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Vitamin C and Skin
Journal of Clinical & Experimental Dermatology Research

Journal of Clinical & Experimental Dermatology Research
Open Access

ISSN: 2155-9554

+44 20 3868 9735

Review Article - (2018) Volume 9, Issue 1

Vitamin C and Skin

Keiji Sugiura* and Mariko Sugiura
Department of Environmental Dermatology and Allergology, Daiichi Clinic, Nittochi Nagoya Bld, Sakae, Nakaku, Nagoya, Japan
*Corresponding Author: Keiji Sugiura, Department of Environmental Dermatology and Allergology, Daiichi Clinic, Nittochi Nagoya Bld, Sakae, Nakaku, Nagoya, Japan, Tel: +81522040834, Fax: +81522040834 Email:

Abstract

Vitamin C (VC) is one of nine water-soluble vitamins. VC is known as ascorbic acid (AA), which is a reduced form of VC. AA plays some essential roles in the human body: (1) protecting skin against UV damage; (2) preventing hyperpigmentation of the skin; (3) improving skin inflammation and reducing photocarcinogenesis; (4) increasing collagen fiber; (5) reducing oxidative stress; and (6) immuno-modulating effects. AA deficiency affects collagen and vessels structure, wound healing and hemostasis, and scurvy. VC and AA are essential for life. We hope development of new medicines using VC or AA because of few adverse side effects of VC and AA.

Keywords: Vitamin C; Skin; Ascorbic acid; Pigmentation, Collagen fiber, Aging, Ultraviolet, Dermatoses

Introduction

There are 13 vitamins, nine of which are water-soluble, with the remaining four being lipid-soluble. Vitamin C (VC) is one of the watersoluble vitamins. The body weight of VC is 176.12, and its chemical structure, C6H8O6, is shown in Figure 1.

clinical-dermatology-Vitamin-C

Figure 1: The structure of Vitamin C.

VC localizes in the mitochondria, peroxisomes, and other subcellular compartments of tissues [1]. VC is absorbed via the gastrointestinal tract and enters the blood. The saturated concentration of VC is 400 mg/day, and this concentration is controlled by excretion through the kidneys, reuse in the living body, and absorption from the gastrointestinal tract.

VC is known as ascorbic acid (AA), which is a reduced form of VC. There are four types of AA: (1) L-AA; (2) sodium L-ascorbate; (3) Lascorbyl stearate; and (4) L-ascorbyl palminate. L-AA and sodium Lascorbate are water-soluble compounds, and they are often used as enrichments, improving agents, and antioxidants in snacks and beverages. Because L-AA derivatives become L-AA in the skin after permeating through the stratum corneum, we apply these derivatives to skin whitening.

L-ascorbyl stearate and L-ascorbyl palminate are lipid-soluble compounds, and are used as enrichments and antioxidants in fatsoluble foods (batter, cheese and baby foods) or edible fat and oil.

AA deficiency affects collagen and vessels structure, wound healing and hemostasis, and scurvy. AA is related to the prevention or delay of certain organ disorders, including reducing the incidence of agerelated cataracts [2], ameliorating atherosclerosis (early stage) [3], and decreasing the risk of diabetes mellitus [4]. AA plays some essential roles in the human body: (1) protecting skin against UV damage; (2) preventing hyperpigmentation of the skin; (3) improving skin inflammation and reducing photocarcinogenesis; (4) increasing collagen fiber [5,6]; (5) reducing oxidative stress [5,7]; and (6) immuno-modulating effects.

Protect skin against UV damage

UV radiation leads to skin damage due to free radical oxygen [8,9]; such events are related to activation protein-1, growth factor–beta, and nuclear factor–B [10]. These factors trigger the collapse of collagen structure in the skin, resulting in wrinkles, solar elastosis, and coarse texture [11].

VC inhibits such sun-damage-related factors. Farris [12] reported that VC inhibited the biosynthesis of elastin fiber. UV decreased VC of the skin, but topical VC reduced UVB damage in mouse skin [13]. VC modified skin structure and ultrastructure from photo-damaged skin [14]. Skin disorders due to UV damage may increase due to the decreasing ozone layer; thus, we should intake VC or AA as protection against UV.

Prevent skin hyperpigmentation

Skin hyperpigmentation is observed with inflammation, injury, and aging. Keratinocytes release many melanin granules by stimulating inflammatory mediators. This melanin deposits in the epidermis, and some drips into the dermis and then into macrophage phagocytes (melanophage).

There are two types of melanin, oxidized and reduced. The roles of VC or AA are to reduce deep or dark colored (oxidized hyperchromic) melanin to colorless (achromasia) reduced melanin. L-AA or AA act at the tyrosinase active site and reduce oxidized dopaquinone in the melanin synthetic pathway [15,16]. From these, we use VC or AA for skin whitening by intake and/or iontophoresis. The disadvantage of VC and AA is their lack of fast-acting properties.

Improve skin inflammation and reduce photocarcinogenesis

AA is decreased in patients with cancer or inflammation, and Patterson [17] and Block [18] showed that VC-rich foods protect against the development of cancer. There have been reports of intravenous VC therapy used to inhibit angiogenesis [19], at toxicity against cancer cells [20], and as treatment for cancer [21]. High-dose AA acts as a free radical scavenger to kill cancer cells [22].

UV radiation causes skin inflammation, induces p53 gene mutation, and affects the repair of damaged DNA and apoptosis [12]. These events could lead to photocarcinogenesis, but VC reduces this risk [23]. VC decreased pro-inflammatory mediators, resulting in improved wound healing [24]. VC affects fibroblast proliferation and migration, and could shorten healing time in wounds [25,26]. High doses of VC or AA applied topically and/or by injection to the carcinoma or inflammation site may be effective.

Increase collagen fiber

VC aids production and stabilization of collagen synthesis [27]. The role of VC is to accelerate transcription of the collagen gene and/or stabilize collagen-mRNA in vitro [28,29]. VC is a fundamental factor in collagen fiber synthesis [6].

Philippe [14] reported that topical AA may activate dermal synthesis of elastic fibers. Sheldon [6] found that AA played essential roles in collagen production via hydroxylation of lysine and proline. Hydroxyproline and hydroxylysine are necessary for collagen helix formation and collagen cross-link formation, respectively [6]. Intake of VC or AA increased collagen fiber and consequently, decreased wrinkles.

VC promotes fibroblast proliferation for remodeling of skin tissue in wound healing [30]. The dysfunction or breaking of the skin barrier causes infection or invasion by foreign substances, and results in dermatoses or infection. VC is an essential factor of the epithelial barrier, and affects the skin barrier function by elevating the lipid synthesis of the skin barrier [31,32]. VC acts to produce and stabilize collagen synthesis [27]. Ponec [33] reported that VC plays important roles in reconstructed skin for the skin barrier of the stratum corneum. VC protects human tissue as a free-radical scavenger against various pollutants, superoxide, heavy metals, and chemical substances [34-36].

Reduce oxidative stress

We are exposed many oxidative stresses: UV, radiation, smoking, oxidative foods, ischemic conditions, physiological stress, physical stress, and others. These stresses increase active oxygen in the tissue, and this oxygen causes impairment of deoxyribonucleic acid (DNA), degeneration of proteins, deactivation of enzymes, and an excess of oxidative lipids. In turn, these alterations result in ischemic diseases or cancer.

The epidermis could be exposed to more foreign oxidant stress than the dermis, because the concentration of antioxidant molecules in the epidermis is higher than in the dermis, and the capacity of antioxidants in the epidermis is greater than that of the dermis [8,37]. VC is an antioxidant molecule [38] and reduces antioxidant stress. Nusgens [5] reported that an increase of VC could offer protection from free radicals.

The activity of VC is enhanced by vitamin E (VE) [39], and these vitamins are non-enzymatic antioxidant molecules. Murray [23] and Lin [40] reported that a topical solution of VC and VE added ferulic acid to protect from oxidative stress. There are two types of antioxidants, water-soluble and lipid-soluble. Water-soluble antioxidants in plasma include AA, glutathione, uric acid, pyruvate, glucose and bilirubin; the lipid-soluble antioxidants are lycopene, - carotene, alpha-tocopherol, ubiquinol-10, zeaxanthin and lutein [8]. Intake of antioxidants is more essential to protect against aging than elimination of active oxygen. One rule of VC is improvement of skin barrier against oxidative stress and/or foreign-body invasion.

Immuno-modulating effects

AA and VC are necessary against infection via the skin, in neutrophils/macrophages and the skin barrier. AA could possess immune-cell modulating effects [41]. VC enhances chemotaxis, the phagocytes of neutrophils, and uptake or clearance of macrophages [42]. VC plays important roles in the differentiation and maturation of immature T-cells [43] and natural killer cells [44]. It improved neutrophil chemotaxis [45-49], and in combination with VE, enhanced neutrophil functions, including chemotaxis [50]. Johnston proposed that the antihistamine effect of vitamin C was correlated with enhanced chemotaxis [51].

Other roles of VC against neutrophils include phagocytosis, microbial destruction, and oxidant generation [52]. Topical VC can prevent to decrease the number of CD-1a Langerhans cells in the skin due to UV exposure [52,53]. It is interesting that VC decreased histamine levels of allergic disease compared with infection in human studies [54,55]. VC may improve delayed hypersensitivity reactions and itching in dermatoses.

Conclusion

Vitamin C or Ascorbic Acid is essential for life. There are few adverse effects of Vitamin C or Ascorbic Acid and development of new medicines using Vitamin C or Ascorbic Acid should be pursued.

References

  1. D'Aniello C, Cermola F, Patriarca EJ, Minchiotti G (2017) Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and Epigenetics. Stem Cells Int 2017: 8936156.
  2. Yoshida M, Takashima Y, Inoue M, Iwasaki M, Otani T, et al. (2007) Prospective study showing that dietary vitamin C reduced the risk of age-related cataracts in a middle-aged Japanese population. Eur J Nutr 46: 118-124.
  3. Aguirre R, May JM (2008) Inflammation in the vascular bed: importance of vitamin C. Pharmacol Ther 119: 96-103.
  4. Harding AH, Wareham NJ, Bingham SA, Khaw K, Luben R, et al. (2008) Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer-Norfolk prospective study. Arch Intern Med 168: 1493-1499.
  5. Nusgens BV, Humbert P, Rougier A, Richard A, Lapière CM (2002) Stimulation of collagen biosynthesis by topically applied vitamin C. Eur J Dermatol 12: 32-34.
  6. Pinnell SR (1985) Regulation of Collagen Biosynthesis by Ascorbic Acid: A Review. Yale J Biol Med 58: 553-559.
  7. Colven RM, Pinnell SR (1996) Topical vitamin C in aging. Clin Dermatol 14: 227-234.
  8. Godic A, Poljšak B, Adamic M, Dahmane R (2014) The role of antioxidants in skin cancer prevention and treatment. Oxid Med Cell Longev 2014: 860479.
  9. Tyrrell RM (2004) Solar ultraviolet a radiation:an oxidizing skin carcinogen that activates heme oxygenase-1. Antioxid Redox Signal 6: 835-840.
  10. Al-Niaimi F, Chiang NYZ (2017) Topical vitamin C and the skin: mechanisms of action and Clinical applications. J Clin Aesthet Dermatol 10: 14-17.
  11. Chen L, Hu JY, Wang SQ (2012) The role of antioxidants in photoprotection: a critical review. J Am Acad Dermatol 67: 1013-1024.
  12. Meplan C, Richard MJ, Hainaut P (2000) Redox signaling and transition metals in the control of the p53 pathway. Biochem Pharmacol 59: 25-33.
  13. Bisset DL, Chatterjee R, Hannon DP (1990) Photoprotective effect of super-oxide scavenging antioxidants against ultra-violet radiationinduced chronic skin damage in the hairless mouse. Photodermatol Photoimmunol Photomed 7: 56-62.
  14. Philippe GH, Marek H, Pierre C, Charles L, Betty N, et al. (2003) Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo. Exp Dermatol 12: 237-244.
  15. Badreshia-Bansal S, Draelos ZD (2007) Insight into skin lightening cosmeceuticals for women of Color. J Drugs Dermatol 6: 32-39.
  16. Bolognia JL, Orlow SJ (2009) Melanocyte Biology. In: Bolognia JL, Jorizzo JL, Rapini RP, ed. Dermatology. 2nd edition, Elsevier Mosby.
  17. Patterson RE, White E, Kristal AR, Neuhouser ML, Potter JD (1997) Vitamin supplements and cancer risk: the epidemiologic evidence. Cancer Causes Control 8: 786-802.
  18. Block G (1991) Vitamin C and cancer prevention: the epidemiologic evidence. Am J Clin Nutr 53: 270S-282S.
  19. Mikirova NA, Casciari JJ, Riordan NH (2010) Ascorbate inhibition of angiogenesis in aortic rings ex vivo and subcutaneous Matrigel plugs in vivo. J Angiogenes Res 2: 2.
  20. Casciari JJ, Riordan NH, Schmidt TL, Meng XL, Jackson JA, et al. (2001) Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fiber in vitro tumors. Br J Cancer 84: 1544-1550.
  21. Cameron E, Pauling L (1976) Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA 73: 3685-3689.
  22. Juan Du, Joseph J. Cullena, Garry R. Buettner (2012) Ascorbic acid: Chemistry, biology and the treatment of cancer. Biochim Biophys Acta 1826: 443-457.
  23. Murray JC, Burch JA, Streilein RD, Lannacchione MA, Hall RP, et al. (2008) 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 59: 418-425.
  24. Mohammed BM, Fisher BJ, Kraskauskas D, War S, Wayne JS, et al. (2016) Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int. Wound J 13: 572-584.
  25. Desneves KJ, Todorovic BE, Cassar A, Crowe TC (2005) Treatment with supplementary arginine, vitamin C and zinc in patients with pressure ulcers: A randomised controlled trial. Clin Nutr 24: 979-987.
  26. Blass SC, Goost H, Tolba RH, Stoffel-Wagner B, Kabir K, et al. (2012) Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: A PRCT. Clin Nutr 31: 469-475.
  27. Oresajo C, Stephens T, Hino PD, Law RM, Yatskayer M, et al. (2008) Protective effects of a topical antioxidant mixture containing vitamin C, ferulic acid, and phloretin against ultraviolet-induced photodamage in human skin. J Cosmet Dermatol 7: 290-297.
  28. Chojkier M, Houglum K, Solis-Herruzo J, Brenner DA (1989) Stimulation of collagen gene expression by ascorbic acid in cultured human fibroblasts. A role for lipid peroxidation?. J Biol Chem 264: 16957-16962,
  29. Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, Pinnell SR (1981) Regulation of collagen synthesis by ascorbic acid. Proc Natl Acad Sci USA 78: 2879-2882.
  30. Mohammed B, Fisher BJ, Kraskauskas D, War S, Wayne JS, et al. (2016) Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J 13: 572-584.
  31. Savini I, Catani MV, Rossi A, Duranti G, Melino G, et al. (2002) Characterization of keratinocyte differentiation induced by ascorbic acid: Protein kinase C involvement and vitamin C homeostasis. J Investig Dermatol 118: 372–379.
  32. Uchida Y, Behne M, Quiec D, Elias PM, Holleran WM (2001) Vitamin C stimulates sphingolipid production and markers of barrier formation in submerged human keratinocyte cultures. J Investig Dermatol 117: 1307-1313.
  33. Ponec M, Weerheim A, Kempenaar J, Mulder A, Gooris GS, et al. (1997) The formation of competent barrier lipids in reconstructed human epidermis requires the presence of vitamin C. J Investig Dermatol 109: 348-355
  34. Haryanto B, Suksmasari T, Wintergerst E, Maggini S (2015) Multivitamin supplementation supports immune function and ameliorates conditions triggered by reduced air quality. Vitam Miner 4: 1-15.
  35. Sram RJ, Binkova B, Rossner P (2012) Vitamin C for DNA damage prevention. Mutat Res 733: 39-49.
  36. Pozzer A, Zimmermann P, Doering U, Van Aardenne J, Tost H, et al. (2012) Effects of business-as-usual anthropogenic emissions on air quality. Atmos Chem Phys 12: 6915-6937.
  37. Shindo Y, Witt E, Packer L (1993) Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. J Invest Dermatol 100: 260-265.
  38. Shindo Y, Witt E, Han D, Epstein W, Packer L (1994) Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol 102: 122-124.
  39. Bruno RS, Leonard SW, Atkinson J, Montine TJ, Ramakrishnan R, et al. (2006) Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radic Biol Med 40: 689-697.
  40. Lin FH, Lin JY, Gupta RD, Tournas JA, Burch JA, et al. (2005) Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol 125: 826-832.
  41. Riordan HD, Casciari JJ, González MJ, Riordan NH, Miranda-Massari JR, et al. (2005) A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci J 24: 269-276.
  42. Anitra CC, Silvia M (2017) Vitamin C and Immune Function. Nutrients 9: 1211.
  43. Huijskens MJ, Walczak M, Koller N, Briede JJ, Senden-Gijsbers BL, et al. (2014) Technical advance: Ascorbic acid induces development of double-positive T cells from human hematopoietic stem cells in the absence of stromal cells. J Leukoc Biol 96: 1165-1175.
  44. Huijskens MJ, Walczak M, Sarkar S, Atrafi F, Senden-Gijsbers BL, et al. (2015) Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy 17: 613-620.
  45. Vohra K, Khan AJ, Telang V, Rosenfeld W, Evans HE (1990) Improvement of neutrophil migration by systemic vitamin C in neonates. J Perinatol 10: 134-136.
  46. Boura P, Tsapas G, Papadopoulou A, Magoula I, Kountouras G (1989) Monocyte locomotion in anergic chronic brucellosis patients: The in vivo effect of ascorbic acid. Immunopharmacol Immunotoxicol 11: 119-129.
  47. Patrone F, Dallegri F, Bonvini E, Minervini F, Sacchetti C (1982) Disorders of neutrophil function in children with recurrent pyogenic infections. Med Microbiol Immunol 171: 113–122.
  48. Levy R, Schlaeffer F (1993) Successful treatment of a patient with recurrent furunculosis by vitamin C: Improvement of clinical course and of impaired neutrophil functions. Int J Dermatol 32: 832-834.
  49. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F (1996) Vitamin C for the treatment of recurrent furunculosis in patients with imparied neutrophil functions. J Infect Dis 173: 1502-1505.
  50. De la Fuente M, Ferrandez MD, Burgos MS, Soler A, Prieto A, et al. (1998) Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 76: 373-380.
  51. Johnston CS, Martin LJ, Cai X (1992) Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr 11: 172-176.
  52. Toyoda M, Bhawan J (1997) Ultrastructural evidence for the participation of Langerhans cells in cutaneous photoaging processes: a quantitative comparative study. J Dermatol Sci 14: 87-100.
  53. Matsui MS, Hsia A, Miller JD, Hanneman K, Scull H, et al. (2009) Nonsunscreen photoprotection: antioxidants add value to a sunscreen. J Investig Dermatol Symp Proc 14: 56-59.
  54. Clemetson CA (1980) Histamine and ascorbic acid in human blood. J. Nutr 110: 662-668.
  55. Hagel AF, Layritz CM, Hagel WH, Hagel HJ, Hagel E, et al. (2013) Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol 386: 789-793.
Citation: Sugiura K, Sugiura M (2018) Vitamin C and Skin. J Clin Exp Dermatol Res 9: 444

Copyright: © 2018 Sugiura K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.