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a double blind randomized and placebo controlled clinical trial with agaricus sylvaticus fungus in anthropometric profile of women with colon cancer

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b rColoproctology Renata Costa Fortesa,b, ∗, Jhuly Amado Souzab, Maria Rita Carvalho Garbi Novaesc aCurso de Nutric¸ão, Instituto de Ciências da Saúde, Universidade Paulista UNIP, Brasíl

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

Coloproctology

Renata Costa Fortesa,b, ∗, Jhuly Amado Souzab, Maria Rita Carvalho Garbi Novaesc

aCurso de Nutric¸ão, Instituto de Ciências da Saúde, Universidade Paulista (UNIP), Brasília, DF, Brazil

bPrograma de Residência em Nutric¸ão Clínica, Hospital Regional da Asa Norte, Secretaria de Estado de Saúde do Distrito Federal

(HRAN/SES/DF), Brasília, DF, Brazil

cCurso de Medicina, Escola Superior de Ciências da Saúde (ESCS), Fundac¸ão de Ensino e Pesquisa em Ciências da Saúde (FEPECS), Secretaria de Estado de Saúde do Distrito Federal (HRAN/SES/DF), Universidade de Brasília (UnB), Brasília, DF, Brazil

a r t i c l e i n f o

Article history:

Received22February2014

Accepted27July2014

Availableonline28January2015

Keywords:

Anthropometry

Colorectalcancer

Agaricus sylvaticusfungi

a b s t r a c t

Introduction:Colorectalcancerisadiseaseinfluencedbygeneticandenvironmentalfactors Medicinalfungiand/oritsextractshavebeenusedintheadjuvanttherapyofcancerbecause

oftheirpharmacological,nutritionalandimmunomodulatoryproperties

Objective:Toevaluatetheanthropometricprofileofcolorectalcancerwomenafterdietary supplementationwithAgaricus sylvaticusfungus

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:TheAgaricus sylvaticusgroupshowedasignificantincreaseinbodymassindex,arm circumference,percentbodyfatandtricepsskinfold,andnon-significantincreaseinarm musclecircumferenceaftersixmonthsofsupplementation.Theseresultswerenotobserved

intheplacebogroup

Conclusion:TheresultssuggestthatdietarysupplementationwithAgaricus sylvaticusis capa-bletohavebenefitsinanthropometricparametersofwomenwithcolorectalcancer

©2015SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.All

rightsreserved

Corresponding author at: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

2237-9363/©2015SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.Allrightsreserved

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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

FungosAgaricus sylvaticus

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,1pari passuwiththe

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-gusAgaricus sylvaticus.

Methods

Study design

Thestudy consistsofarandomized,double-blind, placebo-controlledstudy,whichwasapprovedbytheEthicsCommittee

onHumanResearch,StateSecretariatofHealth,Distrito Fed-eral(CEP/SES/DF)underProtocol051/04.Thepatients’freeand informedconsent(FIC)wasobtained,andtheirparticipation was voluntary.The study was conductedatthe Proctology OutpatientClinic,HospitaldeBasedoDistritoFederal,Brazil, betweenNovember2004andJuly2006

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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 supplementedwithAgaricus sylvaticus. 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

Agaricus sylvaticus extract

With awidespread geographical distribution and naturally

occurringinBrazil,Agaricus sylvaticuswasfirstdescribed in

Switzerland.ItsidentificationwasconfirmedbytheLondon

RoyalBotanicGardens,whosedocumentationwasprovided

bytheInstituto deBotânica,EnvironmentStateSecretariat,

SãoPaulo,inNovember10,1995.TheAgaricus sylvaticusfungus

(Family:Agaricaceae),whosepopularnameisSunMushroom,

wasobtainedfromaproducerdulyaccreditedbytheEmpresa

BrasileiradePesquisaAgropecuária–Embrapa,fromTapiraí,

StateofSaoPaulo,Brazil.Thefungusextractwasobtainedby

soakingthedehydratedmaterialinhotwaterduring30min;

then,the materialwasliquified,sievedand driedina

des-iccator.Theanalysis ofAgaricus sylvaticus 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, butwithouttheextractofAgaricus sylvaticus(initsplace,the placebogroupreceivedstarch)

Clinical evolution

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

Anthropometric assessment

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

After data acquisition (weight and height), BMI was obtainedbydividingthepatient’sweightinkilogramsbyher

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char-acterizethinness;≥18,5kg/m2and<25kg/m2,normalweight;

≥25kg/m2and<30kg/m2,overweight;and≥30kg/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

Statistical analysis

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;

Follow-up 23.6

23.8 24 24.2 24.4 24.6 24.8 25 25.2

2)

sylvaticus: p= 0.02 andp= 0.02, after three and six months,

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 Agaricus sylvaticus 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

Follow-up

sylvaticus: p= 0.01 andp= 0.0001, after three and six

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Start

3 months

6 months

Tricipital skin fold (mm) Placebo Agaricus

sylvaticus: p= 0.16 andp= 0.05, after three and six months,

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

TheAgaricus sylvaticusgrouppresentedaninitial%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

Follow-up

sylvaticus: p= 0.10 andp= 0.22, after three and six months,

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 placeboandAgaricus sylvaticusgroups,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

Follow-up Placebo Agaricus sylvaticus

sylvaticus: p= 0.09 andp= 0.04, after three and six months,

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Inthisstudy,bothplaceboandAgaricus sylvaticusgroups

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-plementedwithAgaricus sylvaticusandotherfungipromotes

positive effects with respect to nutritional, medicinal and

pharmacologicaleffects,andthatthesesupplementscanbe

usedasadjuvantsincancertreatment.14Medicinalfungiexert

anaboliceffects,becausetheycontainalltheessentialamino

acids,plusimmunonutrientslikearginineandglutaminethat,

intimesofmetabolicstress,becomeconditionallyessential,

contributingtoimprovementsinnitrogenbalance.1,15

Inthis study,theAgaricus sylvaticus 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-cus sylvaticus.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

inAgaricus sylvaticus,aswellasothermedicalconditionsthat couldbenefitthroughthissupplementation

Theauthorsdeclarenoconflictsofinterest

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