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w w w . j c o l . o r g . b r

Journal

of

Coloproctology

Original

Article

A

double-blind,

randomized

and

placebo-controlled

clinical

trial

with

Agaricus

sylvaticus

fungus

in

anthropometric

profile

of

women

with

colon

cancer

Renata

Costa

Fortes

a,b,∗

,

Jhuly

Amado

Souza

b

,

Maria

Rita

Carvalho

Garbi

Novaes

c

aCursodeNutric¸ão,InstitutodeCiênciasdaSaúde,UniversidadePaulista(UNIP),Brasília,DF,Brazil

bProgramadeResidênciaemNutric¸ãoClínica,HospitalRegionaldaAsaNorte,SecretariadeEstadodeSaúdedoDistritoFederal

(HRAN/SES/DF),Brasília,DF,Brazil

cCursodeMedicina,EscolaSuperiordeCiênciasdaSaúde(ESCS),Fundac¸ãodeEnsinoePesquisaemCiênciasdaSaúde(FEPECS),

SecretariadeEstadodeSaúdedoDistritoFederal(HRAN/SES/DF),UniversidadedeBrasília(UnB),Brasília,DF,Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received22February2014 Accepted27July2014

Availableonline28January2015

Keywords:

Anthropometry Colorectalcancer

Agaricussylvaticusfungi

a

b

s

t

r

a

c

t

Introduction:Colorectalcancerisadiseaseinfluencedbygeneticandenvironmentalfactors. Medicinalfungiand/oritsextractshavebeenusedintheadjuvanttherapyofcancerbecause oftheirpharmacological,nutritionalandimmunomodulatoryproperties.

Objective:Toevaluatetheanthropometricprofileofcolorectalcancerwomenafterdietary supplementationwithAgaricussylvaticusfungus.

Methods:Randomized,double-blind,placebo-controlledclinicaltrialwasconductedina publichospitalintheFederalDistrict–Brazilforsixmonths.Sampleof32patientswith colorectalcancer,female,wasseparatedintotwogroups:supplementedwithAgaricus syl-vaticus(30mg/kg/day)andplacebo.Weconductedanthropometry(weight,height,bodymass index,armcircumference,tricepsskinfold,armmusclecircumferenceandfatpercentage) duringthetreatment.Theresultswereanalyzedatthreedifferenttimes(beforethestartof treatment,threemonthsandaftersixmonthssupplementation)usingtheMicrosoftExcel 2007andSPSS19.0,usingStudent’st-testandF,withsignificanceforp≤0.05.

Results:TheAgaricussylvaticusgroupshowedasignificantincreaseinbodymassindex,arm circumference,percentbodyfatandtricepsskinfold,andnon-significantincreaseinarm musclecircumferenceaftersixmonthsofsupplementation.Theseresultswerenotobserved intheplacebogroup.

Conclusion:TheresultssuggestthatdietarysupplementationwithAgaricussylvaticusis capa-bletohavebenefitsinanthropometricparametersofwomenwithcolorectalcancer.

©2015SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.All rightsreserved.

Correspondingauthorat:CursodeNutric¸ão,InstitutodeCiênciasdaSaúde,UniversidadePaulista(UNIP),Brasília,DF,Brazil.

E-mail:fortes.rc@gmail.com(R.C.Fortes). http://dx.doi.org/10.1016/j.jcol.2015.01.001

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Ensaio

clínico

duplo

cego,

randomizado

e

placebo

controlado

com

fungos

Agaricus

sylvaticus

no

perfil

antropométrico

de

mulheres

com

câncer

colorretal

Palavras-chave:

Antropometria Câncercolorretal FungosAgaricussylvaticus

r

e

s

u

m

o

Introduc¸ão: Ocâncercolorretaléumadoenc¸ainfluenciadaporfatoresgenéticose ambi-entais. Autilizac¸ão de fungos medicinais e/oude seus extratostem sidoutilizada no adjuvantetratamentodocâncerdevidoàssuaspropriedadesfarmacológicas,nutricionais eimunomoduladoras.

Objetivo: Avaliar o perfil antropométrico de mulheres com câncer colorretal após suplementac¸ãodietéticacomfungosAgaricussylvaticus.

Métodos:Ensaioclínicorandomizado,duplo-cego,placebo-controladorealizadoemum hos-pitalpúblicodoDistritoFederalBrasilporseismeses.Amostraconstituídapor32pacientes comcâncercolorretal,sexofeminino,separadosemdoisgrupos:suplementadocom Agar-icussylvaticus(30mg/kg/dia)eplacebo.Realizou-seaantropometria(peso,estatura,índice demassacorporal,circunferênciadobrac¸o,dobracutâneatricipital,circunferência muscu-lardobrac¸oepercentualdegordura)aolongodotratamento.Osresultadosforamanalisados emtrêsmomentosdistintos(antesdoiníciodotratamento,comtrêsmeseseapósseis mesesdesuplementac¸ão),utilizandoosprogramasMicrosoftExcel2007eSPSS19.0,por meiodostestesT-studenteF,comsignificânciaparap≤0,05.

Resultados:OgrupoAgaricussylvaticusapresentouaumentosignificativodeíndicedemassa corporal,circunferênciadobrac¸o,percentualdegorduracorporaledobracutânea tricip-tale,aumentonãosignificativodecircunferênciamusculardobrac¸oapósseismesesde suplementac¸ão.Essesresultadosnãoforamobservadosnogrupoplacebo.

Conclusão: Osresultadossugeremqueasuplementac¸ãodietéticacomAgaricussylvaticus écapazdeexercerbenefíciosnosparâmetrosantropométricosdemulherescomcâncer colorretal.

©2015SociedadeBrasileiradeColoproctologia.PublicadoporElsevierEditoraLtda. Todososdireitosreservados.

Introduction

Nowadays,duetoitsincreasingincidence,cancerhasbecome apublichealthproblemworldwide,1paripassuwiththe

pro-gressive aging of the population, as a consequence of an increasedlifeexpectancy.2

Colorectalcancerisacommonanddeadlydisease, influ-encedbygeneticandenvironmentalfactorsandalsobythe mutualinfluenceofboth.Geneticpredispositionisa predom-inantriskfactorforsomeindividuals;however,environmental factors,includingdiet,physicalactivity,smokingandobesity, arealsoincludedamonghigh-riskfactors.2

Asfortheriskofdevelopingcolorectalcancer,patientscan bedividedasfollows:thoselessthan50yearsandno fam-ilyhistoryofcolorectalcancerareatlowrisk;thoseaged50or moreandwithnootherriskfactorsareincludedintheaverage riskgroup;patientswithpersonalhistoryofpolypsor colorec-talcancer,orwithafamilyhistoryofcolorectalcancerorwith first-degreerelativesdiagnosedwithpolypsareclassifiedas high-riskpeople;andfinally,theveryhigh-riskclassification comprisesthosepatientswithpolypoidsyndromes,orwho aresufferingfrominflammatoryboweldisease.3

Most often, a diagnosis of cancer leads to a phase of muchanxietyand distress, possiblytriggering a picture of depression.Inturn,thedepressioncomesinassociationwith somaticsymptomssuchaslossofappetiteandfatigue,which

mayalsobeassociatedwiththecatabolismand/ortreatment ofthedisease.4

The use of medicinal fungi and/or their extracts as dietary supplements hasincreased considerably, thanksto itsanti-tumor,anticarcinogenic,antiviral,anti-inflammatory, hypoglycemic,hypocholesterolemicandhypotensiveeffects, amongothers,andtheseproductsmayberecommendedas adjuvantsinthetreatmentofmalignantneoplasms.5

Considering the prominence of this theme, this study aimedtoevaluatetheanthropometricprofileofwomenwith colorectalcancerafterdietarysupplementationwiththe fun-gusAgaricussylvaticus.

Methods

Studydesign

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Therandomizationprocedureoccurredthroughsequential numbersrandomlygeneratedbycomputer,whereeach ran-domnumber correspondedtoagroupreceiving thefungus (GroupA)orplacebo(GroupB).Thesenumberswereinserted intoopaque,nottranslucentandclosedenvelopes,withthe generationofthenumbersequenceperformedbyaresearcher blindedtothestudy,afterselectionofpatientswithinclusion andexclusioncriteria.Theenvelopeswere opened sequen-tiallyasthepatientswereconsecutivelyrecruitedforthestudy andcontainedthegrouptowhichthepatientwouldbelong. Onlyafterperformingthestatisticalanalysis,itwasrevealed whichgrouphadreceivedplaceboandwhichreceivedAgaricus sylvaticus.

Patients

The sample consisted of patients with colorectal cancer divided into two groups: those who received placebo and those supplementedwithAgaricussylvaticus. Thefollowing inclusioncriteriashouldbefulfilled:femalepatientswitha confirmed diagnosis of colorectal cancer inthe postopera-tivephase,from threemonthstotwoyearsofsurgery,and olderthan20years.Exclusioncriteriawere:pregnantwomen, breastfeedingmothers,bedriddenindividuals,physically dis-abledpeople,patients usinganalternative therapyor with otherchronicnon-communicablediseases,andinmetastasis process.

Agaricussylvaticusextract

With awidespread geographical distribution and naturally occurringinBrazil,Agaricussylvaticuswasfirstdescribed in Switzerland.ItsidentificationwasconfirmedbytheLondon RoyalBotanicGardens,whosedocumentationwasprovided bytheInstituto deBotânica,EnvironmentStateSecretariat, SãoPaulo,inNovember10,1995.TheAgaricussylvaticusfungus (Family:Agaricaceae),whosepopularnameisSunMushroom, wasobtainedfromaproducerdulyaccreditedbytheEmpresa BrasileiradePesquisaAgropecuária–Embrapa,fromTapiraí, StateofSaoPaulo,Brazil.Thefungusextractwasobtainedby soakingthedehydratedmaterialinhotwaterduring30min; then,the materialwasliquified,sievedand driedina des-iccator.Theanalysis ofAgaricussylvaticus compositionwas performedbytheJapanFoodResearchLaboratoriesCenterand revealedthepresenceofcarbohydrates(18.51g/100g),lipids (0.04g/100g),ergosterol(624mg/100g),proteins(4.99g/100g), amino acids (arginine – 1.14%; lysine – 1.23%, histidine – 0.51%,phenylalanine–0.92%,tyrosine–0.67%,leucine–143% methionine–0.32%,valine–1.03%,alanine–1.28%glycine– 0.94%,proline–0.95%,glutamicacid–3.93%,serine–096%, threonine–0.96%,asparticacid–1.81%,tryptophan–0.32% cysteine–0.25%)andtraceamountsofmicronutrients.

Thedryextractwastransformedintotablets,inaccordance withpharmacotechnicalprocedure.Thedosageofthefungus administeredtopatientsfromthesupplementedgroupwas equivalentto30mg/kg/day,dividedintotwodailydoses(six tabletsaday,threeinthemorningandthreeintheafternoon, inbetweenmeals),consideringthemeanweightofthestudy populationoveraperiodofsixmonths.Asforthegroupof patientswhoreceivedplacebo,thetabletswereadministered

inthesamequantities,withthesameexcipientsandenergy, butwithouttheextractofAgaricussylvaticus(initsplace,the placebogroupreceivedstarch).

Clinicalevolution

Patientswerefollowedforsixmonths.Duringthefirstthree months,the visitswere heldfortnightlyforclinical assess-mentand,inthelastthreemonths,thevisitswereheldevery 30days.

Thefoodanamnesis(semiquantitativeand24-hrecallfood consumptionfrequencyquestionnaire)washeldonthefirst and last days ofconsultation. However, the patients were instructedtoremainwiththeusualdiet,inordernotto inter-ferewith theintervention, althoughduringtreatmentthey havereceivedguidelinesonhowtomaintainahealthydiet. Aftera6-month follow-up, anindividualizeddietwas sug-gested forall patients,who,whennecessary, werereferred tootherhealthprofessionals.

The anthropometric assessment was performed using bodymassindex(BMI),tricepsskinfoldthickness(TSF),arm circumference (AC), arm muscle circumference (AMC) and bodyfatpercent(%BF).However,forstatisticalpurposes,we extractedtheaverageoftheresultsobtainedinthreedifferent times:beforestartingsupplementation,afterthreemonthsof treatmentandaftersixmonthsoftreatment.

Allpatientswerefollowedweeklybyresearcherstoclarify anydoubts,checkontheproperuseofthemushroomandfor confirmationoftheschedule,ensuringgreateradherenceto treatmentandcontrolonthecontinuityofthestudy.

We considered as dropouts those patients who did not attendtheconsultationsduringthefullperiodofsixmonths. Thosepatientswho died beforetheend oftreatment were excludedfromthesample.

Anthropometricassessment

Aspecialformofanthropometricassessment,tobefilledinall theconsultations,wasused.Weightdeterminationwas per-formedwiththepatientbarefooted,wearinglightclothingand withoutjewelleryinterferingwiththemeasurementresults. Thepatientshouldremainstandinginthecenterofthescale, withherbodyweightequallydistributedbetweenbothfeet.6

In ordertoobtainthis variable,aPlenna® Resolvedigital

scale(MEA-02500model)withbioimpedance(BIA),capacityof 150kg,with0.1kgvariationandproperlycalibratedwasused. For heightmeasurement, the barefooted patient should stayuprightandinanerectposition,withherbodyliftedat maximumextension,headup,lookingforward,inaFrankfurt position,withherbackandthebackofherkneestouchingthe wallandwithfeettogether.6TheFrankfurtanatomicalplane

extendsfromthebottommarginoftheeyesockettothetop borderoftheauditorycanal.7Patients’heightwasmeasured

onlyonce,incentimeters(cm),witha150-cmlonginelastic measuringtapeattachedtoaflatwallwithoutbaseboardand fixedat50cmfromtheground.Awoodsquarewasplacedon topoftheheadofthepatient;withthis,weobtainedameasure with0.1-cmaccuracy.

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heightinmeterssquared.BMIvalues<18.5kg/m2would

char-acterizethinness;≥18,5kg/m2and<25kg/m2,normalweight; ≥25kg/m2and<30kg/m2,overweight;and30kg/m2,obesity,

accordingtotheclassificationrecommendedbyWorldHealth Organization.8

TSFwas measuredusingaCescorf® quick-reading

com-pass,witharangeupto60mmandaccuracyof±1mm.Three consecutivemeasurementswereobtainedfromTSF,andthe arithmeticaverageofthemeasuredvalueswasconsidered. As for AC measurement, an inextensible-material,150-cm length,1-cmscalemeasuringtapewasused.TheAMCvalue wasobtainedbytheformula:AMC=AC–(0.314×TSF).8

TSF, AC and AMC measures were compared to a Frisancho’s9 referencestandard,and theadequacywas

cal-culatedbydividingthevaluesobtainedbythe50thpercentile andmultiplyingtheresultby100.Astothenutritionalstatus classification,thefollowingvalueswereconsidered:obesity: >120%,overweight:110–120%,normalweight:90–110%,mild malnutrition: 80–90%, moderate malnutrition: 70–80% and severemalnutrition:<70%.10

Thebodyfatpercentage(%BF)wasobtainedalsousingthe Plenna®digitalscale.

Statisticalanalysis

Thepresentedvalueswerecomparedandanalyzedapplying

t-Studentand F statisticaltests,using MicrosoftExcel2007 andSPSS(StatisticalPackagefortheSocialSciences,SPSSInc, Chicago,USA)forWindows,version19.0.Theaccepted statis-ticalsignificanceprobabilitywasp<0.05.

Results

Afterafollow-upofsixmonthsintheProctologyOutpatient Clinic,HospitaldeBasedoDistritoFederal,atotalof40women withcolorectalcancerwhomettheinclusionandexclusion criteriaagreed toparticipateinthe research,and, ofthese patients,twodiedandsixdroppedoutforvarious reasons. Thefinalsampleconsistedof32patientswithameanageof 56.66±14.07years,atstagesI(n=4),II(n=12)andIII(n=16), separatedintogroupsreceivingplacebo(n=16)andAgaricus sylvaticus(n=16).Themeanageswere57.67±13.42yearsand 55.87±15.11 years for placebo and Agaricus sylvaticus sup-plementedgroups,respectively,withnodifferencebetween groups(p=0.39).

As for the body mass index, we observed that the placebogrouphad aninitialBMIof24.25±5.33kg/m2;after

three months, a significant increase in BMI was noted (from 24.25±5.33kg/m2 to 24.40±5.15kg/m2, p=0.01) and

in the sixth month, there was a further increase (from 24.25±5.33kg/m2to24.71±4.73kg/m2,p=0.06),butthislast

resultwasnotstatisticallysignificant(Fig.1).

The supplemented group showed an initial BMI of 24.44±4.59kg/m2;afterthreemonths,asignificantincrease

to 24.91±4.18kg/m2 (p=0.02) was observed, and after six

months a further significant increase to 25.16±3.92kg/m2

occurred,comparedtobaseline(p=0.02)(Fig.1).

Regardingarmcircumference(AC),intheplacebogroupan initialvalueof28.68±5.80cmforthisvariablewasobserved;

Start 3 months 6 months Follow-up

23.6 23.8 24 24.2 24.4 24.6 24.8 25 25.2

Bmi (kg/m

2)

Agaricus sylvaticus Placebo

Fig.1–Evolutionofbodymassindex(BMI)ofwomenwith

colorectalcancerinplacebo(n=16)andAgaricussylvaticus

(n=16)groups,treatedattheProctologyOutpatientClinic,

HospitaldeBasedoDistritoFederal,throughouttheclinical

follow-up.Placebo:p=0.01andp=0.06andAgaricus

sylvaticus:p=0.02andp=0.02,afterthreeandsixmonths,

respectively.Student’st-test.

after three months, this value had suffered a significant decline, to 27.88±4.56cm (p=0.05) and, after six months, a non-significant increase, to 28.39±4.39cm (p=0.31), was observed(Fig.2).

The Agaricussylvaticus group presented initialvaluesof 28.66±4.19cmforAC,withasignificantincreaseoverthree (29.47±4.10cm,p=0.01)andsix(29.68±3,74cm; p=0.0001) monthsofsupplementation(Fig.2).

As fortricipitalskinfoldthickness, it was observedthat theplacebogrouphadaninitialmeanof19.53±8.27mmfor

26.5 27 27.5 28 28.5 29 29.5 30

Start 3 months 6 months

Arm circumference (cm)

Follow-up

Agaricus sylvaticus Placebo

Fig.2–Armcircumference(AC)ofwomenwithcolorectal

cancerofplacebo(n=16)andAgaricussylvaticus(n=16)

groupstreatedattheProctologyOutpatientClinic,Hospital

deBasedoDistritoFederal,throughouttheclinical

follow-up.Placebo:p=0.05andp=0.31andAgaricus

sylvaticus:p=0.01andp=0.0001,afterthreeandsix

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5

0 10 15 20 25

Start 3 months 6 months

Follow-up time

Tricipital skin fold (mm)

Placebo Agaricus

Fig.3–Tricipitalskinfold(TSF)ofwomenwithcolorectal

cancerofplacebo(n=16)andAgaricussylvaticus(n=16)

groupstreatedattheProctologyOutpatientClinic,Hospital

deBasedoDistritoFederal,throughouttheclinical

follow-up.Placebo:p=0.14andp=0.19andAgaricus

sylvaticus:p=0.16andp=0.05,afterthreeandsixmonths,

respectively.Student’st-test.

TSF.Afteranintervalofthreemonths,therewasanincrease to20.43±9.14mm(p=0.14)and aftersixmonths,afurther increaseto20.42±8.33mm(p=0.19).Butthesechangeswere notstatisticallysignificant(Fig.3).

Withinthreemonthsofsupplementation,theAgaricus syl-vaticusgroupshowedanon-significantincreaseinTSF(from 21.41±7.44mm to 22.38±5.95mm; p=0.16), followed after sixmonthsbyasignificantincrease(from21.41±7.44mmto 23.66±5.62mm,p=0.05)(Fig.3).

In the placebo group, after arm muscle circumference measurement,anon-significantdecreaseafterthreemonths (from 23.44±4.42cm to 22.82±3.16cm, p=0.14) and a sig-nificant decrease after sixmonths (from 23.44±4.42cm to 22.30±3.29cm,p=0.03)wereobserved(Fig.4).

These findings were not found in the Agaricus syl-vaticus group, which increased its AMC after three (from 21.94±2.61m to 22.45±2.44cm, p=0.10) and six (from 21, 94±2.61cmto22.28±2.65cm,p=0.22)monthsof supplemen-tation,althoughthesechangeswerenotsignificant(Fig.4).

Astothepercentageofbodyfat,the placebogroup pre-sentedinitiallya%BFof36.33±8.44%.Afterthreemonths,this variable had increased(from36.33±8.44%to 36.46±7.25%,

p=0.44)andinthe sixth month,anewincreasewasagain noted(from36.33±8.44%to37.60±8.07%,p=0.19).Butthese changeswerenotstatisticallysignificant(Fig.5).

TheAgaricussylvaticusgrouppresentedaninitial%BFof 36.88±7.33%.Afterthreemonths,anon-significantincrease to37.88±6.60%(p=0.09)wasfound,andaftersixmonthsa significant increase to 39.56±8.68% (p=0.04) was observed (Fig.5).

Discussion

Inthisstudy,thesamplewasconvenientlycomposedof100% ofwomenwithcolorectalcancer.Scientificevidencesuggests

21 21.5 22 22.5 23 23.5 24

Start 3 months 6 months Follow-up

Arm muscle circumference (cm)

Agaricus Placebo

Fig.4–Armmusclecircumference(AMC)ofwomenwith

colorectalcancerofplacebo(n=16)andAgaricussylvaticus

(n=16)groupstreatedattheProctologyOutpatientClinic,

HospitaldeBasedoDistritoFederal,throughouttheclinical

follow-up.Placebo:p=0.14andp=0.03andAgaricus

sylvaticus:p=0.10andp=0.22,afterthreeandsixmonths,

respectively.Student’st-test.

thatcolorectalcancerismoreprevalentinwomen,affecting moreandmoreoftentheleftcolon.11InBrazil,theInstituto

Nacional do Câncer (INCA) registry for 2012estimated the occurrenceof14,180newcasesofcolorectalcancerinmen andof15,960casesinwomen,correspondingtoanestimated riskof15newcasesper100,000menand16newcasesoutof every100,000women.12

The mean age of our patients was 55 and 57 years for placeboandAgaricussylvaticusgroups,respectively.Inthese groups, the minimum andmaximum ages were 32 and 77 years,respectively.AccordingtoCozerattolinietal.,13more

than90%ofcolonandrectalcancersrelatetoindividualsolder than 50 years,and 75% ofcasesaffect individuals without otherriskfactors,besidesage.

40 39.5 39 38.5 38 37.5 37 36.5 36 35.5 35 34.5

Body fat percentage

Start 3 months 6 months Follow-up

Placebo Agaricus sylvaticus

Fig.5–Bodyfatpercentage(%BF)ofwomenwithcolorectal

cancerofplacebo(n=16)andAgaricussylvaticus(n=16)

groupstreatedattheProctologyOutpatientClinic,Hospital

deBasedoDistritoFederal,throughouttheclinical

follow-up.Placebo:p=0.44andp=0.19andAgaricus

sylvaticus:p=0.09andp=0.04,afterthreeandsixmonths,

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Inthisstudy,bothplaceboandAgaricussylvaticusgroups had aninitialBMIwithinthenormalweight range,with a tendencytobeoverweight.Scientificstudieshaveshown a positivecorrelationbetweenoverweight,obesityandriskof developingseveraltypesofcancer,aswellasinmortalityfrom thisdisease.Itisexpectedthatthe probablemechanism is interconnectedwithhyperinsulinemiaandwithahighlevel ofinsulin-dependentgrowthfactor(IGF-1)andofthose pro-teinsthatbindtoIGF-1,aswellaswiththepracticeofdiets characterizedbytoomuchenergyconsumption.13

Thereisahighercorrelationbetweenexcessweightand riskofcolorectalcancer,inwhichtheabdominalorcentral distributionofbodyfatisthemaincomponentofincreasing thisrisk,asthisoccurrenceisrobustlylinkedtoinsulin resis-tanceandhyperinsulinemia.13However,inthisstudy,visceral

fatwasnotevaluated.

Clinicalandexperimentalstudiesshowthatthediet sup-plementedwithAgaricussylvaticusandotherfungipromotes positive effects with respect to nutritional, medicinal and pharmacologicaleffects,andthatthesesupplementscanbe usedasadjuvantsincancertreatment.14Medicinalfungiexert

anaboliceffects,becausetheycontainalltheessentialamino acids,plusimmunonutrientslikearginineandglutaminethat, intimesofmetabolicstress,becomeconditionallyessential, contributingtoimprovementsinnitrogenbalance.1,15

Inthis study,theAgaricussylvaticus groupobtained bet-teranthropometricresults(BMI,AC,TSF,%BF)versusplacebo, includingin relationtoleanbody mass,despiteno signifi-cantfinding.Scientificevidencesuggeststhatmedicinalfungi havebioactivecompoundsabletopreventthemuscleprotein catabolismcommonlypresentinthesepatients,explainingin parttheresultsobserved.15–17

Themechanismsofactionofexistingbioactivecompounds in fungi are not yet fully explained in the literature, but scientificstudies suggestthat thesesubstances can modu-latecarcinogenesis,notonlyintheearlystages,butalsoin advancedphasesintheprogressionofthedisease,especially bystimulatingtheimmunesystem.14

Wefoundnoscientificpapersintheliteraturethat eval-uatedanthropometryand/orthenutritionalstatusofcancer patientsafterdietarysupplementationwithmedicinalfungi, including those of the Agaricaceae family, species Agari-cussylvaticus.However,clinicalstudiesshowthatmedicinal fungiareabletomodulatethemetabolismofcarbohydrates, proteins and lipids, besides exerting beneficial effects on the hematopoietic, immune and gastrointestinal systems, with positive repercussions on the quality of life ofthese patients.15–24

Majormetabolicalterationsinducedbyadvancedtumors include glucose intolerance, decreased insulin secretion, peripheral insulin resistance, increased synthesis and glucose turnover, increased activity of the Cori cycle, increased protein turnover, increased hepatic protein synthesis, increased muscle protein catabolism, reduced plasma concentration of branched chain amino acids, depletion of lipid deposits, increased lipolysis, increased glycerolandfreefattyacidturnover,reducedlipogenesisand hyperlipidemia.4,5,15,16,20,21,23

The depletion of adipose tissue is responsible, in large part,bytheweightlossobservedincancerpatients.Thisis

due tothe different changes infatty acid metabolism and alsototheoccurrenceoflipolysis,increasedlipidoxidation, reductionoflipogenesisandoflipoproteinlipaseactivity,and increased release of lipolytic tumor factors and hormone-sensitivelipase,resultinginhyperlipidemia.15,16,19,20,22

The beneficial effects ofthese fungihave been demon-strated,withinhibitionofanti-tumoractivityandproliferation ofcancercells,expansionofnaturalkillercellfunctionand ofotherimmunologicalparameters,suchasthesecretionof immunoglobulinsIgA,IgMandIgE,andaprogressionof mono-cyteandmacrophagefunctions.5,16,21,22

Itisnoteworthythat,inadditiontohighbiologicalvalue proteinsandofimmunomodulatoraminoacids(suchas argi-nineand glutamine)thathelpinmuscleproteinanabolism of cancer patients, other substances present in medicinal fungistandout:glucans,proteoglucans,lectins,ergosteroland triterpenes– all withthe abilityofmodulatingthe various metabolicandimmuneactionsinthesepatients.5,15,16,22,23

Conclusion

Ourresultssuggestthatdietarysupplementationwith Agar-icus sylvaticus fungus has the ability to bring benefit for anthropometricparametersofwomenwithcolorectalcancer. However,controlledand randomizedclinicaltrials, in addi-tiontothoseperformedinthisstudy,areneededtoelucidate themechanismsofactionofthebioactiveprinciplespresent inAgaricussylvaticus,aswellasothermedicalconditionsthat couldbenefitthroughthissupplementation.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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Imagem

Fig. 1 – Evolution of body mass index (BMI) of women with colorectal cancer in placebo (n = 16) and Agaricus sylvaticus (n = 16) groups, treated at the Proctology Outpatient Clinic, Hospital de Base do Distrito Federal, throughout the clinical follow-up
Fig. 4 – Arm muscle circumference (AMC) of women with colorectal cancer of placebo (n = 16) and Agaricus sylvaticus (n = 16) groups treated at the Proctology Outpatient Clinic, Hospital de Base do Distrito Federal, throughout the clinical follow-up

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