Available in the diet through fresh vegetables (particularly green leafy vegetables), vegetable oils, grains, nuts, seeds, corn, soy, whole wheat flour, margarine, and in some meat and dairy products, vitamin E, or tocopherol, is the primary lipid-soluble antioxidant found in human skin (via sebum), membranes, plasma, and tissues that protects cells from oxidative stress.1-4 Vitamin E is often used to treat minor burns, surgical scars, and other wounds, although the Food and Drug Administration has not approved its use for skin conditions.
In 1938, Karrer, Fritzsche, Ringier, and Salomon became the first to synthesize alpha-tocopherol,5,6 the main biologically active form of vitamin E.7 In the 1940s, vitamin E was labeled a “chain-breaking” antioxidant for its role in hindering the chain reaction induced by free radicals, and it is known to protect cutaneous cell membranes from peroxidation.8 Most topical formulations contain synthetic laboratory-made alpha-tocopherol or one of its many esters or ethers. As an ingredient in skin care agents, significant evidence has been amassed to suggest that topically applied vitamin E confers photoprotective activity against erythema, edema, sun burn cell formation, and other indicators of acute UV-induced damage as well as responses to chronic UVA and UVB exposure, including skin wrinkling and skin cancer.2,9-14 This column will focus on the topical applications of vitamin E.
Topical uses and findings
The lipophilic nature of vitamin E makes it suitable for topical application and percutaneous absorption through the skin.9,15 Vitamin E is generally used in 1%-5% concentrations alpha-tocopherol or tocopherol acetate in over-the-counter products.16 When topically applied, vitamin E has been shown to hydrate the stratum corneum (SC) and improve water-binding capacity.16 It is also considered an effective ingredient for imparting skin protection and treating atopic dermatitis (AD).2
In 2005, Ekanayake-Mudiyanselage et al. studied whether one application of an alpha-tocopherol–enriched rinse-off product could effectively lead to deposition of alpha-tocopherol on the SC in 13 volunteers. The researchers found that the alpha-tocopherol product raised alpha-tocopherol levels in surface lipids, which remained consistent for at least 24 hours, whereas such levels were reduced in the alpha-tocopherol–free vehicle control group. The alpha-tocopherol rinse-off product also significantly inhibited photo-oxidation of squalene.7
A 2009 6-month study in healthy human volunteers with actinic keratoses demonstrated that while topically applied dl-alpha-tocopherol, of which cutaneous levels were significantly increased at the end of the study, did not significantly change already present lesions, alterations in polyamine metabolism revealed that squamous cell carcinogenesis potential was significantly diminished.17
Patrizi et al., in a 2015 randomized, controlled, double-blind, single center study, assessed the safety and efficacy of MD2011001 cream (a nonsteroidal topical cream including vitamin E, epigallocatechin gallate and grape seed procyanidins) versus placebo, in 44 patients with mild to moderate AD in the perioral/periocular area and/or the neck. The researchers noted a significantly more rapid reduction in affected surface area with the test formulation, compared with placebo; the product was found to be well tolerated and safe as well as effective for mild to moderate AD.18
Also that year, Ruiz-Tovar et al. performed a prospective randomized clinical trial in 60 patients, showing that topical vitamin E ointment reduced postoperative pain.19
The vitamin C, vitamin E, ferulic acid combination
Vitamin E is perceived to be more effective when used in combination with other antioxidant ingredients. Some data suggest a cumulative beneﬁt derived from using oral and topical antioxidant products in combination, including vitamins C and E in particular.20-22 Because vitamin C can restore oxidized vitamin E, combining the antioxidants is a stabilizing factor in topical formulations.23,24 Further, ferulic acid has been shown to stabilize both vitamins, with the topical combination yielding photoprotective effects against UVB exposure, including the significant reduction in thymine dimer formation.9,24,25
A small study of nine patients conducted by Murray et al. in 2008 found that a stable topical preparation of 15% l-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid protected human skin in vivo from UV-induced damage, specifically erythema and apoptosis. The formulation also suppressed p53 activation and limited thymine dimer mutations, which are associated with skin cancer.26
Waibel et al. conducted a double-blind, prospective, single-center, randomized split-face trial in 2015 to study whether laser-assisted delivery of vitamins C and E and ferulic acid after fractional ablative laser procedures to treat photodamage could enhance wound healing. Fifteen healthy men and women (aged 30-55 years) were treated with the combination formulation on one side of the face and vehicle on the other side within 2 minutes of receiving fractional ablative CO2 laser surgery. They also received daily treatments and evaluations during days 1 through 7 of healing. Edema was found to be diminished on the sides treated with the antioxidant combination, compared with vehicle on day 7, and erythema, on days 3 and 5.27