Kwak JY, et al. Ascorbyl coumarates as multifunctional cosmeceutical agents that inhibit melanogenesis and enhance collagen synthesis. Arch Dermatol Res. 2015;307(7):635-43.

ABSTRACT

L-Ascorbic acid (AA) and p-coumaric acid (p-CA) are naturally occurring antioxidants that are known to enhance collagen synthesis and inhibit melanin synthesis, respectively. The purpose of this study was to examine hybrid compounds between AA and p-CA as multifunctional cosmeceutical agents. Ascorbyl 3-p-coumarate (A-3-p-C), ascorbyl 2-p-coumarate (A-2-p-C), and their parent compounds were tested for their effects on cellular melanin synthesis and collagen synthesis. At 100 μM, A-3-p-C and A-2-p-C decreased melanin content of human dermal melanocytes stimulated by L-tyrosine, by 65 and 59%, respectively, compared to 11% inhibition of AA and 70% inhibition of p-CA. A-3-p-C and A-2-p-C were less effective than p-CA but more effective than AA at inhibiting tyrosinase activity. A-3-p-C and A-2-p-C were more effective than p-CA at inhibiting the autoxidation of L-3,4-dihydroxyphenylalanine. At 100-300 μM, A-3-p-C and A-2-p-C augmented collagen release from human dermal fibroblasts by 120-144% and 125-191%, respectively, compared to 126-133% increase of AA and 120-146% increase of p-CA. They increased procollagen type I C-peptide release (A-3-p-C, and A-2-p-C) like AA, and decreased matrix metalloproteinase 1 level (A-2-p-C) like p-CA, implicating that they might regulate collagen metabolism by multiple mechanisms. This study suggests that A-3-p-C and A-2-p-C could be used as multifunctional cosmeceutical agents for the attenuation of certain aspects of skin aging. https://www.ncbi.nlm.nih.gov/pubmed/26078014

Malavolti M, et al. Association between dietary Vitamin C and risk of cutaneous melanoma in a population of Northern Italy. Int J Vitam Nutr Res. 2013;83(5):291-8.

Abstract

Cutaneous melanoma incidence has been increasing during the last few years, and diet has been suggested as one of the lifestyle factors responsible for this increase. Since antioxidant nutrients such as ascorbic acid might prevent skin carcinogenesis, we investigated the risk of cutaneous melanoma related to vitamin C intake in a population-based case-control study in Northern Italy based on 380 melanoma patients and 719 matched controls, to whom we administered a semiquantitative food-frequency questionnaire. After adjusting for potential confounders, odds ratio of melanoma were 0.86 (95 % confidence interval 0.65 – 1.15) and 0.59 (95 % confidence interval 0.37 – 0.94) in the intermediate and highest categories of vitamin C dietary intake respectively, compared with the bottom one. The association between vitamin C and decreased risk persisted after adjustment for some potential confounders. In age- and gender-stratified analyses, this association was seen in young females (< 60 years old), and was found to be enhanced in subjects with phototypes II and III. These results suggest a possible protective activity of vitamin C intake against cutaneous melanoma in specific subgroups of this population of Northern Italy. http://www.ncbi.nlm.nih.gov/ pubmed/25305224

Darr D, et al. Topical Vitamin C protects porcine skin from ultraviolet radiation-induced damage. British Journal of Dermatology. 1992;127(3):247-253.

ABSTRACT

Summary Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (l‐ascorbic acid) functions as a biological co‐factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ’s innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA‐mediated phototoxic reactions (PUVA) and therefore shows promise as a broad‐spectrum photo protectant. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.1992.tb00122.x/full

Eberlein-Konig, B, et al. Protective effect against sunburn of combined systemic ascorbic acid (Vitamin C) and d-alpha-tocopherol (Vitamin E). Journal of the American Academy of Dermatology. 1998;38(1):45-48.

ABSTRACT

Background: UV radiation causes acute adverse effects like sunburn, photosensitivity reactions, or immunologic suppression, as well as long-term sequelae like photoaging or malignant skin tumors. UV radiation induces tissues to produce reactive oxygen species, eicosanoids and cytokines. Inhibition of these mediators might reduce skin damage. Antioxidants such as ascorbic acid and d-α-tocopherol have been found to be photoprotective in some in vitro studies and animal experiments.

Objective: Our purpose was to assess the protective effect of systemic vitamins C and E against sunburn in human beings.

Methods: In a double-blind placebo-controlled study, each of 10 subjects took daily either 2 gm of ascorbic acid (vitamin C) combined with 1000 IU of d-α-tocopherol (vitamin E) or placebo. The sunburn reaction before and after 8 days of treatment was assessed by determination of the threshold UV dose for eliciting sunburn (minimal erythema dose [MED]) and by measuring the cutaneous blood flow of skin irradiated with incremental UV doses against that of nonirradiated skin.

Results: The median MED of those taking vitamins increased from 80 to 96.5 mJ/cm2 (p < 0.01), whereas it declined from 80 to 68.5 mJ/cm2 in the placebo group. Cutaneous blood flow changed significantly (p < 0.05) for most irradiation doses with decreases in those given vitamins and increases in the placebo group.

Conclusion: Combined vitamins C and E reduce the sunburn reaction, which might indicate a consequent reduced risk for later sequelae of UV-induced skin damage. The increase of sunburn reactivity in the placebo group could be related to “priming” by the previous UV exposure. (J Am Acad Dermatol 1998;38:45-8.) www.sciencedirect.com/science/article/pii/S0190962298705377

Lin JY, et al. UV photoprotection by combination topical antioxidants Vitamin C and Vitamin E. Journal of the American Academy of Dermatology. 2003;48(6):866-874.

ABSTRACT

Background: Virtually all plants and animals protect themselves from the sun using vitamins C and E.

Objective: The purpose of this study was to see if a combination of topical vitamins C and E is better for UV protection to skin than an equivalent concentration of topical vitamin C or E alone.

Methods: We developed a stable aqueous solution of 15% L-ascorbic acid (vitamin C) and 1% α-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig skin daily for 4 days. We irradiated (1-5× minimal erythema dose) control- and antioxidant-treated skin using a solar simulator with a 295-nm band-pass filter. On day 5, we measured antioxidant protection factor, erythema, sunburn cells, and thymine dimers.

Results: The combination of 15% L-ascorbic acid and 1% α-tocopherol provided significant protection against erythema and sunburn cell formation; either L-ascorbic acid or 1% α-tocopherol alone also was protective but the combination was superior. Application during 4 days provided progressive protection that yielded an antioxidant protection factor of 4-fold. In addition, the combination of vitamins C and E provided protection against thymine dimer formation.

Conclusion: Appreciable photoprotection can be obtained from the combination of topical vitamins C and E. We suggest that these natural products may protect against skin cancer and photoaging. (J Am Acad Dermatol 2003;48:866-74.) www.sciencedirect.com/science/article/pii/S0190962203007813

Boyce ST, et al. Vitamin C regulates keratinocyte viability, epidermal barrier, and basement membrane in vitro, and reduces wound contraction after grafting of cultured skin substitutes. Journal of Investigative Dermatology. 2002;118(4):565-572.

ABSTRACT

Cultured skin substitutes have become useful as adjunctive treatments for excised, full-thickness burns, but no skin substitutes have the anatomy and physiology of native skin. Hypothetically, deficiencies of structure and function may result, in part, from nutritional deficiencies in culture media. To address this hypothesis, vitamin C was titrated at 0.0, 0.01, 0.1, and 1.0 mM in a cultured skin substitute model on filter inserts. Cultured skin substitute inserts were evaluated at 2 and 5 wk for viability by incorporation of 5-bromo-2′-deoxyuridine (BrdU) and by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) conversion. Subsequently, cultured skin substitute grafts consisting of cultured human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan substrates were incubated for 5 wk in media containing 0.0 mM or 0.1 mM vitamin C, and then grafted to athymic mice. Cultured skin substitutes (n = 3 per group) were evaluated in vitro at 2 wk of incubation for collagen IV, collagen VII, and laminin 5, and through 5 wk for epidermal barrier by surface electrical capacitance. Cultured skin substitutes were grafted to full-thickness wounds in athymic mice (n = 8 per group), evaluated for surface electrical capacitance through 6 wk, and scored for percentage original wound area through 8 wk and for HLA-ABC-positive wounds at 8 wk after grafting. The data show that incubation of cultured skin substitutes in medium containing vitamin C results in greater viability (higher BrdU and MTT), more complete basement membrane development at 2 wk, and better epidermal barrier (lower surface electrical capacitance) at 5 wk in vitro. After grafting, cultured skin substitutes with vitamin C developed functional epidermal barrier earlier, had less wound contraction, and had more HLA-positive wounds at 8 wk than without vitamin C. These results suggest that incubation of cultured skin substitutes in medium containing vitamin C extends cellular viability, promotes formation of epidermal barrier in vitro, and promotes engraftment. Improved anatomy and physiology of cultured skin substitutes that result from nutritional factors in culture media may be expected to improve efficacy in treatment of full-thickness skin wounds. www.sciencedirect.com/science/article/pii/S0022202X15416100