Danielle Selden and Siona Sammartino

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 VIVOCho S, Lee DH, Won C et al. Danielle Selden and Siona Sammartino

2. Vit A Background • Retinoids (animal tissues) • Retinol, Retinal, Retinoic Acid, RetinylEsters • 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 Baseline 90 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 procollagengene expression in human skin in vivo. Dermatology. 2010;221:160-171.