Cosmetics0290 09

9

The Antioxidant Benefits ofOral Carotenoids for Protecting

the Skin Against Photoaging

Pierfrancesco Morganti, PhD

Professor of Applied Cosmetic Dermatology, /I University of Naples,Visiting Professor of China Medical University Shenyang,

R&D Director, Mavi Sud S.r.I., Aprilia (LT), Italy

Summary9.1 The ProtectiveRole of Carotenoids9.2 Bioavailability9.3 Biological Activities9.4 Carotenoidsand Skin Aging9.5 Concluding RemarksReferences

Summary

185186188189191196196

Carotenoids,a groupof morethan600 naturalmolecules,arefat-solublepigmentsresponsiblefor the yellow color of com, the orangecolor of

Aaron Taborand RobertM. Blair (eds.),Nutritional Cosmetics:Beautyfrom Within,185-198,© 2009 William Andrew Inc.

185

186 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS

pumpkins, the red color of tomatoes,and the green color of manyvegetables.

There are two commonly acceptedclassesof carotenoids:(a) carotens,composedof only carbonandhydrogen,and(b) oxycarotenoids,composedof carbon,hydrogen,andoxygen.All of thesecompoundshaveanidenticalbackbonestructureandtheir chemicalandbiochemicalactivitiesarerelatedto their uniquestructure,consistingof an extendedsystemof conjugateddoublebonds.Althoughthe color of fruits andvegetablesis important,theprimaryrole of carotenoidsin natureis to protectfrom ultravioletrays thechlorophyll found in plant leaves.Carotenoidsalso help chlorophyll toabsorblight energy.

In fact, they act like excellentantioxidantsby quenchingsingletoxygen,reactiveoxygenspecies,andthe free radicalsthat areby-productsof meta-bolic processesin vegetableandhumancells or environmentalpollutants.However, the hydrophilic propertiesof oxycarotenoids,like lutein andzeaxantin,allow themto reactwith singletoxygengeneratedin the waterphasemoreefficiently thannonpolar.Both carotenoidsandoxycarotenoidsseemcapableof preventingUV-inducedDNA damage,protectingboththehumaneyesand skin againstphotoaging.

In this chapterwe try to review the distribution and potentialprotectiveactivity of carotenoidsand oxycarotenoidsin the human body and toexplorenewpotentialstrategiesto explainthecausallink betweenoxidativestressand skin aging.

9.1 The Protective Role of Carotenoids

Nutrition playsan importantrole in the treatmentof manydiseases,andanappropriateselectionof nutrientscontributesto thepreventionof disorderssuchashyperlipidermia,hypertension,or vitamin deficiency[1,2]. Withinthis context,carotenoidsare amongthe compoundsthat have attractedagreatdeal of attention[3].

They area classof linearall-trans (E) form C40 polyenesfound in plants,algae, and somebacteriaand fungi. The numberof naturally occurringcarotenoidsreportedcontinuesto rise and has now reachedabout 750(Fig. 9.1). Although animals and humans cannot biosynthesizethem

9: ANTIOXIDANT BENEFITS OF ORAL CAROTENOIDS,MORGANTI 187

Figure 9.1 Structure of some common carotenoids in the human diet.

denovo,carotenoidsareoften present,sometimesin high concentrations,in animal tissue.Animalsobtainthesecompoundsfrom diet or perhaps,insomecases,from associatedmicro-organisms,but they may modify thestructure of the ingestedcarotenoidsto produce new metabolites[4].Chemically,typical carotenoidpigmentsaretetraterpenoids,consistingofeight5-carbonisoprenoidunits.

Carotenoids,responsiblefor the yellow color of corn, the orangecolorof pumpkins,and the red color of tomatoes,have the primary role toprotect the chlorophyll found in plant leaves.As is commonknowl-edge,chlorophyll is the primary sourceof energygenerationin plants.However,you might not be awareof the fact thatchlorophyll is suscep-tible to damagecausedby exposureto excessiveamountsof light, par-ticularly ultravioletrays.Carotenoids,particularlylutein andzeaxanthin,arepresentin the chloroplaststo helpprotectthe chlorophyll from suchdamage.Additionally, carotenoidshelp chlorophyll to collect lightenergy.

Moreover, it has beenshown that thesepigmentsprotectphotosyntheticorganismsagainstpotentially lethal photosensitizationby meansof endo-genousphotosyntheticpigments [5,6]. Therefore,carotenoidpigments


Figure 9.2 Structure of the xanthophylls lutein and zeaxanthin.

may havea protectiverole not only in plantsbut in humansaswell. Thereare two known classesof carotenoids:

• carotens,composedof only carbonand hydrogen,including,a-carotene,�~�-�c�a�r�o�t�e�n�e�, and lycopene

• xanthophylls,composedof carbon,hydrogen,and oxygen,including lutein, zeaxanthin,and �~�-�c�r�y�p�t�o�x�a�n�t�h�i�n

Becausethe hundredsof naturalcarotenoidscontainoneof severalcentersor axesof chirality, they can also occur in variousoptical isomers.Suchconfigurationalchangesmay havea significanteffecton the physicalandbiochemicalpropertiesof the molecules.Hydrocarboncarotenoids,as incarotens,are apolarlipophylic moleculesand are not solublein waterbutarereadily solublein organicsolventsand, to someextent,in fats andoils.The presenceof a hydroxy group,as in xanthophylls,gives the moleculessomepolarity, but suchcompoundsare still predominantlyhydrophobic(Fig. 9.2).

9.2 Bioavailability

Becauseof their hydrophobicity,carotenoidsare not solublein the aque-ous environmentof the gastrointestinaltract. They need to be dissolved!carriedin lipid + bile salt systemsto be absorbedat the enterocytebrushborder. It is importantto remember,in fact, that the uptakeof all carote-noids from diet is influencedby many variablessuch as: (a) the stateofthe food (raw, cooked,and/orprocessed);(b) the presenceand efficiencyof digestive enzymesand other endogenousdigestives; and (c) thecompositionof a meal (presenceof fibers, fat, and its physical form).


Moreover,the location and the physicalform of all the carotenoids(inadditionto age,gender,smokingstatus,andalcoholcomposition)influ-encetheir bioavailabilityandtheirconsequentabsorption.Thus,absorp-tion of carotenoidsand xanthophyllsis enhancedby their transferto thelipid phaseduring cooking in the presenceof oil and by disruptionofthe cellular matrix during mastication[7,8]. Absorbedby the mucusofthe small intestine, they are transportedthrough the enterocyteandhepatocyte, and incorporated into chylomicrons. Finally, they arereleasedinto the systemiccirculationcarriedby high- and low-densitylipoproteins.It was recently shown that the bioavailability of purifiedlutein diet supplementis nearlydoublethat of lutein takenby vegetablesources[9-1 I].

9.3 Biological Activities

The chemicalandbiochemicalactivities of carotenoidsarerelatedto theirunique structure,consistingof an extendedsystemof conjugateddoublebonds.A numberof biological effects thereforehave been attributedtocarotenoids,includingantioxidantactivity,influenceontheimmunesystem,control of cell growth and differentiation,and stimulatoryeffects on gapjunctionalcommunications.However,recentattemptsat dietary manipu-lation appearto be promising in terms of providing protectionagainstcertain solar-inducedeffects presentin photoagedskin. Carotenoidsarepowerful singlet-oxygenquenchersandexhibit additionalantioxidantpro-perties.In fact, their conjugatedpolyenebackbonehasthe ability to delo-calize a charge or an unpaired electron [12]. These physical chemicalpropertiesconferthe ability to act asan antioxidantand to terminatefreeradical reactionsin vitro with the productionof resonance-stabilizedfreeradical structures.Terminationmay be a result of (a) adduct formation,wherethe free radicaljoins onto the polyenechainto producea lessreac-tive free radical; (b) electrontransferfrom thecarotenoidto the free radi-cal to producea lessreactivechargedcarotenoidradical; or (c) donationof a hydrogenmoleculeto the free radical to producea stablecarotenoidradical [13]. However,oxygen speciesthat are efficiently scavengedbycarotenoidsare 102 and peroxyl radicals,and physicalquenchingseemsto be the majorpathwayinvolved in the deactivationof 102.

Moreover, it has been shown that a combinationof carotenoidsplusvitamins E and C are more effective than �~�-�c�a�r�o�t�e�n�e alone [14-16] andmay increasesuperficial skin lipids (Fig. 9.3), skin hydration (Fig. 9.4),


Figure 9.3 Percent increase in superficial skin lipids after dietarysupplementation with carotenoids or carotenoids plus other antioxidants.

Figure 9.4 Percent increase in skin hydration after dietarysupplementation with carotenoids or carotenoids plus other antioxidants.


Figure 9.5 Percent increase in skin pigmentation after dietarysupplementation with carotenoids or carotenoids plus otherantioxidants.

and skin pigmentationof dryness-proneskin (Fig. 9.5), also decreasingoxidativestressat the level of blood serum(Fig. 9.6). Thesemixtures, infact, areable to inhibit the formation of thiobarbituricacid reactivecom-poundsmoreeffectively than singlecomponentswhenthey areusedat thesamemolar level. Such a synergisticantioxidanteffect seemsto be morepronouncedwhen either lycopeneor lutein are presentin the mixture.Thesedata indicatethat doselevels of carotenoidsmay be importantandmay havedifferential effects as well. The higher protectionprovidedbymixturesmayberelatedto the specificpositioningof differentcarotenoidsin the cell membrane(Fig. 9.7).

9.4 Carotenoids and Skin Aging

Skin aging is a complex biological processthat is influencedby bothintrinsic and extrinsic factors that lead to a progressiveloss of the skin'sflexibility and youthful appearance.Natural aging is acceleratedbyenvironmentalfactors and by sun exposurein particular. Macroscopic


Figure 9.6 Oxidative stress level in blood serum after dietarysupplementation with carotenoids or carotenoids plus other antioxidants.

Figure 9.7 Schematic representation of the positioning of carotenoids inthe cell membrane.

changes(skin wrinkling, rough skin texture,and irregular pigmentation)andmicroscopicchanges(degradationof extracellularmatrix moleculesand DNA damage)are the hallmark of photoagingattributed to bothUVB and UVA rays [17,18]. All of theseprocessesare involved in the

9: ANTIOXIDANT BENEFITSOFORAL CAROTENOIDS,MORGANTI 193

initiation andprogressionof skin cancers.Thereis alsoevidenceindicatingthatprolongedUV exposuredepletestheserumandskinof bothcarotenoidsand xanthophylis [19-21].

The protectiveeffectsare thoughtto be relatedto the antioxidantproper-ties of carotenoids.During ultraviolet (UV) irradiation,skin is exposedtophoto-oxidativedamageinducedby the formation of reactiveoxygenandnitrogen species(ROS and RNS). This damageaffects cellular lipids,proteins,and DNA, and is consideredto be involved in the formation oferythema,prematureaging of the skin, photodermatoses,and skin cancer.Carotenoidsareefficient scavengersof ROSand RNS [22].

Whatis importantto underlineis the necessityto control thebaselinecaro-tenoidconcentrationin healthysubjectsparticipatingin a diet supplementstudy. In fact, carotenoiddepletionstudiesmay providea clearpictureofwhetherandwhen they are importantantioxidants.This is becausealmostall the conflicting information on the antioxidantactivity of carotenoidshas been obtainedby administeringcarotenoidsupplementsto alreadywell-fed individuals. Our double-blindplacebo-controlledtrial involvingthe useof lutein/zeaxanthintakenorally andat the sametime appliedtopi-cally hasyieldedinterestingresultson differentcontrolledparameters[23]such as skin hydration (Fig. 9.8), superficial skin lipids (Fig. 9.9), skinelasticity (Fig. 9.10), and lipid peroxidation(Fig. 9.11). Test subjectsfol-lowed a 6-dayrotationalbalancedMediterraneandiet containingno morethan0.5 mg. of �~�-�c�a�r�o�t�e�n�e�/�d�a�y�. As a consequence,15daysbeforestarting,the level of �~�-�c�a�r�o�t�e�n�e in thebloodserumwasmedially0.35±0.6IlmoIlL,whereasduring the supplementationperiod plasma levels increasedmedially to 2.3 ± 1.7umol/L.

What were the unexpectedresults?Xanthophyllsand carotensseem tohave not only an interestingmoisturizing activity but also a combinedmetabolicroute,andthe two influenceeachother.Thus, playinga specificrole asa photoprotectiveagentthanksto its ability to screenout damagingblue and UV light from the sun, lutein/zeaxanthinhas four primaryfunctions:

I. to quenchthe triplet stateof photosensitizermoleculesandthe singletstateof molecularoxygen

2. to actasanantioxidantagainstoxygenandnitrogenreactivespecies


Figure 9.8 Percent increase in skin hydration after treatment with topicallutein, oral lutein, or oral + topical lutein.

Figure 9.9 Percent increase in superficial skin lipids after treatment withtopical lutein, oral lutein, or oral + topical lutein.

9: ANTIOXIDANT BENEFITS OF ORAL CAROTENOIDS, MORGANTI 195

Figure 9.10 Change in skin elasticity (relative elastic retraction) aftertreatment with topical lutein, oral lutein, or oral + topical lutein.

Figure 9.11 Change in skin lipid peroxidation after treatment with topicallutein, oral lutein, or oral + topical lutein.


3. to absorbbluewavelengthlight, which iscurrentlyconsideredmuchmore detrimentalthan UV rays

4. to maintainthe moistureactivity at the level of the humanhorny layer'slipid lamellae

It thereforeappearsthat thesexanthophyllsplayaspecific role as photo-protectiveagentscapableof reducinginflammatoryROS-mediates,modu-lating skin hydration,decreasingskin aging, and, therefore,improving thequality of our life.

9.5 Concluding Remarks

The large group of plant carotenoidspresentin the Mediterraneandietattracts major interest becauseof their potential antiaging and otherbeneficialproperties,presumablybasedon their function as naturalanti-oxidants. Carotenoidsare compoundsof particular interest becauseoftheir extensiveuse in dietary supplements.Their regular, long-termcon-sumptionmay improveantioxidantdefencein vivo and thus help to lowerrisks associatedwith diseasescausedby oxidativedamage.

However, more information on the photoagingactivity of these naturalcompoundsis neededin order to understandhow they act on the varioustarget tissues. Systematicpharmacokineticand dose-responsestudiesare required to determinethe different bioavailability of the individualcarotenoidsand xanthophills, and to estimatethe amountsin diet thatare likely to induce biological effects. Finally, more long-term carote-noid depletionchemical trials with well-characterizeddiet supplementsare necessaryin order to confirm their beneficial antiaging effects inhumans.

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