Vitamin C

Topical Uses of Vitamin C

Several studies exist in the literature to show that topical and oral vitamin C is effective in treating photo-damaged skin, rejuvenation, pigmentation disorders and photo-protection. In this article, we'll review the mechanism of action of vitamin C and discuss its clinical uses in dermatology.

Mechanism of Action
Reactive oxygen species (ROS) are an inherent part of the anabolism and catabolism of tissues, including skin. Most oxygen in the body is used in cellular metabolism. Through a series of 1-electron subtractions, molecular oxygen is in sequence changed to superoxide anion, hydrogen peroxide, hydroxyl radical, and finally, to water. Most reactions occur in mitochondria and are related to energy production. Cellular enzymes and metabolic processes ordinarily keep oxidative damage to cells at minimum. In times of increased oxidative stress, however, including high metabolic demands and outside forces such as sunlight, smoking and pollution, protective controls may not be adequate and oxidative damage may occur. The most damage occurs from free radicals.

Free radicals are defined as atoms or molecules with an unpaired electron; examples include superoxide anion, peroxyl radical and hydroxyl radical. These molecules are extremely chemically reactive and short-lived; they react at the place where they are created. Other reactive molecules such as molecular oxygen, singlet oxygen and hydrogen peroxide are not free radicals per se, but are capable of initiating oxidative reactions and generating free radical species. Together these free radicals and reactive oxygen molecules are called ROS.5

Antioxidants are unstable compounds: this allows them to function in redox reactions. Instability makes them difficult to formulate in an acceptable, stable composition for cosmetic use. This why products that are commercially available should have the support of clinical trials and manufactured with tight quality control.
Low molecular weight antioxidants include L-ascorbic acid (vitamin C) in the fluid phase, glutathione in the cellular compartment, vitamin E in membranes and ubiquinol in mitochondria.5

Antioxidants can be supplied to skin through fast diet and oral supplementation. Physiologic process related to absorption, solubility and transport limit the amount that can be delivered into the skin. Direct application has added advantage of targeting the antioxidants to the area of the skin needing the protection. Based on in vitro studies, vitamin C should be formulated at pH levels less than 3.5 to enter the skin. Tissue levels are saturated after three daily applications; the half-life of tissue disappearance is about 4 days.6

In the skin, ascorbic acid acts as an antioxidant by scavenging and quenching free radicals (protects the aqueous environment) and by regenerating vitamin E from its radical form. After loss of a second electron, the resulting oxidation product dehydroascorbic acid can be regenerated by dehydroascorbic acid reductase, or as frequently happens, may decay as the lactone ring irreversibly opens.5

Vitamin C may also act as a pro-oxidant in the presence of transitional metal ions, such as iron.7 L-ascorbic acid is essential for collagen biosynthesis; it serves as a cofactor for proline and lysine hydroxylases, enzymes necessary for molecular stability and intermolecular cross-linking, respectively.8
It has been reported that vitamin C regulates collagen synthesis and production9 as it stimulates type I procollagen synthesis in cultured human skin fibroblasts.10,11

L-ascorbic acid may inhibit elastin byosynthesis12 and could therefore, be useful for reducing the increased elastin accumulation that occurs in photoaged skin.13

Clinical Studies
There are various cosmetic products 20-23 available in the United States that contain different forms of vitamin C; however, the data presented only applies to products for which there is supporting published literature. These products contain L-ascorbic acid as an active ingredient and differ only in the vehicle in which they are contained.

Vitamin C has a beneficial effect in photodamaged and aged skin. With increasing age, the number of papillae in the epidermal-dermal junction zone in human skin is reduced. It has been reported that with the use of 3% ascorbic acid there is a significant increase in the density and number of dermal papillae. This may explain the therapeutic effect for partial corrections of structural changes associated with the aging process.24,25

Humbert et al, performed a double-blind, randomized study in which they compared vitamin C 5% cream to placebo. Applying the cream daily for 6 months, they observed a statistically significant improvement of hydration, wrinkles, glare and brown spots in the vitamin C 5% group. Analysis of the skin replicas showed that, compared with placebo, there exists a highly significant increase in the density of skin microrelief as well as decrease of deep furrows with the vitamin C over a 6 month period.20

A statistically significant improvement is reported in photoaged skin with the use of 10% ascorbic acid. Biopsies in a study by Fitzpatrick and Rostan showed an increase in Grenz zone collagen and collagen type I.26

Another author reports the efficacy of L-ascorbic acid in photodamage facial skin. Traikovich demonstrated statistically significant improvement in 84.2% of the treated patients over placebo patients. 21

Vitamin C it has also been reported as an effective treatment for melasma. Espinal-Perez et al, performed a study in patients with melasma in Mexico using 5% ascorbic acid versus 4% hydroquinone. They observed that the best subjective improvement was in the hydroquinone group, however colorimetric measures showed no statistical difference. Subjects treated with ascorbic acid and hydroquinone had side effects in 6.5% and 68% respectively; the most common side effects were redness and irritation.22

Besides vitamin C uses in photorejuvenation and melasma, Ikeno et al, performed a study in patients with facial acne vulgaris. They compared topical vitamin C 5% to topical clindamycin 1% (Cleocin). The patients in the vitamin C group showed improvement 75% (28/37) compared with 54.5% (18/33) in the Clindamycin group. Means percentage reductions in inflammatory and non-inflammatory lesion counts were statistically significant in the vitamin C treatment group compared with the Clindamycin treatment group (P=0.01 and P=0.05, respectively).27

Combination Pharmaceutical Studies
The combination of vitamin C with topical retinoids for rejuvenation and treatment of photodamaged skin has been studied. Rachel et al, found that the combination of trichloroacetic acid peels, 0.05% tretinoin and ascorbic acid lotion are more effective than any of the components alone. In this study, they found histological changes such as thicker epidermis, decreased melanocyte hypertrophy and compactation of the basket-weave pattern of the stratum corneum. The skin of these patients was from the postauricular area, skin that does not undergo similar chronic exposure as the face.28

Recently, it has been reported that the combination of vitamin C with retinol is able to reverse, at least in part, skin changes, induced by both chronological aging and photoaging. Seite et al, performed two double-blind studies in aged and photoaged skin. Subjects applied this combination daily for 3- and 6-month periods. They found histological differences from baseline in both groups, such as reduction in type III collagen and thickening of the epidermis.23

It has been reported, that long-term oral administration of ascorbic acid and a-tocopherol significantly reduced the sunburn reaction to UVB radiation, and significantly less thymine dimmers were induced, suggesting that antioxidant treatment may protect against DNA damage of the skin. 29

Editor(s):
Amy McMichael, M.D.
References:
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