doi: 10.1111/j.1365-2222.2011.03923.

Clinical & Experimental Allergy, 110

INVITED REVIEW

2011 Blackwell Publishing Ltd

Vitamin D and its role in allergic disease

M. Reinholz, T. Ruzicka and J. Schauber
Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany

Clinical &
Experimental
Allergy

Correspondence:
Jurgen Schauber, Klinik und Poliklinik
fur Dermatologie und Allergologie,
Ludwig-Maximilians-Universitat
Munchen, Frauenlobstr. 9-11,
80337 Munchen, Germany.
E-mail: juergen.schauber@med.
uni-muenchen.de

Abstract
In Western countries, the incidence of atopy and allergic diseases is high and further rising. While genetic factors certainly play a role, epigenetic or even nutritional factors
might also be important in the pathogenesis of allergies. Vitamin D the sunshine hormone exerts profound effects on both adaptive and innate immune functions involved
in the development and course of allergic diseases. As also the incidence of vitamin D
insufficiency is surprisingly high in the general population, clinical and experimental
studies have started to investigate if correcting vitamin D levels [measured as serum 25
hydroxy vitamin D -25(OH)D] is beneficial or even protective in patients with allergies or
children at risk. This review highlights current data on the effects of vitamin D on the
allergy-mediating immune system and the vitamin D status in atopic patients. Furthermore, the benefits and risks of vitamin D supplementation during pregnancy, childhood
and in adults with respect to the development and course of allergic disease are discussed.
Keywords adult, allergy, asthma, atopy, childhood, pregnancy, Vitamin D, vitamin D
deficiency, vitamin D supplementation
Submitted 06 May 2011; revised 10 October 2011; accepted 10 October 2011

Introduction
Vitamin D can be ingested from foods, but can also be
produced from precursor molecules by man himself.
Initially characterized for its role in bone metabolism it
is now well established that vitamin D also exerts profound effects on our immune system. In particular,
vitamin D regulates the activity of various immune
cells, including monocytes, dendritic cells (DCs), T and
B lymphocytes, as well as immune functions of epithelial cells [1]. Furthermore, some immune cells express
vitamin D-activating enzymes facilitating local conversion of inactive vitamin D into active calcitriol with
subsequent paracrine and autocrine effects [2, 3]. The
impact of vitamin D on immune functions might be
particularly critical as prevalence of hypovitaminosis D
is high with up to 30% in the adult Western population
and up to 70% in the elderly or institutionalized [4].
Similar to this pandemia of hypovitaminosis D [5], the
prevalence of disturbed immune functions leading to
atopy in Western countries is high with reported up to
16% in children in Sweden [6]. Furthermore, epidemiological studies suggest that atopic diseases increased
significantly in most Westernized countries [711].
Actually, low-serum 25 hydroxy vitamin D [25(OH)D]
levels are prevalent in every region studied (e.g. very

low levels are most common in regions such as South

Asia and the Middle East). Older age, female gender,
higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence
of dietary vitamin D fortification are the main factors
that are significantly associated with low 25(OH)D
serum levels [4].
As 25(OH)D serum levels are low in individuals and
vitamin D influences allergy-mediating immune cells
such as T cells and the immune functions of cells forming the barriers against allergens such as epithelial
cells, one might speculate that vitamin D plays a role in
allergy development. Consequently, the first scientists
who hypothesized a link between nutritional intake of
vitamin D and allergies were Wjst and Dold in 1999
[12]. In 2004, Zitterman et al. suggested an effect of
vitamin D deficiency on allergy risk when they
observed an association between low vitamin D status
and low cord blood levels of the tolerogenic cytokine
interleukin (IL)-10 [13]. Furthermore, Camargo et al.
suggested that regional differences in vitamin D status
were responsible for a strong northsouth gradient for
the prescription of EpiPens as emergency treatment for
severe allergic reactions in the USA. [14].
In addition, one has started to ask whether correcting
vitamin D levels affects the incidence and the course of

2 M. Reinholz et al
allergic disease [15]. While some aspects of this issue
have been investigated in clinical studies, many questions remain: Should vitamin D be supplemented in an
effort to prevent allergic diseases? Should the recommended intake differ from the daily dose of more than
400 I.E. of vitamin D, which has been suggested for
bone health [16]? In this review, the basic metabolism
of vitamin D and current data on the effects of vitamin
D on innate and adaptive immune functions will be
outlined. In addition, the available clinical data on the
role of vitamin D in allergic disease will be discussed.
Clinical and experimental data were retrieved from
Pubmed following online searches using the keywords
vitamin D, allergy, atopy, asthma, pregnancy,
childhood, adult, vitamin D deficiency and
vitamin D substitution.
What is the basic biology of vitamin D?
As mentioned above, the vitamin D is a conditional
vitamin that can be produced and activated by various
cells in the human body. UVB irradiation and several
enzymes performing hydroxylation steps are required
for the production of active vitamin D from precursor
molecules. The vitamin D proform 7-dehydro-cholesterol is transformed in the skin under the influence of
UVB irradiation to pre-vitamin-D (cholecalciferol)
(Fig. 1). Pre-vitamin D undergoes a conformational shift
to vitamin D, binds to vitamin-D binding protein
(VDBP) and is transported to the liver where CYP27A1
(25-hydroxylase) hydroxylates vitamin D to calcidiol
[25(OH)D, 25-hydroxy vitamin D]. 25(OH)D is transported by VDBP to the kidney where CYP27B1 (1ahydroxylase) hydroxylates 25(OH)D and the active form
of vitamin D, calcitriol [1,25(OH)D, 1,25-dihydroxy
vitamin D] is produced [17]. Noteworthy, the hydroxylation steps converting 25(OH)D to 1,25(OH)D can also
be performed by other cells in the body such as epidermal keratinocytes and myeloid cells, which express
CYP27A1 and CYP27B1 [18, 19]. Finally, increased or
decreased expression of enzymes metabolizing vitamin

Fig. 1. Metabolic activation of vitamin D.

D such as CYP27B1 is a further regulatory mechanism

in the activation of vitamin D [20].
Sources of vitamin D
Natural sources of vitamin D (cholecalciferol) include
various foods such as fatty fish species (e.g. salmon, eel
and herring), fish liver or cod liver oil. In some industrial countries, artificial sources of vitamin D are fortified foods (e.g. milk, dairy products). Also, many
countries recommend the intake of supplements with
vitamin D usually containing 525 lg (2001000 IU)
cholecalciferol or ergocalciferol. Supplemented ergocalciferol (vitamin D2) is equally effective as in vivo as
cholecalciferol (vitamin D3) in maintaining circulating
25(OH)D concentrations [21].
Currently, a daily intake of 5 lg (equal to 200 IU)
vitamin D is suggested by the Commission of the European Union for adults [22]. In the UK, elderly people
(>65 years) are recommended to take 10 lg (400 IU) of
vitamin D as a supplemental dose [23]. The Nordic dietary vitamin D recommendation for children of 3 years
to adults of 60 years is 7.5 lg/day (300 IU) vitamin D.
Infants younger than 3 years and adults over 60 are
recommended 10 lg/day (400 IU) [23].
Nevertheless, the current guidelines on the daily reference intake of vitamin D and calcium published by
the Institute of Medicine (IOM) of the National Academies, a North-American organization, state that vitamin
D supplemention is not necessary to achieve the recommend level of circulating serum 25(OH)D [24]. The IOM
suggests a daily vitamin D reference intake of 15 lg/
day (600 IU) for individuals between 3 and 70 years of
age irrespective of the source of vitamin D. People > 70
or < 3 years of age are recommended 20 lg (800 IU)
vitamin D.
Earlier, for infants (birth to 12 months), the upper
limit which is tolerated without harm was set at 25 lg/
day (1000 IU) [25, 26] and doses exceeding 1000 lg/
day (40000 IU) have produced toxicity and hypercalcaemia [27].
As mentioned above, vitamin D can also be produced
by the human organism and a whole body exposure to
one minimal erythemal dose of simulated solar ultraviolet irradiation is comparable to taking an oral dose of
250625 lg (10000 and 25000 IU) cholecalciferol [28].
A Dutch study demonstrated that in institutionalized
patients, who had a baseline mean serum 25(OH)D of
28.5 nmol/L, a weekly half-body irradiation of half
minimal erythemal dose (0.5) over 8 weeks resulted in
(almost) sufficient vitamin D blood serum levels of
46.5 nmol/L [29].
Vitamin D status is measured by blood serum 25(OH)
D levels. The guidelines of the IOM define vitamin D
deficiency as serum 25(OH)D levels below 30 nmol/L
2011 Blackwell Publishing Ltd, Clinical & Experimental Allergy, 110

Vitamin D and allergic disease

(<12 ng/mL). People are at risk for vitamin D insufficiency at serum 25(OH)D levels between 30 and
50 nmol/L (12 and < 20 ng/mL). Sufficient vitamin
D is defined as serum 25(OH)D levels of least 50 nmol/L
(20 ng/mL) (Table 1). Serum 25(OH)D concentrations
above 75 nmol/L (30 ng/mL) are not consistently
associated with increased benefit and levels above
125 nmol/L (>50 ng/mL) might even be associated with
adverse effects [24]. Noteworthy, these concentrations
are mainly reflecting recommendations for vitamin D
and bone health. The concentrations needed for
probable immune effects of vitamin D are not known
[30].
Effects of vitamin D on the immune system
As mentioned above, vitamin D has initially been identified for its role in bone metabolism; however, in
recent years, more and more effects of vitamin D on
immune functions were observed. Interestingly, vitamin
D controls effector immune functions, promotes regulatory immune response and induces innate immune
defences. All of these could be relevant in allergic
disease.
Effects of vitamin D on innate immunity
The major task for the immune system is to protect the
individual from external danger. Still, while a powerful
defence against e.g. microbial pathogens has to be
mounted by the immune system in a very short time,
this response has to be fine-tuned to avoid excess
inflammation and tissue damage. The human immune
system is divided into two branches: Adaptive and
innate immunity. Broadly defined, innate immune
responses comprise all mechanisms that resist infection,
but do not require specific recognition of the pathogen.
Several aspects of innate immunity are affected by vitamin D: Vitamin D inhibits the expression of patternrecognition receptors, which activate innate immune
responses such as the Toll-like receptors (TLR) on
monocytes and suppresses TLR-mediated inflammation
[31]. Other studies demonstrate that vitamin D decreases
immune receptor expression also on monocyte-derived
DCs, inhibits DC activation by e.g. LPS and reduces the
Table 1. Classification of vitamin D status as measured by the serum
level of 25 hydroxy vitamin D [25(OH)D] and as outlined by the
Institute of Medicine (IOM). (24) Nota bene: The IOM suggests that 25
(OH)D serum levels above 75 nmol/L are not associated with increased
benefit
Classification of vitamin D status [25(OH)D serum level]
Deficiency
<30 nmol/L
Insufficiency
50 nmol/L
Normal
50125 nmol/L

2011 Blackwell Publishing Ltd, Clinical & Experimental Allergy, 110

function of these cells (e.g. chemotaxis, antigen presentation, maturation) [3234]. Furthermore, vitamin D
induces autophagy in human macrophages, which could
be important in the defence against opportunistic infections [35]. Vitamin D also induces endogenous antimicrobial peptide expression in resident epithelial cells in
skin and lung, thereby strengthening the innate barriers
against environmental allergens [32, 33].
Effects of vitamin D on adaptive immunity
Adaptive immunity comprises cells that specifically recognize and remember pathogens. Lymphocytes such as
T cells with Th1 or Th2 polarization are major players
in adaptive immunity and vitamin D modulates their
functions: Vitamin D decreases pro-inflammatory cytokine release from peripheral mononuclear blood cells
(PMBC) in general and from T cells in particular [36,
37]. In addition, vitamin D inhibits T-cell proliferation
through decreased Th1 cytokine secretion [38, 39]. The
effects on Th2 cells are less clear, one study finds that
vitamin D induces IL-4, IL-5 and IL-13 in vitro, whereas
another study finds no effect [4042]. However, vitamin
D supplementation does not induce Th2 responses
in vivo [43]. Furthermore, pro-inflammatory Th17
responses are also blocked by administration of vitamin
D in mice and man [44]. Also, vitamin D increases
IL-10 and decreases IL-2 production, thereby inducing
a state of hyporesponsiveness in T regulatory cells (Treg)
cells an effect which is also seen with anti-allergic
therapies such as corticosteroids or allergen immunotherapy [36, 45]. Finally, application of vitamin D leads
to inhibition of effector T cells, and vitamin D deficiency may promote autoimmunity by favouring the
inordinate production of Th17 and Th9 cells at the
expense of IL-10-producing Tregs [46].
Effects of vitamin D on IgE secretion, mast cells and
eosinophils
Vitamin D also effects B lymphocyte functions and
modulates the humoral immune response including
secretion of IgE [47]. Allergy-mediating cells such as
mast cells and eosinophils are further vitamin D targets:
Increased cutaneous vitamin D synthesis increases IL-10
production in mast cells, which leads to suppression of
skin inflammation [48]. Also, vitamin D-treated mice
showed reduced airway hyperresponsiveness and
decreased infiltration of eosinophils in the lung [49].
Vitamin D insufficiency in Western countries?
Observations that vitamin D influences immune functions involved in allergic disease have prompted the
question if 25(OH)D serum levels correlate with the risk

4 M. Reinholz et al
for allergies. As mentioned in the introduction, vitamin
D insufficiency is a surprisingly common finding in the
Western population. A Danish study which measured
the distribution of serum 25(OH)D levels of 182 participants at the initial screening in January showed that
67% of the participants were vitamin D insufficient (25
(OH)D < 50 nmol/L), and 18% were vitamin D deficient
[25(OH)D  25 nmol/L] [50]. Another study performed
in Great Britain demonstrated the monthly variation in
serum 25(OH)D in men and women in the 1958 British
birth cohort. The study showed that all participants had
insufficient 25(OH)D levels in the months January to
May, only during July to November, 25(OH)D serum
levels were over 50 nmol/L [51]. A further study measured the serum 25(OH)D concentration levels in
patients with atopic eczema, psoriasis and healthy controls in Finland in winter and found that atopic patients
had significantly lower levels than healthy controls
[52]. Hintzpeter et al. analysed a total of 1763 men and
2267 women (18- to 79-year old) who participated in
large surveys in Germany; 80.9% of men and 88.5% of
women reported vitamin D intakes, which did not meet
the recommended level of 5 lg/day [53]. Furthermore, a
high prevalence of vitamin D deficiency among children
and adolescents was reported in countries with even
moderate climates [54]. Looker et al. showed that twothirds of the USA. American population had sufficient
vitamin D [25(OH)D serum level: 50125 nmol/L]. About
one-quarter were at risk of vitamin D inadequacy [25
(OH)D: 3049 nmol/L] and 8% were at risk of vitamin D
deficiency [25(OH)D: less than 30 nmol/L] [55].
Serum levels of vitamin D and allergic disease
As vitamin D has effects on inflammatory pathways
and cells involved in the development and course of
allergic diseases, several studies have investigated a
relationship between vitamin D and allergic disease.
Vitamin D status and allergic disease in adults
In adult patients, several clinical studies analysed vitamin D levels and the severity of allergic disease such as
asthma and chronic rhinoconjunctivitis (CRS). While in
one study no difference in serum 25(OH)D between
adult asthmatics and controls was observed, Li et al.
found that vitamin D deficiency was highly prevalent
and 25(OH)D status strongly correlated with pulmonary
function (FEV1) in asthmatics [5658]. This is consistent
with observations that higher 25(OH)D serum levels
improve pulmonary function in adults, while insufficient serum levels of 25(OH)D are associated with
severe pulmonary dysfunction [5961]. As vitamin D
enhances the effects of glucocorticoids on PMBCs from
asthmatic patients, correcting serum 25(OH)D levels,

especially in asthmatic patients, might therefore be

beneficial [62].
Interestingly, Hyppoonen et al. showed that IgE concentrations were higher for participants with low 25
(OH)D (<25 nmol/L) and with very high 25(OH)D serum
levels (>135 nmol/L) compared with a reference group
(100125 nmol/L). Thus, low and very high 25(OH)D
levels are associated with elevated IgE levels in adults
[63]. Correcting serum concentrations of 25(OH)D to
physiological levels reduced the IgE level significantly,
further supporting an allergy-protective role for vitamin
D in adults. For other allergic diseases such as CRS,
current clinical studies have shown that CRS patients
had 25(OH)D serum levels that were 4050% lower than
the 25(OH)D serum levels in the control group [57, 58].
In contrast, the incidence of allergic rhinitis (AR) correlated with increasing 25(OH)D serum levels in very
early studies from 1930 and 1962 long before vitamin
D re-entered the spotlight as an allergy influencing factor [64]. Notably, corrections for geographical region
and month of examination did not change this association in those studies. Still, vitamin D intake above current dietary recommendations was not reported to be
associated with an increased risk of adverse events.
However, most studies using higher doses of vitamin D
were not adequately designed to assess long-term harms
[65].
Maternal vitamin D status and allergic disease
development in children
As the predisposition to allergies might already be
acquired in utero or during the development of the
immune system, several studies have investigated if
maternal vitamin D intake influences the allergy risk in
children. Camargo et al. reported that high 25(OH)D
levels during maternity decreased childhood wheezing
by nearly 50% compared with low maternal 25(OH)D.
Consequently, they suggested that cord-blood levels of
25(OH)D are inversely associated with the risk of respiratory infection and childhood wheezing, but not with
incident asthma [66, 67]. This was reproduced in a larger study, which demonstrated that maternal vitamin D
intake during pregnancy decreased the risk of wheeze
symptoms in early childhood [68]. In addition, Erkkola
et al. showed that maternal vitamin D intake from
foods during pregnancy was negatively associated with
the risk of asthma and AR in childhood. Noteworthy,
the intake of vitamin D supplements was not associated
with a decreased risk for allergic disease [69]. The same
was demonstrated by Nwaru et al. in a prospective
study in which maternal vitamin D intake from foods
during pregnancy was negatively associated with the
risk of food allergies at the age of 5 [70]. These
observations were confirmed in a meta-analysis of 11
2011 Blackwell Publishing Ltd, Clinical & Experimental Allergy, 110

Vitamin D and allergic disease

databases performed by Nurmatov et al., who concluded

that high maternal dietary vitamin D and E intakes during pregnancy were protective against the development
of childhood wheezing [71]. In another study, those
results were reproduced, and reduced maternal intake of
vitamin E, vitamin D and zinc during pregnancy was
associated with increased wheezing outcomes in
children [72].
On a molecular level, maternal vitamin D intake during pregnancy increases the mRNA levels of the leucocyte receptors ILT3 and ILT4 in umbilical cord blood.
As ILT3 and ILT4 are critical for the generation of T
suppressor cells and induction of immunological tolerance, this finding may point towards an early induction
of tolerogenic immune responses by maternal vitamin
D intake in the developing child [73].
Still, high vitamin D intake during pregnancy might
also be harmful with respect to allergic disease development: children whose mothers had a 25(OH)D concentration during pregnancy greater than 75 nmol/L had
an increased risk of atopic eczema on examination at
9 months (odds ratio, OR 3.26) and asthma at the age
of 9 years (OR 5.40) compared with children whose
mothers had a concentration of < 30 nmol/L [74].
Vitamin D status and allergic disease in children
As first symptoms of allergic disease are typically seen
during childhood, several studies analysed 25(OH)D
serum levels and allergic disease in children. Indeed, in
children and adolescents, allergic sensitization to 11 of
17 investigated allergens was more common in those
with vitamin D deficiency. In particular, 25(OH)D levels
below 15 ng/mL were associated with peanut (OR 2.39),
ragweed (OR 1.83) and oak (OR, 4.75) allergy [75]. In
children with atopic eczema (AE), mean 25(OH)D serum
levels were significantly higher in patients with mild
disease compared with those with moderate or severe
AE [76].
Moreover, Mullins et al. showed significantly higher
rates of food allergy in children born autumn/winter
(compared with spring/summer), suggesting a relationship between relative food allergy rates and monthly
UV irradiation [77]. They hypothesized that UV light
exposure/vitamin D status may be one of many potential factors contributing to the pathogenesis of
childhood food allergy.
As a mechanism, a multiple hit model was suggested
in which the lack of vitamin D impairs the epithelial
barrier integrity, which leads to increased and inappropriate mucosal exposure to food antigens. In this model,
vitamin D deficiency would also promote a pro-sensitization immune imbalance that compromises immunological tolerance. Thus, the authors suggest that early
correction of vitamin D deficiency might promote
2011 Blackwell Publishing Ltd, Clinical & Experimental Allergy, 110

mucosal defence, maintain healthy microbial ecology

and allergen tolerance, and thereby limit food allergies
in children [78, 79].
Concerning childhood asthma, Brehm et al. observed
that children with asthma had low serum 25(OH)D even
in Costa Rica (probably due to an undersupply of vitamin D). Of 616 children with asthma, 21 (3.4%) had 25
(OH)D serum levels less than 20 ng/mL (considered deficient), and an additional 152 (24.6%) had levels
between 20 and 30 ng/mL (considered insufficient) [80].
Other studies failed to confirm these results, and
Hughes et al. found no association between any of the
UVR- or vitamin D-related measures and childhood
asthma. In contrast, greater time in the sun in winter
between the ages 6 and 15 years increased the odds of
having hayfever, and oral supplementation with cod
liver oil in childhood even increased the odds of a
history of having both asthma and hayfever [81].
Attempts to increase serum vitamin D in allergic
diseases and their effects
Vitamin D supplementation and allergic disease in
children
As serum 25(OH)D can be influenced by either oral supplementation or UVB exposure, and vitamin D might
have an impact on the development of allergic disease,
several investigators examined the outcome of vitamin
D supplementation on the course of allergic disease.
Back et al. showed that children who were supplemented with vitamin D (> 13.1 lg/day) showed an
increased risk to develop either atopic eczema, AR or
allergic asthma [82]. In particular, vitamin D intake led
to an increased risk of developing atopic eczema at the
age of 6 when a positive family history for atopic
eczema was already reported. Similarly, Hypponen et al.
showed that dietary intake of vitamin D during infancy
promoted allergic disease at age 31 [83]. Further supporting a deleterious role for vitamin D supplementation, Milner et al. found that early vitamin
supplementation in children was associated with
increased risk for asthma and food allergies [84]. These
results have prompted the question whether the mode
of application of vitamin D might also be important for
promoting allergic diseases. Indeed, Kull et al. could
show that vitamin D in water-soluble form seemed to
increase the risk of allergic disease up to the age of
4 years compared with supplementation of vitamin D
given in peanut oil [85].
Nevertheless, there might be beneficial effects of vitamin supplementation in specific patient groups: A prospective study published only recently suggested that
vitamin D supplementation in children with asthma
reduces the risk for recurrent respiratory infections and

6 M. Reinholz et al
Table 2. Summary of clinical studies on the role of vitamin D in allergic disease
Author

Year

Outcome

Adults
Black [59]
Pinto [57]
Wjst [64]
Hypponen [63]
Searing [62]
Devereux [58]
Li [56]
Pregnancy
Devereux [68]

2005
2008
2009
2009
2010
2010
2010

Serum 25D levels correlate with pulmonary function.

Serum 25D levels are lower in patients with chronic rhinosinusitis.
The incidence of allergic rhinitis correlates with increased vitamin D supplementation.
High or low 25D levels are associated with elevated serum IgE.
Vitamin D enhances the immunosuppressive function of dexamethasone ex vivo.
25D serum levels do not differ between asthmatics and controls.
Low serum 25D correlates with decreased FEV1, but not with IgE-levels.

2007

Camargo [66]

2007

Gale [74]

2008

Erkkola [69]

2009

Nwaru [70]

2010

Camargo [67]

2010

Nurmatov [71]

2011

Maternal vitamin D intake during pregnancy decreases risk of wheeze symptoms

in early childhood.
High maternal vitamin D intake during pregnancy decreases risk of recurrent wheeze in
early childhood.
Very high maternal serum 25D increases risk of eczema on examination at 9 months
and asthma at the age of 9 years.
High maternal vitamin D intake is negatively associated with the risk of asthma and
allergic rhinitis in childhood.
Increased vitamin D intake during pregnancy is negatively associated with the risk of
food allergies at the age of 5.
High 25D serum levels are inversely associated with risk of childhood wheezing, but
not with incident asthma.
Elevated vitamin D intake during pregnancy is protective for the development of
childhood wheezing (meta-analysis).

Children
Brehm [80]
Hughes [81]

2009
2010

Peroni [76]

2010

Vasallo [78, 79]

2010

Mullins [77]

2011

Sharief [75]
2011
Children vitamin D supplementation
Hypponen [83]
2004

Kull [85]

2006

Sidbury [88]
Back [82]
Urashima [87]

2008
2009
2010

Majak [86]

2011

Low serum concentrations of 25D in children in Costa-Rica are associated with asthma.
Oral supplementation with cod liver oil increases risk for asthma, hayfever. UV
exposure in childhood leads to allergic sensitization.
25D serum levels were significantly higher in patients with mild atopic eczema
compared to severe disease.
Seasonal fluctuations in UVB irradiation and perhaps vitamin D are involved in the
pathogenesis of food allergy in children.
Reduced UV exposure/vitamin D status might be responsible for higher rates of food
allergy of children born in autumn/winter.
Low 25D serum levels are associated with higher incidence of IgE sensitizations.
Vitamin D supplementation in infancy increases the risk for atopic eczema and allergic
rhinitis at age 31.
Vitamin D intake in a water-soluble form increases the risk of allergic disease (vitamin
D in oil has no effect).
Vitamin D supplementation reduces symptoms in winter-related atopic eczema.
Atopic manifestations are more prevalent in children with higher intake of vitamin D.
Vitamin D supplementation in children in winter reduces the rate of influenza infection
and frequency of asthma attacks.
Vitamin D supplementation in children may prevent asthma exacerbation triggered by
acute respiratory infection.

( protective role of vitamin D; deleterious role of vitamin D; no role for vitamin D)

thus the risk for disease exacerbation [86]. Furthermore,

Urashima et al. showed in one of the first randomized
controlled trials (RCT) that vitamin D supplementation
in children during the winter months reduced the rate
of influenza A infections and the frequency of asthma
attacks [87]. Also, a recent pilot RCT demonstrated a
favourable effect of vitamin D supplementation on AE
symptoms in children during winter months [88]. This
effect again could have been mediated by the induction

of endogenous antimicrobial peptides in the skin in AE

by oral vitamin D supplementation [89].
Concluding remarks
There are many unanswered questions concerning the
role of vitamin D in the prevention or the treatment of
allergic disease. Undoubtedly, vitamin D insufficiency
[25(OH)D < 50 nmol/L] is very common in the general
2011 Blackwell Publishing Ltd, Clinical & Experimental Allergy, 110

Vitamin D and allergic disease

population [50] as is the prevalence of atopy and allergic diseases. As vitamin D exerts profound effects on
immune cells involved in the development and the
course of allergies, it is tempting to hypothesize that
there might be a link. However, while experimental and
pre-clinical data point towards a protective role of vitamin D, the clinical results available to date draw a less
clear picture. Indeed, the results of the available studies
are very heterogeneous, and from the data available, no
clear recommendation for vitamin D supplementation
can be derived (Table 2).
In particular, no clear association between vitamin D
status and allergies in adults was detected in observational studies. Asthmatic patients might be the only
ones who could benefit from vitamin D supplementation; however, data on an appropriate dosage or treatment intervals are currently missing [90]. A little bit
more consistent are data derived from studies investigating the influence of vitamin D status during pregnancy and the incidence of allergic diseases in the
offspring. Here, most studies are in favour of a protective role of vitamin D. Childhood wheezing is the disease that is probably most likely to be prevented by
sufficient vitamin D during pregnancy. While not investigated in larger clinical studies, vitamin D derived from
nutritional sources might be most suitable, especially as
very high serum levels of 25(OH)D (which could result
from the intake of large quantities of vitamin D supplements) are associated with adverse effects and an
increased risk for childhood eczema and asthma. In
children, lower 25(OH)D serum levels are also associated
with increased risks for allergic disease. Most published
clinical studies, however, report a link between oral

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based on observational, and often retrospective, studies.
Questionnaires to record intake of vitamin D supplements or consumption of vitamin D containing nutrition are often used and might not reflect reality,
especially when filled in retrospectively. Also, timing,
length of consumption, combination with other nutrients and even the form of application (water-soluble
vitamin D vs. in peanut oil [85]) are factors among
many, which could influence the effect of vitamin D on
the immune functions, and hence allergic disease.
Nevertheless, some promising data from smaller RCTs
were recently published, which indicate a link between
vitamin D deficiency, immune vulnerability and an
increased rate of asthma exacerbations, and winterrelated atopic eczema [87, 88]. While these trials are in
favour a protective role of vitamin D, unfortunately,
until data from larger multicentric prospective studies
become available, no clear recommendation on the use
of vitamin D in the prevention or supportive treatment
of allergies can be formulated.
Acknowledgements
This study was funded by the Deutsche Forschungsgemeinschaft (Emmy Noether Program SCHA 979/3-1
to J.S.) and the Fritz Thyssen Stiftung.
Conflict of interest: The authors declare no conflict of
interest.

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