Vitamin E in Dermatology

Abstract

Vitamin E is an important fat‑soluble antioxidant and has been in use for more than 50 years in dermatology. It is an important ingredient in many cosmetic products. It protects the skin from various deleterious effects due to solar radiation by acting as a free‑radical scavenger. Experimental studies suggest that vitamin E has antitumorigenic and photoprotective properties. There is a paucity of controlled clinical studies providing a rationale for well‑defined dosages and clinical indications of vitamin E usage in dermatological practice. The aim of this article is to review the cosmetic as well as clinical implications of vitamin E in dermatology.
Key words: Cosmetic, dermatology, vitamin E

Full text

© 2016 Indian Dermatology Online Journal | Published by Wolters Kluwer - Medknow 311
Drug Prole
Department of
Dermatology, STD and
Leprosy, Government
Medical College and
Associated SMHS
Hospital, Srinagar,
Jammu and Kashmir,
India
ABSTRACT
VitaminEisanimportantfat‑solubleantioxidantandhasbeeninuseformorethan50yearsindermatology.
Itisanimportantingredientinmany cosmeticproducts.Itprotectstheskinfromvarious deleteriouseffects
dueto solarradiationby actingasa free‑radicalscavenger.Experimentalstudiessuggest thatvitaminE has
antitumorigenicandphotoprotective properties. Thereisapaucityofcontrolled clinical studies providinga
rationaleforwell‑deneddosagesandclinicalindicationsofvitaminEusageindermatologicalpractice.The
aimofthisarticleistoreviewthecosmeticaswellasclinicalimplicationsofvitaminEindermatology.
Key words:Cosmetic,dermatology,vitaminE
HISTORICAL PERSPECTIVE
Vitamin E was rst 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).[1,2]
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 sunower oil.[3]
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,[4] inhibits the production of PGE2
and nitric oxide, and also prevents sunburn
cell formation, ultraviolet (UV) B-induced lipid
peroxidation and edema,[5,6] wherefore it has
a role in epidermal protection from oxidative
stress. Vitamin E also has a role in photoadduct
formation and immunosuppression.[7]
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.[8]
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 nonesteried, optimal
isomer of the antioxidant, vitamins C and E
inhibit the acute UV damage as well as chronic
UV photoaging and skin cancer.[9]
Ferulic acid is a ubiquitous plant antioxidant
and its incorporation into a topical solution of
Vitamin E in dermatology
Mohammad Abid Keen, Iffat Hassan
Address for
correspondence:
Dr. Mohammad Abid
Keen,
Iqbal Abad, KP Road,
Anantnag ‑ 192 101,
Jammu and
Kashmir, India.
E‑mail: keenabid31@
gmail.com
Access this article online
Website: www.idoj.in
DOI: 10.4103/2229-5178.185494
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Cite this article as: Keen MA, Hassan I. Vitamin E in
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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.[10]
DERMATOLOGIC INDICATIONS
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.[11] Vitamin E is one of
the treatment modalities for yellow nail syndrome,[12] in a dosage
of 1000 IU once a day for a period of 6 months.[13]
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.[14,15] Vitamin
E has also been used in dapsone-induced headache.[16]
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.[14]
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.[17]
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.[18]
Other dermatological indications for which there is
little utility for the use of Vitamin E
Atopic dermatitis
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.[19] 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.
Hailey–Hailey disease
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.[20] 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.[21]
Epidermolysis bullosa
Several case reports suggest efcacy of vitamin E (300–600 IU/day)
for the management of epidermolysis bullosa.[22,23] Vitamin E
acts as an antioxidant, thus protecting the cell membranes and
intracellular organelles from lipid peroxidation.[24] 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.[24]
Psoriasis
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 signicant side effects, but
may not be able to compete with the already existing treatment
options for psoriasis.[25]
Cutaneous ulcers
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.[26]
Skin cancer prevention
Mouse studies reported inhibition of UV-induced tumors in mice
fed with α-tocopherol acetate.[27] Multiple human studies have
shown no effects of vitamin E on the prevention or development
of skin cancers.[28,29]
Wound healing
Vitamin E along with zinc and vitamin C, is included in oral
therapies for pressure ulcers and burns.[30] 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.[31]
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Melasma
Vitamin E alone has shown minimal efcacy in the treatment
of melasma.[32] It has been shown to cause depigmentation by
interference with lipid peroxidation of melanocyte membranes,
increase in intracellular glutathione content, and inhibition of
tyrosinase.[33]
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.[34] There
was a signicant 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 efcacy
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).[35]
α-Toc derivatives inhibit tyrosinase in vitro[36] and melanogenesis
in epidermal melanocytes.[37] 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.[38]
Acne vulgaris
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.[39] 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 inammation 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 signicantly
ameliorate retinoid side effects when combined with isotretinoin
in the treatment of acne.[40,41]
Scleroderma
Oxidative stress is signicantly increased in patients with
scleroderma when compared with the healthy controls,
suggesting that free radical induced oxidative injury occurs
in scleroderma.[42] Antioxidants such as vitamin E might,
therefore, be benecial. Vitamin E is also believed to stabilize
lysosomal membranes, potentially inhibiting events involved in
the autoimmune process.[21]
Vitamin E supplementation has resulted in improvement in
the skin of scleroderma patients, although nondermatological
aspects of scleroderma did not improve.[43]
Various components of scleroderma, including morphea,
calcinosis cutis, and Raynaud’s phenomenon respond to
vitamin E.[44] 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 ngertips. He received 800 IU
oral vitamin E daily and applied the vitamin (50 IU per mL) to the
ulcerated ngers twice daily. The ulcerations became less painful
after two weeks and healed almost completely within one month.[45]
Dermatological indications for which there are
anecdotal reports of beneficial effects of vitamin E
Chronic cutaneous lupus erythematosus[46]
Keratosis follicularis[47]
Postherpetic neuralgia[48]
Pseudoxanthoma elasticum[49]
Porphyria cutanea tarda.[50]
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.[51] 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.[52]
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.[53] 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 efcacy of vitamin E in the treatment of
burns and scars have been disappointing.[54,55]
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Topical vitamin E has also been found to be effective in
granuloma annulare.[56] Vitamin E is one of the ingredients in
over-the-counter treatments of skin aging.[57] 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.[58]
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.[59] 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.
SIDE EFFECTS
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.[60]
Topical application of vitamin E can rarely cause contact
dermatitis,[61] erythema multiforme,[62] and xanthomatous
reaction.[63]
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.
CONCLUSION
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-dened 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 benet. 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
Nil.
Conflicts of interest
There are no conicts of interest.
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