1. DIFFERENTIAL EFFECTS OF LOW-DOSE AND HIGH-DOSE BETA-CAROTENE SUPPLEMENTION AND THE SIGNS OF PHOTOAGING AND TYPE I PROCOLLAGEN GENE EXPRESSION IN HUMAN SKIN IN VIVO CHO S, LEE DH, WON C ET AL. Danielle Selden and Siona Sammartino

2. Vit A Background  Retinoids (animal tissues)  Retinol, Retinal, Retinoic Acid, Retinyl Esters  Pro-Vitamin A  Carotenoids (plant derived) Beta-Carotene Beta-Cryptoxanthin Alpha-Carotene  Relevant Functions:  ***Antioxidant  Regulation of Gene Expression (RA)

3. Purpose  Rationale:  Researchers and cosmetic companies are looking for food constituents that can slow cutaneous aging.  Previous studies (antioxidant vs pro-oxidant roles)  Purpose: To establish how two different dosages of β - carotene affect  Photoaging by measuring Facial wrinkles Elasticity UV-Induced DNA Damage Collagen Production and Degradation Visual Changes

4. Approach/Methods/Study Design  Methods:  In-vivo  Subjects: 30, healthy females between the ages of 49-68 Mean age 56  Randomized to two groups 30 mg/day of beta-carotene 90 mg/day of beta-carotene Baseline status used for control  Duration=90 Days  Exclusion Criteria:  2 weeks prior: no use of topical corticosteroids or retinoids  1 month prior: systemic steroid, vitamin intake, phototherapy  Smokers

5. Approach/Methods/Study Design  Measurements  At Baseline & Completion Facial Wrinkles & Elasticity Measured Objectively Photographs of face and visiometer technology Facial Erythema and Pigmentation Buttock Skin Type 1 procollagen, matrix metalloproteinase-1, fibrillin-1 mRNA levels and UV-induced thymine dimer and 8-hydroxy-2’- deoxyguanosine formation Other Tools

6. Result Highlights  29 subjects completed study  Facial wrinkles and elasticity were improved in low- dose beta-carotene group  For Wrinkles Measured by Skin Replica and Visiometer  For Elasticity Cutometer  Clinically visible in some  Oxidative damage in UV-Irradiated skin was reduced in low-dose beta-carotene group  Assessed via 8-OHdG immunostaining  Reduced staining in low-dose group

7. Facial Wrinkle Results Baseline90 Days

8. 8-OHdG Staining 30 mg/day 90 mg/day Baseline 90 Days

9. Author’s Conclusions and Implications  Wrinkles were improved in 3/5 categories for low dose groups only  Low dose beta-carotene showed anti-oxidant effects  High dose is inconclusive Need further study  Overall, Prevention and repair of photoaging can be achieved by only 30 mg/day of beta-carotene, as shown by reduced wrinkles, increased elasticity in photoaged facial skin, up-regulated pro-collagen expression and reduced UV induced cutaneous DNA damage  Doses at 90 mg/day may have deleterious effects

10. Limitations  Lack of tissue serum and tissue beta-carotene levels pre and post-supplementation  Not a Double Blinded Study  No Placebo  Diet?  Fat intake?  Small sample size (30 participants)  Population?

11. Conclusions  Too many limitations  Author’s did acknowledge this  Further research needed for pro-oxidant effects of high dose beta-carotene  Author’s acknowledged this  Sets the stage for further research  Anti-oxidant effects of lose dose beta-carotene seems to be effective  Whole foods diet vs. supplementation

12. Questions?  Q: What primary function of vitamin A can explain the outcomes of this study?  Q: After hearing the results of this study, would you promote the usage of beta-carotene supplementation in low-doses in your practice? Why or why not?

13. References  Cho S, Lee DH, Won C et al. Differential effects of low-dose and high-dose beta-carotene supplementation on the signs of photoaging and type I procollagen gene expression in human skin in vivo. Dermatology. 2010;221:160-171.