URRENT HERAPEUTIC ESEARCH OLUME 64 No - PDF document

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URRENTHERAPEUTICESEARCHOLUME64,No.8,SEPTEMBER AcceptedforpublicationJune24,2003.Reproductioninwholeorpartisnotpermitted.0011-393X/03/$19.002003ExcerptaMedica,Inc. signicantdifferencesinBMIorbodyweightatweek12,buttherewereslightnumericdecreasesinbodyweightandBMIinmen.Therewerenosignsofareboundeffectfromweek12toweek16.Gcambogiareducedabdominalfataccumulationinsubjects,regardlessofsex,whohadthevisceralfataccumulationtypeofobesity.Noreboundeffectwasobserved.ItisthereforeexpectedthatGcambogiamaybeusefulforthepreventionandreductionofaccumulationofvisceralfat.(TherResClinExp.2003;64:551–567)Copyright2003ExcerptaMedica,Inc.Keywords:Garciniacambogia,hydroxycitricacid,visceralfataccumulation,computedtomographyscan.TheprevalenceofoverweighthasincreasedsubstantiallyinJapanduringthepastdecadeanditcontinuestorise.Accordingtorecentstatistics,30%oftheJapaneseadultpopulationmeetsthecurrentdenitionofoverweight(bodymassindex[BMI]25kg/mObesityisaproblemnotonlyintheWesternworldbutalsoinJapan.Itiswellacceptedthatobesityisariskfactorfortype2diabetes,coronaryheartdisease,andhypertension.Severalstudies,how-ever,haveshownthatmeasurementofoveralladiposityorbodyweight,suchaswithBMI,maynotadequatelydescribetherelationshipofbodyfattoItappearsthatvisceralfatarea(VFA)morefullyexplainsthisTheclusteringofhyperinsulinemia,dyslipidemia,type2diabe-tesmellitus,andhypertensioniscalledtheinsulinresistancesyndromebolicsyndrome,syndromeXAccordingly,evaluationofobesityforthepreventionofsyndromeXmustbeconductedusingnotonlybodyweightorBMIbutalsoVFA.Incidentally,ithasbeenreportedthatahigh-carbohydrate(sucrose)dietincreasesvisceralfataccumulationinrats.Therefore,control-lingthesurplusenergyfromahigh-carbohydratedietisexpectedtobeeffectiveinpreventingtheaccumulationofvisceralfat.Severalstudieshavedemonstratedthat(-)-hydroxycitricacid(HCA),theprincipalacidoftherindoftheIndianfruitGarciniacambogia,isacompeti-tiveinhibitorofadenosinetriphosphatecitratelyase,theenzymethatcata-lyzestheextramitochondrialcleavageofcitratetooxaloacetateandacetylcoenzymeA.ThisactionofHCAshouldreducetheacetylcoenzymeApool,thuslimitingtheavailabilityof2-carbonunitsrequiredforfattyacidandcholesterolInvitroandinvivostudiesshowthatHCAinhibitstheactionsofcitratecleavageenzyme,suppressesdenovofattyacidsynthesis,increasesratesofhepaticglycogensynthesis,anddecreasesbodyweightgain.humanstudies,onlysupportingevidenceexistsfortheefcacyofGcambogiainweightcontrol,andithasyettobeassessedinrelationshiptovisceralfat K.Hayamizuetal.WepreviouslyreportedthattheefcacyofHCAdependsoninitialVFAvaluesandwasobviousinsubjectswhoseinitialVFAwas90cm.Becauseweenrolledoverweightorobeseclass1subjects(BMI,25–35kg/m)inthatstudy,highVFAwasnotoneoftheinclusioncriteria.Thegoalofthepresentstudywastoexaminetheeffectsof12weeksofGcambogiatreatmentonvisceralfataccumulationinsubjectshavingaVFA90cmSUBJECTSANDMETHODSAllsubjectshadtobebetweentheagesof20and65yearsandhaveaVFA.Allofthesubjectsweretobegenerallyhealthyandhavenohistoryofdiabetesmellitus;dysfunctionoftheliver,kidney,orheart;orhematologicdisease.OtherinclusionandexclusioncriteriaaregiveninTableI.Mostofthesubjectswereclassiedaslevel1to2(mild)intermsofself-reporteddailyactivityaccordingtothe6thRecommendedDietaryAllowancesfortheJapaneseThisstudywascarriedoutwithsufcientrespectforthespiritoftheDeclara-tionofHelsinkiandwasapprovedbytheinstitutionalreviewboardsofFANCLCorporation,MaebashiHirosegawaClinic(Gunma,Japan),andOnoClinic(Osaka,Japan).Theprocedureswerefullyexplainedtoallthesubjectsinadvance,andallgavetheirwritteninformedconsentbeforeparticipating.TreatmentGcambogiaextractwasprovidedbyNipponShinyakuCo.,Ltd.,Kyoto,Japan.TheHCAconcentrationwas60%asdeterminedbyhigh-performanceliquid TableI.Studyinclusionandexclusioncriteria. InclusioncriteriaAge20–65yearsOverweight(BMI25kg/mVisceralfatarea90cmNofluctuationofBMIbytheendoftherun-inperiodProvisionofwritteninformedconsentExclusioncriteriaDiabetes(fastingplasmaglucose,126mg/dL)Dysfunctionofliver,kidneys,orheartHematologicdiseaseHistoryofdrughypersensitivityorallergicconditionthatmightinterferewiththestudyUseofdrugsordietarysupplementsthatmightinfluencebodyweight,bodyfat,orserumlipidlevelsPregnancyorlactationAnyotherabnormalityofpotentialclinicalsignificance bodymassindex. chromatography.Theactiveherbalwasa270-mgtabletcontaining185.25mgGcambogiaextract.Intheplacebotablet,theactivecompoundwasreplacedwithcellulose(Avicel,AsahiKaseiCorp.,Tokyo,Japan)asaninertingredient.Theexcipientsweredextrinandcellulose.Subjectswereinstructedtotake3tablets30minutesbeforeeachmeal(9tablets/d).Thetotaldailydosewas1667.25mgofGcambogiaextract,containing1000mgofHCA.ProtocolThisstudywasperformedaccordingtoadouble-blind,placebo-controlled,parallel-groupdesign(Figure1).Randomizationwasperformedbyrandomnumbergeneration,andgroupassignmentwasplacedinasealedenvelope.Theprimaryendpointofthisstudywastheeffectsof12weeksofGcambogiaextractadministrationonvisceralfataccumulation.Thesecondaryendpointswerebodyindices(includingheight,bodyweight,BMI,waistandhipcircumfer-ence,andwaist–hipratio[WHR])andlaboratoryvalues(includingtotalcholes-terol[TC],triacylglycerol,andfreefattyacid).Subjectsreceivednotreatmentduringa2-weekrun-inperiod.Afterrun-in,subjectsunderwentbodyweightmeasurement,computedtomography(CT),andlaboratoryanalysis.TheywerethenrandomlyassignedtoeithertheGcambogiagroup(containing1000mgofHCAperday)ortheplacebogroup.Thetreatmentperiodlasted12weeks.Attheendofthetreatmentperiod,bothgroupswereadministeredplacebofor4weekstoassessanyreboundeffect.Subjectswerestartedonadietaryinterventionbyanationallyregistereddietitianineachinstitute.Subjects’intakewaslimitedto2250kcal/dformen Figure1.ProtocoloftheefficacytestofGarciniacambogia.Subjectsreceivednotreatmentduringa2-weekrun-inperiod.CTcomputedtomography. K.Hayamizuetal.and1800kcal/dforwomen.Energyexpenditurewasdeterminedbyques-tionnairescompletedatweeks0,12,and16.Atthesametime,theaforemen-tioneddietitiansassesseddietaryintervention,usingaquestionnaire,ateachThesubjectsunderwentCTatweeks0,12,and16ateithertheMaebashiHirosegawaClinic,usingaToshibaMedicalTCT-300machine(ToshibaCorp.,Tokyo,Japan),ortheOnoClinic,usingaToshibaMedicalX-forcemachine(ToshibaCorp.).VFAandsubcutaneousfatarea(SFA)weredeterminedbytheFATScanProgram(N2SystemCorp.,Osaka,Japan)fromCTimagedataattheleveloftheumbilicus.AllCTscanswereperformedbyradiologistsblindedtoparticipants’grouprandomization.Bodyindicesweremeasuredatweek–2andevery4weeksduringthestudy.Theyincludedheight,bodyweight,BMI,waistandhipcircumference,andWHR.Bloodsampleswerecollectedfromthesubjectsbetween9:00and11:30afteranovernightfast,whichbeganat9:00onthepreviousnight.Laboratoryparameterswereredandwhitebloodcellcounts,hemoglobin,hematocrit,platelets,TC,high-densitylipoproteincholesterol,low-densitylipoproteincho-lesterol,triacylglycerol,freefattyacid,aspartateaminotransferase,alanine-glutamyltransferase,lactatedehydrogenase,bloodureanitrogen,creatinine,fastingplasmaglucose,insulin,acetoaceticacid,3-hydroxy-butyricacid,andtotalketonebodies.Clinicallaboratorydataweremeasuredat–2,0,12,and16weeks.StatisticalAnalysisRatesofchangewerecalculatedfortheCTscansandbodyindices,andthedifferencesineffectsbetweentheGcambogiaandplacebogroupswerecalcu-latedaccordingtotheStudenttest.Theevaluationofreboundwascalculatedaccordingtothepairedtestatweeks12and16.TheanalysisoflaboratoryparameterstodetermineasafetyprolewasperformedusingthepairedandtheStudenttest.Forbaselinedata,weusedmeanvaluescalculatedfromthestartandendpointsoftherun-inperiod.Allanalyseswereconductedatthe2-tailedlevelof0.05.DatawereanalyzedusingthestatisticalprogramStatViewVersion5.0(SASInstituteInc.,Cary,NorthCarolina).RESULTSSubjectCharacteristicsForty-foursubjectswererandomizedatbaselinetoeithertheGcambogia21)ortheplacebogroup(n23)(Figure2).Themean(SEM)VFAwas145.5(6.0)cm,andtheirmean(SEM)BMIwas28.7(0.7)kg/m[BMI25–30kg/m],30patients[68.2%];obesityclassI[BMI30–35kg/m7patients[15.9%];obesityclassII[BMI35–40kg/m],6patients[13.6%];obesityclassIII[BMI40kg/m],1patient[2.3%]).Eighteenofthe21subjects CURRENTTHERAPEUTICRESEARCH
Figure2.Studyflowdiagram.intheGcambogiagroupand21ofthe23placebogroupsubjectscompletedthe16-weekprotocol.ReasonsforsubjectwithdrawalaresummarizedinFigure2.ThenumberofGcambogiaandplacebosubjects,respectively,assessedateachperiodwereasfollows:week0,21and23;week4,19and23;week8,19and22;andweeks12and16,18and21.Thestudysubjectsrangedinagefrom20to65years(mean[SEM]age,age,years).Inananalysisincludingthesubjectswhowithdrew,nosignicantdifferenceswerefoundininitialage,bodyweight,BMI,waistandhipcircum-ference,WHR,VFA,SFA,ortotalfatarea(TFA)betweentheplacebogroupandtheGcambogiagroup(TableIINutrientIntakeTableIIIcomparesthenutrientintakebysubjectsinthe2groups.Inthemalesubjectsinbothgroups,energyexpenditurewasslightlylowerthanthe2250kcal/destablishedbytheirdietaryintervention.Inthefemalesubjectsinbothgroups,energyexpenditurewasapproximatelyequaltothe1800kcal/destab-lishedbytheirdietaryintervention.Duringthe16-weekexperimentperiod,therewerenosignicantbetween-groupdifferencesinnutrientintakeorenergyexpenditure.AbdominalFatDistributionandBodyIndicesAbdominalfatdistributionandbodyindicesareshowninTablesIVandVrespectively.Regardlessofsex,theVFA,SFA,andTFAofsubjectsintheGcambogiagroupweresignicantlylowerat12weeks(0.009,0.003,and K.Hayamizuetal. TableII.Baselinecharacteristicsofstudysubjects(N44).(Valuesaregivenasmean[SEM]unlessotherwisenoted.) GarciniacambogiaPlaceboGroupCharacteristicGroup(n21)(n Age,yMean(SEM)43.7(2.6)45.2(2.7)Range23–6423–65Sex,no.(%)Men11(52.4)13(56.5)Women10(47.6)10(43.5)Bodyweight,kgMen83.9(4.7)78.7(3.2)Women72.8(3.8)74.5(4.2)Height,cmMen170.8(1.8)171.2(1.9)Women154.2(1.4)156.1(1.5)BMI,kg/mMen28.8(1.7)26.8(0.8)Women30.6(1.5)30.6(1.7)Waistcircumference,cmMen94.6(2.9)91.3(1.9)Women97.9(3.0)98.2(2.4)Hipcircumference,cmMen99.8(1.9)100.2(1.9)Women103.5(2.5)104.7(2.4)Men0.94(0.01)0.92(0.01)Women0.95(0.01)0.94(0.01)Visceralfatarea,cmMen156.6(10.5)137.0(7.8)Women138.2(14.4)147.9(13.6)Subcutaneousfatarea,cmMen203.9(30.3)176.1(17.9)Women279.6(21.9)280.4(28.2)Totalfatarea,cmMen363.9(34.6)312.7(16.3)Women414.9(25.1)427.9(34.4) bodymassindex;WHRwaist–hipratio.0.001,respectively)and16weeks(0.001,and0.001,respectively)thanintheplacebogroup(TableIV).WithintheGcambogiagroup,eachofthesefatareasdecreasedby10%to15%frombaselinetoweek16.Whencomparingthendingsatweek12versusweek16intheGcambogiagroup,nosignicantchangeswereobservedinVFA,SFA,orTFA.Therefore, CURRENTTHERAPEUTICRESEARCH
TableIII.ComparisonofnutrientintakeandenergyexpenditurebetweentheGarciniaandplacebogroupsover16weeks(N44).(Valuesaregivenasmean[SEM].) GarciniacambogiaPlaceboGroupNutrientGroup(n21)(n Protein,g/dMen77.7(3.4)71.8(3.1)Women68.3(2.9)69.1(2.2)Fat,g/dMen59.5(4.0)57.4(3.9)Women56.4(3.8)55.6(4.2)Carbohydrate,g/dMen273.5(17.6)285.7(9.1)Women260.0(12.7)264.5(11.2)Energyexpenditure,kcal/dMen2015.5(105.5)2018.3(76.2)Women1869.3(60.1)1862.1(81.3) therewerenosignsofareboundeffectfromweek12toweek16intheGcambogiaAt12weeks,bothbodyweightandBMIwerenumericallybutnotsignicantlylowerintheGcambogiagroupthanintheplacebogroup,andweresigni-cantlylowerintheGcambogiagroupthanintheplacebogroupat16weeks0.04and0.02,respectively,vsplacebo).However,thesendingswereobservedonlyinmen,amongwhomtheWHRintheGcambogiagrouptendedtobelowerthanintheplacebogroup,althoughthedifferencewasnotsignicantTableV).Nosignicantdifferencesinotherindicesweredetectedineithersexbetweenthe2treatmentgroups.ClinicalLaboratoryTestsTheresultsofclinicallaboratorytestsareshowninTableVI.Serumtriacylglyc-erolvaluestendedtodecreaseovertimeintheGcambogiagroupbutnotsignicantly.Themeanvaluesofthehematologic,hemobiochemical,andendo-crinologicdatadidnotchangeintheGcambogiaAdverseEffectsNosubjectwasremovedfromthestudyprotocolfortreatment-relatedadverseeffects.ThefollowingadverseeffectsoccurredintheGcambogiaandplacebogroup,respectively:commoncold,1(4.8%)and10(43.5%);toothache,3(14.3%)and3(13.0%);diarrhea,2(9.5%)and4(17.4%);andheadache,0(0.0%)and4(17.4%). K.Hayamizuetal. TableIV.Mean(SEM)changesinabdominalfatdistributionversusbaselineinpatientswhocompletedthestudy(N39).(Valuesareexpressedas%unlessotherwisenoted.) AllSubjectsMenWomen GarciniaGarciniaGarciniacambogiaPlacebocambogiaPlacebocambogiaPlaceboFatDistribution/GroupGroupGroupGroupGroupGroupStudyWeek(n18)(n21)P*(n8)(n11)P*(n10)(n10)P* VisceralfatareaWeek0,mean(SEM),cm2146.2(9.9)144.9(7.5)–156.2(13.5)142.2(8.1)–138.2(14.4)147.9(13.6)–Week1289.2(2.5)105.1(3.2)0.00987.8(4.6)105.5(5.5)0.03290.2(2.9)104.8(3.2)0.003Week1686.4(2.1)106.9(3.8)0.00182.3(3.5)107.2(5.9)0.00489.7(2.3)106.5(5.2)0.004SubcutaneousfatareaWeek0,mean(SEM),cm2231.3(20.2)223.4(20.2)–170.9(22.7)171.5(18.6)–279.6(21.9)280.4(28.2)–Week1287.6(2.4)106.7(3.1)0.00390.1(2.7)107.0(5.0)0.01785.6(3.8)106.3(3.9)0.001Week1685.4(3.1)108.0(2.6)0.00188.9(3.9)110.5(3.3)0.00182.5(4.7)110.5(3.3)0.001TotalfatareaWeek0,mean(SEM),cm2379.2(21.9)367.9(22.4)–334.6(32.9)313.3(17.8)–414.9(25.1)427.9(34.4)–Week1287.7(1.6)105.6(2.2)0.00187.8(2.6)105.6(3.4)0.00187.6(2.2)105.6(3.4)0.001Week1685.2(2.3)106.3(2.2)0.00184.8(2.9)107.7(3.4)0.00185.5(3.6)104.7(2.7)0.001 *Between-groupdifference.559 CURRENTTHERAPEUTICRESEARCH
TableV.Mean(SEM)changesinanthropometricvalues,bysex,inpatientswhocompletedthestudy(N39).(Valuesareexpressedas%unlessotherwisenoted.) AllSubjectsMenWomen GarciniaGarciniaGarciniacambogiaPlacebocambogiaPlacebocambogiaPlaceboGroupGroupGroupGroupGroupGroupParameter/StudyWeek(n18)(n21)(n8)(n11)(n10)(n10) BodyweightWeek0,mean(SEM),kg75.1(2.9)75.9(2.5)78.2(4.5)77.5(3.0)72.8(3.8)74.3(4.2)Week499.4(0.3)99.8(0.3)99.2(0.5)100.1(0.5)99.4(0.4)99.4(0.4)Week898.8(0.4)99.0(0.4)98.8(0.7)99.7(0.6)98.8(0.5)98.3(0.5)Week1298.2(0.5)99.4(0.5)98.1(0.8)100.3(0.7)98.3(0.6)98.5(0.5)Week1698.0(0.6)*99.9(0.5)98.3(0.8)†100.7(0.7)97.8(0.9)98.9(0.7)BMIWeek0,mean(SEM),kg/m228.9(1.1)28.5(1.0)26.8(1.3)26.7(0.8)30.6(1.5)30.5(1.7)Week499.4(0.3)99.8(0.3)99.3(0.5)99.4(0.4)99.4(0.4)99.4(0.4)Week898.8(0.4)99.0(0.4)98.8(0.7)99.7(0.6)98.8(0.5)98.3(0.5)Week1298.2(0.5)99.4(0.5)98.2(0.8)100.3(0.7)98.3(0.6)98.5(0.5)Week1698.0(0.6)99.9(0.5)98.3(0.8)*100.7(0.7)97.8(0.9)98.9(0.7)WaistcircumferenceWeek0,mean(SEM),cm95.4(2.2)94.5(1.7)92.2(3.1)91.0(2.0)97.9(3.0)98.5(2.3)Week499.6(0.4)100.3(0.4)99.8(0.6)100.6(0.6)99.4(0.6)100.0(0.5)Week899.2(0.5)100.1(0.4)99.7(0.8)100.8(0.5)98.9(0.7)99.4(0.5)Week1298.8(0.6)99.3(0.3)99.1(0.9)99.6(0.3)98.5(0.9)98.9(0.4)Week1698.0(0.7)99.0(0.4)98.3(1.2)99.8(0.4)97.8(0.9)98.3(0.7) (continued)560 K.Hayamizuetal. TableV. AllSubjectsMenWomen GarciniaGarciniaGarciniaGroupGroupGroupGroupGroupGroupParameter/StudyWeek(n18)(n21)(n8)(n11)(n10)(n HipcircumferenceWeek0,mean(SEM),cm100.8(1.7)100.9(1.4)98.4(1.8)98.5(1.4)103.1(2.6)104.6(2.3)Week499.9(0.2)100.1(0.3)99.5(0.4)100.0(0.5)100.1(0.3)100.1(0.3)Week899.4(0.4)99.5(0.3)99.1(0.8)99.3(0.5)99.7(0.2)99.7(0.3)Week1299.0(0.3)99.0(0.3)99.1(0.8)99.0(0.5)98.8(0.2)99.0(0.4)Week1698.6(0.4)98.9(0.3)99.0(0.7)99.0(0.5)98.2(0.3)98.8(0.5)Week0,mean(SEM)0.94(0.01)0.94(0.01)0.94(0.02)0.92(0.01)0.95(0.01)0.94(0.01)Week499.7(0.4)100.2(0.3)100.3(0.4)100.6(0.5)99.3(0.7)99.9(0.4)Week899.8(0.5)100.6(0.4)100.6(0.6)101.4(0.5)99.2(0.8)99.7(0.4)Week1299.8(0.6)100.2(0.3)100.0(0.4)100.5(0.4)99.7(1.0)99.9(0.5)Week1699.4(0.6)100.1(0.4)99.2(0.6)100.8(0.5)99.6(1.1)99.4(0.7) bodymassindex;WHRwaist–hipratio.0.02versusplacebogroup.0.04versusplacebogroup. CURRENTTHERAPEUTICRESEARCH
TableVI.EffectsofGarciniacambogiaonhematologic,hemobiochemical,andendocrinologicparametersinallpatients(N43).(Valuesareexpressedasmean[SEM].) GarciniacambogiaGroupPlaceboGroup NormalWeek0Week12Week16Week0Week12Week16ParameterValue(n21)(n18)(n18)(n23)(n21)(n21) HematologyWBCcount,cells/µL3500–97006695(394)6573(456)7011(494)6533(309)6983(324)*6867(417)*RBCcount,Men,4.38–4.83(0.01)4.79(0.07)4.85(0.09)4.81(0.10)4.85(0.11)*4.88(0.10)†cells×106/µL5.77;women,3.76–5.16Hb,g/dLMen,13.6–14.4(0.4)14.4(0.4)14.5(0.4)14.6(0.3)14.7(0.3)*14.8(0.3)*18.3;women,11.2–15.2Hematocrit,%Men,40.4–45.0(1.1)45.0(1.1)45.0(1.0)45.1(0.5)45.9(0.7)†45.9(0.6)†51.9;women,34.3–45.2Plateletcount,cells×103/µL140–379270(12)265(17)268(18)255(13)235(15)253(15)HemobiochemistryAST,U/L10.0–40.032.0(3.0)31.2(3.3)34.1(4.4)28.8(1.9)30.4(2.5)30.1(2.4)ALT,U/L5.0–45.051.9(8.4)43.2(5.9)48.6(7.8)40.9(4.7)42.5(5.2)43.0(5.4)GGTP,U/L16.0–73.057.9(7.6)62.6(10.0)63.9(9.4)54.7(7.9)55.0(8.8)54.0(8.8)LDH,U/L220.0–430.0344.3(11.8)334.2(14.8)335.7(11.8)354.2(10.9)358.8(19.5)347.9(10.2)BUN,mg/dL8.0–20.013.0(0.7)12.9(0.9)12.9(0.8)12.8(0.5)12.6(0.6)13.3(0.5)Creatinine,mg/dL0.6–1.30.97(0.03)0.94(0.03)0.94(0.03)0.99(0.03)0.94(0.03)†0.92(0.04)†Triacylglycerol,mg/dL50.0–149.0169.1(11.7)154.4(14.1)146.2(15.2)177.4(20.7)183.7(19.0)173.7(19.7)FFA,mEq/L0.10–0.810.73(0.05)0.72(0.05)0.71(0.07)0.73(0.05)0.71(0.07)0.68(0.06)TC,mg/dL150.0–219.0213.4(5.7)208.8(7.7)210.8(6.7)211.8(8.1)213.7(9.0)217.7(9.1) (continued)562 K.Hayamizuetal. TableVI. GarciniacambogiaGroupPlaceboGroup NormalWeek0Week12Week16Week0Week12Week16ParameterValue(n21)(n18)(n18)(n23)(n21)(n HDL-C,mg/dLMen,41.0–48.9(2.4)48.7(2.4)50.7(1.8)47.8(2.2)46.6(2.1)47.9(2.1)80.0;women,LDL-C,mg/dL60–130140.1(4.9)137.3(6.1)139.1(6.4)139.2(6.6)140.2(7.9)143.0(7.4)FPG,mg/dL70–13994.0(2.2)92.1(1.7)94.3(2.8)90.8(1.7)91.3(1.9)90.0(1.6)Acetoaceticacid,55.017.2(2.7)20.6(1.6)21.6(4.3)16.8(1.4)17.8(2.5)16.2(1.6)3-Hydroxybutyricacid,8538.6(6.1)37.8(3.2)45.1(9.7)33.0(3.6)33.2(5.5)30.0(3.5)Totalketonebodies,131.055.8(8.5)58.4(4.3)66.7(13.9)49.8(4.3)51.0(7.6)46.2(4.4)U/mL3.0–18.013.3(2.0)9.9(1.1)11.8(1.6)9.8(1.1)11.9(1.5)11.6(1.5) whitebloodcell;RBCredbloodcell;Hbhemoglobin;ASTaspartateaminotransferase;ALTalanineaminotransferase;GGTP-glutamyltransferase;LDHlactatedehydrogenase;BUNbloodureanitrogen;FFAfreefattyacid;TCtotalcholesterol;HDL-Clipoproteincholesterol;LDL-Clow-densitylipoproteincholesterol;FPGfastingplasmaglucose.0.05versusweek0(paired0.01versusweek0(paired ThedietaryhabitsoftheJapanesehavebeenWesternizedrapidlysincetheendofWorldWarII.Withpoorernutrition(ie,higherfatintake),thecausesofdeathinJapanhavechangedconsiderably.IntheearlyresearchintoobesityinJapanandinWesterncountries,manystudiesinvestigatedtherelationshipbetweenbodyweightorBMIandlifestylediseasessuchastype2diabetes,coronaryheartdisease,andhypertension.Recently,attentionhasfocusedontherelationshipbetweenabdominalfatdistributionandlifestylediseasesbyCTanalysis;inparticular,therelationshipbetweenVFAandmultipleriskfactors(type2diabetesmellitus,dysglycemia,hypertension,coronaryheartdisease,hyperuricemia)hasbeenreported.AccordingtotheJapanSocietyfortheStudyofObesity,visceralfatobesityisdiagnosedwhenVFAis100cm.Theconceptofa“visceralfataccumulation”typeofobesityisnewandveryim-portantforthestudyofobesityasadisease,anditisexpectedtobeusefulinstudiesofthepreventionoftheaforementionedriskfactors.ThepresentstudywasdesignedtoassesstheefcacyofGcambogiainanti–visceralfataccumulationinobesesubjects.Toaccountforprevisceralfatobesity,inclusioncriteriaincludedVFA90cm.TheVFAinclusioncriterionwassetat90cmbecausethatamountaccountedfor“previsceralfatobesity.”Comparedwiththeplacebogroup,theGcambogiagrouphadsignicantde-creasesinVFA,SFA,andTFA;nosignicantdifferenceswereobservedbetweenmaleandfemalesubjects.Furthermore,thetestresultsforabdominalfatareahadsufcientpower(1–ß0.8),sothesamplesizewasappropriate.Inapreviousstudy,wereportedontheefcacyofHCA,butthesubjectswereclassiedasoverweightorobeseusingBMI,whereasinourstudy,bothBMIandVFAwereusedtodeneobesity,andallsubjectswereclassiedasobese.Otherdifferencesbetweenthatstudyandthepresentonearethatthetreatmentperiodwas8weeks,andtherewasnodetaileddietaryintervention.Inthatprevi-ousreport,unlikethepresentone,therewasnoobservedeffectofGcambogiaSFAorTFA.However,thesedifferencesinoutcomeswereexpectedbecauseofthedifferencesinthetreatmentperiods,theVFAlevelsofthesubjects,andtheuseofdietaryintervention.Inthepresentstudy,subjectsintheGcambogiagroupunderwenta4-weekplacebotreatmentaftertheir12-weektreatmenttodetectanyreboundeffect.Nosucheffectwasfound.Thisresultwasexpectedbecausethedecreaseinabdominalfatfromweeks0to12wasmild.ACTscanwasperformedat0,12,and16weeks.Ifthesemeasurementshadbeenconductedevery4weeks,theeffectofGcambogiamayhavebeendetectedatanearlierperiod.Anthropometricindicesincludedbodyweight,BMI,andWHR.BodyweightandBMItendedtobelowerintheGcambogiagroupthanintheplacebogroupatboth12and16weeksbutonlyinmen.IntheirinvestigationofanantiobesityeffectofGcambogia,Heymseldetalreportedthatbodyweightchangeduringtheir12-weekstudyperioddidnotdiffersignicantlybetweenGcambogiaandplacebogroups.Inthatreport,mostofthesubjectswere K.Hayamizuetal.women.Amongthefemalesubjectsinourstudy,bodyweightandBMIdidnotdifferbetweenthe2groups,andtothatextentourresultsandthoseofHeyms-eldetalaresimilar.Theresultsofclinicallaboratorytestsdidnotchangesignicantly,andnoadverseeffectswereobservedatanytimeinthetestperiod.TheGcambogiatabletusedinthisstudywaswelltoleratedthroughoutthe12-weektreat-mentperiod.Gcambogiareducedabdominalfataccumulationinsubjects,regardlessofsex,whohadthevisceralfataccumulationtypeofobesity,andnoreboundeffectwasobserved.ItisthereforehypothesizedthatGcambogiamaybeusefulforthepreventionandreductionofaccumulationofvisceralfat.WethankShintaroYano,MD(MaebashiHirosegawaClinic,Gunma,Japan)andNobuhikoHosokawa,MD(OnoClinic,Osaka,Japan)fortheirhelpfuladviceandencouragementinthisstudy.1.MinistryofHealth,LabourandWelfareJapan.TheNationalNutritionSurveyinJapanTokyo,Japan:Dai-ichiShuppanPublishing;2002:59–60.2.DespresJP,LamarcheB.Effectsofdietandphysicalactivityonadiposityandbodyfatdistribution:Implicationsforthepreventionofcardiovasculardisease.NutrRes.1993;6:137–159.3.BrayGA.Complicationsofobesity.AnnInternMed.1985;103:1052–1062.4.Healthimplicationsofobesity.NationalInstitutesofHealthConsensusDevelopmentConferenceStatement.AnnInternMed.1985;103:1073–1077.5.KissebahAH,FreedmanDS,PeirisAN.Healthrisksofobesity.MedClinNorthAm6.VanItallieTB.Obesity:Adverseeffectsonhealthandlongevity.AmJClinNutr1979;32(Suppl12):2723–2733.7.LarssonB,BjorntorpP,TibblinG.Thehealthconsequencesofmoderateobesity.IntJObes.1981;5:97–116.8.MansonJE,StampferMJ,HennekensCH,WillettWC.Bodyweightandlongevity.A.1987;257:353–358.9.SeidellJC,VerschurenWM,vanLeerEM,KromhoutD.Overweight,underweight,andmortality.Aprospectivestudyof48,287menandwomen.ArchInternMed10.HubertHB,FeinleibM,McNamaraPM,CastelliWP.Obesityasanindependentriskfactorforcardiovasculardisease:A26-yearfollow-upofparticipantsintheFraming-hamHeartStudy..1983;67:968–977. 11.JousilahtiP,TuomilehtoJ,VartiainenE,etal.Bodyweight,cardiovascularriskfactors,andcoronarymortality.15-Yearfollow-upofmiddle-agedmenandwomenineasternFinland..1996;93:1372–1379.12.StamlerR,StamlerJ,RiedlingerWF,etal.Weightandbloodpressure.Findingsinhypertensionscreeningof1millionAmericans..1978;240:1607–1610.13.VanItallieTB.HealthimplicationsofoverweightandobesityintheUnitedStates.AnnInternMed.1985;103:983–988.14.SaitoY,ed.ManualfortheTreatmentofObesity.Tokyo,Japan:IshiyakuPublishers;15.NakamuraT,TokunagaK,ShimomuraI,etal.Contributionofvisceralfataccumula-tiontothedevelopmentofcoronaryarterydiseaseinnon-obesemen.16.MatsuzawaY,ShimomuraI,NakamuraT,etal.Pathophysiologyandpathogenesisofvisceralfatobesity.ObesRes.1995;3(Suppl2):187S–194S.17.ReavenGM.Bantinglecture1988.Roleofinsulinresistanceinhumandisease..1988;37:1595–1607.18.KenoY,MatsuzawaY,TokunagaK,etal.HighsucrosedietincreasesvisceralfataccumulationinVMH-lesionedobeserats.IntJObes.1991;15:205–211.19.LewisYS,NeelakantanS.(-)-Hydroxycitricacid—theprincipalacidinthefruitsofGarciniacambogia.1965;4:619–625.20.WatsonJA,LowensteinJM.Citrateandtheconversionofcarbohydrateintofat.Fattyacidsynthesisbyacombinationofcytoplasmandmitochondria.JBiolChem21.WatsonJA,FangM,LowensteinJM.Tricarballylateandhydroxycitrate:SubstrateandinhibitorofATP:Citrateoxaloacetatelyase.ArchBiochemBiophys.1969;135:209–217.22.SullivanAC,SinghM,SrerePA,GluskerJP.Reactivityandinhibitorpotentialofhydroxycitrateisomerswithcitratesynthase,citratelyase,andATPcitratelyase.JBiolChem.1977;252:7583–7590.23.LowensteinJM.Effectof(-)-hydroxycitrateonfattyacidsynthesisbyratliverinJBiolChem.1971;246:629–632.24.SullivanAC,TriscariJ,HamiltonJG,etal.Effectof(-)-hydroxycitrateupontheaccumulationoflipidintherat.I.Lipogenesis..1974;9:121–128.25.SullivanAC,TriscariJ,HamiltonJG,MillerON.Effectof(-)-hydroxycitrateupontheaccumulationoflipidintherat.II.Appetite..1974;9:129–134.26.SullivanC,TriscariJ.Metabolicregulationasacontrolforlipiddisorders.I.Inuenceof(-)-hydroxycitrateonexperimentallyinducedobesityintherodent.AmJClinNutr27.BerkhoutTA,HavekesLM,PearceNJ,GrootPH.Theeffectof(-)-hydroxycitrateontheactivityofthelow-density-lipoproteinreceptorand3-hydroxy-3-methylglutaryl-CoAreductaselevelsinthehumanhepatomacelllineHepG2.BiochemJ.1990;28.ConteAA.Anon-prescriptionalternativeinweightreductiontherapy.AmJBariatrMedSummer.1993;17–19.29.ThomE.Hydroxycitrate(HCA)inthetreatmentofobesity.IntJObes.1996;20(Suppl4):48.30.RothackerDQ,WaitmanBE.EffectivenessofaGarciniacambogiaandnaturalcaffeinecombinationinweightloss:Adouble-blind,placebo-controlledpilotstudy.IntJObes1997;21(Suppl2):53. K.Hayamizuetal.31.SawadaH,TomiH,TamuraK,etal.EffectofliquidGarciniaextractandsolubleGarciniapowderonbodyweightchange:ApossiblematerialforsuppressingfatJpnOilChemSoc.1997;46:1467–1474.32.HayamizuK,IshiiY,KanekoI,etal.Effectsoflong-termadministrationofextractonvisceralfataccumulationinhumans:Aplacebo-controlleddoubleblindtrial.JOleoSci.2001;50:805–812.33.TheMinistryofHealthandWelfare.6thRecommendedDietaryAllowancesfortheTokyo,Japan:Dai-ichiShuppanPublishing;1999:36–41.34.HeymseldSB,AllisonDB,VasselliJR,etal.Garciniacambogia(hydroxycitricacid)asapotentialantiobesityagent:Arandomizedcontrolledtrial..1998;280:Addresscorrespondenceto:KohsukeHayamizu,MSCentralResearchLaboratoryFANCLCorp.12-13Kamishinano,Totsuka-kuYokohama,Kanagawa244-0806