Photoaging — Update and Treatment, Sheldon R. Pinnell: Melbourne Dermatology Skin Care

Clinical Procedures and Topics

absorption academy acid actual added against aging alpha american antioxidant antioxidants application applied ascorbic ascorbyl cancer caspase cell challenges chemical chemically combination complete compounds concentration concentrations containing converted days derivatives dermatol dermatology dimer effective enter epidemic erythema escalating esters ever exponential ferulic finally fluids fold following formation formulated formulation formulations fourfold free function grichnik immunosuppression include increasing invest irradiation journal maximal monteiro must naturally network noshade percutaneous photoaging photoprotection pinnell plant protect protecting protection provide provides readily riviere sheldon since size skin solution stability stable sunscreens synergistic thymine tocopherol topical topically treatment ultraviolet unstable update used vitamin vitamins work zielinski

Photoaging — Update and Treatment, Sheldon R. Pinnell

Sheldon R. Pinnell, M.D., J. Lamar Callaway Professor, Dermatology.

New methods of photoprotection are needed to curb the epidemic of skin cancer — an epidemic worsened by an aging population, ever-increasing outdoor activities and escalating immunosuppression related to medical treatments.

Sunscreens are not the complete answer.

Recent studies point out that in actual usage individuals apply only 20-25% the amount used to determine SPF values.

Since SPF is an exponential function, actual protection is no more than three to fourfold at this level of application for any sunscreen.

Moreover, the best sunscreens available only protect against 55% of free radicals generated in skin by ultraviolet irradiation.

The skin naturally protects itself from the sun with antioxidants.

These include vitamin C in fluids and vitamin E in stratum corneum and membranes.

My research laboratory is interested in developing antioxidant formulations that can be applied to skin to increase the natural reservoir and provide additional photoprotection.

Since antioxidants are naturally unstable compounds, they provide challenges for formulation.

To work, they must be chemically stable, they must get into skin, and they must be used at meaningful concentrations.

Finally, they must be effective at providing photoprotection.

L-ascorbic acid (vitamin C) can be used topically, but proper formulation is crucial.

It must be at a pH below 3.5 in order to enter skin. It is maximally effective for increasing skin levels at a concentration of 20%. Skin can be saturated in 3 days, and following saturation, half life of removal is about 4 days. It is effective for protecting the skin against UVB and UVA and can protect against UV-immunosuppression.

Alpha tocopherol (vitamin E) can enter skin when applied topically. Maximal percutaneous absorption occurs at 1% concentration. Alpha tocopherol is effective for protecting skin against photoinjury, photocarcinogenesis and UV-immunosuppression.

Because vitamin C and vitamin E are relatively unstable in topical formulations, derivatives (esters) have been synthesized to improve stability.

Vitamin C derivatives include ascorbyl palmitate and magnesium ascorbyl phosphate. Vitamin E derivatives include tocopherol acetate. These derivatives must then be converted in tissue, back to the vitamin to be effective.

These derivatives are successfully converted in the stomach when used in vitamin pills, but not readily converted when used topically for skin protection.

In the human body, antioxidants function as an interactive network, with chemical reconstitution of antioxidants after they are oxidized during protective functions. As a network they work synergistically. Vitamin C and vitamin E, when formulated together at maximal concentrations for percutaneous absorption, provide synergistic photoprotection for skin when applied topically.

We have recently discovered that ferulic acid provides added chemical stability to a solution of vitamin C and vitamin E.

When heated at 45¼C for one month, vitamin E is 100% stable and vitamin C is more than 90% stable.

Ferulic acid is a ubiquitous plant antioxidant and is also used in making plant cell walls.

A solution of 15% L-ascorbic acid, 1% alpha tocopherol and 0.5% ferulic acid provides eight- to ten-fold protection against solar-simulated irradiation of skin. Protection is demonstrated for erythema, sunburn cell formation, caspase-3 and caspase-7 activation and thymine dimer formation. Thymine dimers are critical DNA mutations intimately involved in skin cancer formation.

In summary, topical vitamins C and E stabilized with ferulic acid provide synergistic photoprotection for skin and prevent thymine dimer formation.

Derivatives of vitamins C and E are not readily converted to free vitamins when used topically.

Photoaging — Update and Treatment, Sheldon R. Pinnell Reference List

Pinnell SR: Cutaneous photodamage, oxidative stress, and topical antioxidant protection. Journal of the American Academy of Dermatology. 2003, 48: 1-19.
Lin, J-Y et al.: UV photoprotection by combination topical antioxidants vitamin C and vitamin E . Journal of the American Academy of Dermatology. 48 :866-74, 2003.
Lin J.Y., Lin, F-Y, Burch, J.A., Gupta, R., Grichnik, J.M., Monteiro-Riviere, N.A., Zielinski, J., and Pinnell, S.R. Ferulic Acid Stabilizes a Topical Solution Containing Vitamins C+E and Doubles its Photoprotection for Skin , J Invest Dermatol 122 :883, 2004.
Lin, F-Y, Monteiro-Riviere, N.A., Grichnik, J.M., Zielinski, J.E., and Pinnell, S.R. A Topical Antioxidant Solution Containing Vitamin C, Vitamin E, and Ferulic Acid Prevents Ultraviolet Radiation-Induced Caspase-3 Induction in Skin , J Invest Dermatol 122 :883, 2004.

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Photoaging — Update and Treatment, Sheldon R. Pinnell


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	Photoaging — Update and Treatment, Sheldon R. Pinnell antioxidants, photoprotection, photoaging, ultraviolet light, aging skin."> Sheldon R. Pinnell, M.D., J. Lamar Callaway Professor, Dermatology. New methods of photoprotection are needed to curb the epidemic of skin cancer — an epidemic worsened by an aging population, ever-increasing outdoor activities and escalating immunosuppression related to medical treatments. Sunscreens are not the complete answer. Recent studies point out that in actual usage individuals apply only 20-25% the amount used to determine SPF values. Since SPF is an exponential function, actual protection is no more than three to fourfold at this level of application for any sunscreen. Moreover, the best sunscreens available only protect against 55% of free radicals generated in skin by ultraviolet irradiation. The skin naturally protects itself from the sun with antioxidants. These include vitamin C in fluids and vitamin E in stratum corneum and membranes. My research laboratory is interested in developing antioxidant formulations that can be applied to skin to increase the natural reservoir and provide additional photoprotection. Since antioxidants are naturally unstable compounds, they provide challenges for formulation. To work, they must be chemically stable, they must get into skin, and they must be used at meaningful concentrations. Finally, they must be effective at providing photoprotection. L-ascorbic acid (vitamin C) can be used topically, but proper formulation is crucial. It must be at a pH below 3.5 in order to enter skin. It is maximally effective for increasing skin levels at a concentration of 20%. Skin can be saturated in 3 days, and following saturation, half life of removal is about 4 days. It is effective for protecting the skin against UVB and UVA and can protect against UV-immunosuppression. Alpha tocopherol (vitamin E) can enter skin when applied topically. Maximal percutaneous absorption occurs at 1% concentration. Alpha tocopherol is effective for protecting skin against photoinjury, photocarcinogenesis and UV-immunosuppression. Because vitamin C and vitamin E are relatively unstable in topical formulations, derivatives (esters) have been synthesized to improve stability. Vitamin C derivatives include ascorbyl palmitate and magnesium ascorbyl phosphate. Vitamin E derivatives include tocopherol acetate. These derivatives must then be converted in tissue, back to the vitamin to be effective. These derivatives are successfully converted in the stomach when used in vitamin pills, but not readily converted when used topically for skin protection. In the human body, antioxidants function as an interactive network, with chemical reconstitution of antioxidants after they are oxidized during protective functions. As a network they work synergistically. Vitamin C and vitamin E, when formulated together at maximal concentrations for percutaneous absorption, provide synergistic photoprotection for skin when applied topically. We have recently discovered that ferulic acid provides added chemical stability to a solution of vitamin C and vitamin E. When heated at 45¼C for one month, vitamin E is 100% stable and vitamin C is more than 90% stable. Ferulic acid is a ubiquitous plant antioxidant and is also used in making plant cell walls. A solution of 15% L-ascorbic acid, 1% alpha tocopherol and 0.5% ferulic acid provides eight- to ten-fold protection against solar-simulated irradiation of skin. Protection is demonstrated for erythema, sunburn cell formation, caspase-3 and caspase-7 activation and thymine dimer formation. Thymine dimers are critical DNA mutations intimately involved in skin cancer formation. In summary, topical vitamins C and E stabilized with ferulic acid provide synergistic photoprotection for skin and prevent thymine dimer formation. Derivatives of vitamins C and E are not readily converted to free vitamins when used topically. Photoaging — Update and Treatment, Sheldon R. Pinnell Reference List Pinnell SR: Cutaneous photodamage, oxidative stress, and topical antioxidant protection. Journal of the American Academy of Dermatology. 2003, 48: 1-19. Lin, J-Y et al.: UV photoprotection by combination topical antioxidants vitamin C and vitamin E . Journal of the American Academy of Dermatology. 48 :866-74, 2003. Lin J.Y., Lin, F-Y, Burch, J.A., Gupta, R., Grichnik, J.M., Monteiro-Riviere, N.A., Zielinski, J., and Pinnell, S.R. Ferulic Acid Stabilizes a Topical Solution Containing Vitamins C+E and Doubles its Photoprotection for Skin , J Invest Dermatol 122 :883, 2004. Lin, F-Y, Monteiro-Riviere, N.A., Grichnik, J.M., Zielinski, J.E., and Pinnell, S.R. A Topical Antioxidant Solution Containing Vitamin C, Vitamin E, and Ferulic Acid Prevents Ultraviolet Radiation-Induced Caspase-3 Induction in Skin , J Invest Dermatol 122 :883, 2004. Related Skin Care Information, Products and Expert Discussions Skinceuticals C E Ferulic Published Scientific Data Topical L-Ascorbic Acid: Percutaneous Absorption Studies (Dermatol Surg. 2001;27:137-142) Skinceuticals C E Ferulic Study - Introduction Cosmetic Dermatology Newsletter Summer 2007 Idebenone — Prevage and Priori vs Skinceuticals C E Ferulic Skinceuticals : Skinceuticals Aficionado Topics : Instructions for Absolute Rehydration of Dry and Stressed Skin : A Year of Photoprotection — Results from Topical Vitamin C (as Ascorbic Acid) and Dermatological Sunscreen Use : Lin et aI., 2005 — Journal of Investigative Dermatology 125:826-32 (2005). : Photoaging — Update and Treatment, Sheldon R. Pinnell : Placzek et aI., 2005 — Journal of Investigative Dermatology 124:304-7 (2005) : Skinceuticals Antioxidant Storage Notes — Protective/Preservative Refrigeration : Skinceuticals Foaming Cleanser/SPF 20/B5 Gel Special Set : Skinceuticals Light and Easy Extended Skin Resurfacing/Freshening… : Skinceuticals Normal to Dry Skin Reconditioning Massage : Skinceuticals: Poor Health / Poor Results : File Photoaging — Update and Treatment, Sheldon R. Pinnell for reference.	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