Vitamin D and its role in psoriasis: An overview of the dermatologist and nutritionist

Abstract

Psoriasis is a chronic immune-mediated inflammatory skin disease. Psoriasis lesions are characterized by hyper-proliferation of epidermal keratinocytes associated with inflammatory cellular infiltrate in both dermis and epidermis. The epidermis is the natural source of vitamin D synthesis by sunlight action. Recently, a role for vitamin D in the pathogenesis of different skin diseases, including psoriasis, has been reported. Indeed, significant associations between low vitamin D status and psoriasis have been systematically observed. Due to its role in proliferation and maturation of keratinocytes, vitamin D has become an important local therapeutic option in the treatment of psoriasis. To date, the successful treatment based on adequate dietary intake of vitamin D or oral vitamin D supplementation in psoriasis represent an unmet clinical need and the evidence of its beneficial effects remains still controversial. This information is important either for Dermatologists and Nutritionists to increases the knowledge on the possible bi-directional relationships between low vitamin D status and psoriasis and on the potential usefulness of vitamin D in psoriasis with the aim not only to reduce its clinical severity, but also for delineating the risk profile for co-morbidities cardiac risk factors that may result from psoriasis. In the current review, we analyzed the possible bi-directional links between psoriatic disease and vitamin D.

Full text

Vitamin D and its role in psoriasis: An overview
of the dermatologist and nutritionist
Luigi Barrea
1
&Maria Cristina Savanelli
1
&Carolina Di Somma
2
&
Maddalena Napolitano
3
&Matteo Megna
4
&Annamaria Colao
5
&Silvia Savastano
5
Published online: 7 February 2017
#The Author(s) 2017. This article is published with open access at Springerlink.com
Abstract Psoriasis is a chronic immune-mediated inflamma-
tory skin disease. Psoriasis lesions are characterized by hyper-
proliferation of epidermal keratinocytes associated with in-
flammatory cellular infiltrate in both dermis and epidermis.
The epidermis is the natural source of vitamin D synthesis
by sunlight action. Recently, a role for vitamin D in the path-
ogenesis of different skin diseases, including psoriasis, has
been reported. Indeed, significant associations between low
vitamin D status and psoriasis have been systematically ob-
served. Due to its role in proliferation and maturation of
keratinocytes, vitamin D has become an important local ther-
apeutic option in the treatment of psoriasis. To date, the suc-
cessful treatment based on adequate dietary intake of vitamin
D or oral vitamin D supplementation in psoriasis represent an
unmet clinical need and the evidence of its beneficial effects
remains still controversial. This information is important ei-
ther for Dermatologists and Nutritionists to increases the
knowledge on the possible bi-directional relationships be-
tween low vitamin D status and psoriasis and on the potential
usefulness of vitamin D in psoriasis with the aim not only to
reduce its clinical severity, but also for delineating the risk
profile for co-morbidities cardiac risk factors that may result
from psoriasis. In the current review, weanalyzedthe possible
bi-directional links between psoriatic disease and vitamin D.
Keywords Environmental factors .Vitamin D .Psoriasis .
Dermatologist .Nutritionist .Nutrition
1 Introduction
Psoriasis is a chronic immune-mediated inflammatory skin
disease, with a prevalence of about 2%–3% in the general
population [1]. The primary manifestation of psoriasis most
commonly manifests on the skin, although inflammatory pro-
cesses can occur also in other organs [1]. Indeed, nowadays
psoriasis is considered a systemic pathology, including also
other conditions, from psoriatic arthritis to obesity and meta-
*Silvia Savastano
sisavast@unina.it
Luigi Barrea
luigi.barrea@unina.it
Maria Cristina Savanelli
cristysav@hotmail.com
Carolina Di Somma
cdisomma@unina.it
Maddalena Napolitano
maddy.napolitano@gmail.com
Matteo Megna
mat24@libero.it
Annamaria Colao
colao@unina.it
1
I.O.S. & COLEMAN Srl, Acerra, 80011 Naples, Italy
2
IRCCS SDN, Napoli Via Gianturco 113, 80143 Naples, Italy
3
Dipartimento di Medicina e Scienze della Salute BVincenzo Tiberio^,
Rheumatology Unit, University of Molise, Via Francesco De Sanctis
1, 86100 Campobasso, Italy
4
Dipartimento di Medicina Clinica e Chirurgia, Unit of Dermatology,
Federico II University Medical School of Naples, Via Sergio Pansini
5, 80131 Naples, Italy
5
Dipartimento di Medicina Clinica e Chirurgia, Unit of
Endocrinology, Federico II University Medical School of Naples, Via
Sergio Pansini 5, 80131 Naples, Italy
Rev Endocr Metab Disord (2017) 18:195–205
DOI 10.1007/s11154-017-9411-6
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

bolic disease (MetS), which increased cardiovascular risk in
psoriatic patients [2–4]. Histologically, the dermatosis is char-
acterized by hyperproliferation of keratinocytes, impaired epi-
dermal barrier function at the sites of skin lesions, and skin
infiltration by activated inflammatory cells [5]. The aetiology
of psoriasis is not fully understood. Several factors contribute
to its development, such as auto-immunological, genetic, hor-
monal and psychosomatic issues [6].
Vitamin D, also known as the sunshine vitamin, has long
been known to be a hormone that regulates calcium-
phosphorous homeostasis and safeguards the integrity of the
skeletal system [7]. The epidermis is the natural source of
vitamin D synthesis by the action of ultraviolet light (UV) B
of the sun or other UVB source [8]. On the other hand, evi-
dence is accumulating that vitamin D might represent a key
modulator of immune and inflammation mechanisms [9].
Recently, a role for vitamin D in the pathogenesis of different
skin diseases, including psoriasis, has been reported [9–11].
However, the effectiveness of vitamin D supplementation as
adjunctive treatment option in psoriatic patients still remains
controversial [9–11]. In the current review, we analyzed the
possible bi-directional links between vitamin D and psoriatic
disease.
2 The dermatologist’s point of view
Patients suffering from psoriasis present a broad range of clin-
ical phenotypes. Psoriatic lesions are classified into plaque,
guttate, pustular, and erythrodermic types according to clinical
features, especially regarding lesions size and distribution [1].
Disease onset may occur at any age, including childhood, with
two peak age ranges, 16 to 22 and 57 to 60 years [2,3].
Psoriasis lesions are characterized by hyper-proliferation with
incomplete differentiation of epidermal keratinocytes and de-
creased keratinocyte apoptosis, associated with inflammatory
cellular infiltrate in both dermis and epidermis [12]. Psoriasis
Area and Severity Index (PASI) score is currently the pre-
ferred method for the assessment of the disease severity and
extent [13].
2.1 Effects of vitamin D on skin biology
The role of vitamin D as main regulator of skin physiology
is very complex (Table 1). The epidermis is composed of
four layers: basal layer (stratum basale), spinous layer (stra-
tum spinosum), stratum granulosum and stratum corneum.
The stem cells within the basal layer, which contact the
basement membrane, continually divide during the lifetime
of the organism, providing a source of cells which progres-
sively migrate upwards through the epidermis, differentiat-
ing and stratifying to form the barrier layer of the skin [11,
14]. The process of epidermal differentiation is complex,
sequential, and tightly controlled [11]. The precursor of
vitamin D, 7-dehydrocholesterol, is located in the mem-
branes of keratonocytes of the basal and spinous layer of
epidermis [10]. By the action of UVB (wavelength between
290 and 315 nm), via a photochemical reaction, the B ring
of 7-dehydrocholesterol is broken to form pre-vitamin D3
or cholecalciferol, which is subsequently converted first to
25-hydroxyvitamin D (25OHD) by the enzymes CYP27A1
and CYP2R1 and then to 1,25-hydroxyvitamin D
(1,25(OH)D or calcitriol) the active form of vitamin D, by
CYP27B1 [15]. Physiologically, the active form of vitamin
D and its receptor regulate the differentiation and prolifer-
ation of keratinocytes, the balance of the cutaneous im-
mune system and the process of apoptosis. The
1,25(OH)D has been shown to exert anti-proliferative ef-
fects on keratinocytes [16]. Numerous in vitro and in vivo
studies have demonstrated dose-dependent effects of vita-
min D on proliferation and differentiation of keratinocytes.
Of interest, low concentration of vitamin D promotes
keratinocyte proliferation in vitro, while at higher pharma-
cological doses a clear inhibitory effect became apparent
[14,17]. Moreover, 1,25(OH)D and analogs reduce
S100A7 levels, generally up-regulated in psoriatic skin, in
the reconstituted human epidermis stimulated by IL-22
[18], in interleukin (IL)-17-stimulated keratinocytes and
in skin of patients with psoriasis [19]. Indeed, 1,25(OH)D
regulates the cell proliferation in the stratum basale and
increases the synthesis of keratins (K1 and K10),
involucrin, transglutaminase, loricrin, and filaggrin, in the
stratum spinosum [11,14,15]. Furthermore, vitamin D
helps to regulate the synthesis of glycosylceramides need-
ful for the barrier integrity and permeability in the stratum
corneum [11,14,17]. These actions are due to the capacity
of vitamin D to regulate intracellular calcium level, through
induction of the calcium receptor, and the phospholipase C
enzymes [19,20]. A decrease or deficiency in 1,25(OH)D
or a loss-of-function of its receptor has been shown to dis-
rupt the differentiation of the epidermis, with reduced
levels of involucrin and loricrin and loss of keratohyalin
granules, resulting in hyperproliferation of the basal layer
[11,21–23].
Table 1 Vitamin D actions on skin
Vitamin D actions on skin biology and psoriasis pathogenesis
Regulation of keratinocytes proliferation, differentiation and apoptosis
Regulation of cutaneous immune system (inhibition of T cell
proliferation, Tregs induction)
Down-regulation of pro-inflammatory cytokines
Stimulation of antimicrobial peptides expression
Regulation of barrier integrity and permeability
Vitamin D actions on skin biology and psoriasis pathogenesis
Treg s, Regulatory T cells
196 Rev Endocr Metab Disord (2017) 18:195–205
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2.2 Vitamin D regulation of apoptosis in keratinocytes
Calcitriol stimulates the synthesis of ceramide by inducing the
neutral Mg
2+
-dependent sphingomyelinase (thereby increas-
ing the conversion of sphingomyelin to ceramide) and in re-
turn, ceramide enhances the pro-differentiating effect of
calcitriol on keratinocytes in a feedback loop [10,24]. It has
been demonstrated that physiological concentrations of
calcitriol do not initiate apoptosis in cultured keratinocytes
but, in contrast, pharmacological concentrations of calcitriol
exert a pro-apoptotic effect on keratinocytes [25].
2.3 Effects of vitamin D on the cutaneous immune system
Psoriasis pathogenesis implicates the innate and adaptive seg-
ments of the immune system. In particular, it is centrally con-
trolled by T cells, in which an important role is played by T-
helper (Th)1, Th17 and Th22, interplaying with numerous cell
types via different cytokines, including tumour-necrosis
factor-α(TNF-α), IL-6 and IL-17 [26]. The activity of these
cells is modulated by specific T lymphocytes, named regula-
tory T cells (Treg) [9]. Regulatory T cells (Tregs) are able to
inhibit the immunological response and to preserve the cuta-
neous immunological homeostasis, preventing autoimmune
response against self-antigens [27].
There is an increasing interest on broad regulatory effects
exerted by vitamin D on cells of the adaptive and innate im-
mune system [28]. Indeed, vitamin D acts as a pluripotent
immunomodulator that inhibits proliferation of T lympho-
cytes, induces generation of CD25+/CD4+ Tregs, a phenotype
of T cells promoting tolerance and inhibiting immunity after
stimulation with antigen. Moreover, vitamin D induces the
expression of the C-C chemokine receptor type 10 on surface
of T lymphocytes, a receptor involved in T cell-mediated skin
inflammation, leading their migration from dermal blood ves-
sels to epidermal kerotinocytes [29]. Finally, vitamin D helps
to defend from opportunistic infections, by inducing autoph-
agy in human macrophages, and to support the innate skin
barrier, by stimulating endogenous antimicrobial peptides ex-
pression in resident epithelial cells of the skin [9].
Antimicrobial peptides, like cathelicidins and defensins, have
not only properties against bacteria, fungi and viruses, but also
other immune regulatory properties, including cytokine and
chemokine release, antigen presentation, cell proliferation, in-
creasing vascular permeability, angiogenesis and wound
healing [30].
2.4 Vitamin D and psoriasis linkage
In psoriasis, vitamin D is involved in the maintenance of cu-
taneous barrier homeostasis. Several studies identified an as-
sociation between polymorphisms of vitamin D receptor
(VDR) and psoriasis susceptibility [9]. Richetta et al., have
found that the A-1012G promoter polymorphism of the
VDR gene is associated with psoriasis risk through a lower
expression of VDR mRNA, favoring conditions that may alter
cutaneous barrier and the development of psoriatic lesions
[31]. In addition, in psoriatic skin a decreased expression of
VDR and reduced tight-junction proteins is associated [32].
Tight junctions are fundamental to regulate adhesion and per-
meability of keratinocytes, and to polarize cutaneous cell dif-
ferentiation, to regulate extracellular calcium gradient,
interacting with nuclear and cytoplasmic proteins and
influencing the regulation of specific genes involved in
keratinocytes differentiation and proliferation [32,33].
Different studies have focused on the possible role of low
vitamin D status in the pathogenesis of psoriasis [34–36].
Indeed, several studies reported that vitamin D is a key
modulator of inflammation function [37,38]. The active me-
tabolite of vitamin D exert an anti-inflammatory effect on the
inflammatory profile of human monocytes/macrophage
[39–42], down-regulating the expression and production of
several pro-inflammatory cytokines including TNF-α,IL-
1β,IL-6,andIL-8[43]. Moreover, dendritic cells differentia-
tion, maturation, chemotaxis and antigen presentation seem to
be dampened, and hydrogen peroxide secretion in human
monocytes is also activated by 1,25(OH)D resulting in an
increased oxidative burst potential [9,44]. These anti-
inflammatory effects support a role a low vitamin D status in
the pathogenesis of psoriasis. Recent studies have shown that
1,25(OH)D values are significantly lower in psoriatic patients
than in control subjects, even after adjusting for confounding
factors in a multivariate analysis [11,35]. In another study,
vitamin D levels were lower in women with psoriasis in com-
parison with men, a difference not observed among controls
[45]. Therefore, low levels of vitamin D are negatively asso-
ciated with markers of inflammatory activation (C-reactive
protein, CRP) and obesity [35]. Moreover, other studies
showed that serum vitamin D levels were also reduced in
patients with psoriatic arthritis and being inversely linked to
disease activity [46,47].
2.5 Topical vitamin D in psoriasis treatment
The beneficial effects of vitamin D induced by exposure
to sunlight in the treatment of psoriasis have been
known for decades. The effectiveness on psoriasis of
vitamin D and its derivatives (calcitriol, calcipotriol,
tacalcitol, hexafluoro-1,25(OH)D and maxacalcitol) have
been known since 1985, being confirmed in numerous
trials [45,48]. The therapy with vitamin D, is one of
the most popularly prescribed topical medications for
this disease as the first-line, singly or in combination
with topical corticosteroids, and numerous studies doc-
umented the efficacy and safety of using topical
calcipotriol in the treatment of cases of localized plaque
Rev Endocr Metab Disord (2017) 18:195–205 197
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psoriasis [49–54].Vitamin D analogs are particularly
helpful for hard-to-treat areas such as the face or ingui-
nal regions that are sensitive to steroid-induced atrophy
[55]. Vitamin D analogs do not exhibit tachyphylaxis,
as seen with corticosteroids, and topical treatment can
be continued indefinitely without serious adverse side
effects [9,55]. Additionally, they are effective in the
treatment of psoriatic skin lesions in children and elder-
ly population [56–58]. A recent meta-analysis on the
effectiveness of topical vitamin D therapies evidenced
not only comparable efficacies to corticosteroids when
used as monotherapy, but also superior effects when
vitamin D used in combination with a potent topical
steroid.Accordingtotheseresults, as topical vitamin
D derivatives demonstrated a favorable safety profile,
with Bsteroid-sparing^effects, and should be considered
an indispensable component of the current physician’s
arsenal in the treatment of psoriasis [11].
The therapeutic effects of topical vitamin D occur via
aVDR mediated genomic mechanism resulting in inhi-
bition of keratinocyte proliferation and mediated non-
genomic mechanisms inducing keratinocyte differentia-
tion by increasing intracellular calcium levels [59]. The
anti-inflammatory effects may also result from inhibition
of production of IL-2, IL-6, and interferon-gamma
(IFN-γ). Further, topical calcipotriol inhibits human beta
defensin and proinflammatory cytokines which are
found in increased levels in psoriatic lesions [60].
Allelic variations in individual VDR genes may deter-
mine a different response to treatment: the isoform A
of VDR is associated with a greater therapeutic response
in psoriatic patients [61].
3 The nutritionist’s point of view
Severe psoriasis has been associated with nutritional defi-
ciencies because of an accelerated loss of nutrients, in
particular of vitamin D, from the hyperproliferation and
desquamation of the epidermal layer of skin [62–64].
Vitamin D supplementation is of particular interest to
Nutritionists for two important reasons. First, besides its
topical use, oral vitamin D supplementation represents an
important adjunctive treatment option for psoriatic patients
[9]; second, vitamin D supplementation might be very im-
portant for the prevention of psoriasis-related comorbidity
[65], hypertension [66] and metabolic syndrome [67].
3.1 Food and vitamin D
There are two ways to meet vitamin D requirements in mam-
mals: via nutrition and via synthesis inskin by fromthe sun or
other UVB source [8]. Several recommendations were
published regarding the dietary intake of vitamin D [68–70].
In particular, these recommendations they refer to dietary ref-
erence intakes for calcium and vitamin D updated by the
Institute of Medicine (IOM) in 2010 [71]. To date, as the
evidence for extra-skelatal effects of vitamin D are inconsis-
tent and insufficient, the intake recommendations were based
on beneficial effects of vitamin D only on skeletal health. The
Recommended Dietary Allowances (RDAs) covering require-
ments of ≥97.5% of the population are shown in Table 2.
Other organizations recommended different RDAs: the
Endocrine Society suggested that adults aged 19–50 years re-
quire at least 600 international unit (IU) of vitamin D daily to
maintain bone and muscular function [72]. However, the task
force further annotated that 1500–2000 IU per day are neces-
sary to consistently raise the serum level of 25(OH)D above
30 ng/mL. Finally, for older adults aged 60 and above, the
International Osteoporosis Foundation (IOF) recommended
a RDA of 800–1000 IU in order to reach a serum 25(OH)D
level of 30 ng/mL [73].
The diet is an important determinant of vitamin D status
[71,74]. Some studies have calculated that the amount of
vitamin D intake that would ensure that the majority of the
population (97.5%) maintains plasma 25(OH)D concentra-
tions >25 nmol/l throughout the year is 8.7 mg/d [75]. Only
few foods contain naturally vitamin D, and these foodstuffs
are mainly of animal origin. The vitamin D status is the sum
from the combination of synthesis in the skin after sun expo-
sure and intake of the two main dietary forms of vitamin D:
ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3)
[76]. The first is produced by plants, although fruits and veg-
etables in the human diet contain only minimal amounts of
this nutrient, despite significant amounts of vitamin D2 are
Table 2 Vitamin D dietary reference intakes by life stage
Life-stage group RDA (intake that
covers needs
of ≥97.5% of
population)
Serum 25OHD level
(corresponding to
the RDA)*
IU/d mcg/d ng/ml
Infants (0–12 months) 400** 10** 20
1–70 yr 600 15 20
+ 70 yr 800 20 20
Pregnant 600 15 20
Lactating 600 15 20
The Recommended Dietary Allowances (RDAs) covering requirements
by life stage
RDA,Recommended Dietary Allowance; IU,International Unit
*Measures of serum 25(OH)D levels corresponding to the RDA and
covering the requirements of at least 97.5% of the population
**Reflects adequate intake reference value rather than RDA. RDAs have
not been established for infants
198 Rev Endocr Metab Disord (2017) 18:195–205
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available through dietary supplements. The mushrooms pro-
vide variable amounts of vitamin D2, and if exposed to ultra-
violet light under controlled conditions, the mushrooms can
improve their content of vitamin D2 [77,78]. The vitamin D3
instead, is naturally found in some animal foods, particularly
in fatty fish, including salmon, herring, and mackerel, and in
fish oils [79]. The fish (especially fatty fish and fish liver) have
the highest natural content of vitamin D [80] Also egg yolk
has a high vitamin D3 content [80], which strongly correlates
with the content of vitamin D3 of the hen’s feed [77].
Depending on the hen’sdiet[81] and UVB exposure [82],
the vitamin D3 and 25(OH)D3 were transferred from the
hen to the egg yolk. Regarding of meat products, the content
of vitamin D depends on the contents of vitamin D in the
fodder, the fat content of the meat product, and latitude where
the animals have grazed [83]. Finally, the vitamin D3 is also
available through dietary supplements, and is the form present
in vitamin D-fortified foods such as milk, orange juice, and
cereals. The fortification of food with vitamin D has been
consideredto be the most promising strategywith the broadest
reach and impact [84–86]. In fact, in countries where this
strategy was adopted proved to have a significant influence
on the daily vitamin D intake in the average adult [87]. The
food sources of vitamin D are listed in Table 3[88].
3.2 Bioavailability and influence of processing
and cooking
The vitamin D, like other fat-soluble vitamins (A, E, K), is
absorbed incorporated in mixed micelles from the intestine
into the enterocytes by non-saturable passive diffusion.
Subsequently, the vitamin D is transported in the chylomi-
crons via lymph to the circulation [89]. The more polar me-
tabolite 25(OH)D is absorbed better and faster than vitamin D
because it is also taken up directly from the proximal jejunum
into the portal vein [79]. There are few data on its availability
from natural sources. The absorption of vitamin D from sup-
plements may differ depending on the used vehicle substance,
such as oils, powders, ethanol [90]. For example, it has been
reported that the bioavailability of vitamin D from fortified
hard cheese is equivalent to supplements [91] and that vitamin
D bioavailability is not influenced by the fat content of the
fortified milk [92].
The cooking does not much influence the vitamin D
content of animal foods. Mattila et al. [93] found that, in
eggs boiled for 10 min, the vitamin D3 concentration was
1–6% lower and 25(OH)-D-3 content was 6–11% lower
compared with raw eggs. In addition, also in fish, the
cooking effect was moderate: baking various kinds of fish
(e.g., perch, rainbow trout, Baltic herring) in the oven at
172 °C or 200 °C for 20 min induced a vitamin D3 loss of
<10%, calculated on a dry matter basis [93]. The stability of
vitamin D3 and 25(OH)D and vitamin D2 in foodstuffs
during cooking has been shown to vary widely with heating
process and foodstuffs, with reported retentions in eggs,
margarine and bread after boiling, frying and baking of
between 40% and 88% [94].
3.3 The nutritionist and vitamin D supplementations
Supplements are the most important determinant of varia-
tion in vitamin D intake [85,86,95]A number of studies
showed that the daily intake of vitamin D was higher in
adults using vitamin D supplements than in those without
vitamin D supplementations (348 IU vs 84 IU of vitamin
D) [86]. Most nutritionists recommend the use of vitamin
D3 to treat and prevent vitamin D deficiency, because sev-
eral studies indicating a higher efficacy for vitamin D3 in
raising serum 25(OH)D concentrations when compared to
vitaminD2[96]. Although a significant inter-individual
variation exists, due to different variables including body
weight, sunlight exposure and calcium intake, it has been
calculated that supplementation of 1000 IU of vitamin D3
daily leads to an approximate increase in 25(OH)D levels
by 10–20 ng/mL (25–50 mmol/L), [97–99]. Findings from
randomised placebo-controlled trials conducted during the
winter have shown that each 1 mg of supplemental vitamin
D is associated with an increase in serum 25(OH)D of be-
tween 0.7 nmol/L [100]and2nmol/L[75].
Several studies have observed the safety concerns re-
garding the dosage of vitamin D supplementation.
However, oral vitamin D intakes of up to 10,000 IU daily
were not associated with any harmful effects [101], since
this dose is comparable to the maximum cutaneous vitamin
Table 3 Food sources of vitamin D[88]
Food Amount IUs per serving**
Cod liver oil 1 tablespoon 1360
Swordfish, cooked 3 oz* 566
Salmon (sockeye), cooked 3 oz 477
Tuna fish, canned in water, drained 3 oz 154
Orange juice fortified with vitamin D
(check product labels, as amount
of added vitamin D varies)
1 cup 137
Milk, nonfat, reduced fat, and whole,
vitamin D-fortified
1 cup 115–124
Sardines, canned in oil, drained 2 sardines 46
Liver, beef, cooked 3 oz 42
Egg (vitamin D is found in yolk) 1 large 41
Cheese, Swiss 1 oz 6
The food sources of vitamin D
*1 oz = 28,3495 g
**IU= International Units
Rev Endocr Metab Disord (2017) 18:195–205 199
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D production, and reports of vitamin D intoxication from
cutaneous synthesis alone do not exist [101]. In this con-
text, the IOM and the European Food and Safety Authority
(EFSA) recommend a safe tolerable upper intake level of
4000 IU vitamin D per day for all adults, including preg-
nant and lactating women [102], although, to date, very
few studies have investigated the long-term effects of a
vitamin D intake above the suggested threshold of
4000 IU per day [103,104]. To reach a steady state, after
two to three consecutive months of treatment with vitamin
D supplementation, it’s necessary a re-measurement of
25(OH)D serum levels [98].
Thus, the Nutritionists should consider a general vitamin D
supplementation in populations at high risk for vitamin D
deficiency, such as psoriatic patients [105]. The compounds
of vitamin D commonly used in clinical trials varied from
1,25(OH)D, the physiologically active form of vitamin D, to
1αOHD, alfa-calcidol, requiring only liver metabolism to be
converted to the active form to vitamin D or cholecalciferol,
requiring both liver and kidney metabolism to become active.
Perez et al. observed an overall 88% of clinical improvement
of psoriasis with oral vitamin D with a decrease in mean PASI
scores [61]. The results were confirmed in different studies on
limited number of patients, reporting moderate or greater im-
provement in psoriasis in 25–50% of subjects [106–109]. It
has also been proposed the therapeutic use of systemic alpha-
calcidol in patients with psoriatic arthritis [61]. Another study
demonstrated that a combination ofacitretin and oral calcitriol
resulted in a faster reduction of PASI in patients of chronic
plaque psoriasis [110]. A study on a large population sample
including 70,437 US females over a period of 14 years, ex-
amined the vitamin D intake levels and the incidence of pso-
riasis in the population. After adjusting for confounding var-
iables, the study found that there was no significant associa-
tion between vitamin D intake (dietary, supplementary, and
total vitamin D) and the risk of incident psoriasis. Thus, the
authors proposed that there was no role of dietary or supple-
mental vitamin D intake to prevent the development of psori-
asis [111]. However, current recommendations for dietary in-
take of vitamin D are based only on its effect on skeletal
health, while no information is present as regards psoriasis.
In addition, a discrepancy between recommended RDAs and
actual daily vitamin D intake exists. Therefore, solutions like
food fortification and personalized diet or vitamin D supple-
mentation in psoriatic patients need to be developed. In addi-
tion, taking into account the common association among pso-
riasis, obesity and Mets of which will be discussed in the next
chapter, the advantage of the potential use of oral vitamin D
supplementations to treat psoriasis and metabolic syndrome
concurrently through its anti-inflammatory effects was strong-
ly supported by a comprehensive meta-analysis including the
results of clinical trials using vitamin D supplementation in
psoriasis [106].
3.4 Vitamin D, obesity and psoriasis
Many studies showed the link between psoriasis, obesity
and MetS [112,113].Obesityisanimportant risk factor
for psoriasis [114,115]. The relationship between the two
conditions is probably bidirectional, with obesity, mainly
visceral obesity, predisposing to psoriasis and psoriasis
favouring obesity [116]. In particular, there was a 2-fold
increased risk for psoriasis development in the setting of
obesity as compared with normal weight subjects [117].
In addition, for each unit increment increase in body mass
index (BMI) was reported a 9% higher risk for psoriasis
onset and a 7% higher risk for increased of PASI score
[118]. A further evidence of the link between, obesity,
inflammation and cardiovascular diseases in patients with
psoriasis is provided by several studies reporting a corre-
lation between PASI score and increased of CRP levels
[119] and between psoriasis and waist circumference
[120]. CRP is an acute phase protein significantly associ-
ated with obesity, representing the most sensitive markers
of inflammation and an independent risk for cardiovascu-
lar disease. Waist circumference represents a surrogate
measure of fat distribution highly correlated with visceral
fat [121],themainsourceofinflammatorycytokinesin
obesity [122]. In particular, obesity and psoriasis are both
pro-inflammatory conditions, in which the adipokines bal-
ance is shifted in favor to action pro-inflammatory
adipokines [123,124]. On the one hand, the dominance
of pro-inflammatory adipokines favors either the develop-
ment and the maintenance of obesity and its conse-
quences, including cardiovascular diseases, type 2 diabe-
tes, and MetS [125]; on the other hand, the production of
inflammatory cytokines in visceral obesity represents the
link involved in the complex mechanisms leading to the
exacerbation of psoriasis and to psoriasis co-morbidities
[126]. Indeed, psoriasis is frequently associated with
cardio-metabolic co-morbidities and with an increased
cardiovascular mortality [127,128].
Similarly, there are significant associations between low
vitamin D status and increased risk of obesity and obesity-
related co-morbidities and cardiovascular mortality [127].
In particular, higher BMI leads to lower vitamin D status,
with an inverse association between mortality risk and vi-
tamin D levels, although this association could be indirectly
mediated by the obesity per se [129]. Ju SYet al. performed
a meta-analysis of the dose-response relationship between
blood vitamin D levels and the risk of MetS. Using data on
blood 25(OH)D levels, a monotonically decreasing rela-
tionship was observed for low levels of blood 25(OH)D in
the pooled analyses of 16 cross-sectional studies (OR =0.89
for 30 nmol/L, OR =0.80 for 60 nmol/L, OR =0.71 for
90 nmol/L, and OR =0.63 for 120 nmol/L). A 25 nmol/L
increase in 25(OH)D levels was associated with a 13%
200 Rev Endocr Metab Disord (2017) 18:195–205
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

decrease in the risk of MetS in cross-sectional studies [130].
Several mechanisms might account for the low vitamin D
status in obese subjects, [131]. Besides a low dietary intake
of vitamin D linked to restrictive weight-loss diet regimen,
the most likely explanations for low vitamin D status in
obesity are sequestration of vitamin D in the adipose tissue
[132], volumetric dilution related to the greater volume of
distribution of 25(OH)D, less exposure of skin to sunlight
due to less outdoor activity and air pollution [133].The
associations of low vitamin D status with obesity on the
one hand, and with psoriasis on the other hand, lend support
to the hypothesis for considering vitamin D as a further link
between obesity and psoriasis. In this contest, a vicious
cycle could operate among low vitamin D status, obesity,
and psoriasis, with additive detrimental effects on cardio-
metabolic risk in obese psoriatic patients. According to this
hypothesis, vitamin D supplementation might be of partic-
ular usefulness for the prevention of psoriasis-related
comorbidities.
4Conclusions
Due to its role in proliferation and maturation of keratinocytes,
vitamin D has become an important local therapeutic option in
the treatment of psoriasis. Indeed, significant associations be-
tween low vitamin D status and psoriasis have been system-
atically observed. Although the exact role of vitamin D in the
pathogenesis of psoriasis is unclear, understanding the possi-
ble bi-directional relationships between low vitamin D status
and psoriasis is also important for delineating the risk profile
for co-morbidities that may result from psoriasis, such as obe-
sity, type 2 diabetes, and MetS. To date, the successful treat-
ment based on adequate dietary intake of vitamin D or oral
vitamin D supplementation in psoriasis represent an unmet
clinical need and the evidence of its beneficial effects remains
still controversial. Nevertheless, the Nutritionists should con-
sider a general vitamin D supplementation in populations at
high risk for vitamin D deficiency, such as psoriatic patients.
This information is important either for Dermatologists and
Nutritionists to increase the knowledge on the potential use-
fulness of vitamin D in psoriasis with the aim to reduce not
only its clinical severity, but also cardiac risk factors and pso-
riasis co-morbidities. Future well-designed dietary interven-
tion trials with vitamin D supplementations on large popula-
tion samples are needed to define the specific dose of vitamin
D supplementations for psoriasis.
1,25(OH)D, 1,25-hydroxyvitamin D or calcitriol; 25OHD,
25-hydroxyvitamin D; BMI, body mass index; CRP, C-
reactive protein; IL, interleukin; MetS, metabolic disease;
PASI, psoriasis area and severity index; RDAs, recommended
dietary allowances; TNF, tumor necrosis factor; VDR, vitamin
Dreceptor.
Acknowledgements We would like to acknowledge all the
Collaborators of this review: Antonio Improta, Dr. Lidia Albanese and
Dr. Vincenza Grazia Mele.
Compliance with ethical standards
Conflict of interest statement and funding sources The authors de-
clare that they have no conflict of interest. There was no funding source
for this work.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
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