Vitamin E2

Vitamin is the major lipophilic antioxidant in skin, and it is the most commonly used natural antioxidant in topical formulations. It is found in all parts of the skin, the dermis,

and epidermis, as well as in the stratum corneum, and is believed to play an essential role in the protection of biomolecules from oxidative stress.

Vitamin E is a family of 8 naturally occurring isoforms: four tocopherols (a-, 0-, Y-, 8-form) and four tocotrienols (a-, 0-, y-, 8-form) (Fig. 1) [1]. All forms consist of a chromanol nucleus that carries the redox-active phenolic hydroxyl group, and a lipophilic tail. While tocopherols contain a phytil side chain, the isoprenoid tail of the tocotrienols is polyunsaturated, making the chain more rigid. The side chain is anchored in lipid membranes while the nucleus is located at the lipid/aqueous interface. Even though the radical scavenging activity of the different isoforms is essentially identical, their biological activity after oral administration differs dramatically [2]. This phenomenon can be explained by the existence of an a-tocopherol transfer protein in the liver that positively selects RRR-a-tocopherol and incorporates it into VLDL which leads to recirculation of the a-tocopherol pool, while this transfer protein does not recognize the other forms, which are therefore excreted more rapidly [3].

In skin, as in the other human organs, a-tocopherol is the predominant form of vitamin E with 5 to 10 higher concentrations than y-tocopherol. Delivery of vitamin E to the SC occurs in two different modes. On the one hand it stored into differentiating kera-tinocytes and moves up into the newly formed SC, which leads to a gradient-type distribution of a-tocopherol with decreasing concentrations towards the skin surface [4]. On the other hand, vitamin E is secreted by sebaceous glands and reaches the SC from the outside. In sebaceous gland-rich regions like the face, this delivery mechanism is responsible for the enrichment of the outer SC with vitamin E [5].

Various oxidative stressors have been shown to deplete vitamin E, among other antioxidants. In the epidermis, a dose of at least four minimal erythemal doses (MED) of solar simulated UV radiation (SSUV) is needed to deplete vitamin E [6], while doses as low as 0.75 MED are capable of destroying vitamin E in the human SC [4]. Mouse experiments have shown that a dose of 1 ppm X 2h of ozone (O3) depletes SC vitamin E [7]. Since this concentration of O3 is higher than the naturally occuring levels of tropospheric O3 the biological relevance of these findings for the skin of humans is not yet clear. A one time application of benzoyl peroxide BPO (10% w/v), a concentration commonly used in the treatment of acne, depleted most of the SC vitamin E in human volunteers [8].

Figure 1 Naturally occurring forms of vitamin E. Tocopherols contain a saturated side chain (a), whereas the isoprenoid side chain of tocotrienols is polyunsaturated (b). The a-forms contain both methyl groups on the chromanol nucleus (1,2), whereas the 0-forms contain only methyl group (1), the y-forms only (2), and the S-forms none.

Figure 1 Naturally occurring forms of vitamin E. Tocopherols contain a saturated side chain (a), whereas the isoprenoid side chain of tocotrienols is polyunsaturated (b). The a-forms contain both methyl groups on the chromanol nucleus (1,2), whereas the 0-forms contain only methyl group (1), the y-forms only (2), and the S-forms none.

a-Tocopherol is widely used as an active ingredient in topical formulations. After topical application, it penetrates readily into skin [9]. Since the free form of vitamin E is quite unstable and light-sensitive (it absorbs in the UV-B range), the active hydroxyl group is usually protected by esterification with acetate. This increases the stability but renders the compound redox inactive. When administered orally, vitamin E-acetate is hydrolyzed quantitatively in the intestines [10]. There is some controversy however as to whether a-tocopherol acetate can by hydrolyzed in human skin. Chronic application of a-tocopherol acetate leads to an increase in free vitamin E in both the rat [11] and the mouse [12], where it was recently shown that UV-B increases the hydrolysis of a-tocopherol acetate by induction of nonspecific esterases up to 10 to 30 fold [13]. While one study suggested that bioconversion of a-tocopherol acetate does not occur in human skin [14], significant hydrolysis was demonstrated in recent studies using a human epidermis-tissue culture model [15].

The availability of the free form of vitamin E needs to be considered when analyzing possible health benefits. The majority of studies have been carried out in animal models, while only limited data exists for human studies. Lipid peroxidation is inhibited after topical application of a-tocopherol [16]. Several studies indicate that topically applied a-tocopherol inhibits UVB-induced photodamage of DNA in a mouse model [17] and keratinocyte cultures (trolox) [18]. Protection against Langerhans cell depletion by UV light was observed after topical application of a-tocopherol in a mouse model [19]. a-Tocopherol and its sorbate ester were studied in a mouse model of skin aging. Both antioxi-dants were found to be effective, sorbate even more so than a-tocopherol [20]. Systemic administration of vitamin E in humans (only in combination with vitamin C) increased the MED and reduced changes in skin blood flow after UV-irradiation [21,22]. Yet several studies indicate that a-tocopherol acetate is not as effective as free vitamin E when applied topically. Inhibition of DNA mutation in mice was 5 to 10 times less effective [18]. Also, in a mouse model, unlike free vitamin E, the acetate form seemed to be ineffective [23]. In summary, even though some health benefits of vitamin E supplementation have been shown, there is still a need for controlled studies in humans under physiological conditions.

Recently, the tocotrienol forms of vitamin E have become a focus of interest, since they have been found to be more efficient antioxidants in some model systems than tocoph-erols [24]. Even if they are not bioavailable after oral supplementation, topical application circumvents the exclusion by a-TTP in the liver. In fact, free tocotrienols readily penetrate into mouse skin [9], and tocotrienyl acetate is hydrolyzed in skin homogenates and in murine skin in vivo [25]. Topical application of a tocotrienol-rich fraction has been demonstrated to protect mouse skin from UV- and O3-induced oxidative stress [26,27]. In conclusion, tocotrienols bear a potential that yet remains to be explored.

Sultry Skin

Sultry Skin

Get All The Support And Guidance You Need To Be A Success At Sultry Skin. This Book Is One Of The Most Valuable Resources In The World When It Comes To Having Beautiful Skin.

Get My Free Ebook

Post a comment