cardiovaskuler 2.docx

8/10/2019 cardiovaskuler 2.docx

1/18

Thenew englandjournalofmedicine

reviewarticle

medicalprogress

TransFattyAcidsandCardiovascularDisease

DariushMozafarian,M.D.,M.P..,Martijn!."atan,Ph.D.,Al#ertoAscherio,M.D.,Dr.P..,Meir$.%tam&'er,M.D.,Dr.P..,

and(alterC.(illett,M.D.,Dr.P..

rans 'ats, unsaturated 'atty acids with at least one dou#le

#ondinthetranscon)guration*Fig.+,are'ormedduringthe&artialhydro-

genationo'vegeta#leoils,a&rocessthatconvertsvegeta#leoilsint

osemi-solid 'ats 'or use in margarines, commercial cooing, and manu'acturing &ro-cesses.Fromthe&ers&ectiveo'the'oodindustry,&artiallyhydrogenatedvegeta#leoilsareattractive#ecauseo'theirlongshel'li'e,theirsta#ilityduringdee&-'rying,and their semisolidity, which can #e customized to enhance the &alata#ility o'#aedgoodsandsweets.Theaverageconsum&tiono'industrially&roducedtrans'attyacidsinthe/nited%tatesis0to1&ercento'totalcaloriesconsumed.+Major

sources o' trans 'ats are dee&-'ried 'ast 'oods, #aery &roducts,&acaged snac'oods,margarines,andcracers*Ta#le+.2aturallyoccurringtrans'atsarecon-sumedinsmalleramounts*a#out3.4&ercento'totalenergyintaeinmeatsanddairy&roducts'romcows,shee&,andotherruminants5thesetrans'atsare&ro-duced#ytheactiono'#acteriaintheruminantstomach.TheFoodandDrugAdministration*FDAruledthat,efective$anuary

+,0336,the nutrition la#els 'or all conventional 'oods and su&&lements must indicate thecontento'trans'attyacids.0Thisrulingre&resentsthe)rstsu#stantivechangeto'ood la#eling since the re7uirement 'or the listing o' #asic &er-serving nutritionalin'ormationwasaddedin+883.TheDe&artmento'Agriculturemadealimitedin-taeo'trans'attyacidsaeyrecommendationo'thenew'ood-&yramidguidelines,1

su#se7uenttotherecommendationso'theDietary9uidelinesAdvisoryCommitteethat the consum&tion o' trans 'atty acids #e e&t #elow + &ercent o' total energy

intae.:

The 2ew;or City De&artment o' ealth and Mental ygiene has ased

03,333 restaand +:,333u&&liers toe &artially hnatedoils'romitch

to&rovide'ooood&roductstreeo'industrially&roducedtyacids.4Densenacted,andaisconsiderinlegislationtoateindustriaucedtrans'a'oodsu&&lie=acho'the

nswas&rom&

videncethatciono'trans'aacidsincreasriso'coronrtdisease*Cisarticlereveevidenceo'&gicalandcelectso'transids,therelattweentheintans'atandCndeath'romcauses,anddia#etes5andth#ilityand&om&licationsingorelimineconsum&tion'attyacids'riallyhydrogeegeta#leoils/nited%tate

T


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heChanning>a#oratory,De&art-

o'Medicine,!righamand(omen?sal and arvard Medical %chool,eDe&artmentso'2utritionandmiology,arvard%choolo'Pu#lic@allin!oston*D.M.,A.A.,M.$.%.,.5andtheDivisiono'uman2utri-(ageningen/niversity,and(agenin-

genCenter'orFood%ciences@#othin(ageningen,the2etherlands*M.!."..Addressre&rintre7ueststoDr.Mozafarianatthearvard%choolo'Pu#licealth,664untingtonAve.,!ldg.0,m.1+4,!oston,MA30++4,oratdmozafaBhs&h.harvard.edu.

2=ngl$Med0336514:+63+-+1.

Copyright 2006 Massachusetts Medical Socie

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TheNewEnglandJournalofMedicineDownloadedfromnejm.orgonJanuary12,2015.Forperonalueonly.Noo!heruewi!hou!permiion.

"opyrigh!#200$Maachue!!Medical%ocie!y.&llrigh!reer'ed.


calories 'rom saturated or cis unsaturated 'atsOleicAcid

Cisdou#le#ond

ElaidicAcid

Transdou#le#ond

Car#on

ydrogen

Eygen

theconsum&tiono'trans'attyacidsraiseslevelso' low-density li&o&rotein *>D> cholesterol, re-duces levels o' high-density li&o&rotein *D>cholesterol,andincreasestheratioo'totalcho-lesteroltoD>cholesterol,a&ower'ul&redictoro'theriso'CD.0+Trans'atsalsoincreasethe#loodlevelso'triglyceridesascom&aredwiththeintaeo'other'ats,03increaselevelso'>&*ali-&o&rotein,00andreducethe&articlesizeo'>D>cholesterol,01eacho'whichmay'urtherraisetheriso'CD.Thus,trans'attyacidshavemar-edly adverse efects on serum li&ids. Although

these efects would #e eE&ected to increase theriso'CD,therelation#etweentheintaeo'trans'atsandtheincidenceo'CDre&ortedin&ros&ectivestudieshas#eengreaterthanthat&re-dicted#ychangesinserumli&idlevelsalone,03,00

suggestingthattrans'attyacidsmayalsoinu-enceotherris'actors'orCD.

Figure1.StructureofCisandTransFattyAcids.

!otholeicacidandelaidicacidare+G-car#on'attyacidswithasingled

ou#le

#ond.owever,oleicacidhasacisdou#le#ond*hydrogenatomsare

on

thesamesideo'the#ond,whichcausesa#endorininthe'attya

cidchain,whereaselaidicacidhasatransdou#le#ond*hydrogenatoms

areono&&ositesideso'the#ond,whichstraightensthe'attyacidchain.

The

trans#ondim&artsastructuremoresimilartothato'saturated'ats,alter-

ingthe&hysiological&ro&ertiesandefectso'the'attyacid.Hnelaidic

acid,thedou#le#ondoccursattheninthcar#onatom*trans-+G+nI8.Par

tially

hydrogenatedoilscontainmiEtureso'isomersinwhichthetrans#ond

mayoccuranywhere#etweenthe:thandthe+3thcar#on5smalleramoun

tso'

isomerswithasecondtransdou#le#ond*trans,trans-+G0arealso&resent.

P;%H>9HCA=CT%

FTA2% FATCHD%

SerumLipidsThe main efects o' tra

y acids on serumli&idlevelshave#eeneva

ncontrolleddi-etary trials.The efect

um li&id levels o'isocaloricre&lacemento'

ed'atorcisun-saturated'atswithtrans

calculated'romameta-analysiso'+0ran

d,controlledtri-

als o' trans 'atty acid c&tion &u#lished


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through2ovem#er0334*Fig.0.Thesedatawere

derived 'rom 40: su#jects in 18 se&arate study

grou&sorstudy&eriodsG-+8withtheuseo'&revi-

ously descri#ed methods03 *Mensin ,Maas-

tricht /niversity &ersonal communication and

esta#lished efects o' saturated and cisunsatu-

rated 'ats on serum li&id levels.03

As com&ared

with the consum&tion o' an e7ual num#er o'

SystemicInammation

ecentevidenceindicatesthattrans'ats&romote

inammation.Hnwomen,greaterintaeo'trans'attyacidswasassociatedwithincreasedactivityo'thetumornecrosis'actor*T2Fsystem5amongthosewithahigher#ody-massindeE,greaterin-taeo'trans'attyacidswasalsoassociatedwithincreased levels o' interleuin-6 and C-reactive&rotein.0:Hnastudyo'overweightwomen,great-erintaeo'trans'atwasagainassociatedwithincreasedactivityo'theT2Fsystemandincreasedlevelso'interleuin-6andC-reactive&rotein.04

Hn&atientswithesta#lishedheartdisease,mem-#ranelevelso'trans'attyacids*a#iomarero'thedietary intae o' trans 'ats were inde&endentlyassociatedwithactivationo'systemicinamma-toryres&onses,includingsu#stantiallyincreasedlevelso'interleuin-6,T2F-,T2Frece&tors,andmonocytechemoattractant&rotein+.06

Hnammatoryefectshavealso#eenre&ortedinrandomized,controlledtrials.Hn&atientswithhy&ercholesterolemia, the&roductiono'interleu-in-6andT2F-#yculturedmononuclearcellswasgreatera'teronemontho'asoy#ean-mar-garinediet*6.


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lar-celladhesionmolecule+,and=-selectin.04Thiso#servedincreasein=-selectinlevelswassimilarto)ndingsinarandomizedtrialwhenoleicacidorcar#ohydratewasre&lacedisocaloricallywithtrans'at.0GHnanothertrial,consum&tiono'trans'attyacidsim&airedendothelial'unction,asre-

ected#yareductionin#rachialarteryow-medi-atedvasodilatation#y08&ercent,ascom&aredwithintaeo'saturated'at.1:

OtherE!ects

Trans'attyacidsmayinuenceotherris'

actors

'orcardiovasculardisease.Hncontrolledtrials,con-sum&tion o' trans 'at reduced the activity o'serum&araoEonase,14anenzymethatiscloselyas-sociatedwithD>cholesterol,andim&airedthe&ost&randialactivityo'tissue&lasminogenacti-vator.16Trials evaluating the efects o'the con-sum&tion o' trans 'atty acids on insulin sensi-tivity have shown varia#le results.+G,1D> cholesterol &articles,01increasedrateso'

a&oA-Hcata#olism,:8andchangesinserumli&idlevels.03,00Trans'attyacidsalsoincreasethecel-lularaccumulationandthesecretiono''reecho-lesterol and cholesterol esters #y he&ocytes invitro.:to>D>andvery-low-densityli&o&rotein*>D>cholesterol.ThisincreasedactivitymayeE&laindecreasesinthelevelso'D> andincreasesinthelevelso'>D>and >D> cholesterol seen with intae o' trans'attyacids.03,00

Thecellularmechanismsrelatingtrans'atstoinammatory&athwaysandother,nonli&id&ath-ways are not well esta#lished. Monocytes andmacro&hages, endothelial cells, and adi&ocytesmayeach&layarole.Trans'attyacidsmodulatemonocyteandmacro&hageres&onsesinhumans,increasingthe&roduction#ymonocyteso'T2F-and interleuin-60


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Ta"le1.TypicalTransFattyAcidContentofFoods#roducedor#repared$ith#artially%ydrogenated&egeta

inthe'nitedStates.

TypeofFood TransFattyAcidContent(

No'Daily=nergy

No'Total Hntae'or0333-calgOTy&ical%erving gO+33g FattyAcids Diet

Fastorfro)enfoods

French'ries :.


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H2TA"= FTA2% FAT2D CADHA%C/>A DH%=A%=

ro&inion,conductingrandomizedlong-termtotesttheefectso'trans'atintaeontheenceo'cardiovasculareventswould#eun-al,giventheadverseefectso'trans'atsonmli&idlevelsandinammation.There'ore,ditiontoshort-termrandomizedtrialso'in-ediateend&oints,care'ully&er'ormedo#ser-

vationalstudies&rovideareasona#lea&&roach'orevaluatingtheefectso'trans'atoncardiovascu-larhealth.

C%,

na&er-calorie#asis,trans'atsa&&eartoincrease

theriso'CDmorethananyothermacronutri-ent, con'erring a su#stantially increased ris atlowlevelso'consum&tion*+to1&ercento'totalenergyintae.00,41-44Hnameta-analysiso''our&ros&ectivecohortstudiesinvolvingnearly+:3,333

+63:nengl

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medical&rogress

Ta"le1.-Continued.

TypeofFood TransFattyAcidContent(

No'Daily=nergy

No'Total Hntae'or0333-calgOTy&ical%erving gO+33g FattyAcids Diet

/argarines

egeta#leshortening 0.a#oratory,Dr.anniaCam&os5therangesareshown.Fortheother'oods,theto&national#randswerecom#inedintoonesam&le'oranalysis.The&ro&ortiono'thetotalsam&lethateach#randconstitutedwasdetermined#ythe#rand?s&ercentmaretshareinthenationalmaret&lace,asdetermined

'rommaret-shareandconsum&tionstatistics*Ta#le!ase,es&onsiveData#ase%ervicesand'romarvardcohort&ilotconsum&tiondatare&resentinganationalsam&le.

QThecontentsandty&eso'&artiallyhydrogenatedoilsweredetermined'romreci&ein'ormation*arvardFoodCom&o-sitionData#ase,#asedon&acagingand/%DAsources,andthetrans'attyacidcontento'theseoilswascalculatedonthe#asiso'gas-chromatogra&hyanalysiso'similar'oods.Forthe'astor'rozen'oods,thetrans'atcontento'theoilswascalculated'romthe'attyacidcom&ositiono'theoilsin'rench'ries5'orgranola#ars,'romamiEo'&artiallyhydro-genatedsoy#eanoilandhouseholdvegeta#leshortening5and'or#rea'ast#ars,'romhouseholdvegeta#leshortening.

aluesare&erta#les&oon*giventhatthereisnoty&icalservingsize.

su#jects,41-46includingu&datedanalyses'romth

e

twolargeststudies,a0&ercentincreaseinener-gyintae'romtrans'attyacidswasassoc

iated

witha01&ercentincreaseintheincidencD*&ooledrelativeris,+.01584&ercentconeinterval,+.++to+.1


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dial in'arction has also #een evaluatedin threeretros&ectivecaseKcontrolstudies4G-63*Fig.:.Theadditiono'thesestudiestothemeta-analysisin-creasedthemagnitudeo'theassociation#etweentrans'attyacidsandtheriso'CD*&ooledrela-tiverisin&ros&ectiveandretros&ectivestudies,

+.08584&ercentcon)denceinterval,+.++to+.:85PV3.33+.Cli'tonetal.showedthatthe&ositiveassociation#etweenlevelso'trans'atinadi&osetissueandtheriso'non'atalmyocardialin'arc-

tion was mitigated a'ter +886, when trans 'ats

wereeliminated'rommargarinessoldinAustraliaandtrans'atlevelsdecreasedin#othcase&atientsandcontrols.63

Sudden,eathfromCardiacCauses

%omedatasuggestthattrans'attyacidsmayin-

creasetheriso'suddendeath'romcardiaccauses.Hnastudythatcom&aredadi&osetissueo#tainedat auto&sy 'rom 66 &atients with sudden death'romcardiaccauseswiththato#tained'rom0G6healthyage-andseE-matchedcontrols,levelso'

trans 'at were not 'ound to #e associated withsuddendeath'romcardiaccauses.6+Hncontrast,inalarger,community-#asedcaseKcontrolstudy*+


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to#erelatedtothe+G-car#onisomers*trans-+G+andes&eciallytrans-+G05similarisomer-s&eci)crelationswereseeninstudiesevaluatingsystem-ic inammation.0:-06 A'ter adjustment 'or thelevelso'othermem#rane'attyacids,highertrans-+G0levelswereassociatedwithatri&lingo'the

riso'suddendeath'romcardiaccauses*oddsratio'orinter7uintilerange,1.34584&ercentcon-)denceinterval,+.


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Figure5.#otential#hysiologicalE!ectsofTransFattyAcids.

Changesinhe&atocyte&roduction,secretion,andcata#olismo'li&o&roteins,togetherwithefectson&lasmacholesteryleste

&rotein*C=TP,&ro#a#lyaccount'oradverseefectso'trans'attyacidsonserumli&idlevels*PanelA.TheefectonC=TPis

notdirect#utmediatedthroughefectsonmem#raneornuclearrece&tors*dashedline.Trans'attyacidsalsoalter'attyacid

ismand,&ossi#ly,inammatoryres&onseso'adi&ocytes.Hnaddition,nitricoEideKde&endentendothelialdys'unctionandincreasedl

circu-

latingadhesionmolecules*solu#leintercellularadhesionmolecule+YsHCAM-+Zandsolu#levascular-celladhesionmolecule+

+Zareseenwithtrans'atintae.Trans'attyacidsalsomodulatemonocyteandmacro&hageactivity*PanelD,asmani'ested#y

d

&roductiono'inammatorymediators.=acho'theseefectshas#eenseenincontrolledstudiesinhumansandmay,individuconcert,increasetheriso'atherosclerosis,&la7ueru&ture,suddendeath'romcardiaccauses,anddia#etes.Thesu#cellular

sms'ortheseefectsarenotwellesta#lished,#uttheymay#emediated#yefectsonmem#ranerece&torsthatlocalizewithandnced

#ys&eci)cmem#rane&hos&holi&ids*Panel!,suchasendothelialnitricoEide*2synthaseortoll-lierece&tors5#ydirect#

trans'attyacidstonuclearrece&torsregulatinggenetranscri&tion,suchasliverLrece&tor*PanelC5and#ydirectorindirecn

endo&lasmicreticulum*=res&onses,suchasactivationo'$un2-terminalinase*$2".%uchhy&othesizedsu#cellular&athw

whichhave#eenshowntoeEist'orother'attyacids@re7uire'urtherinvestigation.T2F-[denotestumornecrosis'actor[,

tiveoEygens&ecies,2F-\!nuclear'actor\!,andm2Amessenger2A.

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6o.of


10/18

6o.of

Typeand7earofStudy

Pros&ectivecohortstudies

Su"8ects E2ents

2urses?ealth%tudy,033444

ealthPro'essionalsFollow-u&%tudy,

033446

Al&ha-Toco&herol!eta-Carotene

CancerPrevention%tudy,+88


11/18

medical&rogress

verseassociation.41,4:,68,


12/18

acids,assisted#yadvice'romhealthcare

ders a#out how to avoid the main 'oodsainingtrans'ats*Ta#le+.Physiciansandoth-ealthcare&roviderscanalsosu&&ortinsti-nalchangestoreducetheuseo'trans'atinservices at schools, hos&itals, and other

sites.he amounts o' trans 'at in 'oods can varylyde&endingonthecontento'&artiallyhy-enatedoils,withsome'oodscontaininglittleo trans 'atty acids and other, similar 'oods

aininghighlevels.cholesterol*dietarytrials

3

!asedonre&lacementwithcar#ohydrates*&ros&ectivestudies

!asedonadditional#ene)tso're&lacementwithcisunsaturated'ats*&ros&ectivestudies

virtuallynotrans'attyacids,whereasthesame'oods in the /nited %tates contain 4 to +3 g o'trans 'atty acids &er serving *as discussed #y%tenderetal.elsewhereinthisissueo'theJour-nal


13/18

intae.Threeefectswereestimated#asedontheefectso'isocaloricre-

&lacemento'trans'atswithcismono-or&olyunsaturated'ats*avera

gedefectontheratioo'totaltoD>cholesterolincontrolledtrials*assh

own

inFig.0andtherelationo'thisratiototheincidenceo'CD0+5#asedon

there&ortedrelationo'trans'attyacidintae,su#stituted'orcar#ohyd

rateintae,withtheincidenceo'CDina&ooledanalysiso'&ros&ectives

tud-

ies*asshowninFig.:5and#asedontheadditional&otential#ene)t

si'trans'atswerere&lacedwithcismono-or&olyunsaturated'ats*aver

agedefect,ascalculated'romthe&ooledanalysiso'the&ros&ectivestudies

andthediferenceinrelativerisresulting'romtrans'ats#eingre&la

ced#ycar#ohydratesascom&aredwithcisunsaturated'atsinu&dated0

334

analyses'romtwocohorts.44,46

availa#le in 'ormulations that are 'ree o' trans'atty acids.The mandated la#eling o' trans 'atcontent0 may &rovide an additional im&etus 'orsuchchanges.Hthas#eennotedthattheFDAac-nowledgesthe&otentialharmo'consum&tiono'anyamounto'industrially&roducedtrans'at,yetitalsomaintainsthat&artiallyhydrogenatedoilsare#asicallysa'e.


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centCDeventseachyear.Theseestimatesare#asedonthere&lac

emento'trans'atswithcar#ohydrates.Hn&ractice,how-ever, trans 'ats in &artially hydrogenated oilswouldmostcommonly#ere&lacedwithunhydro-genated*cisunsaturated'ats,6whichmayhaveadditional &otential #ene)ts as com&ar

ed withcar#ohydrates. H' such additional &otential #en-e)t is considered, greater &ro&ortionso' CDevents *+0 to 00 &ercent might #e averted *Fig.4.Partialhydrogenationalsolargelydestroys[-linolenic acid, the &lant-#ased nI1 'atty acid.Although the cardiovascular #ene)ts o'[-lino-

lenic acid are not esta#lished conclusively,G1there&lacement o' &artially hydrogenated 'ats withunhydrogenatedoilscontaining[-linolenicacid*such as soy#ean oil may 'urther reduce theriso'CD#yincreasingthe&o&ulationintaeo'nI1'attyacids.

Conclusions

nthe#asiso'evidence'rominvitroeE&erimen-talstudies,dietarytrials,and&ros&ectiveo#ser-

3eferences

vationalstudies,theconsum&tiono'trans'atty

acids 'rom &artially hydrogenated oils &rovidesnoa&&arentnutritional#ene)tandhasconsider-a#le &otential 'or harm. Although the elimina-tiono'&artiallyhydrogenatedoils'rom'oodsmay#e challenging 'or restaurants and 'ood manu-'acturersinthe/nited%tates,eE&erienceinothercountriesindicatesthatsuch'atscanlargely#ere&laced#ycisunsaturated'atswithoutincreas-ingthecostorreducingthe7ualityoravaila#ilityo''oods.ealthcare&rovidersshouldadvisecon-

sumersa#outhowtominimizetheintaeo'trans'ats,consumersshouldrecognizeandavoid&rod-uctscontainingtrans'atsandrestaurantsand'oodmanu'acturers should choose to use alternative'ats in 'ood &roduction and &re&aration.Theseste&sshouldhel&reducetheconsum&tiono'trans'attyacids,&ossi#lyresultinginsu#stantialhealth#ene)tssuchasavertingthousandso'CDeventseachyearinthe/nited%tates.%u&&orted#yagrant*"3G->-3i&ides+880511188-:+3.11.$udd$T,Clevidence!A,MuesingA,(ittes$,%uninM=,Podczasy$$.Dietarytrans'attyacidsefectson&lasmali&idsandli&o&roteinso'healthymenandwom-en.Am$Clin2utr+88:548G6+-G.10.Almendingen",$ordal,"ierul'P,%andstad!,Pedersen$H.=fectso'&ar-tiallyhydrogenated)shoil,&artiallyhy-drogenatedsoy#eanoil,and#utteronse-rumli&o&roteinsand>&YaZinmen.$>i&ides+884516+1


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15.AroA,$auhiainenM,Partanen,%al-

minenH,MutanenM.%tearicacid,trans'attyacids,anddairy'atefectsonserumandli&o&roteinli&ids,a&oli&o&roteins,li&o&rotein*a,andli&idtrans'er&roteinsinhealthysu#jects.Am$Clin2utr+88cholesterolandonserumli&idsand a&oli&o&roteins a meta-analysis o'63controlledtrials.Am$Clin2utr0331

5awler>,McDonald9!,>evy(C.Trans'attyacidsandsystemicinammationinheart'ailure.Am$Clin2utr033:5G3+40+-4.0?.an %2, >ea >%, >ichtenstein A,Ausman>M,%chae'er=$,Meydani%2.='-'ecto'hydrogenatedandsaturated,rela-tiveto&olyunsaturated,'atonimmuneandinammatory res&onses o' adults withmoderate hy&ercholesterolemia.$ >i&ides03305:1::4-40.0@.!aerD$,$udd$T,Clevidence!A,Tracy

P. Dietary 'atty acids afect &lasmamarerso'inammationinhealthymen'edcontrolleddietsarandomizedcross-overstudy.Am$Clin2utr033:5cholesterolandim&airsendothelial'unc-tioninhealthymenandwomen.Arterio-sclerThrom#asc!iol033+50++011-M,vanTolA,"atanM!.e&lacemento'di-etarysaturated'atwithtrans'atreducesserum&araoEonaseactivityinhealthymenandwomen.Meta#olism033054++41:-.Muller,%eljeotH,%olvoll",Peder-sen$H.Partiallyhydrogenatedsoy#eanoilreduces &ost&randial t-PA activity com-&aredwith&almoil.Atherosclerosis033+5+44:6


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st&randial insulinemia and glyce-

o#ese&atientswith2HDDM.Dia-Care+88ichten-

stein A, Ausman >M,$auhiainen M,$onesP$.ydrogenated'atconsum&tionafectsacylation-stimulating&roteinlev-elsandcholesterolesteri)cationratesinmoderatelyhy&ercholesterolemicwomen.$>i&ides033+5:0+G:+-G.;0.%aravanan 2, asee# A, =htesham2],9ha'oorunissaL.Diferentialefectso'dietarysaturatedandtrans-'attyacidson eE&ression o' genes associated withinsulinsensitivityinratadi&osetissue.=ur$=ndocrinol03345+41+48-64.;5.PietinenP,AscherioA,"orhonenP,etal.Hntaeo''attyacidsandriso'coro-naryheartdiseaseinacohorto'Finnishmen the Al&ha-Toco&herol, !eta-Caro-teneCancerPrevention%tudy.Am$=&ide-miol+88ancet033+514


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llagherP$,>am&eFC.Transiso-

'oleicandlinoleicacidsinadi&oseandsuddencardiacdeath.>ancet1:40.Hntaeo'ruminanttranscidsandriso'coronaryheartdis-Am$Clin2utr*in&ress.ett(C,%tam&'erM$,Manson$=,taeo'trans'attyacidsandriso'ry heart disease among women.+88151:+4G+-4.es A, Foran$A, Car&enter D,on MC, "nuth !A, %chwager %$.assessment o' organic contami-n 'armed salmon. %cience 033:506-8.nis%M,9reenT$,alseyT".ari-

nthetrans'attyacidcontento'within a 'ood category im&lica-restimationo'dietarytrans'attytaes.$AmColl2utr+8885+G044-

sen".Hsthe7ualityandcosto'

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