tomato carotenoids supplementation: photo-protection and ... · ski cskin cancer. ... treatment...

Tomato carotenoids supplementation:Tomato carotenoids supplementation:Photo-protection and skin anti-aging activityPhoto-protection and skin anti-aging activity

Joseph LevyJoseph LevyJoseph LevyJoseph Levy

Faculty of Health SciencesFaculty of Health SciencesFaculty of Health SciencesBenBen--Gurion UniversityGurion University, Beer-Sheva, Israel

Faculty of Health SciencesBenBen--Gurion UniversityGurion University, Beer-Sheva, Israel

Cosmeceuticals Summit 2009March 9- 11, 2009Cosmeceuticals Summit 2009March 9- 11, 2009c 9 , 9Orlando, FL

c 9 , 9Orlando, FL

Photooxidative Stress Photooxidative Stress Photooxidative Stress Photooxidative Stress UV

LIGHT

Reactive OxygenSpecies (ROS)

AntioxidantsAntioxidants

DDamage

DNA LIPIDS PROTEINS

Photooxidative Stress Photooxidative Stress --P bl f SP bl f S d kid ki

Photooxidative Stress Photooxidative Stress --P bl f SP bl f S d kid kiProblems of SunProblems of Sun--exposed skinexposed skinProblems of SunProblems of Sun--exposed skinexposed skin

SunburnSkin AgingSki CSkin Cancer

Tomato carotenoids Tomato carotenoids d Ski H l hd Ski H l h

Tomato carotenoids Tomato carotenoids d Ski H l hd Ski H l hand Skin Healthand Skin Healthand Skin Healthand Skin Health

E d Ph t t tiE d Ph t t tiEndogenous Photo protection Endogenous Photo protection Cosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureProtection against Sunburn Cell Protection against Sunburn Cell Formation Formation Lycopene and protection from erythemaLycopene and protection from erythemaLycopene and protection from erythemaLycopene and protection from erythema

Is it only lycopene? Is it only lycopene? y y py y pUVUV--A and UVA and UV--B B

Exogenous Exogenous PhotoprotectionPhotoprotectionPhotoprotection Photoprotection

UV exposure during a conservative vacation accounts only for about 1/3 f h h l UV1/3 of the average erythemal UV doses within a year

Endogenous Photoprotection

i i dii i diHuman intervention studiesHuman intervention studiesThis presentation will address the concept of Photoprotection by dietary means



Endogenous Photo protection Endogenous Photo protection Cosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureProtection against Sunburn Cell Protection against Sunburn Cell ggFormationFormationL d t ti f thL d t ti f thLycopene and protection from erythemaLycopene and protection from erythema

Is it only lycopene?Is it only lycopene?Is it only lycopene? Is it only lycopene? UVUV--A and UVA and UV--B B

P m tP m t M m tM m tParametersParameters MeasurementsMeasurementsDensity ultrasoundultrasoundThickness (B(B scan)scan)Thickness (B(B--scan)scan)

ScalingRoughness Surface EvaluationSurface EvaluationSmoothness of Living Skin (SELS)of Living Skin (SELS)WrinklingWrinkling

Hydration CorneometryCorneometry

Transepidermal TEWLTEWLwater loss

Antioxidants mixture Vs.Antioxidants mixture Vs. PPlacebolaceboAntioxidants mixture Vs. Antioxidants mixture Vs. PPlacebolacebo66..0 0 mg Lycopenemg Lycopene44..88 mg ßmg ß--CaroteneCarotene44..8 8 mg ßmg ß CaroteneCarotene10 10 mg mg αα--TocopherolTocopherol7575 µg Seleniumµg Selenium75 75 µg Seleniumµg Selenium

(n= 13)D ti 12 kDuration: 12 wk; measurements: wk=0, wk12

Serum levels

Treatment PlaceboTreatment Placebo

wk 0 wk 12 wk 0 wk 12

β-Carotene 0.68 1.33* 0.46 0.46L 0 52 0 88* 0 49 0 60Lycopene 0.52 0.88* 0.49 0.60α-Tocoperol 32.8 31.9 33.8 35.8

A typical ultrasound B-scan shows the density and thickness of the dermis

Epidermis Dermis Subcutaneous

Dermis + Epidermis =Thi k f th kiThickness of the skin

bl k f l d iblack areas are of low density bright yellow are of high density

Diff k 12 k 0Diff k 12 k 0Difference wk 12 vs. wk 0Difference wk 12 vs. wk 0

Treatment PlaceboDensity + 7% * +0.3%Thickness +14% * 1 4%Thickness +14% - 1.4%

Skin surface evaluation

White area sho degree of scalingWhite area show degree of scaling

hRed area and steepness of peaks show roughness of skin

Diff k 12 k 0Difference wk 12 vs wk 0

Treatment Placebo

Scaling - 60% * - 30%Roughness - 33% * - 16%

Mechanism ???Mechanism ???

In a ongoing new studyIn a ongoing new study

New Human Skin Study

A placebo controlled, double blind, cross-over studyover study

Special emphasis on molecular markers of UVA damage in human volunteersg

Performed by leading skin research university group in Europe

Study parameters2. Assessment of skin barrier function / anti-aging by

skin physiological parameters (measurement with bioengineering methods)

a. Transepidermal water loss of the skinp

b. Skin elasticity

c Skin hydrationc. Skin hydration

d. Skin colour

e. MED – Erythema

f. PPD - Tanningg

Study parameters

1. Molecular Parameters (skin biopsies):to be assessed by RT-PCRto be assessed by RT PCR

mRNA Expression of HO-1 (oxidative stress)

ICAM-1 (skin irritation)ICAM-1 (skin irritation)

MMP-1 (photoaging)

Col1A1 and Col1A2 (skin rejuvenation)

IL-1, IL-6 (skin inflammation)

Lyc-O-Mato 6%Lyc O Mato 6% Dietary Supplementation Study

P t tiProtectionagainst Sunburn Cell Formation

•Sunburn cells, are apoptotic (dead) cells, which are indicative of damage caused by UV

exposureexposure

Study Objective•Determination of the efficacy of oral supplementation of

Lyc-O-Mato in preventing photo-aging, as measured by the histological analysis of sunburn cellsy g y

•Test Products•Group 1 –Lyc-O-Mato 6% capsules per day, (10 mg

L )Lycopene)•Group 2 –Placebo control capsules (containing Soybean

oil))•Study Period•10 weeks of supplementation

Effect Of Dietary Supplementation Study-C t’dCont’d

Study Population•10 female and male subjects, 18 + years of age, with

skin Type Ⅰ and Ⅱ

•Protocol•Subjects were randomized into two balanced groups of

five. •Subjects returned the clinic at the end of week 10 for

radiation of 2 MED.radiation of 2 MED. •Subjects returned 24 hours later for 3mm punch biopsy

for sunburn cell counts.

Number of Sunburn Cells per Sq. mm

1200

1000

1200

600

800PlaceboLyc-O-Mato 6%

400

Lyc O Mato 6%

0

200

After 10 weeks ingestion

•In conclusion, Daily Dietary Supplementation can provide year round protection against UV radiation damage.

UV light and other forms of oxidativeUV light and other forms of oxidativeUV light and other forms of oxidative stress can modify the cellular genome UV light and other forms of oxidative stress can modify the cellular genome by causing DNA damage and cell deathby causing DNA damage and cell deathdeath.death.

What is the mechanism What is the mechanism of tomato extract of tomato extract

protection ?protection ?

DNA damage after consumption of LycDNA damage after consumption of Lyc--OO--Mato drink Mato drink Experimental design: double-blind, cross-over study,Experimental design: double-blind, cross-over study,

Carotenoid consumption per day:6 mg lycopene4 mg phytoene4 mg phytoene3 mg phytofluene1 mg β-carotene1 8 h l

Porrini, M., Riso, P., Brusamolino, A., Berti, C., Guarnieri, S. and Visioli, F. British J Nutrition, 93: 93-9, 2005

1.8 mg α-tocopherol,

Reduction in HReduction in H22OO22--induced DNA damage of human induced DNA damage of human lymphocytes by Lyclymphocytes by Lyc--OO--Mato drinkMato drink

70 No changeNo change 42% change42% change

50

60in

tail **

30

40

DN

A i

10

20%

before afterPlacebo

0before after

LycoMato

Porrini, M., Riso, P., Brusamolino, A., Berti, C., Guarnieri, S. and Visioli, F. British J Nutrition, 93: 93-9, 2005

Placebo LycoMato

Lycopene and other tomato Lycopene and other tomato carotenoids, in skin protection.carotenoids, in skin protection.

Wilhelm Stahl, Helmut Sies Institute for Physiological Chemistry IHeinrichHeinrich--HeineHeine--UniversitätUniversität, Düsseldorf, Germany

Wilhelm Stahl, Helmut Sies Institute for Physiological Chemistry IHeinrichHeinrich--HeineHeine--UniversitätUniversität, Düsseldorf, Germany

Irradiated Skin–Redness after 24h of UV-ExposureUV Exposure

1 2 3 4 5

a-Value

Photoprotective Effects of Lycopene: Study Design

9 Volunteers (skin type II) (∆-a-Value at 1.25 MED)

Study Design

MED)

40 g Tomato Paste/day = 16 mg Lycopene/day ith li ilwith olive oil

10 Week Supplementation

Carotenoid Serum Levels (HPLC) Carotenoid Skin Levels (Chromametry)

Erythema Formation (Sunburn Reaction) Chromametry: ∆-a-Value

Stahl et al. J. Nutr. 131: 1449-1451 (2001)

Results

• At week 10, erythema formation was 40% lowerlower in the

Results

group that consumed tomato paste compared with controls

Conclussion

ProtectionProtection against UV light-induced erythema, can be acheived by ingestion of a commonly consumed dietarydietaryy g y yysource of lycopene.



E d Ph t t tiE d Ph t t tiEndogenous Photo protection Endogenous Photo protection Cosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureProtection against Sunburn Cell Protection against Sunburn Cell FormationFormationLycopene and protection from erythemaLycopene and protection from erythemaLycopene and protection from erythemaLycopene and protection from erythema


Can lycopene aloneCan lycopene aloneCan lycopene alone replace the tomato?Can lycopene alone replace the tomato?replace the tomato?replace the tomato?

Phytonutrient content in LYCPhytonutrient content in LYC--OO--MATOMATO®® 77% % -- Standardized Tomato ExtractStandardized Tomato Extract

TocopherolsPhytosterols

0.7%

Standardized Tomato ExtractStandardized Tomato Extract

Other carotenoids

Tocopherols(Vit E) 2%

LycopeneLycopenePhytofluene

0.3%

7%7%

Ph t

Phytofluene0.7%

Beta carotene

Phytoene0.7%

Beta-carotene0.2%

Photoprotective Effects of Tomato Products vs Lycopeneroducts vs Lycopene

36 Volunteers (skin type II)

Synthetic Lycopene Lyc-O-Mato Capsules Lyc-O-Mato Drink

12 Week Supplementation

y

Serum Levels of Lycopene, Phytoene, Phytofluene: HPLC

Total carotenoid Skin Level (Reflection spectrophotometry)

Erythema Formation (∆-a-Value at 1.25 MED) Sunburn Reaction to solar light simulator

Carotenoid daily intake during the study

Carotenoids Lyc O Mato Lyc O mato LycopeneCarotenoids(mg/d)

Lyc-O-Matodrink

Lyc-O-matocapsules

Lycopenesynthetic

Lycopene 8.2 9.8 10.2

Phytoene 4.5 1.0 -

Phytofluene 3.2 0.9 -

Relative Sun-Protective EffectsLyc-O-Mato Synthetic Lyc-O-Mato

100

Drink LycopeneCapsules0

75

n on d

ay 0

50

otec

tion

-val

ue o

25

Pro

of ∆

-a-

0Week: 0 4 12 0 4 12 0 4 12

%

The longerlonger you consume the betterbetter protection you getThe combinationcombination of lycopene with other tomato carotenoid is more protectivemore protective than synthetic lycopene

Week: 0 4 12 0 4 12 0 4 12

The longer you consume the betterprotection you get

Why Phytofluene and Phytoene areWhy Phytofluene and Phytoene areWhy Phytofluene and Phytoene are Why Phytofluene and Phytoene are so beneficial? so beneficial?



E d Ph t t tiE d Ph t t tiEndogenous Photo protection Endogenous Photo protection Cosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureCosmetics: Skin structure and textureProtection against Sunburn Cell Protection against Sunburn Cell FormationFormationLycopene and protection from erythemaLycopene and protection from erythemaLycopene and protection from erythemaLycopene and protection from erythema


Phytofluene and Phytoene absorb light in UVPhytofluene and Phytoene absorb light in UV--A A and UVand UV--BB

LycopenePhytoene Phytofluene

and UVand UV BB

UV-B UV-A visible

banc

e A

bsor

b

250 300 350 400 450 500Wavelength (nm)

• Major carotenoids in tomatoes and in tomato

Phytofluene and Phytoene Features & Benefits:

• Major carotenoids in tomatoes and in tomato extracts (not present in synthetic preparations)

• Absorb UV-A and UV-B respectively

• Both are colorless carotenoids• Both are colorless carotenoids

PhytoenePhytoene

Phytofluene

Most sun care products Most sun care products provide optimal protection provide optimal protection from UVUV--BB, but incomplete f m , mp

protection from UVUV--AAp

h d h fl ll Phytoene and Phytofluene as well as other tomato phyto-nutrients:other tomato phyto-nutrients:

May provide the additional protectionMay provide the additional protectionMay provide the additional protection May provide the additional protection against the damaging oxidative free against the damaging oxidative free

radicalsradicals


Erythema is inflammationErythema is inflammation

TIME Magazine; FebruaryTIME Magazine; February 2323,, 20042004 Vol.Vol. 163163 No.No. 88TIME Magazine; February TIME Magazine; February 2323, , 2004 2004 Vol. Vol. 163 163 No. No. 88

Wh b hWh b hWhat may be the What may be the mechanisms for the mechanisms for the

anti-inflamtoryanti-inflamtoryanti inflamtory response?

anti inflamtory response?response?response?

Reduction in TNFReduction in TNF--α production in LPSα production in LPS--challenged whole challenged whole blood by Lycblood by Lyc--OO--Mato drink supplementationMato drink supplementation

g/m

l 34% reduction34% reduction40

**ion

ng 30ro

duct

i

20

NFα

pr

10

before afterPlacebo

TN

before afterLycoMato

0

Riso, P, Visioli, F., Grande, S., Guarnieri, S., Gardana, C., Simonetti, P., and Porrini, M J Agric Food Chem, 54: 2563-2566, 2006.

Placebo LycoMato

A growing body of evidence demonstratesA growing body of evidence demonstrates that these compounds can serve important f ti i d d t f di t ti id tfunctions independent of direct antioxidant chemistry, by modulating enzyme activity and gene expression.

What is the molecular mechanism ofWhat is the molecular mechanism ofWhat is the molecular mechanism of What is the molecular mechanism of tomato carotenoids in skin protection tomato carotenoids in skin protection

from UV and oxidative damage?from UV and oxidative damage?

(Nrf 2)

Cancer Res 2006; 66(17): 8421-9)

• They observed that low dose UVB exposure led to stimulation of Nrf 2exposure led to stimulation of Nrf 2 transcription factor and activation of chemo protective defense programchemo protective defense program.

• However, intriguingly, they found that high d UVB l d d l idose UVB exposure led to down-regulation of this protective mechanism.

•• Suggesting that this contribute toSuggesting that this contribute toSuggesting that this contribute to Suggesting that this contribute to environmental carcinogenic environmental carcinogenic effects of UVB.effects of UVB.

Carotenoids may provide the Carotenoids may provide the additional protection neededadditional protection neededadditional protection neededadditional protection needed

Endogenous (dietary) Photoprotection Endogenous (dietary) Photoprotection by tomato oleoresin by tomato oleoresin (Lyc(Lyc--OO--Mato)Mato) is is by to ato o eo esby to ato o eo es ( yc( yc OO ato)ato) ssefficient as confirmed by efficient as confirmed by

Human intervention studies Human intervention studies

Thank youy

SummaryAntioxidants, positively affect skin texture

Dietary carotenoids provide moderate protectionDietary carotenoids provide moderate protection against UV-induced erythema (sunburn)

Carotenoids can be applied as supplements with theCarotenoids can be applied as supplements with the diet, or in enriched functional food products

For protection doses > 10 15 mg carotenoids/day areFor protection, doses > 10-15 mg carotenoids/day are needed; intervention > 6 wk

A ti id t ti it ( d/ UV b ti ) i thAntioxidant activity (and/or UV-absorption are) is the main mechanisms of protection

tomato carotenoids supplementation: photo-protection and ... · ski cskin cancer. ... treatment...

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