Turmeric Uses, Benefits & Dosage - Drugs.com

Curcumin is primarily available in capsule form from commercial manufacturers. The most common regimen is one to three 500 mg capsules daily with or without ... Skiptomaincontent Close Professionals NaturalProducts(Pro) Turmeric Print Save Turmeric ScientificName(s):CurcumalongaL.CommonName(s):Curcuma,Curcumin,Haldi,Indiansaffron,Turmeric MedicallyreviewedbyDrugs.com.LastupdatedonJan7,2022. ClinicalOverviewUse Useofcurcumin(turmeric)asapharmacologicagentislimitedduetoitslowsystemicbioavailabilityfollowingoraldosing.Curcuminisusedasaspiceincurrypowdersandmustard.Itismarketedwithclaimsofpotentantioxidantactivity,improvingboneandjointhealth,andreducinginflammation,butclinicaltrialsarelimited.Itsefficacyintreatingnumerouscancershasbeeninvestigated.Curcuminhasbeenshowntoprovideantidepressantandanxiolyticeffectsinpeoplewithmajordepressivedisorder;however,clinicaltrialsarelimited.Dosing Curcuminisprimarilyavailableincapsuleformfromcommercialmanufacturers.Themostcommonregimenisonetothree500mgcapsulesdailywithorwithoutfood.Inonestudy,patientstookone500mgcapsuletwicedailywithorwithoutfoodfor8weeksfortreatmentofmajordepressivedisorder.Powderedturmericroothastraditionallybeenusedasastimulantandcarminativeatdosagesof0.5to3g/day.Dosagesof3to6g/dayhavebeeninvestigatedforprotectiveeffectsagainstulcers.Analgesiceffectshavebeenreportedwithdosesof1.5to2g/day.Dailyoraldosesof3,600mghavebeentypicallyusedinclinicaltrials,butdosagesofupto8g/dayhavealsobeenused.HigherdosesareassociatedwithadverseGIeffects.Contraindications Avoiduseifhypersensitivetoanyofthecomponentsofcurcumin.Avoiduseduringpregnancyandlactationduetoemmenagogueanduterinestimulanteffects.Theherbshouldnotbeusedinpatientswithgallstonesorbileductorpassageobstruction.Pregnancy/Lactation Avoiduse.Documentedemmenagogueandabortifacienteffects.Interactions C.longamaypotentiallyinteractwithCYP2D6andCYP3Asubstrates.AdverseReactions Clinicaltrialsreportfewadversereactions(eg,dyspepsia,pruritus).Rarecasesofcontactdermatitisandanaphylaxishavebeenreported.Toxicology Limitedclinicaldataareavailable.Theoralmedianlethaldose(LD50)ofcurcumininratsandmicewashigherthan2,000mg/kgbodyweight. ScientificFamily ZingiberaceaeBotany ThegenusCurcumaL.maycontainmorethan100species,withCurcumalongaL.probablythebestknown.SynonymouswithCurcumadomesticaVal,turmericisaperennialplantfoundthroughoutSoutheastAsia,aswellasChina,Australia,andtheSouthPacific.IndiaandThailandhavethehighestdiversitywithatleast40speciesineachcountry.Theplantgrowstoaheightof0.9to1.5mandproduceslarge,oblongleavesandfunnel-shaped,dull-yellowflowers.Thethickrhizomeisyellowishincolorexternallyanddeeporangetoreddish-browninternally.Thelateralrhizomescontainmoreyellowcoloringthanthebulb.Thedriedprimarybulbandsecondarylateralrhizomesarecollected,cleaned,boiled,anddriedforuseinmedicinalandfoodpreparations.1,2,3,4,5History Traditionally,turmerichasbeenusedasafood,cosmetic,andmedicine.Turmericisaspicewithawarmandbittertasteusedprimarilyasacomponentofcurrypowdersandsomemustards.Itsdistinctiveyellowcolorhascommercialapplicationsasacoloringagentincheese,butter,andotherfoods.2,3,5Turmericanditsnaturalcurcuminoidshavebeenusedmedicinallyoverthecenturiesindifferentpartsoftheworld.InthetraditionalAyurvedicmedicalsystem,turmericisawell-recognizedtreatmentfornumerousrespiratoryconditions(eg,asthma,bronchialhyperactivity,allergies),liverdisorders,anorexia,rheumatism,diabeticwounds,cough,andsinusitis.5,6IntheIndiansubcontinent,turmericismedicinallyvaluedforitswoundhealingproperties.IntraditionalChinesemedicine,turmericisusedtotreatconditionsthatcauseabdominalpain.Turmerichasanti-inflammatoryactivityandwasusedtotreatsprainsandswellinginancientHindumedicine.5,6Chemistry Therhizomecontainsupto7%ofanorange-yellow,volatileoil.Tumeroneandartumeronetogethercompriseabout60%oftheoil,andzingiberenecomprisesabout25%.Cineole,d-phellandrene,d-sabinene,andborneolarepresentinlowconcentrations.Themajoryellowpigmenthasbeenidentifiedascurcumin(diferuloylmethane),aphenolicantioxidant.Unlikemostnaturalantioxidantsthatcontainbeta-diketoneorpolyphenolicfunctionalgroups,curcuminpossessesbothactivemoieties.Itssuperiorantioxidantactivityhasbeenattributedtothisstructuralcombination.CurcuminmodulatestheNrf2-keap1pathwayinthecellandbindstoantioxidantresponsiveelementsinDNAthatreducethereactiveoxygenspecies.Othercurcuminoidsstructurallyrelatedtocurcuminarealsofoundintheextractandincludedemethoxy-curcuminandbis-demothoxy-curcumin.Additionally,theturmericrhizomecontainsprotein,fat,minerals,andcarbohydrates.2,3,4,5,6,7,8,9,123UsesandPharmacology Mostclinicaltrialsfocusontheactiveprinciplecurcuminindividuallyratherthanonturmeric.Themedicinaluseofcurcuminislimitedduetoitslowsystemicbioavailabilityfollowingoraldosinglimits.Curcuminishydrophobicandcannotbegivenintravenously;italsodisappearsrapidlyfromtissuesafterintraperitonealadministration.Anencapsulatedliposomalformhasbeenexaminedinanimals2,10,11andnumerousapproachescontinuetobeinvestigatedtoimproveitsbioavailability,includingconcomitantuseofblackpepper(Pipernigrum)oroneofitsactiveconstituentspiperine.12,13,123AnalgesicAdultswithosteoarthritisofthekneeexperiencedasignificantreductioninseverityofpainandfunctionwhenadministered500mgtwicedailyofC.longarhizomeextract(12.6%w/wpolysaccharides)inarandomized,single-blind,placebo-controlled,comparativestudy(n=120).Adecreaseinuseofrescueanalgesic(acetaminophen)wasalsosignificantinthetreatedgroup.StudymedicationacceptabilitywashighestfortheC.longagroupwhoalsoexhibitedthefewestadverseeffects.87Asystematicreviewandmeta-analysisof8randomizedclinicaltrials(N=734)publishedbeforeDecember2014foundanoverallmoderatetolargeeffectofZingiberaceaeextracts(includingturmeric,ginger,andgalangal)onchronicpaincomparedwithplacebo;however,substantialheterogeneitywasfound.Significantlylowersubjectivepainwasreportedwiththeintervention(P=0.004).Astrongdose-responserelationshipwasalsodemonstrated.Patientgroupsincluded3studiesinpatientswithosteoarthritisofthekneeorhip,and1studyeachinpatientswithgonarthritis,irritablebowelsyndrome,musclesorenessfollowingexercise,postoperativepain,andprimarydysmenorrhea.The2trialsthatusedcurcuminorcurcuminoids(n=90)used1,500mg/day(combinedwith15mg/dayofblackpepperextracttoenhancebioavailability)for6weeksinosteoarthritispatientsand2,000mg/dayfor3weeksinpatientsrecoveringfromsurgery.105Anoninferioritytestfoundcurcuminextract(1,500mg/day;500mg3timesdaily)tobeaseffectiveasibuprofen(1,200mg/day;400mg3timesdaily)forimprovingpainandfunctioninosteoarthritispatientsina4-weekdouble-blind,randomized,controlledcomparatorstudythatenrolled367adultswithprimarykneeosteoarthritis.Curcuminimprovedoverallosteoarthritisindexscores(P=0.01),pain(P=0.018),andfunction(P=0.01).Themeanageofparticipantswas60yearsconsistingofapproximately90%women.Theincidenceofadverseeventswassimilarbetweengroups;however,significantlymorepatientsintheibuprofengroupexperiencedabdominalpainanddistension.109A2016systematicreviewandmeta-analysisthatevaluated8randomizedcontrolledtrialsreportedsignificantlyreducedpainscoresforcurcumincomparedtoplaceboinarthritispatients(eg,osteoarthritis,rheumatoidarthritis).Dosesweresimilaracrossthestudieswithabout1g/daygivenintheabsenceofotheranalgesicsandabout500mg/daygivenconcomitantlywithpainkillers.Durationoftreatmentsrangedfrom4weeksto4months.Nosignificantdifferencewasobservedforpooledresultsbetweencurcuminandanalgesicmedications(ie,ibuprofen,diclofenac,glucosamine)suggestingabout1g/dayofcurcuminmayhavesimilareffectstotheseanalgesicagents.113Anti-inflammatoryCurcuminhasbeenshowntointerferewiththeeicosanoidpathway,involvingcyclooxygenaseandlipoxygenaseenzymes,reflectingthetraditionaluseofturmericinAyurvedicandChinesemedicalsystemsforinflammation.64Olderclinicaltrialshavebeenconductedcomparingcurcuminwithphenylbutazone.2Thetherapeuticeffectofcurcuminwascomparabletothatofhydrocortisoneintreatingexperimentalpulmonaryfibrosis.65Atotalof100hemodialysispatientswhoalsoexperiencedtreatment-resistanturemicpruritusforatleast6weekswererandomizedinadouble-blindtrialtoreceive1,500mgofturmericdailyorplacebofor8weeks.Bothgroupsexperiencedsignificantlyreducedtotalpruritusscoresaftertreatment(P=0.0001foreach).Theauthorsreportedthatthemeanreductionintheturmericgroup(13.6)wassignificantlybetterthanthemeanreductionintheplacebogroup(7.2)(P=0.001).Additionally,themeandecreaseinC-reactiveproteinwassignificantlygreaterwithturmericthanplacebo(−0.8mg/Lvs0.4mg/L,respectively;P=0.012).100Managementofacuteinflammationpainsubsequenttoremovalofimpactedmolarswasexploredinarandomized,controlled(n=90)trial.Boththeactivecontrol(mefenamicacid)andcurcumin(400mg3timesdaily×24hours)wereeffectiveinreducingpostoperativeinflammatorypainwithpatientsinthecurcumingroupreportingsignificantlyhigherreductionsinpainateachtimepoint(P=0.0001each).Additionally,morepatientsinthecurcumingroupreportedhigherpainscorereductionsofeither6or7thanthecontrolgroup(57%vs24%,respectively,fortreatmentvscontrol),whereasscorereductionsinthecontrolgroupweremostly4or5(55.6%).124ArthritisInarandomized,single-blind,placebo-controlled,comparativestudy(n=120),adultswithosteoarthritisofthekneeexperiencedasignificantreductioninseverityofpainandfunctionwhenadministered500mgtwicedailyofC.longarhizomeextract(12.6%w/wpolysaccharides).Adecreaseinuseofrescueanalgesic(acetaminophen)wasalsosignificantinthetreatedgroup.TheC.longagroupalsoexhibitedthefewestadverseeffects.87Anoninferioritytestfoundcurcuminextract(1,500mg/day;500mg3timesdaily)tobeaseffectiveasibuprofen(1,200mg/day;400mg3timesdaily)forimprovingpainandfunctioninosteoarthritispatientsina4-weekdouble-blind,randomized,controlledcomparatorstudythatenrolled367adultswithprimarykneeosteoarthritis.Curcuminimprovedoverallosteoarthritisindexscores(P=0.01),pain(P=0.018),andfunction(P=0.01).109A2016systematicreviewandmeta-analysisthatevaluated8randomizedcontrolledtrialsreportedsignificantlyreducedpainscoresforcurcumincomparedtoplaceboinarthritispatients(eg,osteoarthritis,rheumatoidarthritis).Dosesweresimilaracrossthestudieswithabout1g/daygivenintheabsenceofotheranalgesicsandabout500mg/daygivenconcomitantlywithpainkillers.Durationoftreatmentsrangedfrom4weeksto4months.Nosignificantdifferencewasobservedforpooledresultsbetweencurcuminandanalgesicmedications(ie,ibuprofen,diclofenac,glucosamine),suggestingapproximately1g/dayofcurcuminmayhavesimilareffectstotheseanalgesicagents.Functionaloutcomes,includingmorningstiffnessandmovements,alsoimprovedwithcurcumin,howeverfundamentalimprovementinarthritissymptomswerenotseen.Atdosesupto1,200mg/daygivenforupto4months,turmericpreparationsandcurcuminwereconsideredsafe.113Arandomized,single-blindpilotstudywasconductedin45adultswithrheumatoidarthritiswhowererandomlyassignedtocurcumin500mg,diclofenac50mg,orthecombinationofthe2agentstwicedailyfor8weeks.All3groupsexperiencedsignificantimprovementsfrombaselineindiseaseactivityscores(DAS)andAmericanCollegeofRheumatology(ACR)jointscores.Thecurcumingroup’simprovementsinDASandACRscoresweresignificantlybetterthanthediclofenacgroup’sscores.91CancerCurcuminanditsanalogsexhibitgrowthsuppressiveactivityagainstabroadrangeoftumorsincludingskin,forestomach,duodenal,gallbladder,andcolonatmultiplestagesofdevelopment,includinginitiation,promotion,andmetastasis.2,3,14,15,16,17,88Severalmechanismsofactionareproposedforcurcumin’santicanceractivity,includinginhibitingexpressionofgrowthandmetastases-promotinggenes;regulationofmoleculartargetsthatcontrolcelladhesion,apoptosis,andinvasion;andregulationofenzymesthatcontroltumorgrowth.14,15,16,17,18,88Studieshavealsoindicatedthatcurcuminhasaradiosensitizingeffectoncancercellcultures.19,20AnimaldataNumerousstudiesinanimalmodelssupportcurcumin’spossiblesuppressionoftumorigenicactivityofawidevarietyofcarcinogensinvolvedinleukemiaandcolon,duodenum,esophagus,forestomach,stomach,liver,breast,oralcavity,andprostatecancers.5,14,17However,notallexperimentshaveshownpositiveresults.Astudyinratsfailedtodemonstrateanyeffectsinthepreventionofprostatecarcinoma.21ClinicaldataPhase1,2,and3clinicaltrialsofcurcuminarebeingconductedbytheNationalCancerInstitute.22Aphase1studyismeasuringthelevelsofcurcuminanditsmetabolitesinnormalcolorectaltissueinpatientsundergoingcolorectalendoscopyorcolorectalcancersurgeryfollowinga14-daycourseofcurcumin.Anopen-labelstudyisexaminingtheshort-termeffectsofsupplementationwithaturmericextractonpatientswithnewlydiagnosedheadandnecksquamouscellcarcinoma.Aphase2trialisassessingwhethercurcumincancauseregressionofcolorectalandduodenaladenomatouspolypsinpatientswithfamilialadenomatouspolyposis.Anotherphase1trialisinvestigatingtheuseofplantexosomesindeliveringandimprovingthebioavailabilityofcurcuminfortreatingcolontumorsandnormalcolontissue.Additionalstudiesincludeassessmentoftheefficacyofcurcuminandashwagandhaextractintreatinghigh-graderelapsedormetastaticosteosarcoma,andexaminationofcurcumin’santi-inflammatoryandanti-oxidativepropertiesasatherapeuticoptioninpancreaticcancerpatients.22Resultsofadouble-blind,randomized,placebo-controlledtrial(n=44)inadultswithfamilialadenomatouspolyposisdocumentednosignificantdifferenceinpolypburden(sizeornumber)inpatientstreatedfor12monthswithcurcumin(100%pure,3g/day)comparedtoplacebo.Treatmentwaswelltoleratedwith1reportofprurituslikelyrelatedtocurcumin.120TheefficacyofcurcumininpreventingcolorectalcancerhasbeeninvestigatedbytheNationalCancerInstitute.14,22Insmokers,turmeric1.5g/dayfor30daysreducedtheurinaryexcretionofmutagenscomparedwithcontrols.23Trialshavebeenconductedinpatientswithcolorectalcancerrefractorytostandardtherapy,primarilytoexploretoleranceandsafety.24,25Alimitednumberofpatientsdemonstratedstableradiologicalconditionsforupto4monthsaftercurcumintreatment.Administrationofcurcuminto12patientswithcolorectalcancershowedpharmacologicallyactivelevelsoftheagentinthetargettissue.26ReductioninthebiologicalmarkerM1Gaftercurcuminusewasattributedtoanantioxidantactionofcurcumininthetumor.Clinicaloutcomeswerenotreported.Investigatorsconcludedthatpharmacologicallyactivelevelsofcurcumincouldnotbeachievedinpatientswithhepaticmetastasesbecauseofpoororalbioavailability.2Anopen-labelclinicaltrialin41smokersfoundnoreductioninprocarcinogeniceicosanoids,prostaglandinE2or5-hydroxyeicosatetraebiucacid,inaberrantcryptfociornormalflatmucosaduringtreatmentwithoralcurcumin2or4g/dayfor30days.However,treatmentwithoralcurcumin4g/dayfor30daysreducedaberrantcryptfociformation.27Inarandomized,placebo-controlledclinicaltrial,acombinationofsoyisoflavones(40mg)andcurcumin(100mg)decreasedserumprostatespecificantigen(PSA)inpatientswhosebaselinePSAwasmorethan10ng/mL.28Aphase2trialofcurcumininpatientswithpancreaticcancerwasconductedwithoralcurcumin.Twenty-onepatientsreceivedoralcurcumin8g/daywithouttreatment-relatedtoxicityforupto18months.Changesincytokinelevels(elevatedatbaseline)wererecorded,anonsignificantreductioninnuclearfactorkappaBwasshowninmostpatients,andradiologicalstabilitywasdemonstratedin2patients.10Theefficacyofcombinedtreatmentofcurcuminandgemcitabineinpatientswithadvancedpancreaticcancerhasbeenevaluated.29,30Aphase1trialwithcombinedtreatmentofcurcuminanddocetaxelinpatientswithadvancedandmetastaticbreastcanceradministeredcurcumin6,000mg/dayfor7consecutivedaysevery3weeksincombinationwithdocetaxel.Thetreatmentdosedidnotleadtodose-limitingtoxicity;rather,thepillburdenfromthenumberofcurcumincapsulesperdaylimiteddosing.31CardiovasculareffectsAnimaldataStudiesinanimalshavedemonstratedanti-plateleteffects,aswellaspositiveeffectsonlipidprofiles,includingadecreasedsusceptibilityoflow-densitylipoprotein(LDL)tooxidation.32,33,34Inexperimentalatherosclerosisinrabbits,animalsreceivingtheextracthadlessdamagefromfattystreaksinthethoracicandabdominalaortasat30daysthandidthoseinthecontrolgroups.Markersofoxidativestresswerealsoimprovedinthetrialgroup.8ClinicaldataAdditionalclinicaltrialdataareneededtoevaluateefficacy.Amonghealthyvolunteers,curcumin500mg/dayfor7daysdecreasedserumcholesterolandlipidperoxidelevelsandincreasedhigh-densitylipoprotein(HDL).2A500mgdailycurcuminsupplementwasmoreeffectivethan6g/dayinreducingserumcholesterolandtriglyceridelevels.35Anotherstudydocumentedsimilarresultsinpatientswithacutecoronarysyndrome.36Noeffectonlipidprofilewasobservedinatrialevaluatingtheeffectofturmeric1.5g/dayonurinaryexcretionofmutagens.23Adoseofcurcumin300mgorallytwicedailyover8weeksreducedinflammatorycytokinesandmarkersofoxidativestressonendothelialdysfunctioncomparablewiththatofatorvastatininpatientswithtype2diabetes.37Anotherdouble-blindrandomizedclinicaltrialinThaipatientswithtype2diabetes(n=240),observedsignificantimprovementinatherogenicriskduring6monthsofsupplementationwithcurcuminoid750mg/day(250mg3timesdaily)thatfolloweda3-monthlead-inofdietandlifestyleeducation.Antiatherogenicactivity,measuredbypulsewavevelocity,adiponectin,leptin,insulinresistance,triglycerides,uricacid,andtotalbodyfatwereallsignificantlyimprovedat6months(P<0.001)aswasvisceralfat(P<0.05).Themajorityoftheseparameterswerealsosignificantlyimprovedatthe3-monthvisit.Compliancewascomparablebetweenthetreatmentandplacebogroupwithnoserioussideeffectsreported.97Ameta-analysisof7treatmentsacross6studiesthatincluded172subjectsfoundasignificantreductioninthesystemicinflammationbiomarker,C-reactiveprotein,withstandardizedcurcuminoidpreparationsthatweretakenforatleast4weeks.Dosesrangedfrom200to6,000mg/daywithvariablebioavailability.Overhalfofthestudies(4/6)wereratedhigh-quality,whiletheother2werelow-quality;overallheterogeneitywashigh.96Anothermeta-analysisof7randomized,controlledtrials(N=649)inpatientswithcardiovascularriskfactors(eg,type2diabetes,metabolicsyndrome)identifiedanoverallsignificantpositiveeffectforturmericand/orcurcuminproductsonLDLcholesterol(P<0.0001)andtriglycerides(P=0.007)withnosignificantheterogeneity.Subgroupanalysisrevealedsignificantimprovementinpatientswithmetabolicsyndrome(N=136;P<0.0001)butnotinthosewithhyperglycemia.Noseriousadversereactionswerereported.119CNSeffectsAnimaldataInvitroandinvivostudieshaveexaminedcurcumin’scomplexmechanismofaction.2,38,39,40,41CurcuminmaytargetseveralpathophysiologicalpathwaysinvolvedinAlzheimerdiseaseincludingthebeta-amyloidcascade,tauphosphorylation,neuroinflammation,oroxidativestress.Itspoorbioavailabilityandinsolubilityinwatercreatestherapeuticlimitations;however,curcuminanaloguesmaywarrantfurtherinvestigationforAlzheimertreatment.40,42ClinicaldataTherearelimitedclinicaltrialdataontheuseofcurcuminintreatingAlzheimerdisease.Inarandomizedclinicaltrial,thelowbioavailabilityofcurcumin1to4g/dayfor6monthsmayhavecontributedtonoimprovementincognitiveperformanceinpatientswithmildtomoderateAlzheimerdisease.Nobeneficialeffectwasdocumentedonproinflammatorybiomarkerssuchasserumamyloid-betapeptideandisoprostanes.43AnotherstudyfoundthatvitaminD3mayinteractwithcurcuminoidstostimulatebeta-amyloidclearancebyactivatingtypeImacrophagesinpatientswithAlzheimerdisease.44,45In46middle-agedandelderly(age50to90years)non-dementedvolunteerswithclinicalhistoriesconsistentwithnormalagingormildneurocognitivedisorder,administrationofahighlybioavailablecolloidalcurcumin(180mg/dayTheracurmin)for18monthsimprovedverbalmemoryperformanceasseenwithsignificantlybetterdifferencesinlong-termrecallscorescomparedtoplacebo(effectsized=0.68,P=0.05).Additionally,differencesinthemeasureofattentionwasalsofoundtobesignificantlybetterinthecurcumingroupcomparedtocontrols(d=0.55).Nosignificantchangebetweengroupswasseenforvisualmemoryassessments.DepositionofamyloidplaquesandtautangleswasfoundtobesignificantlyimprovedwithcurcumincomparedtoplacebointhehypothalamusandwerecorrelatedsignificantlywiththechangesinBeckDepressionInventoryscores(P=0.02).Findingsfromthisdouble-blind,randomized,placebo-controlledtrialwereadjustedforageandeducation;apolipoproteinE4statusorfamilyhistoryofdementiawasnotfoundtosignificantlyaffecttheresults.118Improvementsinsustainedattention,workingmemory,andpreventionofcognitionlossinolderhealthyadultshasalsobeendocumented.123Arandomizedcontrolledtrialcomparedsafetyandefficacyofcurcuminwiththatoffluoxetinein60patientswithmajordepressivedisorder(withoutsuicidalideation).After6weeks,curcumin1,000mg/daywasfoundtobeequivalenttofluoxetine20mg/dayinproportionofrespondersbasedonHamiltondepressionscalescores;however,patientsoncombinationtherapyshowedabetterresponsethaneitherofthemonotherapyregimens.Noneoftheresponseswerestatisticallysignificant.Fewerpatientsoncurcuminachievedremission.Curcuminwaswelltoleratedwithonlymildgastritisandnauseareported.95Bothplaceboandcurcumin(1,000mg/day)providedsignificantimprovementsfrombaselinetoweek4inself-reporteddepressiveandanxietyscoresinsubjectswithmajordepressivedisorderparticipatinginan8-week,randomized,double-blind,placebo-controlledtrial(N=56).However,beneficialeffectscontinuedfromweek4to8onlyinthecurcumingroup.Additionally,curcuminadministrationresultedinasignificantandgreaterbenefitthanplaceboinasubgroupofparticipantswithatypicaldepression.101Asmalldouble-blindtrialrandomized48elderlyprediabetespatients(medianage,71to75years)toreceiveasingledoseofturmeric(1g),cinnamon(2g),both(1and2g,respectively),orplacebopriortoawhite-breadbreakfasttodetermineacuteeffectsonworkingmemory.Ofatotalscoreof3,postprandialworkingmemoryincreasedoverthe6-hourobservationperiodfrom2.6to2.9(P=0.05)withturmericuserscomparedwithnon-turmericusers.Thesechangeswerenotnotedwithcinnamonusersandwereindependentofbodyfat,glycemia,insulin,orAlzheimerdiseasebiomarkers.99DiabetesAnimaldataAnimalstudiesindiabeticmiceandratshaveshownhypoglycemiceffectsforcurcumin.3,46,47,48Areviewdocumentedcurcumin’sbeneficialeffectsinreducingthecomplicationsoftype2diabetesincludinghepaticfibrosis,retinopathy,neuropathy,andnephropathy.49Curcuminmaysuppressadvancedglycationendproducts,thereforereducingoxidativestress,inflammation,andhepaticstellatecellactivation.49Curcuminsupplementationinratsover7weeksimprovedmuscleinsulinresistancebyincreasingoxidationoffattyacidandglucose.50Inanexperimentaltype1diabetesanimalmodel,curcuminimprovedleftventricularfunctionandreducedfibrosisandhypertrophyinrats.51ClinicaldataLimitedclinicaltrialdataareavailable.Inhealthyvolunteers,oralturmeric2.8g/dayfor4weekshadnoeffectonfastingbloodglucoselevels.52A4-weekpilotstudyexaminedtheeffectsondiabeticmicroangiopathyusingalecithinformulationofcurcuminatadoseof1gorallyperdayin25diabeticpatients.Curcuminimprovedmicrocirculationanddecreasededemawhencomparedwithcontrols.53A500mgcurcuminregimenadministered3timesdailytotype2diabeticnephropathypatientsina2-monthrandomized,double-blind,andplacebo-controlledstudyimprovedurinaryproteinexcretionandexpressionoftransforminggrowthfactorandinterleukin(IL)-8.54Curcuminextractwasevaluatedforpreventionoftype2diabetesin240adultpatientswithprediabetesinarandomized,double-blind,placebo-controlledtrial.Aftera3-monthrun-inwithinstructionsondietandexercise,patientswererandomizedtoreceive3oralcapsulescontainingcurcuminoid250mgpercapsuleormatchingplacebotwicedailyfor9months.Adiagnosisoftype2diabeteswasseenin16.4%ofplacebopatients,comparedwith0%inthecurcumingroup.Ascomparedwithplacebo,thecurcumingrouphadsignificantlylowerresultsforhemoglobinA1c,fastingplasmaglucose,and2-houroralglucosetolerancetestglucoselevel.Thecurcumingroupalsohadsignificantchangesin9-monthvaluesforreductionsinbodymassindexandwaistcircumference,improvedbeta-cellfunction,andincreasedadiponectin.Bodymassandwaistcircumferencewerenumericallybutnotstatisticallylowerat3monthsand6monthswithcurcumin.89Anothersmalldouble-blindtrialrandomized48elderlyprediabetespatients(medianage,71to75years)toreceiveasingledoseofturmeric(1g),cinnamon(2g),both(1and2g,respectively),orplacebopriortoawhite-breadbreakfasttodetermineacuteeffectsonworkingmemory.Ofatotalscoreof3,postprandialworkingmemoryincreasedoverthe6-hourobservationperiodfrom2.6to2.9(P=0.05)withturmericuserscomparedwithnon-turmericusers.Thesechangeswerenotnotedwithcinnamonusersandwereindependentofbodyfat,glycemia,insulin,orAlzheimerdiseasebiomarkers.99TheTAK-MetStrial,adouble-blind,randomizedcontrolledtrialcomparingtheefficacyofpowderedblackseeds(kalongi)andturmericasmono-andcombinationtherapyinPakistanimaleswithmetabolicsyndromereportedsignificantimprovementsincholesterol,LDL-cholesterol,andC-reactiveproteinafter8weeksofturmericmonotherapy(2.4g/day)comparedtoplacebo.Combinationtherapy(900mg/dayblackseeds+1.5g/dayturmeric)resultedinsignificantimprovementsinpercentbodyfat,alllipidparameters,fastingbloodglucose,andC-reactiveproteincomparedtoplacebo.Comparedtobaseline,theplacebogroupexhibitedsignificantimprovementsinbodymassindexandpercentbodyfatbytheendofthestudy.Mildadverseeffects(ie,dyspepsia,pruritus)werereportedat4weeksin4patientsreceivingturmericwithonlytheadditionalreportofweaknessandweightreductioninthecombinationtherapygroupleadingtowithdrawalofonepatientat6weeks.103Similarly,inaphase3double-blind,randomizedcontrolledtrialinIran,supplementationwithaproprietarycombination(curcuminoid500mg/piperine5mgtwicedaily)for8weeksin100menandwomendiagnosedwithmetabolicsyndromewhohadnotpreviouslytakenlipid-loweringmedicationresultedinasignificantimprovementinoxidativeandinflammatorymarkers,includinghs-C-reactiveprotein,superoxidedismutase,malondialdehyde,andfastingbloodglucose(P<0.001each).Theauthorsalsoconductedameta-analysisof8randomizedcontrolledtrials(N=562)anddeterminedtheeffectofcurcuminoidsonC-reactiveproteintoberobustwithpotentialpublicationbiasnoted.107GallbladderInarandomized,double-blindstudyinvolving12patients,acurcumin20mgdoseinduced30%contractionsinthegallbladder.5,66Asimilarstudyadministeringcurcumin40and80mgproduced50%and70%contractionofthegallbladdervolume,respectively.5,67Anotherclinicalstudydocumentedreducedpainandpostoperativefatigueafterlaparoscopiccholecystectomyinpatientstreatedwith500mgoforalcurcuminevery6hours.68GastrointestinalTurmericandcurcuminhavebeenfoundtocausespecieschangesinthegutmicrobiotaofhealthyadultswithcurcuminprimarilyresponsibleforthechanges.Incontrasttoplacebo,responsesofthegutmicrobiotatoturmericandcurcuminwerehighlypersonalizedandnon-uniform,butnotrandom.RespondersexhibiteduniformincreasesinClostridiumspecies,Bacteroidesspecies,Citrobacterspecies,Cronobacterspecies,Enterobacterspecies,Enterococcusspecies,Klebsiellaspecies,Parabacteroidesspecies,andPseudomonasspeciesaswellasdecreasesinBlautiaandRuminococcusspecies.122,122AnimaldataPretreatmentofratswithcurcuminfor5daysbeforeinductionofcolitisresultedinareductionincolonicinflammation,histologicdamage,andinflammatorymarkers.Curcuminrecipientsalsodemonstratedreducedweightlosscomparedwithcontrols.55Anotheranimalstudyshowedthattreatmentofmicewithcurcuminreducedtheincidenceofdiarrheaandthedisruptionofcolonicarchitecture.56Curcuminreducedkeyinflammatorysignalingthroughp38MAPKactivation,enhancedIL-10,andreducedIL-1–betaincolonicmucosalbiopsiesandcolonicmyofibroblastsisolatedfromchildrenandadultswithactiveirritableboweldisease.57Curcumin’sprotectiveeffectsmaybeIL-10–dependentasshownbyitslimitedeffectivenessonTh-1–mediatedcolitisinIL-10–deficientmice.58ClinicaldataApilotstudyinvestigatedtheuseofstandardizedturmericrootextract1,800or3,600mg/dayin207patientswithirritablebowelsyndrome.Improvementinqualityoflifescoreswasreportedbybothgroups.Atrendfavoringthehigherdosagewasobservedinaposthocanalysisofabdominalpainanddiscomfort.46AsimilarpilotstudyconductedinpatientswithCrohndiseasefoundfavorableresults.59Arandomized,double-blind,placebo-controlled6-monthtrialin89patientsgivencurcuminasmaintenancetherapyforulcerativecolitisshoweddifferencesinrelapseratecomparedwithplacebo.Thedoseofcurcuminusedwas1gtwicedailyincombinationwithstandardmaintenancetherapyofmesalamineorsulfasalazine.60Improvementincolitishasbeenattributedtotheanti-inflammatoryandantioxidanteffectsofcurcumin.46,55,56Resultsfromanimalstudies61anduncontrolledtrials62,63suggestaroleforturmericinthetreatmentofduodenalorgastriculcer.A2016double-blind,randomized,placebo-controlledtrialinvestigatedadjunctiveuseofcurcuminin68Iranianadultswithgastricpain,dyspepsiasymptoms,andconfirmedgastricorduodenalulcersinthepresenceofH.pylori.InadditiontostandardH.pyloritripletherapy,patientsreceivedcurcumin500mgpluspiperine5mgdailyasadjunctivetherapy.Thesamenumberofpatientsinbothgroupshaddocumentedinfectioneradication(73.3%)andsignificantimprovementinalldyspepsiasymptoms,exceptvomiting,withtotalseverityscoresalsoimproved(P<0.001).However,adjunctiveuseofcurcuminledtosignificantlygreaterimprovementsinbelching(P=0.028),upperabdominaldullache(P=0.002),stomachpainbeforemeals(P=0.004),andtotaldyspepticseverityscores(P<0.001).Morepatientsinthecurcumingroupreachedanon-dyspeptictotalscorebytheendofthestudythanthoseintheplacebogroup(27.6%vs6.7%,respectively;P<0.001)andsignificantlymorehadresolutionofdyspepsiawithcurcuminalso(P=0.042).Treatmentwaswelltoleratedwithnoseriousadverseeventsreported.111HepatoprotectiveAprotectiveeffectagainstchloroquine-inducedhepatotoxicitywasdemonstratedbycurcuminadministeredtorats.69Curcumingivenadjunctivelywithantituberculosistherapyreducedtheincidenceofhepatotoxicityinpatientsinaclinicaltrial.70Thebenefitofturmericin48adultpatientswithelevatedserumALTlevelswasinvestigatedina12-week,randomized,placebo-controlledtrial.Patientsreceived2fermentedturmericpowder500mgcapsulesormatchingplacebo3timesdaily.Significantreductionsatweek12comparedwithplacebowereseenwithfermentedturmericpowderforALTandAST.Nosignificantdifferencebetweengroupswasseenforgammaglutamyltransferase,alkalinephosphatase,totalbilirubin,orlipidlevels.90IronmetabolismAdministrationofasingle6gdoseofcurcumacontainingmixedcurcuminoids(120mgcurcumin)tohealthymalevolunteersresultedinsignificantdecreaseinhepcidinlevelsat3timepointsover48hourspostingestion.Serumferritinlevelswerealsosignificantlydecreasedcomparedtoplacebo(P=0.015);however,serumiron,transferrin,transferrinsaturation,andglucoselevelswerenotsignificantlyaffected.TransientGIsymptomsoccurredin2participants;noseriousadverseeventswerereported.Theresultsofthisproof-of-conceptdouble-blind,randomized,controlledcross-overstudy(n=18)confirmedearlierresultsdemonstratedinvitro.116MucocutaneousconditionsOrallichenplanusisthemucosalcounterparttocutaneouslichenplanus;bothareT-cellmediatedautoimmunediseases.Theefficacyofcurcuminintreatmentoforallichenplanus(OLP)wasexploredinadouble-blind,randomized,placebo-controlledtrialthatenrolled20patientswithconfirmeddiagnosisoferosive-atrophicOLP.Inadditiontoroutinetreatmentwithdexamethasone0.5mgmouthwashandNystatinsuspension,patientsreceivedoralcurcumin2,000mg/day(1,000mgtwicedaily)orplacebofor4weeks.Boththetreatmentandplacebogroupsexperiencedsignificantreductionsfrombaselineinseverityofpainandburningaswellasinthetypeandseverityoflesionsat2and4weeks;nostatisticallysignificantdifferencewasobservedbetweengroups.110Administrationofturmericwithblackpepper(400mg+100mg;2capsules3timesdailyfor3months)producedasignificantimprovementinmouthopeningandburningsensation(P<0.01each)inpatientswithoralsubmucousfibrosisinadouble-blind,randomized,comparatortrial(n=40).Serumsuperoxidedismutaselevelswerealsosignificantlyimproved(P<0.05).Nosignificantdifferencewasfoundinpatientstreatedwithturmeric/blackpepperandthosetreatedwithnigellasativa.Bothinterventionswerewelltolerated.117OphthalmicDelayedonsetofcataractshasbeenassociatedwiththeuseoforalcurcumininrats.However,theeffectwasonlyobservedatlowdosages(0.002%),andahigherdosageof0.01%showednobenefit.71Inaclinicaltrialamongpatientswithchronicanterioruveitis,curcuminappearedtobecomparablewithstandardcorticosteroidtherapyat375mg3timesaday.2SkinconditionsInvitrostudiesandanimalexperimentssuggestaroleforcurcumininwoundhealing.Aninvitrostudydemonstratedprotectiveeffectsofcurcuminagainsthydrogenperoxideinhumankeratinocytesanddermalfibroblasts.9Oralpretreatmentwithcurcumin100mg/kghastenedwoundhealinginmiceexposedtopostoperativegammaradiation.72Enhancementofcollagensynthesisandmarkersofwoundhealingweredemonstrated.Histologicalassessmentofwoundbiopsyspecimensshowedimprovedcollagendepositionaswellasincreasedfibroblastandvasculardensities.Asmall,randomized,placebo-controlledtrialwasconductedin30breastcancerpatientsundergoingradiationtherapytoevaluatethebenefitoforalcurcumin2g3timesdailybeginningatthestartofradiation.Patientswerepermittedtousetopicalagents(eg,hydrocortisone,silversulfadiazine)thatconstituteusualcareforradiationdermatitis.Thecurcumingrouphadsignificantlylowerradiationdermatitisscoresandincidenceofmoistdesquamationcomparedwiththeplacebogroup.92Arandomized,double-blindstudyevaluatedthebenefitofcurcumin1g/dayin96warveteranswithchroniccutaneouscomplicationsfromsulphur-mustardexposure.Curcuminwasstatisticallysuperiortoplaceboforimprovementsat4weeksforitching,dermatologylifequalityindexscores,labvaluesincludinginterleukin(IL)-8,calcitoningene-relatedpeptide,andhigh-sensitivityC-reactiveprotein.IL-6changewasnotstatisticallybetterwithcurcuminversusplacebo.93AphaseIV,double-blind,randomized,placebo-controlled,single-center,pilotstudy(n=21)soughttodemonstratealocaltherapeuticresponseinpatientswithmoderatetosevereplaquepsoriasistooralCurcumaextractwhenactivatedbylocalvisiblelightphototherapyinadditiontowhole-bodyultraviolet(A)phototherapy(minusthelocalplaquearea).Plaquelesionswerelargerthan4cm2.Curcumaextract72mg/day(100mgstandardizedC.longawith12mgcurcuminpertablet)wastaken48to72hourspriortostartingthephototherapyregimenoftwiceaweek×2months;groupswererandomizedtoreceiveeitherrealorsimulatedvisiblelighttreatmenttotheexperimentalplaquearea.Atfollowupvisit9of18,100%ofthepatientsreceivingrealvisiblelighttherapyexperiencedimprovementinlesionstoatleast"moderate"comparedto40%intheplacebo(simulated)group.Byvisit18attheendofthestudy,evolutionoflesionimprovementto"slight"wasexhibitedby81%and30%ofrealversussimulatedlighttherapy,suggestingapossiblenewandsafertherapeuticmethodforthesepatients.106Asystematicreviewofalternativetherapiesforpsoriasisfoundpreliminaryhigh-qualityevidencetosupportarecommendationoforalphospholipid-basedcurcuminonatrialbasisasadjunctivetreatmentforpatientswithpsoriasis.Evidenceforuseoftopicalcurcumininthesepatientsislimited.121VitaminElevelsA6-weekrandomizedcontrolledtrialinvestigatedtheeffectofcurcuminonserumvitaminElevelsinIranianpatientswithmetabolicsyndrome(n=120).Curcumin-phospholipidcomplex(1g/day;equivalentto200mg/daypurecurcumin)supplementationresultedinasignificantreductioninthemeanvitaminElevelscomparedtobaseline(−0.12micromol/L;P=0.004).Additionallythemeanreductionbetweenthecurcumin-phospholipidaswellasthecurcumin(1g/day)groupsandcontrolswassignificant(P=0.004andP=0.005,respectively).TheincreaseinratiosofvitaminEtototalcholesterol,LDL,andtriglyceridesobservedinthecontrolgroupweremitigatedwiththecurcumintreatments.ThiswasalsotruefortheincreaseobservedwiththevitaminE:HDLratioincontrolsthatwassignificantlylowerintheinterventiongroups.114Dosing Curcuminisprimarilyavailableincapsuleformfromcommercialmanufacturers.Itismarketedwithclaimsofpotentantioxidantactivity,improvingboneandjointhealth,andreducinginflammation.Onetothree500mgcapsulesdailywithorwithoutfoodisthemostcommonregimenrecommendedbymanufacturers.Inonestudy,patientstookone500mgcapsuletwicedailywithorwithoutfoodfor8weeksfortreatmentofmajordepressivedisorder.101Powderedturmericroothastraditionallybeenusedasastimulantandcarminativeatdosagesof0.5to3g/day.Dosagesof3to6g/dayhavebeeninvestigatedforprotectiveeffectsagainstulcers.62,63Dailyoraldosesofcurcumin3,600mghavebeenadvocatedforuseinclinicaltrials25butdosagesofupto8g/dayhavebeenusedinpatientswithadvancedpancreaticcancer.10Ahighlyabsorbablecolloidalnanoparticleformulationhasbeenusedat1,800mg/dayformemoryimprovementandreductionofamyloiddepositioninnon-dementedadults.118HigherdosesareassociatedwithadverseGIeffects.2Pregnancy/Lactation Avoiduseduringpregnancyandlactationbecausepotentialemmenagogueandabortifacienteffectshavebeendocumented.73,74,75Estrogenicandantiandrogeniceffectsaredocumentedinanimalmodels.76AnextractofC.longahadacontraceptiveeffectinmalerats.Areductioninspermmotilitywasobservedinratsreceivingturmeric500mg/kg/dayasanaqueousoralcoholicextract.77Interactions AgentswithAntiplateletProperties:Herbs(Anticoagulant/AntiplateletProperties)mayenhancetheadverse/toxiceffectofAgentswithAntiplateletProperties.Bleedingmayoccur.Considertherapymodification.78,79,80,81Anticoagulants:Herbs(Anticoagulant/AntiplateletProperties)mayenhancetheadverse/toxiceffectofAnticoagulants.Bleedingmayoccur.Considertherapymodification.78,79,80,81Herbs(Anticoagulant/AntiplateletProperties):Mayenhancetheadverse/toxiceffectofotherHerbs(Anticoagulant/AntiplateletProperties).Bleedingmayoccur.Considertherapymodification.78,79,80,81NonsteroidalAnti-InflammatoryAgents:Herbs(Anticoagulant/AntiplateletProperties)mayenhancetheadverse/toxiceffectofNonsteroidalAnti-InflammatoryAgents.Bleedingmayoccur.Considertherapymodification.78,79,80,81Salicylates:Herbs(Anticoagulant/AntiplateletProperties)mayenhancetheadverse/toxiceffectofSalicylates.Bleedingmayoccur.Considertherapymodification.80,81ThrombolyticAgents:Herbs(Anticoagulant/AntiplateletProperties)mayenhancetheadverse/toxiceffectofThrombolyticAgents.Bleedingmayoccur.Considertherapymodification.78,79,80,81C.longasignificantlyinhibitedtheformationofthedextromethorphanmetabolites,dextrorphan(DOR)and3-methoxymorphinan(3-MM),inadose-dependentandlinearfashion.Urinemetabolicratioofdextromethorphan:DORwassignificantlyincreased,whilethedextromethorphan:3-MMratiowasinsignificantlyincreased.C.longahasgreatpotentialtoinhibitCYP2D6enzymeactivities.102Acasereportnotedaprobableinteractionbetweenturmeric(2.5g/dayfor5days)andthevitaminKantagonistfluindionethatresultedinasuddenincreaseina56-year-oldwoman’spreviouslystabilizedinternationalnormalizedratio(INR)from2or3upto6.5.However,noclinicalsignsofbleedingwereobserved.NoinformationwasdocumentedthatidentifiedthisinteractionasanINRlabinteractionversusapharmacologicalone.98Acasereportofprobableinteractionbetweenturmeric(atleast15spoonsful/day)andtacrolimuswasreportedina56-year-oldmalelivertransplantpatient.Allotherpossiblecausesofelevatedtacrolimusandacutekidneyinjurywereruledout.TheinteractionwasattributedtolikelyinterferenceoftacrolimusmetabolismbyturmericviatheP4503Asystem,whichledtoacutecalcineurininhibitornephrotoxicity.DatafromanimalstudiesregardingthepotentialforturmerictoaffecttheP450systemsupportedtheconclusion.112OtherinteractiondataSomestudieshavereportedinsignificantpharmacokineticdruginteractionswithnaturalproducts.Limitedinformationaswellaspotentiallyhighinterpatientvariabilityinclinicalresponsewarrantscautiousinterpretationand/orapplicationofthesedatainpractice.Asmallpharmacokineticinteractionsstudyinhealthyvolunteerswhoreceivedcurcuminoid4g4timesdailyfor2dayspriortooraladministrationofsingledosesofmidazolam,flurbiprofen,andacetaminophenfoundnosignificantchangesinpharmacokineticparametersincludingCmax,areaunderthecurve,andterminalhalf-life.Investigatorsselectedtheseagentstoprobecytochrome(CYP)3a(midazolam),2C9(flurbiprofen),sulfotransfer,andUDP-glucuronosyltransferase(acetaminophen).94AdverseReactions Trialshavegenerallyreportedfewadversereactionsassociatedwithturmericorcurcuminingestion,evenatthehighdosagesusedincancertrials.10,25GI-relatedsymptomshavebeenreported.2,7,25,103Allergiccontactdermatitiswasreportedin2patientsafterusingcurcumin-containingchlorhexidinesolutions,82andpatchtestswerepositiveforcurcumininbothcases.Acaseofanaphylaxisafterturmericingestionhasbeendocumented.83Overa3-dayperiod,thepatientexperiencedrecurrenturticariaandangioedemathatwasunresponsivetotreatmentwithepinephrine,antihistamines,andcorticosteroids.Allergytestingforturmericwaspositive.Areviewidentified3studies(n=121)and10casereportsconfirmingallergenicpotentialofcurcuminviapatchandskinpricktesting.104A2017FDASafetyAlertdocumented2acuteserioushypersensitivitycasesresultingfromtheIVinjectionofacurcuminemulsioncompoundedwithpolyethyleneglycol(PEG)40castoroil.Thelatterisanungradedproductthatisnotsuitableforhumanconsumptionandisknowntocausehypersensitivityreactions.Bothpatientshadapositivehistoryofallergies;1casewasfatal.ThesafetyprofileofcurcuminadministeredbytheIVroutehasnotbeenestablished.TheFDArecommendationwasfortherecallofallunexpiredproductscontainingtheungradedPEG40castoroilbythecompoundingagent,ImprimisRx.115Turmericcontainsrelativelyhighconcentrationsofoxalate,andincreasedlevelsofurinaryoxalateexcretionhavebeendemonstrated.52Althoughtheriskofkidneystoneformationmaybeincreasedinsusceptibleindividuals,reportsofkidneyproblemsarelacking.Theadditionofcurcumintothedietsofmiceinducediron-deficiencyanemia,includingadeclineinserumiron,decreasedhematocrit,decreasedtransferrinsaturation,andappearanceofhypochromicRBCs.Curcuminalsodecreasedironlevelsinthebonemarrowandspleen.84Datacollectedbetween2004and2013among8UScentersintheDrug-inducedLiverInjuryNetworkrevealed15.5%(130)ofhepatotoxicitycaseswascausedbyherbalsanddietarysupplementswhereas85%(709)wererelatedtomedications.Ofthe130relatedcasesofliverinjuryrelatedtosupplements,65%werefromnon-bodybuildingsupplementsandoccurredmostofteninHispanic/Latinoscomparedtonon-Hispanicwhitesandnon-Hispanicblacks.Livertransplantwasalsomorefrequentwithtoxicityfromnon-bodybuildingsupplements(13%)thanwithconventionalmedications(3%)(P<0.001).Overall,thenumberofsevereliverinjurycaseswassignificantlyhigherfromsupplementsthanconventionalmedications(P=0.02).Ofthe217supplementproductsimplicatedinliverinjury,turmericwasamongthe22%(116)ofthesingle-ingredientproducts.108Toxicology Evaluationofmicetreatedwithshort-andlong-termC.longaethanolicextractsof100mg/kg/dayfor90daysfoundnoseriousadversereactions.Weightwasnotaffectedbylong-termtreatment;however,changesinheartandlungweightwerereported,andwhiteandredbloodcelllevelswerereduced.85Theoralmedianlethaldose(LD50)ofcurcumininratsandmicewashigherthan2,000mg/kgbodyweight.86Noclinicalophthalmic,bodyweight,feedconsumption,ororganweightchangesweredocumentedina90-daytoxicitystudyinrats.Furthermore,noadverseeffectsfromthetoxicitystudywerenotedonhematology,serumchemistry,andurinalysis.IndexTerms CurcumadomesticaValReferences 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