WeightLossNutritional Supplements JoanM.Eckerson
Abstract
Obesityhasreachedwhatmaybeconsideredepidemicproportionsinthe UnitedStates,notonlyforadultsbutforchildren.Becauseofthemedical implicationsandhealthcarecostsassociatedwithobesity,aswellasthenegative socialandpsychologicalimpacts,manyindividualsturntononprescription nutritionalweightlosssupplementshopingforaquickfix,andtheweightloss industryhasrespondedbyofferingavarietyofproductsthatgeneratesbillionsof dollarseachyearinsales.Mostnutritionalweightlosssupplementsarepurported toworkbyincreasingenergyexpenditure,modulatingcarbohydrateorfatmetabolism,increasingsatiety,inducingdiuresis,orblockingfatabsorption.To reviewtheliterallyhundredsofnutritionalweightlosssupplementsavailableon themarkettodayiswellbeyondthescopeofthischapter.Therefore,severalofthe mostcommonlyusedsupplementswereselectedforcriticalreview,andpractical recommendationsareprovidedbasedonthefindingsofwellcontrolled,randomizedclinicaltrialsthatexaminedtheirefficacy.Inmostcases,thenutritional supplementsreviewedeitherelicitednomeaningfuleffectorresultedinchangesin bodyweightandcompositionthataresimilartowhatoccursthrougharestricted dietandexerciseprogram.Althoughthereissomeevidencetosuggestthatherbal formsofephedrine,suchasmahuang,combinedwithcaffeineorcaffeineand aspirin(i.e.,ECAstack)iseffectiveforinducingmoderateweightlossinoverweightadults,becauseoftherecentban onephedramanufacturersmustnowuse ephedra-freeingredients,suchasbitterorange,whichdonotappeartobeas effective.Thedietaryfiber,glucomannan,alsoappearstoholdsomepromiseasa possibletreatmentforweightloss,butotherrelatedformsofdietaryfiber, includingguargumandpsyllium,areineffective.
Keywords
Dietarysupplements Ephedra Obesity Overweight Complementary medicine Alternativemedicine Herbalmedicine Chromium Calcium
Chitosan Pyruvate Garcinia Psyllium Citrusaurantium Bitterorange
Guarana Herbalcaffeine Conjugatedlinoleicacid
From: NutritionalSupplementsinSportsandExercise
Editedby:M.Greenwood,D.Kalman,J.Antonio, DOI:10.1007/978-1-59745-231-1_8, HumanaPressInc.,Totowa,NJ
225
ObesityhasreachedepidemicproportionsintheUnitedStates, notonlyforadultsbutforadolescentsandchildren,aswell.Accordingtodatafromthe2001–2004NationalHealthandNutrition ExaminationSurveyreleasedbytheCentersforDiseaseControl, 32%ofadultsintheUnitedStateswereobese[bodymassindex (BMI) 30kg m2],and66%wereconsideredoverweight(BMI 25kg m2).Incomparison,theincidencesofoverweightandobese adultsin1974were47.7%and14.6%,respectively.Althoughthe numberofoverweightadultshasdramaticallyincreasedduringthe last30years,theincreaseinthenumberofoverweightchildrenand adolescentsisevenmorealarming.In1970,theincidenceofoverweightchildrenwas4.2%comparedto17.5%in2004,whichrepresentsanincreaseofmorethan400%.Becauseofthemedical implicationsandhealthcarecostsassociatedwithobesity,aswell asthenegativesocialandpsychologicalimpacts,manyindividuals turntononprescriptionnutritionalweightlosssupplementshoping foraquickfixorananswertotheirunsuccessfulattemptsatdieting andexercisetoloseweight.Infact,ithasbeensuggestedthatmany individualspreferdietarysupplementsandprescriptionweightloss drugstomakinghealthierlifestylechanges (1)
Theweightlossindustryhasrespondedtotherisingratesof obesityand,asaresult,generatesbillionsofdollarseachyear throughthesaleofavarietyofproductsandcommercialweight lossbusinesses.In2001,Americansspentmorethan$36billionon videos,books,low-caloriefoodsanddrinks,sugarsubstitutes,medicaltreatments,commercialweightlosschains,over-the-counter (OTC)drugs,andofcoursenutritionalsupplementstoassistin their‘‘battleofthebulge’’ (2).Infact,retailsalesofOTCnutritional weightlosssupplementsalonewereestimatedtobemorethan$1.3 billionin2001 (3).
Weightlosssupplementsarenotjustusedbyoverweightindividuals.Resultsofamultistatesurveyconductedin1998byBlancket al. (4) indicatedthat7%ofadultsatthattimeusedOTCweightloss supplementsandthatthegreatestconsumerswereobeseyoung women(28.4%).Interestingly,however,7.9%ofnormalweight womenalsoreportedusingdietarysupplementsforweightloss. Giventhatobesityrateswilllikelycontinuetoclimboverthenext
1.INTRODUCTION
226 Eckerson
severalyearsand,correspondingly,theuseofOTCnutritional weightlosssupplementsbyobeseandoverweightindividualswill alsocontinuetoincrease,itisimportantforhealthprofessionalsto understandthephysiologicalmechanismsbywhichtheseproducts arepurportedtoresultinweightloss,aswellastheirsafetyand efficacy.MostOTCweightlosssupplementsarepurportedtowork byincreasingenergyexpenditure,modulatingcarbohydrateor fatmetabolism,increasingsatiety(feelingoffullness),inducing diuresis,orblockingfatabsorption.
2.NUTRITIONALSUPPLEMENTSTHATINCREASE ENERGYEXPENDITURE
2.1.EphedraAlkaloidsandHerbalCaffeine
Ephedra,alsoknownas mahuang,isprobablyoneofthemost widelyrecognizednutritionalsupplementsusedforweightloss. Becauseofseveralsafetyconcerns—hypertension,arrhythmias, heartattack,stroke,andevendeath—theU.S.FoodandDrug Administration(FDA)removedephedraproductsfromtheU.S. marketin2004becausetheriskofitsusewasdeemedgreaterthanits benefitsforweightloss.
EphedraisderivedfromashrubthatisnativetoChina(Ephedra sinica)andhasbeenusedformorethan5000yearsasanatural treatmentforasthmaandotherconditions (5).Theephedrine alkaloidspresentintheplantcontainsympathomimeticcompounds [i.e.,centralnervoussystem(CNS)stimulants]andareasourceof ephedrineandpseudophedrine,whichareusedinmanydecongestantsandcoldmedicines.Thehistoryofephedrineasaweightloss supplementgoesbackto1972whenaDanishphysicianinElsinore, Denmarkwhowastreatinghisasthmaticpatientswithacompound thatcontainedephedrineandcaffeinenoticedthattheywereexperiencingunintentionalweightloss.Hiscompoundbecameknownas theElsinorepill,andby1977itwasbeingusedbymorethan70,000 patients (6).Beforetheyweretakenoffthemarketin2004,dietary supplementsthatcontainedephedrinealkaloidswereregulated undertheDietarySupplementsHealthandEducationAct (DSHEA),butephedrineandpseudoephedrineareregulatedby thegovernmentasdrugs.
WeightLossNutritionalSupplements 227
Ephedrineandnorephedrineareanalogsofmethamphetamine andamphetamine,respectively,andthereforearepotentCNSstimulantsthatactasboth a-and b-adrenergicagonists,releasing epinephrinefromsympatheticneurons (7).Theactionofephedra onadrenergicreceptorsincreasesthermogenesisandsuppresses hunger,whichinturnpromotesweightloss (5).Inanimalstudies, ithasbeenshownthatephedrinestimulatesthermogenesisinbrown adiposetissueviatheactivationof b-receptors;however,because humanshavelittlebrownadiposetissue,itisbelievedthatthermogenesisprimarilyoccursintheskeletalmuscle (6).
Arecentmeta-analysisbyShekelleetal. (8) thatexaminedthe efficacyandsafetyofephedraandephedrine-containingproducts foundthattheyhavemodestshort-termbenefits(upto6months) andareassociatedwithanincreasedriskofexperiencinganadverse event.Intheirstudy (8),ephedraresultedinweightlossthatwasonly 0.9kg( 2lb)morepermonththanwasachievedwithaplacebo,but ledtoa2.2-to3.6-foldincreaseintheoddsofexperiencingpsychiatric, autonomic,orgastrointestinalproblemsandarrhythmiasoftheheart.
Inanefforttomaximizefatburning,ephedrinehasbeenusedin combinationwithcaffeineandaspirin,whichisoftenreferredtoas anECAstack.Itisbelievedthatwhenthesethreecompoundsare takentogether(recommendedratio:60mgephedrine/200mgcaffeine/300mgaspirin),itresultsinanevengreaterthermogeniceffect thanthatofephedraaloneandmaybemoreeffectiveforinducing weightloss (9,10).Herbalequivalentsthatareoftenusedasa substituteforcaffeineinnutritionalweightlosssupplementsinclude guarana,kolanut,yerbamate,greentea,andyohimbe.Similarly, willowbarkisoftenusedinplaceofaspirin.HydroxycutTM isjust oneexampleofawellknownOTCproductthatcontainedanECA stack(mahaung,guarana,andwillowbark)beforetheFDAban in2004.
Thereissomeevidencetosuggestthatthecombinationofephedra withcaffeineand/oraspirin(ortheirherbalconstituents)mayindeed bemoreeffectiveforinducingweightlossthanephedraalone.Inan extensivereview,Greenway (6) examinedthesafetyandefficacyof ephedrinepluscaffeine(EC)andreportedthatthecombinationwas aseffectiveassomeprescriptionweightlossdrugsandwasassociated withfewersideeffects.InthestudiesreviewedbyGreenway (6),the acutesideeffectsforECwereconsideredmildandtransient,and
228 Eckerson
aftercontinuoustreatmentfor4to12weeksthereportedsideeffects werenotsignificantlydifferentfromthoseofaplacebo.Asaresult, Greenway (6) suggestedthatthebenefitsofECoutweightheassociatedrisksandpointedoutthatmanyoftheseriousadverseevents thathavebeenreportedintheliteraturearevoluntarycasereports thathavenoplaceboorcontrolgroupsforcomparison.Therefore,in hisopinion (6),theargumentforremovingherbalproductscontainingephedrinewassomewhatunfounded.
Hutchins (11) alsoindicatedthatmanyoftheephedraalkaloidrelateddeathsreportedintheliteratureoccurredinindividualswith preexistingcardiovascularconditionsorrisksand,therefore,thedangersassociatedwithephedrauseinhealthyindividualsmaybewidely speculative.Inaddition,Dulloo (12) suggestedthatmixturesofephedrineandcaffeinemayofferaviable,cost-effectiveapproachtothe treatmentofobesityandhasrecommendedthatmorelarge-scaleclinicaltrialsbeconductedtogainabetterunderstandingoftherisksand benefitsassociatedwiththecombinationofephedrineandcaffeine.
Intwoseparatestudies,Boozeretal. (5,13) alsoreportedthatma huang(herbalephedra)combinedwitheitherguarana (5) orkola nuts (13) wasmoreeffectiveforweightlossinoverweightmenand womenthanplaceboandresultedinnoadverseeventsandminimal sideeffects.Inthestudythatexaminedtheeffectsofmahuangand guarana (5),thetreatmentwasacommercialherbalmixturecalled Metabolife-3561,whichcontainedanequivalentof72mgofephedrineand240mgofcaffeine.Following8weeksofsupplementation,thetreatmentgrouplostsignificantlymorebodyweight(4.0 –3.4kg)andpercentbodyfat(2.1% – 3.0%fat)versustheplacebo group(0.8 – 2.4kgand0.2% – 2.3%fat,respectively).Intheother studybyBoozeretal. (13) thatexaminedtheeffectsofmahuang andkolanutonweightloss,theherbalpreparationwasequivalent to90mgofephedrineand192mgofcaffeine;whencomparedto placebo,itresultedinsignificantdecreasesinbodyweight(5.3 – 5.0 vs.2.6 – 3.2kg)andfatweight(4.3 – 3.3vs.2.7 – 2.8kg).Inboth studies (5,13),theherbalpreparationsalsoresultedinsignificant improvementsinthebloodlipidprofilesofthesubjects.Kalmanand Minsch (14) alsoshowedthatsupplementationofanECAstack (20mgephedrine þ 200mgcaffeine þ 325mgaspirin)for6weeksin overweightmenresultedinweightlossthatwassignificantlygreater whencomparedtoplacebo(4.17vs.0.68kg,respectively).In
WeightLossNutritionalSupplements 229
agreement,Dalyetal. (15) alsoreportedthatanECAcombination (75–150mgephedrine þ 150mgcaffeine þ 330mg)resultedinmodestsustainedweightloss(2.2–5.2kg)in24obeseindividualscomparedtoplaceboandreportedthatthedoseswerewelltoleratedand hadnomeaningfuleffectsonheartrate,bloodpressure,insulinand glucoseconcentrations,orcholesterollevels.
Insomewhatcontrasttothestudiesdescribedabove,Vukovich etal. (16) reportedthatacuteadministration(3hours)ofherbal ephedrineandcaffeineatdosesof20mgand150mg,respectively, significantlyincreasedheartrate(22.7% – 5.5%),systolicblood pressure(9.1% – 2.2%),andrestingenergyexpenditure(REE) (8.5% – 2.0%)comparedtobaselinevalues.Althoughtheauthors (16) didnotdirectlyexaminetheeffectsoftheherbalmixtureon bodyweight,theysuggestedthattheincreaseinREEwouldbe negligibleintermsofweightloss.
Basedonmostofthefindingsintheliterature,itappearsthat herbalephedrinecombinedwithcaffeineorwithcaffeineandaspirin iseffectiveforinducingmoderateweightlossinoverweightadults whoareotherwisehealthyandhavenopreexistingcardiovascularor cerebrovascularconditions.Becauseofsafetyconcerns,andconsideringthatmanyindividualsmightbeunawareofunderlyingconditionsthatmaypredisposethemtoanincreasedriskfromherbal preparationsthatmimicbothcaffeineandephedra,consultation withaphysicianpriortotheirusemaybewarrantedasaprecaution.
2.2.BitterOrange (CitrusAurantium)
ThebanofephedrabytheFDAin2004hasledtotheproliferationofanumberof‘‘ephedra-free’’dietarysupplements.Manyof theseproductscontainbitterorange,whichisalsoknownas Citrus aurantium,zhishi,Sevilleorange,orsourorangeandreferstoa smallcitrustree(C.aurantium)anditspeelandfruit (17).Theactive componentsinbitterorangearesynephrineandoctopamine,which arestructurallysimilartoepinephrineandnorepinephrine,respectively.Therefore,thesecompoundsarealsochemicallyrelatedto ephedrineandarebelievedtoaffect a-receptorsand b3 receptors, butnot b1 or b2 receptors.Becausesynephrinedoesnotaffect b1 or b2 receptors,itisreportedlylessactiveintheCNSthanephedrine andistheorizedtohavefeweradverseeffects (17)
230 Eckerson
Thereissomeconfusionintheliterature,however,regardingthe actionofsynephrine.Forexample,Fugh-BermanandMyers (17) havereportedthatsynephrine(andoctopamine)activate b3 adrenoreceptorsbutnot b1 or b2 receptors,whichacttostimulatetheheart(b1 and b2)andresultinsystemicvasodilation(b2).However,Bentetal. (18) andPenzaketal. (19) reportedthattheextractscontainedin bitterorangeprimarilystimulate a1-adrenergicreceptorsbecausethey resemblephenylephrine(aselective a receptoragonistcommonlyused asanasaldecongestantthatisalsoknownasNeo-Synephrine)and wouldresultinvasoconstrictionandincreasedbloodpressure.
Itappearsthatmuchoftheconfusionliesinthefactthatthereare severalisomersofsynephrineincludingpara(p)-synephrine,meta (m)-synephrine,andortho(o)-synephrine,andthatitisnotexactly knownwhichoftheseisomersorcombinationofisomersarepresent innutritionalweightlosssupplementsproducts.Inaddition,thereis someconfusionastowhichsynephrinealkaloidsareactuallypresent inbitterorangeitself (20).Thisinformationiscritical,asthese variousisoformsexhibitdifferentpharmacologicalproperties.The differencesinthestudies (17–19) mentionedaboveregardingthe exactmechanismofactionofbitterorangearerelatedtothedifferent synephrineisoformsthateachauthorsuggestsiscontainedinthe extract.Forexample,Penzaketal. (19) andBentetal. (18) stated thatitcontains m-synephrine(i.e.,phenylephrine),whereasFughBermanandMyers (17) specificallystatedthat m-synephrine(phenylephrine)is not presentin C.aurantium andthatitsmostactive componentis p-synephrine.Blumenthal (21) hasalsostatedthatthe typeofsynephrineinbitterorangepeelis p-synephrineandthatithas beenincorrectlycharacterizedas m-synephrinebyvariousauthors. However,intheirtechnicalreportoftheconstituentsofbitterorange, Allisonetal. (20) statedthattheywereunabletofindanyconvincing datathatbitterorangesolelycontains m-synephrineor p-synephrine. Consideringforamomentthatbitterorangecontainsonly p-synephrineandthereforeselectivelyactivates b3 receptors,it seemsreasonabletosuggestthatthisisoformwouldbeableto induceweightlosswithfewersideeffectsthanotherCNSstimulants,including m-synephrine.However,becauseoftheirselective activationof b3 receptors,thesecompoundsmaybeineffectivein humans.Animalstudiesusingfatcellsfromrats,hamsters,anddogs haveshownthat b3 agonists,suchassynephrineandoctopamine,
WeightLossNutritionalSupplements 231
havepotentlipolyticeffects;however,theyareweakstimulatorsin humanfatcells (17).Humanadipocytesrespondtoactivationof b1 or b2 receptorsandhavelittleexpressionfor b3 receptors.Therefore, itrequireshighconcentrationsofsynephrine(0.1–1.0mM)to stimulatefatcellsinhumans (22).
AsindicatedbyAllisonetal. (20),itislikelythatmostweightloss productscontainingbitterorangecontainboth p-and m-synephrine. Intheirtechnicalreport,Allisonetal. (20) analyzedaweightloss supplementcalledUltimateThermogenicFuelTM,whichstatedon thelabelthatitcontained m-synephrinefrombitterorange.The authorsdidindeedfindthattheproductcontainedboththe p-and m-isoforms.Therefore,ifbitterorangecontainsonly p-synephrine, themanufacturersoftheseweightlossproductsareeitheradding synthetic m-synephrineorareincludingotherCNSstimulants(e.g., guarana,caffeine,mahuang,yohimbe) (20).Asevidenceofthis,one needsonlytoreadthelabelonseveralothercommonlyusedOTC weightlosssupplementstoseethatmostdo,infact,includeseveral CNSstimulantsasaproprietaryblendtoboostthethermogenic effect.Forexample,inadditiontobitterorange,XenadrineEFXTM (CytodyneLLC)alsoincludestyrosine,greentea,yerbamate,and guarana.Similarly,CortiSlimTM (WindowRockHealthLaboratory) containsbitterorange,chromium,andgreentea,whichareall believedtohaveaneffectonweightloss.
Giventhatthesenewlyreformulatedweightlosssupplements containbitterorange,aswellasseveralotherbotanicalsthatalso havesympathomimeticactivity,thereissomeconcernthattheypose thesamerisksasephedra.Tohelpclarifythispoint,Halleretal. (23) examinedthepharmokineticsandcardiovasculareffectsoftwo oraldietaryweightlosssupplementscontainingbitterorangein10 healthyadultswhorangedinagefrom18to49years.Thesubjects weregivenasingledoseofAdvantraZTM (46.9mgsynephrine), Xenadrine-EFX(5.5mgsynephrine,5.7mgoctopamine,239.2mg caffeine),oraplaceboonthreeoccasionsthatwereseparatedbya 1-weekwashoutperiod.Theresultsshowedthat,comparedtothe placebo,Xenadrine-EFXincreasedsystolicbloodpressure(SBP) (9.6 – 6.2mMHg)anddiastolicbloodpressure(DBP)(9.1 – 7.8mM Hg),withpeakincreasesoccurring 2hoursafteringestion.AdvantraZ,however,hadnomeaningfuleffectsonbloodpressure. Heartrate(HR)wassignificantlyelevated6hoursafterdosing
232 Eckerson
withbothXenadrine-EFX(16.7 – 12.4b min –1)andAdvantra Z(11.4 – 10.8b min–1)comparedtoplacebo.Thepharmokinetics weresimilarforthetwosupplementsandshowedthatboth synephrineandoctopaminearepoorlyabsorbedand/orrapidly metabolizedwhentakenorally.Thetimetopeakplasmaconcentrationwas1to2hours,andthehalf-lifewasapproximately3hours forbothtreatments.
ThefindingthatAdvantraZ,whichcontainedeighttimesthe amountofsynephrineasXenadrine-EFX,hadnoeffectonblood pressuresuggeststhatithasminimalpharmacologicalactivity (23). However,whenbitterorangeiscombinedwithotheractiveherbal ingredients,aswasthecasewithXenadrine-EFX,thebloodpressureincreasedsignificantly.Thefindingthatbothsupplements resultedinashort-termincreaseinHRalsosuggeststhatbitter orangemayhavesome b1-adrenergicactivity (23).
Inastudythatexaminedthecardiovasculareffectsofbitter orange—intheformofsourorangejuice(SOJ)—Penzaketal. (19) reportedfindingssimilartothoseofHalleretal. (23).The specificpurposeoftheirstudy (19) wastoquantifythecontentof bothsynephrineandoctopamineinSOJanddetermineitseffectson SBP,DBP,meanarterialpressure(MAP),andHRin12normotensive(SBP/DBP 140/90mmHg)youngadults(agerange20–27 years).Eachsubjectservedashisorherowncontrolandconsumed either8ozoffreshlysqueezedSOJ( 14mgsynephrine)followedby repeatingestion8hourslater,or8ozofwaterusingthesame protocol,witha1-weekwashoutbetweenthetwotrials.
TheresultsshowedthatSOJhadnosignificant(p > 0.05)effect onanyoftheparametersmeasured(SBP,DBP,MAP,HR)when comparedtowatereventhoughtheSOJcontainedwhattheauthors (19) representedas 28mgof m-synephrine(andnooctopamine), whichisanamountcomparabletothatincludedincommonlyused decongestantmedicationscontainingphenylephrine.Theauthors (19) alsotestedregularorangejuicefromfrozenconcentrateand foundnotracesofsynephrineoroctopamine,whichindicatesthat thesecompoundsarederivedonlyfromthefruitof C.aurantium.
Penzaketal. (19) suggestedthattheirlackofsignificantfindings couldhavebeenduetothepoorbioavailabilityofsynephrine, whichwouldagreewiththefindingsofHalleretal. (23),asthey alsoreportedthatsynephrinewaspoorlyabsorbed.Interestingly,
WeightLossNutritionalSupplements 233
however,Penzaketal. (19) didnotquantifytheisomers(i.e., p-and m-)ofthesynephrinecontainedintheSOJeventhoughtheyimplied thatitcontainedthe m-form.Therefore,inthisauthor’sopinion,it maybethatSOJprimarilycontains p-synephrine,whichwould explaininpartwhytherewerenosignificantcardiovasculareffects, asitwouldnotactivate b1 or b2 receptors.
BaseduponthefindingsofHalleretal. (23) andPenzaketal. (19),itappearsthatbitterorange alone maybeconsideredsafer thanephedra.However,whenitiscombinedwithothersympathomimeticssuchasguarana,caffeine,greentea,ortyrosine,itmay resultintransientincreasesinbloodpressureandHR.
Inoneofthefirstclinicalstudiestoinvestigatetheeffectofbitter orangeonweightloss,Colkeretal. (24) examinedtheeffectofan herbalmixturethatcontained975mgof C.aurantium extract(6% synephrinealkaloid),900mgofSt.John’swort(3%hypericum),and 528mgofcaffeineonbodyfatin20overweight(BMI > 25kg/m2),but otherwise,healthyadults.Thesubjectswererandomlyplacedina controlgroup(n =4),aplacebogroupthatingestedmaltodextrin (n =7),ortheactivetreatmentgroup(n =9);ifapplicable,thesubjectsingestedtheirrespectivesupplementoncedailyfor6weeks.All subjectsparticipatedinacircuittrainingexerciseprogramthreetimesa weekfor45minutespersessionandreceivedindividualcounseling fromaregistereddietitian tocomplywithan1800kcal d–1 dietrecommendedbytheAmerican HeartAssociation.
Thechangeinbodyweightfrombaselineto6weeksforthegroup takingthe C.aurantium was1.4kgcomparedto0.9kgintheplacebo group,and0.4kginthecontrolgroup.Thechangeinbodyfatand percentfat[viabioelectricalimpedanceanalysis(BIA)]foreachofthe threegroupswas–3.1kg/–2.9%,–0.63kg/0.8%,and–1.8kg/–2.2%, respectively.Thelossinbodyfatandpercentfatwassignificantly greaterinthe C.aurantium groupthanineithertheplaceboorthe controlgroup;however,therewereno significantdifferencesbetween thegroupsinregardtobodyweight,basalmetabolicrate,blood pressure,HR,orelectrocardiographicmeasurements.
Basedonthesefindings,theauthors (24) suggestedthatthe combinationof C.aurantium withSt.John’swortandcaffeinewas safeandeffectivewhencombinedwithadietandexerciseprogram forinducingweightlossandfatlossinhealthy,overweightadults. Theseresultsshouldbeinterpretedwithcaution,however,because
234 Eckerson
thechangeinpercentbodyfat(–2.9%)overthe6-weeksupplementationperiodwaslessthantheerrorthatistypicallyassociatedwith BIA( 3%–5%),andthistechniqueisnottypicallyregardedasa criterionmeasureofbodycomposition (25)
Morerecently,Saleetal. (26) examinedtheacuteeffectsof Xenadrine-EFXonmetabolismandsubstrateutilizationduringrest andduringtreadmillwalkingin10overweightmales(> 20%fat).To gatherrestingdata,thesubjectsingestedthesupplementandlaid supinefor7hours.Baselinemeasurementsweretakenduringthe firsthour;andexpiredgases,bloodpressure,andHRweremeasured andavenousbloodsampleobtainedevery30minutesfortheremaining6hours.Duringtheexercisearmofthestudy (26) thesubjects ingestedthesupplementoraplacebo,andat1hourafteringestionthey exercisedonatreadmillfor1hourat60%oftheirestimatedHR reserve.Venousbloodwasanalyzedfornonesterfiedfattyacids (NEFAs),glycerol,glucose,andlactate;andexpiredgaseswereused tocalculateenergy(ATP)productionandsubstrateutilizationfrom carbohydrateandNEFAsforboththerestingandexerciseconditions.
Theresultsshowedthattherewasnosignificanteffectofthe supplementontotalATPutilizationduringthe6hoursofrestor duringthe60minutesoftreadmillwalking.However,therewasa shiftinATPproductionandsubstrateutilizationduringbothphases ofthestudy,whichdemonstratedanincreaseinATPproduction fromcarbohydrateandadecreaseinNEFAs,aswellasanincreasein carbohydrateoxidation.Infact,theincreaseincarbohydrateoxidationatrestwasshowntobeashighas30%.Weightlosssupplements aretypicallypromotedtoincreasefatutilization;however,these findingsindicatethatXenadrine-EFXstimulatescarbohydrateuse andactually decreases ATPproductionfromfat.
Basedonthesefindings,itappearsthatthisproductwouldnot haveanyfavorableeffectsonbodyweight.However,morelong-termstudiesdesignedtoexamineitseffectonweightloss,bothwith andwithoutexercise,arewarrantedtoverifythisstatement.One positivefindingfromthestudy (26) wasthatXenadrine-EFXhad noeffectonrestingHRorbloodpressure(eitherSBPorDBP), whichisincontrasttothefindingsofHalleretal. (23).Zenketal.
(27) alsoreportedthatacommercialweightlossproductcalledThe LeanSystem7(iSatoryGlobalTechnologies),whichcontainsbitter orange,guarana,dehydroepiandrosterone(DHEA),andyerba
WeightLossNutritionalSupplements 235
mateamongitsseveningredients,hadnoeffectonHRorblood pressure(SBPorDBP)following8weeksofsupplementationin47 overweightadultswhowerealsofollowingalow-caloriedietandan exerciseprogram.Perhapsmoreimportantly,however,Zenketal. (27) reportedthatthisproducthadnoeffectonBMI,bodyweight, fatweight,orfat-freeweightcomparedtoplacebo,eventhoughthe restingmetabolicratewassignificantly(p =0.03)increasedinthe treatmentgroup(7.2 – 1.6kcal d–1).
Basedontheavailableresearch,itdoesnotappearthatbitter orangeiseffectiveforweightloss.Moreover,becausesafetyinformationislimited,individualswithpreexistingcardiacproblemsand/or hypertensionshouldproceedwithcautionbeforeusingweightloss supplementscontainingbitterorangebecauseitismostcommonly usedinherbalmixturesthatcontainseveralotherCNSstimulants.In addition,futurestudiesarewarrantedtogainabetterunderstanding oftheexactisomerscontainedinvariousformsofbitterorange,asthe potencyvarieswidelybetweenthedifferentstereo(–)andpositional (m-and p-)isomers.Inshort,itappearstobe‘‘buyerbeware’’atthe presentmomentwithregardtothedifferenttypesofsynephrinethat manufacturersmaybeincludingintheirweightlossproducts,particularlyastheydonotnecessarilyneedtoregisterwiththeFDAorget FDAapprovalbeforeproducingorsellingtheseproducts.
2.3.Pyruvate
Pyruvate(PYR),athree-carboncompoundsynthesizedinthe bodyviaglycolysis,hasbeenstudiedforitseffectsonweightloss sincethelate1970swhenStankoetal. (28) foundthatPYRanda relatedthree-carboncompoundknownasdihydroxyacetone (DHA)reducedthedevelopmentoffattyliversinratsfedethanol. Follow-upstudiesperformedbythesameresearchgroup (29,30) usingratandpigmodelsalsoshowedthatPYRandDHAsupplementationresultedinincreasedenergyexpenditureandfatreduction,possiblythroughtheresultsofincreasedthermogenesis. Stankoetal. (31,32) havealsoreportedsignificanteffectsofPYR andDHAonweightlossinhumans.Inonestudy (32) thatexaminedtheeffectofPYR(19g d–1)andDHA(12g d–1)supplementationfor3weeksin21obesewomeningestingalow-caloriediet,it wasfoundthatthecombinationofPYR-DHAresultedinsignificantlygreaterlossesinbodyweight(6.5kg)andfatweight(4.3kg)
236 Eckerson
comparedtoplacebo(5.6kgand3.5kg,respectively),whichrepresentedadifferenceof 2lbbetweengroups.Inarelatedstudy, Stankoetal. (31) alsofoundthatwhenobesewomenwhofirst lostweightonalow-caloriedietweresubsequentlyplacedonahighcaloriedietwithPYR,theyregainedweightatasignificantly (p < 0.05)slowerratecomparedtoahigh-caloriedietwithout PYR.Basedonthesefindings,itwasconcludedthatPYRand PYR-DHAwhencombinedwithalow-caloriedietresultsingreater weightlossversuscalorierestrictionalone (32) andattenuates weightgainduringhypercaloricconditions (31).
AlthoughmanyofthestudiesconductedbyStankoandcolleagues (31
34) resultedinpositivefindings,itisimportanttonote thatheownsseveralpatents (29) forPYR-DHA;andalthough manyresearchersusepatentsasameanstoprotecttheirintellectual property,itisconsideredbysometorepresentaconflictofinterest. Inaddition,thedosagesrecommendedforthepatientswerelarge (i.e.,22–44g d–1),representingupto20%ofdailyenergyintake, andwereingestedconcurrentlywithalow-caloriediet (31,33).
TogainabetterunderstandingoftheefficacyofPYRonweight losswithoutcaloricrestriction,Kalmanetal. (35) determinedthe effectoflow-dosePYRonbodycompositionin51overweight(BMI > 25kg m2)menandwomenconsuminga2000kcal d–1 diet.In theirstudy (35),thesubjectsrandomlyreceivedaweightlossproductthatcontainedPYR(6g d–1)andDHA(50mg d–1)(n =18) oraplacebo(maltodextrin6g d–1; n =18)for6weeks,andanother 15subjectsservedasacontrolgroup.SubjectsinthePYRandPL groupsmetwitharegistereddietitianevery2weeksandreceived counselingtofollowa2000kcal d–1 diet(50%carbohydrate,20% protein,30%fat),andallsubjectscompletedacircuittraining protocolthreetimesaweekfor 45minutesat60%oftheirpredictedmaximalHR.Bodycompositionwastestedatbaselineand every2weeksthereafterusingBIA.Therewerenosignificantdifferencesbetweenthethreegroupsatbaseline;andattheendofthe6weekperiod,theresultsshowedthatnoneofthegroupsexperienced asignificantchangeinbodyweight.However,PYRresultedina significantdecreaseinfatweight(–2.1kg)andpercentfat(–2.6%), aswellasasignificantincreaseinfat-freeweight(1.5kg).Therewere nosignificantdifferencesinfatweightandfat-freeweightfrom baselineto6weeksfortheplaceboandcontrolgroups.Itis
–
WeightLossNutritionalSupplements 237
unknownifanyofthedifferencesinbodycompositionweresignificantlydifferentbetweengroupsbccauseitdoesnotappearthat theauthors (35) performedastatisticalanalysistodetermine between-groupdifferencesafterbaseline.Theauthors (35) stated thatPYRsupplementationof6g d–1 for6weeksresultsinmodest decreasesinfatweightandaconcomitantincreaseinfat-freeweight whenperformedinconjunctionwithexercise.Theseresultsshould beinterpretedwithcaution,however,asthebodycompositionwas notassessedusingacriterionmethod,anditappearsthatincompletestatisticalanalyseswereperformed.
Kalmanetal. (36) performedasimilarstudythatwaspublished 1yearlatertoexaminetheeffectsofexercise(45–60minutesthree timesaweek)andPYR6g d–1 for6weeksonbodycompositionin 26overweightmenandwomencomparedtoplacebo.Theresultsof thisstudy (36) showedthatPYRresultedinastatisticallysignificant(p < 0.001)decreaseinbodyweight(1.2kg),fatweight (–2.5kg),andpercentfat(–3.0%),whereastheplacebogroup experiencednochangesoverthe6weeksofsupplementationand training.
IncontrasttothefindingsofKalmanetal. (35,36),amorerecent study (37) thatexaminedtheeffectofPYRduringtrainingonbody compositionreportednosignificanteffectscomparedtoplacebo.In thisstudybyKoh-Banerjeeetal. (37),23untrainedwomenwere assignedtoreceiveeitherPYR(10g d–1)oraplacebofor30days whileparticipatinginasupervisedexerciseprogram.Priortoand followingsupplementation,bodyweight,fatweight,andpercentfat wereassessedusingunderwaterweighing,whichisacommonly acceptedcriterionmethodforassessingbodycomposition. AlthoughthePYRgroupgainedlessweight(PYR0.3 – 0.3kgvs. placebo1.2 – 0.3kg),lostmorefatweight(PYR–0.4 – 0.5kgvs. placebo1.1 – 0.5kg),andlostagreaterpercentageofbodyfat(PYR –0.65% – 0.6%vs.placebo0.1% – 0.5%),theresultswerenot statisticallysignificant(p =0.16)whencomparedtoplacebo. Thesefindings (37) areinagreementwiththoseofStoneetal. (38),whoalsoreportedthatPYRsupplementation( 9g d–1)for 5weekshadnosignificanteffectonbodycompositionortraining adaptationsincollegefootballplayers.
AlthoughseveralstudieshaveshownthatPYR,bothwithand withoutDHA,resultsinpositiveeffectsonbodyweightandbody
238 Eckerson
composition (31 –36),mostofthesestudieswereperformedinthe samelaboratory,andsupplementationoccurredinconjunction withextremelylowcaloriediets (30 –33) .Incontrast,theresultsof othermorerecentwellcontrolledstudiesinwhichsubjectsmaintainedtheirnormaldiet (37 ,38) showednoeffectofPYRwhen comparedtoplacebo.Inaddition ,consideringthatthesubjects usedinmostofthestudiesthatshowedpositiveresultswereoverweightorobese,theweightlossinducedbyPYR( 2–3lb)waswhat maybeconsideredmodestatbest.Therefore,futurestudiesconductedbyseveralindependentlaboratoriesarenecessarytogaina betterunderstandingoftheefficacyPYRonbodycomposition beforeitcanberecommendedwithconfidenceasatreatmentfor weightloss.
3.SUPPLEMENTSTHATMODIFYCARBOHYDRATE ANDFATMETABOLISM
3.1.ChromiumPicolinate
Chromiumisapopularweightlosssupplementthathasbeenon themarketforanumberofyears.From1996through2003,salesof chromiumintheUnitedStatesincreasedfrom$65millionto$106 million (39).Chromiumisanessentialtracemineralthatenhances insulinactivityand,therefore,isinvolvedincarbohydrate,protein, andfatmetabolism.Mostdietaryweightlosssupplements(80%of allchromiumsales)containchromiumpicolinate(CrP),anorganic compoundoftrivalentchromiumandpicolinate,whichisaderivativeoftryptophan (39,40).BecauseCrPfacilitatestheactionof insulin,itisbelievedtodecreasebodyfat,increaseleanmass,and increasebasalmetabolism (39,40).However,moststudiesthathave examinedtheeffectofCrPonbodyweightandleanmassusing humanshavenotshownmanypositiveeffects.
Pittleretal. (40) conductedameta-analysisof10randomized clinicaltrialsthatexaminedtheeffectofCrPonbodyweightreduction.Theresultsshowedthatbodyweightdecreased1.1to1.2kg (0.08–0.2kg wk–1)comparedtoplaceboduringanintervention periodrangingfrom6to14weeks,withdailydosagesranging from188to924 mg.Inaddition,noadverseeventswerereported
WeightLossNutritionalSupplements 239
inthestudiesthatalsoexaminedthepotentialadversesideeffectsof chromiumsupplementation (18,41)
Morerecently,Lukaskietal. (39) examinedtheeffectofCrPon bodyweightandbodycomposition(fatweightandfat-freeweight) viadual-energyx-rayabsorptiometry(DEXA)in83women(age range19–50years)withaBMIrangeof18–30kg m2.Thesubjects inthetreatmentgroup(n =27)ingestedanequivalentof200 mgof CrPfor12weeks,andtheothersubjectseitherrandomlyreceived 1720 mgpicolinicacid(n =27)oraplacebo(n =29).Allsubjects werecounseledbyaregistereddietitianandmaintaineda2000kcal diet(51%carbohydrate,18%protein,31%fat)tocontrolfor chromiumintakeduringthe12-weekstudy.
Theresultsshowedthatbodyweight[–1.0kg(placebo)to–1.3kg (CrP))andfat-weight(–1.1kg(CrP)to–1.4kg(placebo)]significantlydecreasedoverthe12-weekintervention.However,there werenosignificantdifferencesamongthethreegroups,whichindicatesthatthecalorierestriction,notCrP,wasresponsibleforthe weightloss.Therewerenosignificanteffectsacrosstimeforanyof thegroupsforfat-freeweightorbonemineraldensitydetermined fromDEXA.ThesefindingssupportthoseofPittleretal.(40) andsuggestthatCrPisasafe,butineffectivedietaryweightloss supplement.
3.2.Chitosan
Chitosan,apositivelychargedpolysaccharidethatisapolymer ofglucosamine,isderivedfromtheshellsofcrustaceans(i.e.,crabs, shrimp,lobster) (3,42).Itispurportedtoblockfatabsorption;and althoughtherearesomedataonanimalstosuggestthatitmightbe aneffectiveweightlosssupplement,thereislittlesupportforitsuse inhumans.Inonestudy (43),itwasfoundthatchitosanprevented anincreaseinweightinmicethatwerefedahigh-fatdietfor9weeks, andanotherstudyusinghamsters (44) reportedthatchitosan decreasedfoodintakeandbodyweight.
However,intheirreviewarticle,PittlerandErnst (42) performed ameta-analysisonfiverandomizedclinicaltrialsthatexaminedthe effectofchitosanonbodyweightinobeseandoverweightindividualsandreportedthat,inthreeofthefivestudies,chitosanhadno significanteffectonbodyweightcomparedtoaplacebo.The
240
Eckerson
dosagesusedinthestudiesrangedfrom0.48to3.1g d–1 andwere4 to12weeksinduration.However,inthestudythatusedthelowest dose,chitosanwascombinedwith Garciniacambogia (1.1g d–1), whichisalsocommonlyusedinmanydietaryweightlosssupplements.Whenexaminingtheotherfourstudiesthatusedchitosan alone,threeresultedinnosignificantfindings.Allfivestudiesused inthemeta-analysisreportedminoradversegastrointestinaleffects followingchitosansupplementation,includingconstipation,flatulence,bloating,nausea,andheartburn (42).
Aspreviouslymentioned,chitosanisapositivelychargedpolymer thatisbelievedtoblock,or‘‘trap,’’theabsorptionoffatbybinding withnegativelychargedfatmoleculesinthelumenoftheintestine (3).Ifmalabsorptionoffatdoesresultfromproductscontaining chitosan,itwouldbeexpectedthattherewouldbeanincreasein fecalfatexcretion.Totestthishypothesis,GadesandStern (45) quantifiedthefecalfatcontentinsubjectswhosupplementedwith anOTCproductcalledAbsorbitol(Natrol,Chatsworth,CA,USA).
Fifteenmales(age26.3 – 5.9years;BMI25.6 – 2.3kg m2)consumed fivemealsperdaycontaining15gfat(total75g d–1)for12days.
Thefirst4daysservedasacontrolperiod,followedbya4-day supplementationperiodinwhichthesubjectsreceivedchitosan 4.5g d–1.Thesubjectswerethenplacedbackonthecontroldiet foranother4days.Allfecalmatterondays2to12wascollectedto beanalyzedforfatcontent.
Theresultsshowedthatchitosansupplementationsignificantly (p =0.02)increasedfecalfatexcretionby1.1 – 1.8g d–1 (from6.1 –1.2to7.2 – 1.8g d–1),whichtheauthors (45) consideredclinically negligible.Theystatedthattheproductwouldhavenomeaningful effectonenergybalanceorweightloss.Basedonthesefindings (45) andthoseofPittlerandErnst (42),chitosandoesnotappeartobe effectiveforreducingbodyweightinhumansandisassociatedwith gastrointestinaldiscomfort,includingconstipation,flatulence,and bloating.
3.3. Garciniacambogia (HydroxycitricAcid)
Garciniacambogia,alsoknownasbrindelberry,isatropicaltree nativetoIndiathatbearsyellowish,pumpkin-shapedfruit.Both thenaturalfruitandrindcontainhydroxycitricacid(HCA),which hasbeenshowntodecreasefatsynthesis(lipogenesis),spare
WeightLossNutritionalSupplements 241
carbohydrate,suppressfoodintake,andattenuatebodyweightgain (46).Theextractof G.cambogia isacomponentofmanydietary supplements(i.e.,CitrimaxTM,CitrileanTM),includingabottled drinkingwatercalled‘‘SkinnyWater1.’’Mostoftheseproducts claimthatwheningested30minutespriortoameal,theysuppress appetiteandblockcarbohydrateabsorption.
Ingeneral,theresultsforHCAasadietaryweightlosssupplementforhumansarenotpromising.Inanarticlethatexaminedthe effectofHCAasapotentialantiobesityagent,Heymsfieldetal. (46) reviewedsevenotherstudiesthathadexaminedtheeffectof HCAaloneorincombinationwithotheringredientsonbodyweight andfatweightinoverweighthumans,includingtwopeer-reviewed articles,fourabstracts,andoneopen-labelstudyfromanindustrial publication.Ofthesevenstudiesreviewed,fivereportedsignificant (p < 0.05)effectsofHCAaloneorincombinationwithanother weightlossagentonweightlossandfatloss;onestudythatfailed toincludestatisticsreportedthatsubjectswhoingestedHCA þ chromiumfor8weekslost 7poundsmorethansubjectsona placebo(HCA11.14lbvs.placebo4.20lb).However,Heymsfield etal. (46) notedthatinfiveofthestudiesHCAwastakenin combinationwithotheractiveingredientsthatcouldalsopotentiallyresultinweightloss(i.e.,CrP, L-carnitine,chitosan,herbal formsofcaffeine);therefore,thestudiesofferedlittleinsightintothe specificweightlosseffectsofHCA.Otherlimitationsincludedalack ofaplacebogroupordoubleblindinginonestudyandtheuseof near-infraredinteractancetoassessbodycompositioninanother, whichisconsideredbymanytobeaninvalidmethodformeasuring bodycomposition (46).
TogainabetterunderstandingoftheeffectofHCAaloneonbody composition,aswellasovercomesomeofthelimitationspreviously reportedintheliterature,Heymsfieldetal. (46) conductedtheir own12-weekdouble-blindplacebo-controlledstudyusingoverweight subjects(ages18–65years;BMI > 27–38kg m2)whowereeither randomizedtoreceive1500mg d–1 HCA(3 500mg d–1 30minutes priortomeals)(n =42)oraplacebo(n =42).Bodyweightandfat weight(viaDEXA)wereassessedatbaselineandat12weeks. Allsubjectswereprovidedwith5040kJ/daydietplan(i.e., 1200kcal)with50%,30%,and20%ascarbohydrate,protein,and fat,respectively.
242 Eckerson
Theresultsshowedthatsubjectsinbothgroupslostasignificantamountofweightoverthe12weeks;however,therewasno significantdifferencebetweenthetwogroups(placebo4.1 – 3.9kg vs.HCA3.2 – 3.3kg; p =0.14).Inaddition,therewasnosignificantdifferenceinpercentbodyfatlostbetweentheHCAand placebogroups(2.16% – 2.06%vs.1.44% – 2.15%,respectively). Basedontheseresults,HCAwasdeemednomoreeffectivethan placeboforreducingbodyweightandfatweightinoverweight individuals.
Kovacsetal. (47) alsofoundthatsupplementationwith 500mg d –1 HCAaloneorincombinationwithmedium-chaintriglyceridesfor2weeksdidnotresultinincreasedsatiety,fatoxidation,24-hourREE,orbodyweightloss(–1.0kgforplacebovs. –1.5kgforHCAalone)comparedtoplaceboin11overweight malesubjects(BMI27.4 – 8.2kg m 2 ).However,inafollow-up studythatwasalso2weeksindurationbutusedalargerdose, investigatorsfromthissamelaboratory (48) reportedthat 900mg d –1 HCAreducedenergyintakeby15%to30%,butdid notresultinanysignificantchangesinsatietyorbodyweight.The authors (48) suggestedthatHCAmaynotprimarilyserveasa weightlossagent,butcouldbeeffectiveforpreventingweight regaininoverweightindividuals,sinceitresultedinreducedenergy intake.
Inanotherrelatedstudy,Kriketosetal. (49) examinedtheeffect ofHCAonfatoxidationandthemetabolicratein10sedentarymen (ages22–38years;BMI22.4–37 6kg m2)usingadouble-blind, crossoverdesign.ThesubjectsvisitedthelaboratoryonfouroccasionstoexaminetheeffectsofHCA3.0g d–1 for3daysanda placeboonmetabolicparametersbothwithandwithoutmoderately intenseexercise(30minutesat40%VO2maxfollowedby15minutes at60%VO2max).TheresultsshowedthatHCAhadnoeffecton therespiratoryexchangeratioorenergyexpenditureatrestor duringexercise,indicatingthatithadnoeffectonfatoxidation. AlthoughtheirstudydidnotdirectlyexaminetheeffectofHCA onbodyweightloss,theauthors (49) commentedthatthelack ofmetabolicchangessuggestthatHCAwouldbeineffectivefor inducingweightlossinindividualsconsumingatypicalmixeddiet. Inagreement,vanLoonetal. (50) alsoreportedthatacuteHCA supplementation(18g d–1)hadnosignificanteffectsontotal
WeightLossNutritionalSupplements 243
carbohydrateorfatoxidationin10trainedcyclistsatrestorduring submaximalexercise.
AlthoughtheresultsofseveralearlystudiesreviewedbyHeymsfieldetal. (46) suggestedthatHCAincombinationwithother ingredients,includingCrPandherbalcaffeine,enhancedweight loss,morerigorouswellcontrolledstudiesthatusedHCAalone suggestthatitisnotaneffectivedietaryweightlosssupplement comparedtoplacebo.Interestingly,however,arecentstudy (51) usingratssuggeststhattheredefinitelyisadifferenceinefficacy betweenproductsandthatthedosagesusedinhumanstudiesmight betoolowtoresultinsignificantfindings.
Intheirstudy,Louter-vandeHaaretal. (51) comparedthe effectsofthreeHCA-containingproductsonWistarrats(RegulatorTM,CitrinKTM,CitriMax)atdosescorrespondingto150and 200mg kg–1 onfoodintakeandbodyweightafterbothsingledose andrepeateddose(4days)administration.RegulatorandCitrinK significantlyreducedfoodintakefollowingbothsingleand repeateddoseadministration,whereassimilardosesofCitriMax showedlittleeffectonfoodintake.Repeatedadministrationof RegulatorandCitrinKalsoreducedbodyweight.Basedupthe results,theauthors (51) suggestedthatbecauseCitrimaxhaslow efficacy,humanstudiesthatusedCitriMax (47,48,50) likelyfound noresultsbecausethedosewastoolow.Evenwiththesefindings, however,itisimportanttokeepinmindthattheresultsofstudies usinganimalmodelsthathaveshownpositiveeffectsofHCAon foodintake,fatoxidation,andbodyweightlosshavenotnecessarilybeenreflectedinhumanstudies.Althoughmoreresearchthat examinestheeffectofHCAonweightlossandbodycomposition usinghigherdosesandforlongerperiodsoftimeiswarranted, mostofthecurrentresearchsuggeststhatitisanineffectivedietary weightlosssupplementwheningestedalone.
3.4.ConjugatedLinoleicAcid
Conjugatedlinoleicacid(CLA)isacollectivetermusedto describeagroupofpositionalandgeometricallyconjugated(i.e., alternatingsingleanddoublebonds)isomersoflinoleicacid[afatty acid(FA)]thatarenaturallyfoundinanimalfat,dairy,andpartially hydrogenatedvegetableoils (52,53).CLAisalsosoldcommercially asadietaryweightlosssupplement.MostCLAproductssoldOTC
244 Eckerson
havea40%:40%contentof cis-9,trans-11(c9t11)FAand trans-10, cis-12(t10c12)FA;theremaining20%istypicallycomposedof otherconjugatedFA( 1%–4%)andothernonconjugatedFA ( 15%–19%).Thec9t11CLAisomeraccountsfor85%to90% ofthetotalnaturalCLAcontentinthediet,whereasdietaryintake ofthet10c12isomerisnegligible (54).WhenthesetwoCLAisomers arecombinedinapproximatelyequalamounts,severalanimalstudieshaveshownstrongevidencethatCLAhasanticarcinogenicand antiatherogeniceffects,aswellaspositiveeffectsonbodycompositionandbloodlipidprofiles (41,52,53,55).Themechanismsof actionthatmayexplainhowCLApromotesweightlossarenot wellunderstood,butithasbeentheorizedthatitmayelicitpositive effectsonbodycompositionby:1)inhibitinghormone-sensitive lipoproteinlipasewhich,inturn,inhibitslipogenesis(fatsynthesis);
2)promotingadipocyteapoptosis(programmedcelldeath);3)preventingtriglcyceride(TG)accumulationinadipocytes;4)downregulatingtheexpressionofleptin;and5)modulatingglucose andfatmetabolismtoincreaseenergyexpenditure (56).Itiswell documentedthatCLAelicitsfavorableeffectsonbodycomposition andlipidprofilesinanimals;however,studiesontheeffectofCLA onbodyweightandbodycompositioninhumanshaveproduced conflictingfindings.
TriconandYaqoob (53) reviewed18studiesthatexaminedthe effectofbodyweightandbodycompositionusinghumansubjects andfoundthattheresultsweremuchlesspromisingthanthose foundforanimalstudiesusingmiceandpigs.Theamountusedin thestudiesreviewedrangedfrom0.7to6.8g d–1,mostofwhich containeda1:1mixtureofc9t11andt10c12CLAisomers.Ofthe 18studies,4demonstratedmodestreductionsinfatweight,2studies weredeemedinconsistentbecauseadose-responserelationwasnot found,andtheremaining12studiesshowednoeffectofCLAon bodycomposition (53).AlthoughfourstudiesreviewedbyTricon andYaqoob (53) didshowpositiveresultsforCLAonbody composition,uponcloserexaminationsomeofthefindingsare lessthandramatic.Forexample,Riserusetal. (57) examined theeffectofCLA4.2g d –1 for4weeksonabdominalfatand cardiovascularriskfactorsin25obesemenwithsyndromeXtype symptoms(i.e.,abdominalobesity ,hypertension,dyslipidemia, impairedfastingglucose)andreportedasignificant( p =0.04)
WeightLossNutritionalSupplements 245
decreaseinsagittalabdominaldiametercomparedtoplacebo. However,thechangewas < 1cm(–0.57cm),andtherewerenosignificant differencesbetweengroupsforbodyweight,waistcircumference,waistto-hipratio,orbloodlipidconcentrations[cholesterol,highdensity lipoprotein(HDL),lowdensitylipopotein(LDL),TG]following supplementation.
Inanotherstudyshowingpositiveresults,Gaullieretal. (56) reportedthatsupplementationwithtwoisomersofCLAfor1year reducedbodyfatinoverweight(BMI25–30kg m2),butotherwise healthyadultmenandwomen(n =180).Intheirstudy (18),60subjectsingestedTG-CLA4.5g d–1 (n =60),FA-CLA4.5g d–1 (n =61),oraplacebo(oliveoil4.5g d–1)(n =59).After1yearof supplementation,bothCLAgroupsdemonstratedsignificant decreasesinbodyweight( FA-CLA,–1.1 – 3.7kg; TG-CLA, –1.8 – 3.4kg)comparedtoplacebo( 0.2 – 3.0kg),whichrepresents anapproximateweightlossofonly2.4to4.0lbovertheentireyear (0.20–0.33lbpermonth).Thefactthatthestandarddeviationis greaterthanthemeanchangevalueforeachgroupalsosuggeststhat theremayhavebeenconsiderablevariationinbodyweightexhibited bythesubjectsduringthe1-yearperiod,withsomesubjectslikely demonstratingnotableincreases.
Incontrast,Triconetal. (55) usedacrossoverdesigntoexamine theeffectofthreedosesofhigh-gradec9t11(0.59,1.19,or2.38g d–1) andt10c12CLA(0.63,1.26,or2.52g d–1)forthreeconsecutive 8-weekperiodsseparatedbya6-weekwashoutperiod.Theresults showedthattherewasnosignificanteffectofeitherisomeronbody weight,BMI,orbodycomposition(viaskinfoldmeasurements andBIA)atanydose.Inagreement,Malpuech-Brugereetal. (52) alsoreportednoeffectofhighgradec9t11ort10c12CLAsupplementationatdosagesof1.5or3.0g d–1 administeredinadairydrink for18weeksonbodyweightorbodycomposition(viaDEXA)in81 overweightmen.
Althoughanimalstudieshaveprovidedstrongevidencetoindicate thatCLAhaspositiveeffectsonbodycomposition,itspotentialasan antiobesitytreatmentforhumansismuchlesspromising.Brownand McIntosh (41) suggestedthattheconflictingfindingsinhuman researchmaybedue,inpart,tothefactthatthemechanismofaction ofCLAisisomer-specificandthatthedosagesusedinhumantrials aremuchlessthanthoseusedinanimalstudies.Researchfromtheir
246 Eckerson
ownlaboratory (41) hasshownthatthet10c12CLAisomer decreaseshumanadipocyteTGcontentanddifferentiation,whereas thec9t11isomerincreasesTGaccumulationandadipocyte-specific geneexpressioninhumanfatcells.Inarelatedstudy,Triconetal. (55) showedthatthesesametwoCLAisomersalsohadopposing effectsonbloodlipidprofilesinhealthyadults,witht10c12resulting inincreasesintheLDL:HDLcholesterolandtotalHDLcholesterol ratios,whereasc9t11resultedinadecreaseintheseratios.Giventhat thec9t11andt10c12CLAisomersappeartohaveoppositeeffectson adiposity,BrownandMcIntosh (41) speculatedthattheinconclusive findingsinhumanstudiescouldbeduetotheuseofmixedisomersfor supplementation,whichmaynegateeachotherand,thus,resultinno significantchangeinbodyfat.Althoughfuturestudiesarewarranted toexaminetheeffectofisomer-specificdosesofCLAonbodycomposition,thereisnoconclusiveevidence,todate,tosuggestthat supplementationwitheitheramixtureofCLAisomersorsingle CLAisomersresultsinanymeaningfuleffectsonbodycomposition inhumans.
3.5.Calcium
Calciumistypicallyknownforitsroleinmaintainingbone densityandbonemineralhomeostasis.However,evidencenow suggeststhatcalciummayalsoplayaroleinadipocytelipid kineticstohelpdecreasebodyfat.Thepotentialofcalciumto induceweightlosswasfirstreportedduringthelate1980swhen Metzetal. (58) demonstratedareductioninfatweightinhypertensiveratsthatwereingestinghighamountsofcalciumand sodium;andBurseyetal. (59) foundthatincreasingdietary calciumfrom0.1%to2.0%resultedinlessweightgaininboth leanandobeseZuckerrats.Interestingly,itwasnotuntil1999 withthepublicationoftwoabstracts (60,61) thatmoreresearch begantofocusonthisunexpectedrelationshipbetweencalcium andbodyfat.
Theexactmechanismofactionbywhichcalciumexertsitseffecton bodyweightisnotentirelyclear,however,Zemeletal. (62) proposed thatlowdietarycalciumintakestimulatesdihydroxyvitaminDand parathyroidhormone(PTH)which,inturn,simulatetheuptakeof calciumintoadipocytes.Thisinflux ofintracellularcalciumresults inincreasedlipogenesis(i.e.,fatsynthesis)anddecreasedlipolysis
WeightLossNutritionalSupplements 247
(i.e.,fatbreakdown),withthenetresultbeinganincreaseinbodyfat. Incontrast,highdietaryintakeof calciumhastheoppositeeffectand inhibitsvitaminDandPTH,whichdecreasestheuptakeofcalcium intotheadipocytesand,inturn,increaseslipolysisanddecreases lipogenesis,resultinginweightloss (62).
Thediscoveryofanapparentinverserelationshipbetweendietary calciumintakeandbodyweighthasledtoseveraloriginalinvestigationsandthereevaluationofpreviouslypublisheddatatoexamine theefficacyofbothdietaryandsupplementalcalciumonbody composition.Forexample,Daviesetal. (63) reanalyzedfiveclinical trialsthatincluded780womenbetweentheirthirdandeighthdecades oflifeandfoundthatineachofthefivestudiesthecalcium/protein rationegativelypredictedBMIand/orchangeinbodyweight.In contrast,Shapsesetal. (64) combineddatafromthree25-week randomized,double-blindplacebo-controlledtrialstoreexamine theeffectofcalciumsupplementation(1000mg d–1,calciumcitrate) onbodyweightandfatweightinpre-andpostmenopausalwomen (N =100).Theyfoundnosignificantdifferencesforcalciumversus placeboandnosignificantactionofcalciumsupplementationon menopausalstatus.Theresultsfromseveraloriginalinvestigations (65
69) designedspecificallytoexaminetheeffectofcalciumon bodycompositionhavealsoresultedinconflictingfindings.
Zemeletal. (69) placed32obesesubjects(ages18–60years;BMI 30.0–39.9kg m2)onacalorie-restricteddiet(500kcal d–1 deficit) for24weeksandrandomizedthemtoastandarddiet(400–500mg dietarycalciumperdaysupplementedwithplacebo),ahigh-calcium diet(standarddietwithcalciumcarbonate800mg d–1),orahigh dairydiet(dietarycalcium1200–1300mg d–1 intheformofdairy productssupplementedwithplacebo).Theresultsshowedthatall subjectslostbodyweightasaresultofcaloricrestriction;however, thoseassignedtothehighcalcium(supplemental)andhighdairy dietlost8.58 – 1.1kgand11.07 – 1.63kgofbodyweight,respectively,whichwasgreaterthanthelossdemonstratedbythesubjects onthestandarddiet(6.60 – 2.58kg).Asimilartrendalsooccurred forfatweight,withthehighcalciumandhighdairygroupsexperiencinggreaterlosses(5.61 – 0.98kgand7.16 – 1.22kg,respectively) comparedtothoseonthestandarddiet(4.81 – 1.22kg),witha significantportionofthefatlossineachgroupoccurringinthe trunkregion.AlthoughthesamplesizeinthestudybyZemeletal.
–
248 Eckerson
(69) wasrelativelysmall,theirfindingsindicatethatcalciumsignificantlyaugmentsweightlosssecondarytocalorierestrictionand thatdairyproductshaveagreatereffectthansupplementalformsof calcium.Basedontheseresults,aswellastheirfindingthatcalcium regulateslipogenesisandlipolysisintheadipocyte (62),Zemeland colleaguessubmittedapatentfortreatingobesitywithcalcium (70).
IncontrasttothefindingsofZemel etal.(69),severalstudieswitha largernumberofsubjects (65–68) havefailedtofindasignificant relationshipbetweencalciumintakeandbodycomposition.Gunther etal. (67) determinedtheeffectoflong-term(1year)supplementation withdairycalciumon135healthy,normalweightwomen(ages18–30 years).Theyfoundnosignificantchangesinbodyweightorfatweight betweengroupsthatconsumedacontroldiet(< 800mg d–1),amoderate dairydiet(1000–1100mg d–1),orahighdairydiet(1300–1400mg d–1).
Inagreement,Haubetal. (68) showedthatacalcium-fortifiedbeverage (1125mg d–1)supplementedover1yearhadnoeffectonbodyweight,fat weight,orabdominalfatin37postmenopausalwomen(ages48–75 years)eventhoughsupplementationmorethandoubledthecalcium/ proteinratio.Barretal. (65) alsoshowedthatthreeservingsofmilkper dayhadnoeffectonweightlossorothermetabolicriskfactorsinolder adults;andina1-yearstudyusing178preschoolchildren(ages3–5 years),DeJonghetal. (66) reportedthattherewerenosignificant correlationsbetweenpercentbodyfatandfatmasschangesand dietarycalciumintake,andnosignificantdifferencesbetweencalciumsupplementedgroups(1000mg d–1)versusplacebo.
Thereisanoverwhelmingamountofevidencethatcalciumhas beneficialeffectsonbonehealthandmetabolism.However,itsroleas aweightlosssupplementhasnotbeenfirmlyestablished,asretrospectivestudiesandoriginalinvestigationshaveresultedinconflicting findings.Therefore,morelarge-scaleclinicaltrialsarenecessaryto helpgainabetterunderstandingoftheroleofcalciumonadiposity usingawiderangeofsubjectpopulations.Althoughmanyindividuals whoareattemptingtoloseweighttendtoeliminatedairyproducts, noneofthestudiesreviewedhereinreportedasignificantincreasein bodyweightfollowingincreasedcalciumintake.Therefore,solongas energyintakeislessthanenergyexpenditure,itdoesnotappearthat theadditionofcalcium-richdairysourcestothedietwouldleadto anysubstantialincreasesinbodyweightandmayhelpmanyindividualsmeettheirdailycalciumrequirements.
WeightLossNutritionalSupplements 249
4.SUPPLEMENTSTHATINCREASESATIETY
4.1.Glucommannan,GuarGum,andPsyllium
Anumberofdietaryweightlosssupplementscontainwatersolublefiber,whichistheorizedtoabsorbwaterinthegut,thereby decreasingfeelingsofhungerand,inturn,reducingfoodintake, whichultimatelyleadstoweightloss.Examplesofsomeofthemost commonsourcesoffiberintheseproductsareglucomannan,psyllium,andguargum.
Glucomannan(Amorphophalluskonjac)isahighlyviscousdietaryfibernativetoAsiathatisderivedfromthekonjacroot(also knownaselephantyam);itiscomposedofapolysaccharidechainof glucoseandmannose(42).AnearlystudybyWalshetal. (71) that examinedtheeffectofglucomannan(3g d–1 8weekstakenbefore meals)onobesepatients( 20%ofidealbodyweight)foundthatit wasmoreeffectivethanplaceboforinducingweightloss,resulting inameanlossof2.49kg( 5.5lb).AmorerecentreviewbyKeithly andSwanson (72) alsoreportedthatatdosesof2to4g d–1 glucomannanresultedinsignificantweightlossinoverweightindividuals byincreasingsatiety.Moreover,itappearstobewelltolerated.
Thedietaryfiberguargum,derivedfromtheIndianclusterbean Cyamposistetragonolobus,isfoundinanumberofnaturalweight losspreparations.Todetermineitseffectivenessforreducingbody weight,PittlerandErnst (73) conductedameta-analysisof11 randomizedcontrolledtrialsthatrangedfrom3weeksto6months. Theyfoundthattherewasnosignificantdifferenceinoverweight subjectswhoreceivedguargum(7.5–21.0g d–1)comparedtothose whoreceivedplacebo(meandifferencebetweenguargumandplacebowas–0.04kg).Ofthe11studiesreviewed,7alsoreported severaladversegastrointestinaleffectsfromguargum,including flatulence,diarrhea,gastricpain,andnausea (73).Becauseofthe relatedadverseeventsandthefactthatitresultedinminimalweight losscomparedtoplacebo,PittlerandErnst (73) didnotrecommend guargumasadietarytreatmentforweightloss.
TheresultsofastudybyBirketvedtetal. (74) thatexaminedthe effectofthreedietaryfibersupplementscontainingglucomannan and/orguargumonweightlosswereconsistentwiththefindingsof thestudiesdescribedabove.Intheirstudy (74),176menandwomen randomlyreceivedoneofthreedietaryfibersupplementsoraplacebo
250 Eckerson
for5weekswhileconsumingabalanceddietof1200kcal d–1.Thefiber supplementsallcontainedglucomannanandincludedChrombalance1 (glucomannan),Appe-Trim1 (glucomannanandguargum),andGlucosahl1 (glucomannan,guargum,andalgninate).Theresultsshowed thatallthreefibersupplementsinconjunctionwiththedietresulted insignificantlymoreweightlossthandidtheplaceboanddietalone; however,therewerenosignificantdifferencesbetweenthethree treatments(3.8 – 0.9,4.4 – 2.0,and4.1 – 0.6kgforChrombalance, Appe-Trim,andGlucosahl,respectively),whichresultedinanaverageweightlossofapproximately0.8kg wk–1.Thesefindingssuggestthatglucomannaniseffectiveforinducingbodyweightlossand thatguargumandalginatehavenoaddedeffect (74)
Psyllium,derivedfromthehusksofripeseedsfromtheplant Plantagoovata or Plantagopsyllium(26,42),istheactiveingredient inmanynonprescriptionlaxativesandfibersupplementsincluding thewellknownbrandMetamucil1.Althoughpsylliumhasbeen showntobeeffectiveforloweringtotalcholesterolandLDL cholesterol,itdoesnotappeartobeaseffectiveasotherfibertypes forreducingbodyweightandisassociatedwithgastrointestinal disturbances,includingbloatingandflatulence (75)
Dietaryfiberiswellknownforitsbenefitsoncolonhealthandis commonlyusedforthetreatmentofhighcholesterollevels (75) Although,thereissomeevidencetosuggestthatfibersupplements maybeusefulforincreasingsatietyandinducingweightloss,there appearstobeadifferenceintheefficacyofthevariousdietary fibersupplements,withglucomannanshowingthemostpromising effects.Therefore,furtherstudiesarewarrantedtoexaminethe safetyandefficacyofglucomannanasanadjuvanttreatmentfor weightlosstohelpdecreasethehighprevalenceofoverweightand obesityintheUnitedStates.
5.OTHERDIETARYSUPPLEMENTS
Otherdietarysupplementsthathavebeenpurportedtoinduceweight lossaseithertheirprimaryorsecondaryactionincludeherbalpreparationssuchasdandelion,bladderwrack,sunflower,germander,and St.John’swort;theprohormoneDHEA;ß-hydroxy-ß-methylbutyrate,
WeightLossNutritionalSupplements 251
whichisametaboliteoftheaminoacidleucine;andyerbamate,which wouldhaveactionssimilartothoseofmahaung,citrusaurantium,and guarana (3,9).Stillothersincludelicorice,vitaminB5,medium-chain triglycerides,and L-carnitine (3).Researchregardingtheefficacyof thesesupplementsforweightlosshasprimarilyresultedinnonsignificant findingsand,insomecases,supplementationhasresultedinserious adverseeffects (3,9).Therefore,theuseofthesedietarysupplements asatreatmentforobesityappearstobelargelyunwarranted.
6.CONCLUSION
Althoughtheuseofdietarysupplementsforweightlossiswidespread,theevidencefortheirefficacyandsafetyisnotoverwhelmingly convincing.Inmostcases,theseproductseitherelicitnomeaningful effectdespitethemanufacturer’s claims,orresultinchangesinbody weightandcompositionthatarecomparabletothosethatoccur througharestricteddietandexerciseprogram,whichcanresultin weightlossofupto1.5to2.5kg wk–1 (76).Thereissomeevidenceto suggestthatherbalformsofephedrine,suchasmahuang,combined withcaffeineorasanECAstackiseffectiveforinducingmoderate weightlossinoverweightadults.However,becauseoftherecentban onephedra,manufacturersmustnowuse‘‘ephedra-free’’ingredients, suchasbitterorange,whichdonotappeartobeaseffectiveandmay stillpossessthepotentialforadverse effects,particularlyinindividuals withpreexistingcardiovascularorcerebrovascularconditions.The dietaryfiberglucomannanalsoappearstoholdsomepromiseasa possibletreatmentforweightloss;however,moreresearchiswarrantedtoexamineitsefficacy,particularlywhenconsumedalone,to confirmthefindingsofpreliminaryresearch.
Itisimportanttorememberthatdietarysupplementsarenot regulatedlikedrugs,whichmustundergorigorousclinicaltesting usingbothanimalandhumanmodelsbeforeenteringthemarket. Therefore,themanufacturersofdietaryweightlosssupplements canmakeclaimsregardingtheeffectivenessoftheirproducts withoutnecessarilyconductingclinicalresearchtrialsfirst.Infact, inJanuary2007,theFederalTradeCommissionreceiveda$25 millionsettlementfromthemanufacturersoffourwell-known dietaryweightlosssupplementsfordeceptiveadvertising:Xenadrine
252 Eckerson
EFX,CortiSlim,TrimSpaTM,andOne-A-DayWeightSmartTM.
Whenmakingthedecisiontousedietarysupplements,itistherefore criticaltorelyonevidence-basedresearchand/ordieteticprofessionalsversusinfomercialsandadvertisementsfromfitnessand bodybuildingmagazines.
Thefutureofdietarysupplementsforweightlossdependsonwell designed,largescaleclinicalstudiesandmorestringentregulation ofthedietarysupplementindustry.Currently,however,thereare fewdietarysupplementsdesignedforweightlossthatcanberecommendedwithmuchconfidence.
REFERENCES
1.RadimerKL,SubarAF,ThompsonFE.Nonvitamin,nonmineraldietary supplements:issuesandfindingsfromNHANESIII.JAmDietAssoc 2000;100:447–454.
2.BryantJ.Fatisa$34billionbusiness.AtlantaBusinessChronicleSeptember24, 2001.http://atlanta.bizjournals.co/atlanta/stories/2001/09/24/story4.html/.Accessed May11,2007.
3.SaperRB,EisenbergDM,PhillipsRS.Commondietarysupplementsfor weightloss.AmFamPhysician2004;70:1731–1738.
4.BlanckHM,KhanLK,SerdulaMK.Useofnonprescriptionweightloss products:resultsfromamultistatesurvey.JAMA2001;286:930–935.
5.BoozerCN,NasserJA,HeymsfieldSB,WangV,ChenC,SolomonJL. Anherbalsupplementcontainingmahuang-guaranaforweightloss:a randomized,double-blindtrial.IntJObes2001;25:316–324.
6.GreenwayFL.Thesafetyandefficacyofpharmaceuticalandherbalcaffeine andephedrineuseasaweightlossagent.ObesRev2001;2:199–211.
7.YoungR,GlennonRA.Discriminativestimuluspropertiesof(-)ephedrine. PharmacolBiochemBehav1998;60:771–775.
8.ShekellePG,HardyML,MortonSC,etal.Efficacyandsafetyofephedraand ephedrineforweightlossandathleticperformance:ameta-analysis.JAMA 2003;289:1537–1545.
9.AllisonDB,FontaineKR,HeshkaS,MentoreJL,HeymsfieldSB.Alternative treatmentsforweightloss:acriticalreview.CritRevFoodSciNutr 2001;41:1–28.
10.KovacsEMR,MelaDJ.Metabolicallyactivefunctionalfoodingredientsfor weightcontrol.ObesRev2006;7:59–78.
11.HutchinsGM.Dietarysupplementscontainingephedraalkaloids.NEnglJ Med2001;344:1095–1097.
12.DullooAG.Herbalstimulationofephedrineandcaffeineinthetreatmentof obesity.IntJObes2002;26:590–592.
WeightLossNutritionalSupplements 253
13.BoozerCN,DalyPA,HomelP,etal.Herbalephedra/caffeineforweightloss: a6-monthrandomizedsafetyandefficacytrial.IntJObes2002;26:593–604.
14.KalmanCM,MinschA.Ephedrine,caffeine,andaspirinenhancefatlossunder nonexercisingconditions[abstract].JAmCollNutr1997;16(Suppl2):S149.
15.DalyPA,KriegerDR,DullooAG,YoungJB,LandsbergL.Ephedrine, caffeine,andaspirin:safetyandefficacyfortreatmentofobesity.IntJObes 1993;17(Suppl1):S73–S78.
16.Vukovich,MD,SchoormanR,HeilmanC,JacobP,BenowitzNL.Caffeineherbalephedracombinationincreasesrestingenergyexpenditure,heartrate, andbloodpressure.ClinExpPharmacolPhysiol2005;32:47–53.
17.Fugh-BermanA,MyersA.Citrusaurantium,aningredientofdietarysupplementsmarketedforweightloss:currentstatusofclinicalandbasicresearch. ExpBiolMed2004;229:698–704.
18.BentS,PadulaA,NeuhausJ.Safetyandefficacyofcitrusaurantiumforweight loss.AmJCardiol2004;94:1359–1361.
19.PenzakSR,JannMW,ColdJA,HonYY,DesaiHD,GurleyBJ.Seville(sour) orangejuice:synephrinecontentandcardiovasculareffectsinnormotensive adults.JClinPharmacol2001;41:1059–1063.
20.AllisonDB,CutterG,Poehman,ET,MooreDR,BarnesS.Exactlywhich synephrinealkaloidsdoescitrusaurantium(bitterorange)contain?IntJObes 2005;29:443–446.
21.BlumenthalM.Bitterorangepeelandsynephrine.Part1.HerbalGram 2005;66.AmericanBotanicalCouncil.http://www.herbalgram.org/herbalgram/articleview.asp?a=2833&p=Y/.AccessedMay11,2007.
22.CarpeneC,GalitzkyJ,FontanaE,AtgieC,LafontanM,BerlanM.Selective activationofbeta3-adrenoreceptorsbyoctopamine:comparativestudies inmammalianfatcells.NaunynSchmiedebergsArchPharmacol 1999;359:310–321.
23.HallerCA,BenowitzNL,JacobPIII.Hemodynamiceffectsofephedra-free weight-losssupplementsinhumans.AmJMed2005;118:998–1003.
24.ColkerCM,KalmanDS,TorinaGC,PerlisT,StreetC.EffectsofCitrus aurantium,caffeine,andSt.John’swortonbodyfatloss,lipidlevels,and moodstates,inoverweighthealthyadults.CurrTherRes1999;60:145–152.
25.HeywardVH,StolarczykLM.AppliedBodyCompositionAssessment. HumanKinetics,Champaign,IL,1996,pp47–54.
26.SaleC,HarrisRC,DelvesS,CorbettJ.Metabolicandphysiological effectsofingestingextractsofbitterorange,greenteaandguaranaat restandduringtreadmillwalkinginoverweightmales.IntJObes 2006;30:764–773.
27.Zenk,JL,LiekamSA,KassenLJ,Kuskowski,MA.EffectofLeanSystem7on metabolicrateandbodycomposition.Nutrition2005;21:179–185.
28.StankoRT,MendelowH,ShinozukaH,AdibiSA.Preventionofalcoholinducedfattyliverbynaturalmetabolitesandriboflavin.JLabClinMed 1978;91:228–235.
29.StankoRT.Methodsforpreventingbodyfatdepositioninmammals.US PatentNo.4,812,479.March14,1989.
254 Eckerson
30.StankoRT,AdibiSA.Inhibitionoflipidaccumulationandenhancementof energyexpenditurebytheadditionofpyruvateanddihydroxyacetonetoarat diet.Metabolism1986;35:182–186.
31.StankoRT,ArchJE.Inhibitionofregaininbodyweightandfatwithaddition of3-carboncompoundstothedietwithhyperenergeticrefeedingafterweight reduction.IntJObesRelatMetabDisord1996;20:925–930.
32.StankoRT,TietzeDL,ArchJE.Bodycomposition,energyutilization, andnitrogenmetabolismwithaseverelyrestricteddietsupplementedwith dihydroxyacetoneandpyruvate.AmJClinNutr1992;55:771–776.
33.StankoRT,ReynoldsHR,HoysonR,JonoskyJE,WolfR.Pyruvatesupplementationonalowcholesterol,lowfatdiet:effectsonplasmalipidconcentrationsand bodycompositioninhyperlipidemicpatients.AmJClinNutr1994;59:423–427.
34.StankoRT,FergusonTL,NewmanCW,NewmanRK.Reductionofcarcass fatinswinewithdietaryadditionofdihydroxyacetoneandpyruvate.JAnim Sci1989;67:1272–1278.
35.KalmanD,ColkerCM,StarkR,MinschA,WiletsI,AntonioJ.Effectof pyruvatesupplementationonbodycompositionandmood.CurrTherRes 1998;59:793–802.
36.KalmanD,ColkerCM,WeletsI,RoufsJB,AntonioJ.Theeffectsofpyruvate supplementationonbodycompositioninoverweightindividuals.Nutrition 1999;15:337–340.
37.Koh-BanerjeePK,FerreiraMP,GreenwoodM,etal.Effectsofcalcium pyruvatesupplementationduringtrainingonbodycomposition,exercise capacity,andmetabolicresponsestoexercise.Nutrition2005;21:312–319.
38.StoneMH,SanbornK,SmithLL,etal.Effectsofin-season(5weeks)creatine andpyruvatesupplementationonanaerobicperformanceandbodycompositioninAmericanfootballplayers.IntJSportsNutr1999;9:146–165.
39.LukaskiHC,SidersWA,PenlandJG.Chromiumpicolinatesupplementation inwomen:effectsonbodyweight,composition,andironstatus.Nutrition 2007;23:187–195.
40.PittlerMH,StevinsonC,ErnstE.Chromiumpicolinateforbodyweight reduction:meta-analysisofrandomizedtrials.IntJObes2003;27:522–529.
41.BrownJM,McIntoshMK.Conjugatedlinoleicacidinhumans:regulationof adiposityandinsulinsensitivity.JNutr2003;133:3041–3046.
42.PittlerMH,ErnstE.Dietarysupplementsforbody-weightreduction:a systematicreview.AmJClinNutr2004;79:529–536.
43.HanLK,KimuraY,OkudaH.Reductioninfatstorageduringchitin-chitosan treatmentinmicefedahighfatdiet.IntJObes1999;23:174–179.
44.TrautweinEA,JurgensenU,ErbersdoblerHF.Choleserol-loweringand gallstone-preventingactionofchitosanswithdifferentdegreesofdeacetylation inhamstersfedcholesterolrich-diets.NutrRes1997;17:1053–1065.
45.GadesMD,SternJS.Chitosansupplementationandfecalfatexcretioninmen. ObesRes2003;11:683–688.
46.HeymsfieldSB,AllisonDB,VasselliJR,PietrobelliA,GreenfieldD,NunezC. Garciniacambogia(HCA)asapotentialanti-obesityagent.JAMA 1998;280:1596–1600.
WeightLossNutritionalSupplements 255
47.KovacsEMR,Westerterp-PlantegaMS,SarisWHM.Theeffectsof2-week ingestionof(-)-hydroxycitrateand(-)-hydroxycitratecombinedwithmediumchaintriglyceridesonsatiety,fatoxidation,energyexpenditureandbody weight.IntJObes2001;25:1087–1094.
48.Westerterp-PlantengaMS,KovacsEMR.Theeffectof(-)-hydroxycitrateon energyintakeandsatietyinoverweighthumans.IntJObes2002;26:870–872.
49.KriketosAD,ThomsonHR,GreeneH,HillJO.(-)-Hydroxycitricaciddoes notaffectenergyexpenditureandsubstrateoxidationinadultmalesinapostabsorptivestate.IntJObes1999;23:867–873.
50.VanLoonLJC,vanRooijenJJM,NiesenB,VerhagenH,SarisWHM, WagenmakersAJM.Effectsofacute(-)-hydroxycitratesupplementationon substratemetabolismatrestandduringexerciseinhumans.AmJClinNutr 2000;72:1445–1450.
51.Louter-vandeHaar,J,WielingaPY,ScheurinkAJW,NieuwenhuizenAG. Comparisonoftheeffectsofthreedifferent(-)-hydroxycitricacidpreparations onfoodintakeinrats.NutrMetab2005;2:23.
52.Malpuech-BrugereC,WihelminePHG,Verboeket-vandeV,MensinkRP, etal.Effectsoftwoconjugatedlinoleicacidisomersonbodyfatmassin overweighthumans.ObesRes2004;12:591–598.
53.TriconS,YaqoobP.Conjugatedlinoleicacidandhumanhealth:acritical evaluationoftheevidence.ClinNutrMetabCare2006;9:105–110.
54.MeinertLarsenT,ToubroS,GudmundsenO,AstrupA.Conjugatedlinoleic acidsupplementationfor1ydoesnotpreventweightorbodyfatregain.AmJ ClinNutr2006;83:606–612.
55.TriconS,BurdgeGC,KewS,etal.Opposingeffectsofcis-9,trans-11and trans-10,cis-12conjugatedlinoleicacidonbloodlipidsinhealthyhumans.Am JClinNutr2004;80:614–620.
56.GaullierJM,HalseJ,HoyeK,etal.Conjugatedlinoleicacidsupplementation for1yreducesbodyfatmassinhealthyoverweighthumans.AmJClinNutr 2004;79:1118–1125.
57.RiserusU,BerglundL,VessbyB.Conjugatedlinoleicacid(CLA)reduced abdominaladiposetissueinobesemiddle-agedmenwithsignsofthemetabolicsyndrome:arandomizedcontrolledtrial.IntJObes 2001;25:1129–1135.
58.MetzJA,KaranjaN,TorokJ,McCaronDA.Modificationoftotalbodyfatin spontaneouslyhypertensiveratsandWistar-Kyotoratsbydietarycalciumand sodium.AmJHypertens1988;1:58–60.
59.BurseyRG,SharkeyT,MillerGD.Highcalciumintakelowersweightinlean andfattyZuckerrats[abstract].FASEBJ1989;3137:A265.
60.TeegardenD,LinYC,WeaverCM,LyleRM,McCabeGP.Calciumintake relatedtochangeinbodyweightinyoungwomen[abstract].FASEBJ 1999;13:A873.
61.ZemelMB,ShiH,ZemelPC,DiRienzoD.Calciumandcalcium-richdairy productsreducebodyfat[abstract].FASEBJ1999;12:LB211.
62.ZemelMB,ShiH,GreerB,DiRienzoD,ZemelP.Regulationofadiposityby dietarycalcium.FASEBJ2000;14:1132–1138.
256 Eckerson
63.DaviesKM,HeaneyRP,ReckerRR,etal.Calciumintakeandbodyweight. JClinEnocrinolMetab2000;85:4635–4638.
64.Shapses,SA,StanleyH,HeymsfieldSB.Effectofcalciumsupplementationon weightandfatlossinwomen.JClinEndocrinolMetab2004;89:632–637.
65.BarrSI,McCarronDA,HeaneyRP,etal.Effectsofincreasedconsumptionof fluidmilkonenergyandnutrientintake,bodyweight,andcardiovascularrisk factorsinhealthyolderadults.JAmDietAssoc2000;100:810–817.
66.DeJonghED,BinkleyTL,SpeckerBL.Fatmassgainislowerincalciumsupplementedthaninunsupplementedpreschoolchildrenwithlowdietary calciumintakes.AmJClinNutr2006;84:1123–1127.
67.GuntherCW,LegowskiAP,LyleRM,etal.Dairyproductsdonotleadto alterationsinbodyweightorfatmassinyoungwomenina1-yintervention. AmJClinNutr2005;81:751–756.
68.HaubMD,SimonsTR,CookCM,RemigVM,Al-TamimiEK,HolcombCA. Calcium-fortifiedbeveragesupplementationonbodycompositioninpostmenopausalwomen.NutrJ2005;4:21.
69.ZemelMB,ThompsonW,MilsteadA,MorrisK,CampbellP.Calciumand dietaryaccelerationofweightandfatlossduringenergyrestrictioninobese adults.ObesRes2004;12:582–590.
70.ZemelMB,ShiH,ZemelPC.Materialsandmethodsforthetreatmentor preventionofobesity.USpatentno.6,384,087;May7,2002.
71.WalshDE,YaghoubianV,BehforoozA.Effectofglucomannanonobese patients:aclinicalstudy.IntJObes1984;8:289–293.
72.KeithlyJ,SwansonB.Glucomannanandobesity:acriticalreview.AlternTher HealthMed2005;11:30–34.
73.PittlerMH,ErnstE.Guargumforbodyweightreduction:meta-analysisof randomizedtrials.AmJMed2001;110:724–730.
74.BirketvedtGS,ShimshiM,ErlingT,FlorholmenJ.Experienceswiththree differentfibersupplementsinweightreduction.MedSciMonit 2005;11:PI5–P18.
75.PittlerMH,SchmidtK,ErnstE.Adverseeventsofherbalfoodsupplementsfor bodyweightreduction:asystematicreview.ObesRev2005;6:93–111.
76.CowburnG,Hillsdon,M,HankeyCR.Obesitymanagementbylife-style strategies.BrMedBull1997;53:389–408.
WeightLossNutritionalSupplements 257 View publication stats