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Topical Vitamin C
J Am Acad Dermatol. 2003 Jan;48(1):1-19.
Cutaneous photodamage, oxidative stress, and topical antioxidant protection.
Pinnell SR.
Duke University Medical Center, Department of Medicine, Division of Dermatology, Durham, North Carolina 27707, USA.
New methods to protect skin from photodamage from sun exposure are necessary if we are to conquer skin cancer and photoaging. Sunscreens are useful, but their protection is not ideal because of inadequate use, incomplete spectral protection, and toxicity. Skin naturally uses antioxidants (AOs) to protect itself from photodamage. This scientific review summarizes what is known about how photodamage occurs; why sunscreens--the current gold standard of photoprotection--are inadequate; and how topical AOs help protect against skin cancer and photoaging changes. This review is intended to be a reference source, including pertinent comprehensive reviews whenever available. Although not all AOs are included, an attempt has been made to select those AOs for which sufficient information is available to document their potential topical uses and benefits. Reviewed are the following physiologic and plant AOs: vitamin C, vitamin E, selenium, zinc, silymarin, soy isoflavones, and tea polyphenols. Their topical use may favorably supplement sunscreen protection and provide additional anticarcinogenic protection.
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Br J Dermatol. 1992 Sep;127(3):247-53.
Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage.
Darr D, Combs S, Dunston S, Manning T, Pinnell S.
Duke University Medical Center, Division of Dermatology, Durham, NC 27710.
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 photoprotectant.
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Dermatol Surg. 2001 Feb;27(2):137-42.
Topical L-ascorbic acid: percutaneous absorption studies.
Pinnell SR, Yang H, Omar M, Monteiro-Riviere N, DeBuys HV, Walker LC, Wang Y, Levine M.
Duke University Medical Center, Department of Medicine, Durham, North Carolina 27707, USA.
BACKGROUND: Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect skin from these insults.
OBJECTIVE: This study defines formulation characteristics for delivering L-ascorbic acid into the skin to supplement the skin's natural antioxidant reservoir.
METHODS: L-ascorbic acid or its derivatives were applied to pig skin. Skin levels of L-ascorbic acid were measured to determine percutaneous delivery.
RESULTS: L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days. Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid.
CONCLUSIONS: Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics.
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J Am Acad Dermatol. 2003 Jun;48(6):866-74.
UV photoprotection by combination topical antioxidants vitamin C and vitamin E.
Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, Monteiro-Riviere NA, Pinnell SR.
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
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% alpha-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig skin daily for 4 days. We irradiated (1-5x 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% alpha-tocopherol provided significant protection against erythema and sunburn cell formation; either L-ascorbic acid or 1% alpha-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.
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Exp Dermatol. 2003 Jun;12(3):237-44.
Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo.
Humbert PG, Haftek M, Creidi P, Lapière C, Nusgens B, Richard A, Schmitt D, Rougier A, Zahouani H.
Department of Dermatology, Hospital Saint Jacques, University of Franche-Comté, Besançon, France.
Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.
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J Invest Dermatol. 2001 Jun;116(6):853-9.
Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis.
Nusgens BV, Humbert P, Rougier A, Colige AC, Haftek M, Lambert CA, Richard A, Creidi P, Lapière CM.
Laboratory of Connective Tissues Biology, Tour de Pathologie, University of Liège, Sart Tilman, Belgium.
Ascorbic acid (vitamin C) is a cofactor required for the function of several hydroxylases and monooxygenases. It is not synthesized in humans and some other animal species and has to be provided by diet or pharmacologic means. Its absence is responsible for scurvy, a condition related in its initial phases to a defective synthesis of collagen by the reduced function of prolylhydroxylase and production of collagen polypeptides lacking hydroxyproline, therefore, they are unable to assemble into stable triple-helical collagen molecules. In fibroblast cultures, vitamin C also stimulates collagen production by increasing the steady-state level of mRNA of collagen types I and III through enhanced transcription and prolonged half-life of the transcripts. The aim of the experimental work has been to evaluate the effect on dermal cells of a preparation of vitamin C topically applied on one side vs placebo on the other side of the dorsal face of the upper forearm of postmenopausal women. Biopsies were collected on both sides and the level of mRNA measured by non competitive reverse transcription-polymerase chain reaction made quantitative by the simultaneous transcription and amplification of synthetic RNA used as internal standards. The mRNA of collagen type I and type III were increased to a similar extent by vitamin C and that of three post-translational enzymes, the carboxy- and amino-procollagen proteinases and lysyloxidase similarly increased. The mRNA of decorin was also stimulated, but elastin, and fibrillin 1 and 2 were not modified by the vitamin. The expression of matrix metalloproteinases 1, 2, and 9 was not significantly changed, but an increased level of tissue inhibitor of matrix metalloproteinase 1 mRNA was observed without modification of tissue inhibitor of matrix metalloproteinase 2 mRNA. The stimulating activity of topical vitamin C was most conspicuous in the women with the lowest dietary intake of the vitamin and unrelated to the level of actinic damage. The results indicate that the functional activity of the dermal cells is not maximal in postmenopausal women and can be increased.
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