PEER-REVIEW | DERMATOLOGY | Key points Vitamin C is the most


powerful antioxidant 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 infra-red rays cause oxidative stress and this is neutralized by vitamin C


Oxidative stress can cause a cascade of events in the skin leading to photoaging and photocarcinogenesis


Vitamin C exerts beneficial effects on the formation of collagen in addition to the prevention of collagen breakdown caused by solar radiation


Vitamin C has also


shown to exert anti-inflammatory effects through inhibition of the transcription factor NFκB


Interference with the enzyme tyrosine kinase means that vitamin C exerts anti-pigmentation effects, albeit weaker than some of the other available products on the market


Recent studies have shown that methods, such as nanoparticles multi-layered microemulsions for graded delivery, ultrasound,


ticle es,


iontophoresis, laser resurfacing, and microdermabrasion can help to enhance penetration of vitamin C.


Anti-pigmentary effect


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 thereby decreasing melanin formation42,43


. A clinical study examining the effect of a


topical formulation containing 5% vitamin C and a chemical penetration enhancer reported a significant decrease in pigmentation caused by melasma after 16 weeks44


. Although vitamin C has been shown to suppress


melanin production, its clinical effects may not be as effective as other topical products containing hydroquinone45


.


Adverse reactions of vitamin C Vitamin C is generally well-tolerated and has a good safety profile. The combination of vitamin C with other topical anti-ageing agents has been used without any reports of significant adverse reactions. Minor adverse reactions such as skin irritation and oxidative changes of vitamin C causing yellow staining of the skin and clothes, and hypopigmented hair can occur18 dermatitis has been reported46–48


. Rarely, contact . References


1. Manela-Azulay M, Bagatin E. Cosmoceuticals vitamins. Clin Dermatol 2009; 27: 469-474


2. ZetterströM R. Nobel Prize 1937 to Albert von Szent-Györgyi: identification of vitamin C as the anti-scorbutic factor. Acta Paediatr 2009; 98(5): 915-9


3. Farris PK. Cosmetical Vitamins: Vitamin C. In: Draelos ZD, Dover JS, Alam M. editors. Cosmoceuticals. Procedures in Cosmetic Dermatology. 2 nd ed. New York: Saunders Elsevier; 2009. p. 51-6


4. Carpenter KJ. The discovery of vitamin C. Ann Nutr Metab 2012; 61: 259-264


5. Duconge J, Miranda-Massari JR, Gonzalez MJ, Jackson JA, Warnock W, Riordan NH. Pharmacokinetics of Vitamin C: insights into the oral and intravenous administration of ascorbate. P R Health Sci J. 2008 Mar;27(1):7-19


6. Pinnell SR, Yang H, Omar M, et al. Topical L-ascorbic acid: percutaneous absorption studies. Dermatol Surg. 2001;27(2):137-42


7. 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


8. Lupo MP. Antioxidants and vitamins in cosmetics. Clin Dermatol 2001;19:467–473


9. Perricone NV. The photoprotective and anti-inflammatory effects of topical ascorbyl palmitate. J Ger Dermatol 1993;1:5–10. 37


10. Perricone NV. Topical vitamin C ester (ascorbyl palmitate). J Ger Dermatol 1997;5:162–70


11. Smart RC, Crawford CL. Effect of ascorbic acid and its synthetic, lipophilic derivative ascorbyl palmitate on phorbol ester-induced skin-tumor promotion in mice. Am J Clin Nutr 1991;54:1266S–73S. 36


12. Meves A, Stock SN, Beyerle A, 32 


Pittelkow MR, Peus D. Vitamin C derivative ascorbyl palmitate promotes ultraviolet-B-induced lipid peroxidation and cytotoxicity in keratinocytes. J Invest Dermatol. 2002 Nov;119(5):1103-8.


13. Kobayashi S, Takehana M, Itoh S, et al. Protective effect of magnesuim-L- ascorbyl-2-phosphate against skin damage induced by UVB irradiation. Photochem Photobiol 1996; 64:224–8


14. Geesin JC, Gordon JS, Berg RA. Regulation of collagen synthesis in human dermal fibroblasts by the sodium and magnesium salts of ascorbyl-2- phosphate. Skin Pharma- col 1993;6:65–71


15. Hata R, Senoo H. L-ascorbic acid 2-phosphate stimulates collagen accumulation, cell proliferation, and formation of a three-dimensional tissue-like substance by skin fibroblasts. J Cell Physiol 1989;138:8 –16


16. Kurata S, Hata R. Epidermal growth factor inhibits transcription of type I collagen genes and production of type I collagen in cultured human skin fibroblasts in the presence and absence of L-ascorbic acid 2-phosphate, a long acting vitamin C derivative. J Biol Chem 1991;266:9997– 10003


17. Kameyama K, Sakai C, Kondoh S, et al. Inhibitory effect of magnesium-L- ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo. J Am Acad Dermatol 1996;34:29–33


18. Telang PS. Vitamin C in dermatology. Indian Dermatol Online J 2013; 4(2): 143-146


19. Rhie G, Shin MH, Seo JY, et al. Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo. J Invest Dermatol 2001;117:1212-7


20. Tyrrell RM. Solar ultraviolet A radiation: an oxidizing skin carcinogen


that activates heme oxygenase-1. Antioxid Redox Signal. 2004;6(5):835-40.


21. Godic A, Poljšak B, Adamic M, Dahmane R. The role of antioxidants in skin cancer prevention and treatment. Oxid Med Cell Longev. 2014;2014:860479.


22. 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


23. Traikovich SS. Use of Topical Ascorbic acid and its effects on Photo damaged skin topography. Arch Otorhinol Head Neck Surg 1999;125:1091-8.


24. Chen L, Hu JY, Wang SQ. The role of antioxidants in photoprotection: a critical review. J Am Acad Dermatol. 2012 Nov;67(5):1013-24.


25. Sato Y, Arai KY, Nishiyama T, et al. Ascorbic acid deficiency leads to epidermal atrophy and UVB-induced skin pigmentation inSMP30/GNL knockout hairless mice. J Invest Dermatol. 2012 Aug;132(8):2112-5. doi: 10.1038/ jid.2012.105. Epub 2012 Apr 12.


26. Hering TM, Kollar J, Huynh TD, Varelas JB, Sandell LJ. Modulation of extracellular matrix gene expression in bovine high-density chondrocyte cultures by ascorbic acid and enzymatic resuspension. Arch Biochem Biophys 1994;314: 90-8. 73


27. Farris PK. Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions. Dermatol Surg. 2005;31(7 Pt 2):814-7


28. Zussman J, Ahdout J, Kim J. Vitamins and photoaging: do scientific data support their use? J Am Acad Dermatol 2010;63:507-25


29. Bissett DL, Chatterjee R, Hannon DP. Photoprotective effect of superoxide- scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse.


Photodermatol Photoimmunol Photomed 1990;7:56-62


30. Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatol Surg 2002;28(3):231-6


31. Humbert PG, Haftek M, Creidi P, et al. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation:double-blind study vs. placebo. Exp Dermatol 2003; 12(3):237-44


32. McArdle F, Rhodes LE, Parslew R, Jack CI, Friedmann PS, Jackson MJ. UVR-induced oxidative stress in human skin in vivo: effects of oral vitamin C supplementation. Free Radic Biol Med. 2002 Nov 15;33(10):1355-62.


33. Toyoda M, Bhawan J. Ultrastructural evidence for the participation of Langerhans cells in cutaneous photoaging processes: a quantitative comparative study. J Dermatol Sci 1997;14:87–100


34. Matsui MS, Hsia A, Miller JD, et al. Non-sunscreen photoprotection: antioxidants add value to a sunscreen. J Investig Dermatol Symp Proc 2009; 14(1): 56-9


35. Meplan C, Richard MJ, Hainaut P. Redox signaling and transition metals in the control of the p53 pathway. Biochem Pharmacol 2000;59:25-33


36. Darr D, Combs S, Dunston S, Manning T, Pinnell S. Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage. Br J Dermatol 1992;127:247-53


37. 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


Future developments Clinical studies on the efficacy of different formulations of topical vitamin C in human skin remain limited. The challenge lies with developing a stable formulation and finding the most efficient transepidermal delivery method for the esterified forms of vitamin C (e.g. ascorbyl palmitate, MAP etc.) in order to maximise the concentration of active vitamin C in the skin. Recent studies have shown that methods such as nanoparticles, multi-layered microemulsions for graded delivery, ultrasound, iontophoresis, laser resurfacing, and microdermabrasion can help to enhance penetration of vitamin C18,49,50


. However, these


studies remain small and there are no comparative studies to determine the optimal delivery method. Also, further larger studies are needed to confirm the synergistic effect of vitamin C with other antioxidants and growth factors. Methods to deliver huge doses of vitamin C via oral and intravenous means have been


January/February 2016 | prime-journal.com


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