Kinetics of carotenoid concentration in human skin after topical and systemic administration of antioxidants

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1 Department of Dermatology and Allergology Charité - Universitätsmedizin Berlin Kinetics of carotenoid concentration in human skin after topical and systemic administration of antioxidants M. E. Darvin 1, L. Zastrow 2, O. Doucet 2, J. Lademann 1 1 Charité Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology, Berlin, Germany 2 Coty Lancaster S.A.M., Monaco

2 Skin aging is determined by 3 parameters Genetic aspects Environmental influences (mainly UV radiation of the sun) Lifestyle

3 Penetration of sun light into the human skin UV Visible IR EP DE 1% 16% 20% 57% 77% 65% 65% 28% CT 1% 5% 21% 17% 8%

4 Action spectrum of the formation of free radicals 0,008 0,007 RGact sp = X rad / mg per mj / cm 2 0,006 0,005 0,004 0,003 0,002 0, Wavelength (nm) Consequence: Skin aging, immunosuppression, skin cancer L. Zastrow, et al. Skin Pharmacol. Physiol. 22, (2009)

5 Antioxidants defense system of the human organism Beta-Carotene Lycopene Lutein Coenzyme Q10 Vitamin A Vitamin C Vitamin E Vitamin D Darvin et al. Skin Pharmacol. Physiol. 19: , 2006

6 Determination of the Carotenoids in the past (High Performance Liquid Chromatography) Determination of Lycopene und ß-Carotene with HPLC Invasive: Blood and tissue samples Problem: Light and oxygen sensitive, time consuming, expensive Talwar et al. Clin Chim Acta 270: , 1998

7 Determination of the Carotenoids now (Resonance Raman Spectroscopy) - non-invasive method - fast method - selective detection method Darvin et al. J. Phys. D: Appl. Phys. 38: , 2005

8 Raman spectroscopic measurements

9 Comparison of the average concentration of carotenoids in different volunteers 0,0011 Concentration of the Carotenoids [a. u.] 0,0010 0,0009 0,0008 0,0007 0,0006 0,0005 0,0004 0,0003 0,0002 0,0001 Smoker Smoker 0,0000 voluntees

10 0,08 The carotenoid concentration in the skin during the course of one year 0,07 0,06 seasonal increase Carotenoids, a.u. 0,05 0,04 0,03 0,02 "A" "B" "A" 0,01 Volunteer 6 0, Day number Darvin et al. J. Biomed. Optics, 13(4): 1-9, 2008

11 0,08 The carotenoid concentration in the skin during the course of one year ,07 Carotenoids, a.u. 0,06 0,05 0,04 0,03 0,02 0, ; 2; 4; 7: Stress conditions (illness (inflammation), fatigue, working stress) 3; 5; 6: Normal lifestyle (absence of stress, increased amount of fruit and vegetables in the daily food spring summer autumn winter 4 7 0, Darvin et al. J. Biomed. Optics, 13(4): 1-9, 2008 Day number

12 Antioxidants and skin aging

13 Younger skin by fruits and vegetables? correlation between furrows and wrinkles and lycopene light exposed skin area (forehead) 20 volunteers (50 years)

14 Measurements of the skin surface structure (skin roughness) with Primos 4.0 system

0-0,05-0,1-0,15-0,2 0 2 4 6 8 10 12 14 Length [mm] 2 mm

15 Skin surface structure of 2 volunteers (both 44 years old) 2 mm Depth [mm 0,2 0,15 0,1 0,05 0-0,05-0,1-0,15-0, Length [mm] 2 mm Depth [mm 0,2 0,15 0,1 0,05 0-0,05-0,1-0,15-0, Length [mm]

16 Correlation between the lycopene concentration in the skin and the roughness of the skin of volunteers 0,00025 y = x R 2 = 0.79 Concentration of lycopene [arb. units] 0, , , , , Roughness [mm] Darvin et al. European Journal of Pharmaceutics and Biopharmaceutics, 69: , 2008

17 How can we increase the concentration of antioxidants in the skin? 1. Healthy diet rich in fruit and vegetables 2. Reduction of all stress factors (smoking, alcohol, illness, stress at work and at home, ) 3. Topical or systemic application of antioxidants (crème, food supplements)

18 Systemic application of antioxidants Be careful!!! Antioxidants can produce free radicals itself if their concentration exceeds a critical value Antioxidants are safe if they are applied in a physiological mixture and concentration

19 Comparison between topical and systemic application of antioxidants Study protocol Verum crème and verum pills with antioxidants in physiological mixture and concentration Verum crème with and without carotenoids Placebo crème and placebo pills without antioxidants 6 study groups (every group consisted of 15 volunteers) Application: 2 times daily Period of investigation: 8 weeks Determination of the carotenoids (marker substances)

20 Study protocol Applied Study 1 Study 2 Study 3 Study 4 Study 5 Study 6 Study 7 Substances Placebo crème x x Placebo pills x Verum crème x x x Verum pills x x x x Verum crèmes without carotenoids

21 2,5 2,0 1,5 1,0 0,5 0,0 Cheek Visit1 Visit2 Visit3 Identical studies Carotinoid concentration [a. u.] Study 3 V Crème Study 2 P Pills Study 5 Study 4 Study 5 Study 7 V Crème no Car. Study 6 V Crème Study 1

22 2,5 2,0 1,5 1,0 0,5 0,0 Cheek Visit1 Visit2 Visit3 Identical studies Placebo Carotinoid concentration [a. u.] Study 3 V Crème Study 2 P Pills Study 5 Study 4 Study 5 Study 7 V Crème no Car. Study 6 V Crème Study 1

23 2,5 2,0 1,5 1,0 0,5 0,0 Cheek Visit1 Visit2 Visit3 Identical studies Verum Carotinoid concentration [a. u.] Study 3 V Crème Study 2 P Pills Study 5 Study 4 Study 5 Study 7 V Crème no Car. Study 6 V Crème Study 1

24 2,5 2,0 1,5 1,0 0,5 0,0 Cheek Visit1 Visit2 Visit3 Identical studies A B A+B Carotinoid concentration [a. u.] Study 3 V Crème Study 2 P Pills Study 5 Study 4 Study 5 Study 7 V Crème no Car. Study 6 V Crème Study 1

25 2,5 2,0 1,5 1,0 0,5 0,0 Cheek Visit1 Visit2 Visit3 Identical studies Carotinoid concentration [a. u.] Study 3 V Crème Study 2 P Pills Study 5 Study 4 Study 5 Study 7 V Crème no Car. Study 6 V Crème Study 1

26 2,5 2,0 1,5 1,0 0,5 0,0 Cheek Visit1 Visit2 Visit3 Identical studies Carotinoid concentration [a. u.] Study 3 V Crème Study 2 P Pills Study 5 Study 4 Study 5 Study 7 V Crème no Car. Study 6 V Crème Study 1

27 Kinetics of the antioxidants after the end of the application Concentration of Beta-Carotine [%] Crème Pills Time [weeks Darvin et al. Journal of Dermatological Science, doi: /j.jdermsci

28 Summary 1 Antioxidants are the best antiaging strategy Crème versus pills Pills: You can never eat yourself young Pills can easily applied AO from pills accumulate slowly in the skin Pills give a long-term protection Physiological mixtures and concentrations!!! Crème: AO accumulate quickly in the skin crème can reduce furrows and wrinkles crème has a short-term protection The combined application of crème and pills is better than the single application

29 Summary 2 - For combined crème pill application well balanced products are necessary - It has to be secured that the crème does not prohibit the action of the pills - It has to be checked that the antioxidants are applied in the right mixtures and concentrations, so that they act antioxidative and NOT pro-oxidative - Raman spectroscopic and ESR measurements are well suitable for optimization and quality control A healthy diet rich in fruit and vegetables is the best and safest anti aging strategy

30 Acknowledgements Dr. A. Patzelt H. Richter PD. Dr. M.C. Meinke Prof. Dr. W. Sterry The project is supported by the European Commission (EFRE) and the Senate of Berlin

One-year study on the variation of carotenoid antioxidant substances in living human skin: influence of dietary supplementation and stress factors

Journal of Biomedical Optics 134, 044028 July/August 2008 One-year study on the variation of carotenoid antioxidant substances in living human skin: influence of dietary supplementation and stress factors