Current Nutrition Reports (2020) 9:226–235

https://doi.org/10.1007/s13668-020-00322-4

NUTRITION AND AGING (Y GU, SECTION EDITOR)

Role of Vitamins in Skin Health: a Systematic Review

Annunziata Dattola 1 & Martina Silvestri 2 & Luigi Bennardo 2 & Maria Passante 2 & Elisabetta Scali 2 & Cataldo Patruno 2 &
Steven Paul Nisticò 2

Published online: 29 June 2020

# Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract
Purpose of Review Skin is the main defense organ of the human body against external insults (ultraviolet radiations, infections by
pathogenic microorganisms, and mechanical and chemical stress). The integrity and functions of the skin barrier are supported by
an adequate supply of micronutrients, such as several vitamins. The purpose of this review was to analyze all vitamin-related skin
problems.
Recent Findings The World Health Organization has estimated that more than 2 billion people worldwide experience deficien-
cies in the intake of essential vitamins and minerals; the percentage of adults all over the world using daily vitamin supplements,
for treatment or prevention of chronic disease, has increased very rapidly in recent years.
Summary In this review, 65 studies have been selected in order to examine the role of the main vitamins and their derivatives
involved in maintaining the well-being of the skin and their use as prophylactic and therapeutic agents in the management of skin
disorders.

Keywords Skin health . Vitamins . Ubiquinone

Introduction maintaining the well-being of the skin and their use as pro-
phylactic and therapeutic agents in the management of skin
Skin is the main defense organ of the human body against disorders.
external insults (ultraviolet radiations, infections by pathogen-
ic microorganisms, mechanical and chemical stress). The in-
tegrity and functions of the skin barrier are supported by an
Material and Methods
adequate supply of micronutrients, such as several vitamins.
In this review The World Health Organization has estimated
Pubmed and Scimago-Scopus search engines were consulted
that more than 2 billion people worldwide experience defi-
to write this review; keywords searched include “vitamin A”,
ciencies in the intake of essential vitamins and minerals; in
B, C, D, E, K, “coenzyme Q10” AND “skin”, and “cutane-
fact the percentage of adults all over the world using any daily
ous”. Articles that did not bring any new information were
vitamin supplement, for treatment or prevention of chronic
excluded after a full reading. Article selection flowchart is
disease, has increased very rapidly in recent years. In this
better described in Fig. 1.
review, 65 studies have been selected in order to examine
the role of the main vitamins and its derivatives involved in
Vitamin A
This article is part of the Topical Collection on Nutrition and Aging
Vitamin A is not synthesized by the human body, but it needs
* Luigi Bennardo to be supplied through diet. Vitamin A and its metabolites are
luigibennardo10@gmail.com essential for a lot of functions, including immune activity,
vision, epithelial barrier function, and cellular differentiation;
1
Department of Dermatology, University of Rome “Tor Vergata”, vitamin A is obtained from animal sources such as meat, dairy
Rome, RM, Italy products and fish (retinol and retinyl ester) and from colored
2
Department of Health Sciences- Unit of Dermatology, Magna fruits and vegetables (beta-carotenoid or provitamin A) [1].
Graecia University, Catanzaro, Italy The retinoid family includes retinol and its natural derivatives
Curr Nutr Rep (2020) 9:226–235 227

Fig. 1 Article selection flowchart Records idenfied through database

searching

PUBMED/MEDLINE/EMBASE

SCOPUS/SCIMAGO

(n=2,872)

Duplicates removed

(n=1,002)

Records screened by
title and abstract

(n=1,870)
Records excluded based on tle
and abstract

(n= 1,522)

Records selected for

analysis of full text

(n=348)
Full-text arcles excluded:

(n=283)

• Limited results reported

(n=67)
Arcles
• Not original research
included in the review (n=71)
• Overlap with included
(n=65) arcles (n=53)
• Not a populaon of
interest (n=26)
• Not in English (n=47)
• Small sample size (n=22)

such as retinaldehyde, retinoic acid, and retinyl esters, as well
as a large number of synthetic derivatives [2]. Retinoids inter-
act with cellular and nucleic acid receptors including the cel-
lular retinoic acid-binding protein (CRABP) types I and II, the
cellular retinol binding protein, and the nuclear retinoic acid
receptor family called RARs. Their action consists in the reg-
ulation of cellular differentiation improving photoaging
through the increase of epidermal proliferation leading to skin
thickening and deposition of glycosaminoglycans [3].
Additionally vitamin A plays a role in neoplastic transforma-
tion and carcinogenesis because of its antioxidant function
that decreases free radical damage to DNA [4]. Vitamin A
also regulates numerous processes in adaptive and innate im-
munity involving helper T cells and B cells, neutrophils, mac-
rophages, and natural killer cells, and it increases body’s de-
fenses against infectious processes [5•]. Retinoids can be
classified into various generations based on structural features
and time of introduction:
– I generation: Retinol, retinaldehyde, tretinoin, isotreti-
noin, alitretinoin
– II generation: Etretinate, acitretin
– III generation: Adapalene, tazarotene, bexarotene
– IV generation: Seletinoid G
Isotretinoin or 13-cis-retinoic acid administered orally is
indicated for the treatment of severe nodulocystic acne; it acts
by inhibiting the activity of the sebaceous glands and blocking
the proliferation of Propionibacterium acnes; furthermore, it
normalizes the differentiation of the follicular epithelium re-
ducing the formation of comedones [6]. Isotretinoin is a tera-
togenic and embryotoxic molecule; therefore, its use is
228
contraindicated in women who are pregnant or could become
pregnant during treatment. Isotretinoin is also indicated for the
treatment of various dermatological conditions beyond acne,
including hidradenitis suppurativa, ichthyoses, rosacea, scar-
ring alopecia, and non-melanoma skin cancer prophylaxis,
because of its effect on epidermal cells growth and differenti-
ation and on sebaceous glands activity; moreover, the drug
shows immunomodulatory and anti-inflammatory properties
[7].
Tretinoin or all-trans retinoic acid represents one of the
most important topical treatments for inflammatory and non-
inflammatory acne, normalizing the follicular epithelial
hyperkeratinization, reducing the proliferation of P. acnes
and the formation of new comedones. Several studies have
shown effectiveness of topical Tretinoin in the treatment of
photoaging and chronoaging.Tretinoin causes an increase in
the thickness of the granular cellular layer, in the undulation of
the dermo-epidermal junction, and a reduction in the
vacuolization of the melanocytes. In the dermis was observed
the development of micro vascularization (angiogenesis) and
the deposition of elastic material and glycosamine glycans
(GAGs) [6].
Vitamin A alcohol or all-trans retinol is an endogenous
natural retinoid and is a precursor of retinoic acid and retinal.
Retinol derivatives are widely used in cosmetology for their
antioxidant and anti-aging properties. They can stimulate col-
lagen and elastic fibers biosynthesis and reduce the expression
of collagenase 1. Retinol is well tolerated by keratinocytes and
is associated with less skin irritation compared with tretinoin
[8].
Alitretinoin or 9-cis-retinoic acid is an endogenous retinoid
that binds to all subclasses of retinoic acid receptors (RARs)
and retinoid X receptors (RXRs), performing anti-inflamma-
tory, immunomodulatory, and apoptotic effects. Alitretinoin
0.1% gel is the FDA-approved topical treatment for localized
Kaposi’s sarcoma. Due to its immunomodulatory effect, the
systemic use of Alitretinoin has proved to be effective for the
treatment of recalcitrant chronic hand eczema. Alitretinoin
downregulates the activity of inflammatory cells and reduces
inflammatory chemokines (TNF-alpha, IL-4, IL-1beta, and
IL-12p40) making the drug effective in the treatment of
palmoplantar pustular psoriasis [9].
Acitretin is a second-generation retinoid used in several
hyperkeratotic and inflammatory dermatoses and non-
melanoma skin cancers: psoriasis, Darier disease, pityriasis
rubra pilaris, ichthyoses, Grover disease, lichen planus, and
lupus erythematosus. It works by targeting specific receptors
(cellular retinoic acid-binding protein (CRABP), the epider-
mal growth factor (EGF) receptor, and retinoic acid nuclear
receptors (RARs)) in the skin that are involved in controlling
the growth cycle of skin cells; furthermore, acitretin has im-
munomodulatory and anti-inflammatory effects, reducing the
proliferation of polymorphonuclear leukocytes in the stratum
Curr Nutr Rep (2020) 9:226–235
corneum and stimulating cytotoxicity mediated by T cells.
Side effects of the drug are dose-related and include cheilitis,
drying of mucous membranes, and elevation of serum triglyc-
eride and cholesterol levels. Acitretin, like other oral retinoid
drugs, is teratogenic; it is therefore contraindicated in women
of childbearing age unless appropriate contraceptive methods
are used [10].
Adapalene, a third-generation retinoid, is a 6-[3-(1-
adamantyl)-4-methoxyphenyl]-2-naphthoic acid and presents
biological activities similar to tretinoin, but compared with the
latter, the adapalene has a greater affinity for the retinoic acid
receptor (RAR) β and γ [11]; it regulates the processes of
keratinization and also carries out an anti-inflammatory action
due to the blocking of the activity of the lipoxygenase of
arachidonic acid. The anti-inflammatory activity of adapalene
explains the minor skin irritation following its use; further-
more, it remains confined to the superficial layers of the epi-
dermis accumulating in the hair follicles, giving a more
targeted action. The appearance of erythema, burning, and
dryness represent the main side effects [12]. Treatment with
adapalene could be responsible for embryopathy; however,
since the drug has minimal skin absorption, it seems unlikely
that it will induce malformations [13].
Tazarotenic acid is a synthetic retinoid able to selec-
tively bind with the retinoid receptor family (RAR), in
particular RARβ and RARγ, thus improving its thera-
peutic index. Tazarotene can be used as monotherapy or
as combination therapy in several dermatological dis-
eases: psoriasis, nail psoriasis, acne, photoaging, basal
cell carcinomas, and various keratinization disorders. A
double-blind, randomized, vehicle-controlled trial com-
pared the effectiveness of tazarotene 0.1% gel and ve-
hicle gel in 31 patients with fingernail psoriasis, dem-
onstrating that treatment with tazarotene 0.1% gel can
significantly reduce onycholysis and pitting and is well
tolerated [14]. Studies suggest that tazarotene may nor-
malize cellular changes and hinder progression to pre-
cancerous states; furthermore, it improves fine wrin-
kling, hyperpigmentations, pore size, telangiectasia, and
elastosis [15]. Weinstein et al. demonstrated that
tazarotene creams 0.05% and 0.1% applied once daily
were effective in the treatment of psoriasis reducing
plaque thickness, scaling, and erythema. The mechanism
of action of tazarotene is the regulation of gene tran-
scription, normalizing the abnormal differentiation of
keratinocytes in psoriatic plaques, reducing epidermal
hyperproliferation and inflammation, the main pathogen-
ic factors in psoriasis [16]. Studies highlight that
tazarotene can induce BCC regression possibly by syn-
ergistic anti-proliferative and pro-apoptotic pathways
[17]. An open-label clinical trial evaluated the efficacy
and tolerability of topical tazarotene 0.1% gel in twenty
patients with basal cell carcinoma; the study showed a
Curr Nutr Rep (2020) 9:226–235
complete response in 16 of the 30 lesions treated (53%)
after 5 to 8 months of treatment [18].
Bexarotene is a retinoid X receptor (RXR)-selective, li-
censed for the treatment of cutaneous T cell lymphoma
(CTCL).
Seletinoid G is a novel synthetic retinoid belonging to the
fourth generation, which selectively binds RAR-γ, expressed
more in epidermis compared with other RARs. It appears to be
as effective as tretinoin in the treatment of photoaging present-
ing a lower risk of skin irritation. Topical treatment with
seletinoid G would in fact lead to an increase in the expression
of type I procollagen, tropoelastin, and fibrillin-1 and a reduc-
tion of MMP-1 [6] .
Vitamin B
Vitamins B are a group of water-soluble vitamins contained in
many natural foods (bananas, potatoes, lentils, tuna, etc.) and
involved in cellular metabolism which includes vitamin B1 or
thiamine, vitamin B2 or riboflavin, vitamin B3 or niacin or
nicotinamide, vitamin B5 or pantothenic acid, vitamin B6 or
pyridoxine, vitamin B8 or biotin, vitamin B9 or folate, and
vitamin B12 or cobalamin. Among these the most important
in the skin is vitamin B3, involved in DNA repair, cellular
energy metabolism, and in regulation of transcription
processes.
Vitamin B3
Vitamin B3 or vitamin PP or niacinamide (also known as
nicotinamide) is a component of coenzymes involved in hy-
drogen transfer, and it has numerous beneficial effects on the
skin. Topical use of niacinamide stabilizes the skin barrier,
reducing transepidermal water loss and stimulating protein
synthesis (filaggrin, keratin, involucrin) and ceramides, mak-
ing it useful in the treatment of atopic dermatitis. Topical
application of nicotinamide increased ceramide, free fatty ac-
id, and cholesterol synthesis and decreased transepidermal
water loss in dry skin [19], which are the main pathogenetic
factors underlying the barrier defect of atopic dermatitis.An
anti-inflammatory effect and reduction in production of a va-
riety of inflammatory cytokines (IL-1β, IL-6, IL-8, TNF),
have also been demonstrated which justifies its use in the
treatment of acne, rosacea, and other skin inflammatory states
[20]. Topical formulations of niacinamide can be used in the
treatment of acne vulgaris; in a randomized double-blind, con-
trolled trial, 160 patients with inflammatory acne were treated
with 4% nicotinamide gel or 4% erythromycin gel twice a day
for 8 weeks. In both groups, there was a reduction in the rate of
inflammatory lesions, but the group treated with 4% nicotin-
amide gel showed a significantly greater improvement in seb-
orrhea [21].The use of oral niacinamide for the prevention of
non-melanoma skin cancers has been discussed to date. Its
229
anti-carcinogenic role may be due to its contribution in
DNA repair processes and in the prevention of ultraviolet-
induced immunosuppression (UV). Furthermore, nicotin-
amide is a fundamental component of two coenzyme mole-
cules that play important reactions in the body: nicotinamide
adenine dinucleotide (NAD) and nicotinamide adenine dinu-
cleotide phosphate (NADP). NAD plays a key role in the
production of adenosine triphosphate (ATP), a molecule that
acts as a carrier of chemical energy within cells. Therefore,
nicotinamide is involved in energy-dependent cellular pro-
cesses, including DNA repair that may justify its role as che-
mopreventive agent against skin cancer [22] reducing the in-
cidence of actinic keratoses and non-melanoma skin cancers
in high-risk individuals. A phase 3, double-blind, randomized
clinical trial evaluated the effectiveness of oral nicotinamide
in reducing the onset of non-melanoma skin cancers (basal
cell carcinomas and squamous cell carcinomas) and actinic
keratosis. At 12 months, the incidence of new non-
melanoma skin cancers was 23% lower in the nicotinamide
group than in the placebo group [23].
Bissett et al. evaluated the effect of 5% topical niacinamide
in 50 female white subjects with facial photoaging signs. The
study showed a reduction in fine wrinkles, hyperpigmented
spots, red spots and skin radiance (yellowing) and in addition,
an improvement in skin elasticity following topical treatment
with niacinamide which proved to be well tolerated and prom-
ising in improving the appearance of aging facial skin [24].
Nicotinamide is safe, with few side effects and with no report-
ed case of teratogenicity. Topical use is not associated with
photosensitization and skin irritation. The main side effects
due to the systemic use of nicotinamide include nausea,
vomiting, headache, and fatigue [25].
Vitamin B8
Vitamin B8, also known vitamin B7 or H or biotin, is a water-
soluble vitamin that is an essential cofactor for four carboxyl-
ases, which catalyze essential steps in metabolic pathways
such as gluconeogenesis, fatty acid synthesis, and amino acid
catabolism; recent evidences demonstrated that biotin also
plays important roles in cell signaling, epigenetic regulation
of genes, and chromatin structure. Biotin is present in many
foods, mostly bound to proteins, and is also produced by nor-
mal gut flora; meat, fish, poultry, eggs, dairy products, and
some vegetables are the main food sources. Biotin deficiency
(serum levels lower than 200 ng/L) can be congenital/genetic
or acquired; the latter is rare. Genetic form is due to a
holocarboxylase enzyme deficiency(neonatal type) or to a
lack of biotinidase enzyme (infantile type); causes of acquired
biotin deficiency include states of malabsorption, alcoholism,
pregnancy, prolonged use of antibiotics, drugs such as
Isotretinoin, and valproic acid intake [26•]. Clinical signs of
biotin deficiency include periorific scaly dermatitis,
230
conjunctivitis, alopecia, skin infection, ataxia, ketolactic
acidosis/organic aciduria, convulsions, hypotonia, and devel-
opmental delay in infants and children [27]. While the neuro-
logical symptoms occur at severe biotin deficiency, the der-
matological manifestations often appear early and are impor-
tant indicators of deficiency [28]. Biotin is involved in the
production of keratin; therefore, it may contribute to the
well-being of nails and hair. There are some case reports dem-
onstrating that oral biotin may improve hair loss and nail
growth in cases of acquired and inherited biotin deficiency
which are uncommon but still few evidences on the benefit
of oral biotin supplementation in healthy subjects [29].
Boccaletti et al. evaluated the efficacy of oral biotin 5 mg/
day on two young patients with uncombable hair syndrome,
characterized by dry, frizzy, and light-colored hair, described
as blond or silvery with a glistening sheen. Patients obtained
excellent results in terms of hair appearance; however, scan-
ning electron microscopy showed no structural changes in the
hair. After 2 years of follow-up, hair normality was main-
tained without biotin, while it was necessary to continue the
integration of biotin to control the nails fragility [30]. Biotin
deficiency has been shown to be a key factor in the pathogen-
esis of seborrheic dermatitis; a study conducted on twenty-five
children suffering from generalized seborrheic dermatitis
showed the efficacy of treatment with vitamin B complex
and biotin. Skin lesions improved within 4–8 days and cleared
completely within 15–30 days [31].
Vitamin C
Vitamin C, also known as ascorbic acid or L-ascorbic acid, is a
water-soluble vitamin with antioxidant properties that make it
essential for skin health. Skin contains high concentrations of
vitamin C (in total skin it ranges from 0.4 to 1 mg/100 g of
wet-tissue weight) concentrated in the intracellular compart-
ments, transported by blood vessels of dermal layer.
Ascorbate has a great reducing potential and reacts with many
reactive oxygen and nitrogen species in vitro (including sin-
glet oxygen, superoxide, hydroxyl and water-soluble peroxy
radicals and hypochlorous acid) modulating negative effects
of UV-induced ROS. Moreover, vitamin C protects cells from
oxidative stress by carrying out a synergistic action with vita-
min E and replenishing it [32]. Ascorbic acid takes part in
several important reactions; noradrenaline synthesis; mainte-
nance of the functional activity of vitamin E; prostaglandin
and prostacyclin metabolism; and transport of long chain fatty
acids through membranes contributing to the synthesis of car-
nitine [33]. Of great importance for skin health is the role that
ascorbic acid plays in collagen and elastine synthesis that has
been extensively studied: it is a cofactor for both prolyl and
lysyl hydroxylases that catalyze the formation of hydroxypro-
line and hydroxylysine, and ascorbate seems to regulate the
transcripts of type I and III collagen genes. In vitro, fibroblasts
Curr Nutr Rep (2020) 9:226–235
stimulated with ascorbic acid increase the gene expression of
collagen. Elderly human skin fibroblasts are able to increase
their proliferative capacity when treated with adequate levels
of ascorbic acid [34]. Moreover, the activity of vitamin C in
the normalization of lipid profiles (glucosphingolipids and
ceramides) of the stratum corneum barrier has been suggested
[35].
It has been reported that vitamin C levels are lower in aged
or photodamaged skin [36], and adequate levels of ascorbic
acid can help counteract the negative effects of UV irradiation.
Vitamin C deficiency is associated with the loss several skin
functions: altered wound healing (associated with deficit in
collagen production), thickening of the stratum corneum,
and subcutaneous bleeding (due to the fragility and alteration
of the connective tissue morphology) [37]. Recent in vivo
studies showed evidence of vitamin C effects in the skin.
Ninety-day oral supplementation with a fermented papaya
preparation or an antioxidant cocktail in 60 healthy males
and females aged 40–65 years, presenting clinical signs of
skin aging, showed an improvement in skin elasticity,
moisture, and antioxidant capacity [38]. Oral supplemen-
tation also demonstrated a reduction in the intensity of
general skin spots, brown spots, UV spots, and improve-
ment in erythema, skin texture, and appearance of pores
[39]. The efficacy of topical application of vitamin C de-
pends on the formulation of the cream or serum used on the
skin, because it is a water-soluble molecule repelled by
physical barrier repelled of epidermal cells. Ascorbate
phosphatidylcholine (PC) liposome penetrates through the
epidermis and showed anti-inflammatory and antioxidant
properties on human skin irradiated with UVA/UVB [40].
A double-blind, placebo-controlled study examined the ef-
fect of a topical 5% L-ascorbic acid formulation applied on
the forearms and neck of 19 patients over a 6-month peri-
od. After 3 months, an improvement in the global score
(based on hydration, roughness, laxity, softness, fine lines
and coarse wrinkles) was appreciated, and it is further in-
creased after 6 months [41]. Vitamin C inhibits the activa-
tion of AP-1 and downregulates matrix metalloproteinases
(MMPs), reducing collagen damage. In clinical studies,
solutions containing vitamin C have been shown to reduce
thymine dimer changes induced by UV rays and the for-
mation of apoptotic cells from sunburn, potentially reduc-
ing the risk of photocarcinogenesis. Several clinical studies
have shown that solutions containing vitamin C reduce
UV-induced thymine dimer mutations and formation of
apoptotic cells from sunburn, protecting the skin from the
risk of photocarcinogenesis [42] .
Vitamin D
Vitamin D3, also known as cholecalciferol, is a fat-soluble
prohormone steroid that has endocrine, paracrine, and
Curr Nutr Rep (2020) 9:226–235
autocrine functions. The endocrine effects of vitamin D are
mainly based on the control of serum calcium homeostasis.
The paracrine and autocrine effects of vitamin D are expressed
on the cells that express the nuclear receptors of vitamin D and
include the inhibition of cell proliferation, the control of cel-
lular differentiation, and apoptosis that can influence the pro-
cesses of carcinogenesis and in the immunity [43]. Vitamin
D3 can be defined as “sunshine vitamin” since its production
in the body depends on sun exposure. 7-dehydrocholesterol in
the plasma membranes of keratinocytes and dermal fibroblasts
is converted to previtamin D3 which enters in the systemic
circulation, and it is converted by a hepatic hydroxylase into
25-hydroxyvitamin D (25(OH)D or calcidiol). 25(OH)D is
converted in the kidney to its active hormonal form 1,25-
dihydroxyvitamin D (1,25(OH)2D; calcitriol) [44]. Vitamin
D is involved in the mechanisms of regulation of the immune
system; it regulates the action of suppressor T lymphocytes,
the synthesis of cytokines, and acts by modulating the pro-
cesses of cellular apoptosis [45]. The role of vitamin D in the
genesis of skin cancers (melanoma, basal cell carcinoma, and
squamous cell carcinoma) is still debated. Vitamin D can in-
hibit the processes of tumor invasion and angiogenesis mech-
anisms, by blocking cell proliferation [46, 47]. Furthermore, it
seems that treatment with vitamin D can reduce the risk of
DNA damage resulting from ultraviolet radiation, by increas-
ing the p53 protein nuclear accumulation and the reduced
formation of nitric oxide [48]. Topical application of vitamin
D preparations has led to a reduction in the progression of
non-melanoma skin cancers [49]. If further studies are re-
quired to demonstrate the correlation between tumors and vi-
tamin D, its effects on hyperkeratosis are well known. The
derivatives of vitamin D (calcipotriol) in fact are widely used
in the treatment of mild psoriasis, with locations that are not
widespread on the skin surface. Its anti-proliferative action on
keratinocytes promotes reduction of the thickness of psoriatic
patches; furthermore, its immunoregulating action improves
the control of the disease. Vitamin D3 determines the reduc-
tion of interferon gamma and recruitment of granulocytes
through the inhibition of the synthesis of IL-2 and IL-6. It also
leads to inhibition of cytotoxic t cells and natural killer cells.
Vitamin E
Vitamin E, or tocopherol, is the term given to the most abun-
dant group of lipid-soluble antioxidant in human cells, discov-
ered in 1922; it is found in various foods and oils such as
wheat germ oil, sunflower oil, safflower oil, seeds, corn,
soy, and green leafy vegetables. Tocopherol deficiency is rare,
generally related to intestinal malabsorption disorders and has
been associated with a syndrome of edema with papular ery-
thema or seborrhoiec changes, dryness, and depigmentation in
premature infants [50]. Studies suggest that vitamin E levels
are dependent on the density of sebaceous glands in the skin
231
[51]. There are eight naturally forms of vitamin E: alpha, beta,
gamma, and delta classes of tocopherol and tocotrienols.
Natural tocopherols occur in the RRR configuration, while
the synthetic form, found in many commercial preparations,
consists of eight possible stereoisomers and is called all-rac-
alpha-tocopherol (or d-a-tocopherol) [52]. Alpha-tocopherol
can inhibit platelet aggregation, downregulating intracellular
cell adhesion molecule (ICAM-1) and the vascular cell adhe-
sion molecule (VCAM-1) and decreasing the adhesion of
blood cell components to the endothelium. Moreover, vitamin
E stimulates the release of prostacyclin, which is a vasodilator
and inhibitor of platelet aggregation [53]. Alpha-tocopherol
concentration is higher in the epidermis (31 nmol/g) than in
the dermis (16 nmol/g). Vitamin E inhibits the production of
reactive oxygen species molecules and acts as the first line of
defense against lipid peroxidation, protecting the viability of
cell membranes. The antioxidant activity of vitamin E is
strongly dependent on the action of other biological agents,
such as ascorbic acid, vitamin B3, selenium, and glutathione.
The powerful antioxidant activity makes the vitamin E impor-
tant in the prevention of skin aging, and it has proved to be a
useful treatment for many skin conditions: melasma, scar for-
mation preventing and atopic dermatitis [54]. Topical vitamin
E application has proved to be safe with few side effects and
low incidence of mild irritations. Formulations containing
0.2% of a-tocopherol lead to an increase in vitamin E levels
in the stratum corneum and a reduction in lipid peroxidation
in vivo, in this way protects the skin from the adverse effects
of oxidative stress and photoaging [33]. Vitamin E in a dosage
of 1000 IU once a day for a period of 6 months represents an
effective treatment for yellow nail syndrome, characterized by
slowing of nail growth, which takes on a yellowish color and a
transverse curvature, chronic bronchitis, and sinusitis [55].
Vitamin E could also have beneficial effects in acne vulgaris,
preventing the lipid peroxidation of sebum, damaged by bac-
terial growth, which contributes to inflammatory acne [56].
Vitamin E supplementation has proven to be useful in the
treatment of scleroderma, as it may stabilize lysosomal mem-
branes and also regulate autoimmune process. Various reports
have shown that oral vitamin supplementation at doses rang-
ing from 200 to 1200 IU per day resulted in an improvement
of several typical aspects of scleroderma, including morphea,
calcinosis cutis, and Raynaud’s phenomenon [57]. Many stud-
ies have shown that alpha tocopherol can have beneficial ef-
fects in the treatment of melasma thanks to its depigmenting
action; in fact it interferes with lipid peroxidation of melano-
cyte membranes, increases the intracellular glutathione con-
tent, and inhibits tyrosinase [58].
Vitamin K
The term vitamin k identifies a series of compounds deriving
from 2-methyl-1,4-naphthoquinone. Vitamin K is a fat-
232
Table 1 Summary of vitamin’s skin effects
Vitamin Mechanism of action
Vitamin A Normalization of keratinocyte
differentiation processes [3]
and reduction in the size and
secretion of the sebaceous glands [6]
Vitamin B3 Anti-inflammatory effect [20];
synthesis of proteins and ceramides
important for the skin barrier and
reduction in trans epidermal water
loss [19]; contribution in DNA repair
processes [22]
Vitamin B8 Involved in the production of keratin [29]
and in several metabolic pathways
(gluconeogenesis, fatty acid synthesis,
amino acid catabolism) [26]
Vitamin C Inhibition of reactive oxygen accumulation [32];
involved in collagen synthesis processes [34]
Vitamin D Immunomodulatory effect [45]; control of
keratinocyte proliferation and calcium
homeostasis [43]; reduction of UV-induced
DNA damage [48]
Vitamin E Antioxidant activity [54] and reduction in
lipid peroxidation [53]
Vitamin K Involved in the activation processes of
some coagulation factors [59]; antioxidant
activity [61••]
Coenzyme Q10 Antioxidant activities against environmental
aggressions; component of mitochondrial
respiratory chain [64]
soluble vitamin and exists naturally as vitamin K1
(phylloquinone) and vitamin K2 (menaquinone). Vitamin K
is fundamental for coagulation as it takes part in the activation
processes of some coagulation factors such as factors II, VII,
IX, X, and protein C and protein S; in fact vitamin K1 and K2
are required for carboxylation of all vitamin k-dependent pro-
teins. Vitamin K is also involved in the synthesis of
osteocalcin and matrix GLA protein. Vitamin K is found in
plant and animal foods and is also synthesized by intestinal
bacteria flora; its absorption occurs at various levels of the
intestine, and its deficiency can contribute to significant bleed-
ing, poor bone development, osteoporosis, and increased car-
diovascular disease [59, 60].
Studies have shown that vitamin K determines beneficial
effects in the healing processes of acute and chronic skin
wounds. A randomized clinical trial, conducted on sixty-
three patients, investigated the effects of 1% Vitamin K cream
on skin wound healing process, suggesting that topical appli-
cation of Vitamin K reduces healing time in treated patients.
The acceleration of wound healing processes promoted by
vitamin K is probably secondary to its ability to increase
wound contraction and improve the epithelialization process
and the formation of fibroblasts, collagen fibers, and blood
Curr Nutr Rep (2020) 9:226–235
Role in skin diseases
Treatment of psoriasis [10, 16],
acne [6], prevention of skin
cancer [4], photoaging and photo damage [3]
Treatment of acne [21], atopic dermatitis [19],
actinic keratosis [23], and prevention of skin
cancers [22] and photoaging [24]
Treatment of seborrheic dermatitis [31] and several
hair and nail disorders [29]
Treatment and prevention of photoaging [36] and
photocarcinogenesis [42]
Treatment of psoriasis [45] and prevention of
non-melanoma skin cancers [49]
Treatment of scleroderma [57], yellow nail
syndrome [55], acne [56], and melasma [58].
Prevention of skin aging [33]
Treatment of acute and chronic skin wounds [61••]
and laser-induced purpura [62]
Treatment of skin aging [65]
vessels. Moreover, vitamin k seems to improve wound
healing thanks to its antioxidant capacity, eliminating reactive
oxygen species (ROS) [61••]. A prospective study, conducted
on twenty adult patients, evaluated the effectiveness and safe-
ty of topical vitamin K formulation on laser-induced purpura;
the study showed that a combination of 1% vitamin K and
0,3% retinol cream accelerated the resolution of laser-induced
purpura [62]. Topical application of vitamin K has been used
for the prevention of vascular manifestations of aging and in
the resolution of the pigmentation of bruises. Vitamin K can
facilitate the removal of extravascular blood from the skin,
which would justify its effectiveness in accelerating the dis-
appearance of bruises and reducing the severity of after effects
of laser treatments [63].
Ubiquinone
Ubiquinone (coenzyme Q10, Q10) is a powerful endogenous
fat-soluble antioxidant, present in all human cells, which par-
ticipates in different reactions that occur in the body; it is a
fundamental component of the mitochondrial respiratory
chain, working as an electron carrier and participating in cel-
lular energy production processes. The skin is continuously
Curr Nutr Rep (2020) 9:226–235 233

Table 2 Levels of evidence of the

role of vitamins in skin disorders Vitamin Level of evidence

Vitamin A • Treatment of psoriasis (1a) and acne (1a)

• Prevention of skin skin cancer (2a), photoaging, and photo damage (1a)
Vitamin B3 • Treatment of acne (2a), atopic dermatitis (3a), actinic keratosis (1b)
• Prevention of skin cancers (1b) and photoaging (1b)
Vitamin B8 • Treatment of seborrheic dermatitis (1a) and several hair and nail disorders (1a)
Vitamin C • Treatment and prevention of photoaging (1a) and photocarcinogenesis (2b)
Vitamin D • Treatment of psoriasis (1a)
• Prevention of non-melanoma skin cancer (3a)
Vitamin E • Treatment of scleroderma (3a), yellow nail syndrome (4), acne (4), and melasma (4)
• Prevention of skin aging (3a)
Vitamin K • Treatment of acute and chronic skin wounds (2b) and laser-induced purpura(2b)
Coenzyme Q10 • Treatment of skin agin (2b)

Levels of evidence: 1A systematic reviews of randomized control trials; 1B individual RCT; 2A systematic
reviews of cohort studies; 2B individual cohort study; 3A systematic reviews of case-control studies; 3B individual
case-control study; 4 case series (and poor quality cohort and case-control studies)

subjected to stresses of different nature, and the resulting dam-
age can be repaired through processes that require energy.
With increasing age, energy production, and mitochondrial
activity decrease in the cells, consequently, various structural
alterations occur in the tissues. At the skin level, the classic
signs of aging appear, such as wrinkles and lines and loss of
elasticity [64]. In the skin, endogenous Q10 levels decline
with increasing age and UV-irradiation. A controlled, ran-
domized study enrolling 73 non-smoking females evaluated
the efficacy of two formulas, a cream and a serum, containing
Q10. Topical application of Q10 allows the penetration of the
coenzyme into the skin, which is metabolically transformed,
carrying out an antioxidant action contributing to the mainte-
nance of cellular energy levels. People of all ages can benefit
from regular treatment with Q10 [65].
Conclusions
Vitamins modulate multiple biological functions that influ-
ence skin health; they represent an important ingredient in
several cosmetic products as they play a fundamental role as
antioxidant agents capable of counteracting the formation of
free radicals and support the endogenous antioxidant system
that intervene both in cellular aging processes and in the de-
velopment of certain skin pathological conditions. In fact the
use of vitamins in the dermatological field is not limited only
to cosmetics as they can be used as therapeutic or preventive
agents in some skin disease. A summary of all vitamins effects
on skin has been reported in Table 1. Levels of evidence on
the use of vitamins in the treatment of skin conditions/aging
are reported in Table 2. Further studies are needed to better
understand the roles of vitamins and their mechanisms of
action in order to develop potential therapeutic agents and/or
cosmetic products to improve barrier function and treat skin
disease.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflict of
interest.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.
References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
•• Of major importance
1. Moise AR, Noy N, Palczewski K, Blaner WS. Delivery of retinoid-
based therapies to target tissues. Biochemistry. 2007;46(15):4449–
58.
2. Antille C, Tran C, Sorg O, Saurat JH. Penetration and metabolism
of topical retinoids in ex vivo organ-cultured full-thickness human
skin explants. Skin Pharmacol Physiol. 2004;17(3):124–8.
3. Griffiths CEM, Finkel IJ, Tranfaglia MG, et al. An in-vivo exper-
imental model for topical retinoid effects on human skin. Br J
Dermatol. 1993;29:389–99.
4. Dawson MI. The importance of vitamin A in nutrition. Curr Pharm
Des. 2000;6(3):311–25.
5•. . Huang Z, Yu L, Qi G, Brand D, Zheng SG. Role of vitamin A in
the immune system. J Clin Med. 2018;7(9):258 This review high-
lights the role of vitamin A in immunity research and briefly
introduces the clinical application of vitamin A in the treat-
ment of several infectious diseases.
234
6. Layton A. The use of isotretinoin in acne. Dermatoendocrinol.
2009;1(3):162–9.
7. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the
treatment of acne vulgaris. J Am Acad Dermatol. 2006;54:644–6.
8. Ganceviciene R, Liakou AI, Theodoridis A, Makrantonaki E,
Zouboulis CC. Skin anti-aging strategies. Dermatoendocrinol.
2012;4(3):308–19.
9. Bubna AK. Alitretinoin in dermatology-an update. Indian J
Dermatol. 2015;60(5):520. https://doi.org/10.4103/0019-5154.
164426.
10. Pilkington T, Brogden RN. Acitretin : A review of its pharmacolo-
gy and therapeutic use. Drugs. 1992;43(4):597–627.
11. Czernielewski J, Michel S, Bouclier M, Baker M, Hensby JC.
Adapalene biochemistry and the evolution of a new topical retinoid
for treatment of acne. J Eur Acad Dermatol Venereol.
2001;15(Suppl 3):5–12.
12. Millikan LE. Adapalene: an update on newer comparative studies
between the various retinoids. Int J Dermatol. 2000;39(10):784–8.
13. Piskin S, Uzunali E. A review of the use of adapalene for the
treatment of acne vulgaris. Ther Clin Risk Manag. 2007;3(4):
621–4.
14. Bianchi L, Soda R, Diluvio L, Chimenti S. Tazarotene 0.1% gel for
psoriasis of the fingernails and toenails: an open, prospective study.
Br J Dermatol. 2003;149(1):207–9.
15. Ogden S, Samuel M, Griffiths CEM. A review of tazarotene in the
treatment of photodamaged skin. Clin Interv Aging. 2008;3(1):71–
6.
16. Weinstein GD, Koo JY, Krueger GG, Lebwohl MG, Lowe NJ,
Menter MA, et al. Tazarotene cream in the treatment of psoriasis:
two multicenter, double-blind, randomized, vehicle-controlled
studies of the safety and efficacy of tazarotene creams 0.05% and
0.1% applied once daily for 12 weeks. J Am Acad Dermatol.
2003;48(5):760–7.
17. Orlandi A, Bianchi L, Costanzo A, Campione E, Giusto Spagnoli L,
Chimenti S. Evidence of increased apoptosis and reduced prolifer-
ation in basal cell carcinomas treated with tazarotene. J Invest
Dermatol. 2004;122(4):1037–41.
18. Peris K, Fargnoli MC, Chimenti S. Preliminary observations on the
use of topical tazarotene to treat basal-cell carcinoma. N Engl J
Med. 1999;341(23):1767–8.
19. Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S. Nicotinamide
increases biosynthesis of ceramides as well as other stratum
corneum lipids to improve the epidermal permeability barrier. Br
J Dermatol. 2000;143(3):524–31.
20. Gehring W. Nicotinic acid/niacinamide and the skin. J Cosmet
Dermatol. 2004;3(2):88–93.
21. Weltert Y, Chartier S, Gibaud C, Pechenart P, Girard F, Courau S,
et al. Double blind clinical evaluation of the efficacy of nicotin-
amide gel versus 4% erythromycin gel in the treatment of moderate
acne in predominantly inflammatory componenet. Les Nouvelles
dermatologiques. 2004;23:385–94.
22. Nazarali S, Kuzel P. Vitamin B derivative (nicotinamide)appears to
reduce skin cancer risk. Skin Therapy Lett. 2017;22(5):1–4.
23. Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA,
McKenzie CA, et al. A phase 3 randomized trial of nicotinamide for
skin-cancer chemoprevention. N Engl J Med. 2015;373:1618–2.
24. Bissett DL, Miyamoto K, Sun P, Li J, Berge CA. Topical niacin-
amide reduces yellowing, wrinkling, red blotchiness, and hyperpig-
mented spots in aging facial skin. Int J Cosmet Sci. 2004;26(5):
231–8.
25. Bains P, Kaur M, Kaur J, Sharma S. Nicotinamide: mechanism of
action and indications in dermatology. Indian J Dermatol Venereol
Leprol. 2018;84(2):234–7.
26•. . Almohanna HM, Ahmed AA, Tsatalis JP, Tosti A. The Role of
vitamins and minerals in hair loss: a review. Dermatol Ther
(Heidelb). 2019;9(1):51–70 The authors performed a broad
Curr Nutr Rep (2020) 9:226–235
literature search of Google Scholar and Pubmed in search of
papers that study the relationship between vitamins, minerals,
and hair loss.
27. Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase defi-
ciency. Expert Rev Endocrinol Metab. 2008;3(6):715–24
CAMBIARE NEL TESTO DATA.
28. Limat A, Suormala T, Hunziker T, Waelti ER, Braathen LR,
Baumgartner R. Proliferation and differentiation of cultured human
follicular keratinocytes are not influenced by biotin. Arch Dermatol
Res. 1996;288:31–8.
29. Patel DP, Swink SM, Castelo-Soccio L. A review of the use of
biotin for hair loss. Skin Appendage Disord. 2017;3(3):166–9.
30. Boccaletti V, Zendri E, Giordano G, Gnetti L, De Panfilis G.
Familial uncombable hair syndrome: ultrastructural hair study and
response to biotin. Pediatr Dermatol. 2007;24:E14–6.
31. Messaritakis J, Kattamis C, Karabula C, Mataniotis N. Generalized
seborrhoeic dermatitis. Clinical and therapeutic data of 25 patients.
Arch Dis Child. 1975;50(11):871–4.
32. Chen L, Hu JY, Wang SQ. The role of antioxidants in
photoprotection: a critical review. J Am Acad Dermatol.
2012;67(5):1013–24.
33. Zussman J, Ahdout J, Kim J. Vitamins and photoaging: do scien-
tific data support their use? J Am Acad Dermatol. 2010;63(3):507–
25.
34. Phillips CL, Combs SB, Pinnell SR. Effects of ascorbic acid on
proliferation and collagen synthesis in relation to the donor age of
human dermal fibroblasts. J Invest Dermatol. 1994;103:228.
35. Ponec M, Weerheim A, Kempenaar J, et al. The formation of com-
petent barrierlipids in reconstructed human epidermis requires the
presence of vitamin C. J Invest Dermatol. 1997;109:348.
36. Rhie G, Shin MH, Seo JY, Choi WW, Cho KH, Kim KH, et al.
Aging- and photoaging-dependent changes of enzymic and nonen-
zymic antioxidants in the epidermis and dermis of human skin
in vivo. J Investig Dermatol. 2001;117:1212–7.
37. Sauberlich HE. A history of scurvy and vitamin C. In: Packer L,
Fuchs J, editors. Vitamin C in health and disease. 1st ed. New York:
Marcel Dekker, Inc; 1997. p. 1–24.
38. Bertuccelli G, Zerbinati N, Marcellino M, Nanda Kumar NS, He F,
Tsepakolenko V, et al. Effect of a quality-controlled fermented
nutraceutical on skin aging markers: an antioxidant-control,
double-blind study. Exp Ther Med. 2016;11:909–16.
39. Costa A, Pereira ESP, Assumpção EC, Dos Santos FBC, Ota FS,
De Oliveira Pereira M, et al. Assessment of clinical effects and
safety of an oral supplement based on marine protein, vitamin C,
grape seed extract, zinc, and tomato extract in the improvement of
visible signs of skin aging in men. Clin Cosmet Investig Dermatol.
2015;8:319–28.
40. Serrano G, Almudever P, Serrano JM, Milara J, Torrens A,
Exposito I, et al. Phosphatidylcholine liposomes as carriers to im-
prove topical ascorbic acid treatment of skin disorders. Clin Cosmet
Investig Dermatol. 2015;8:591–9.
41. Humbert PG, Haftek M, Creidi P, Lapie’re C, Nusgens B, Richard
A, et al. Topical ascorbic acid on photoaged skin:clinical, topo-
graphical and ultrastructural evaluation; double-blind study vs pla-
cebo. Exp Dermatol. 2003;12:237–44.
42. Murray JC, Burch JA, Streilein RD, Iannacchione MA, Hall RP,
Pinnell SR. A topical antioxidant solution containing vitamins C
and E stabilized by ferulic acid provides protection for human skin
against damage caused by ultraviolet irradiation. J Am Acad
Dermatol. 2008;59(3):418–25.
43. Vanchinathan V, Lim HW. A dermatologist’s perspective on vita-
min D. Mayo Clin Proc. 2012;87:372–80.
44. Mostafa WZ, Hegazy RA. Vitamin D and the skin: focus on a
complex relationship: a review. J Adv Res. 2015 Nov;6(6):793–
804.
Curr Nutr Rep (2020) 9:226–235
45. Piotrowska A, Wierzbicka J, Żmijewski MA. Vitamin D in the skin
physiology and pathology. Acta Biochim Pol. 2016;63(1):17–29.
46. Osborne JE, Hutchinson PE. Vitamin D and systemic cancer: is this
relevant to malignant melanoma? Br J Dermatol. 2002;147:197–
213.
47. De Haes P, Garmyn M, Verstuyf A, De Clercq P, Vandewalle M,
Degreef H, et al. 1,25-Dihydroxyvitamin D3 and analogues protect
primary human keratinocytes against UVB-induced DNA damage.
J Photochem Photobiol B. 2005;78:141–8.
48. Gupta R, Dixon KM, Deo SS, Holliday CJ, Slater M, Halliday GM,
et al. Photoprotection by 1,25 dihydroxyvitamin D3 is associated
with an increase in p53 and a decrease in nitric oxide products. J
Invest Dermatol. 2007;127:707–15.
49. Tang JY, So PL, Epstein EH Jr. Novel hedgehog pathway targets
against basal cell carcinoma. Toxicol Appl Pharmacol. 2007;224:
257–64.
50. Passi S, Morrone A, De Luca C, Picardo M, Ippolito F. Blood levels
of vitamin E, polyunsaturated fatty acids of phospholipids,
lipoperoxides and glutathione peroxidase in patients affected with
seborrheic dermatitis. J Dermatol Sci. 1991;2:171–8.
51. Ekanayake-Mudiyanselage S, Thiele J. Sebaceous glands as trans-
porters of vitamin E. Hautarzt. 2006;57:291–6.
52. Rizvi S, Raza ST, Ahmed F, Ahmad A, Abbas S, Mahdi F. The role
of vitamin e in human health and some diseases. Sultan Qaboos
Univ Med J. 2014;14(2):e157–65.
53. Brigelius-Flohé R, Traber MG. Vitamin E: function and metabo-
lism. FASEB J. 1999;13:1145–55.
54. Thiele JJ, Hsieh SN, Ekanayake-Mudiyanselage S. Vitamin E:crit-
ical review of its current use in cosmetic and clinicaldermatology.
Dermatol Surg. 2005;31:805–13.
55. Al Hawsawi K, Pope E. Yellow nail syndrome. Pediatr Dermatol.
2010;27:675–6.
56. Ayres S Jr, Mihan R. Acne vulgaris: therapy directed at pathophys-
iologic defects. Cutis. 1981;28:41–2.
235
57. Ayres S Jr, Mihan R, Levan NE. Raynaud’s phenomenon, sclero-
derma and calcinosis cutis: response to vitamin E. Cutis. 1973;11:
54–62.
58. Badreshia-Bansal S, Draelos ZD. Insight into skin lightening
cosmeceuticals for women of color. J Drugs Dermatol. 2007;6:
32–9.
59. DiNicolantonio JJ, Bhutani J, O’Keefe JH. The health benefits of
vitamin K. Open Heart. 2015;2(1):e000300.
60. Rina E. Eden, Jean M. Coviello. Vitamin K deficiency. [Updated
2019 Mar 29]. In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2019 Jan-.
61••. . Pazyar N, Houshmand G, Yaghoobi R, Hemmati AA, Zeineli Z,
Ghorbanzadeh B. Wound healing effects of topical Vitamin K: a
randomized controlled trial. Indian J Pharmacol. 2019;51(2):88–
92 In this randomized controlled trial. 63 patients after elec-
trocautery treatment were divided randomly into three
groups: group A received 1% Vitamin K cream; group B
received 1% phenytoin cream; control group received
Eucerin cream. Topical Vitamin K showed a significant
healing when compared with control group.
62. Lou WW, Quintana AT, Geronemus RG, Grossman MC. Effects of
topical vitamin K and retinol on laser-induced purpura on
nonlesional skin. Dermatol Surg. 1999;25(12):942–4.
63. Hemmati AA, Houshmand G, Ghorbanzadeh B, Nemati M,
Behmanesh MA. Topical vitamin K1 promotes repair of full thick-
ness wound in rat. Indian J Pharmacol. 2014;46(4):409–12.
64. Trifunovic A, Larsson NG. Mitochondrial dysfunction as a cause of
ageing. J Intern Med. 2008;263:167–78.
65. Knott A, Achterberg V, Smuda C, Mielke H, Sperling G,
Dunckelmann K, et al. Topical treatment with coenzyme Q10-
containing formulas improves skin’s Q10 level and provides anti-
oxidative effects. Biofactors. 2015;41(6):383–90.
Publisher’s Note Springer Nature remains neutral with regard to jurisdic-
tional claims in published maps and institutional affiliations.