Vitamin C and Skin Health
Written by: Alexander J. Michels, Ph.D. Linus Pauling Institute. Oregon State University
Reviewed by: Zoe Diana Draelos, M.D. Consulting Professor. Department of Dermatology.Duke University School of Medicine Durham, NC
Reviewed by: Zoe Diana Draelos, M.D. Consulting Professor. Department of Dermatology.Duke University School of Medicine Durham, NC
The antioxidant properties of vitamin C (ascorbic acid) and its role in collagen synthesis make vitamin C a vital molecule for skin health. Dietary and topical ascorbic acid have beneficial effects on skin cells, and some studies have shown that vitamin C may help prevent and treat ultraviolet (UV)-induced photodamage. However, the effects of vitamin C in the skin are not well understood due to limited research. This article discusses the potential roles of vitamin C in the skin and summarizes the current knowledge about vitamin C in skin health.
Content and Availability
Vitamin C is a normal skin constituent that is found at high levels in both the dermis and epidermis. The vitamin C content of the epidermis is higher than the dermis, although the vitamin C concentrations in both layers are approximately equal to that of other water-soluble antioxidants, including uric acid and glutathione. Aging, however, causes a decline in vitamin C content in both the epidermis and dermis. Excessive exposures to UV light or pollutants (e.g., cigarette smoke and ozone) may also lower vitamin C content, primarily in the epidermis.
Vitamin C in the skin is normally transported from the bloodstream. Transport proteins specific for ascorbic acid are found on cells in all layers of the skin. Keratinocytes have a high capacity for vitamin C transport, possibly to compensate for limited vascularization of the epidermis. Oral supplementation with vitamin C effectively increases vitamin C levels in the skin . However, when plasma vitamin C levels are saturated, skin vitamin C concentrations no longer increase. Optimum skin concentrations of the vitamin are not yet known.
Vitamin C can be provided to the skin through topical application. The stratum corneum is the primary obstacle to efficient vitamin C absorption from external sources; removal of the stratum corneum by laser, chemical, or mechanical methods enhances absorption. Although similar studies are still required for humans, studies in laboratory animals show that percutaneous vitamin C absorption greatly depends on pH. Preparations with a pH below 4.0 aid in transport by promoting the uncharged form of vitamin C, ascorbic acid. Although concentrations of vitamin C up to 30% have been used for animal studies, maximal absorption was achieved with a 20% vitamin C solution, with higher concentrations showing lower absorption. Topical application of ascorbic acid will cross the epidermis into the underlying dermal layers.
The stability of vitamin C in topical solutions is a concern, as exposures to air, heat, and/or light may slowly degrade vitamin C. Although the natural form of vitamin C, ascorbic acid, is the most effective for topical administration, it is the least stable in solution. However, stable synthetic derivatives, such as ascorbate phosphate, are considered to have limited permeability and function in skin. Another stable lipid-soluble derivative, ascorbyl palmitate, also has limited absorption, and one in vitro study with cultured skin cells found that the administration of ascorbyl palmitate had some toxic effects. Yet, the stability of topical vitamin C solutions may be increased by the addition of other antioxidant compounds (e.g: ferulic acid increases the stability of vitamin c).
Human studies with subjects using topically applied solutions of 0.6%-10.0% vitamin C or its synthetic derivatives have not reported adverse effects.
Symptoms of vitamin C deficiency (knowns as scurvy) appear once plasma concentrations of ascorbic acid drop below 10 micromolar, a level that can be prevented by consuming as little as 10 mg of ascorbic acid daily. Cutaneous manifestations of scurvy result from declines in collagen synthesis, leading to disruption of connective tissue and fragility of blood vessels. Early symptoms in the skin include a thickening of the stratum corneum and spots of small subcutaneous bleeding. As scurvy progresses, wound healing is impaired due to the loss of mature collagen, which allows wounds to remain open. Skin lesions caused by vitamin C deficiency are remediated by an adequate intake of vitamin C.
Functions in Healthy Skin
Vitamin C limits the damage induced by ultraviolet (UV) light exposure. Vitamin C is not a “sunscreen” because it does not absorb light in the UVA or UVB spectrum. Rather, the antioxidant activity of vitamin C protects against UV-induced damage caused by free radicals . Vitamin C transport proteins are increased in keratinocytes in response to UV light, suggesting an increased need for vitamin C uptake for adequate protection.
UV light decreases vitamin C content of skin, an effect that is dependent on the intensity and duration of UV exposure. In cultured keratinocytes, the addition of vitamin C reduces UV-related DNA damage and lipid peroxidation, limits the release of pro-inflammatory cytokines, and protects against apoptosis. Vitamin C also modulates redox-sensitive cell signaling in cultured skin cells and consequently increases cell survival following UV exposure.
In two rodent studies, addition of ascorbic acid to the diet reduced the size and number of dermal neoplasms and skin tumors induced by chronic UV exposure. To date, no other studies with UV exposure and oral ascorbic acid supplementation in animal models have been published.
In two human studies, oral vitamin C supplementation alone did not significantly increase Minimal Erythemal Dose (MED), a measure of photoprotection from UV light in skin. Overall, limited data suggest that vitamin C consumption alone provides insufficient antioxidant protection against UV irradiation. However, multiple studies have found that oral supplementation with a combination of vitamin C and vitamin E effectively increases MED and decreases erythema-induced blood flow to damaged areas of skin . Thus, interactions between the two antioxidant vitamins may be necessary to achieve UV protection by dietary means.
Topical application of vitamin C, alone or in combination with other compounds, may result in greater photoprotection than oral supplementation because of the more direct route of administration. In one mouse study, topical application of ascorbic acid delayed the effects of chronic high-dose UVB exposure on the skin, including a reduction in skin wrinkling and the development of skin tumors. In pig models, topical application of vitamin C reduced the number of sunburned cells, decreased erythema response, and reduced DNA damage induced by UVA exposure. Topically applied combinations of vitamin C and vitamin E are more effective in preventing photodamage than either vitamin alone. In particular, this combination of antioxidant vitamins decreased the immunosuppressive effects of UV exposure , increased MED, and decreased cell damage.
Limited human studies are available on photoprotection by topical application of vitamin C. Although topical ascorbic acid reduces radicals in UV-exposed human skin , only one study examined its effect on UV-induced erythemal response; this study reported no significant benefit of topical vitamin C . Like animal research, human studies using combinations of vitamin C and vitamin E have documented UV protective effects.
The accumulation of oxidative damage to proteins is a distinguishing feature of both photodamage (photoaging) and intrinsic aging; such oxidative damage can lead to changes in skin structure. In addition to its antioxidant functions, vitamin C regulates the synthesis of the structural protein collagen. The role of vitamin C in the hydroxylation of collagen molecules is well characterized . Hydroxylation of collagen is necessary for its extracellular stability and support of the epidermis.
In cell culture models, vitamin C supplementation has many beneficial effects in combating photodamage. Specifically, vitamin C has been shown to stabilize collagen mRNA, thus increasing collagen protein synthesis for repair of the damaged skin . This occurs concurrently with a decrease in elastin production; the elastin protein is often overproduced in response to photodamage. Vitamin C also increases the proliferation rate of fibroblasts, a capacity that is decreased with age . Further, vitamin C stimulates DNA repair in cultured fibroblasts .
Human studies often assess skin health by changes in depth or number of wrinkles and by the individual’s perception of skin health. Two observational studies found that higher intakes of vitamin C from the diet were associated with better skin appearance, with notable decreases in skin wrinkling. The use of vitamin C (3-10%) in topical applications for at least 12 weeks has been shown to decrease wrinkling, reduce protein fiber damage, decrease apparent roughness of skin, and increase production of collagen. Topical vitamin C has also been shown to reverse some of the age-related structural changes in the interface between the dermis and the epidermis . However, the effects of topical vitamin C are not apparent in all individuals, and interestingly, one study found that individuals with high dietary intakes of vitamin C showed no or little effect of a topical administration.
One of the distinctive features of scurvy is poor wound healing. Vitamin C levels decrease rapidly at a wound site . Although inflammatory responses often increase free radicals at the site of injury and the presence of vitamin C may limit free radical damage, free radicals may play a complex role in the healing response that is not yet understood . However, the increased demand for dermal collagen synthesis may increase utilization of vitamin C. Vitamin C may have additional roles in wound healing, for example, by promoting keratinocyte differentiation , stimulating the formation of the epidermal barrier, and re-establishing the stratum corneum.
Studies on the effect of vitamin C supplementation on wound healing have reported somewhat mixed results. Data from laboratory animals and humans show that vitamin C deficiency results in poor wound healing, and vitamin C supplementation in deficient individuals shows significant benefits . Although vitamin C levels appear to increase collagen synthesis and decrease inflammatory responses at the site of the wound, neither vitamin C supplementation or increased plasma vitamin C status increases wound closure time in otherwise healthy individuals. This suggests that vitamin C may only affect specific facets of the wound healing response. Topical ascorbic acid has not been properly evaluated prior to or during wound healing in humans.
Vitamin C is included in oral therapies for pressure ulcers (bed sores) and burns, along with vitamin E, zinc, and other nutritive factors .
Higher intakes of dietary vitamin C have been correlated with a decreased risk of dry skin , suggesting that ascorbic acid may have effects on trans-epidermal water loss (TEWL). In cell culture models, addition of vitamin C promotes the synthesis of barrier lipids, which would establish a functioning stratum corneum with low water permeability . One study using topical vitamin C in human subjects correlated its use with decreased skin roughness . However, another study suggested vitamin C increased TEWL when applied to the skin . Thus, the effects of vitamin C on skin dryness are not clear.
Environmental pollutants, such as ozone, can decrease vitamin C levels in the skin and lead to free radical damage. Smoking also leads to increased wrinkling and decreased collagen synthesis, which corresponds to a decline in plasma vitamin C levels ; however, it is unclear if this correlates to lower vitamin C levels in skin. Topical ascorbic acid has not been evaluated against pollution-related damage.
Topical vitamin C may be useful against acne to reduce inflammatory lesions. However, studies have primarily focused on the use of sodium ascorbyl phosphate, a synthetic derivative that may be poorly absorbed by the skin . Topical vitamin C may also have mild skin lightening effects that are caused by reductions in melanin production and melanin oxidation.
Vitamin C is an essential part of skin health both as a small molecular weight antioxidant and as a critical factor for collagen synthesis. Vitamin C contributes to photoprotection, decreases photodamage, and is needed for adequate wound healing. Oral supplementation with vitamin C may help prevent UV-induced damage, especially in combination with supplemental vitamin E. Dietary vitamin C may also provide photoprotection, but the extent of the protective effects will require additional research. Topical application of vitamin C appears to be an effective route for delivering ascorbic acid to the skin because ascorbic acid appears to be taken up readily at an acidic pH. Despite inconsistencies in vitamin C preparations and study design, the data suggest that vitamin C is most effective in protecting against damage induced by UV light and also has utility in the treatment of photodamage and/or skin wrinkling. Although vitamin C appears to benefit dry skin and may support wound healing, further research is needed to determine the effect of vitamin C on both. Lastly, the greatest effects of vitamin C supplementation are seen when it is combined with other micronutrients, such as vitamin E and zinc.