ChemotherapyandAntiOxidants

Inthepastfewyearsithasbecomecommonpracticebyoncologiststoadvisepatientswhoare
undergoingchemotherapynottotakeantioxidantsupplements.Thereasoningbehindthisadviceis
thatchemotherapydestroyscancercellsbyinducingfreeradicalsandbypromotingoxidationofthe
cancercells.Antioxidants,onthecontrary,dotheexactopposite,i.e.theypreventfreeradicals(by
bindingtothem)andtheoxidationofcells.Intheory,therefore,itwouldseemtofollowlogicallythat
antioxidantsmayinterferewithchemotherapyandreduceitseffectiveness.Asweshallsee,inreality
itisnotassimpleasthat.
AsoncologistsalsoadviseagainsttheuseofChineseherbalremediesduringchemotherapy,Ishall
approachthissubjectfromtwoangles:
1. Whetheritistruethatantioxidantsinterferewithchemotherapy
2. WhetherthisappliestoChineseherbs
1.DOANTIOXIDANTSINTERFEREWITHCHEMOTHERAPY?
Oneparticulararticlewasinfluentialinshapingtheopinionthatantioxidantsinterferewith
chemotherapy.ThiswasthearticlewrittenbyDrGabriellaD'AndreafromtheMemorialSloan
KetteringCancerCenter,NewYorkinCancerJournalforCliniciansin2005.i
Inthisarticle,DrD'Andreastatesthat,"mechanisticconsiderationssuggestthatantioxidantsmight
reducetheeffectsofconventionalcytotoxictherapies.Preclinicaldataarecurrentlyinconclusiveand
alimitednumberofclinicalstudieshavenotfoundanybenefit.Cliniciansshouldadvisetheirpatients
againsttheuseofantioxidantdietarysupplementsduringchemotherapyorradiotherapy.Such
cautionshouldbeseenasthestandardapproachforanyunprovenagentthatmaybeharmful."
ItisinterestingthatDrD'Andreaagreesthat"preclinicaldataarecurrentlyinconclusive"andyetshe
stillcomestotheconclusionthat"cliniciansshouldadvisetheirpatientsagainsttheuseofantioxidant
dietarysupplementsduringchemotherapyorradiotherapy."Itisalsointerestingthatsheshould
attributetheopinionthatantioxidantsmightreducetheeffectsofcytotoxictherapyto"mechanistic
considerations":asweshallsee,theyareexactlythat,i.e."mechanistic".
Indeed,DrD'Andreatakesamechanisticviewinsaying"radiotherapyandmanychemotherapy
agentsactbyproducingfreeradicalssomevitaminsandsupplements,includingvitaminsCandE,
areantioxidantsandbindtofreeradicals,preventingoxidativedamage."Shecontinues:"Thereare
considerableinvitroandanimaldatashowingthatvitaminCandotherantioxidantscanprotectcells
againstradiationandchemotherapy.Itseemslikelythattheywouldthereforereducetreatment
relatedtoxicitiesandtherearepromising,althoughnotunequivocal,datathatthisindeedisthecase.
However,italsofollowsthatantioxidantsmightprotectcancercells,therebyreducingtheoncologic
effectivenessofcytotoxictherapy.Thisisthereasonwhymostoncologistsdiscouragepatientsfrom
usingantioxidantsduringtreatment."
However,DrD'Andreaherselfreportsthat"invitrostudieshavereportedthatvitaminsA,C,andE,
aswellascarotenoids,canenhancetheeffectivenessofchemotherapyandradiotherapy."Proponents
ofantioxidanttherapysayexactlythis,i.e.thattheprotectiveeffectsofantioxidantsareselectivefor
normalcells,suchthattheycanreducetoxicitieswithoutcompromisingoncologicefficacy.Theyalso
saythatantioxidantsaredirectlycytotoxicandcanactuallyincreasetheeffectivenessofcytotoxic
treatments.
DrD'AndreasaysthatthereareinvitrodatasuggestingadirectantitumoreffectforvitaminCbut

shequestionstheirvalidity.D'Incalcietalreviewedtheliteratureonantioxidantsandchemotherapy
forthelast15yearsandcametomuchmorecautiousconclusionsthanthosereachedbyD'Andrea.
D'Incalcietalsaythat"Studieshaveexploredtheeffectofpredominantlyantioxidantvitaminsand
folateonefficacyortoxicitymediatedbycisplatinandanthracyclins.Cisplatintoxicityinrodentswas
amelioratedbyvitaminE.Thedesignofclinicalstudiesofdietaryagentsincombinationwith
cytotoxicagentshasbeenveryheterogeneousandresultshavebeeninconclusive."iiTheyconclude
cautiouslythat"whilstpreclinicalexperimentshintatapotentialbenefitofcertaindietaryagents,the
evidenceemanatingfromclinicalstudiesdoesnotallowfirmconclusionstobemade.Futurestudies
shouldexplorephysiologicaldosesofdietaryagentandincludepharmacokineticand
pharmacodynamicmeasurements."iii
OtherresearcherstoocontestD'Andrea'sconclusions.Theymaintainthatantioxidantsgivenduring
chemoandradiotherapyinduceapoptosis,aprocesswherebycancercellsdieoffinanatural
manner.Cancercellsthatdieoffduetoapoptosisareliterallydigestedandremovedbyphagocytes,
thuspreventingtheinflammatoryresponseinducedbychemotherapy.Bycontrast,oxidationinduced
bychemotherapykillscancercellsinamannerthatresultsinmassesofdeadcells(withbroken
membranes)thatproduceinflammationandtoxicresponse.
Allcellshaveafinitelifespanandcelldeathoccursmainlyasaresultofpassivenecroticprocesses
orduetoanactiveprocessofprogrammedcelldeath,"apoptosis".Apoptosisisthemostcommon
mechanismbywhichthebodyeliminatesdamagedorunneededcellswithoutlocalinflammationfrom
leakageofcellcontents.
Cellsthatareundergoingapoptosisexhibitacharacteristicpatternofmorphologicchanges,including
cellshrinkage,condensation,fragmentationofthenucleusandbubblingoftheplasmamembrane,
knownas"blebbing",chromatincondensationandnucleosomalfragmentation.Theresulting
membraneboundapoptoticbodiesareconsumedbyneighboringcellsorbymacrophages.Incontrast,
thenecroticmodeofcelldeathrepresentsapassiveconsequenceofmechanicaldamageorexposure
ofthecellstotoxins(suchaschemotherapy).
However,someantineoplasticdrugskilltumorcellsbyinducingapoptosis.Asdescribedabove,this
highlycontrolledmechanismofcelldeathisthoughttobephysiologicallyadvantageousbecause
apoptoticcellsareremovedbyphagocytosisbeforetheylosetheirpermeabilitybarrier,thus
preventinginductionofaninflammatoryresponsetothedyingcells.Incontrast,necroticcellslyse
andreleasetheircontentsintotheextracellularspace,thusinducinginflammation.
Shacteretalexaminedtheeffectsofoxidativestressonchemotherapyinducedcellkilling.They
foundthatH2O2(hydrogenperoxide)inhibitstheabilityoffourdifferentchemotherapydrugs(VP
16,doxorubicin,cisplatin,andAraC)toinduceapoptosisinhumanBurkittlymphomacells.H2O2
shiftstheformofcelldeathfromapoptosistopyknosis/necrosis,whichoccursafterasignificant
delaycomparedwithchemotherapyinducedapoptosis.Itcanalsolowerthedegreeofcellkillingby
thesedrugs.TheseeffectsofH2O2canbepreventedbytheantioxidantagentsDesferal,Tempol,and
dimethylsulfoxide.
PhagocytosisbymonocytederivedmacrophagesofVP16treatedlymphomacellsisalsoinhibitedby
H2O2.CellskilledwithH2O2(withorwithoutVP16)doultimatelyundergophagocytosis,butthis
occursonlyaftertheyhavelosttheirpermeabilitybarrier.Thus,membraneintactapoptoticcellsare
recognizedandphagocytosedbymonocytederivedmacrophages,butmembraneintact
pyknotic/necroticcellsarenot.Theresultssuggestthatchemotherapyinducedapoptosisand
phagocytosisofcancercellsmaybeenhancedbyincludingcertainantioxidantagentsinthetreatment
protocol.iv
Inotherwords,therearesituationswhentheoxidativestressinducedbychemotherapyitselfmay

actuallyhindertheeffectsofchemotherapyandtheadditionofantioxidantsmay
actuallyhelpchemotherapytoworkinamorenatural,noninflammatoryway(i.e.throughapoptosis
ratherthannecrosis).
DrKennethConklinconfirmsthisinhisarticle"ChemotherapyAssociatedOxidativeStress:Impact
onChemotherapeuticEffectiveness".vInthisarticle,DrConklinsaysthat"Antineoplasticagents
induceoxidativestressinbiologicalsystems.Duringcancerchemotherapy,oxidativestressinduced
lipidperoxidationgeneratesnumerouselectrophilicaldehydesthatcanattackmanycellulartargets.
Theseproductsofoxidativestresscanslowcellcycleprogressionofcancercellsandcausecellcycle
checkpointarrest,effectsthatmayinterferewiththeabilityofanticancerdrugstokillcancercells.
Thealdehydesmayalsoinhibitdruginducedapoptosisbyinactivatingdeathreceptorsandinhibiting
caspaseactivity[thelatterwouldslowdowncelldisassembly].Theseeffectswouldalsodiminishthe
efficacyofthetreatment.Theuseofantioxidantsduringchemotherapymayenhancetherapyby
reducingthegenerationofoxidativestressinducedaldehydes."vi
DrConklinalsoconductedastudyonpatientswhowerereceivingchemotherapy(anthracyclines)for
breastcancerandlymphoma.CoenzymeQ10wasadministeredinconjunctionwithchemotherapy.
ResultsshowedthattheadministrationofQ10resultedinfewercardiomyopathy(asideeffectof
anthracyclines).DrConklinsaysinthesummaryofthestudy:"Thereisconcernwithintheoncology
communitythatconsumptionofantioxidantsduringchemotherapywillreducetheeffectivenessofthe
treatment.Cytotoxicantineoplasticagentsgeneratereactiveoxygenspecies(ROS)inbiological
systemsandmanyoncologistscontendthatthisaccountsfor,orcontributesto,theanticancer
activityofthedrugs.However,allofthedrugshave[theirown]establishedmechanismsofaction
thatdonotdepend[always]upontheirproductionofROS.ROScanreducetheefficacyof
chemotherapybecausetheyinterferewithcellcycleprogressionandapoptoticmechanisms.Thus,
antioxidantsshouldnotinterferewiththemechanismofactionofantineoplasticagents,andmay
enhancetheireffectsbypreventingtheimpactofROSonthecellcycleandapoptosis.Theresultsof
thepresentstudysupportthecontentionthatantioxidantsdonotinterferewiththeanticancereffects
ofantineoplasticagents.Additionally,theadministrationofcoenzymeQ10duringthe
patients'anthracyclinebasedchemotherapyappearstohavepreventedanycardiacdamage."vii
Blocketalalsoreviewedtheliteratureonantioxidantsandchemotherapyandcametothesame
conclusion.DrBlock,oftheBlockCenterforIntegrativeCancerTreatment,says:"Thisreview
demonstratesthatthereisnoscientificsupportfortheblanketobjectiontousingantioxidantsduring
chemotherapy.Inaddition,italsoappearsthatthesesupplementsmayhelpmitigatethesideeffectsof
chemotherapy."viii
Thestudyconsidered845articlesand19trialsmettheinclusioncriteria.Antioxidantsevaluated
were:glutathione(7),melatonin(4),vitaminA(2),anantioxidantmixture(2),vitaminC(1),N
acetylcysteine(1),vitaminE(1)andellagicacid(1).Subjectsofmoststudieshadadvancedor
relapseddisease.
Theconclusionwasthatnoneofthetrialsreportedevidenceofsignificantdecreasesinefficacyfrom
antioxidantsupplementationduringchemotherapy.Manyofthestudiesindicatedthatantioxidant
supplementationresultedineitherincreasedsurvivaltimes,increasedtumorresponses,orboth,as
wellasfewertoxicitiesthancontrols.15of17trialsthatassessedchemotherapytoxicities,including
diarrhea,weightloss,nervedamageandlowbloodcounts,concludedthattheantioxidantgroup
sufferedsimilarorlowerratesofthesesideeffectsthanthecontrolgroup.
CoauthorDr.RobertNewman,ProfessorofCancerMedicineatM.D.AndersonCancerCentersaid,
"Thisstudy,alongwiththeevolvingunderstandingofantioxidantchemotherapyinteractions,
suggeststhatthepreviouslyheldbeliefsaboutinterferencedonotpertaintoclinicaltreatment."ix
Theauthorsnotedthatreducingsideeffectsmayhelppatientsavoidhavingtocutbackontheir
chemotherapydosing,interruptscheduledtreatments,orabandontreatmentaltogether.Thisinturn,is

likelytofavorablyimpacttreatmentoutcomes.
2.CHINESEHERBSANDCHEMOTHERAPY
HowdoesthisaffecttheuseofChineseherbsduringchemotherapy?Muchoftheabovediscussion
onantioxidantsandchemotherapyactuallydoesnotapplytoChineseherbsastheycontainfew
antioxidantsandindosesthatwouldbeakintothosefoundinfoods.Betacarotene,forexample,isa
powerfulantioxidant.Betacaroteneisfoundincarrots,sweetpotatoes,kale,spinach,wintersquash,
cilantro(coriander)andthyme.
OnlyHypericum(StJohn'sWort)maypresentsomeinteractionwithchemotherapy.Infact,thisherb
lowerstheavailabilityofsomedrugsasitactivatesthedrugmetabolizingenzymecytochromeP450
CYP3A4.HypericumisusedinChinesemedicinebutnotwidelyanditisnotincludedinChemo
Support.VeryfewChineseherbscontainVitCand,iftheydo,itwouldbeinminimaldoses.
TheonlyingredientofChemoSupportthathasamildantioxidanteffectisDangGuiRadixAngelicae
sinensis:consideringthisisonlyoneoutof16ingredients,theoverallantioxidanteffectofChemo
Supportisnegligible.Inconclusion,eating2poundofcarrots,drinkingaglassoforangejuiceanda
cupofgreenteawoulddeliverfarmoreantioxidantsthan6tabletsofChemoSupport.Thereis
thereforeabsolutelynojustificationforrecommendingnottotakeChemoSupportwhileon
chemotherapy.
3.CHEMOSUPPORT:PROTOCOLANDDOSAGE
ChemoSupportworksbetterifitisstartedsometimebeforethebeginningofchemotherapyand
continuedforabout4weeksaftertheend.Itisimportanttonotethat"duringthetreatment"means
duringthecourseoftreatment,i.e.alsointhedaysofbreakfromthetreatment.Thedosageisas
follows:
Twoweeksbeforethestartoftreatment:3tabletsaday
Fourdaysbeforethestartoftreatment:2tabletstwiceaday
Duringthetreatment:3tabletsthreetimesaday
Aftertheendoftreatmentfor4weeks:2tabletstwiceaday
Itisbesttotakethetabletsawayfrommeals,i.e.about1hourbeforeorafterameal,swallowedwith
hotwater.Thetabletsshouldalsobetakenseparatelyfromothermedication,atleast1houraway.If
thepatientfeelsverynauseousandfindsitdifficulttoswallowthetablets,thesecouldbecrushedand
powdered,immersedinasmallamountofhotwaterwiththreeslicesoffreshgingerandthewater
sippedslowly.
Thedosageduringtreatmentindicatedaboveshouldbeadjustedaccordingtotheseverityoftheside
effectsandtheabovedosagecouldbereducedorincreased.
IfthepatientisreceivingbothchemoandradiotherapyandistakingbothChemoSupportandRadio
Support,thedosageofeachshouldbereduced.Adjustmentscanbemadeaccordingtothepatient's
sideeffectsandtimingoftherapiesinthissituationbyusingahigherratioofChemoSupportduring
thedayssurroundingchemotherapyorwhenitssideeffectsareheightened.Similarly,thedosage
ofRadioSupportcanbeincreasedifthesideeffectsexperiencedfromradiotherapyaremoresevere,
orduringthedayssurroundingtheadministrationofradiotherapy.
ChemoSupportshouldbediscontinuedapproximatelyfourweeksaftertheendofthetreatmentwhen
theconditionshouldbereassessedandadifferentformulagiven.Bycontrast,RadioSupportshould
becontinuedforatleast6weeksaftertheendofradiotherapy.
TESTIMONIALS

AInthepast21/2years,Ihavebeendiagnosedwithrectalcancerandlivercancermetastases.Iama
52yearoldman.Throughoutmytreatment,whichhasbeen,tosaytheleast,extremelychallenging,
Ihavereceivedacupuncturetreatmentsregularlytorelievethesideeffectsofmychemotherapyandto
helpmehealfrommysurgeries.
However,althoughIhaveweatheredmytreatmentsprettywell,Iwascontinuingtogetmoreand
morefatiguedwithfoggythinkingandwasbeginningtohaveseveredigestiveissues.
"MyacupuncturistprescribedChemoSupporttohelpmewiththesesideeffects.WhenIbeganto
takeit(intheweeksbetweenmysemimonthlychemotherapy)InoticedalmostimmediatelythatI
wasabletothinkclearerandtofeelstronger.Infact,witheachsubsequentchemotreatmentIseemto
bemoreresilient,havinglessseverereactionstothosetreatmentswithmorerestfulsleep,nomore
digestiveissues.Myqualityoflifehasimprovedtremendouslyoverall,betweentheacupunctureand
now,becauseoftheChemoSupport."
C.S.
"IhavetreatedovertwentypatientswithChemoSupportforanaverageoffourtosixmonths.Ihave
observedandmypatientshavereportedtofindChemoSupportbeneficialforimprovingenergyand
indecreasingthesideeffectsofnauseaandvomiting."
LucyPostolova,L.Ac.
LosAngeles,CA
"At[our]clinicweusebothChemoSupportandRadioSupportformanyofourpatients.Ihave
definitelyseenlessfatigueinthewomenIhavetreatedwithChemoSupport.Theyreportthattheir
energyandstaminaareimprovedandthereislessoccurrenceofanemiaassociatedwith
chemotherapy.Oneofmypatientswasreferredtomeaftershehadundergonetworoundsof
chemotherapy.Shewasexhausted,verydepressed,andfeltverydryanddepleted.ShewasonChemo
Supportforthelastroundoftherapyandshefeltmuchlessexhausted,herenergyincreasedandshe
hadfewersensationsofheatandnightsweating."
RobinGermain,L.Ac.
SanFrancisco,CA
"Ihavebeentreatingseveralwomenwithbreastcancerwhohavebeenundergoingchemotherapy.
ThepatientwhoistakingChemoSupporthashadconsiderableimprovementwithherdigestive
function.PriortotakingChemoSupport,shewassufferingfromburning,painfuldiarrheawhichisno
longeraproblem.Sheisverypleasedwithherherbaltreatment."
DianneGobrogge,L.Ac.
Wilmington,NC
"WefindChemoSupporttobebeneficialintheinitialtreatmentofStageIandStageIIbreastcancer,
andespeciallyincombinationwithotherformulas(suchasBrocadeSinewswithChemoSupportfor
usewithTaxolandGloriousSeaandChemoSupportwhenusingNavelbine).Alongwith
acupuncture,ChemoSupportishelpfulinsupportingtheQiandhelpingthepatienttolerate
chemotherapy."
BeverlyBurns,L.Ac.
SanFrancisco,CA

i.GabriellaM.D'Andrea,MD"UseofAntioxidantsDuringChemotherapyandRadiotherapyShould
BeAvoided",CancerJournalforClinicians200555:31921.
ii.D'IncalciM,StewardW,GescherA"ModulationofResponsetoCancerChemotherapeuticAgents
byDietConstituentsIstheAvailableEvidenceSufficientlyRobustforAdvicetoPatients?",Cancer

TreatmentReview,May2007,pp223229.
iii.Ibid.
iv.ShacterE,WilliamsJ,HinsonR,SentrkerS,LeeY"OxidativeStressInterfereswithCancer
Chemotherapy:InhibitionofLymphomaCellApoptosisandPhagocytosis,Blood96:307132000."
v.ConklinK,"ChemotherapyAssociatedOxidativeStress:ImpactonChemotherapeutic
Effectiveness",IntegrativeCancerTherapies3(4)2004:294300.
vi.Ibid.,p.294.
vii.ConklinK"CoenzymeQ10forPreventionofAnthracyclineInducedCardiotoxicity",Journalof
theSocietyofIntegrativeOncology20075:188.
viii.BlockK,KochA,NewmanR,TothyP,GyllenhaalC,"ImpactofAntioxidantSupplementation
onChemotherapeuticEfficacy:aSystematicReviewoftheEvidencefromRandomizedControlled
ClinicalTrials",CancerTreatmentReview,2007Aug33(5):40718.
ix.ScienceDailyApr.27,2007.

Copyright(c)GiovanniMaciocia2009