Mesozeaxanthin.docx

Mesozeaxanthin.docx

《Mesozeaxanthin.docx》由会员分享，可在线阅读，更多相关《Mesozeaxanthin.docx（13页珍藏版）》请在冰豆网上搜索。

Mesozeaxanthin

Meso-zeaxanthin:

acutting-edgecarotenoid

ByRichardBone

∙

∙

∙

∙Print

∙Comment

∙Email

Currentevidencedemonstratesthatthecarotenoidslutein,zeaxanthinandmeso-zeaxanthinarereadilybioavailableandifsupplementedwilleffectivelyincreasemacularpigmentlevels.Thedistinctionbetweeneachremainsafocusofresearchinmanylabs.JohnTLandrum,PhD,andRichardABone,PhD,investigate

Nowhereinthehumanbodyisthenutritionalsignificanceofcarot-enoidsmoreevidentthanintheretina.1,2,3Here,atthecentreoftheretina（the?

fovea?

）,dietaryxanthophyllsareaccumulated,constitutingthemacularpigmentsormaculalutea.4,5

Theseyellowcompoundsareconcentratedtothegreatestextentwithintheinnerretinallayerssothatbluelight,focuseduponthefoveabythelensandcornea,isfilteredandattenuatedbeforereachingthecriticallyfunctionalphotoreceptorandretinalpigmentepitheliumlayersintheouterretina.6

Theconcentrationoftheseyellowcarotenoidsfoundinthemacularregionoftheretinaintheeyeisabout10,000timesgreaterthanthatfoundinblood,attestingtoamechanismofactiveaccumulationbythistissue.7

Thecarotenoidsofthemacularpigmentareclassifiedasxanthophyllsandarestructurallyrelatedtoalpha-andbeta-carotene;theydifferfromthesecarotenesonlybythepresenceofhydroxylgroups.Itisstartlingthattheretinaaccumulatesonlythexanthophyllsluteinandzeaxanthin,twoofaboutadozenabundantcarotenoidsfoundintheblood,whilenoteventracesoftheothercarotenoidsarefoundinthistissue.

Othertissuesofthebody,suchastheliver,skinandfat,alsohavedetectablelevelsofallserumcarotenoids,butappeartohavelittleornospecificity.8,9Oneexceptiontothisisthehumanlens.Here,liketheretina,onlyluteinandzeaxanthinarepresent,thoughapparentlyatmuchlowerconcentrationsthanintheretina.10,11,12

Luteinandzeaxanthineachexistinanumberofdifferentisomericformsinnature.13,14Thisisbecauseofthestructuralvariabilityinthethree-dimensionalgeometryofcovalentlybondedcarbonatoms.Inadditiontothe?

bent?

orcis-carotenoidsthatresultfromthetwopossiblearrangementsofeachdoublebondinthepolyenechain,thepresenceoftheoxygenatomsontheendgroupsinthemoleculesalsoconferstheopportunityforstereoisomerismduetothehandednessorchiralnatureofthetetrahedralcarbon.

Becauseofthespecificityofthecarotenoidbiosyntheticpathwaysinhigherplants,thedietofhumansisalmostdevoidofallbuttwostereoisomersofluteinandzeaxanthin.Otherisomersinmosthumanfoodsourcesarepresentinverylowquantities.Thepresenceofthezeaxanthinisomer,meso-zeaxanthin,inahighpercentageinthemacularpigment,isanunexpectedandinterestingscientificmystery.15,16（Seesidebar,below.）

Functionalityofxanthophyllsintheeye

Whatmightbethefunctionsofthexanthophyllsinthehumaneye?

Asearlyas1933,WallsandJuddnotedthatcolourmatchinginthecentralfieldofvisionwasinfluencedbyayellowpigment.17Oneoftheearliestsuggestionsonthefunctionofmacularpigment,itsabilitytoabsorbbluelight,wasputforwardbyGeorgeWald,whowontheNobelPrizein1967fordiscoveriesabouttheprimaryphysiologicalandchemicalvisualprocessesintheeye.18

Theimperfectrefractionofthedifferentwavelengthsoflightbyalens,calledchromaticaberration,hasbeenknownforcenturiestolimitthequalityoftheimageseenbyanobserver.Rudduckhypothesisedthatbyreducingthetransmittanceofbluelightthroughtheretina,themacularpigmentswouldimprovevisualacuitybydiminishingtheeffectsofanychromaticaberrationduetothelensandcornea.19Walls,andlaterReadingandWeales,suggestedthatthemacularpigmentmightreducetheamountofatmosphericallyscatteredbluelightreachingthephotoreceptors,whichresultsinahazyappearanceofdistantobjects.20,21

Recently,ithasbeentheorisedthatmacularpigmentisboundtovisualfunctionforindividualstoimprovecontrastsensitivity,thoughthisideastillisnotuniversallyaccepted.22,23,24Anumberofepidemiologicalstudies（butbynomeansall）25haveimplicatedluteinandzeaxanthininthereductionofriskforeyedisease,specificallyage-relatedmaculardegeneration（AMD）andcataracts.26,27,28,29

BothhigherserumlevelsofluteinandzeaxanthinandincreasedlevelsofdietaryintakewerecorrelatedwithlowerriskforadvancedformsofAMDbytheEDCCstudy.30,31AsimilarfindinghasemergedfromtheAREDstudy.32Notably,bothofthesearelargestudiesincludingseveralthousandsubjects.Inotherstudies,riskofcataractsinbothmalesandfemaleswasfoundtobelowerbynearly20percentforsubjectswhohaveahighdietaryintakeofluteinandzeaxanthin.Again,thesestudiesincludedlargenumbersofsubjects.26,27

Becausethesetwoeyediseasesaccountforamajorityofthereducedvisionfunction（cataracts）andnewcasesofadultblindness（AMD）inWesternpopulations,thepossibilitythatdietarycomponentsmaysubstantiallylowertheriskfortheiroccurrence,ordelaythemostsevereeffects,posessomecompellingquestions.Amongthem,willdietarysupplementationaltermacularandlensxanthophylllevels?

Andifso,dothesehigherlevelsdemonstrablyreduceordelayincidencesofAMDandcataracts?

Partialanswerstothesequestionshaveemergedfromnumerousstudiesontheeffectsofsupplementation.Dietarysupplementscontaininglutein,zeaxanthinand,veryrecently,meso-zeaxanthin,havebecomeavailablecommerciallyintheUS.Thebiologicalavailabilityofasupplement—theextenttowhichitisabsorbedfromthedietasmeasuredbyitspresenceintheblood—isakeyfactoressentialforitstransporttofunctionallysignificantsites.Serumstudiesshowthattheresponsesofindividualstodietarysupplementationwithlutein/zeaxanthinand/ormeso-zeaxanthinvaryoverawiderangeandthatadailydoseofaslittleas2.4mg/dayofluteincanresultinanaverageserumincreaseof120percent.33,34

Factorsthathaveemergedassignificantlyaffectingtheresponseofindividualstocarotenoidintakearetheextentofdissolutionandthepresenceofothercarotenoids.35Tanumihardjorecentlyshowedthatdramaticallyincreasedserumlevelsresultforxanthophyllsthatarefullydissolvedinoilascomparedtothoseinsuspensions.36Inanotherrecentstudy,acombinedsupplementcomposedof10mg/dayofluteinand10mg/dayofzeaxanthinresultedinsteady-stateserumlevelsforeachcarotenoidthatwasapproximatelyhalfthatobservedinadoseof10mgofonlyluteinoronlyzeaxanthin.37,38Athighlevelsofintake,asaturationlimitfortheabsorptionofcarotenoidsisapparentlyreachedandthetwocompetetosomeextent.

Theabilityofsupplementationtoaltermacularpigmentlevelshasbeendemonstratedinseveraldifferentlaboratoriessinceouroriginalreportin1997.38,39,40,41,42Measurementofmacularcarotenoidsinvivoisanexcitingareaofinvestigation,andmanycontendingmethodologieshavebeendeveloped.（Seesidebar,below.）Unfortunately,thereisnomethodologycurrentlyavailablefortheinvivomeasurementoflensxanthophylls.

Anotherapproachistheinvitrostudyoftissuecultures.Celllinesderivedfromenterocytes（CaCo-2）,43,44,45retinalpigmentepitheliumcells（ARPE-19）46,47,48,49andhumanlensepithelialcells50areallbeinginvestigatedasinvitromodelsforcarotenoidmetabolism.Researchersusingeachofthesecelllineshaveconfirmedthatxanthophyllsaccumulatewithinthecells.Awiderangeofstudiesusingthesecelllinesisunderwaytohelpestablishthefunctionsofxanthophylls.Especiallyinterestingandrelevantarestudiesoftheabilityofxanthophyllstoprotectretinalpigmentepitheliumandhumanlensepitheliumcellsfromlight-induceddamage.

Therapeuticeffects

Becausetheretinacontainsamixtureofcarotenoids,productdevelopersareleftwithachoiceofwhichcarotenoidsandofhowmuchofeachwouldbeanidealsupplement.Researchershaveseenthatduringsupplementationwithlutein,zeaxanthinandmeso-zeaxanthin,individualsmayrespondoverawiderangeoflatitudes;inter-subjectvariabilitycanbedramatic.51Whilesmalldailydosesoflutein,forexample2.4mg/day,areadequatetoproducechangesinthemacularpigmentopticaldensityofsomesubjects,othersapparentlydonotrespondatdosesthatareasgreatas20mg/day.51Clearly,itisnotyetpossibletopredictabestdoseforanygivenindividual.

Partofthecauseforthelowresponseinsomesubjectsmayliewiththemethodology.Whenheterochromaticflickerphotometryisutilisedtomeasuremacularpigmentopticaldensity,areferencepointischosenintheperipheralretinaandallchangesaremeasuredrelativetothispoint.Inatleastonestudy,evidenceindicatesthatincreasesinpigmentationatthereferencepointmayhavecontributedtoanapparentlowresponseinthesubjects.38

Ithasbeenrecentlydemonstratedthatthemeso-zeaxanthinpresentintheeyeisametabolicproductthatoriginatesfromlutein.52Monkeysthatwerecompletelydeficientinmacularpigmentationregainedthesecarotenoidswhensupplementedoveraperiodofmanyweeks.Thosegivenpurezeaxanthinwerefoundtohaveonlythatcarotenoidpresentintheretina,whereasthosefedluteinwerefoundtohavebothluteinandmeso-zeaxanthin,supportingourhypothesisthatmeso-zeaxanthinisderivedfromlutein.15Asyetresearcherslackacompleteunderstandingofthepathwaybywhichtheconversionoccurs.3

Supplementation

Thepossibilityofraisingthedensityofmacularpigmentintheeyethroughdietarymodificationwasfirstputtothetestin