Effects of a High vs Moderate Volume of Aerobic Exercise on Adiposity Outcomes in

27 Pages·2015·0.22 MB·English

Research
OriginalInvestigation
Effects of a High vs Moderate Volume of Aerobic Exercise
on Adiposity Outcomes in Postmenopausal Women
A Randomized Clinical Trial
ChristineM.Friedenreich,PhD;HeatherK.Neilson,MSc;RachelO’Reilly,MSc;AaloDuha,MD;
YutakaYasui,PhD;AndriaR.Morielli,BSc;ScottC.Adams,MSc;KerryS.Courneya,PhD
InvitedCommentarypage776
IMPORTANCEBodyfatincreasespostmenopausalbreastcancerrisk.Physicalactivitymay
Supplementalcontentat
decreaseriskthroughadipositychanges,buttheoptimaldoseofactivityisunknown. jamaoncology.com
OBJECTIVE Tocomparetheeffectsof300vs150min/wkofmoderatetovigorousaerobic
exerciseonbodyfatinpostmenopausalwomen.
DESIGN,SETTING,ANDPARTICIPANTS TheBreastCancerandExerciseTrialinAlbertawasa
12-month,2-armed,2-centerrandomizeddose-comparisontrialconductedfromJune2010
throughJune2013.Participantswere400inactivepostmenopausalwomenwithbodymass
index22to40,disease-free,nonsmokers,andnonusersofexogenoushormones.
INTERVENTIONS Fived/wkofaerobicexercise(3d/wksupervised,2d/wkunsupervised)for
30min/session(moderate-volume)or60min/session(highvolume)achieving65%to75%
ofheartratereserveforatleast50%ofeachsession.Participantswereaskednottochange
usualdiet.
MAINOUTCOMESANDMEASURES Totalbodyfat,measuredfromdualenergyx-ray
absorptiometryscans,wastheprimaryoutcome.Othermeasuresincludedsubcutaneous
andintra-abdominalfatfromcomputedtomographyscans,weight,andwaistandhip
circumferences.
RESULTS Of400women,384providedbaselineandfollow-upadipositymeasurements.
Median(interquartilerange)adherenceatfullprescriptionforthehigh-and
moderate-volumegroupswas254(166-290)and137(111-150)min/wk,respectively.Mean
reductionsintotalfatweresignificantlylargerinthehigh-vsmoderate-volumegroup
(least-squaresmeandifference,−1.0%[95%CI,−1.6%to−0.4%],P=.002).Subcutaneous
abdominalfatandwaisttohipratiodecreasedsignificantlymoreinthehigh-volumegroup
(least-squaresmeandifference,−10.8[95%CI,−19.5to−2.2]cm2,P=.01,and−0.01[95%CI,
−0.02to0.00],P=.04,respectively).Changesinweightandintra-abdominalfatwerenot
significantlydifferentbetweengroups(least-squaresmeandifference,−0.7[95%CI,−1.6to
0.2]kg,P=.11,and−1.5[95%CI,−5.9to2.9]cm2,P=.50,respectively).Somedose-response
effectswerestrongerforobesewomen.
CONCLUSIONSANDRELEVANCE Inpreviouslyinactivepostmenopausalwomen,a1-year
prescriptionofmoderatetovigorousexercisefor300min/wkwassuperiorto150min/wkfor
reducingtotalfatandotheradipositymeasures,especiallyinobesewomen.Theseresults
suggestadditionalbenefitofhigher-volumeaerobicexerciseforadiposityoutcomesand
AuthorAffiliations:Author
possiblyalowerriskofpostmenopausalbreastcancer.
affiliationsarelistedattheendofthis
article.
TRIALREGISTRATION clinicaltrials.gov:NCT01435005 CorrespondingAuthor:ChristineM.
Friedenreich,PhD,Departmentof
CancerEpidemiologyandPrevention
Research,CancerControlAlberta,
AlbertaHealthServices,HolyCross
Centre,Room514,POBoxACB,2210
SecondStSW,Calgary,ABT2S3C3,
JAMAOncol.2015;1(6):766-776.doi:10.1001/jamaoncol.2015.2239 Canada(christine.friedenreich
PublishedonlineJuly16,2015. @albertahealthservices.ca).
766 (Reprinted) jamaoncology.com
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VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen OriginalInvestigation Research
P
hysicalactivityisaninexpensive,noninvasivestrat-
egyfordiseasepreventionadvocatedbypublichealth AtaGlance
agenciesinNorthAmerica1,2andinternationally3with
•Wecomparedadipositychangesin400inactive
recommendationstobephysicallyactiveatleast150min/wk postmenopausalwomenrandomizedto1yearof
atmoderateintensity,or60to75min/wkatvigorousinten- high-volume(300min/wk)ormoderate-volume(150min/wk)
sity,foroverallhealth.Anestablishedbenefitofphysicalac- exercise.
tivityisbodyweightregulation.Consensusexiststhatphysi- •Meanexerciseminutesperweekinthemoderate-volume
calactivityiseffectiveforpreventingweightgain4-7andthat andhigh-volumegroups,respectively,were91%and85%of
prescribed.
generally,sustainedphysicalactivityformorethan150min/wk
•Meanexercisedurationwaslessthan150min/wkfor22.5%of
producesmodestweightlossof2to3kgforoverweightand
womeninthehigh-volumegroup.
obese adults,4,8,9 with higher volumes (eg, 225 to 420 •Meanreductionsintotalbodyfat,subcutaneousabdominalfat,
min/wk10)resultingingreaterweightloss.11,12 BMI,andwaisttohipratioweresignificantlygreater(P<.05)
Postmenopausalwomenmayderiveuniquebenefitfrom forwomenprescribed300min/wkaerobicexercise.
exercise because there is a tendency for total13-15 and •Benefitsassociatedwiththe300-min/wkprescriptionwere
abdominal16weightgainaftermenopause;moreover,bodyfat, enhancedforobesewomen(BMI(cid:2)30)withrespecttoweight,
BMI,waistandhipcircumference,andsubcutaneous
abdominalfat,andadultweightgainincreasetheriskofpost-
abdominalfat.
menopausalbreastcancer.17-21Endometrialandcoloncan-
cers,themetabolicsyndrome,type2diabetesmellitus,and
cardiovasculardiseasearealsomediatedthroughpostmeno-
pausaladiposity.22Physicalactivitydecreasespostmeno- Participants
pausalbreastcancerrisk17,18partlybyregulatingbodyfat.23It Eligiblewomenwerepostmenopausal,aged50to74years,
isunknown,however,towhatextenthigherexercisevol- hadabodymassindex(BMI)(calculatedasweightinkilo-
umesinfluencepostmenopausalbodyfat. gramsdividedbyheightinmeterssquared)of22to40,were
Thedose-responsebenefitsofexercisecanbeestimated inactive37(≤120min/wkornomorethan3d/wkmoderate-
mostaccuratelyfromwell-poweredrandomizedclinicaltrials intensityrecreationalactivitylessthan30minutes/session;
(RCTs).However,fewRCTswithadiposityoutcomeshavebeen baselineestimatedmaximumoxygenconsumption[V˙O2max]
designedtocompareexercisedurations,10,24-33and,toour nomorethan34.5mL/kg/minor,ifestimatedV˙O2maxwas
knowledge,nonehaveprescribedmoderatetovigorousexer- 34.6-37.0mL/kg/min,7-dayaccelerometercountlessthan
ciseformorethan250min/wkexclusivelytopostmeno- 10000 steps/d), and had no previous cancer diagnosis
pausalwomen.Dose-comparisontrialshaveoftenbeenshorter exceptnonmelanomaskincancerandnomajorcomorbid
than6months,24,27,31,34includedmen10,24,29,31-33or50orfewer conditionorrecentreconstructivesurgery.Womencould
participantsperarm,10,24,25,27,28,30-32,34prescribedlowerex- maintainacceptableheartandlungfunctioninasubmaxi-
ercisedurationorintensity,26,32,35and/ordidnotmeasurevis- maltreadmilltest,werenonusersofexogenoushormones
ceralfat.10,24,25,27,29-31,34,35PreviouslyintheAlbertaPhysical ordrugsaffectingestrogenmetabolism,nonsmokers,con-
ActivityandBreastCancerPrevention(ALPHA)trial,weran- sumednomorethan2drinksofalcohol/d,Englishspeaking,
domized320postmenopausalwomento225min/wkmoder- notintendingtobeawaylongerthan4weeksconsecutively
atetovigorousaerobicexerciseorusualinactivityforape- (8weekstotal)duringtheintervention,andnotparticipating
riodof12monthsandshowedthatbodyweight,totalfat,and inorplanningaweightlossprogram.Thestudyprotocol
intra-abdominalandsubcutaneousabdominalfatdecreased (seeSupplement1)wasapprovedbytheAlbertaCancer
significantlyvscontrols.Inexploratoryanalyses,favorable Research Ethics Committee and the Conjoint Health
dose-responsetrendswerefoundbetweenmeanbodyfatre- ResearchEthicsBoardoftheUniversityofCalgary,andthe
ductionandexerciseadherenceoflessthan150,150to225, HealthResearchEthicsBoardoftheUniversityofAlberta.
andmorethan225min/wk.36However,theALPHATrialwas Allparticipantsprovidedwritteninformedconsent.
notdesignedtoexaminedose-responseeffects.IntheBreast
CancerandExerciseTrialinAlberta(BETA),wetestedwhether RandomizationandBlinding
greateradipositychangesoccurininactive,postmenopausal Womenwererandomlyallocated1:1toaerobicexercisefor150
womenrandomizedtoahigh-volume(300min/wk)vsmod- or300min/wk.Randomizationwasstratifiedbystudycen-
erate-volume(150min/wk)exerciseprescription.Thegoalwas terandbaselineBMIusingblocksizesof4or6withinstrata.
toinformphysicalactivityguidelinesforweightcontroland TherandomallocationsequencewasgeneratedusingRsoft-
theprimarypreventionofpostmenopausalbreastcancer. ware(version2.11)38anduser-definedfunctions.Allocations
wereconcealedinnumberedenvelopespreparedbystaffun-
relatedtothestudyteam.StudycoordinatorsinCalgaryand
Edmontonenrolledparticipantsandassignedthemtoanin-
Methods
tervention.Staffwereblindedtorandomizationgroupdur-
TheBreastCancerandExerciseTrialinAlbertawasa2-cen- ing anthropometric measurements and full-body dual-
ter,2-armedRCTconductedinCalgaryandEdmonton,Al- energyx-rayabsorptiometry(DXA)scans.Thestudyradiologist
berta,Canada.Detailsofthestudydesignandmethodswere (A.D.)wasblindedtorandomizationgroupwhenreviewing
previouslypublished.37 computedtomographicscans.
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Research OriginalInvestigation VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen
Intervention careLunarProdigyDXAandGEHealthcareenCOREsoftware
Exercisevolumewasincreasedgraduallyovera12-week toassesspercentbodyfat,leanbodymass,andfatmass.
ramp-upperiod.37Thegoalbyweek13wastoattain5d/wk Percentbodyfatwascalculatedas100%×[fatmass/(fat
aerobicexercisefor30minutes(moderatevolume)or60min- mass+leanmass)].Subcutaneousabdominalfatandintra-
utes(highvolume)persession,achieving65%to75%maxi- abdominalfatweremeasuredfromcomputedtomographic
mumheartratereserveforatleasthalfofeachworkout(fit- scansof4singleslicescenteredattheumbilicususingaPhil-
nesslevelswerereassessedevery3months).Womenreceived ipsBrillianceBigBoreoraToshibaAquilion.Dataweretrans-
PolarFT4heartratemonitors(PolarElectro)touseineachsu- ferredtoourstudyradiologist(A.D.)attheCrossCancerIn-
pervisedorunsupervisedsession.Fromweeks13through52, stitute,Edmonton,whoreviewedeachscanandusedimage
womenwereprescribedsupervisedsessions3d/wk(West- analysissoftware(AquariusIntuitionbyTeraRecon,Inc)tode-
sideRecreationCentre,Calgary,ortheBehavioralMedicineFit- marcateandquantifysubcutaneousandintra-abdominalfat.
nessCentre,UniversityofAlberta,Edmonton)andunsuper-
visedhome-basedexercise2d/wk.Weeklyexerciselogswere SampleSize
usedtodocumentactivitytypes,totalexerciseduration,ex- Samplesizecalculationswerebasedonthestandard2-sample
ercisedurationat65%to75%ofmaximumheartratere- meancomparisonformula49(pp301-304)withα=.05(2sided)for
serve, mean heart rate, and Borg Ratings of Perceived thecomparisonofmean12-monthchangeswithnoadjust-
Exertion.39Exercisefrequency,duration,andmeanheartrate mentforbaselinevalues.Theexercisedoseeffectontotalbody
weredeterminedfromheartratemonitorsandrecordedbyex- fatwastheprimaryoutcomeofinterest.Totalbodyfatwas
ercisetrainers;participantsreportedtypesofactivityandBorg measuredinabsolute(kilograms)andrelative(percentbody
Ratings.Participantswereinstructednottochangeusualdiet. fat)scales.Expectedstandarddeviationsandinterventionef-
Anyaerobicactivitythatraisedheartrateto65%to75% fectswerebasedonestimatedvaluesfromtheALPHATrial.36
ofheartratereservewaspermittedduringthetrial.Inthefirst Initiallyasamplesizeof150participantspergroupwascho-
2sessions,eachparticipantmetoneononewithastudyex- sen,allowing95%powertodetectagroupdifferenceof2.6%
ercisetrainerwhoprovidedorientationtothetrainingfacil- inpercentfatchangeand3.8%infatmasschange.Allowing
ityandavarietyofaerobicequipmentincludingtreadmills,sta- 10%losstofollow-up,samplesizewasincreasedto165per
tionarybicycles,andellipticaltrainers.Trainersalsoprovided group.Ultimately,200participantspergroupwererandom-
acomprehensiveexerciseeducationalguide37developedfor izedgivenahigher-than-expectedvolunteerresponse,pro-
BETAthatincludedhome-basedexerciseexamplesandproper viding95%powertodetectgroupdifferencesof2.3%and3.3%
exercisetechniqueinstructionsforspecificactivities. inpercentfatchangeandfatmasschange,respectively.
BaselineandFollow-upMeasures StatisticalAnalysis
Anumberofvariableswereassessedfordescriptivepurposes Baselinecharacteristicswerecomparedbetweengroupsusing
andtoassesspossibleconfoundingoreffectmodification. 2-samplettestsforcontinuousvariablesorχ2testsforcat-
Demographicinformation,includingrace/ethnicity,andmedi- egoricalvariables.Meanadherencewascharacterizedsepa-
calhistorywasobtainedbyself-completedquestionnaireat ratelyformoderate-andhigh-volumegroupsandwascalcu-
baselineand12-monthfollow-up.Inaddition,participants latedasmeanexerciseminutesperweekrecordedinexercise
completedthePastYearTotalPhysicalActivityQuestion- logs,weeks1through52,andalsobetweenweeks13and52
nairecapturingthefrequency,duration,andintensityofalloc- aftertheinitial12-weekramp-upperiod.Meanexercisetime
cupational,household,recreational,andwalkingorbicy- spentat65%to75%ofheartratereserve(fromheartratemoni-
clingtoworkactivities,40aswellastheCanadianadaptation tors)wassimilarlydescribed.Differencesin12-monthchange
oftheUSNationalCancerInstitute’spast-yearDietHistory inhypothesizedconfoundingand/ormediatingvariableswere
Questionnaire.41Metabolicequivalent(MET)valueswereas- comparedbetweenrandomizationgroupsusing2-sample
signedtoeachactivityusingtheCompendiumofPhysical ttests.Allstatisticaltestswere2sidedwithasignificancelevel
Activities42-44toderiveMET-hoursperweekforeachactivity of.05.AnalyseswereperformedusingSAS(SAS9.2forLinux,
domain.Caloricandnutrientintakeswereestimatedusing SASInstituteInc)andgraphicswereproducedusingR(Rver-
Diet*Calc.45 sion3.1.1forWindows).
Atbaselineand12months,submaximalcardiorespira-
torytestswereconductedusingamultistage,modifiedBalke IntentiontoTreat
treadmillprotocol46;V˙O2maxwasestimatedaspreviously Theintention-to-treatprimaryanalysiswasbasedonleast-
described.37Atthetimeoffitnesstesting,standingheightand squaresmeandifferencesin12-monthadipositychangesbe-
weightweremeasuredbyresearchstaffusingabalancebeam tweenmoderate-andhigh-volumegroupsderivedfromlin-
scaleandstadiometer.Measuresweretakeninduplicate(ifdis- earmodelsadjustedforbaselineadiposityandstudylocation
crepant,athirdmeasurewastaken)andthenaveraged.Waist (EdmontonorCalgary).Sensitivityanalysesexcludedpartici-
andhipcircumferencesweredeterminedusingananthropo- pantswhoself-reportedmorethan1000kcal/dchangeinpast-
metricmeasuringtapeandtheNationalInstitutesforHealth yearenergyintake,andalsoreplacedmissing12-monthadi-
protocol.47(pp7-13)48 posityvalueswithbaselinevalues.
Full-bodyDXAscansweretakenusingaHologicDiscov- Effectmodificationbybaselineage(continuous)and
eryADXAsystemandHologicQDRsoftwareoraGEHealth- BMI(continuous)wasassessedusingstatisticaltestsfor
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VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen OriginalInvestigation Research
interactionandlinearmodelsthatpredicted12-monthadi-
Figure.ConsolidatedStandardsofReportingTrials(CONSORT)Diagram:
positychange.Covariatesbaselineadiposity,studylocation
FlowofParticipantsThroughtheBreastCancerandExerciseTrial
(Calgary or Edmonton), and randomization group were inAlberta,Alberta,Canada,2010Through2013
included in the models, as well as interaction terms
betweenrandomizationgroupandbaselineBMIorage.To 8794Self-referrals and
describeinteractions,least-squaresmeangroupchanges invited to participate
werecalculated,stratifiedbyBMI(<30,≥30)orage(<60,
≥60years). 2028Assessed for eligibility
Exploratory
1165Did not meet
Aper-protocolanalysiswasundertaken,repeatingthepri- inclusion criteria
maryanalysisonlyforwomenwhowereexerciseadherent,ie,
90%to100%ofprescriptionforthemoderate-volumegroup
863Interested and attended
(135-150min/wk)orameanofatleast90%ofprescriptionfor information session
thehigh-volumegroup(≥270min/wk),weeks13to52,based
onexerciselogs.Also,inanexploratorydose-responseanaly-
463Excluded
sisthatcombinedthe2interventiongroups,testsforlinear 222Ineligible
trendwereperformedrelatingadipositypercentagechangeto 22Physician screen results
81Blood screen results
3categoriesofexerciseadherence(weeks1-52);categoriescor- 70Fitness test results
respondedtocutpointsassociatedwithweightloss(≤150,>150 49Other reasons
to<250,≥250min/wk).4 241Declined to participate
400Randomized
Results
200Randomized to high- 200Randomized to moderate-
ParticipantswererecruitedfromJune2010throughApril2012. volume exercise volume exercise
ThetrialconcludedbyJune2013whenallparticipantshad
completed12-monthinterventions.Of400randomized 5Discontinued study 9Discontinued study
women,384(96.0%)providedbaselineand12-monthmea- participation participation
surementsforatleast1adiposityoutcome(Figure).Drop-out 22MNoendaicdahle rreeanstons 21MNoendaicdahle rreeanstons
rateswere2.5%and4.5%forthehigh-andmoderate-volume 1Personal reasons 5Personal reasons
groups,respectively.Noseriousadverseeventswerere- 1Relocation
ported.Therewerenosignificantdifferencesbetweengroups
atbaselineexceptforethnicity(Table1).ThemeanBMIwas 195Returned for 12-month 191Returned for 12-month
measurements measurements
consistentwithanoverweightpopulation,andthemeanage 195Computed tomography scan 189Computed tomography scan
was59years(5%wereolderthan70years). 192Dual x-ray absorptiometry 187Dual x-ray absorptiometry
192Anthropometry 185Anthropometry
Adherence
Median(interquartilerange)adherenceforthemoderate-
andhigh-volumegroupswas129(106-138)and228(156- 70%oflogentrieswerewalking,ellipticaltraineruse,andrun-
262) min/wk, respectively, during the 52-week period. ning.Therewerenogroupdifferencesin12-monthmean
Excludingtheramp-upperiod,adherencewas137(111-150) changesinenergyintake(P=.48),dietaryfatintake(P=.53),
and254(166-290)min/wk,respectively,representing91% ornonrecreationalphysicalactivity(occupationalactivity,
and85%oftargetedamounts.Additionaladherencedata P=.68;householdactivity,P=.76;walkingorbikingtoorfrom
areprovidedineTable1inSupplement2.Themedian(in- work,P=.29).
terquartilerange)intenseexercisetimeaccordingtoheart
ratemonitors(excludingtheramp-upperiod)was88(53- Intention-to-TreatAnalysis
115)and128(66-185)min/wkforthemoderate-andhigh- Least-squaresmeanreductionsintotalbodyfatweresignifi-
volumegroups,respectively,representing59%and43%of cantlylargerinthehigh-vsmoderate-volumegroup(−2.41
prescribeddurations. [95%CI,−2.97to−1.85]vs−1.45[95%CI,−2.01to−0.89]kg,
Duringthe12-monthperiod,totalrecreationalactivityin- P=.01;−2.2%[95%CI,−2.6%to−1.7%]vs−1.2%[95%CI,−1.7%
creasedmoreinthehigh-vsmoderate-volumegroup(26.5vs to−0.7%],P=.002)(Table2).Subcutaneousabdominalfatalso
14.2MET-h/wk;P<.001),asdidestimatedV˙O2max(5.09vs3.96 decreasedsignificantlymoreinthehigh-volumegroup,aswell
L/kg×min;P=.05).Womeninthe2groupsengagedinsimi- astotalabdominalfat,BMI,waistcircumference,andwaistto
laractivitieswithintheexerciseprescription(eTable2in hipratio(Table2).Weightchangerangedfrommorethan3%
Supplement2).Supervisedactivitiesaccountingformorethan weightgain(9%ofmoderate-volumegroup,6%ofhigh-
75%oflogentrieswereuseoftheellipticaltrainer,walking, volumegroup)tomorethan5%weightloss(27%ofmoderate-
andbicycling.Home-basedactivitiesaccountingformorethan volumegroup,34%ofhigh-volumegroup);meanweight
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Research OriginalInvestigation VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen
Table1.ParticipantBaselineCharacteristicsintheBreastCancerandExerciseTrialinAlberta,
Alberta,Canada,2010Through2013
ModerateVolume HighVolume
BaselineCharacteristic (n=200) (n=200) PValue
Employedfulltime,No.(%) 59(29.5) 71(35.5) .20
Educatedbeyondhighschool,No.(%) 155(77.5) 155(77.5) >.99
Marriedorcommon-law,No.(%) 139(69.5) 136(68.0) .75
Whiterace,No.(%) 186(93.0) 172(86.0) .02
Age,mean(SD),y 59.5(5.1) 59.4(4.8) .81
Totalenergyintake,mean(SD),kcal/d 1474.0(541.4) 1462.1(588.2) .83
Pastyearphysicalactivity,mean(SD),MET-h/wka
Total 96.4(48.2) 93.7(44.1) .57
Recreational 9.9(13.6) 8.5(9.4) .22
Maximaloxygenconsumption,mean(SD),mL/kg/min 26.8(5.0) 26.7(5.3) .84
Weight,mean(SD),kg 77.4(13.0) 77.3(13.0) .97
BMI,mean(SD) 29.4(4.4) 29.1(4.4) .41
Circumference,mean(SD),cm
Waist 98.6(10.8) 98.7(11.0) .97
Hip 109.9(10.0) 109.4(9.9) .64
DXAmeasurements,mean(SD)
Bodyfat,% 40.7(5.9) 40.5(5.8) .72
Totalfatmass,kg 31.0(8.7) 30.8(8.6) .80 Abbreviations:BMI,bodymassindex
Totalleanmass,kg 44.0(5.7) 44.1(5.5) .90 (calculatedasweightinkilograms
dividedbyheightinmeterssquared);
CT-measuredfatarea,mean(SD),cm2
CT,computedtomography;DXA,dual
Intra-abdominal 133.4(49.3) 125.6(50.8) .12 x-rayabsorptiometry;MET,metabolic
equivalent.
Subcutaneous 313.8(99.0) 314.1(97.9) .98
aSelf-reportedinthePastYearTotal
Intra-abdominal+subcutaneous 447.3(131.2) 439.8(130.9) .57
PhysicalActivityQuestionnaire.
Table2.ChangesinAdiposityBetweenBaselineand12MonthsintheBreastCancerandExerciseTrialinAlberta,
Alberta,Canada,2010Through2013
ModerateVolume HighVolume
LSMeanChange LSMeanChange LSMeanDifference
AdiposityMeasure No.a (95%CI)b No.a (95%CI)b (95%CI)c PValued
Weight,kg 185 −1.79(−2.46to−1.11) 192 −2.52(−3.19to−1.85) −0.73(−1.62to0.15) .11
BMI 185 −0.70(−0.95to−0.44) 192 −1.05(−1.31to−0.80) −0.36(−0.69to−0.02) .04
Circumference,cm
Waist 185 −4.37(−5.33to−3.41) 192 −5.66(−6.61to−4.71) −1.29(−2.55to−0.03) .05
Hip 185 −2.14(−2.87to−1.42) 192 −2.39(−3.11to−1.68) −0.25(−1.20to0.70) .61
Waisttohipratio 185 −0.025(−0.031to−0.018) 192 −0.034(−0.041to−0.027) −0.009(−0.018to0.000) .04
DXAmeasurements
Totalleanmass,kg 187 −0.31(−0.59to−0.04) 192 0.00(−0.28to0.27) 0.31(−0.05to0.68) .09
Bodyfat,% 187 −1.2(−1.7to−0.7) 192 −2.2(−2.6to−1.7) −1.0(−1.6to−0.4) .002
Totalfatmass,kg 187 −1.45(−2.01to−0.89) 192 −2.41(−2.97to−1.85) −0.96(−1.71to−0.22) .01
CT-measuredfatarea,cm2
Intra-abdominal 189 −11.9(−15.2to−8.64) 195 −13.4(−16.7to−10.2) −1.50(−5.85to2.85) .50
Subcutaneous 189 −23.7(−30.2to−17.1) 195 −34.5(−41.0to−28.0) −10.8(−19.5to−2.16) .01
Intra-abdominal+ 189 −35.6(−44.2to−26.9) 195 −47.8(−56.4to−39.1) −12.2(−23.7to−0.70) .04
subcutaneous
Abbreviations:BMI,bodymassindex(calculatedasweightinkilogramsdivided β(adiposityatbaseline)+β(location)+β(randomizationgroup),where
1 2 3
byheightinmeterssquared);CT,computedtomography;DXA,dualx-ray adiposityatbaselinecorrespondstotheadiposityoutcomemodeled.
absorptiometry;LS,least-squares. cLeast-squaresestimateofthedifferencebetweenmoderate-andhigh-volume
aNumberofwomencompletingmeasuresatbaselineand12months,forwhom groups,usingmodelspecifiedinfootnoteb.
achangecouldbecalculated,withineachrandomizationgroup. dPvaluederivedfrommodelspecifiedinfootnoteb,andcorrespondstothe
bValuesareintheformofleast-squaresmean(lower95%confidencelimitto nullhypothesisthattheLSmeandifferencebetweenhigh-and
upper95%confidencelimit)basedonthemodel,adipositychange=β + moderate-volumegroupsequals0againstthe2-sidedalternativehypothesis.
0
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VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen OriginalInvestigation Research
Table3.ChangesinAdiposityinEachInterventionGroupStratifiedbyBaselineBodyMassIndexintheBreastCancer
andExerciseTrialinAlberta(BETA),Alberta,Canada,2010Through2013
ModerateVolume HighVolume
LSMeanChange LSMeanChange LSMeanDifference PValue
AdiposityMeasure BMI No.a (95%CI)b No.a (95%CI)b (95%CI)c forInteractiond
Weight,kg <30 114 −1.81(−2.49to−1.14) 119 −1.68(−2.35to−1.01) 0.13(−0.74to1.01)
.02
≥30 71 −1.74(−3.13to−0.34) 73 −3.83(−5.19to−2.48) −2.10(−3.94to−0.26)
BMI <30 114 −0.68(−0.94to−0.43) 119 −0.73(−0.99to−0.48) −0.05(−0.38to0.28)
.03
≥30 71 −0.72(−1.26to−0.18) 73 −1.56(−2.08to−1.04) −0.84(−1.55to−0.13)
Circumference,cm
Waist <30 114 −4.05(−5.15to−2.95) 119 −4.30(−5.41to−3.20) −0.26(−1.69to1.18)
.01
≥30 71 −4.93(−6.67to−3.18) 73 −7.82(−9.51to−6.12) −2.89(−5.19to−0.59)
Hip <30 114 −2.35(−3.04to−1.65) 119 −1.73(−2.43to−1.04) 0.61(−0.29to1.52)
.04
≥30 71 −1.68(−3.21to−0.16) 73 −3.40(−4.86to−1.94) −1.71(−3.72to0.29)
Waisttohipratio <30 114 −0.020(−0.029to−0.012) 119 −0.029(−0.038to−0.021) −0.009(−0.020to0.002)
.17
≥30 71 −0.031(−0.042to−0.020) 73 −0.041(−0.052to−0.030) −0.010(−0.024to0.005)
DXAmeasurements
Totalleanmass,kg <30 114 −0.10(−0.42to0.22) 118 0.41(0.10to0.73) 0.51(0.10to0.92)
.22
≥30 73 −0.60(−1.11to−0.08) 74 −0.66(−1.17to−0.14) −0.06(−0.74to0.62)
Bodyfat,% <30 114 −1.5(−2.0to−1.0) 118 −2.3(−2.9to−1.8) −0.8(−1.5to−0.1)
.55
≥30 73 −0.4(−1.3to0.4) 74 −1.7(−2.5to−0.8) −1.2(−2.4to−0.1)
Totalfatmass,kg <30 114 −1.60(−2.14to−1.06) 118 −2.02(−2.56to−1.48) −0.42(−1.13to0.29)
.07
≥30 73 −1.15(−2.32to0.02) 74 −2.97(−4.12to−1.82) −1.82(−3.38to−0.26)
CT-measuredfatarea,cm2
Intra-abdominal <30 114 −11.0(−14.9to−7.08) 121 −12.2(−16.1to−8.25) −1.17(−6.32to3.98)
.55
≥30 75 −13.5(−19.3to−7.68) 74 −16.2(−22.0to−10.4) −2.72(−10.5to5.05)
Subcutaneous <30 114 −24.7(−32.3to−17.1) 121 −29.7(−37.2to−22.1) −4.95(−14.9to4.97)
.03
≥30 75 −24.6(−35.9to−13.3) 74 −44.7(−56.0to−33.4) −20.1(−35.3to−4.91)
Intra-abdominal+ <30 114 −35.7(−45.6to−25.8) 121 −41.7(−51.6to−31.7) −5.96(−19.0to7.03)
subcutaneous .07
≥30 75 −38.9(−54.1to−23.6) 74 −61.7(−76.9to−46.5) −22.9(−43.3to−2.42)
Abbreviations:BMI,bodymassindex(calculatedasweightinkilogramsdivided cLeast-squaresestimateofthedifferencebetweenmoderate-volumeand
byheightinmeterssquared);CT,computedtomography;DXA,dualx-ray high-volumegroups,usingmodelspecifiedinfootnoteb.
absorptiometry;LS,least-squares. dPvalueforinteractioncorrespondstothetestforinteractionbetween
aNo.representsthenumberofwomencompletingmeasuresatbaselineand randomizationgroupandbaselineBMIbasedonthefollowingmodel:
12monthstoforwhomachangecouldbecalculatedtowithineach adipositychange=β +β(adiposityatbaseline)+β(location)+
0 1 2
randomizationgroup. β(randomizationgroup)+β (baselineBMI)+β(baselineBMI×
3 4 5
bValuesareintheformofleast-squaresmean(lower95%confidencelimitto randomizationgroup),whereBMIwastreatedasacontinuouscovariateand
upper95%confidencelimit)basedonthemodel,adipositychange=β + adiposityatbaselinecorrespondstotheadiposityoutcomemodeled.Forthe
β1(adiposityatbaseline)+β2(location)+β3(randomizationgroup),whe0re outcomeofBMIchange,β4wasexcludedfromthemodel.
adiposityatbaselinecorrespondstotheadiposityoutcomemodeled.
changeswere−2.5%(moderatevolume)and−3.3%(highvol- thehigh-volumeprescription,whereaswomen60yearsor
ume),correspondingto−1.79(95%CI,−2.46to−1.11)and−2.52 olderexperiencedgreaterreductionswiththemoderate-
(95%CI,−3.19to−1.85)kg,respectively(Table2).Asensitiv- volumeprescription.
ityanalysisexcluding10womenwhodidnotadheretodi-
etaryinstructionshadanegligibleimpactonprimaryresults. ExploratoryAnalyses
Replacingmissing12-monthadipositymeasureswithbase- Inaper-protocolanalysisof138adherentwomen(Table4),
linevalues(n=11to15inmoderate-volumegroup;n=5to8 least-squaresmeanchangesintotalfatwere−3.63(95%CI,
inhigh-volumegroup)alsohadlittleimpact. −4.52 to −2.75) kg vs −1.86 (95% CI, −2.90 to −0.82) kg
Significantinteractionswerefoundbetweenrandomiza- (P=.005),or−3.4%(95%CI,−4.3%to−2.6%)vs−1.3%(95%
tiongroupandbaselineBMI(Table3),showingstronger CI, −2.3% to −0.4%; P<.001), for high- and moderate-
dose-responseeffectsforobesewomen(BMI≥30)with volumegroups,respectively.SimilarlyforBMI,waistcircum-
respecttoweight,BMI,waistandhipcircumference,and ference,andsubcutaneous,intra-abdominal,andtotalab-
subcutaneousabdominalfatchanges.Nosignificantinterac- dominalfat,meanchangesweresignificantlylargerforthe
tions were found with baseline age except for intra- high-volumegroup.Inanexploratoryanalysisthatcom-
abdominal fat change (P for interaction = .02); women binedinterventiongroups,favorabledose-responsetrends
youngerthan60yearsexperiencedgreaterreductionswith wereobservedbetweenexerciseadherenceandadiposityper-
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Research OriginalInvestigation VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen
Table4.ChangesinAdiposityBetweenBaselineand12MonthsinaPer-ProtocolAnalysisofAdherentParticipantsaintheBreastCancer
andExerciseTrialinAlberta,Alberta,Canada,2010Through2013
Moderate High
LSMeanChange LSMeanChange LSMeanDifference
AdiposityMeasure No.b (95%CI)c No.b (95%CI)c (95%CI)d PValuee
Weight,kg 58 −2.41(−3.57to−1.25) 80 −3.67(−4.67to−2.67) −1.25(−2.64to0.13) .08
BMI 58 −0.89(−1.34to−0.44) 80 −1.58(−1.97to−1.19) −0.69(−1.23to−0.15) .01
Circumference,cm
Waist 58 −5.00(−6.82to−3.17) 80 −7.35(−8.93to−5.77) −2.35(−4.53to−0.18) .03
Hip 58 −2.77(−3.92to−1.62) 80 −3.74(−4.72to−2.75) −0.97(−2.33to0.40) .16
Waisttohipratio 58 −0.023(−0.037to−0.010) 80 −0.039(−0.050to−0.027) −0.016(−0.032to0.000) .05
DXAmeasurements
Totalleanmass,kg 58 −0.61(−1.11to−0.12) 80 −0.06(−0.49to0.38) 0.56(−0.03to1.14) .06
Bodyfat,% 58 −1.3(−2.3to−0.4) 80 −3.4(−4.3to−2.6) −2.1(−3.2to−1.0) <.001
Totalfatmass,kg 58 −1.86(−2.90to−0.82) 80 −3.63(−4.52to−2.75) −1.78(−3.00to−0.55) .005
CT-measuredfatarea,cm2
Intra-abdominal 58 −10.9(−16.5to−5.29) 80 −18.3(−23.2to−13.4) −7.39(−14.1to−0.66) .03
Subcutaneous 58 −21.5(−33.3to−9.71) 80 −44.2(−54.4to−33.9) −22.7(−36.7to−8.62) .002
Intra-abdominal+subcutaneous58 −32.7(−47.6to−17.8) 80 −62.3(−75.3to−49.3) −29.6(−47.4to−11.8) .001
Abbreviations:BMI,bodymassindex(calculatedasweightinkilogramsdivided cValuesareintheformofleast-squaresmean(lower95%confidencelimitto
byheightinmeterssquared);CT,computedtomography;DXA,dualx-ray upper95%confidencelimit)basedonthemodel,adipositychange=β0+
absorptiometry;LS,least-squares. β1(adiposityatbaseline)+β2(location)+β3(randomizationgroup),where
aWomenassignedtothemoderate-volumegroupwereadherentifthey adiposityatbaselinecorrespondstotheadiposityoutcomemodeled.
completed90%to100%oftheexerciseprescription(mean,135-150 dLeast-squaresestimateofthedifferencebetweenmoderate-andhigh-volume
min/wk),weeks13to52atfullprescription;womenassignedtothe groupsusingmodelspecifiedinfootnotec.
high-volumegroupwereadherentiftheycompletedatleast90%ofthe ePvaluederivedfrommodelspecifiedinfootnotecandcorrespondstothenull
exerciseprescription(mean,(cid:2)270min/wk),weeks13to52atfull hypothesisthattheLSmeandifferencebetweenhigh-andmoderate-volume
prescription. groupsequals0againstthe2-sidedalternativehypothesis.
bNumberofwomencompletingbaselineand12-monthmeasurements,for
whomchangecouldbecalculated,withineachrandomizationgroup.
centchange(eFigureinSupplement2);thegreatestreduc- vscontrols.Threeadditionaldose-comparisonRCTscom-
tionsoccurredinwomenreportingmorethan250min/wkof pared walking durations for reducing postmenopausal
exercise. adiposity,25,27,34butonly1smallpilotstudy(n=26)27showed
adose-responseeffect,withmeanfatreductionsofapproxi-
mately3%to4%and1%to2%for225and150min/wkpre-
scriptions,respectively.Collectively,thesefindingssupportthe
Discussion
useofaerobicexerciseforatleast225min/wkforgreaterre-
Duringa12-monthperiod,inactivepostmenopausalwomen ductionsinpostmenopausaltotalbodyfat.
withBMIof22to40prescribed300vs150min/wkofmod- Adiposetissueisanimmunologically54andmetaboli-
eratetovigorousaerobicexerciseexperiencedasignifi- callyactiveendocrineorgan55thatisasourceofinflamma-
cantlygreaterreductioninmeantotalbodyfat(by1kgor torycytokines,adipokines,oxidativestress,andnotably,the
1%bodyfat).MeanreductionsinBMI,waistcircumference, primarysourceofsexhormonesaftermenopause,56whichare
waisttohipratio,subcutaneousabdominalfat,andtotal proposed57-61biomarkersforbreastcancerrisk.Weshowedpre-
abdominalfatwerealsosignificantlygreaterinthegroup viouslyinpostmenopausalwomenthattotalfatlossmedi-
prescribed300min/wk.Dose-responseeffectswerestron- atedexercise-inducedchangesincirculatingestradiolandsex
gerforobesewomen(BMI≥30)withrespecttochangein hormonebindingglobulinconcentrations62andthatde-
weight,BMI,waistandhipcircumference,andsubcutane- creasedlevelsofleptin63andC-reactiveprotein64relatedto
ousabdominalfat. totalfatloss.Hence,ourfindingsfortotalfatlossareconsis-
The2%totalfatlossachievedinBETAduringa12-month tentwithdecreasedbreastcancerrisk,possiblythroughthese
periodwith300min/wkapproximated36,50,51orexceeded52,53 mechanisms.
reductionsinsimilartrialsprescribing150to225min/wkmod- Abdominalfatwarrantsseparateevaluationbecauseex-
eratetovigorousexercisetopostmenopausalwomen.Inthe ercisemayexertdifferenteffectsonabdominalvstotalfat,65
Dose-ResponsetoExerciseinPostmenopausalWomen(DREW) andabdominalfatisariskfactorforpostmenopausalbreast,
RCT(n=464),nodose-responseeffectwasfoundforreduc- pancreatic,andendometrialcancers.17Itisunclearwhether
ingbodyweightorpercentbodyfat.26,35However,exercisein visceralobesityincreasespostmenopausalbreastcancerrisk,
DREWwasoflowerintensity(50%V˙O2max)anddurationthan althoughthereisbiologicplausibility66givenitsassociation
inBETA,averaging72,136,and192min/wkin3exercisegroups withinsulinresistance,type2diabetes,andthemetabolic
772 JAMAOncology September2015 Volume1,Number6 (Reprinted) jamaoncology.com
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VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen OriginalInvestigation Research
syndrome,67,68whichareproposedcausalmechanisms.69-71 firstdose-comparisonRCTtoassesschangesinpostmeno-
Ourprimaryanalysisshowednodose-responseeffectforintra- pausalsubcutaneousandintra-abdominalfat.Moreover,
abdominalfat,withbothgroupsexperiencingmeanreduc- BETAhadexceptionalpowerof95%todetectsmallgroup
tionsofapproximately−12to−13cm2,similartoALPHATrial differencesintotalbodyfatchange,ourprimaryoutcome.A
participants(−16.5cm2)36butsuperiortoothercomparable limitationofBETAwasthatwedidnotevaluate420min/wk
trials.53,72Astrongergroupdifferenceintheper-protocolanaly- (recommendedforcancerprevention17)becauseofadher-
sis(−10.9vs−18.3cm2)suggestspossiblythatnonadherence enceconcerns,andconsequently,ourresultsdonotreflect
contributedtoournullfindings.Otherexplanationsmightin- theentiretyofthedose-responsecurve.Ourresultsmaynot
clude effect modification by age, similar exercise generalizetotype2diabetics,womenwithuncontrolled
intensities,73,74orinsufficientlyhighexerciseprescriptions.75 hypercholesterolemia,orhormonetherapyusersbecauseof
Incontrast,clearbenefitwasfoundfromprescribing exclusioncriteria.37Ourstudyincludedpostmenopausal
300vs150min/wkforsubcutaneousabdominalfatreduc- womenwithBMIof22to40whoweremostlyyoungerthan
tion,withameanreductioninthehigh-volumegroup(−34.5 70yearsoldandmotivatedtoexercise.Yetadherencewas
cm2) comparable to that of exercisers in ALPHA (−32.0 challenging;22.5%ofwomeninthehigh-volumegroup
cm2)36butlargerthaninotherpostmenopausaltrials.53,72 exercisedlessthanameanof150min/wkatfullprescrip-
Previous dose comparison RCTs in postmenopausal tion,whichlikelyattenuateddose-responseeffectsinthe
women25,27,34,35didnotassesssubcutaneousabdominalfat, intention-to-treatanalysis.Nonadherenceshouldbeconsid-
although some reported waist circumference, which is ered when sample size requirements are calculated for
related.76TheDREWtrial35(<200min/wk,50%V˙O2max) futureexercisetrialsthattesthighervolumesorintensities
reportednodose-responseeffectforwaistcircumference, ofexercise.
whereasDallecketal27reportedgreaterreductionsprescrib-
ing225vs150min/wkofwalking.Aposthocanalysisby
Bergstrometal77demonstratedthegreatestwaistreduc-
Conclusions
tionsforwomenadheringto210min/wkaerobicexercise.
Therefore,similartototalbodyfat,greaterreductionsin Aprobableassociationbetweenphysicalactivityandpost-
postmenopausal subcutaneous abdominal fat might be menopausalbreastcancerrisk17,18issupportedbymorethan
achievedwithmorethan200min/wkhigher-intensityaero- 100epidemiologicstudies,withstrongbiologicrationalesup-
bicexercise.Althoughtheclinicalsignificanceofsubcutane- portingfatlossasanimportant(thoughnottheonly)media-
ousabdominal(vsvisceral)fatisunclearandsomewhat torofthisassociation.57-59Ourfindingsofadose-responseef-
controversial,78,79 correlations between subcutaneous fectofexerciseontotalfatmassandseveralotheradiposity
abdominalfatandcardiometabolicriskfactorsareevidentin measuresincludingabdominalfat,especiallyinobesewomen,
women.79-82Postmenopausalweightlosshasinducedfavor- provideabasisforencouragingpostmenopausalwomentoex-
ablechangesintheexpressionofproposedgenebiomarkers erciseatleast300min/wk,longerthantheminimumrecom-
ofcancerriskwithinsubcutaneousabdominalfat.83 mendedforcancerprevention.1,3,17,89,90Werecognizethatex-
Exercise-inducedweightlossvarieswidelybetween ercisealonemaynotsufficeforachieving,forexample,a10%
individuals,84,85whichwasapparentinBETA.Forexample, weightlosstargetinobesewomen.91,92However,theoptimal
29womenexperiencedmorethan3%weightgain.Compen- doseforbreastcancerpreventionshouldalsobeinformedby
satorychangesintotalenergyexpenditureorenergyintakecan effectsonothermediatingpathwaysbesidesadiposityandide-
occurduringexerciseinterventiontrials,35,86,87particularlyat ally,evidencefromanRCTwithbreastcancerendpoints.One
higherexercisevolumes,35butananalysisexploringcompen- meta-analysisestimateda33%increaseinestrogenreceptor–
sationwasbeyondthescopeofthisreport.Futureexerciseef- positive/progesteronereceptor–positivepostmenopausal
ficacytrialsmayincorporateaweightmaintenancedietintheir breastcancerriskwithevery5-unitincreaseinBMI.21Given
protocol,asdescribedrecently,33tominimizethiseffect.Ef- themeanBMIreductionsinBETA,4.6%and6.9%breastcan-
fectmodificationmightfurtherexplainheterogeneitybe- cerriskreductionsmayoccurforwomenprescribed150vs
causeobesewomeninBETAexperiencedmorebenefitfrom 300min/wkofaerobicexercise,anaddeddosebenefitof2.3%.
the300min/wkprescription.Obesewomenmayexperience Inobesewomen,theaddeddosebenefitmaybegreater,ap-
moredramaticdose-responseeffectsgivenagreaterpropen- proximately5.5%,given4.8%and10.3%riskreductionswith
sityforfatloss.Moreover,dose-responseeffectsvariedbyage 150-vs300-min/wkprescriptions.Exploratoryanalysessug-
withrespecttointra-abdominalfat.Whereasthereasonforthis gestthatsomeofourresultswereattenuatedbymodestad-
effectisunclear,previousstudiesshowedthatyounger(<70 herence;thatintra-abdominalfatchangemayfollowadiffer-
years)vsolder(70-79years)postmenopausalwomenexperi- ent dose-response curve than total body fat, possibly
encedgreaterreductionsintotalfat52,88andintra-abdominal warrantingadifferentexerciseprescriptionordietarymodi-
fat52overtimewithincreasingaerobicactivity. fication;andthat300vs150min/wkmayprovidedifferent
Experimental evidence from well-powered RCTs is benefitdependingonBMIandage.Researchexaminingdif-
requiredtosupportphysicalactivityrecommendations,and ferentexerciseprescriptions,individualpropensityforfatloss,
BETAprovidesthisevidence.Toourknowledge,BETAisthe tendencytowardexercisecompensation,andpredictorsofex-
largestlong-termRCTtocompareexercisedosesofmore erciseadherencemayenhancetheimpactofahighervslower
than225min/wkinhealthypostmenopausalwomenandthe exerciseprescription.
jamaoncology.com (Reprinted) JAMAOncology September2015 Volume1,Number6 773
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Research OriginalInvestigation VolumeofAerobicExerciseandAdiposityinPostmenopausalWomen
ARTICLEINFORMATION SpeedAndrews,PhD.Assistancewithinformation 7.StehrMD,vonLengerkeT.Preventingweight
AcceptedforPublication:May27,2015. sessionswasprovidedinCalgarybyBrigidLynch, gainthroughexerciseandphysicalactivityinthe
PhD;andFabiolaAparicio-Ting,PhD.Calgary elderly:asystematicreview.Maturitas.2012;72(1):
PublishedOnline:July16,2015. exercisetrainerswereCarrieAnderson,BKin;Alia 13-22.
doi:10.1001/jamaoncol.2015.2239. Bharwani,BKin;ShannonBrown,BPE;Ashley 8.RichardsonCR,NewtonTL,AbrahamJJ,SenA,
OpenAccess:Thisarticleispublishedunder Cuthbert,BEd;SueDaniel,BN;JulieGowansBKin; JimboM,SwartzAM.Ameta-analysisof
JAMAOncology’sopenaccessmodelandisfree MargueriteGraham,BEd;ErinKorsbrekMKin; pedometer-basedwalkinginterventionsandweight
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AECCOScpaau’RhnlitgdeochaeioeolrmlrlyyrCo,)iAo;oAfDflnMlobfteigeerlpioyrdaatliatarcAint,oilmndCbneaeePs,nrn:rUtaeDtandvo,eieaAvfpneO(labFtrrnisretoiicmretnotydaeRleoonHengftseryCoeea,afaiCllctCrghuhcaamh,SnrN,yecm,reeCviirnliascgloegnsa,,ry, JawACManrrhSsandoocweK;nwfACaoNeonirlgradrdee,,eWyBaMrslKrKlSiogiUuncnhzn;;,tiCNikM,vi,BienScBKrdocSsiyPlincetTF;y.S;EoEoLlrrodfiibstnmAe,aMMlosbB,nceAeMtGrl;oatSoTanncawge;eneaAmxirnael,pyrWPPslcohshihsyaDDeietH;;eetJMir,snea,BadniwnArlneyee;i,rfrese,r 9Iar(s8a.son)yl:Tda7shott4eeom7dmr-io7zaag5eeto5dircoo.crbdoeiAcnvit,eerMxwoelolraetcndtiisdltelormiaaSnel,sdtS.aAhw-aimmeniagoJlhnyMtyseilsoAdso,.se2f:t0a11l.;124
Alberta,Canada(Friedenreich);CrossCancer Norris,MSc;JanelPark,BKin;LindaTrinh,PhD; 10.DonnellyJE,HonasJJ,SmithBK,etal.Aerobic
Institute,CancerControlAlberta,AlbertaHealth StephanieVoaklander,BScKin,BEdSec;andLynne exercisealoneresultsinclinicallysignificantweight
Services,Edmonton,Alberta,Canada(Duha); Wong,MScPT.StudyrecruiterswereJennieDuke, lossformenandwomen:MidwestExerciseTrial2.
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