INTRODUCTION

Vitamin E was discovered in 1922 at the University of California in Berkeley by Evans and Bishop. ‘Tocopherol’ is derived from the Greek words ‘tocos’, meaning ‘offspring’, and ‘phero’, meaning ‘to provide a person with power’. While some antioxidants, such as glutathione or ubiquinol-10, can be synthesized by humans, vitamin E is supplied by oral intake only. The main natural sources of vitamin E are fresh vegetables, vegetable oils, cereals, and nuts. Recent studies suggest that the majority of men and women in the US fail to meet the current recommendations for vitamin E intake. The lipophilic antioxidant vitamin E has been used for more than 50 years in clinical and experimental dermatology. However, while 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 has led to the development of numerous new formulations for use in cosmetics and skin care products. This chapter reviews basic mechanisms and possible cosmeceutical as well as clinical implications of the recent advances in cutaneous vitamin E research.

TERMINOLOGY AND DEFINITIONS

Vitamin E is the major lipophilic antioxidant in plasma, membranes, and tissues. The term ‘vitamin E’ collectively refers to the eight naturally occurring molecules (four tocopherols and four tocotrienols) which exhibit vitamin E activity. Tocotrienols differ from tocopherols in that they have an isoprenoid instead of a phytyl side chain; the four forms of tocopherols and tocotrienols differ in the number of methyl groups on the chromanol nucleus (α- has three, β- and γ- have two, and δ- has one; Fig. 7.1). In humans, α-tocopherol is the most abundant vitamin E homolog, followed by γ-tocopherol. To compare the potency of different vitamin E derivates, their biologic activities are measured and compared to RRR-α-tocopherol. The potency is expressed as international units (IU) α-tocopherol equivalents (α-TE) and was developed for oral supplementation.

Fig. 7.1 Chemical structure of tocopherols and tocotrienols.

Tocopherols (α: R₁ = R₂ = CH₃, 430.7 g mol⁻¹; β: R₁ = CH₃, R₂ = H, 416.7 g mol⁻¹; γ: R₁ = H, R₂ = CH₃, 416.7 g mol⁻¹; δ: R₁ = R₂ = H, 402.7 g mol⁻¹);

Tocotrienols (α: R₁ = R₂ = CH₃, 424.7 g mol⁻¹; β: R₁ = CH₃, R₂ = H, 410.6 g mol⁻¹; γ: R₁ = H, R₂ = CH₃, 410.6 g mol⁻¹; δ: R₁ = R₂ = H, 396.6 g mol⁻¹)

INDICATIONS AND BIOLOGIC ACTIVITY

After more than half a century of research there is still little convincing evidence of vitamin E’s effectiveness in treating specific dermatologic disorders. In trials and case reports, oral vitamin E supplementation is recommended in the therapy of yellow nail syndrome, vibration disease, epidermolysis bullosa, cancer prevention, claudication, cutaneous ulcers, collagen synthesis, and wound healing. Clearly, with vitamin E not being a pharmaceutical, there is a lack of placebo-controlled studies for treatment of these conditions. However, in the field of skin care, which includes cosmeceuticals, there is a large body of experimental evidence pointing to, in particular, photoprotective effects (for review, see Table 7.1). Moreover, recent studies indicate that vitamin E may reveal dermatologic benefits that exceed the purpose of cosmetics and may extend into an area that has recently been termed ‘cosmeceuticals’.

Recently, Tsoureli-Nikita et al performed a clinical single-blind, placebo-controlled study in which 96 atopic dermatitis patients were treated with either placebo or oral vitamin E (400 IU/day) for 8 months. They found an improvement and near remission of atopic dermatitis and a 62% decrease in serum IgE levels based on initial conditions in the vitamin E-treated group. The correlation between α-tocopherol intake, IgE levels, and the clinical manifestations of atopy indicates that oral vitamin E could be an excellent therapeutic adjunct for atopic dermatitis (Tsoureli-Nikita et al 2002). Other multi-clinical double-blinded studies revealed a significant improvement of chloasma and pigmented contact dermatitis lesions using topical vitamins E and C, with the combination clearly proving superior to the single vitamin treatment groups. Topical formulations used for depigmentation that contain, besides the commonly used hydroquinone and sunscreen, vitamins C and E, appear to be safe and efficient. Further research in well-designed controlled trials is needed to clarify the role of vitamin E and its derivates in the above-mentioned and further skin disorders.

MECHANISMS OF ACTION

Vitamin E is among the early recognized biologic antioxidants, and its redox and free radical chemistry are well documented. The major antioxidant role of vitamin E is generally considered to be the arrest of chain propagation by scavenging lipid peroxyl radicals. The initial oxidation product of tocopherol is the metastable tocopheroxyl radical, which can be either reduced to tocopherol by co-antioxidants, or reacts with another lipid peroxyl radical, yielding tocopherol-quinone. Thus, one molecule of tocopherol has the ability to scavenge two peroxyl radical molecules. Since the physiologic molar ratio of tocopherols to polyunsaturated phospholipids, first-line targets of oxidative attack, is less than about 1 : 1000 in most biologic membranes, regeneration of tocopherol is essential for its high antioxidant efficacy in vivo. Several hydrophilic co-antioxidants, such as ascorbate and glutathione, can regenerate vitamin E from the tocopheroxyl radical and thus enhance the antioxidant capacity of vitamin E. Furthermore, there is some in vitro evidence that ubiquinol-10 (‘coenzyme Q’) protects α-tocopherol from photo-oxidation by recycling mechanisms. Hence, the lack of such ‘co-antioxidants’ from the antioxidant network may diminish the antioxidant properties of vitamin E and result in limited antioxidant protection of lipid bilayers or other lipophilic domains.