Vitamin E was first described in 1922 by Herbert M Evans and Katherine Bishop. In 1936, it was biochemically characterized and named tocopherol (Greek: “tocos” meaning offspring and “phero” meaning to bring forth).
SOURCES AND FORMS OF VITAMIN E
Vitamin E is synthesized by plants and must be obtained through dietary sources. Richest sources are nuts, spinach, whole grains, olive oil, and sunflower oil.
There are eight types of vitamin E (α-,β-,γ-, and σ-tocopherols and their related corresponding tocotrienols), γ-tocopherol being the most abundant tocopherol in diet, whereas α-tocopherol (α-Toc) is the most abundant vitamin E derivative in human tissues and sera.
VITAMIN E AND EPIDERMIS: MOLECULAR ASPECTS
γ-Tocopherol levels exceeding those of α-Toc in human skin, inhibits the production of PGE2 and nitric oxide, and also prevents sunburn cell formation, ultraviolet (UV) B-induced lipid peroxidation and edema, wherefore it has a role in epidermal protection from oxidative stress. Vitamin E also has a role in photoadduct formation and immunosuppression.
STABILITY OF VITAMIN E
Stability of vitamin E depends on its form, dl-α-Toc acetate being the most stable.
Vitamin E, occurring naturally in food in the form of α-Toc oxidizes slowly when exposed to air. The stability of topical vitamin E may be increased by the use of vitamin E conjugates, which are esters of tocopherol, resistant to oxidation but can still penetrate skin layers.
Although many cosmeceuticals contain vitamins C and E, very few are actually effective in topical application because the stability is compromised as soon as the product is opened and exposed to air and light.
However when a stable formulation delivers a high concentration of nonesterified, optimal isomer of the antioxidant, vitamins C and E inhibit the acute UV damage as well as chronic UV photoaging and skin cancer.
Ferulic acid is a ubiquitous plant antioxidant and its incorporation into a topical solution of 15% l-ascorbic acid and 1% of α-Toc improves chemical stability of the vitamins (C + E) and doubles photoprotection to solar-stimulated irradiation of skin from fourfold to eightfold.
Yellow nail syndrome: (Level of evidence IV)
The yellow nail syndrome includes slow growing, opaque yellow nails with exaggerated yellow curvature, lymphedema, and chronic respiratory disorders such as chronic bronchitis, pleural effusions, and chronic sinusitis. Vitamin E is one of the treatment modalities for yellow nail syndrome, in a dosage of 1000 IU once a day for a period of 6 months.
Dapsone-induced hemolysis and headache: (Level of evidence IV)
In various studies to ascertain the protective effect of Vitamin E on the hemolysis associated with dapsone treatment, it was seen that (dl-α-tocopheryl acetate) in a dose of 800 IU/day confers a partial protective effect against dapsone-induced hemolysis in patients with dermatitis herpetiformis. Vitamin E has also been used in dapsone-induced headache.
Headache is a recognized effect of methemoglobinemia, and reduction of previously elevated methemoglobin concentration is presumably the mechanism by which vitamin E improves this symptom, as improved methemoglobin concentration seems to be the most consistent laboratory parameter in studies of vitamin E for protection against dapsone side effects.
Subcorneal pustular dermatoses: (Level of evidence IV)
Vitamin E (d-α-tocopheryl acetate) 100 IU/day, gradually increasing to 400 IU/day for 4 weeks is one of the therapeutic modalities in subcorneal pustular dermatoses, particularly those showing unsatisfactory response to conventional medications.
Cutaneous amyloidosis: (Level of evidence IV)
Tocoretinate is a hybrid compound of retinoic acid and tocopherol. In a study designed to evaluate the effects of topical tocoretinate on lichen amyloidosis and macular amyloidosis, it was concluded that topical tocoretinate reduces the clinical symptoms of lichen and macular amyloidosis.
Other dermatological indications for which there is little utility for the use of Vitamin E
A single-blind, placebo-controlled study was performed by Tsoureli-Nikita et al. in which 96 atopic dermatitis patients were treated with either placebo or oral vitamin E (400 IE/day) for 8 months. They found an improvement and near remission of atopic dermatitis and a 62% decrease in serum IgE levels in the vitamin E-treated group. Vitamin E decreases serum levels of IgE in atopic subjects. The correlation between vitamin E intake, IgE levels, and the clinical manifestations of atopy indicate that vitamin E could be a therapeutic tool for atopic dermatitis.
In 1975, Ayres and Mihan reported control of the condition of three patients with Hailey–Hailey disease by oral administration of vitamin E in the form of d-α-tocopheryl acetate in doses of 800–1200 IU/L. The exact mechanism by which Vitamin E controls this disease is unknown, but its antioxidant action in protecting cell membrane from lipid peroxidation, thus perhaps preventing the formation of autoimmune antibodies, may be an important factor.
Several case reports suggest efficacy of vitamin E (300–600 IU/day) for the management of epidermolysis bullosa. Vitamin E acts as an antioxidant, thus protecting the cell membranes and intracellular organelles from lipid peroxidation. It is possible that in case of epidermolysis bullosa, there is a genetic defect that effects the storage of Vitamin E in the tissues or in the ability of tissues to use it, which necessitates an additional supply.
A natural product, called “Mirak,” for the treatment of psoriasis has recently become available in many European countries. Mirak consists of natural spring water, valconic earth, and vitamin E cream. It induces a modest therapeutic effect compared with placebo, without any significant side effects, but may not be able to compete with the already existing treatment options for psoriasis.
Vitamin E has been seen to be useful in the treatment of pressure sores in doses of 800 IU/L gradually increasing to 1600 IU/L in four patients.
Skin cancer prevention
Mouse studies reported inhibition of UV-induced tumors in mice fed with α-tocopherol acetate. Multiple human studies have shown no effects of vitamin E on the prevention or development of skin cancers.
Vitamin E along with zinc and vitamin C, is included in oral therapies for pressure ulcers and burns. The antioxidant supplementation through vitamins E and C and the mineral zinc has been seen to apparently enhance the antioxidant protection against oxidative stress and allow less time for wound healing.
Vitamin E alone has shown minimal efficacy in the treatment of melasma. It has been shown to cause depigmentation by interference with lipid peroxidation of melanocyte membranes, increase in intracellular glutathione content, and inhibition of tyrosinase.
In a randomized, double-bind, placebo-controlled trial, a combination of oral proanthocyanidin plus vitamin A, C, and E was assessed in 60 Phillipino females with bilateral epidermal melasma. The antioxidants were taken twice a day for 8 weeks and were compared with placebo intake by mexametric and Melasma Area and Severity (MASI) score analysis. There was a significant reduction in MASI scores and pigmentation by mexametry in malar regions.
Pycnogenol is a standardized extract of the bark of the French maritime pine (Pinus pinaster), a well-known, potent antioxidant, several times more powerful than vitamin E and in addition, regenerates vitamin E and increases the endogenous antioxidant enzyme system. Therefore its efficacy in the treatment of melasma was investigated in a clinical study in which 30 women with melasma took one 25 mg tablet of pycnogenol with meals three times daily, that is, 75 mg pycnogenol per day for a period of 30 days. These patients were evaluated clinically by parameters such as the melasma area index, pigmentary intensity index, and by routine blood and urine tests. After a 30-day treatment, the average melasma area of the patients decreased by 25.86 ± 20.39 mm (2) (P < 0.001) and the average pigmentary intensity decreased by 0.47 ± 0.51 unit (P < 0.001).
α-Toc derivatives inhibit tyrosinase in vitro and melanogenesis in epidermal melanocytes. The antioxidant properties of α-Toc, which interferes with lipid peroxidation of melanocyte membranes and increases the intracellular glutathione content, could explain its depigmenting effect.
In one of the studies conducted in a series of 98 patients, the emphasis was based on the correction of the defective keratinization of sebaceous follicles with a combination of vitamin E and vitamin C. This was seen to prevent the formation of comedones, thus depriving the Propionibacterium acnes of a culture medium. Vitamin E prevents lipid peroxidation of serum from bacterial-induced leakage through follicles and sebaceous glands, thus preventing inflammation due to peroxide irritation.
Vitamin E has also been used with high doses of isotretinoin to ameliorate isotretinoin-induced side effects. However, studies have demonstrated that vitamin E does not significantly ameliorate retinoid side effects when combined with isotretinoin in the treatment of acne.
Oxidative stress is significantly increased in patients with scleroderma when compared with the healthy controls, suggesting that free radical induced oxidative injury occurs in scleroderma. Antioxidants such as vitamin E might, therefore, be beneficial. Vitamin E is also believed to stabilize lysosomal membranes, potentially inhibiting events involved in the autoimmune process.
Vitamin E supplementation has resulted in improvement in the skin of scleroderma patients, although nondermatological aspects of scleroderma did not improve.
Various components of scleroderma, including morphea, calcinosis cutis, and Raynaud's phenomenon respond to vitamin E. The dose of vitamin E in these reports ranged from 200 to 1200 IU per day.
One patient successfully treated was a 45-year-old man with Raynaud's phenomenon, probable early scleroderma, and ulceration and gangrene of the fingertips. He received 800 IU oral vitamin E daily and applied the vitamin (50 IU per mL) to the ulcerated fingers twice daily. The ulcerations became less painful after two weeks and healed almost completely within one month.
Dermatological indications for which there are anecdotal reports of beneficial effects of vitamin E
Chronic cutaneous lupus erythematosus
Porphyria cutanea tarda.
Recommended dose of vitamin E
In case of vitamin E, the recommended intake (6–10 mg of α-tocopherol or the equivalent) is based solely on an estimate of how much tocopherol the average person consumes. In a healthy adult who had been on a normal diet it would take an estimated 4 years to fully deplete body stores of vitamin E.
TOPICAL VITAMIN E IN DERMATOLOGY
Topical vitamin E has emerged as a popular treatment for a number of skin disorders owing to its antioxidant properties. It has been seen that reactive oxygen species have the ability to alter the biosynthesis of collagen and glycosaminoglycans in skin. Most of the over-the-counter antiaging creams contain 0.5%–1% of vitamin E.
One of the most popular applications of vitamin E is the treatment of burns, surgical scars, and wounds. However, studies looking at the efficacy of vitamin E in the treatment of burns and scars have been disappointing.
Topical vitamin E has also been found to be effective in granuloma annulare. Vitamin E is one of the ingredients in over-the-counter treatments of skin aging. Topical application of the gel containing 2% phytonadione, 0.1% retinol, 0.1% vitamin C, and 0.1% vitamin E has been seen to be fairly or moderately effective in reducing dark under-eye circles, especially in cases of hemostasis.
VITAMIN E INTAKE DURING PREGNANCY AND CHILDHOOD
Vitamin E supplements in pregnancy usually contain only small doses of vitamin E, although adverse effects have not been observed even at higher doses. Theoretically, however, due to the involvement of cytochrome P450 system in the metabolism of orally supplemented RRR-α-tocopherol, drug interactions have to be taken into account when supranutritional doses of Vitamin E are provided. There is no published report documenting adverse fetal effects due to use of topical vitamin products.
Most of the people do not experience any side effects when taking the recommended daily dose. High dose can cause nausea, diarrhea, stomach cramps, fatigue, weakness, headache, blurred vision, rash, bruising, and bleeding.
Vitamin E being a fat-soluble vitamin, administration of a dose higher than daily requirement results in accumulation inside the body, resulting in hypervitaminosis E. Healthy adults taking vitamin E daily at a dose of 100 mg for more than 1 year are likely to get hypervitaminosis E, manifesting as reduced platelet aggregation and interference with vitamin K metabolism resulting in bleeding tendencies.
Topical application of vitamin E can rarely cause contact dermatitis, erythema multiforme, and xanthomatous reaction.
CONTRAINDICATIONS OR SPECIAL PRECAUTIONS
There are no contraindications to the use of vitamin E. Patients with coagulation disorders or taking anticoagulant medications should be monitored for increased bleeding tendencies.
Despite development of new formulations for use in cosmetics and skin care products, there is a lack of controlled clinical trials providing a rationale for well-defined dosages and clinical indications for oral and topical vitamin E. After so many years of research on vitamin E, it is still unclear as to whether millions of dollars worth of vitamin E products paid for by patients and consumers have been of any benefit. A better understanding of this vitamin may help in evaluating the indications and dosage regimens for the prevention and treatment of acute and chronic skin disorders.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
1. Evans HM, Emerson OH, Emerson GA. The isolation from wheat germ oil of an alcohol, alphatocopherol, having the properties of vitamin E
J Biol Chem. 1936;113:319–32
2. Fernholz E. On the constitution of α-tocopherol J Am Chem Soc. 1938;60:700–5
3. Bunnel RH, Keating J, Quaresimo A, Parman GK. Alpha-tocopherol content of foods Am J Clin Nutr. 1965;17:1–10
4. Jiang Q, Christen S, Shigenaga MK, Ames BN. Gamma-tocopherol, the major form of vitamin E
in the US diet, deserves more attention Am J Clin Nutr. 2001;74:714–22
5. Yoshida E, Watanabe T, Takata J, Yamazaki A, Karube Y, Kobayashi S. Topical application of a novel, hydrophilic gamma-tocopherol derivative reduces photo- inflammation in mice skin J Invest Dermatol. 2006;126:1633–40
6. Beharka AA, Wu D, Serafini M, Meydani SN. Mechanism of vitamin E
inhibition of cyclooxygenase activity in macrophages from old mice: Role of peroxynitrite Free Radic Biol Med. 2002;32:503–11
7. Thiele JJ, Hsieh SN, Ekanayake-Mudiyanselage S. Vitamin E
: Critical review of its current use in cosmetic and clinical dermatology Dermatol Surg. 2005;31:805–13
8. Thiele JJ, Ekanayake-Mudiyanselage S. Vitamin E
in human skin: Organ-specific physiology and consideration for its use in dermatology Mol Aspects Med. 2007;28:646–67
9. Burke KE, Clive J, Combs GF Jr, Commissoo J, Keen CL, Nakamura RM. Effects of topical and oral vitamin E
on pigmentation and skin cancer induced by ultraviolet irradiation in Skh: 2 hairless mice Nutr Cancer. 2000;38:87–97
10. Lin FH, Lin JY, Gupta RD, Tournas JA, Burch JA, Selim MA, et al Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin J Invest Dermatol. 2005;125:826–32
11. Ayres S Jr, Mihan R. Yellow nail syndrome: Response to vitamin E
Arch Dermatol. 1973;108:267–8
12. Norton L. Further observations on the yellow nail syndrome with therapeutic effect of oral alpha-tocopherol Cutis. 1985;36:457–62
13. Al Hawsawi K, Pope E. Yellow nail syndrome Pediatr Dermatol. 2010;27:675–6
14. Prussick R, Ali MA, Rosenthal D, Guyatt G. The protective effect of vitamin E
on the hemolysis associated with dapsone treatment in patients with dermatitis herpetiformis Arch Dermatol. 1992;128:210–3
15. Kelly JW, Scott J, Sandland M, Van der Weyden MB, Marks R. Vitamin E
and dapsone-induced hemolysis Arch Dermatol. 1984;120:1582–4
16. Cox NH. Vitamin E
for dapsone-induced headache Br J Dermatol. 2002;146:174
17. Ayres S Jr, Mihan R. Letter: Subcorneal pustular dermatoses controlled by vitamin E
Arch Dermatol. 1974;109:914
18. Terao M, Nishida K, Murota H, Katayama I. Clinical effect of tocoretinate on lichen and macular amyloidosis J Dermatol. 2011;38:179–84
19. Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. Evaluation of dietary intake of vitamin E
in the treatment of atopic dermatitis: A study of the clinical course and evaluation of the immunoglobulin E serum levels Int J Dermatol. 2002;41:146–50
20. Ayres S Jr. Hailey-Hailey disease: Response to vitamin E
therapy Arch Dermatol. 1983;119:450
21. Ayres S Jr, Mihan R. Is Vitamin E
involved in the autoimmune mechanism? Cutis. 1978;21:321–5
22. Sehgal VN, Vadiraj SN, Rege VL, Beohar PC. Dystrophic epidermolysis bullosa in a family: Response to vitamin E
(tocopherol) Dermatologica. 1972;144:27–34
23. Ayres S Jr. Epidermolysis bullosa controlled by vitamin E
Int J Dermatol. 1986;25:670–1
24. Sehgal VN, Sanyal RK. Vitamin E
therapy in dystrophic epidermolysis bullosa Arch Dermatol. 1972;105:460
25. Seyger MM, van de Kerkhof PC, van Vlijmen-Willems IM, de Bakker ES, Zwiers F, de Jong EM. The efficacy of a new topical treatment for psoriasis: Mirak J Eur Acad Dermatol Venereol. 1998;11:13–8
26. Hauch JT. A new treatment for resistant pressure sores Can Med Assoc J. 1957;77:125–8
27. Gerrish KE, Gensler HL. Prevention of photocarcinogenesis by dietary vitamin E
Nutr Cancer. 1993;19:125–33
28. van der Pols JC, Heinen MM, Hughes MC, Ibiebele TI, Marks GC, Green AC. Serum antioxidants and skin cancer risk: An 8-year community-based follow-up study Cancer Epidemiol Biomarkers Prev. 2009;18:1167–73
29. McNaughton SA, Marks GC, Green AC. Role of dietary factors in the development of basal cell cancer and squamous cell cancer of the skin Cancer Epidemiol Biomarkers Prev. 2005;14:1596–607
30. Ellinger S, Stehle P. Efficacy of vitamin supplementation insituations with wound healing disorders: Results from clinical intervention studies Curr Opin Clin Nutr Metab Care. 2009;12:588–95
31. Barbosa E, Faintuch J, Machado Moreira EA, Gonçalves da Silva VR, Lopes Pereima MJ, Martins Fagundes RL, et al Supplementation of vitamin E
, vitamin C, and zinc attenuates oxidative stress in burned children: A randomized, double- blind, placebo-controlled pilot study J Burn Care Res. 2009;30:859–66
32. Hayakawa R, Ueda H, Nozaki T, Izawa Y, Yokotake J, Yazaki K, et al Effect of combination treatments with vitamin E
and C on chloasma and pigmented contact dermatitis: A double blind controlled clinical trial Acta Vitaminol Enzymol. 1981;3:31–8
33. Badreshia-Bansal S, Draelos ZD. Insight into skin lightening cosmeceuticals for women of color J Drugs Dermatol. 2007;6:32–9
34. Handog EB, Galang DA, de Leon-Godinez MA, Chan GP. A randomized, double-blind, placebo-controlled trial of oral procyanidin with vitamins A, C, E for melasma among Filipino women Int J Dermatol. 2009;48:896–901
35. Ni Z, Mu Y, Gulati O. Treatment of melasma with Pycnogenol Phytother Res. 2002;16:567–71
36. Shimizu K, Kondo R, Sakai K, Takeda N, Nagahata T, Oniki T. Novel vitamin E
derivative with 4-substituited resorcinol moiety has both antioxidant and tyrosinase inhibitory properties Lipids. 2001;36:1321–6
37. Ichihashi M, Funasaka Y, Ohashi A, Chakraborty A, Ahmed NU, Ueda M, et al The inhibitory effect of DL-alpha-tocopheryl ferulate in lecithin on melanogenesis Anticancer Res. 1999;19:3769–74
38. Marmol VD, Solano F, Sels A, Huez G, Libert A, Lejeune F, et al Glutathione depletion increases tyrosinase activity in human melanoma cells J Invest Dermatol. 1993;101:871–4
39. Ayres S Jr, Mihan R. Acne vulgaris: Therapy directed at pathophysiologic defects Cutis. 1981;28:41–2
40. Strauss JS, Gottlieb AB, Jones T, Koo JY, Leyden JJ, Lucky A, et al Concomitant administration of vitamin E
does not change the side effects of isotretinoin as used in acne vulgaris: A randomized trial J Am Acad Dermatol. 2000;43:777–84
41. Kus S, Gün D, Demirçay Z, Sur H. Vitamin E
does not reduce the side-effects of isotretinoin in the treatment of acne vulgaris Int J Dermatol. 2005;44:248–51
42. Stein CM, Tanner SB, Awad JA, Roberts LJ 2nd, Morrow JD. Evidence of free radical-mediated injury (isoprostane overproduction) in scleroderma Arthritis Rheum. 1996;39:1146–50
43. Ayres S Jr, Mihan R. Vitamin E
and dermatology Cutis. 1975;16:1017–21
44. Ayres S Jr, Mihan R, Levan NE. Raynaud's phenomenon, scleroderma and calcinosis cutis: Response to vitamin E
45. Ayres S Jr, Mihan R. Lupus erythematosus and vitamin E
: An effective and nontoxic therapy Cutis. 1979;23:49–52 54
46. Ayres S Jr, Mihan R, Levan NE. Raynaud's phenomenon and possibly early scleroderma-response to vitamin E
Arch Dermatol. 1971;104:570–1
47. Ayres S Jr, Mihan R. Keratosis follicularis. (Darier's disease). Response to simultaneous administration of vitamins A and E Arch Derm. 1972;106:909–10
48. Ayres S Jr, Mihan R. Letter: Post-herpes zoster neuralgia: Response to vitamin E
therapy Arch Dermatol. 1973;108:855–6
49. Ayres S Jr, Mihan R. Pseudoxanthoma elasticum and epidermolysis bullosa: Response to vitamin E
(tocopherol) Cutis. 1969;5:287–94
50. Ayres S Jr, Mihan R. Porphyria cutanea tarda: Response to vitamin E
.A review and two case reports Cutis. 1978;22:50–2
51. Vitamin E
Med Lett Drugs Ther. 1975;17:69–70
52. Horwitt MK. Status of human requirements for vitamin E
Am J Clin Nutr. 1974;27:1182–93
53. Tanaka H, Okada T, Konishi H, Tsuji T. The effects of reactive oxygen species on the biosynthesis of collagen and glycosaminoglycans in cultured human dermal fibroblasts Arch Dermatol Res. 1993;285:352–5
54. Ashamalla L, Maurice M, Sidhom K. Topical vitamin E
in granuloma annulare Int J Dermatol. 1988;27:348
55. Chiu A, Kimball AB. Topical vitamins, minerals and botanical ingredients as modulators of environmental and chronological skin damage Br J Dermatol. 2003;149:681–91
56. Baumann LS, Spencer J. The effects of topical vitamin E
on the cosmetic appearance of scars Dermatol Surg. 1999;25:311–5
57. Jenkins M, Alexander JW, MacMillan BG, Waymack JP, Kopcha R. Failure of topical steroids and vitamin E
to reduce postoperative scar formation following reconstructive surgery J Burn Care Rehabil. 1986;7:309–12
58. Mitsuishi T, Shimoda T, Mitsui Y, Kuriyama Y, Kawana S. The effects of topical application of phytonadione, retinol and vitamins C and E on infraorbital dark circles and wrinkles of the lower eyelids J Cosmet Dermatol. 2004;3:73–5
59. Brigelius-Flohé R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A. The European perspective on vitamin E
: Current knowledge and future research Am J Clin Nutr. 2002;76:703–16
60. Toxic effects of vitamin overdosage. Med Lett Drugs Ther. 1984;26:73–4
61. Goldman MP, Rapaport M. Contact dermatitis to vitamin E
oil J Am Acad Dermatol. 1986;14:133–4
62. Saperstein H, Rapaport M, Rietschel RL. Topical vitamin E
as a cause of erythema multiforme-like eruption Arch Dermatol. 1984;120:906–8
63. Parsad D, Saini R, Verma N. Xanthomatous reaction following contact dermatitis from vitamin E
Contact Dermatitis. 1997;37:294