Key points: • • •
Vitamin C is the most powerful anti-oxidant in the skin and L-ascorbic acid is its most active biological form Stability and permeability are two important factors in the delivery of vitamin C into the skin Solar radiation in the form of ultraviolet and some infrared rays cause “oxidative stress” and this is neutralised by vitamin C “Oxidative stress” can cause a cascade of events in the skin leading to what is clinically evident as “photoageing” Vitamin C exerts beneficial effects on the formation of collagen in addition to prevention of collagen breakdown caused by solar radiation Vitamin C has also shown to exert anti-inflammatory effects through inhibition of the transcription factor NFĸB Interference with the enzyme tyrosine kinase means that vitamin C exerts anti-pigmentation effects, albeit a bit weaker than some of the other available products in the market
slow down the cell cycle allowing for repair of the damaged DNA and the induction of a process of programmed cell death called apoptosis.11 Therefore raised levels of p53 indicate solar radiationinduced cellular damage and topical application of vitamin C has shown to decrease the levels of p53 upon radiation, a testimony of the photoprotective effects of vitamin C.4 AP-1 is a protein that is activated as a result of reactive oxygen species formation and leads to up-regulation of a number of proteases called matrix metalloproteases (MMPs).1 These proteases act to degrade and damage collagen in the dermis leading to some of the photoageing effects observed. Vitamin C has shown to inhibit the activation of AP-1 which would lead to a reduction in MMPs and a reduction in collagen damage. Langerhans cells CD1a are antigenpresenting cells present in the epidermis, which act by initiating a protective immune response. Their numbers are decreased upon reactive oxygen species formation and hence solar radiation can lead to a decrease in a particular cellular immune response. Products containing vitamin C have shown to prevent the reduction of these cells upon solar radiation, further demonstrating the anti-oxidant effect of vitamin C.12 Other effects of vitamin C on skin: In addition to the anti-oxidant effect achieved through neutralisation of the oxidative stress, vitamin C has also demonstrated a number of additional beneficial effects on the skin. Vitamin C is essential for collagen biosynthesis and serves as a co-factor for prolyl and lysyl hydroxylase, important enzymes responsible for cross-linking and stabilisation of collagen fibres.13 Vitamin C has also shown to activate transcription factors such as pro-collagen mRNA that lead to collagen synthesis. Impairment of collagen has been observed clinically in the presence of vitamin C, and Scurvy is a great example of this.14 In summary, vitamin C exerts its beneficial effects on collagen both through collagen biosynthesis as well as inhibition of collagen breakdown through down-regulation of the activity of MMPs. Beneficial effects of vitamin C on elastin were also observed. Elastin is an enzyme that degrades elastic fibres leading to the characteristic appearance of photoageing known as solar elastosis. In vitro studies have shown that vitamin C inhibits the biosynthesis of elastin.15 An anti-inflammatory effect of vitamin C has also been observed both clinically and in cultured human cells. Laboratory studies have
Spotlight On Vitamin C
shown that vitamin C inhibits activation of transcription factor NFĸB, a transcription factor responsible for the production of a number of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-8. These cytokines are responsible for a number of inflammatory pathways implicated in certain dermatoses.16 Despite these anti-inflammatory effects, vitamin C is not primarily used in practice for inflammatory dermatoses. Vitamin C also plays a role as an anti-pigmentation agent. It interacts with copper ions at tyrosinase-active sites and inhibits the action of the enzyme tyrosinase – the main enzyme responsible for the conversion of tyrosine into melanin - and therefore can be used in anti-pigmentation treatment.17 Conclusion: Environmental triggers such as pollution, smoking, and in particular harmful solar radiation cause damage to the cells through the formation of reactive oxygen species. Vitamin C is the most powerful anti-oxidant in the skin and is able to provide photoprotection through neutralisation of the oxidative stress cascade. This photoprotective effect is complimentary to the “sunscreen effect” provided by the application of sunblocks, the latter absorbing or reflecting ultraviolet light but not primarily neutralising free radicals. Objective parameters studied in laboratory setting have shown a reduction in a number of parameters that correlate to photoaging, all of which are reduced by the use of vitamin C. Furthermore, vitamin C has shown to have beneficial effects in collagen synthesis as well as anti-inflammatory and anti-pigmentation effects. A number of different formulations exist with L-ascorbic acid proving the most biologically active when formulated appropriately. Dr. Firas Al-Niaimi is a consultant dermatologist and laser surgeon and works at sk:n clinics in London. He trained in Manchester and subsequently did a prestigious advanced surgical and laser fellowship at the world-renowned St. John’s Institute of dermatology at St. Thomas’ Hospital in London. He has authored more than 80 publications including chapters of books and is on the advisory board for a number of respected journals. Dr Al-Niaimi is also a speaker and advisor for L’Oréal. REFERENCES: 1. Farris PK. Cosmetical Vitamins: Vitamin C. In: Draelos ZD, Dover JS, Alam M. editors. Cosmeceuticals. Procedures in Cosmetic Dermatology. 2 nd ed. New York: Saunders Elsevier; 2009. p. 51-6. 2. Traikovich SS. Use of Topical Ascorbic acid and its effects on Photo damaged skin topography. Arch Otorhinol Head Neck Surg 1999;125:1091-8. 3. Austria R, Semenzato A, Bettero A. Stability of vitamin C derivatives in solution and topical formulations. J Pharm Biomed Anal. 1997;15(6):795-801. 4. Lin FH, Lin JY, Gupta RD, Tournas JA, et al. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol. 2005;125(4):826-32. 5. Pinnell SR, Yang H, Omar M, et al. Topical L-ascorbic acid: percutaneous absorption studies. Dermatol Surg. 2001;27(2):137-42. 6. Lee S, Lee J, Choi YW. Skin permeation enhancement of Ascorbyl palmitate by lipohydro gel formulation and electrical assistance. Bio Pharma Bull 2007;30:393-6. 7. Tyrrell RM. Solar ultraviolet A radiation: an oxidizing skin carcinogen that activates heme oxygenase-1. Antioxid Redox Signal. 2004;6(5):835-40. 8. Fisher GJ, Wang ZQ, Datta SC, et al. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med. 1997;337(20):1419-28. 9. Hanson KM, Simon JD. Epidermal trans-urocanic acid and the UV-A-induced photoaging of the skin. Proc Natl Acad Sci 1998;95:10576–10578. 10. Shindo Y, Witt E, Han D, et al. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol. 1994;102(1):122-4. 11. Meplan C, Richard MJ, Hainaut P. Redox signaling and transition metals in the control of the p53 pathway. Biochem Pharmacol 2000;59:25-33. 12. Oresajo C, Stephens T, Hino PD, et al. Protective effects of a topical antioxidant mixture containing vitamin C, ferulic acid, and phloretin against ultraviolet-induced photodamage in human skin. J Cosmet Dermatol. 2008;7(4):290-7. 13. De Tullio MC. Beyond the antioxidant: the double life of vitamin C. Subcell Biochem. 2012;56:49-65. 14. Grosso G, Bei R, Mistretta A, et al. Effects of vitamin C on health: a review of evidence. Front Biosci (Landmark Ed). 2013;18:1017-29. 15. Farris PK. Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions. Dermatol Surg. 2005;31(7 Pt 2):814-7. 16. Murray JC, Burch JA, Streilein RD, et al. A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. J Am Acad Dermatol. 2008;59(3):418-25. 17. Matsuda S, Shibayama H, Hisama M, et al. Inhibitory effects of novel ascorbic derivative VCP- IS-2Na on melanogenesis. Chem Pharm Bull 2008;56:292-7.
Aesthetics | January 2015
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