Herbs in Chronic Kidney Disease Panacea Or Poison?

Herbs in Chronic Kidney Disease Panacea or Poison?

Anar Dossa B.Sc.Pharm. CDE October 12, 2007 BC Nephrology Days NoniNoni onon thethe 9999

„ KillsKills harmfulharmful microbes,microbes, lowerslowers bloodblood pressurepressure –– H.H. SimSim (1993)(1993)

„ InhibitsInhibits growthgrowth oror completelycompletely eradicateseradicates somesome cancerscancers suchsuch asas LewisLewis lunglung carcinomacarcinoma andand SarcomaSarcoma--180180 byby stimulatingstimulating thethe immuneimmune systemsystem –– A.A. HirazumiHirazumi (1997)(1997) NoniNoni onon thethe 9999

„ GoodGood sourcesource ofof potassiumpotassium andand vitaminvitamin CC –– N.N. PeerzadaPeerzada (1990)(1990)

„ MorindaMorinda andand itsits distributorsdistributors makemake nono curativecurative claimsclaims forfor itsits productproduct NoniNoni onon thethe 9999

„ ‘‘AA simplesimple giftgift fromfrom aa pristinepristine paradiseparadise hashas setset inin motionmotion aa missionmission thatthat willwill capturecapture thethe attentionattention ofof thethe worldworld’’ „ SalesSales inin CanadaCanada andand US:$72,000,000US:$72,000,000 inin firstfirst yearyear „ LucrativeLucrative leadershipleadership bonusesbonuses –– payspays 88 levelslevels Noni Juice

• Case : hyperkalemia despite adhering to low potassium diet

• Upon questioning, had started noni juice purchased from health food store

• Asked to stop consuming noni juice because other juices known to have high potassium content

• Heard from relative that noni juice had cured him of cancer

Am J Kidney Dis 2000:35(2);310-2 Noni Juice

• Brother who also had renal disease took noni juice and instructed him to take noni juice regularly to improve energy level

• “did not understand the power of noni juice”

• Never returned to clinic

Am J Kidney Dis 2000:35(2);310-2 Noni Juice – Literature Search

• No information on internet or medical literature on potassium content • Lab assay: potassium = 56.3 mEq/L • Orange Juice: potassium = 51 mEq/L

Am J Kidney Dis 2000:35(2);310-2 „ NaturalNatural KidneyKidney FlushFlush HerbalHerbal TeaTea „ 75%75% CanadiansCanadians havehave usedused herbalherbal medicinemedicine „ MoreMore commoncommon inin peoplepeople withwith chronicchronic conditionsconditions „ WomenWomen >> MenMen „ 75%75% worldworld populationpopulation dependdepend onon botanicalbotanical medicinesmedicines forfor basicbasic healthhealth carecare

Bagnis et al Am J Kidney Dis 2004;44:1-11 HowHow manymany ofof youyou havehave usedused aa herbalherbal product?product?

„ NotNot forfor oror againstagainst „ NextNext yearyear maymay bebe sayingsaying somethingsomething differentdifferent „ EvidenceEvidence basedbased WhyWhy areare youyou takingtaking herbalherbal supplement?supplement?

„ MedicalMedical systemsystem tootoo impersonalimpersonal „ HolisticHolistic approachapproach isis notnot takentaken byby healthhealth carecare providersproviders whereaswhereas itit isis withwith alternativealternative healthhealth carecare practitionerspractitioners „ PatientPatient centeredcentered vsvs treatmenttreatment centeredcentered HistoricalHistorical PerspectivePerspective

„ PostPost secondsecond worldworld warwar „ ↑↑ syntheticsynthetic drugsdrugs „ Science vs blind faith „ ↓↓ herbalherbal productsproducts PrescribedPrescribed MedicationsMedications

„„ BirthBirth defectsdefects „„ SevereSevere sideside effectseffects „ PrescribedPrescribed medicationsmedications „ ArtificialArtificial „ ToxicToxic

„ HerbalHerbal productsproducts „ NaturalNatural „ SafeSafe PlantsPlants

„ SynthesizeSynthesize complexcomplex moleculesmolecules forfor structurestructure andand functionfunction „ RichRich sourcesource ofof chemicalschemicals „ PurifiedPurified chemicalschemicals fromfrom plantsplants havehave beenbeen usedused asas medicinesmedicines „ DigoxinDigoxin,, morphinemorphine „ >50%>50% ofof westernwestern drugsdrugs areare derivedderived fromfrom plantsplants

„ PartsParts ofof plantsplants oror crudecrude extractsextracts „ HerbalHerbal medicinesmedicines „ Hundreds of chemicals „ Influenced by species, variety, part of plant „ Conditions of growth (soil, temperature, water) StandardizationStandardization

„ UniqueUnique identifieridentifier „ NotNot necessarilynecessarily activeactive ingredientingredient „ DifficultDifficult „ SeldomSeldom accomplishedaccomplished NationalNational InstitutesInstitutes ofof HealthHealth GlucosamineGlucosamine „ CouldCould notnot findfind satisfactorysatisfactory sourcesource ofof glucosamineglucosamine andand chondroitinchondroitin forfor studystudy „ BatchBatch toto batchbatch variabilityvariability „ ManufacturedManufactured itit themselvesthemselves „ HowHow areare patientspatients goinggoing toto accessaccess this?this?

Medical Letter 2002:44(1140);84-86 NaturalNatural HealthHealth ProductProduct RegulationsRegulations „ NaturalNatural healthhealth productsproducts cancan bebe soldsold eithereither asas foodfood oror drugsdrugs „ VoluntaryVoluntary „ DrugDrug „ DrugDrug IdentificationIdentification NumberNumber „ FoodFood „ DoDo notnot provideprovide adequateadequate safetysafety informationinformation onon theirtheir labelslabels DrugDrug IdentificationIdentification NumberNumber (DIN)(DIN)

„ LackLack ofof DINDIN doesdoes notnot implyimply inferiorityinferiority „ DINDIN doesdoes notnot guaranteeguarantee safetysafety oror qualityquality „ ApplyingApplying forfor DINDIN isis voluntaryvoluntary „ SameSame productproduct cancan bebe soldsold asas drugdrug (DIN)(DIN) oror foodfood (no(no DIN)DIN) KavaKava andand LiverLiver FailureFailure

„ UsedUsed forfor manymany indicationsindications includingincluding insomniainsomnia „ StudyStudy atat VGHVGH „ FourFour casescases ofof liverliver toxicitytoxicity inin CanadaCanada „ ThirtyThirty--ninenine casescases ofof liverliver injuryinjury inin GermanyGermany „ 33 fatalitiesfatalities Kava may be identified as: •kava •ava •maluk •kava kava •ava pepper •meruk •kava-kava •ava root •milik •kava root •awa •kew •kava-kava root •gea •Rauschpfeffer •kavain •gi •sakau •kava pepper •intoxicating pepper •tonga •kavapipar •intoxicating long pepper •Wurzelstock •kawa •kao •yagona •kawa kawa •Piper methysticum •yangona •kawa pepper •Macropiper Latifolium •yaqona •kawapfeffer •Piper inebrians •maori kava •rhizoma di kava- kava www.hc-sc.gc.ca/english/protection/warnings/2002/2002_56ebk.htm TheThe ChallengeChallenge

„ SomeSome ofof thesethese productsproducts havehave drugdrug identificationidentification numbers,numbers, othersothers dodo notnot ChineseChinese HerbalHerbal ProductProduct forfor WeightWeight LossLoss CausesCauses RenalRenal FailureFailure

„ 7070 patientspatients requiredrequired dialysis,dialysis, transplantationtransplantation „ 1818 developeddeveloped urothelialurothelial cancercancer „ CauseCause „ AristolochicAristolochic AcidAcid „ Probably included in product by mistake

Medical Letter 2002:44(1140);84-86 PCPC SpesSpes forfor ProstateProstate HealthHealth

„ contaminatedcontaminated withwith „ WarfarinWarfarin „ AlprazolamAlprazolam „ IndomethacinIndomethacin „ DiethylstilbestrolDiethylstilbestrol

Medical Letter 2002:44(1140);84-86 TungTung ShuehShueh

„ PromotedPromoted forfor problemsproblems ofof thethe heart,heart, liverliver andand kidneykidney „ ChemicalChemical analysisanalysis perper pill:pill: „ 3.86mg3.86mg indomethacinindomethacin „ 16mg16mg mefenamicmefenamic acidacid „ 8mg8mg diclofenacdiclofenac „ 0.73mg0.73mg diazepamdiazepam „ Directions:Directions: 44 pillspills threethree timestimes perper dayday

Annals of Pharmacotherapy 1996:30;79-80 TungTung ShuehShueh

„ ListsLists 2121 activeactive ingredientsingredients „ DiazepamDiazepam andand mefenamicmefenamic acidacid „ NotNot includedincluded „ SyntheticallySynthetically derivedderived „ AdulteratedAdulterated purposefullypurposefully RedRed YeastYeast RiceRice andand RhabdomyolysisRhabdomyolysis

„ 2828 y.o.y.o. renalrenal transplanttransplant patientpatient „ RefusedRefused statinstatin therapytherapy „ OptedOpted toto naturallynaturally lowerlower cholesterolcholesterol „ CPKCPK inin 22 monthsmonths waswas 26002600 U/LU/L (N<(N< 130130 U/L)U/L) „ CPKCPK ↓↓ 600600 U/LU/L 22 weeksweeks afterafter herbherb discontinueddiscontinued

Canadian Adverse Reaction Newsletter 2003:13(3) RedRed YeastYeast RiceRice andand RhabdomyolysisRhabdomyolysis

„ ContainsContains anan ingredientingredient similarsimilar toto lovastatinlovastatin „ StatinsStatins interactinteract withwith cyclosporinecyclosporine increasingincreasing statinstatin levelslevels

Canadian Adverse Reaction Newsletter 2003:13(3) ChineseChinese HerbalHerbal RemediesRemedies

„ MultiMulti--ingredientingredient combinationscombinations „ DifficultDifficult toto findfind informationinformation „ PowerfulPowerful radio/TVradio/TV advertisementsadvertisements „ VeryVery expensiveexpensive Natural Health Products – New Regulations

http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/npn_label_e.pdf WhatWhat doesdoes thethe newnew labellinglabelling mean?mean? „ InformedInformed choicechoice „ AssuranceAssurance ofof thethe productproduct’’ss „ SafetySafety „ QualityQuality „ ClaimClaim „ ConfidenceConfidence inin knowingknowing whatwhat isis onon thethe labellabel isis inin thethe bottlebottle http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/npn_label_e.pdf http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/npn_label_e.pdf http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/npn_label_e.pdf http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/npn_label_e.pdf NaturalNatural HealthHealth ProductProduct RegulationsRegulations „ EffectiveEffective JanuaryJanuary 1,1, 20042004 „ TransitionTransition periodperiod „ 22 yearsyears „ Site licensing and employ good manufacturing processes „ 66 yearsyears „ Product licensing, DIN products will be transferred to NPN or DIN-HM (homeopathic medicine)

http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/nhp_regs_e.html 2006 Canadian Cholesterol Guidelines Can J Cardiol 2006;22:913-927 TraditionalTraditional ChineseChinese HerbalistsHerbalists

„ TreatingTreating peoplepeople withwith CKDCKD forfor thousandsthousands ofof yearsyears „ ConcoctionsConcoctions includeinclude diureticsdiuretics ++ herbsherbs STST

„ CombinationCombination ofof 1212 herbsherbs usedused inin ChinaChina andand JapanJapan forfor kidneykidney diseasedisease „ AnimalAnimal studiesstudies „ Decreased blood pressure and protein excretion „ PediatricPediatric IgAIgA nephropathynephropathy „ Decreased protein excretion „ InsufficientInsufficient evidenceevidence toto recommendrecommend atat thisthis timetime

Wojcikowki et al J Lab Clin Med 2006;147:160-6 St.St. JohnJohn’’ss WortWort

„ AntidepressantAntidepressant „ ProposedProposed mechanismmechanism ofof actionaction „ InhibitsInhibits reuptakereuptake ofof serotonin,serotonin, dopamine,dopamine, norepinephrinenorepinephrine „ EffectivenessEffectiveness „ MildMild toto moderatemoderate depressiondepression St.St. JohnJohn’’ss WortWort

„ ToxicityToxicity „ GenerallyGenerally wellwell toleratedtolerated „ Insomnia,Insomnia, anxiety,anxiety, headacheheadache „ DoseDose „ VariableVariable dependingdepending onon standardizationstandardization St.St. JohnJohn’’ss WortWort

„ DrugDrug interactionsinteractions „ ManyMany seriousserious interactionsinteractions reportedreported „ CanCan decreasedecrease cyclosporinecyclosporine levelslevels byby 3030--70%70% „ Has led to transplant rejection „ BannedBanned inin FranceFrance duedue toto manymany drugdrug--herbherb interactionsinteractions

•www.naturaldatabase.com KidneyKidney Disease:SpecialDisease:Special ConsiderationsConsiderations „ UnpredictableUnpredictable pharmacokineticspharmacokinetics „ PolypharmacyPolypharmacy „ St.JohnSt.John’’ss WortWort andand CyclosporineCyclosporine „ DialyzabilityDialyzability „ CalciumCalcium CarbonateCarbonate „ HealthHealth foodfood storestore insteadinstead recommendedrecommended calciumcalcium citratecitrate withwith magnesiummagnesium WatchWatch outout forfor herbalsherbals with:with:

„ AntiAnti--inflammatoryinflammatory activityactivity „ MayMay affectaffect kidneykidney functionfunction „ WeightWeight lossloss activityactivity „ MayMay affectaffect electrolyteselectrolytes „ MayMay affectaffect bloodblood pressurepressure „ DiureticDiuretic activityactivity Monitoring

• If you wish to use, be informed, monitor closely

• Record brand and ingredients

• Always maintain same brand

• Include in your medication list Monitoring

• Keep a diary – start low and increase slowly – consider starting at half the dose recommended on the label – report adverse reactions – reassess, reassess, reassess Limitations

• Product used in studies not necessarily what is available on the market • Long-term safety not generally known • Qualifications of individual providing products GuidingGuiding PrinciplesPrinciples

„ DoDo nono harmharm „ NeedNeed forfor dialoguedialogue „ WithWith patientspatients „ WithWith otherother healthhealth carecare providersproviders „ TakeTake responsibilityresponsibility forfor recommendationsrecommendations „ RespectRespect patientpatient autonomyautonomy

Heather Boon, B.Sc.Pharm, PhD ReportingReporting AdverseAdverse ReactionsReactions

„ Phone:Phone: 11--866866--234234--23452345 „ Fax:Fax: 11--866866--678678--67896789 „ Online:Online: www.healthcanada.gc.ca/medeffectwww.healthcanada.gc.ca/medeffect „ Form:availableForm:available inin thethe CPSCPS –– lastlast pagepage ReferencesReferences

„ www.naturaldatabase.comwww.naturaldatabase.com „ Available free on-line if you have UBC library card „ www.quackwatch.comwww.quackwatch.com „ ChandlerChandler F.F. Herbs:everydayHerbs:everyday referencereference forfor healthhealth professionals.professionals. Ottawa,Ottawa, CPhACPhA && CMACMA 20002000 „ CochraneCochrane DatabaseDatabase ofof SystematicSystematic ReviewsReviews „ Chinese medicinal herbs for diabetic kidney disease