

o Examinecurrentresearch(last5years)onsupplementalzincandascorbicacidandtheireffectsonwoundhealingIme

o IntegratecurrentresearchandguidelinestomakeappropriateintervenIonsforpopulaIonswithwoundsorpressureulcersatSSRRH

IcebreakerCASESTUDY

71YOMthatpresentswithStageIIIPUPoapproximately40-50%last3daysNocurrentsupplementsareorderedWL3lbssinceadmission7daysagoCurrentBMI22.4kg/m2

² WhatareyourgeneralintervenIonsasadieIIan?

Background:vitaminCo RDA:75-90mg/dayo UL:2,000mg/dayo Roleinwoundhealing

o  Cofactorinthecross-linkage,synthesis,andstructuralstabilizaIono  Lysineandproline

o Dietarysources:citrus,tomatoes,potatoes,bellpeppers,berries

o  InU.S.deficiencyisrare

o Dietaryintake30-180mgà70-90%absorbedo Doses>1000mgà<50%absorbed

Background:zinco  RDA:8-11mg/dayo  UL:40mg/dayo  Roleinwoundhealing

o  CofactorinsynthesisofDNA,RNA,proteino  FormaIonofgranulatedandepithelialIssueo  AnI-inflammatoryandanImicrobialeffects

o Dietarysources:redmeat,seafood,wholegrains,forIfiedcereals

o  Deficiencyisrareo Plasmazincboundtoalbumino Assaysofzincunreliableinstateofsepsis,infecIon,trauma,stress

o Smallerdosesmorereadilyabsorbedo HighdosesupplementalzincàimmunesuppressionandreducedcopperabsorpIon

Background:pressureulcers(PUs)

•  Whenpressureonabonysiteobstructscapillarybloodflow,causingIssuenecrosis

•  Keyriskfactors•  PoornutriIonalstatus

•  MalnutriIon:Presenceof2ofthe6characterisIcs•  UWL:5%WLin1monthor10%WLin6months•  Inadequatedietaryintake

•  InfecIon,sepsis,trauma•  IncreasesREE•  Wounds/PUsputsgreaterdemandonbody

•  LinkbetweennutriIonalstatusandtheincidence,progression,andhealingofPUs

Background:pressureulcers(PUs)

•  Incidencewithage•  27.2%ofpeopleoverage70•  33.8%ofpeopleoverage80

•  Incidenceamongestablishments•  0.4to38%inhospitals•  2.2to24%inSNFs•  0to17%inhomehealthagencies

² TotalcosttotreatPUsintheU.S.=$11billionannually,$37,800onaveragetotreatONEPU

² PosesahighcostburdenforhospitalstotreatPUs

InterventionsatSutter•  OutdatedPracCce

•  500mgvitaminCBID•  220mgzincsulfate(50mgelementalzinc)•  Proteinsupplement-EnsureComplete•  Juven-HMBmetabolitewithglutamine andarginine

•  CurrentPracCce

•  MVIwithminerals•  100mgVitaminC•  25mgZinc

•  BoostPlussupplement•  60mgVitaminC•  4.5mgZinc

Let’sExaminetheResearch…

SpeciSicnutritionalsupportacceleratespressureulcerhealingandreduceswoundcareintensityinnon-malnourishedpatientsvanAnholt,etal.

•  BACKGROUND:•  PUsposeahighcostburdenonhealthcaresystemsworldwide•  PaIents’riskofdevelopingPUsis2-to3-foldhigherwhenmalnourishedorunderweight

•  Previousresearchhasshownprovidinganoralnutri-onalsupplement(ONS)improvesnutriIonalstatusandlowersincidenceofPUdevelopmentinthosemalnourished•  Whataboutthosenon-malnourished?

RESEARCHSTUDY1

RESEARCHSTUDY1PURPOSE:ToinvesCgatethepotenCalofanarginine-andmicronutrient-enrichedONStoimprovehealingofPUsinnon-malnourishedpaCentswhowouldusuallynotbeconsideredforextranutriConalsupport.HYPOTHESIS:Thesupplementrichinprotein,arginineandmicronutrientswillpromoteneoangiogenesis,sCmulatecollagensynthesis,andhaveaposiCveeffectonwoundhealing.

Participants•  47paIentsrecruitedfrom8healthcarecentersin4countries(CzechRepublic,Belgium,TheNetherlands,Curacao)

•  Inclusioncriteria:•  18to90yearsold•  AtleastoneStageIIIorIVpressureulcer(EPUAPclassificaIonsystem)•  ReceivingstandardcareandstandarddietwithoutnutriIonalsupplementsatleast2weeksbeforethestudy

•  Exclusioncriteria:•  Malnourished

•  Age18-70YO:BMI<18.5•  Ageabove70YO:BMI<21

•  SeveremedicalcondiIons,non-pressure-relatedulcers,dietrestricIons,lifeexpectancy<6mo,useofcorIcosteroids

•  4subjectsdroppedout

RESEARCHSTUDY1

Methods•  22subjectsrandomlyallocatedtoreceiveaspecificONS•  1serving(200mL):250kcal,20gprotein,250mgvitaminC,9mgzinc(othermicronutrients)

•  21subjectsrandomlyallocatedtoreceiveanon-caloric,flavoredplacebo

•  Allsubjectsreceived200mLservingsTIDbetweenmeals•  productcompliancewasrecorded

•  Allreceivedthesame,standardinsItuIonaldiet•  Volumeconsumedwasrecorded

•  Lengthofstudy,8weeks

RESEARCHSTUDY1

Methodscontinued

•  Assessedweeklyover8weeks•  PUSA:measuredlength+widthusingaruler•  PUSHscore:0(completelyhealed)to17(greatestseverity)

•  SA,exudate,typeofwoundIssue•  TotalnumberofdressingsappliedintheweekandImeforapplicaIon

•  Assessedatbaselineandweek8•  Weight,BMI,MalnutriIonUniversalScreeningTool(MUST)score,bloodparameters(vitaminC,zinc)

RESEARCHSTUDY1

*NostaIsIcaldifferencesbetweenthegroupsatbaseline*NostaIsIcaldifferencesbetweenPUcharacterisIcsbetweengroupsatbaseline

ResultsRESEARCHSTUDY1

Fig1.PUSizeONSgrouphealedsignificantlyfasterthanthecontrolgroup(P=0.016)

Fig2.PUSHscorePUSHscoresimprovedsignificantlyintheONSgroupcomparedtothecontrolgroup(P=0.033)

ONSgroup(closedsymbol) Controlgroup(opensymbol)


Fig3.NumberofDressingsSignificantlyfewerdressingswererequiredintheONSgroupthaninthecontrolgroup(P=0.045)

Fig4.TimespentofchangingdressingsSignificantlylessImewasrequiredtochangethedressingsintheONSgroupversusthecontrolgroup(P=0.022)

ONSgroup(closedsymbol) Controlgroup(opensymbol)


Table3.NutriConalbloodparametersNostaIsIcallysignificantdifferencesbetweenbloodparametersintheONSandcontrolgroupswiththeexcepIonofvitaminCincreasinglysignificantlyintheONSgroupbetweenbaselineandtheendofthestudy(P=0.015)

Table4.AmountconsumedoftheONSandcontrolproductSignificantlymoreproductwasconsumedbythecontrolgroupthantheONSgroup(P=0.042)

ONSGroup ControlGroup

75.8±3.7% 86.5±2.3%

Conclusion•  Thehigh-protein,arginine-andmicronutrient-enrichedONSacceleratedthehealingofPUs,asindicatedby:•  SignificantreducIoninPUsize•  SignificantdecreaseinPUSHtoolscores•  Significantlyfewerdressingsrequired•  LessImerequiredtochangethedressings

•  SynergisIceffectbetweenarginine,vitaminC,zinctoimprovewoundhealing

•  SupplementaIonwillimprovequalityoflifeofnon-malnourishedpaIentsandsavecostsbydecreasingwoundcare

RESEARCHSTUDY1

Timetowoundclosureintraumapatientswithdisordersinwoundhealingisshortenedbysupplementscontainingantioxidantmicronutrientsandglutamine:APRCTBlass,etal.

•  BACKGROUND:•  Ascorbicacidandzincarearributedanimportantroleinwoundhealing

•  ClinicaldataoncasualrelaIonshipwaslackingbetweenmicronutrientsupplementaIonandwoundhealing

RESEARCHSTUDY2

RESEARCHSTUDY2PURPOSE:ToinvesCgatehowdietarymeasuresincludingmicronutrientsupplementaCon(includingascorbicacidandzinc)improvesthewoundhealingprocess.HYPOTHESIS:ThewoundclosureintraumapaCentswithdisordersinwoundhealing(DWH)isacceleratedbysupplementaConofanCoxidantmicronutrientsandglutamine.

•  DWH:failuretoclosewithconInuedexcreIon10daysasertrauma)

Participants•  20CaucasiantraumapaIentswithDWHwererecruitedfromUniversityHospitalofBonn,Germany

•  Exclusioncriteria:•  ENorTPN•  CurrentsupplementaIonwithvitaminsandtraceminerals•  ConsumpIonofforIfiedjuices•  ExtremecomorbidiIes•  PUsasprimarydiagnosis•  ICUstayorsepsis

•  All20subjectscompletedthestudy

RESEARCHSTUDY2

Methods

•  10subjectsrandomlyallocatedtotheverumgroup•  ReceivedtwosachetsperdayofGlutaminePlus®granulate•  500mgAA,6.6mgzinc,20gglutamate

•  10subjectsrandomlyallocatedtotheplacebogroup•  Receivedtwosachetsperdayoftasteless,isoenergeIcmaltodextrine

•  BothgroupsinstrucIons:•  MixtheenIresachetwithyogurt,dessertorbeverageandconsumeimmediately•  Documentintakeinadiary

•  Allreceivedaprotein-richdietprovidedbyahospitalcaterer•  ForIfiedjuiceswereexcluded•  Subjectsrecordeddailyintakes

•  Lengthofstudy,14days

RESEARCHSTUDY2

Methodscontinued•  Measuredond0andd14

•  Anthropometricdata•  NutriIonalstatus•  DeterminedbyaSubjecIveGlobalAssessment(SGA)

•  Well-nourished:SGAA•  Moderatelymalnourishedorsuspectedtobemalnourished:SGAB•  Severelymalnourished:SGAC

•  DeterminedriskformalnutriIon•  NutriIonalRiskScreening-2002

•  BloodSamples•  Ascorbicacidandzinc

•  Measuredond0,d7,andd14•  ParametersofmicrocirculaIon:oxygensaturaIon,bloodflow,bloodvelocity•  Non-invasivewhitelightspectrometer

•  Woundtemperature•  Timetowoundclosure(studyentrytonosecreIon,inflammaIonorinfecIon)

RESEARCHSTUDY2


Table3.Nutrientstatus(plasmaconcentraCons)atd0andd14Median[quarIles].Nutrientstatusiscomparableinbothgroupsatbaseline.d0:baseline;d14:aser14-daysupplementaIon;n.s.:notsignificant

²  NostaIsIcaldifferenceofzincorascorbicacidplasmaconcentraIonsbetweend0andd14inboththeplaceboandverumgroups

²  NostaIsIcalevaluaIonofzincwasperformed“duetolownumberofpaIentsconcerned”


Figure1.Timetowoundclosure[days]SignificantdifferenceinImetowoundclosurebetweengroups

ConclusionRESEARCHSTUDY2

•  SupplementaIonofanIoxidantmicronutrientsandglutamineisassociatedwithanacceleratedwoundclosureinpaIentswithDWH•  SpeculatedglutaminesupplementaIonintheverumgroupmaintainedplasmaglutaminelevels;increasedintracellularglutamineavailability;thussupporIngthehealingprocess•  Glutamine:majornitrogensourceforrapidlyproliferaIngfibroblastsandepithelialcells.

•  SpeculatedvitaminCsupplementaIoncausedreducIonininflammaIoninverumgroup

•  “Theunderlyingmechanism(s)remainsdebatable”

Anutritionalformulaenrichedwitharginine,zincandantioxidantsforthehealingofpressureulcers:arandomizedtrialCereda,etal.

•  BACKGROUND:•  PrevioustrialsonspecificnutriIonalsupplementsforthetreatmentofPUshavebeensmall,inconsistentintheirformulaIons,ordidnotstandardizefortheproteinandcaloriecontentofthesupplements.

•  Nootherstudiesevaluatedtheindependentroleofarginine,zincandvitaminCwhenincludedinareadilyavailablecommercialformuladesignedtoimprovewoundhealing

RESEARCHSTUDY3

RESEARCHSTUDY3PURPOSE:Toperformalarge,randomizedtrialinmalnourishedpaCentstoevaluatewhethersupplementaConwitharginine,zincandanCoxidantswithinahigh-calorie,high-proteinformulaimprovesPUhealing.HYPOTHESIS:Theoralformulaenrichedwitharginine,zincandanCoxidantsisbeneficialtothehealingofPUs.

Participants•  200malnourishedadultswithPUsStageII-IVrecruitedfrom7sites,Italy

•  Long-termcareorhomecareservices•  Inclusioncriteria:•  Malnourished(oneofthefollowing)

•  LowBMI•  Forage<65:BMI<20kg/m2

•  Forage≥65:BMI<21kg/m2

•  RecentunintenIonalWL•  ≥10%in3months•  ≥5%in1month

•  Lowserumalbumin•  Reducedoralintake

•  <60%ofesImateddailyenergyrequirementstheweekprior

•  AbletodrinkONSs•  Providewrirenconsent

•  Exclusioncriteria:•  ArIficialnutriIon,uncontrolledDM,renalorhepaIcinsufficiency,HF,PVD,COPD,

neoplasIcdisease,obesity,infectedwound,orsepsis•  138subjectscompletedthetrial•  200includedinanalysisusinglinearregressionmodels

RESEARCHSTUDY3

Methods•  101subjectsrandomlyallocatedtotheexperimentalformula

•  1serving(100mL):125.8kcal,10gprotein,1.5gArginine*,125mgvitaminC*,4.5mgzinc*(othermicronutrients)

•  99subjectsrandomlyallocatedtothehomemade,controlformula•  1serving(100mL):127.2kcal,10gprotein,19mgvitaminC,2.3mgzinc(othermicronutrients)

•  Caloriesandgramsofproteinequivalentinbothforumlas•  Bothgroupsreceivedtwoborles(400mL)perdayoftheirrespecIveformulas•  Adherencewasmonitoredthroughoutthestudy

•  Dietaryintakesnotstandardized•  Lengthofstudy,8weeks

RESEARCHSTUDY3

Methodscontinued•  Measuredatbaselineandweek8:•  Bodyweight•  Bradenscale:measuresriskofPU

•  Score≤18predicIveforPUdevelopment

•  Measuredatbaseline,week4,andweek8:•  PUarea(unstatedhow)

•  Measuredatbaselineandevery2weeks:•  Totaldailyenergyandproteinintakes(includingONSs)

•  3-dayquanItaIvefooddiary,assessedbyRD•  Measuredonadailybasis:•  Amountofformulaconsumed

•  Typeofdressingandfrequencyofitschangewasindividualized

o AllmethodswerestandardizedbetweenfaciliIeso Thesamepersonassessedallsubjectsateachfacility

RESEARCHSTUDY3

²  Experimentalandcontrolformulascontainedsameamountofproteinandcalories

²  StaIsIcallydifferentintheamountofzinc,vitaminC,arginine*

ResultsPrimaryendpoints•  ReducIoninPUareaatweek8,% XX

Secondaryendpoints•  ≥40%reducIoninPUareaatweek8,% XX•  Completehealing,% X•  ReducIoninPUareaatweek4,% X•  WoundinfecIons,%•  Meandressings,n

RESEARCHSTUDY3

X:experimentalgroupwithsignificantlymore%personsatweek4X:experimentalgroupwithsignificantlymore%personsatweek8


•  Adherencetotreatment:•  84.8%±15.2%inexperimentalgroup•  83.7%±16.3%incontrolgroup

•  TreatmentresultedinincreaseBWat8weeksinbothgroups

Showssignificance

ConclusionRESEARCHSTUDY3

•  “OveralltreatmentwaseffecIveinimprovingPUhealinginboththeexperimentalandcontrolgroups”

OverallConclusion:AddiIonalprovisionofarginine,zincandanIoxidantsinthenutriIonalsupportofpaIentswithPUswaseffecIveinimprovingPUhealing•  MeanreducIoninPUareaatweek8•  ≥40%reducIoninPUareaatweek8

Comparisonofstudies

Study1 Study2 Study3

Numberofsubjects 43 20 200

TestedmalnourishedpopulaIon ✔ ✔

Testednon-malnourishedpopulaIon ✔ ✔

IsolatedzincandvitaminC

Supplementcontainedglutamine ✔

Supplementcontainedarginine ✔ ✔

ONSgrouphadacceleratedwoundhealing ✔ ✔ ✔

AcceleratedwoundhealingexclusivelycausedbysupplementalvitaminC&zinc

WhatdoesthePressureUlcerPreventionandTreatment:Clinical

PracticeGuidelinessayaboutcurrentresearch….?

-NPUAP,EPUAP,PPPIA

•  “methodologicalflawsandstudysizehaveprecludedconfirmaIonofclinicallysignificantresults…becausepreviousstudiesoftheindividualnutrientsfailedtoshowbenefit,theauthorshavepostulatedasynergisIceffectamongthenutrients.”–2014CochraneDatabaseSystemReview

•  “The2014CochraneReview…invesIgatedtheeffectofnutriIonalsupplementaIononthehealingofPUs[in]14studies….TheauthorsconcludedthereisgenerallynoclearevidenceofimprovedPUhealingwithnutriIonalsupplements….Mostofthetreatmentstudieswereunclearandhadahighriskofbias.”–NPUAP,EPUAP,2015

Zinc:•  “High-dosezincsupplementaIon(>40mg/d)isnotrecommendedbecauseitcanadverselyaffectcopperstatus…inhibithealing…induceacopperdeficiency[which]maybeharmfulascopperisessenIalforcollagencross-linking.”

•  “Noevidence-basedresearchexiststoproveit’sbeneficialtogivemegadosesofzincovertheuppertolerablelimitof40mg/dtopromotewoundhealingunlessclinicalsignsofzincdeficiencyarepresent,andsupplementaIonshouldbestoppedoncedeficiencyiscorrected.”

-NPUAP,EPUAP2015•  “InthepresenceofaconfirmedorexpectedzincdeficiencygeneralpracIceistogiveZnSO4220mg(50mgelementalZn)bidfornolongerthantwoorthreeweeks.”

-A.N.D.Nutri-onCareManual

VitaminC:•  “Researchdoesn’tsupportgiving[rouIne]megadosesofvitaminCtoacceleratewoundhealing…physiologicaldosesshouldbeconsidered[only]whendietarydeficiencyisdiagnosed.”

•  “Theinclusionoffruitsandvegetablesinthedietcanachievethedailyrecommendedintake”

-NPUAP,EPUAP2015•  “MembersofthegeneralpopulaIonshouldnotrouInelyexceedtheUL,which…appliestointakefrombothfoodandsupplements….DosesgreaterthantheULmaycausenausea,diarrheaorabdominalcramps.”

-IOM’sDietaryReferenceIntakes

NocurrentresearchhasdirectlyandappropriatelydeterminedthatsupplementalzincandvitaminCacceleratewoundhealing.

Adietitian’sMNTgoalforPUs:

•  MaintainadequatenutriIonstatusbyprovidingopImumdietaryandfluidintake

•  IdenIfyandtreatcausesofpoornutriIonalintake•  MonitorweightstatusrouInelytodetectunexpectedorunintenIonalweightloss

•  SelectnutriIonintervenIonstoimproveormaintainnutriIonalstatus,includingtheuseoforalsupplementsornutriIonsupport,ifwarranted

“InadequatedietaryintakemayrequireamulIvitamin/mineralsupplement;however,theuseofspecificsupplements(i.e.vitaminCandzinc)isonlyrecommendedwhenatruedeficiencyoccurs.”

-A.N.D.Nutri-onCareManual

DetectingDeSiciencies:•  PlasmazinclevelsnaturallydecreasewithinflammaIon,andlabtesIngmaynotrepresenttotalbodystores•  Assayisrarelydone

•  Physicalassessmentcanhelpdeterminedeficiencies•  Tongue,skin,nails,hair,lips

•  Ifpre-exisIngmalnutriIonisevident,correctdeficienciestoimprovenutriIonalstatus

•  Liberalizedietandencouragepointake•  ONS-Boost•  SuggestnutriIonsupport,ifappropriate

Assessment&Discussion:

WhatisonepieceofinformaIonyouwilltakeawayfromtodayspresentaIononPUs?

vvv

Empoweryourselfto…

•  UsewhatwehavelearnedtodayfromthispointforwardtoappropriatelyassessandmakenutriIonalrecommendaIonsforpaIentswithPUs•  A.N.D.NutriIonCareManual•  2014PressureUlcerPreven-onandTreatment:ClinicalPrac-ceGuideline,fromNPUAP,EPUAP,PPPIA

SummaryI S S U PP LEMENTAL Z I N C AND V I TAM IN C E S S ENT I A L

TO THE TREATMENT O F P RE S SURE U L CER S ?

•  Preliminarycasestudy•  BackgroundinformaIononPUs•  Researchfromthreerecentstudies•  Comparisonofresults•  Currentguidelines•  Discussion

THANK YOU

QUESTIONS?

zinc and vitamin c supplementation in the treatment of ...€¦ · background: pressure ulcers...

Documents