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Although there are hundreds of naturally-occurring antioxidants, most of those currently used in the cosmetic industry are believed to work synergistically to regenerate and enhance the power of each other The antioxidants that have been identified as working cooperatively have been referred to as network antioxidants17 For example, after an antioxidant disarms a free radical by eliminating the odd number of electrons (by either adding or removing an electron), it is unable to function further as an antioxidant unless it is recycled The five antioxidants that have been labeled as network antioxidants are vitamins C and E, glutathione, lipoic acid, and Coenzyme Q10 (CoQ10) Vitamin C or CoQ10 can recycle vitamin E, donating electrons to vitamin E to return the nutrient to its antioxidant state Vitamin C and glutathione can be recycled by lipoic acid or vitamin C These network antioxidants are being included in an increasing number of cosmetic preparations It is likely that many antioxidants work synergistically, and that the term network antioxidant applies to many more antioxidants than the five identified as the network
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These are found in the lipophilic portion of the cell membrane and include vitamin E, carotenoids, and CoQ10 Further, idebenone, the synthetic analog of CoQ10, and food-derived lycopene are also fat-soluble antioxidants
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FIGURE 34-1 Tocopherol
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studies on elderly subjects that exhibit high plasma tocopherol levels23 25 For this reason, vitamin E is considered by many to be a necessary and powerful antioxidant In addition, vitamin E seems to offer photoprotection when taken orally and applied topically Numerous reports indicate that the topical application of alpha-tocopherol to animal skin is effective in lowering the production of sunburn cells,26,27 reducing the damage caused by chronic UVB exposure,28,29 and inhibiting photocarcinogenesis30 Specifically, researchers have found that oral and topical vitamin E supplementation in certain animals diminishes the effects of photoaging, inhibits the development of skin cancer, and counteracts immunosuppression induced by UV radiation30 33 In 1992, Trevithick et al noted that topical d- tocopherol acetate diminished erythema because of sunburn, edema, and skin sensitivity in mice when application occurred following exposure to UVB radiation34 In a study in which tocopherol 5% was applied to mice prior to UVB exposure, Bissett et al observed a 75% decrease in skin wrinkling, a rise in tumor latency, and a reduction of cutaneous tumors; however, vitamin E failed to affect UVA-induced skin sagging35 In a different study in which subjects applied tocopherol (5% 8%) cream facially for 4 weeks, Mayer observed diminished skin roughness, shorter length of facial lines, and reduced wrinkle depth as compared to placebo36 Oral and topical administration of vitamin E have been demonstrated to inhibit UV-induced erythema and edema in animals37 In humans, it has been shown that UV-induced expression of human macrophage metalloelastase, a member of the MMP family involved in degradation of elastin, could be inhibited by pretreatment with vitamin E (5%) In this study, vitamine E was applied to the skin under light-tight occlusion 24 hours before UV treatment38 A double-blind, placebo-controlled study examined the protective effects of orally administered vitamin E [400 international units (IU) per day] against UVinduced epidermal damage in humans The subjects were followed for a 6-month period Minimal erythema dose (MED) and histologic response were determined at baseline, 1 month, and 6 months In this study, there was no significant difference between the placebo group and those treated with vitamin E and the investigators concluded that daily ingestion of 400 IU of oral alphatocopherol daily did not provide any
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meaningful photoprotection39 Other authors have suggested that if vitamin E provides any photoprotection at all, it may require interaction with other antioxidants, such as vitamin C, to do so40 This notion was supported by the study of Lin et al who showed in Yorkshire pigs that the combined application of 1% -tocopherol with 15% Lascorbic acid provided superior protection against erythema and sunburn cell formation compared to either 1% alphatocopherol or 15% L-ascorbic acid alone41 WOUND HEALING Oxygen radicals form in response to injury and further inhibit recovery by attacking DNA, cellular membranes, proteins, and lipids It is believed that antioxidants act to ameliorate wounds by reducing the damage induced by free oxygen radicals, which are released by neutrophils in the inflammatory phase of the healing process42 In the late 1960s, Kamimura et al performed quantitative research demonstrating that topically applied vitamin E penetrates into the deep dermis and subcutaneous tissue43 Numerous scientists, as well as many laypersons, have interpreted this to mean that topically applied vitamin E may improve wound healing Contradictory results have emerged from animal studies undertaken to evaluate the effects of vitamin E on wound healing, however This may be explained by the fact that unlike other vitamins, tocopherols exhibit species-specific mechanisms of action44 In a prospective, double-blind, randomized study on humans, Jenkins et al tried to diminish scarring in burn patients following reconstructive surgery by applying topical vitamin E The researchers observed no difference between the control and treatment groups, however, and nearly 20% of the patients reported local reactions to the vitamin E cream45 In another study,46 the primary author and a collaborator assessed the cosmetic benefit resulting from the use of topically applied vitamin E to surgical scars In a double-blind fashion, patients applied 320 IU of dtocopheryl/gram of Aquaphor to one side of the scar and Aquaphor alone to the other side of the scar The patients were followed for 6 months At the conclusion of the study, the vitamin E preparation failed to improve the cosmetic appearance of surgical scars, and even made the scars worse in a few subjects FORMS OF VITAMIN E Vitamin E is a family of compounds called tocopherols, includ-
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ing, as mentioned above, alpha-, beta-, gamma-, and delta-tocopherol Alphatocopherol is the most active form and the form on which the recommended daily allowance (RDA) is based The names of all types of vitamin E begin with either d or dl, designations that refer to differences in chemical structure The d form is the natural form and dl is the synthetic form The natural form is more active and better absorbed Synthetic vitamin E supplements contain only alpha-tocopherol, while food sources contain several different tocopherols, including alpha-, delta-, and gamma-tocopherol Vitamin E forms are listed as either tocopherol or the esterified tocopheryl followed by the name of the substance to which it is attached, as in tocopheryl acetate The two forms are very similar but tocopherol displays better absorption, while tocopheryl forms exhibit slightly better shelf life In health food stores, the most common oral forms of vitamin E are d- tocopherol, d- tocopheryl acetate, and alpha-tocopheryl succinate The vitamin E forms typically used in cosmetics are alphatocopheryl acetate and alpha-tocopheryl linoleate These compounds are less likely to elicit contact dermatitis than dtocopheryl and are more stable at room temperature However, the tocopherol esters are also more poorly absorbed by the skin than the tocopherol forms,47 and may not exert the same photoprotective effects One study demonstrated that alpha-tocopheryl acetate or alphatocopheryl succinate not only failed to prevent photocarcinogenesis, but also may have enhanced it48 Because the alpha-tocopherol esters are included in many skin lotions, cosmetics, and sunscreens, further studies are needed to determine if the tocopherol esters indeed promote or contribute to photocarcinogenesis SIDE EFFECTS The primary author s study46 as well as the one by Jenkins45 suggest that the incidence of contact dermatitis because of topical vitamin E application may be relatively high for certain forms of tocopherol45 Tocopherol acetate seems to be the worst culprit,49 but allergy to dl- -tocopheryl nicotinate has also been reported50 In 1992, Swiss researchers evaluated 1000 cases of an atypical papular and follicular contact dermatitis provoked by vitamin E linoleate that was an additive to cosmetics The conclusion was that oxidized vitamin E derivatives can operate synergistically in vivo as haptens or as irritants51
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The topical application of vitamin E has also been linked with contact urticaria, eczematous dermatitis, and erythema multiforme-like reactions52 The recommended dose of oral vitamin E is 22 IU per day; however, many physicians recommend 400 IU twice per day In 1988, a thorough literature review by Bendich and Machlin found extended use of oral vitamin E up to 3000 mg/d to be safe53 A subsequent study by Kappus and Diplock established as absolutely safe vitamin E doses up to 400 mg/d, doses between 400 mg and 2000 mg as unlikely to cause adverse reactions, and doses greater than 3000 mg/d over an extended period as a potential source of side effects54 Because vitamin E can contribute to a blood-thinning effect, patients on anticoagulant therapy are advised to avoid high doses of vitamin E ( 4000 IU)55 Although there is likely no clinically significant reduction in platelet aggregation in those with normal platelets, patients are frequently advised to suspend vitamin E supplementation prior to surgery This is essential for patients with abnormal platelets, vitamin K deficiency, or those taking antiplatelet agents56 SUMMARY Vitamin E has been used to treat or protect against various dermatologic conditions including skin cancer, dystrophic epidermolysis bullosa, discoid lupus erythematosus, yellow nail syndrome, granuloma annulare, atopic dermatitis, pemphigus, and lichen sclerosus et atrophicus, among others37 Results have varied just as widely as the range of diseases treated In fact, some authors have reported that the use of oral vitamin E will reduce the side effects of retinoids57; however, other studies have not shown this benefit58 The most promising reason for research into the dermatologic use of vitamin E appears to be its antioxidant activity The potency of vitamin E as an antioxidant can be increased through combination with other antioxidants Vitamin E also appears to offer a ripe area for research into its potential for therapeutic benefit in the prevention and treatment of skin cancer and photoaging In addition, vitamin E displays emollient properties, and is stable, easy to formulate, and relatively inexpensive, rendering it a popular additive to antiaging preparations
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