2. 186 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS
pumpkins, the red color of tomatoes, and the green color of many
vegetables.
There are two commonly acceptedclassesof carotenoids:(a) carotens,
composed only carbonandhydrogen,and(b) oxycarotenoids,
of composed
of carbon,hydrogen,andoxygen.All of thesecompounds havean identical
backbone structureandtheir chemicalandbiochemicalactivitiesarerelated
to their uniquestructure,consistingof an extendedsystemof conjugated
doublebonds.Although the color of fruits and vegetables important,the
is
primary role of carotenoids natureis to protectfrom ultraviolet rays the
in
chlorophyll found in plant leaves. Carotenoidsalso help chlorophyll to
absorblight energy.
In fact, they act like excellentantioxidantsby quenchingsinglet oxygen,
reactiveoxygenspecies, ndthe free radicalsthat areby-productsof meta-
a
bolic processes vegetableand humancells or environmentalpollutants.
in
However, the hydrophilic propertiesof oxycarotenoids,like lutein and
zeaxantin,allow themto reactwith singletoxygengenerated the water
in
phasemore efficiently than nonpolar.Both carotenoidsandoxycarotenoids
seemcapableof preventingUV-inducedDNA damage, rotectingboththe
p
humaneyesand skin againstphotoaging.
In this chapterwe try to review the distribution and potential protective
activity of carotenoidsand oxycarotenoidsin the human body and to
explorenew potentialstrategies explainthe causallink betweenoxidative
to
stressand skin aging.
9.1 The Protective Role of Carotenoids
Nutrition playsan importantrole in the treatment f many diseases, an
o and
appropriate selectionof nutrientscontributesto the preventionof disorders
such ashyperlipidermia,hypertension, r vitamin deficiency[1,2]. Within
o
this context,carotenoidsare amongthe compoundsthat have attracteda
greatdeal of attention[3].
They are a classof linearall-trans (E) form C40 polyenesfound in plants,
algae, and somebacteriaand fungi. The numberof naturally occurring
carotenoidsreportedcontinuesto rise and has now reachedabout 750
(Fig. 9.1). Although animals and humans cannot biosynthesizethem
3. 9: ANTIOXIDANT BENEFITS OF ORAL CAROTENOIDS,MORGANTI 187
Figure 9.1 Structure of some common carotenoids in the human diet.
de novo, carotenoids often present,sometimes high concentrations,
are in
in animal tissue.Animals obtainthesecompounds from diet or perhaps,n
i
some cases,from associated micro-organisms, ut they may modify the
b
structure of the ingestedcarotenoidsto produce new metabolites[4].
Chemically,typical carotenoidpigmentsare tetraterpenoids, consistingof
eight 5-carbonisoprenoidunits.
Carotenoids, esponsible the yellow color of corn, the orangecolor
r for
of pumpkins,and the red color of tomatoes,have the primary role to
protect the chlorophyll found in plant leaves.As is common knowl-
edge,chlorophyll is the primary sourceof energygenerationin plants.
However,you might not be awareof the fact that chlorophyll is suscep-
tible to damagecausedby exposureto excessive amountsof light, par-
ticularly ultravioletrays. Carotenoids, articularlylutein and zeaxanthin,
p
are presentin the chloroplaststo help protectthe chlorophyll from such
damage.Additionally, carotenoidshelp chlorophyll to collect light
energy.
Moreover, it has been shown that thesepigmentsprotectphotosynthetic
organismsagainstpotentiallylethal photosensitization meansof endo-
by
genousphotosyntheticpigments [5,6]. Therefore,carotenoidpigments
4. 188 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS
Figure 9.2 Structure of the xanthophylls lutein and zeaxanthin.
may havea protectiverole not only in plantsbut in humansas well. There
are two known classes carotenoids:
of
• carotens, omposed only carbonand hydrogen,including,
c of
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
Because hundreds naturalcarotenoids
the of containone of severalcenters
or axes of chirality, they can also occur in various optical isomers.Such
configurationalchangesmay have a significanteffect on the physicaland
biochemicalpropertiesof the molecules.Hydrocarboncarotenoids,as in
carotens,are apolarlipophylic moleculesand are not solublein waterbut
are readily solublein organicsolventsand, to someextent,in fats and oils.
The presence a hydroxy group, as in xanthophylls,gives the molecules
of
somepolarity, but such compoundsare still predominantlyhydrophobic
(Fig. 9.2).
9.2 Bioavailability
Because their hydrophobicity,carotenoidsare not solublein the aque-
of
ous environmentof the gastrointestinal ract. They need to be dissolved!
t
carriedin lipid + bile salt systemsto be absorbedat the enterocytebrush
border. It is importantto remember,in fact, that the uptakeof all carote-
noids from diet is influencedby many variablessuch as: (a) the stateof
the food (raw, cooked,and/orprocessed); b) the presence
( and efficiency
of digestive enzymesand other endogenousdigestives; and (c) the
compositionof a meal (presenceof fibers, fat, and its physical form).
5. 9: ANTIOXIDANT BENEFITS OF ORAL CAROTENOIDS,MORGANTI 189
Moreover,the location and the physicalform of all the carotenoids(in
additionto age,gender,smokingstatus,and alcohol composition)influ-
encetheir bioavailability andtheir consequent absorption.T hus,absorp-
tion of carotenoids and xanthophyllsis enhanced their transferto the
by
lipid phaseduring cooking in the presence oil and by disruption of
of
the cellular matrix during mastication[7,8]. Absorbedby the mucusof
the small intestine, they are transportedthrough the enterocyteand
hepatocyte, and incorporated into chylomicrons. Finally, they are
releasedinto the systemiccirculation carriedby high- and low-density
lipoproteins. It was recently shown that the bioavailability of purified
lutein diet supplements nearlydoublethat of lutein takenby vegetable
i
sources[9-1 I].
9.3 Biological Activities
The chemicalandbiochemicalactivities of carotenoids arerelatedto their
unique structure,consistingof an extendedsystemof conjugateddouble
bonds.A numberof biological effects thereforehave been attributedto
carotenoids,ncluding antioxidantactivity,influenceon theimmunesystem,
i
control of cell growth and differentiation, and stimulatoryeffects on gap
junctional communications. owever,recent attemptsat dietary manipu-
H
lation appearto be promising in terms of providing protection against
certain solar-inducedeffects presentin photoagedskin. Carotenoidsare
powerful singlet-oxygenquenchers andexhibit additional antioxidantpro-
perties.In fact, their conjugatedpolyenebackbone hasthe ability to delo-
calize a charge or an unpaired electron [12]. These physical chemical
propertiesconferthe ability to act asan antioxidantand to terminatefree
radical reactionsin vitro with the productionof resonance-stabilized free
radical structures.Termination may be a result of (a) adduct formation,
wherethe free radicaljoins onto the polyenechainto producea lessreac-
tive free radical; (b) electrontransferfrom the carotenoidto the free radi-
cal to producea less reactivechargedcarotenoidradical; or (c) donation
of a hydrogenmoleculeto the free radical to producea stablecarotenoid
radical [13]. However, oxygen speciesthat are efficiently scavenged by
carotenoidsare 102 and peroxyl radicals,and physical quenchingseems
to be the major pathwayinvolved in the deactivationof 102.
Moreover, it has been shown that a combination of carotenoidsplus
vitamins E and C are more effective than ~ - c a r o t e n e alone [14-16] and
may increasesuperficial skin lipids (Fig. 9.3), skin hydration (Fig. 9.4),
6. 190 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS
Figure 9.3 Percent increase in superficial skin lipids after dietary
supplementation with carotenoids or carotenoids plus other antioxidants.
Figure 9.4 Percent increase in skin hydration after dietary
supplementation with carotenoids or carotenoids plus other antioxidants.
7. 9: ANTIOXIDANT BENEFITS OF ORAL CAROTENOIDS,MORGANTI 191
Figure 9.5 Percent increase in skin pigmentation after dietary
supplementation with carotenoids or carotenoids plus other
antioxidants.
and skin pigmentationof dryness-prone skin (Fig. 9.5), also decreasing
oxidative stressat the level of blood serum (Fig. 9.6). Thesemixtures,in
fact, are able to inhibit the formation of thiobarbituricacid reactivecom-
poundsmoreeffectively than single components when they areusedat the
samemolar level. Such a synergisticantioxidanteffect seemsto be more
pronouncedwhen either lycopeneor lutein are presentin the mixture.
Thesedata indicatethat doselevels of carotenoids may be importantand
may have differential effects as well. The higher protectionprovided by
mixturesmay be relatedto the specific positioningof differentcarotenoids
in the cell membrane (Fig. 9.7).
9.4 Carotenoids and Skin Aging
Skin aging is a complex biological processthat is influenced by both
intrinsic and extrinsic factors that lead to a progressiveloss of the skin's
flexibility and youthful appearance.Natural aging is acceleratedby
environmentalfactors and by sun exposurein particular. Macroscopic
8. 192 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS
Figure 9.6 Oxidative stress level in blood serum after dietary
supplementation with carotenoids or carotenoids plus other antioxidants.
Figure 9.7 Schematic representation of the positioning of carotenoids in
the cell membrane.
changes(skin wrinkling, rough skin texture,and irregular pigmentation)
andmicroscopicchanges(degradation extracellularmatrix molecules
of
and DNA damage)are the hallmark of photoagingattributed to both
UVB and UVA rays [17,18]. All of theseprocesses involved in the
are
9. 9: ANTIOXIDANT BENEFITSOFORAL CAROTENOIDS,MORGANTI 193
initiation andprogression skin cancers. hereis alsoevidenceindicating
of T
thatprolongedUV exposure depletesthe serumandskin of both carotenoids
and xanthophy [19-21].
lis
The protectiveeffectsare thoughtto be relatedto the antioxidantproper-
ties of carotenoids. uring ultraviolet (UV) irradiation,skin is exposedto
D
photo-oxidativedamageinducedby the formation of reactiveoxygenand
nitrogen species(ROS and RNS). This damageaffects cellular lipids,
proteins,and DNA, and is considered be involved in the formation of
to
erythema,prematureaging of the skin, photodermatoses, skin cancer.
and
Carotenoids efficient scavengers f ROS and RNS [22].
are o
Whatis importantto underlineis the necessity control the baselinecaro-
to
tenoidconcentration healthysubjectsparticipatingin a diet supplement
in
study. In fact, carotenoiddepletionstudiesmay provide a clearpicture of
whetherand when they are importantantioxidants.This is because almost
all the conflicting information on the antioxidantactivity of carotenoids
has been obtainedby administeringcarotenoidsupplementsto already
well-fed individuals. Our double-blindplacebo-controlled trial involving
the useof lutein/zeaxanthin takenorally and at the sametime appliedtopi-
cally hasyieldedinterestingresultson differentcontrolledparameters [23]
such as skin hydration (Fig. 9.8), superficial skin lipids (Fig. 9.9), skin
elasticity (Fig. 9.10), and lipid peroxidation(Fig. 9.11). Test subjectsfol-
lowed a 6-day rotationalbalancedMediterranean diet containingno more
than0.5 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 the bloodserumwasmedially0.35 ± 0.6IlmoIlL,
whereas during the supplementationperiod plasma levels increased
medially to 2.3 ± 1.7 umol/L.
What were the unexpectedresults?Xanthophylls and carotensseem to
have not only an interesting moisturizing activity but also a combined
metabolicroute, and the two influenceeachother.Thus, playing a specific
role asa photoprotective agentthanksto its ability to screenout damaging
blue and UV light from the sun, lutein/zeaxanthinhas four primary
functions:
I. to quenchthe triplet stateof photosensitizer oleculesand
m
the singletstateof molecularoxygen
2. to act asan antioxidantagainstoxygenand nitrogenreactive
species
10. 194 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS
Figure 9.8 Percent increase in skin hydration after treatment with topical
lutein, oral lutein, or oral + topical lutein.
Figure 9.9 Percent increase in superficial skin lipids after treatment with
topical lutein, oral lutein, or oral + topical lutein.
11. 9: ANTIOXIDANT BENEFITS OF ORAL CAROTENOIDS, MORGANTI 195
Figure 9.10 Change in skin elasticity (relative elastic retraction) after
treatment with topical lutein, oral lutein, or oral + topical lutein.
Figure 9.11 Change in skin lipid peroxidation after treatment with topical
lutein, oral lutein, or oral + topical lutein.
12. 196 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS
3. to absorbblue wavelengthlight, which is currentlyconsidered
muchmore detrimentalthan UV rays
4. to maintainthe moistureactivity at the level of the human
horny layer'slipid lamellae
It thereforeappearsthat thesexanthophyllsplayaspecific role as photo-
protectiveagentscapableof reducinginflammatoryROS-mediates, modu-
lating skin hydration,decreasing
skin aging, and, therefore,improving the
quality of our life.
9.5 Concluding Remarks
The large group of plant carotenoidspresentin the Mediterraneandiet
attracts major interest becauseof their potential antiaging and other
beneficialproperties,presumablybasedon their function as natural anti-
oxidants. Carotenoidsare compoundsof particular interest becauseof
their extensiveuse in dietary supplements. heir regular, long-termcon-
T
sumptionmay improveantioxidantdefencein vivo and thus help to lower
risks associatedwith diseases caused oxidativedamage.
by
However, more information on the photoagingactivity of these natural
compoundsis neededin order to understand how they act on the various
target tissues. Systematic pharmacokineticand dose-response studies
are required to determinethe different bioavailability of the individual
carotenoidsand xanthophills, and to estimatethe amountsin diet that
are likely to induce biological effects. Finally, more long-term carote-
noid depletion chemical trials with well-characterized diet supplements
are necessaryin order to confirm their beneficial antiaging effects in
humans.
References
1. HaslerClvl. (1998) Functionalfood: their role in disease preventionand
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2. Boelsma HendriksHF,RozaL. (2001)Nutritionalskincare:healtheffects
E,
of micronutrientsandfatty acids.Am J Clin Nutr 73(5): 853-864.
3. HeinrichV, WielnschM, TronnierH. (1998)Photoprotection
from ingested
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4. BrittonG, Liacen-Jensen ,Pfander (eds.)(2004)CarotenoidsHandbook.
S H
Birkhauser erlag, Basel.
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5. Sistrom WR, Griffiths M, Dtanier RY. (1956) A note on the porphyrins
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6. Mathews-RothMM, SistromWR. (1959) Function of carotenoidpigmentsin
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7. Sommerburg KeunenJE, Bird AC, van Kuijk FJ. (1998) Fruits and vege-
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![186 PROTECTYOUR SKIN WITH NATURAL ANTIOXIDANTS
pumpkins, the red color of tomatoes, and the green color of many
vegetables.
There are two commonly acceptedclassesof carotenoids:(a) carotens,
composed only carbonandhydrogen,and(b) oxycarotenoids,
of composed
of carbon,hydrogen,andoxygen.All of thesecompounds havean identical
backbone structureandtheir chemicalandbiochemicalactivitiesarerelated
to their uniquestructure,consistingof an extendedsystemof conjugated
doublebonds.Although the color of fruits and vegetables important,the
is
primary role of carotenoids natureis to protectfrom ultraviolet rays the
in
chlorophyll found in plant leaves. Carotenoidsalso help chlorophyll to
absorblight energy.
In fact, they act like excellentantioxidantsby quenchingsinglet oxygen,
reactiveoxygenspecies, ndthe free radicalsthat areby-productsof meta-
a
bolic processes vegetableand humancells or environmentalpollutants.
in
However, the hydrophilic propertiesof oxycarotenoids,like lutein and
zeaxantin,allow themto reactwith singletoxygengenerated the water
in
phasemore efficiently than nonpolar.Both carotenoidsandoxycarotenoids
seemcapableof preventingUV-inducedDNA damage, rotectingboththe
p
humaneyesand skin againstphotoaging.
In this chapterwe try to review the distribution and potential protective
activity of carotenoidsand oxycarotenoidsin the human body and to
explorenew potentialstrategies explainthe causallink betweenoxidative
to
stressand skin aging.
9.1 The Protective Role of Carotenoids
Nutrition playsan importantrole in the treatment f many diseases, an
o and
appropriate selectionof nutrientscontributesto the preventionof disorders
such ashyperlipidermia,hypertension, r vitamin deficiency[1,2]. Within
o
this context,carotenoidsare amongthe compoundsthat have attracteda
greatdeal of attention[3].
They are a classof linearall-trans (E) form C40 polyenesfound in plants,
algae, and somebacteriaand fungi. The numberof naturally occurring
carotenoidsreportedcontinuesto rise and has now reachedabout 750
(Fig. 9.1). Although animals and humans cannot biosynthesizethem](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)