Vitamin E in human skin: organ-specific physiology and considerations for its use in dermatology.

Vitamin E has been used for more than 50 years in experimental and clinical dermatology. While a large number of case reports were published in this time, there is still a lack of controlled clinical studies providing a rationale for well defined dosages and clinical indications. In contrast, advances in basic research on the physiology, mechanism of action, penetration, bioconversion and photoprotection of vitamin E in human skin has led to the development of numerous new formulations for use in cosmetics and skin care products. This article reviews basic mechanisms and possible cosmetic as well as clinical implications of the recent advances in cutaneous vitamin E research. Experimental evidence suggests that topical and oral vitamin E has antitumorigenic, photoprotective, and skin barrier stabilizing properties. While the current use of vitamin E is largely limited to cosmetics, controlled clinical studies for indications such as atopic dermatitis or preventions of photocarcinogenesis are needed to evaluate the clinical benefit of vitamin E.

Vitamin E: critical review of its current use in cosmetic and clinical dermatology.

BACKGROUND AND OBJECTIVE: The lipophilic antioxidant vitamin E has been used for more than 50 years in clinical and experimental dermatology. However, although a large number of case reports were published, there is still a lack of controlled clinical studies providing a rationale for clinical indications and dosage. In contrast, advances in basic research on the physiology, mechanism of action, penetration, bioconversion, and photoprotection of vitamin E in human skin have led to the development of numerous new formulations for use in cosmetics and skin care products. RESULTS: This article reviews the basic mechanisms and possible cosmetical and clinical implications of the recent advances in cutaneous vitamin E research. Experimental evidence suggests that topical and oral vitamin E has anticarcinogenic, photoprotective, and skin barrier-stabilizing properties. CONCLUSION: Although its current use is largely limited to cosmetics, controlled clinical studies for indications such as atopic dermatitis or prevention of photocarcinogenesis are needed to evaluate the clinical benefit of vitamin E.

Oral supplementation with all-Rac- and RRR-alpha-tocopherol increases vitamin E levels in human sebum after a latency period of 14-21 days.

In human skin, highest alpha-tocopherol levels are found in facial sebum. We hypothesized that the bioavailability of vitamin E in human skin is, at least in part, dependent on sebaceous gland secretion. To test this, 24 volunteers were subjected to a randomized daily supplementation with either 400 mg RRR-alpha-tocopheryl acetate (RRR-alpha-toc) or 400 mg all-rac-alpha-tocopheryl acetate (all-rac-alpha-toc) for 14 days. Fasting blood samples, facial sebum samples, and lower-arm skin-surface lipids (SSL) were taken at time-points between 0-21 days. Samples were analyzed by HPLC for alpha-tocopherol and squalene concentrations. Increased serum alpha-tocopherol levels were detectable as early as 12 h after supplementation of RRR-alpha-toc or all-rac-alpha-toc and peaked on day 7. No significant changes were observed in lower-arm SSL. Remarkably, while unchanged until day 14, alpha-tocopherol sebum levels were increased on day 21 in both the RRR-alpha-toc and the all-rac-alpha-toc group by 87% and 92%, respectively. With respect to dietary supplementation of vitamin E and its bioavailability in human skin, these results suggest that (1) sebaceous gland secretion is a relevant delivery mechanism; (2) the bioavailabilities of RRR-alpha-toc and the all-rac-alpha-toc are similar; and (3) significant accumulation requires a daily supplementation period of at least 2-3 weeks.

Ultraviolet a induces generation of squalene monohydroperoxide isomers in human sebum and skin surface lipids in vitro and in vivo.

At the outermost surface of human skin, skin surface lipids are first-line targets of solar ultraviolet radiation. Therefore, we hypothesized that ultraviolet A and ultraviolet B irradiation induce photo-oxidation of skin surface lipids. To test this, sebum samples were collected from facial skin of 17 healthy volunteers, weighed, and immediately irradiated with either ultraviolet B or ultraviolet A. Squalene, the major sebum lipid, as well as photo-oxidation products were identified in sebum lipid extracts by high-performance liquid chromatography analysis. Upon ultraviolet A exposures squalene was depleted in a concentration-dependent manner, whereas an unidentified sebum lipid photo-oxidation product was detected. Using high-performance thin layer chromatography, high-performance liquid chromatography, atmospheric pressure chemical ionization mass spectrometry, and nuclear magnetic resonance, unidentified sebum lipid photo-oxidation product was identified as a mixture of squalene monohydroperoxide isomers. Squalene monohydroperoxide isomers purified from sebum were identical with squalene monohydroperoxide isomers synthesized by preparative photo-oxidation of squalene. Squalene monohydroperoxide isomers were formed even after small suberythematogenic doses of ultraviolet A (5 J per cm2). Whereas physiologic baseline levels of squalene monohydroperoxide isomers in human skin were only slightly above detection limits, squalene monohydroperoxide isomer levels were strongly increased by suberythematogenic doses of ultraviolet A both in vitro and in vivo. High-performance liquid chromatography results could be complemented by a straightforward thin layer chromatography method for rapid screening of lipid peroxide formation in human sebum/skin surface lipids. In conclusion, specific squalene monohydroperoxide isomers were identified as highly ultraviolet A sensitive skin surface lipid breakdown products that may serve as a marker for photo-oxidative stress in vitro and in vivo.

Photoaging is associated with protein oxidation in human skin in vivo.

There is increasing evidence for the generation of reactive oxygen species in skin upon ultraviolet exposure, but little is known about their pathophysiologic relevance in human skin in vivo. We hypothesized that chronic and acute photodamage is mediated by depleted antioxidant enzyme expression and increased oxidative protein modifications. Biopsies from patients with histologically confirmed solar elastosis, from non-ultraviolet-exposed sites of age-matched controls, and from young subjects were analyzed. To evaluate the influence of acute ultraviolet exposures, buttock skin of 12 healthy subjects was irradiated repetitively on 10 d with a solar simulator and compared intraindividually to non-ultraviolet-treated contralateral sites. The antioxidant enzymes catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase were investigated by immunohistochemistry. Protein carbonyls were analyzed by immunohistochemical and immunoblotting techniques in human skin and in cell models. Whereas overall expression of antioxidant enzymes was very high in the epidermis, low baseline levels were found in the dermis. In photoaged skin, a significant depletion of antioxidant enzyme expression was observed within the stratum corneum and in the epidermis. Importantly, an accumulation of oxidatively modified proteins was found specifically within the upper dermis of photoaged skin. Upon acute ultraviolet exposure of healthy subjects, depleted catalase expression and increased protein oxidation were detected. Exposures of keratinocytes and fibroblasts to ultraviolet B, ultraviolet A, and H2O2 led to dose-dependent protein oxidation and thus confirmed in vivo results. In conclusion, the correlation between photodamage and protein oxidation was demonstrated for the first time, which hence may be a relevant pathophysiologic factor in photoaging.