PEER-REVIEW | DERMATOLOGY | L-ascorbic acid to below pH 3.5, which has shown to


greatly aid in its penetration, largely due to the transformation from the charged to the uncharged form of the molecule6


. In one example of the


currently available L-ascorbic acid product (Skinceuticals by L’Oreal), the addition of ferulic acid aids in both the stabilisation of the molecule as well as achieving an acidity of a pH below


3.5 7 .


Saturation of tissue is achieved after three daily applications of L-ascorbic acid, and the half-life in tissue is about four days6


. Two other common topical


formulations of vitamin C include ascorbyl-6- palmitate and magnesium ascorbyl phosphate (MAP). Unlike L-ascorbic acid, which is hydrophilic and unstable, both ascorbyl-6-palmitate and MAP are lipophilic, esterified forms of vitamin C, which are stable at neutral pH8


.


Ascorbyl palmitate is hydrolysed to form ascorbic acid and palmitic acid8


. Ascorbyl palmitate is thought to


have an antioxidant and anti-inflammatory effect. However, studies on the efficacy of ascorbyl palmitate have shown conflicting results. While there is some evidence to suggest that ascorbyl palmitate can reduce UV-induced erythema9 inhibit tumour production11


, improve inflammation10 , and others suggest that it may be


toxic to keratinocytes in the presence of UVB. The mechanism for this is unclear but it is thought that when ascorbyl palmitate is oxidised, it generates ascorbyl free radicals that may cause damage to cell membranes12 Magnesium ascorbyl phosphate appears to be the most


.


stable and preferred ascorbyl ester. Due to its lipophilic nature, it is easily absorbed into the skin. MAP is dephosphorylated when it crosses the epidermis, and is converted to ascorbic acid8


. In laboratory studies, MAP


has been shown to scavenge free radicals and increase collagen production13–16


. In clinical studies, a 10% MAP


cream demonstrated significant improvement in melasma and senile freckles17


. Examples of other stable esterified derivatives of


vitamin C are disodium isostearyl 2-0 L-ascorbyl phosphate, ascorbic acid sulphate, and tetraisopalmitoyl ascorbic acid18


. Although esterified forms of vitamin C are a potential


way to stabilise the molecules and improve penetration through the stratum corneum, one study showed that daily application of MAP, ascorbyl-6-palmitate and other ascorbic acid derivatives did not increase the levels of L-ascorbic acid in the skin6


. The optimal concentration of vitamin C depends on its


formulation. In most cases, for it to be of biological significance, it needs to be higher than 8%6


26  . Studies have shown that a concentration above 20% does not increase January/February 2016 | prime-journal.com


its biological significance and in contrary may cause some irritation6


. The most


available reputable products of vitamin C today are therefore in the range of 10–20% to exert an antioxidant effect and with lower concentrations for its role in anti-inflammatory conditions.


Mechanism of action and clinical applications Vitamin C as a potent antioxidant Intrinsically aged skin has been shown to have 70% less concentration of various antioxidants including L-ascorbic acid compared to young skin19


. In The optimal concentration of


vitamin C depends on its formulation. In most cases, for it to be of


biological significance, it needs to be higher than


8%. Studies have shown that a concentration above 20% does not


increase its biological significance and, in


contrary, may cause some irritation.


addition to this, environmental factors such as solar radiation, pollution, and smoking can accelerate damage to the skin through the generation of so-called ‘oxidative stress’20


. Although the skin


has its inherent antioxidant defence mechanism to cope with oxidative stress, chronic, and excessive exposure can overwhelm the antioxidant capacity, and lead to photoaging, immunosuppression, and photocarcinogenesis21


. Trans-urocanic acid is a by-product of


filaggrin present in the skin, which acts as a chromophore for photons of solar radiation (mainly ultraviolet (UV) and to a degree, infrared) leading to the formation of singlet oxygen. This triggers a cascade of events leading to the formation of so-called ‘reactive oxygen species’ or ‘free radicals’22


. These


are highly toxic unstable molecules that can cause damage to nucleic acids,


proteins, and cell membranes. Antioxidants such as vitamin C act by neutralizing the singlet oxygen cascade and therefore limiting the formation of reactive oxygen species. This occurs predominantly by a process of electron transfer and/or donation3,23


.


Protection against photoaging UV-induced reactive oxygen species induce erythema and pigmentation, and can lead to alteration of the collagen and elastin components in the skin. This gives rise to the appearance of sunburn and clinical


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68