JPediatr(RioJ).2014;90(5):440---448
www.jped.com.br
REVIEW
ARTICLE
Vitamin
E
concentration
in
human
milk
and
associated
factors:
a
literature
review
夽
,
夽夽
Mayara
S.R.
Lima
∗,
Roberto
Dimenstein,
Karla
D.S.
Ribeiro
UniversidadeFederaldoRioGrandedoNorte,Natal,RN,Brazil
Received6March2014;accepted15April2014 Availableonline19June2014
KEYWORDS
VitaminE; Alpha-tocopherol; Humanmilk; Lactation; Newborn
Abstract
Objective: TosystematizeinformationaboutvitaminEconcentrationinhumanmilkandthe
variablesassociatedwiththiscompositioninordertofindpossiblecausesofdeficiency, sup-portingstrategiestopreventitinpostpartumwomenandinfants.
Source: Studiespublishedbetween2004and2014thatassayedalpha-tocopherolinhumanmilk
ofhealthywomenbyhighperformanceliquidchromatographywereevaluated.Thekeywords usedwere‘‘vitaminE’’,‘‘alpha-tocopherol’’,‘‘milk,human’’,‘‘lactation’’,andequivalents inPortuguese,intheBIREME,CAPES,PubMed,SciELO,ISIWebofKnowledge,HighWirePress, Ingenta,andBrazilianDigitalLibraryofThesesandDissertationsdatabases.
Summaryofthefindings: Ofthe41publicationsfoundonthesubject,25whosefulltextwas
availableandmettheinclusioncriteriawereselected.The alpha-tocopherolconcentrations foundinmilkwere similarinmostpopulationsstudied.The variablephaseoflactationwas showntoinfluencevitaminEcontentinmilk,whichisreduceduntilthematuremilkappears. Maternalvariablesparity,anthropometricnutritionalstatus,socioeconomicstatus,and habit-ualdietaryintakedidnotappeartoaffectthealpha-tocopherollevelsinmilk.However,the influence of the variables maternal age,gestational age,biochemical nutritional status in alpha-tocopherol,andmaternalsupplementationwithvitaminEhadconflictingresultsinthe literature.
Conclusion: Alpha-tocopherol concentration in milk decreases during lactation, until the
maturemilkappears.Toconfirmtheinfluenceofsomematernalandchildvariablesonmilk vitaminEcontent,furtherstudieswithadequatedesignareneeded.
©2014SociedadeBrasileiradePediatria.PublishedbyElsevierEditoraLtda.Allrightsreserved.
夽 Pleasecitethisarticleas:LimaMS,DimensteinR,RibeiroKD.VitaminEconcentrationinhumanmilkandassociatedfactors:aliterature review.JPediatr(RioJ).2014;90:440---8.
夽夽
StudyconductedattheUniversidadeFederaldoRioGrandedoNorte(UFRN),Natal,RN,Brazil.
∗Correspondingauthor.
E-mail:[email protected](M.S.R.Lima). http://dx.doi.org/10.1016/j.jped.2014.04.006
VitaminEconcentrationinhumanmilk 441
PALAVRAS-CHAVE
VitaminaE; Alfa-tocoferol; Leitehumano; Lactac¸ão; Recém-nascido
Concentrac¸ãodevitaminaEnoleitehumanoefatoresassociados:umarevisãode literatura
Resumo
Objetivo: Sistematizar informac¸ões sobre aconcentrac¸ão devitamina E noleite humanoe
variáveis associadas aessacomposic¸ão, afimde encontrar possíveiscausasde deficiência, subsidiandoestratégiasparaprevenc¸ãodestaempuérperaselactentes.
Fontedosdados: Foramavaliadosestudospublicadosentre2004e2014quedeterminaramo
alfa-tocoferolnoleitehumanodemulheressaudáveisporCromatografiaLíquidadeAlta Efi-ciência. Os descritoresutilizados foram‘‘leite humano’’,‘‘alfa-tocoferol’’, ‘‘vitamina E’’, ‘‘lactac¸ão’’ e seus equivalentes em inglês, nas bases de dados BIREME, Periódicos CAPES,
PubMed,SciELO,ISIWebofKnowledge,HighWirePress,IngentaeBibliotecaDigitalBrasileira
deTeseseDissertac¸ões.
Síntesedosdados: Das41publicac¸õesencontradassobreatemática,25foramselecionadas,
por possuirem texto completo disponível e se encaixarem nos critérios de inclusão. As concentrac¸ões encontradas de alfa-tocoferol no leite foram semelhantes na maioria das populac¸õesestudadas.Avariávelfasedelactac¸ãomostrouinfluenciaroconteúdodessa vita-mina noleite,quevaisendo reduzido atéoleite maduro.Asvariáveismaternas paridade, estadonutricionalantropométrico,condic¸ãosocioeconômicaeingestãodietéticahabitual pare-cemnãoafetarosníveisdealfa-tocoferolnoleite.Entretanto,ainfluênciadasvariáveisidade materna,idadegestacional,estadonutricionalbioquímicoemalfa-tocoferolesuplementac¸ão maternacomvitaminaEpossuiresultadosconflitantesnaliteratura.
Conclusão: Aconcentrac¸ãodealfa-tocoferolnoleitediminuidurantealactac¸ão,atéchegar
aoleitemaduro.Paraconfirmarainfluênciadealgumasvariáveismaternasedacrianc¸asobre avitaminaEdoleiteaindasãonecessáriosmaisestudos,comdesenhoadequado.
©2014SociedadeBrasileiradePediatria.PublicadoporElsevierEditoraLtda.Todososdireitos reservados.
Introduction
Alpha-tocopherol,themaincomponentofagroupof com-pounds knownasvitamin E,is apowerfulantioxidantand themainfat-solublevitaminresponsibleforprotectingcell membranesagainstperoxidation.Asalipophiliccompound, itaccumulatesincirculatinglipoproteins,cellmembranes, andfattydeposits,reactingwithfreeradicalsandmolecular oxygen,protectingpolyunsaturatedfattyacids(PUFAs)and lipoproteinsfromperoxidation.1,2
This vitaminis extremelyimportantin theearlystages oflife,fromconceptiontopostnataldevelopment.During pregnancy, placental transfer of vitamin E tothe fetus is limited, makingbreast milkthe only source of this nutri-ent for infantsthat areexclusively breastfed.This intake representsan important wayto supply the newborn with an essentialantioxidantprotection andstimulateimmune systemdevelopment.3
ConsideringtheimportanceofvitaminEforthenewborn, many studies aimed to determine the levels of alpha-tocopherolinbreastmilk.However,theliteraturepresents conflictingdataregardingthislevel,suchasthosefoundby Schweigertetal.4inGermanwomen,whoobserved alpha-tocopherollevelsinthecolostrumthatweretwo-foldhigher thanthosefoundinBangladeshiwomen.5
Thesedifferencesmaybeduetosomefactorsthatcan causechangesintheconcentrationofalpha-tocopherolin milk.Nascimentoand Issler6 highlightthat changesin the nutritional composition of milk depend on the stage of
lactation,timeoftheday, timesincelastmeal,nutrition, maternal age, gestationalage of the newborn, and other individualmaternalaspects.
Studies on the association of variables with alpha-tocopherol content in human milk have been performed. Therefore,consideringtheimportanceofvitaminEandthe breastmilkforthenewbornandthedifferentfindingsinthe literatureaboutthissubject,thisreviewaimedto system-atizeinformationonthelevelsofalpha-tocopherolinhuman milk and variables associated with this concentration, in ordertoclarifywhichfactorsinfluencethecompositionof vitaminEinmilk.
Methods
Studies published between January of 2004 and February of2014intheBIREME,CAPESjournals,PubMed,SciELO,ISI WebofKnowledge,HighWire Press,Ingenta, andBrazilian DigitalLibraryofThesesandDissertationsdatabaseswere searched.Inordertofindstudiespertainingtothesubjectof interest,specificdescriptorswereusedduringtheresearch: human milk, alpha-tocopherol, vitamin E, lactation, and theirPortugueseequivalents.
442 LimaMSetal.
onthetopic,whichalthoughdisclosedthelevelsof alpha-tocopherolobtainedbytheanalysisofhumanmilk,hadas mainobjectivetostudyvitaminlossprocesses, determina-tionmethods,amongothers,ratherthantheconcentration ofthisnutrientinmilk.
Thevariablesconsideredforthereviewontheir associ-ationwithalpha-tocopherolcontentinmilkwereidentified throughtheliteraturereview.Thus,thevariablesselected werethosemostcommonlyusedinthestudies:stageof lac-tation(colostrum,transitional,andmaturemilk);maternal age; socioeconomic status; parity; gestational age of the newborn;biochemical nutritionalstatus of maternal vita-minE;maternalanthropometricnutritionalstatus;maternal habitualdietaryintake;andsupplementationwithvitamin E.
Lactationstage
Colostrum milk is the first milk secretion,which remains until the seventh or tenth day postpartum. It is a thick liquidofhigh densityandgenerallyyellowishin colordue toitshighcontentofcarotenoids.Thismilkisalsorichin antibodies,protectingthebabyagainstinfections,andhas thepropertyoffacilitatingtheestablishmentofa predomi-nantlybifidintestinalfloraandlaxativeeffect,whichaidsin theeliminationofmeconium.6 Studieshavedemonstrated theprotectiveeffectofbreastfeedingwithcolostrummilk withinthefirst hourof life infighting neonatalmortality, pointing to the importance of this practice immediately afterdelivery.7
Aroundtheeightanduptothe15thdaypostpartum,the milkiscalled‘‘transitionalmilk’’,andchangesinits compo-sition continue to occur, until approximately two weeks postpartum,whenthemilkcompositionbecomesmore sta-ble,thusbeingcharacterizedasmaturemilk.6
Theconcentrationofalpha-tocopherolincolostrummilk inmostofthestudiedpopulationsissimilar;however,some results divergefrom the mean found by the others,such asthestudiesconductedinGermany4andSpain,8inwhich the values of the vitamin in the colostrum were much higherthanthoseobservedinBangladesh5andPoland,9for instance.Inthefirsttwostudies,however,itisemphasized thatthesamplesizewassmall,andthattheGermanstudy4 foundavariationinthecompositionofalpha-tocopherolin milk,asdemonstratedbythestandarddeviation(Table1). Therefore,itwouldbeinterestingtostudyagreaternumber oflactatingtoconfirmthesevalues.
In the case of Bangladesh, theobserved concentration maybeduetothecharacteristics ofthestudypopulation, i.e., extremelypoor women withvery bad health indica-tors,whichmakesthemmorepronetothedevelopmentof nutritionaldeficiencies.However,despitethelowerlevelsof thisnutrientinthemilkofthesewomen,thatstudy demon-stratedthatthisamountissufficienttomeetthenutritional requirements of the infant. According to Ahmed et al.,5 thisfactcan beexploredtopromotecolostrumfeedingin developingcountries suchasBangladesh, where acertain rejectionofthatmilkhasbeenrecorded.
In transition milk, the values found in different popu-lationswere alsosimilar,withtheexception of onestudy conductedinRussia,10whichpresentedlowermeanvalues,
aswell asthe studyby Quiles etal.,8 whose valueswere higherthan others.Kodentsova and Vrzhesinskaya,10 how-ever,usedsamplesofwomenwhowerebetweenthethird andtenthdaysoflactationtogetherwithothers,whowere betweenthe14thand20thdays,whichmayhaveinfluenced theresults.
In mature milk, Polish studies9,11 have also observed lower values when compared to others. The same was observedinagroupofBrazilianadolescents,demonstrating thatageinfluencesthecontentofvitaminEinbreastmilk, accordingtotheauthors.12 Anotherobservationinrelation tomaturemilkreferstothestudyconductedbyTokus¸o˘glu etal.13 inTurkey,whichshowedlevelsofalpha-tocopherol thatweresimilartothoseincolostrummilk.Quilesetal.,8 inSpain,alsoshowedresultsthatwerehigherthanthemean valuesforthismilk;butthisvaluereferstoonly15women andthesmallsamplesizemayhaveinfluencedtheresults.
Table 1 shows that there is a downward trend in
the content of alpha-tocopherol secreted in breast milk over the course of lactation stages, being higher in colostrum.4,8,9,14---17 According to Debier,3 these changes occurduetotheincreaseinfatglobulesasthemilkmatures. Afterthefirstdaysoflactation,triglyceridesynthesisinthe mammaryglandanditssecretioninmilkincrease,withouta proportionalincreaseinthesecretionofphospholipidsand othercomponentsoftheglobulemembrane.
Therefore,thereisasignificantreductionintheamount of some components of the fat globule, including alpha-tocopherol, since most of the vitamin E is secreted as a constituentofthemembraneoftheseglobules.
Althoughtheamountofalpha-tocopherolofferedtothe infantishigheratthephaseofcolostrummilkwhen com-paredtotransitionalandmaturemilk,thereisanincrease inthevolumeofmilkingestedbythenewbornwithtime, in order tomeet the infant’s nutritional needs.However, Garcia et al.15 observed that the concentration of alpha-tocopherol,consideringtheinfant’sneed(4mg/day)18 and the daily consumption of 780mL/day of milk, indicates an apparent nutritional inadequacy of transitionalmilk in their study, conducted in Northeastern Brazil. Consider-ingthis fact,it hasbeen observedthat other studiesalso showed this possible insufficient supply, when analyzing thecontentofalpha-tocopherolintransitionalandmature milk.
Some authors have studied the content of alpha-tocopherol in breastmilk inorderto helpestablish a DRI (DietaryReferenceIntake)for infants.19,20Itisknownthat therecommendationof4mg/dayofvitaminEfor children aged0to6 monthswasestimatedaccording tothemean intakeofthisnutrientthroughconsumptionofhumanmilk bytheinfants.Moreover,itisanadequateintake(AI),which isthemeanvalueestimatedwhentherecommendeddietary intake(RDA)hasyettobeestablished.18Traber1statesthat the amount ofvitamin E recommendedfor dailyintake is stillcontroversial,andseveralorganizationshaveproposed differentvalues.
V
itamin
E
concentration
in
human
milk
443
Table1 Studiesontheconcentrationofalpha-tocopherol(gdL)inbreastmilkatdifferentstagesoflactationpublishedbetween2004-2014,orderedbyyearofpublication.
n◦ Authors/Year Place Typeofstudy Samplesize Colostrummilk
␣-TOH(g/dL)
Transitionmilk
␣-TOH(g/dL)
Maturemilk
␣-TOH(g/dL)
Observations
1 Martysiak-Zurowska etal.,201317
Poland Longitudinal 48a 999.0±151.0 445.0±95.0 292.0±84.0
(1stmonth)
207.0±66.0 (3rdmonth)
Therewasno significantdifference betweenthe concentrationsat1 and3months. 2 Griloetal.,201327 Brazil Cross-sectional 93 1,147.6±582.9 - -
-3 Clemente,201325 Brazil Randomized
double-blind clinicaltrial
36(control) 40(naturalsuppl.) 33(synthetic suppl.)
1,665.2±160.2 1,387.1±176.5b
1,802.0±208.1b
- - Therewasno significantdifference betweenthe
concentrationsofthe groups.
4 Szlagatys-Sidorkiewicz etal.,20129
Poland Longitudinal 49 886.0 - 110.0
-5 Szlagatys-Sidorkiewicz etal.,201211
Poland Cross-sectional case-control
25 - - 100.0c
-6 Antonakouetal., 201121
Greece Prospective longitudinal
64(1stmonth)
39(3rdmonth)
23(6thmonth)
- - 357.5±146.4 348.9±180.9 366.1±202.4
Therewasno significantdifference betweenthe concentrationsat1, 3,and6months. 7 Dimensteinetal.,
201129
Brazil Clinicaltrial 30 1,155.4±811.0b - -
-8 Liraetal.,201123 Brazil Cross-sectional 103 1,124.1±551.3 - -
-9 Dimensteinetal., 201022
Brazil Cross-sectional 25(adolescents) 47(adults)
1,417.0±680.5 1,309.3±775.3
- - Therewasno significantdifference betweenthe
concentrationsofthe twogroups.
10 Dimensteinetal., 201032
Brazil Cross-sectional 30 1,603.4±911.0 - -
-11 Garciaetal.,201030 Brazil Clinicaltrial 37(control)
36(supplement)
986.3±749.4 (1stday)
1,175.8±732.2 (2ndday)
1,455.8±1,094.0 (1stday)b
- - Therewasno significantdifference betweenthe concentrations.
12 Garciaetal.,200915 Brazil Longitudinal 32 1,236.1±202.4 335.9±43.1 -
-13 Tjerina-Saénzetal., 200936
-444
Lima
MS
et
al.
Table1(Continued)
n◦ Authors/Year Place Typeofstudy Samplesize Colostrummilk
␣-TOH(g/dL)
Transitionmilk
␣-TOH(g/dL)
Maturemilk
␣-TOH(g/dL)
Observations
14 Orhonetal.,200931 Turkey Cross-sectional
Case-control
20 1,326.6±68.9c - -
-15 Sziklai-Lászlóetal., 200916
Hungary Cross-sectional 30a - 414.0±217.0 300.0±116.0
-16 Bisharaetal.,200835 Canada Cross-sectional 24 - - 250.0 Studyconductedwith
mothersofpreterm infants.
17 Azeredo&Trugo, 200812
Brazil Cross-sectional 72 - - 116.3±9.0 Studyconductedwith adolescents.
18 Tokus¸o˘gluetal.,200813 Turkey Cross-sectional 92 - - 984.0±213.0
-19 Kamaoetal.,200719 Japan Cross-sectional 51 - - 396.0±184.0
-20 Kodentsova& Vrzhesinskaya,200610
Russia Cross-sectional 23 - 260.0±30.0 - Concentration obtainedfromthe meanof12samples ofcolostrumfrom postpartumwomenat termandmaturemilk of11preterm postpartumwomen. 21 Quilesetal.,20068 Spain Longitudinal
Case-control
15 2,455.0c 1636.7c 861.4c
-22 Sakuraietal.,200520 Japan Cross-sectional 115 - - 309.0±159.0
-23 Campos,200514 Brazil Longitudinal 18 1,313.9±798.7 392.5±173.6 389.9±69.8
-24 Schweigertetal., 20044
Germany Longitudinal 21 2,200.9±1,339.5 - 568.5±219.7
-25 Ahmedetal.,20045 Bangladesh Cross-sectional 105 919.1±364.8 - -
-␣-TOH,alpha-tocopherol.
a Totalsamplesize,buteachconcentrationvaluereferstogroupswithsmallersamplenumbers,whichcomprisethewholegroup. b Datarefertothepre-supplementationtime.
VitaminEconcentrationinhumanmilk 445
Atthematuremilkstage,whenthissecretionnolonger undergoes majorcompositional variations,levels of alpha tocopherolappeartoremainconstantovertime.Thiswas verified in Poland17 and Greece,21 where collections of maturemilkwereperformedindifferentmonthsduringthe postpartumperiod,yieldingvaluesofalpha-tocopherolthat didnotdiffersignificantly(Table1).
Ageandmaternalsocioeconomicstatus
Theconsumptionofvitaminsbyadolescencesisquite defi-cient, especially fat-soluble vitamins.14 Adolescents are particularly susceptible to nutritional risks due to inade-quatedietaryhabits,astheyprefertoconsumehigh-energy contentfoods that are low inmicronutrients.12 Moreover, thepregnantadolescenthastoaddherowngrowth require-mentstootherrequirementsimposedbypregnancy.22
Therefore, when pregnancy and subsequent lactation occurinadolescence,nutritionalrisksassociatedwiththis conditionmayincrease.Hencethehypothesisthatthemilk ofadolescent mothersmay showloweramountsof alpha-tocopherolthanthemilkofadultmothers.12
In the study by Dimenstein et al.,22 there was no difference (p=0.50) between alpha-tocopherol levels in the colostrum of Brazilian adolescent and adult mothers (Table1).Theauthorsemphasize,however,thatthemean agefortheadolescentmotherswas17.2±1.4years,which minimizestheimpactofmenarcheontheirnutritional sta-tus,asitistheproximitybetweenmenarcheandpregnancy thatpotentiatessuchimpact.However,otherstudieshave notfoundthisassociation.5,13,23
OnlyAzeredoandTrugo,12analyzingthecontentof alpha-tocopherolinmaturemilkofadolescentsfromsoutheastern Brazil, concluded that the concentration of this vitamin in their breast milk is equivalent to less than half of that reported for the milk of adult women in developing countries.However,thisstudy didnotusea controlgroup ofadultwomen,butonlycomparedtheirresultstostudies withmaturemilkofadultpostpartumwomen.
Maternal socioeconomicstatusalso does notappearto berelatedtotheconcentrationofalpha-tocopherolinmilk. The association between these variables was studied by someauthors,whoobservedthatincomeandmaternal edu-cationallevelwerenotassociatedwithvitaminEcontentin breastmilk.5,13
However, if studies were performed in different loca-tions, comparing the extremes of socioeconomic status categorization,thesedifferenceswouldperhapsappear,as themeanconcentrationofalpha-tocopherolinthemilkof populations of extreme social deprivation is lower when comparedtothatofpopulationswithbettersocioeconomic status(Table1).
Parityandgestationalageofthenewborn
Insomemammals,thenumberofbirthsis directly associ-atedwithincreasedlevelsofvitaminEinmilk.Onepossible explanation for this fact is the increased mobilization of tissues containing alpha-tocopherol, such as the adipose tissue.4
Someauthorssuggestthatparitymayinfluencevitamin levels such as retinol in breast milk, when the previous
lactationgeneratedahighmobilizationofthereservesand hightransfertothemammarygland.Thismobilizationisalso influencedbymaternaladiposityinmultiparouswomen,and maycontributetohighervitamincontentinthebreastmilk ofthesewomen.24Thishypothesiscanbeextendedto alpha-tocopherol,asthelatter,similarlytoretinol,isafat-soluble vitaminstoredinadiposetissue.
Themajorityofstudiesontheassociationbetween par-ity and the concentration of alpha-tocopherol in breast milk found no association between these variables.5,23,25 However,Campos,14 inBrazil,found largeramountsinthe transitionmilkofprimiparouswomen.Regardingthemature milk,multiparouswomenhadhigherconcentrationsofthe vitamin.However,furtherstudiesareneededtoclarifythis association,asthisstudywasperformedwithasmallsample size(nineprimiparousandninemultiparouswomen).
Anothervariablewhoseassociation withthenutritional composition of human milk was studied was the new-born’sgestational age. Premature neonates (less than 37 weeks of gestation) are at most risk of developing vita-min E deficiency, as they require a greater supply of antioxidantnutrients due to exposure to oxidative stress causedbyinfections, oxygen,mechanical ventilation,and intravenous nutrition. Premature infants with vitamin E deficiencyhavelowhemoglobinlevels,morphological alter-ations such as anisocytosis and fragmented red cells, reticulocyteresponse,increaseinthenumberofplatelets, andhyperbilirubinemia.26
The hypothesis of differences in vitamin E concentra-tiondependingonthedurationofpregnancyhasnotbeen confirmed.10,23,27Quilesetal.,8however,inastudyof Span-ishwomen,observed that milkfrommothers of full-term infantshadsignificantly higheramountsof thisvitamin at allstagesoflactation(p<0.05).
Theseconflictingdatademonstratetheneedforfurther studiesregardingtheconcentrationofvitaminEinthemilk ofmothersofpreterminfants,astheplacentaltransferof thisvitamin during pregnancy is limited.28 This limitation makesthesupply ofalpha-tocopherolthroughbreastmilk evenmoreessential,especiallyforpreterminfants,whose gestationalage,andtherefore,transferofnutrientstothe fetusthroughtheplacenta,isevenlower.
Biochemicalnutritionalstatusinalpha-tocopherol andmaternalanthropometricnutritionalstatus
Most studies that evaluated the association between the concentration of alpha-tocopherol in blood and maternal milk demonstrate that this correlation does not exist in colostrumandmaturemilk,12,15,23,29---32indicatingtoa proba-blevitamintransferlimitationfromplasmatothemammary gland.
446 LimaMSetal.
Although the mechanisms involved in the uptake of alpha-tocopherolbythemammaryglandarenotcompletely understood, it is believed that part of alpha-tocopherol reaches the milkthrough LDL receptors andanother part canbe transportedthroughcellsurface receptors(SR-B1) that bind to HDL and LDL without lipoprotein internal-ization. There is also the suggestion that it occurs via lipoprotein lipase (LPL), as observed in experiments with rats.3,33 Additionally, a study in cows demonstrated that thesecretion of alpha-tocopherol tothe milk followsthe Michaelis-Menten kinetics, i.e., itspassage fromblood to milkoccursthrough activetransportthrough membranes, with no further increase in the secretion of this vitamin in milk when the maximum secretion capacity has been reached.34
Dimensteinetal.29 pointoutthatthesuggestionof dis-tinct mechanisms of transport and the fact that there is noassociation betweenalpha-tocopherolin plasmaandin colostrumundersupplementationconditions,reinforcethe hypothesisthatthemammaryglandcanexpressalpha-TPP protein,thealpha-tocopherolcarrierprotein.Azeredoand Trugo12 alsosuggestthatthetransportofvitaminEtomilk mayinvolvemembraneandintracellularreceptorsfor alpha-TTPinmammaryepithelialcells.
The studybyGarciaetal.,15 however,found apositive correlation between the biochemical nutritional status in alpha-tocopherolanditsconcentrationintransitionalmilk (r=0.456,p=0.009),demonstratingtheimportanceof ade-quate maternal nutritional status. A study performed in Russiaalsodemonstratedthis correlation.10 However,this associationhasbeenstudiedonlyinthemilkofmothersof pretermnewborns,withasmallsamplesize(13women).
According to Garcia et al.,15 the presence of an asso-ciation between the levels of alpha-tocopherol in plasma and in milk found only in the transition phase indicates thatthevitamintransportmechanismstothecolostrumare morecomplex,probablyinvolvingother routesin addition tothosethat are predominantin transitional and mature milk.Thereisanopenfieldforstudiesevaluatingthe asso-ciationbetween theconcentration ofvitamin Ein plasma andbreastmilk,especiallyincolostrumandmaturemilk.
Regardingthe maternalanthropometricnutritional sta-tusduringpregnancy,themostcommonlyusedindicatorto assess itsassociation withalpha-tocopherol in milkis the bodymass index (BMI).The hypothesis that maternal BMI mayberelatedtothecontentofthevitamininmilk presup-posesthatthisindicatoris,in mostcases,proportionalto bodyfatcontent.Therefore,sinceadiposetissueisastorage siteforalpha-tocopherol,thehighertheBMIofthe lactat-ingwoman,thegreaterthelevelsofvitaminstoredinthis tissueandconsequentlyreleasedintothemilk.
However, no study has demonstrated an association betweenBMIandvitaminEinbreastmilk.5,12,13,23Thus,the presentresultsindicatethatthelevelsofalpha-tocopherol inmilkappeartobeindependentfromthematernalbody mass.
MaternalhabitualdietaryintakeandvitaminE supplementation
A variable widely studied by researchers that analyzed vitamin E in breast milk is maternal dietary intake of
micronutrients, in order to understand whether the diet influencesthenutritionalcompositionofbreastmilk.
Antonakouetal.,21 inGreece,askedwomeninthe post-partumperiodregardingtheintakeoffoodsrichinvitamin E through three dietary recalls.The results indicate that the intake of vitamin E appears tohave no effecton its concentrationinbreastmilk,whichiscorroboratedbythe fact that, although the mean intake of vitamin by the womenwaslowerthantherecommended,the micronutri-ent contentinmilkachieved therecommendedlevelsfor infants.
InCanada,Bisharaetal.35 usedasemiquantitativefood frequencyquestionnairetoassessdietaryintakeofvitamin E bymothers oflow-birth weightpreterm infants.In that study,noassociation wasfound betweenalpha-tocopherol intakeanditsconcentrationinmilk.
Szlagatys-Sidorkiewicz et al.,9 based on a three-day nutritionaldiary madeby49Polishwomen,observed that theconcentrationofvitaminEinbreastmilkwasnot corre-latedwiththeirrespectivedietaryintake.Inthatstudy,the concentrationofvitaminEinmilkwasnothigherinwomen who received the vitamin supplements recommended for pregnant and lactating women, compared to those who did not (p=0.332). Also in Poland, Martysiak-Zurowska etal.17obtainedsimilarresults,withnocorrelationbetween dietaryvitaminEintakeandtheuseofsupplementswiththe concentrationofalpha-tocopherolinbreastmilk.
Another study, which analyzed breast milk in Russian womenwhoreceivedvitaminsupplementscontaining alpha-tocopherol during gestation and lactation, also found no difference in the concentration of vitamin E in the milk of these women, when compared to those who did not receive the multivitamins.10 However, a study in Canada observed a positive correlation between vitamin E found in milkandmultivitaminsupplementation, asreportedby surveyparticipants.36
Dimenstein et al.,29 when analyzing tocopherol in the milk of 30 adult women in NortheasternBrazil, observed that supplementation with a capsule containing synthetic vitaminE(49.4mgdl-alpha-tocopherol) didnotleadtoan increase in the concentrationof the vitaminin colostrum 24hoursafter supplementation.According totheauthors, thisindicatesthatthepassageofthisvitaminislimitedand raises thequestionofthevalidityofofferingsupplements containingvitaminEwithracemicmixtures.
However, in their study in the same Brazilian pop-ulation, Garcia et al.,30 using a supplemented and a non-supplemented group, observed that 24hours after supplementation withthe abovementionedcapsule, there wasasignificantincreaseintheamountofalpha-tocopherol inthecolostrumofthesupplementedgroup(p=0.04),which did not occur in controls. Thus, the fact that Dimenstein etal.29didnotfindanyinfluenceofsupplementationmight havebeencausedbytheabsenceofacontrolgroupinthe study,asthecontentofalpha-tocopherolincolostrumtends todecreaseoverthefirstfewdaysoflactation.
VitaminEconcentrationinhumanmilk 447
The capsule offered to women in the two abovemen-tioned studies also contained an overdose of vitamin A. According to Green et al.,37 in situations of supplemen-tation,thetransferofvitaminAtothemammaryglandalso occursviachylomicronsanddependsonthebindingsiteof the latter and lipolysis of triacylglycerols via LPL action. Garciaet al.30 concluded, therefore, thatthis increasein circulatingchylomicrons,withtheincrease inLPLactivity inthemammarygland,alsostimulatedtheuptakeof alpha-tocopherolpresentinthecapsuleordietarytocopherol,by increasingitsbioavailability.
Clemente25 also found significantly higher amounts of alpha-tocopherol in colostrum of Brazilian postpartum womensupplemented inthe postpartumperiodwithboth naturalandsyntheticalpha-tocopherol,whencomparedto acontrolgroupthatwasnotsupplemented.Itisnoteworthy that24hoursaftersupplementation,womenthatreceived supplementswithnaturalvitaminhad101%morevitaminin thecolostrumthanwomeninthecontrolgroup,while the mothersinthegroupthatreceivedthesynthetic supplemen-tationhadonly51.6%more,showingagreatereffectiveness ofnaturalsupplementationcomparedtosynthetic.
Basedontheresultsofthesestudies,itcanbeconcluded thatmaternaldietaryintakeofvitaminEthroughtheusual diet does not affect the vitamin concentration in breast milk. However, in situations of supplementation, studies haveshown increasedlevelsofalpha-tocopherolin breast milk(especiallywhenthisisperformed inthe postpartum period),whileothersdidnotobservethisassociation.
Thus,theactualeffectsofsupplementationon tocoph-erollevelsinbreastmilkarestillunknown,andthereis a greatneedfor newstudiestoinvestigatethisassociation. Furthermore,itisimportanttonotewhichtypeof supple-mentationisoffered, asitsabsorptionmayormaynotbe favored,dependingonthechemicalformused.
Finalconsiderations
The knowledge of factors that can influence vitamin E contentin humanmilkcan provide importantinformation for the preventionof itsdeficiency in postpartum women andinfants,assomeofthesevariablescanbecontrolled.
Basedonthisreview,it wasobserved thatthe concen-tration of alpha-tocopheroltends todecreaseasthe milk becomesmature.Parity,anthropometricnutritionalstatus, socioeconomicstatus,andhabitualdietaryintakeofvitamin Ebythemotherdonotappeartoaffectthelevelsof this nutrientinbreastmilk.
However, variables such as maternal age, alpha-tocopherolbiochemicalnutritionalstatus,gestationalage, andmaternalvitamin Esupplementationstilldemonstrate controversies regarding their association with vitamin E contentof human milkand thus, furtherstudies are nec-essary.
However, itis important toobserve thatin most stud-iesthat observedan association betweenthese variables, this association did not occur in colostrum milk, but in transitional and mature milk. This indicates possible milkhomeostasisduringcolostrumsecretion,inwhich the concentration of alpha-tocopherol does not vary in most cases,regardlessofinfluencingfactors.Thisfacthighlights
the importance of feeding the newborn in the first days postpartum, which will provide an important antioxidant defenseandensuretheproperdevelopmentoftheimmune system, as colostrum has a high concentration of alpha-tocopherol. Furthermore, the reduction of this vitamin contentin the transitionaland mature milk indicates the need toreview the recommendations of vitamin E intake for infants, as current recommendations are not met by themilksat thesestagesof lactationinsomepopulations studied.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgments
ToHeleniAiresClemente,forhercontributionand sugges-tionsthatimprovedthisstudy.
References
1.TraberMG.VitaminE.In:ErdmanJrJW,MacdonaldIA,Zeisel SH,eds.Presentknowledgeinnutrition.10thed.Washington, D.C:ILSIPress;2012.p.214---29.
2.DebierC,LarondelleY.VitaminsAandE:metabolism,rolesand transfertooffspring.BrJNutr.2005;93:153---74.
3.DebierC.VitaminEduringpre-andpostnatalperiods.Vitam Horm.2007;76:357---73.
4.SchweigertFJ,BatheK,ChenF,BüscherU,DudenhausenJW. Effectofthestageoflactationinhumansoncarotenoidlevels inmilk,bloodplasmaandplasmalipoproteinfractions.EurJ Nutr.2004;43:39---44.
5.AhmedL,NazrulIslamS,KhanMN,HuqueS,AhsanM. Antioxi-dantmicronutrientprofile(VitaminE,C,A,copper,zinc,iron) ofcolostrum:associationwithmaternalcharacteristics.JTrop Pediatr.2004;50:357---8.
6.NascimentoMB,IsslerH.Breastfeeding:makingthedifference inthedevelopment,healthandnutritionoftermandpreterm newborns.RevHospClin.2003;58:49---60.
7.Boccolini CS, Carvalho ML, Oliveira MI, Pérez-Escamilla R. Breastfeedingduringthefirsthouroflifeand neonatal mor-tality.JPediatr(RioJ).2013;89:131---6.
8.QuilesJL,OchoaJJ,Ramirez-TortosaMC,LindeJ,BompadreS, BattinoM,etal.CoenzymeQconcentrationandtotal antiox-idantcapacityofhumanmilkatdifferentstages oflactation inmothersofpretermandfull-term infants.FreeRadicRes. 2006;40:199---206.
9.Szlagatys-SidorkiewiczA,ZagierskiM,JankowskaA,ŁuczakG, MacurK,B˛aczekT,etal.LongitudinalstudyofvitaminsA, E andlipidoxidativedamageinhumanmilkthroughoutlactation. EarlyHumDev.2012;88:421---4.
10.KodentsovaVM, VrzhesinskayaOA. Evaluationof thevitamin statusinnursingwomenbyvitamincontentinbreastmilk.Bull ExpBiolMed.2006;141:323---7.
11.Szlagatys-Sidorkiewicz A, Zagierski M, Luczak G, Macur K, B˛aczekT,Kami´nskaB.Maternalsmokingdoesnotinfluence vita-minAandEconcentrationsinmaturebreastmilk.Breastfeeding Med.2012;7:285---9.
12.AzeredoVB,TrugoNM.Retinol,carotenoids,andtocopherolsin themilkoflactatingadolescentsandrelationshipswithplasma concentrations.Nutrition.2008;24:133---9.
448 LimaMSetal.
Turkishlactatingmothersunderdifferentsocio-economic sta-tus.IntJFoodSciNutr.2008;59:166---74.
14.Campos JM. Perfil dos níveis de vitaminas A e E no leite de doadoras primíparas e multíparas em bancos de leite humano [dissertation]. Recife, PE: Universidade Federal de Pernambuco;2005.
15.GarciaLR,RibeiroKD,AraújoKF,AzevedoGM,PiresJF,Batista SD, et al. Níveisde alfa-tocoferol no soro e leitematernos depuérperasatendidasemmaternidadepúblicadeNatal.Rio GrandedoNorteRevBrasSaudeMaternInfant.2009;9:423---8. 16.Sziklai-LászlóI,MajchrzakD,ElmadfaI,CserMA.Seleniumand
vitaminEconcentrationsinhumanmilkandformulamilkfrom Hungary.JRadioanalyticalNuclChem.2009;279:585---90. 17.Martysiak-Zurowska D, Szlagatys-Sidorkiewicz A, Zagierski C.
Concentrations of alpha- and gamma-tocopherols in human breastmilkduringthefirstmonthsoflactationand ininfant formulas.MaternChildNutr.2013;9:473---82.
18.Institute of, Medicine., US., National Academy of Sciences, (USA).,Dietaryreferenceintakesforvitamin,C.,vitamin,E., seleniumand,carotenoids.WashingtonDC:NationalAcademy Press;2000.
19.Kamao M, Tsugawa N, Suahra Y, Okano T. Determination of fat-solublevitamins inhumanplasma,breastmilk, andfood samples: application in nutrition survey for establishment of ‘‘Dietary Reference Intakes for Japanese’’. JHealth Sci. 2007;53:257---62.
20.SakuraiT,FurukawaM,AsohM,KannoT,KojimaT,YonekuboA. Fat-solubleandwater-solublevitamincontentsofbreastmilk fromJapanesewomen.JNutrSciVitaminol.2005;51:239---47. 21.Antonakou A, Chiou A, Andrikopoulos NK, Bakoula C,
Mata-las AL. Breast milk tocopherol content during the first six monthsinexclusivelybreastfeedingGreekwomen.EurJNutr. 2011;50:195---202.
22.DimensteinR,PiresJF,GarciaLR,LiraLQ.Concentrac¸ãode alfa-tocoferolnosoroecolostromaternodeadolescenteseadultas. RevBrasGinecolObstetr.2010;32:267---72.
23.LiraLQ,LimaMS,MedeirosJM,daSilvaIF,DimensteinR. Cor-relation of vitamin A nutritional status on alpha-tocopherol in the colostrum of lactating women. Matern Child Nutr. 2011;9:31---40.
24.Meneses F, Trugo NM. Retinol, b-carotene, and lutein+ zeaxanthin inthe milk of Braziliannursing women: associa-tions withplasmaconcentrations and influences ofmaternal characteristics.NutrRes.2005;25:443---51.
25.ClementeHA.Avaliac¸ãodasuplementac¸ãocomvitaminaE,na formanaturalousintética,emmulheresnopós-parto
imedi-atoesuaconcentrac¸ãonocolostro[dissertation].Natal,RN: UniversidadeFederaldoRioGrandedoNorte;2013.
26.BuonocoreG,PerroneS,LonginiM,VezzosiP,MarzocchiB, Paf-fettiP,etal.Oxidativestressinpretermneonatesatbirthand ontheseventhdayoflife.PediatrRes.2002;52:46---9. 27.Grilo EC, Lira LQ, Dimenstein R, Ribeiro KD. Influência da
prematuridadeedopesoaonascersobreaconcentrac¸ãode ␣-tocoferolnoleitecolostro.RevPaulPediatr.2013;31:473---9. 28.Didenco S, Gillingham MB, Go MD, Leonard SW, Traber MG, McEvoyCT.IncreasedvitaminEintakeisassociatedwithhigher ␣-tocopherol concentration in the maternal circulation but higher ␣-carboxyethyl hydroxychroman concentration in the fetalcirculation.AmJClinNutr.2011;93:368---73.
29.DimensteinR, Lira L, Medeiros AC, Cunha LR, StamfordTL. Efeitodasuplementac¸ãocomvitaminaEsobreaconcentrac¸ão dealfa-tocoferolnocolostrohumano.RevPanSaludPublica. 2011;29:399---403.
30.Garcia L, Ribeiro K, Araújo K, Pires J, Azevedo G, Dimen-stein R. Alpha-tocopherol concentration inthe colostrum of nursingwomensupplementedwithretinylpalmitateand alpha-tocopherol.JHumNutrDiet.2010;23:529---34.
31.OrhonFS,UlukolB,KahyaD,CengizB,Bas¸kanS,TezcanS.The influenceofmaternalsmokingonmaternalandnewbornoxidant andantioxidantstatus.EurJPediatr.2009;168:975---81. 32.DimensteinR,MedeirosAC,CunhaLR, AraújoKF,Dantas JC,
MacedoTM,et al.VitaminEinplasmaandhumancolostrum underfasting and postprandialconditions. J Pediatr (RioJ). 2010;86:345---8.
33.MardonesP,RigottiA.CellularmechanismsofvitaminEuptake: relevancein a-tocopherol metabolismand potential implica-tionsfordisease.JNutrBiochem.2004;15:252---6.
34.JensenSK,JohannsenAK,HermansenJE.Quantitativesecretion andmaximalsecretioncapacityofretinol,beta-caroteneand alpha-tocopherolintocows’milk.JDairyRes.1999;66:511---22. 35.BisharaR, Dunn MS,Merko SE, DarlingP. Nutrient composi-tionofhindmilkproducedbymothersofverylowbirthweight infantsborn at less than 28weeks’ gestation. J Hum Lact. 2008;24:159---67.
36.Tijerina-SáenzA, InnisSM,Kitts DD. Antioxidantcapacity of humanmilkanditsassociationwithvitaminsAandEandfatty acidcomposition.ActaPaediatr.2009;98:1793---8.
