Fructoseisanintermediaryinthemetabolismofglucose,butthereisnobiologicalneedfordietary

fructose.Wheningestedbyitself,fructoseispoorlyabsorbedfromthegastrointestinaltract,anditis
almostentirelyclearedbytheliverthecirculatingconcentrationis0.01mmol/Linperipheralblood,
comparedwith5.5mmol/Lforglucose.
Fructosediffersinseveralwaysfromglucose,theotherhalfofthesucrose(sugar)molecule(4).
Fructoseisabsorbedfromthegastrointestinaltractbyadifferentmechanismthanthatforglucose.
Glucosestimulatesinsulinreleasefromtheisolatedpancreas,butfructosedoesnot.Mostcellshave
onlylowamountsoftheglut5transporter,whichtransportsfructoseintocells.Fructosecannotenter
mostcells,becausetheylackglut5,whereasglucoseistransportedintocellsbyglut4,aninsulin
dependenttransportsystem.Finally,onceinsidethelivercell,fructosecanenterthepathwaysthat
provideglycerol,thebackbonefortriacylglycerol.Thegrowingdietaryamountoffructosethatis
derivedfromsucroseorHFCShasraisedquestionsabouthowchildrenandadultsrespondtofructose
aloneorwhenitisaccompaniedbyglucose.Inonestudy,theconsumptionofhighfructosemeals
reduced24hplasmainsulinandleptinconcentrationsandincreasedpostprandialfasting
triacylglycerolsinwomen,butitdidnotsuppresscirculatingghrelin,amajorappetitestimulating
hormone(4).
Fructoseismetabolized,primarilyintheliver,byphosphorylationonthe1position,aprocessthat
bypassestheratelimitingphosphofructokinasestep(4).Hepaticmetabolismoffructosethusfavors
lipogenesis,anditisnotsurprisingthatseveralstudieshavefoundchangesincirculatinglipidswhen
subjectseathighfructosediets(4).InthestudyconductedbyAeberlietal(1),dietaryfactors,
especiallyfructose,wereexaminedinrelationtobodymassindex,waisttohipratio,plasmalipid
profile,andLDLparticlesizein74Swissschoolchildrenwhowere614yold.Inthatstudy,plasma
triacylglycerolswerehigher,HDLcholesterolconcentrationswerelower,andlipoprotein(LDL)
particlesizewassmallerintheoverweightchildrenthaninthenormalweightchildren.Fatterchildren
hadsmallerLDLparticlesize,and,evenaftercontrolforadiposity,dietaryfructoseintakewastheonly
dietaryfactorrelatedtoLDLparticlesize.Inthisstudy,itwasthefreefructose,andnotsucrose,that
wasrelatedtotheeffectofLDLparticlesize.Studiesinrodents,dogs,andnonhumanprimateseating
dietshighinfructoseorsucroseconsistentlyshowhyperlipidemia(4).ThecurrentreportbyAeberliet
alsuggeststhatthehigherintakeoffructosebyschoolagechildrenmayhavedetrimentaleffectson
theirfutureriskofcardiovasculardiseasebyreducingLDLparticlesize.Itisinterestingthatthisstudy
didnotfindarelationofdietaryfructosewithtriacylglycerolsbutdidfindarelationwiththemore
concerninglipidparticle,LDLcholesterol.Anotherrecentreporthasproposedahypothesisrelating
fructoseintaketothelongknownrelationbetweenuricacidandheartdisease(3).TheADPformed
fromATPafterphosphorylationoffructoseonthe1positioncanbefurthermetabolizedtouricacid.
Themetabolismoffructoseintheliverdrivestheproductionofuricacid,whichutilizesnitricoxide,a
keymodulatorofvascularfunction(3).ThestudiesbyAeberlietalandNakagawaetalsuggestthat
therelationoffructosetohealthneedsreevaluation

HavelPJ.Dietaryfructose:implicationsfordysregulationofenergyhomeostasisand
lipid/carbohydratemetabolism.NutrRev2005;63:13357.
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