•

This month's issue features Holstein breeding, donor milk pasteurization, milk lactose in mammals, and the cheese food matrix. TheDaddyofAllCows

• Holsteincattlearethedominantdairybreedworldwide.• NearlyallHolsteincattlearedescendantsofjusttwobulls.• Introducingmoremalediversitymayinfluenceandimprovefertility.

Holsteincattlehavebecomethedominantdairybreedworldwide.Theseblackandwhitecowshavebecomesynonymouswithdairyinmanycountriesandtheyproducebillionsoflitersofmilk.Thishasbeenfacilitatedbyartificialinseminationtechnologythatisthebasisforherdreplacementandgeneticimprovementprogramsaroundtheworld.Withthisinmind,Yueetal.[1]conductedastudytoexaminehowmuchgeneticdiversityexistsinthemalechromosomallineagesofmoderncattle.Thegenomeofcattleconsistsof30pairsofchromosomes.Aswithotherspecies,twoofthesechromosomesaresexchromosomes,namedXandY.MaleshaveoneY-chromosomeandoneX-chromosome,whereasfemaleshavetwoX-chromosomes.ThismeansthatallmaleoffspringofonebullinheritanidenticalY-chromosomefromtheirsire.Soifthemaleancestralanimalshavebeenfewinnumber,thevariationingenesthatsitontheY-chromosomeisverylimited.ConsideringthattheY-chromosomecontainsgenesthataremajorcontributorstomalefertility[2],itbecomesaveryimportantfactorformanagementofdairyherds,andforaccessingthegenepoolthatmaycontributetoselectivebreeding.AstudybyYueetal.[3]setouttodetermineY-chromosomediversityamongstHolsteincattle.Thescientistsdugintotherecordsanddatabasesforover60,000HolsteinsintheUSAandover220,000Holsteinsfrominternationalsources.Theserecordsincludepedigreeinformationthatcouldbeusedtotracetheancestryofdairycattleuptorecenttimes.

Yueetal.[3]identifiedtherecordsofbullsfromelectronicdatabasesheldbytheNationalAssociationofAnimalBreeders(USA)beginninginthe1940s,andthenphysicalrecordsthatwentbackbeyondthoseyears.TheearliestrecordsrelatingtotheoriginalimportofHolsteincattleintotheUSAabout150yearsago.However,therewasasignificantchangeinpatternsofsireusewhenartificialinseminationwasintroducedinthe1960s,soanimalsborninthoseyearsweregivenspecialattentionasfoundersofmoderncattle.Theycomparedthesewiththepedigreesavailableonbullsfromover35countriesgoingbackasfarasthe1950s.Next,thestudyfocusedonY-chromosomeDNAdatathathadbeendeterminedfor257modern-daybulls[1].TheY-chromosomeofcattleisparticularlyrichinrepeatedregionsofidenticalorsimilarDNAsequence,referredtoascopynumbervariants(CNV).The257bullsweregrouped

accordingtothefounderanimalsthatgaverisetotheirpedigreeline.Thescientistshaddatafromtheseanimalsthatmeasuredtheirreproductivecapacityorfertility,whichhadbeenpreviouslylinkedtotheY-chromosomeCNV.Theresearchshowedthat,outofover62,000bullsbornintheUSAbetween1950and2013,over99%werethedescendantsofonlytwobulls.Inotherwords,allofthebullsfrommoderntimeshaveonlyoneoftwoY-chromosomes.ThisrepresentsanextremebottleneckinthemalelineofHolsteindairycattle.Whywouldalltheseprogeniesarisefromonlytwobulls?Clearly,farmerswanttousethebestbullstobreedtheirherds.It’stheirwayofincreasingtheefficiencyandeconomicviabilityoftheirenterprise.Followingtheintroductionofartificialinseminationandasystemtodeliversemenacrossthecountry,itwaspossibleforfarmerstochoosetheverybest,andtheseanimalswerefromthetwobullsthatwereidentified.It’salsopossiblethatbullswereremovedfromthepoolduetogenesthatcausedinheriteddisorders.Yueetal.[3]speculatedthatthebottleneckcouldhavecontributedtodecliningfertilityratesindairycattle,whichappearstobecorrelatedwiththeincreaseinmilkproductionthathasbeenaprimarytargetofimprovementstrategies.ThelimitationinY-chromosomesamongstHolsteinbullsmayrestrictattemptstoreverseadeclineinmalefertility.HowcouldthelimitednumberofY-chromosomesbereversed?ThesimplestanswerwouldbetolookoutsidetheUSAforbullswithdifferentfoundersandalternativeY-chromosomes,thenimportsemen.Unfortunately,whenYueetal.[3]analyzedthepedigreesfromover220,000Holsteinbullsintheinternationaldatabase,theyfoundthesameeffectandthesamefounders.Theseniorscientistinthestudy,Dr.Liu,hassincedevelopedadifferentstrategy.Hehas

SPLASH!® milkscienceupdateNovember2017Issue

gonebacktoarchivedsamplesoffrozensemenandfoundabullfromadifferentlinetouseforbreeding[4].Theremaybesimilararchivesamplesheldinrepositoriesaroundtheworld.Thealternativewouldbetocrossbreedusingotherproductivedairybreedsasthesourceofsemen,buttheimpactofthisstrategyonherdimprovementislikelytobemorecomplex.Moderngenomictoolsshouldhelptoironoutthecomplexities.

YueX.P.,DechowC.,ChangT.C.,DeJarnetteJ.M.,MarshallC.E.,etal.(2014)CopynumbervariationsoftheextensivelyamplifiedY-linkedgenes,HSFYandZNF280BY,incattleandtheirassociationwithmalereproductivetraitsinHolsteinbulls.BMCGenomics15:113.

YueX.P.,ChangT.C.,DeJarnetteJ.M.,MarshallC.E.,LeiC.Z.,etal.(2013)CopynumbervariationofPRAMEYacrossbreedsanditsassociationwithmalefertilityinHolsteinsires.JDairySci96:8024-8034.

YueX.P.,DechowC.,LiuW.S.(2015)AlimitednumberofYchromosomelineagesispresentinNorthAmericanHolsteins.JDairySci98:2738-2745. DukeA.(2017)RecoveringlostgeneticdiversityinHolsteinsisfocusofprofessors’research.PennStateNews

http://news.psu.edu/story/467412/2017/05/08/research/recovering-lost-genetic-diversity-holsteins-focus-professors.

ContributedbyProfessorPeterWilliamsonAssociateProfessor,PhysiologyandGenomicsUniversityofSydney,Australia

AlternativeMethodstoPasteurizeDonorMilkHoldPromise• VariousmethodsofpasteurizationhavebeenproposedforhumandonormilkotherthanHolderpasteurization,the

currentstandard.• Reducingtheperiodofheatingduringpasteurizationappearstokillmanypathogenswithlessdamagetotheproteinsin

humanmilkthanHoPdelivers.• High-pressuretreatments,ultrasonicprocessing,andUVirradiationallappearsomewhateffectiveatpasteurizingmilk,

butinallcasesmoreresearchisrequiredbeforetheycanbewidelyconsideredasalternatives.Inthepastfewmonths,SPLASH!hasassessedhowwellHolderpasteurization,orHoP,killsvirusesandbacteria,andtheextenttowhichitaffectsthenutrients,immuneproteins,anddigestiveaidsinhumanmilk.BecauseHoPiswidelyusedbymilkbanksallovertheworld,theseoutcomesarepotentiallyimportantforahugenumberofinfants,particularlythosebornprematurely.Inthisfinalarticleintheseries,othermethodsofpasteurizingmilkarebroughtintofocus.NexttoHoP,weknowrelativelylittleabouttheirperformance.Yetvariousstudiesshowthattheyholdsomepromisetowardsachievingtheideal—ameansofreliablypreventinggermsfromproliferatinginmilk,whilealsoretainingthefunctionofhumanmilk’sproteins.HoPitselfisaneminentlysimpleprocess.Milkisheatedto62.5ºCforhalfanhour.Thismethodisgoodatkillingpathogens,evenextremelydangerousonessuchasEbola.HoP’sweaknessisthatitdamagessomeimmuneproteinssuchasantibodiesandcertaincytokines,andmayalterthedigestibilityofmilkforinfantsby,forexample,reducingthefunctionofanenzymecalledbile-salt-stimulatedlipase.

ThesimplestinnovationofHoPistoalterthetemperatureapplied,andtheperiodofheating.Asperitsname,High-Temperature–Short-Time(HTST)pasteurizationdoesexactlythis,raisingthetemperatureofdonormilkto72ºCforjust15secondsorso,followedbyimmediatecooling.Accordingtoareviewoftheevidencepublishedthisyear[1],HTST,whichhasbeenusedbythedairyindustrysincethe1930s,isatleastequivalenttoHoPwhenitcomestodestroyinggerms,andoutperformsHoPatleavingintactsomevitaminsandimmuneproteins,includinglactoferrinandanumberofcytokines.Afewyearsago,RangmarGoelzandhiscolleaguesattheUniversityHospitalandChildren’sHospitalinTuebingen,Germany,setouttomeasurehowantibodieswereimpactedbythreedifferentheatingregimes.Knowingthatcytomegalovirus—avirusthatbecomesreactivatedduringlactation

andisexcretedintomilk—isdestroyedwithamerefivesecondsofheatingto62.5ºC,theteamwantedtoknowtheproportionofantibodiesthatwouldremainifroughlythisorslightlymoreheattreatmentwereappliedtomilk[2].Theyfoundthatfivesecondsofheatingto62ºC,65ºC,or72°Chadvirtuallynoeffectonarangeofantibodies,suggestingthattheHTSTstandardof72ºCfor15secondscouldbereducedifcytomegalovirusweretheonlyconcern.Butothergermsmatter.Hence,asimilarstudy[3]byCharlesCzankandateambasedatTheUniversityofWesternAustralia,inCrawley,alsosoughtaminimalyeteffectivetemperaturetreatment—butdefinedaminimaltreatmentaswhatisnecessarytoinactivatefivebacterialspeciesthatareamongthemostcommoncontaminantsofhumanmilk:Staphylococcusaureus,Enterobactercloacae,Bacilluscereus,andStaphylococcusepidermidis.TheymeasuredtheretentionofsecretoryIgA,lysozyme,andlactoferrin,andreportthatkeepingHoP’s30-minutepasteurizationperiodwhileloweringthetemperatureto57°Cwoulddestroy99.9%ofthe

cellsofthesespeciesandkeepintactatleast90%ofthethreeimmuneproteins.Asidefromheating,humanmilkcanbepasteurizedbyapplyinghighpressures,ultravioletradiation,orultrasonicprocessing.Ultrasonicpasteurizationisprobablythemostexoticofthesemethodssinceitseekstocreatemicroscopicbubbles,whichrapidlycollapseandproduceshockwaves.Theshockwavesbringassociatedpressuresof50MPaaswellasaburstofheatofupto5,000°Cineachmicroscopicbubble’simmediatearea.TheUniversityofWesternAustraliateamalsotestedthismethod[4],andfoundthattheretentionratesoflysozymeandotherhumanproteinsweregenerallylowerinultrasonicallypasteurizedmilkthaninthelab’sprevious57°Cheat-treatmentstudy,andthatultrasonicpasteurizationoftenrequiresalittlebitofheattobegoodatkillingbacteria—specificallybacteriaofthespecies,StaphylococcusepidermidisandEscherichiacoli.LukasChristenandcolleaguesinthesamelabmeasuredbile-salt-stimulatedlipaseasopposedtoimmuneproteinsandfoundthatmorethan90%ofthisenzymesurvivedultrasonicpasteurizationaslongasthemilk’soveralltemperatureremainedbelow51.4ºC[5].Ifthemilkgotanyhotter,bile-salt-stimulatedlipaseactivityrapidlydiminished.Liketemperature,pressurecausesvariouschangeswithinabacterialcellthatbodepoorlyforitssurvival.Highpressures—intheorderof400to800MPa—areproposedasameansofdonormilkpasteurizationwhenappliedforfiveto10minutesatatime.ThestudiespublishedsofardonotcompletelyagreeaboutwhetherthismethodisbetterthanHoPatpreservingantibodies[1],butconsiderasrelevantpossibilitiesthatitiseithersuperiororthesame—implicitlyacceptingthatpressuretreatmentishighlyunlikelytobeanyworse.Lastyearareviewofhigh-pressureprocessingresearchconcluded,morepositively,thatthismethoddoesappeartobebetteratmaintaininghumanmilkproteinsthanHoP,whilstefficientlyinactivatingpathogens[6].Thefourthpasteurizationmethodcurrentlyunderbroadconsiderationisultravioletradiation.AlthoughUVlightisawell-knowndisinfectant,milkisannoyinglyopaqueforUVtobeastraightforwardoption—asitisforwater—andsoUVradiationcanonlypenetratemilk’soutersurface.Stirringconstantlyduringthepasteurizationprocessgetsaroundthisproblem,however.Aswithhigh-pressurepasteurization,fewstudieshaveassessedUVpasteurization’saffectonawiderangeofpathogensandimmunoproteins.Butthosethatarepublishedaregenerallypositive.Intwoseparatestudies,Christenetal.sawadecreaseinfivespeciesofbacteriaandretentionofbile-salt-stimulatedlipaseafterUV-irradiation[7],andlessbacterialgrowthafterUV-processingthanafterHoP-processingwhensampleswereafterwardleftat37°Cforafewhours[8].However,anotherstudybythelabattheUniversityofWesternAustraliareportedthatUVirradiationfailedtocompletelyhaltcytomegalovirusgenetranscription,cautioningthatthemethodrequiresfullerevaluation[9].Forthemoment,HoPistherulefordonormilk.Inmanywaysthatseemsreasonable;HoP’seffectivenessagainstgermsisintunewiththecautionarytoneoftheHippocraticOath.Yet,theevidencesuggeststhatshorterheattreatmentsandsomeothermethodsprobablyalsoavoiddoingharm,meanwhileallowingdonormilktodoevenmoregood.Forthemtoberolledoutamongmilkbanks,however,theevidencethattheykillallmannerofpathogensneedstobebolsteredwithmoretestsonmorepathogens.Ifthatisestablished,infanthealthstandstogain.

PeilaC.,EmmerikN.E.,GiribaldiM.,StahlB.,RuitenbergJ.E.,vanElburgR.M.,MoroG.E.,BertinoE.,CosciaA.&CavallarinL.2017.HumanMilkProcessing:ASystematicReviewofInnovativeTechniquestoEnsuretheSafetyandQualityofDonorMilk.JournalofPediatricGastroenterologyandNutrition.64(3):353-61.

GoelzR.,HihnE.,HamprechtK.,DietzK.,JahnG.,PoetsC.&ElmlingerM.2009.EffectsofDifferentCMV-Heat-Inactivation-MethodsonGrowthFactorsinHumanBreastMilk.PediatricResearch.65(4):458-61.

CzankC.,PrimeD.K.,HartmannB.,SimmerK.&HartmannP.E.2009.RetentionoftheImmunologicalProteinsofPasteurizedHumanMilkinRelationtoPasteurizerDesignandPractice.PediatricResearch.66(4):374-9.

CzankC.,SimmerK.&HartmannP.E.2010.SimultaneousPasteurizationandHomogenizationofHumanMilkbyCombiningHeatandUltrasound:EffectonMilkQuality.J.DairyResearch.77:183–9.

ChristenL.,LaiC.T.&HartmannP.E.2012.UltrasonicationandtheQualityofHumanMilk:VariationofPowerandTimeofExposure.JournalofDairyResearch.79:361-6.

SousaS.G.,DelgadilloI.&SaraivaJ.A.2016.HumanMilkCompositionandPreservation:EvaluationofHigh-pressureProcessingasaNonthermalPasteurizationTechnology.CriticalReviewsinFoodScienceandNutrition.56(6):1043-60.

ChristenL.,Lai,C.T.,HartmannB.,Hartmann,P.&GeddesD.T.2013.Ultraviolet-CIrradiation:ANovelPasteurizationMethodforDonorHumanMilk.PLoSONE.8(6):e68120.

ChristenL.,Lai,C.T.,HartmannB.,Hartmann,P.&GeddesD.T.2013.TheEffectofUV-CPasteurizationonBacteriostaticPropertiesandImmunologicalProteinsofDonorHumanMilk.PLoSONE.8(12):e85867.

LloydM.L.,HodN.,JayaramanN.,MarchantE.A.,ChristenL.,ChiangP.,HartmannP.,ShellaG.R.&SimmerK.2016.InactivationofCytomegalovirusinBreastMilkUsingUltraviolet-CIrradiation:OpportunitiesforaNewTreatmentOptioninBreastMilkBanking.PLoSONE.11(8):e0161116.

ContributedbyAnnaPetherickProfessionalsciencewriter&editorwww.annapetherick.com

MilkLactoseFromAtoZebra• Lactoseistheprimarycarbohydrateinmostmammalmilks,butitsconcentrationvariesconsiderablyacrossspecies.• Milklactoseconcentrationisintimatelytiedtoaspecies’lifehistoryandecologicalniche.• Speciesthatfastduringlactation,includingbearsandwhales,producemilkswithverylittlelactose,whereasspeciesthat

lactateforprolongedperiodsoftime,likehumans,producemilkwithhigherlactoseconcentration.Ifyouhaveahardtimedigestinglactosefromcow’smilk,youmaywanttoavoiddrinkingmonkeymilk.Rhesusmacaquemonkeysproducemilkwith8%lactose,almosttwicetheamountfoundincow’smilk.Withabarelydetectablequantityoflactose,abetteroptionforintolerantindividualswouldbemilkfromgreyseals(thatis,ifyoucangetpastthatitisalso70%fishy-tastingfatandprobablynotthemostappetizingchoiceforyourmorningbowlofcereal).Understandingwhyrhesusmonkeysmakesuchhigh-sugarmilk,greysealsmakesuchlow-sugarmilk,andwhyothermammals,likecows,aresomewhereinbetweenrequiresconsiderationofbothwhattheoffspringneedstogrowanddevelopandwhatthemotherneedstomaximizeherreproductivesuccess.Farfromjustastoryaboutsugar,understandinglactosevariationinmilkisastoryofmammalianadaptationanddiversity.

UniqueandComplex

Lactoseisadoublesugar,ordisaccharide,composedofoneglucosemoleculeandonegalactosemolecule.Althoughthereareotherdisaccharidesinnature,theglucose-galactosecombinationisuniquetomilk.Indeed,thesynthesisoflactosedependsuponthepresenceandactivityofanotheruniquemilkingredient,theproteinalpha-lactalbumin[1].Beforealpha-lactalbuminbecomesabioactivewheyproteininmilk,itfunctionsasanenzymeresponsibleforbindingglucoseandgalactoseinsidemammarycells.Becauseonlymammarycellsexpressthealpha-lactalbumingene,onlymammarycellsareabletomakelactose.Lactosesynthesisseemslikeacomplicatedprocess—whydon’tthemammaryglandssimplypassonthemonosaccharidesglucoseandgalactoseinmilkinstead?Onereasonmaybebecausecomplexmoleculesofferanadvantageoversinglemolecules[2].Osmoticconcentrationisameasureofhowmanymoleculesareinasolution;onelactosemoleculehashalftheosmoticconcentrationoftwomonosaccharides.Becauselactoseexertslessosmoticpressureperunitmassthanglucose,morecarbohydratescanbetransferredinmilkwhilemaintainingthesameionconcentration(akaisosmotic)asthemother’splasma[1].Thefactthatlactoseisauniquesugaroffersanotheradvantagetomammals.Bacterialovetodineonsugars,andmostcarbohydratemacronutrientsinnaturecontainonlyglucose.Onlybacteriathatevolvedtheabilitytodigestlactosewouldbeabletocolonizemilk(eitherinthemammaryglandorthedigestivetractoftheinfant)[2].Thus,thenoveltyoflactosemayhaveofferedaprotectiveeffect,forbothmothersandinfants,againstalargenumberofmicrobesintheenvironment[2].

TheFirstMilk-Makers

Lactationisanevolutionarilyoldadaptation.Mammalsthatlayeggs(monotremes,suchastheplatypus),mammalswithpouches(marsupials,likethekoala),andmammalswithplacentas(eutherians,likehumans)alllactatebutdivergedmorethan100millionyearsago.Thissuggestslactationmaybeevenolderandhaveitsoriginsfromapre-mammalancestorover150millionyearsago[1].Lactosemaynothavebeenontheingredientlistinthefirstmilks—atleastnotonitsown.Monotremesandmarsupialsaretheoldestmammallineagesandhaveoligosaccharides(carbohydratesmadeof3–10monosaccharides)astheirprimarycarbohydrates[1-3].Theirmilksarenotcompletelylactosefree—thereisusuallyalactosemoleculeattheendofthesugarchain—buttheylackanyfreelactosemolecules[2].Coupledwiththisobservationisthesmallamountofalpha-lactalbuminmadebymonotremes.Urashima[3]havearguedthatthiswastheancestralcondition:thefirstmilkscontainedoligosaccharidesandmostlikelylackedanyfreelactose.Overtime,mammaryglandsbegantomakemorealpha-lactalbumin,whichinturnincreasedtheproductionoflactose.Finally,lactosebecameanimportantenergysourceforsomemarsupialsandeutherianinfants,andwasproducedseparatelyfromoligosaccharidechains[3].Manymammalianmilkshavelittletonolactose[2],indicatingthat,despitebeinganancientmilkingredient,itisnotrequiredformammaliandevelopment.Take,forexample,bears,whichastonishinglygivebirthandlactatewhilehibernating(andbyextension,whilefasting).Bearmotherscannotreplenishresourcesintheden,andmilkproductionmust,therefore,balancethenutritionalneedsofthebearcubswiththesurvivalofthemother.Themother’smainconcernisconservingglucose,tofuelherbrain,andwater[4].Bothofthesegohand-in-handwithlactose.Lactosecreatesanosmoticgradientanddrawswaterintothecellsofthemammarygland;thehighertheconcentrationoflactose,themorewater(andthus,themoredilutethemilk)[2].High-fat,low-sugarmilksarethesolution.Fat,unlikecarbohydrates,canbestoredforarainy(ormilky)day.Andifyouarealargemammal,likeabear,youcanstoreenoughfattoprovideenergyforyourgrowingcubsduringhibernation[4].Whalesandsealsmaynothibernate,buttheydolactatewhilefasting,andnotsurprisinglyalsoproducehigh-fat,low-sugar(andwater)milks[2,4].Theirlargebodysizeallowsthemtostorelargeamountsoffat,allowingforsomeremarkableadaptations.The

bluewhalegainsnearly100,000poundsofblubberduringpregnancytomaintainlactationforroughlysixmonths[5].Thehoodedsealonlylactatesforfourdays,butinthistimetransfersapproximately60poundsoffattoheroffspring[2,4].

SomeLikeItSweet

Forfastingbears,whales,andseals,theproductionofhigh-sugarmilks(whicharesynonymouswithhighwaterandlowfat)wouldquicklydepletematernalglucoseandwaterstores,andfailtosupportinfantgrowthanddevelopment.Forprimates(agroupthatincludeshumans,apes,monkeys,lemurs,lorises,andtarsiers),theoppositescenarioistrue.Primatesnurseforlongerthanwouldbepredictedformammalsoftheirbodysize.Toputitinperspective,a12,000-poundelephantnursesforroughlythesameamountoftimeasa40-poundchimpanzee.Theproductionofhigh-fat,low-sugarmilkamongprimateswouldquicklydepletematernalresources[6].Moreover,mostprimatespeciesnurseondemand.Frequentnursingstimulateslactosesynthesisinthemammarygland,whichsubsequentlyincreasesmilk’swatercontent[6].Therelationshipbetweenlactoseandwateralsoisclearlydemonstrated

whenlookingatmilksofmammals,suchaszebras,thatliveinaridenvironments[6].Zebramilkisnearly90%water,andthemilklactoseconcentrationissimilartothatofmilkfromprimates(around7%)[2].Inzebras,selectionfavoredincreasedlactosesynthesisandextremelydilutemilkstopreventdehydrationininfantswithhighwaterturnover;inprimates,selectionfavoredtheproductionoflow-energymilkstosupportanextendedinfancyperiod[2,6].Thisisanexquisiteexampleofconvergentevolution;twodifferentevolutionarylineagesconvergedonthesamesolution(highsugarmilks)tosolvedifferentproblems.

SugarBabies

Lactoseisprobablybestknownasthesugarthatcausesintestinaldiscomfortinthemajorityofhumans.Buttakingastepbackandlookingatlactoseacrossmammalsputsitinamuchmorepositivelight.Manyadulthumansmaybelactoseintolerant,buthumaninfants,likeallprimateinfants,arehighlydependentonlactoseforsuccessfulgrowthanddevelopment.Indeed,muchofthediversityweseeinmammals’lifehistorypatternsandecologicalnichesisonlypossiblebecauseofthisuniqueandcomplexsugar.

OftedalO.T.2013.Originandevolutionofthemajorconstituentsofmilk.In:McSweeneyPLH,FoxPF(Ed.)AdvancedDairyChemistryVolume1A:Proteins,4thEdition,Springer:NewYork,pp.1–42.

OftedalO.T.,IversonS.J.1995.Comparativeanalysisofnonhumanmilks:phylogeneticvariationinthegrosscompositionofmilks.In:JensenRG(Ed.)HandbookofMilkComposition.AcademicPress,SanDiego,pp.749–788.

UrashimaT.,FukudaK.,MesserM.2012.Evolutionofmilkoligosaccharidesandlactose:ahypothesis.Animal6(3):369–374. OftedalO.T.2000.Useofmaternalreservesasalactationstrategyinlargemammals.ProceedingsoftheNutritionSociety59:99–106. OftedalO.T.1997.Lactationinwhalesanddolphins:evidenceofdivergencebetweenbaleen-andtoothed-species.JournalofMammaryGlandBiologyand

Neoplasia2:205–230. HindeK.,MilliganL.A.2011.Primatemilk:proximatemechanismsandultimateperspectives.EvolutionaryAnthropology20:9–23.

ContributedbyDr.LaurenMilliganNewmarkResearchAssociateSmithsonianInstitute

CheeseandButterHaveDifferentEffectsonLDLCholesterol• AnewstudyfindsthatconsumingbutterinducesasignificantlygreaterincreaseinLDLcholesterolcomparedwith

cheese,andtheeffectsareparticularlypronouncedinparticipantswithhighbaselineLDLcholesterol.• Theresultssuggestthatthecheesefoodmatrixhelpsattenuatesomeofthecardiometaboliceffectsofconsuming

saturatedfats.• Thenewstudyaddstotheevidencethattheeffectsofdietarysaturatedfatsoncardiovasculardiseaseriskmaydepend

onthefoodsource.

Saturatedfattyacids(SFAs)havelongbeenconsidereddetrimentaltocardiovascularhealth,withdietaryguidelinesadvocatingforarestrictionofdietarySFAstoreducetheriskofcardiovasculardisease(CVD)[1].However,increasedconsumptionofSFAsmaynotalwaysbeassociatedwithincreasedCVDrisk,andtheeffectsofSFAsonCVDriskmayinsteaddependonthefoodsource[2-5].AnewrandomizedcontroltrialconductedbyProfessorBenoitLamarcheofUniversitéLavalcomparedthecardiometaboliceffects

ofconsumingsaturatedfatsinbuttercomparedwithconsumingsaturatedfatsincheese[6].“Thebasisofthisprojectwasthecontroversyabouttheeffectsofsaturatedfatsoncardiovasculardisease,”saysDidierBrassard,agraduatestudentinLamarche’slaboratoryandthefirstauthorofthenewstudy.“Sotheideawastocomparetwodifferentfoodsourcesofsaturatedfats,whichinourprojectwasbuttercomparedwithcheese,aswellastocomparethatwithothernutrients,”hesays.Inadditiontocheeseandbutter,theresearchersalsogaveparticipantsdietsrichinmonounsaturatedfattyacids(MUFAs),polyunsaturatedfattyacids(PUFAs),andcarbohydrates.Brassardandhiscolleaguescomparedtheeffectsofthesefivedietsonanumberofcardiometabolicriskfactors,includingbloodlipidconcentrationsandbloodpressure.“OneofthemostinterestingfindingsofthispaperwasthatbutterinducesasignificantlygreaterincreaseinLDLcholesterolthancheese,”saysBrassard.“Sosaturatedfatincheeseandsaturatedfatinbutterdonotbehavethesamewhentheyaredigested,”hesays.“AnewthingwasthattheeffectsoccurredespeciallyamongthepeoplewhohadagreaterconcentrationofLDLcholesteroltostartwith,”saysBrassard.HDLcholesterolconcentrationsweresimilarafterthecheeseandbutterdiets,althoughtheyweresignificantlyhigherthanafterthecarbohydratediet.Therewasnosignificantdifferencebetweentheeffectsofthedietsoninflammationmarkers,bloodpressure,andinsulin-glucosehomeostasis.Thedifferencesintheeffectsofbutterandcheeseareconsistentwithpreviousstudies.“Otherrandomizedcontroltrialsinthepasthaveshownthatsaturatedfatsinbutterandcheesebehavedifferentlywhentheyareeateninequalamounts,”saysBrassard.Inaddition,ameta-analysisshowedthatforasimilarintakeofsaturatedfatsandratioofSFAstoPUFAs,theconsumptionofhardcheesesignificantlyreducedLDLcholesterolandHDLcholesterolcomparedwithbutter[5].

TheresearchershypothesizedthatthecheesefoodmatrixwasresponsiblefortheattenuationofthecardiometaboliceffectsassociatedwiththeconsumptionofSFAs.PreviousstudiessuggestedthatthebeneficialeffectsofcertaindairyproductsonCVDriskappeartobemediatedbythedairymatrix[7].“Therearealsorandomizedcontroltrialsthatsupportedtheideathatthefoodsourceandthefoodmatrixmayinfluencetheeffectofsaturatedfatsonhealth,”saysBrassard[4].Theresearcherstriedtoestimatetheeffectofthecheesematrixoncholesterol.“Thewholeideawasjusttolookathowmuchsaturatedfatwasinthediet,andbasedonpreviouslypublishedequations,comparethepredictedeffectonLDLversuswhatwasobserved,”saysBrassard[8].“Whatwaspredictedandtheobservedconcentrationweredifferent,”hesays.“Whatwecansayisthattherearenutrientsincheesethatarereducingthe

overalleffectofsaturatedfatssothattheydonotinduceasmuchchangeinbloodlipidscomparedwithbutter,”saysBrassard.“Whatweshowinthispaperisthatthefoodmatrixmatters,asdifferentfoodswiththesamenutrientscanhavedifferenteffectsoncardiometabolicriskfactors,mainlybloodlipidsandLDLcholesterol,”saysBrassard.“Soit’simportanttolookbeyondnutrientsandthinkintermsoffoods,”hesays.It’sstillunclearwhatcomponentsofthefoodmatrixmayberesponsibleforinfluencingCVDrisk.“Thisisprettyelusiveatthemoment,”saysBrassard.Researchershavehypothesizedthattheeffectsofthecheesematrixmaybemediatedbycalcium,orminerals,orthepresenceofbacteria.“Thereareacoupleofhypotheses,butnothingisclearatthemoment,”saysBrassard.ArecentstudybyLamarche’slabshowedthatthecheesematrixmodulatestheeffectsofdairyfatonlipidmetabolism[9].“Theyshowedthatthecheesematrixinfluencesdigestion,”saysBrassard.“Sothisisanotherpossibilityforwhythecheesematrixinducesadifferentresponsethanthebuttermatrix,”hesays.Lamarche,Brassardandtheircolleaguesplantocontinuestudyingtheeffectsofthefoodmatrix.Anotherstudyoftheirslooksattheeffectsofthefoodmatrixoncholesteroleffluxcapacity,amarkerofHDLfunctionality[9].“Weobservedafoodmatrixeffect,asbutterinducesagreaterchangeincholesteroleffluxcapacitythancheese,”saysBrassard.“Thatstudyalsosupportsthenotionthatthefoodmatrixinfluenceslipidmetabolism,”hesays.Thesestudiesaddtothegrowingevidencethatthefoodsourceofsaturatedfatsisimportantinassessingtheirhealthimpacts.“Fromapublichealthperspective,it’simportanttolookbeyondnutrientsandthinkintermsoffood,becausedifferentfoodshavedifferenteffects,andthisisanotherexampleofthat,”saysBrassard.

VanHornL.,CarsonJ.A.,AppelL.J.,BurkeL.E.,EconomosC.,KarmallyW.,LancasterK.,LichtensteinA.H.,JohnsonR.K.,ThomasR.J.,VosM.,Wylie-RosettJ.,Kris-EthertonP.,AmericanHeartAssociationNutritionCommitteeoftheCouncilonLifestyleandCardiometabolicHealth,CouncilonCardiovascularDiseaseintheYoung,CouncilonCardiovascularandStrokeNursing,CouncilonClinicalCardiology,StrokeCouncil.RecommendedDietaryPatterntoAchieveAdherencetotheAmericanHeartAssociation/AmericanCollegeofCardiology(AHA/ACC)Guidelines:AScientificStatementFromtheAmericanHeartAssociation.Circulation.2016Nov29;134(22):e505-e529.

deSouzaR.J.,MenteA.,MaroleanuA.,CozmaA.I.,HaV.,KishibeT.,UlerykE.,BudylowskiP.,SchünemannH.,BeyeneJ.,AnandS.S.Intakeofsaturatedandtransunsaturatedfattyacidsandriskofallcausemortality,cardiovasculardisease,andtype2diabetes:systematicreviewandmeta-analysisofobservationalstudies.BMJ.2015Aug11;351:h3978.

ChowdhuryR.,WarnakulaS.,KunutsorS.,CroweF.,WardH.A.,JohnsonL.,FrancoO.H.,ButterworthA.S.,ForouhiN.G.,ThompsonS.G.,KhawK.T.,MozaffarianD.,DaneshJ.,DiAngelantonioE.Associationofdietary,circulating,andsupplementfattyacidswithcoronaryrisk:asystematicreviewandmeta-analysis.AnnInternMed.2014Mar18;160(6):398-406.

deOliveiraOttoM.C.,MozaffarianD.,KromhoutD.,BertoniA.G.,SibleyC.T.,JacobsD.R.Jr,NettletonJ.A.Dietaryintakeofsaturatedfatbyfoodsourceandincidentcardiovasculardisease:theMulti-EthnicStudyofAtherosclerosis.AmJClinNutr.2012Aug;96(2):397-404.

deGoedeJ.,GeleijnseJ.M.,DingE.L.,Soedamah-MuthuS.S.Effectofcheeseconsumptiononbloodlipids:asystematicreviewandmeta-analysisofrandomizedcontrolledtrials.NutrRev.2015May;73(5):259-75.

BrassardD.,Tessier-GrenierM.,AllaireJ.,RajendiranE.,SheY.,RamprasathV.,GigleuxI.,TalbotD.,LevyE.,TremblayA.,JonesP.J.,CoutureP.,LamarcheB.ComparisonoftheimpactofSFAsfromcheeseandbutteroncardiometabolicriskfactors:arandomizedcontrolledtrial.AmJClinNutr.2017Apr;105(4):800-809.

ThorningT.K.,BertramH.C.,BonjourJ.P.,deGrootL.,DupontD.,FeeneyE.,IpsenR.,LecerfJ.M.,MackieA.,McKinleyM.C.,MichalskiM.C.,RémondD.,RisérusU.,Soedamah-MuthuS.S.,TholstrupT.,WeaverC.,AstrupA.,GivensI.Wholedairymatrixorsinglenutrientsinassessmentofhealtheffects:currentevidenceandknowledgegaps.AmJClinNutr.2017May;105(5):1033-1045.

MensinkR.P.,ZockP.L.,KesterA.D.,KatanM.B.EffectsofdietaryfattyacidsandcarbohydratesontheratioofserumtotaltoHDLcholesterolandonserumlipidsandapolipoproteins:ameta-analysisof60controlledtrials.AmJClinNutr.2003May;77(5):1146-55.

Drouin-ChartierJ.,TremblayA.J.,Maltais-GiguèreJ.,CharestA.,GuinotL.,RiouxL.,LabrieS.,BrittenM.,LamarcheB.,TurgeonS.L.,CoutureP.Differentialimpactofthecheesematrixonthepostprandiallipidresponse:arandomized,crossover,controlledtrial.AmJClinNutr.2017Oct;pii:ajcn165027.

ContributedbyDr.SandeepRavindranFreelanceScienceWriterSandeepr.com

EditorialStaffofSPLASH!milkscienceupdate:Dr.DanielleLemay,ExecutiveEditorDr.KatieRodger,ManagingEditorAnnaPetherick,AssociateEditorProf.KatieHinde,ContributingEditorDr.LaurenMilliganNewmark,AssociateEditorDr.RossTellam,AssociateEditorDr.SandeepRavindran,AssociateEditorProf.PeterWilliamson,AssociateEditorCoraMorgan,EditorialAssistantTasslynGester,CopyEditor

FundingprovidedbyCaliforniaDairyResearchFoundationandtheInternationalMilkGenomicsConsortium

TheviewsandopinionsexpressedinthisnewsletterarethoseofthecontributingauthorsandeditorsanddonotnecessarilyrepresenttheviewsoftheiremployersorIMGCsponsors.