INTRODUCTION

Vitamin C is a naturally occurring antioxidant incorporated into cosmeceuticals for the purpose of preventing and treating sun-damaged skin. Most plants and animals have the capacity to synthesize vitamin C. In humans, however, vitamin C cannot be synthesized because of loss of the ability to produce L-glucono-gamma-lactone oxidase, the enzyme necessary for its production. Vitamin C must instead be obtained from dietary sources such as citrus fruits and leafy green vegetables (Fig. 8.1). Interestingly, oral supplementation with vitamin C produces only a limited increase in skin concentration. This is because even with ingestion of massive doses, the absorption of vitamin C is limited by active transport mechanisms in the gut. Therefore, vitamin C has become a popular topically applied cosmeceutical.

Fig. 8.1 Citrus fruits, such as oranges, are a rich dietary source of vitamin C

Three forms of vitamin C are found in cosmeceuticals marketed as creams, serums, and patches. The first form is the active form of vitamin C, L-ascorbic acid. Early formulations of L-ascorbic acid often turned yellow due to the oxidation byproduct dehydroascorbic acid produced upon exposure to air. For this reason, many cosmetic chemists turned to more stable esterified derivatives, such as ascorbyl-6-palmitate and magnesium ascorbyl phosphate. Stability studies comparing all three compounds have demonstrated that magnesium ascorbyl phosphate is the most stable in solution and emulsion followed by ascorbyl-6-palmitate, while L-ascorbic acid is least stable. In spite of these findings, cosmeceuticals containing all forms of vitamin C can be purchased in the marketplace today.

OXIDATIVE STRESS, AGING SKIN, AND VITAMIN C

Antiaging research has elucidated the role of reactive oxygen species in the pathogenesis of photoaging. Reactive oxygen species (ROS) including superoxide anion, peroxide, and singlet oxygen are generated when human skin is exposed to ultraviolet (UV) light. These ROS mediate their deleterious effects by causing direct chemical alterations of DNA, cell membranes, and proteins including collagen.

Oxidative stress can also activate certain cellular events mediated by transcription factors. ROS upregulate transcription factor activator protein-1 (AP-1). AP-1 increases matrix metalloproteinase (MMP) production resulting in collagen breakdown. Nuclear transcription factor kappa B (NF-κB) is also induced by oxidative stress and produces a number of inflammatory mediators that contribute to skin aging. Additionally, ROS increase elastin mRNA levels in dermal fibroblasts which may provide an explanation for the elastotic changes found in the photoaged dermis.

The skin relies on a complex system of enzymatic and nonenzymatic antioxidants to protect itself from harmful ROS. L-ascorbic acid is the most plentiful antioxidant in human skin. This water-soluble vitamin functions in the aqueous compartment of the cell. Vitamin C sequentially donates electrons, neutralizes free radicals, and protects intracellular structures from oxidative stress. Following the donation of the first electron, a more stable ascorbate free radical is formed and after the second electron is donated, dehydroascorbic acid remains. Dehydroascorbic acid can be converted back to L-ascorbic acid by dehydroascorbic acid reductase or may be broken down as the lactone ring opens. Vitamin C also helps regenerate the oxidative form of vitamin E, a potent lipid-soluble antioxidant. In this regard, these two vitamin antioxidants appear to function synergistically within the cell.

In a compounding manner, while UV light increases production of intracellular ROS, it is at the same time impairing the skin’s ability to neutralize them. UVB exposure depletes skin of many key antioxidants, including vitamin C. It is known that exposure to UV light depletes the skin reservoir of vitamin C in a dose-dependent manner. Even minimal exposure to 1.6 MED (minimal erythema dose) can decrease vitamin C levels to 70% of normal, while exposing murine skin to 10 times MED further increases depletion to 54% of normal. In addition, ozone depletes stores of vitamins C and E in epidermal cells. Thus environmental exposure impairs the skin’s natural defense mechanisms against oxidative stress.

VITAMIN C: EFFECTS ON COLLAGEN AND ELASTIN SYNTHESIS

Vitamin C is essential for collagen biosynthesis. Ascorbate serves as a cofactor for prolyl and lysyl hydroxylase, the enzymes responsible for stabilizing and cross-linking collagen. Ascorbate can also stimulate collagen synthesis directly by activating its transcription and stabilizing procollagen mRNA. Scurvy serves as prototype for the physiologic changes that occur when vitamin C is lacking and collagen biosynthesis is impaired.

In view of this, it is no surprise that topically applied vitamin C has been shown to enhance collagen production in human skin. Skin biopsies taken from postmenopausal women who applied 5% L-ascorbic acid to one forearm and vehicle to the other showed an increase in mRNA levels of collagen I and III. Additionally, levels of tissue inhibitor of MMP-1 were also increased, suggesting that topical vitamin C may mitigate collagen breakdown. Interestingly, mRNA levels of elastin, fibrillin, and tissue inhibitor of MMP-2 remained unchanged. The authors note that those most affected by topical vitamin C had low dietary intake of vitamin C and conclude that the functional activity of dermal cells can be improved by topically applied vitamin C.

L-ascorbic acid also appears to influence elastin biosynthesis. In vitro studies suggest elastin biosynthesis by fibroblasts may be inhibited by ascorbate. This may be helpful in reducing the elastin accumulation that is characteristic of photoaged skin.

PHOTOPROTECTION BY VITAMIN C

While sunscreens remain the mainstay for protecting skin against UV-induced changes, topical antioxidants are gaining favor. Recent studies suggest that while sunscreens reduce UV-induced erythema and thymine dimer formation, they do little to protect skin from free radicals. Sunscreens, even when applied properly, block only 55% of free radicals produced by UVA exposure. This is important in that UVA is believed to be significant in the pathogenesis of skin aging and possibly melanoma formation. These data suggest that in order to optimize UV protection, sunscreens should be used in conjunction with topical antioxidants.

L-ascorbic acid is known to have photoprotective effects on skin. Vitamin C does not act as a sunscreen per se as it does not absorb sunlight in the UV spectrum. Topical L-ascorbic acid has been shown to protect porcine skin from UVB-induced erythema and sunburn cell formation. Topical application of 10% vitamin C was shown to decrease UVB-induced erythema by 52% and the number of sunburn cells by 40–60%. Pre-treatment with topical vitamin C prior to PUVA mitigated phototoxic injury as measured by sunburn cells and resulted in a normal histology devoid of the usual PUVA-associated findings.

While vitamin C alone can confer photoprotection, it appears to function optimally in conjunction with vitamin E. In studies designed to evaluate this synergy, vitamins C and E were applied alone or in combination for 4 days to pig skin and then irradiated with a solar simulator (295 nm). On day 5, antioxidant protection factor was measured including erythema, sunburn cells, and thymine dimers. The combination of 15% L-ascorbic acid and 1% α-tocopherol provided superior photoprotective effects (fourfold) that were progressive over the 4-day period. Both antioxidants conferred photoprotection when applied alone but to a lesser degree than when used in combination.

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