Low vitamin D levels are associated with atopic dermatitis,
but not allergic rhinitis, asthma, or IgE sensitization, in the
adult Korean population
Hui Mei Cheng, MD,a Sunmi Kim, MD,b Gyeong-Hun Park, MD, PhD,c Sung Eun Chang, MD, PhD,d
Seunghyun Bang, PhD,e Chong Hyun Won, MD, PhD,d Mi Woo Lee, MD, PhD,d Jee Ho Choi, MD, PhD,d and
Kee Chan Moon, MD, PhDd Perth, Australia, and Chuncheon, Hwaseong, and Seoul, Korea
Background: The effect of vitamin D on allergic conditions is
unclear. In particular, large-scale, population-based studies
examining this relationship in adult Asian populations are
lacking.
Objective: To evaluate the association between serum vitamin D
levels and allergic conditions in the general adult Korean
population.
Methods: A cross-sectional study was performed by using data
collected from 15,212 individuals 19 years or older who
participated in the Korean National Health and Nutrition
Examination Survey from 2008 to 2010. The confounder-
adjusted mean serum 25-hydroxyvitamin D (25[OH]D) levels of
participants with and without allergic conditions (including
atopic dermatitis, asthma, allergic rhinitis, and increased total
and allergen-specific serum IgE) were compared by using
multiple linear regression analyses. Multiple logistic regression
analyses with confounder adjustment estimated the odds ratios
(ORs) for developing each condition according to adequate,
inadequate, or deficient serum 25(OH)D levels.
Results: After adjusting for potential confounders, mean serum
25(OH)D levels were significantly lower in participants
diagnosed with atopic dermatitis than in those without this
diagnosis (mean 6 SE, 18.58 6 0.29 ng/mL vs 19.20 6 0.15 ng/
mL; P 5 .02). Compared with participants with adequate
vitamin D levels (>_20 ng/mL), confounder-adjusted ORs of
atopic dermatitis were significantly higher in those with
inadequate (12-19.99 ng/mL) or deficient (<12 ng/mL) levels
(OR [95% CI], 1.50 [1.10-2.06] and 1.48 [1.04-2.12],
respectively; P 5 .02). This relationship was not observed in
participants with the other allergic conditions.
Conclusion: Vitamin Dinsufficient adult individuals within the
general Korean population have an increased likelihood of
atopic dermatitis, but not asthma, allergic rhinitis, or IgE
sensitization. (J Allergy Clin Immunol 2014;133:1048-55.)
From aRoyal Perth Hospital, Perth, Western Australia; bthe Department of Family
Medicine, Kangwon National University Hospital, Chuncheon; cthe Department of
Dermatology, Dongtan Sacred Heart Hospital, Hallym University College of Medi-
cine, Hwaseong; dthe Department of Dermatology, Asan Medical Center, University
of Ulsan College of Medicine, Seoul; and eAsan Institute for Life Sciences, Seoul.This
report was presented at the 9th Asian Dermatological Congress in Hong Kong, on July
10-13, 2013.
Disclosure of potential conflict of interest: The authors declare that they have no relevant
conflicts of interest.
Received for publication August 23, 2013; revised October 27, 2013; accepted for pub-
lication October 29, 2013.
Available online December 31, 2013.
Corresponding author: Gyeong-Hun Park, MD, PhD, Department of Dermatology, Dong-
tan Sacred Heart Hospital, Hallym University College of Medicine 7, Keunjaebong-gil,
Hwaseong-si, Gyeonggi-do 445-170, Korea. E-mail: borelalgebra@gmail.com.
0091-6749/$36.00
2013 American Academy of Allergy, Asthma & Immunology
http://dx.doi.org/10.1016/j.jaci.2013.10.055
1048
Key words: Vitamin D, allergy, atopic dermatitis, asthma, allergic
rhinitis, IgE, Asian, Korean, adult, KNHANES
Vitamin D receptors are expressed on nearly all types of
immune cells, including T cells, B cells, neutrophils, macro-
phages, and dendritic cells.1 The function of vitamin Dknown
to regulate calcium and phosphate homeostasisis thought to be
highly complex, and its potential roles in cardiovascular,
neoplastic, infectious, and autoimmune diseases have been
investigated in recent studies.2-5
Vitamin D exerts its immunomodulatory effects on both the
innate and adaptive immune systems,6 and its suppressive effects
are known to play a role in various autoimmune diseases.4
Reduced vitamin D levels have been reported in conditions
such as rheumatoid arthritis, type 1 diabetes mellitus, inflamma-
tory bowel disease, and multiple sclerosis, all of which are
commonly mediated by TH1 cells.4 Indeed, using vitamin D
analogues to treat psoriasis is now common clinical practice.
However, the effect of vitamin D on allergic conditions is less
clear.
Previous experimental studies show that vitamin D may
enhance TH2 cell responses not only by inhibiting TH1 cells,
which shifts the balance of T cells toward TH2,7 but also via a
direct effect on naive T-cell differentiation into TH2 cells.8 How-
ever, clinical studies show varying results.1 While some studies
report a protective role of vitamin D in atopic dermatitis (AD),9
asthma,10 allergic rhinitis (AR),11 and allergic sensitization12 in
childhood, others support a deleterious effect.13-15 Furthermore,
studies thus far have largely focused on evaluating children or
pregnant mothers in white, African-American, or Hispanic popu-
lations. To date, there are insufficient numbers of large-scale,
population-based studies examining the association between
allergic conditions and serum vitamin D levels, particularly
among adult Asian populations. Thus, the present study aimed
to evaluate the association between serum vitamin D levels and
allergic conditions, namely, AD, asthma, and AR as well as IgE
sensitization to allergens, in an adult Korean population.
METHODS
Study population
This study was based on data acquired from the Korean National Health and
Nutrition Examination Survey (KNHANES), a survey conducted by the Korea
Center for Disease Control and Prevention to garner nationally representative
and reliable statistical data regarding the health, behavior associated with
health, nutrition, and food intake status of the Korean population. Data were
collected from 2008 to 2010, which corresponded to the second and third years
of KNHANES IV (2007-2009) and the first year of KNHANES V (2010-
2012). The survey included a health interview, a nutritional survey, a physical
J ALLERGY CLIN IMMUNOL
VOLUME 133, NUMBER 4
Abbreviations used
25(OH)D: 25-Hydroxyvitamin D
AD: Atopic dermatitis
AR: Allergic rhinitis
BMI: Body mass index
KNHANES: Korean National Health and Nutrition Examination
Survey
OR: Odds ratio
RSV: Respiratory syncytial virus
examination, and blood tests. The institutional review board at the Korea
Centers for Disease Control and Prevention approved the protocol, and all
participants signed informed consent forms.
Both KNHANES IV and V adopted the stratified multistage cluster
sampling design by using the rolling-survey sampling method. Therefore,
the rolling sample collected during each year is the probability sample
representing the general Korean population, and they are homogeneous and
independent from each other. In 2008, 2009, and 2010, a total of 36,188
individuals (12,528, 12,722, and 10,938, respectively) were sampled, and
29,235 of these individuals (9,744, 10,533, and 8,958, respectively)
participated in the surveys. Among the 29,235 participants, we subsequently
excluded the following participants: younger than 19 years (n 5 7,424);
those whose 25-hydroxyvitamin D (25[OH]D) levels were not measured
(n 5 2,703); those who did not completely answer questions regarding AD,
asthma, AR, occupation, income, education, physical activity, regular
walking, or smoking (n 5 3,607); those without body mass index (BMI)
measurement (n 5 46); and those with a chronic disease that might affect
vitamin D metabolism, including liver cirrhosis, renal failure, pulmonary
tuberculosis, and malignancies (n 5 243). Thus, a final total of 15,212
participants was eligible for our study (Fig 1).
Variable definitions
The following question was used to assess physician-diagnosed AD for
each participant: Have you been diagnosed with AD by a doctor? Physician-
diagnosed asthma and AR were also determined by using similar questions.
The season in which the examination occurred was classified as follows:
spring (March to May), summer (June to August), autumn (September to
November), and winter (December to February). The region of residence for
each participant was grouped as follows: urban (Seoul, Gyeonggi, Busan,
Daegu, Incheon, Gwangju, Daejeon, and Ulsan) and rural (Gangwon,
Chungbuk, Chungnam, Jeonbuk, Jeonnam, Gyeongbuk, Gyeongnam, and
Jeju), as described previously.16 Occupation was classified on the basis of
Korean Standard Classification of Occupations as follows: group 1 (managers,
professionals, and related workers); group 2 (clerks); group 3 (service and
sales workers); group 4 (skilled agricultural, forestry, and fishery workers);
group 5 (craft, equipment, and machine operating and assembling workers);
group 6 (elementary workers); and group 7 (housewives, students, and the
unemployed). In this study, groups 1, 2, 3, and 7 were merged into a single
group and groups 4, 5, and 6 were also merged, because the latter groups
were previously reported to have significantly higher serum 25(OH)D levels
than the former groups.17 Participants who performed moderate physical
activity for more than 30 minutes per day on more than 5 days per week
and/or strenuous physical activity for more than 20 minutes per day on
more than 3 days per week were assigned to the regular exercise group. Reg-
ular walking was designated as yes for those who walked for more than 30
minutes per day on more than 5 days per week, as described previously.16 In-
come was defined as the log transformation of the monthly equivalent house-
hold income (in US $), which was calculated by dividing the household
income by the square root of the number of household members in accordance
with the method recommended by the Organization for Economic Co-
operation and Development.18 Before log transformation, US $1 was added
to the monthly equivalent household income to retain the participants who re-
ported no income. Education level was classified into the following categories:
CHENG ET AL 1049
graduation from elementary school or lower, middle school, high school, and
college and above. Cigarette smoking was indicated as yes for participants
who had smoked 100 cigarettes or more during their lifetime and no for
those who had never smoked or smoked fewer than 100 cigarettes during their
lifetime.
Height and weight were measured as described previously,19 and the BMI
was calculated in kilograms per square meter. The BMI was categorized as
normal or underweight (<23 kg/m2), overweight (ranging from 23 kg/m2 to
<25 kg/m2), and obese (> _25 kg/m2) according to the modified World Health
Organization criteria for the Asia-Pacific region.20
Blood samples were collected from the antecubital veins, refrigerated
immediately, transported to the central testing facility in cold storage, and
analyzed within 24 hours of sampling. Serum 25(OH)D levels were measured
as described previously21 and categorized as adequate (> _20 ng/mL), inade-
quate (ranging from 12 to <20 ng/mL), or deficient (<12 ng/mL) according
to the guidelines set by the Food and Nutrition Board of the Institute of
Medicine.22 Total and allergen-specific serum IgE levels against Dermatopha-
goides farinae, cockroach, and dog allergens were obtained in 2010 from 1588
participants who were randomly sampled from every age and sex group in each
district to represent the general Korean population. IgE levels were measured
by using a 1470 Wizard gamma-counter (PerkinElmer, Turku, Finland) with
ImmunoCAP 100 (Phadia, Uppsala, Sweden). Total IgE levels of more than
150 U/mL were defined as increased,23 and participants with allergen-
specific IgE levels of 0.35 kU/L or more were regarded as sensitized.12
Statistical analyses
Statistical analyses were performed by using the statistical software
package R version 3.0.1 (The R Foundation for Statistical Computing, Vienna,
Austria), and 2-sided P values of less than .05 were considered statistically
significant. To produce unbiased national estimates representing the general
Korean population, we used KNHANES sample weights accounting for the
complex sampling design to each participant.24 We estimated the means and
SDs or the proportions and SEs of the participants demographic variables,
socioeconomic factors, health behavior factors, BMI, and serum 25(OH)D
level according to their AD, asthma, AR, and increased total and allergen-
specific serum IgE level status. The differences in the participant characteris-
tics according to the presence of these conditions were analyzed by using the
design-based Wilcoxon rank-sum test for complex sample survey data or the
Pearson x2 test with Rao-Scott adjustment.
To estimate the mean serum 25(OH)D levels in participants with and
without the above-mentioned allergic conditions, we performed simple and
multiple linear regression analyses by using the generalized linear model for a
complex survey design. The estimated means of serum 25(OH)D levels were
calculated in the following ways: no adjustment for potential confounders;
confounder adjustment for age and sex (model 1); and confounder adjustment
for age, sex, season at blood sampling, region of residence, occupation, regular
exercise, and regular walking (model 2).
To estimate odds ratios (ORs) of AD, asthma, AR, and increased total and
allergen-specific serum IgE levels according to serum 25(OH)D levels, we
conducted simple and multiple logistic regression analyses by using the
generalized linear model for a complex survey design. The ORs and 95% CIs
were calculated in the following ways: no adjustment for potential
confounders; confounder adjustment for age and sex (model 1); and
confounder adjustment for age, sex, region of residence, income, education,
smoking, and BMI (model 2).
RESULTS
General characteristics
A total of 15,212 participants were included in the study, and
the general characteristics of this study population are presented
in Table I. Of these 15,212 participants, 1,588 were further tested
for total and allergen-specific serum IgE levels for D farinae,
cockroach, and dog allergens; these IgE measurements are
presented in Table II.
1050 CHENG ET AL
FIG 1. Flowchart of the study population.
Differences in mean serum 25(OH)D levels based on
the presence of AD, asthma, AR, and allergic
sensitization
From this adult Korean population, we determined whether
vitamin D (25[OH]D) levels correlated with any of the allergic
conditions by comparing the estimated mean values. Without
adjusting for potential confounders, the mean 25(OH)D levels
were significantly lower in participants diagnosed with AD or AR
and significantly higher in participants with increased serum IgE
levels (Table III). However, when adjusted for confounding factors
by using model 1 (age and sex) and model 2 (age, sex, season at
blood sampling, region of residence, occupation, regular exercise,
and regular walking), mean 25(OH)D levels were significantly
lower only in participants diagnosed with AD compared with
those without an AD diagnosis. Thus, regardless of the adjustment
model, the association remained significant between mean serum
25(OH)D levels and AD diagnosis, but not with asthma, AR, or
increased total or allergen-specific serum IgE levels.
Differences in the risk of developing AD, asthma,
AR, and allergic sensitization based on serum
25(OH)D levels
We also evaluated whether the different 25(OH)D levels were
associated with any of the allergic diseases by estimating OR
values and found a similar trend as above (Table IV). Without
adjusting for potential confounders, the odds of AD and AR diag-
nosis were significantly higher in participants with inadequate or
deficient 25(OH)D levels. Also, without adjusting for potential
confounders, the odds of increased total serum IgE level was
significantly lower in those with inadequate or deficient 25(OH)
D levels. When adjusted for confounding factors by using model
1 (age and sex) and model 2 (age, sex, region of residence,
income, education, smoking, and BMI), only the odds for AD
J ALLERGY CLIN IMMUNOL
APRIL 2014
remained significantly higher in participants with both inadequate
and deficient 25(OH)D levels. Thus, the association between
lower-than-normal 25(OH)D levels and AD diagnosis was signif-
icant using both adjustment models. Again, however, this
relationship was not observed in asthma, AR, or increased total
or allergen-specific serum IgE levels.
DISCUSSION
In this study, we set out to determine whether vitamin D levels
correlated with any of the well-known allergic diseases in an adult
Asian population, which has not yet been addressed in previous
studies. Our results demonstrate that study participants diagnosed
with AD had significantly lower vitamin D levels. Likewise, the
odds of being diagnosed with AD were also significantly higher in
participants with inadequate or deficient vitamin D levels. Neither
of these findings was observed in asthma, AR, or IgE sensitization
to allergens in the confounder-adjusted regression models. These
results are consistent with findings from a previous association
study showing that vitamin Ddeficient participants in a primarily
adult obese population had an increased risk of AD but not asthma
or AR.25 Furthermore, our results can be extrapolated to the
general adult Korean population because the present study used
data from a nationally representative sampling of the population.
The pathogenesis of AD is attributed to immune and skin-
barrier abnormalities,26 and vitamin D may play beneficial roles
in ameliorating both abnormalities. Vitamin D decreases inflam-
matory responses through helping to tolerize dendritic cells and
convert CD41 T cells into regulatory T cells.4 In addition, vitamin
D inhibits IL-12, IL-2, and IFN-g production, thereby reducing
TH1 cell production, activation, and function.4 TH1-mediated
inflammatory responses predominate in chronic lichenified
lesions,27 which are a characteristic of adult AD.28 Furthermore,
vitamin D is important in maintaining the epidermal permeability
barrier29 and in promoting antimicrobial activity,30 both of which
J ALLERGY CLIN IMMUNOL CHENG ET AL 1051
VOLUME 133, NUMBER 4

TABLE I. General characteristics of the total study population

AD P Asthma P AR P
Characteristic Total No Yes value No Yes value No Yes value

Total
n 15,212 14,820 392 14,737 475 13,421 1,791
% 100.0 97.0 6 0.2 3.0 6 0.2 97.1 6 0.2 2.9 6 0.2 86.8 6 0.4 13.2 6 0.4
Age (y) 44.0 6 15.1 44.3 6 15.1 35.5 6 13.7 <.001 43.9 6 15.0 47.9 6 17.8 .002 45.0 6 15.2 37.9 6 12.5 <.001
Sex .45 .09 .03
Male 50.6 6 0.4 50.6 6 0.4 48.3 6 3.0 50.7 6 0.4 45.5 6 3.0 51.0 6 0.5 47.6 6 1.4
Female 49.4 6 0.4 49.4 6 0.4 51.7 6 3.0 49.3 6 0.4 54.5 6 3.0 49.0 6 0.5 52.4 6 1.4
Season at blood sampling .12 .22 .40
Spring 25.7 6 2.1 25.7 6 2.1 27.1 6 3.5 25.6 6 2.1 30.0 6 3.5 25.4 6 2.1 27.5 6 2.6
Summer 27.0 6 2.1 27.0 6 2.1 25.4 6 3.3 27.0 6 2.1 25.8 6 3.1 27.1 6 2.1 26.5 6 2.6
Autumn 24.6 6 2.0 24.7 6 2.0 19.9 6 2.8 24.6 6 2.0 25.2 6 3.1 24.8 6 2.0 22.9 6 2.3
Winter 22.7 6 2.0 22.6 6 2.0 27.6 6 3.6 22.8 6 2.0 19.0 6 2.9 22.7 6 2.0 23.1 6 2.5
Region of residence .67 .01 .04
Urban 70.5 6 1.1 70.4 6 1.1 71.6 6 2.9 70.3 6 1.1 76.3 6 2.3 70.1 6 1.1 73.0 6 1.7
Rural 29.5 6 1.1 29.6 6 1.1 28.4 6 2.9 29.7 6 1.1 23.7 6 2.3 29.9 6 1.1 27.0 6 1.7
Occupation <.001 .053 <.001
Groups 1, 2, 3, and 7 73.5 6 0.7 73.2 6 0.7 82.7 6 2.2 73.4 6 0.7 78.2 6 2.3 72.1 6 0.8 82.7 6 1.1
Groups 4, 5, and 6 26.5 6 0.7 26.8 6 0.7 17.3 6 2.2 26.6 6 0.7 21.8 6 2.3 27.9 6 0.8 17.3 6 1.1
Regular exercise .69 .24 .80
No 84.1 6 0.4 84.1 6 0.4 83.2 6 2.2 84.1 6 0.4 81.5 6 2.4 84.1 6 0.5 83.8 6 1.0
Yes 15.9 6 0.4 15.9 6 0.4 16.8 6 2.2 15.9 6 0.4 18.5 6 2.4 15.9 6 0.5 16.2 6 1.0
Regular walking .63 .09 .046
No 67.2 6 0.5 67.2 6 0.5 65.9 6 2.7 67.3 6 0.5 62.3 6 3.0 66.8 6 0.6 69.5 6 1.2
Yes 32.8 6 0.5 32.8 6 0.5 34.1 6 2.7 32.7 6 0.5 37.7 6 3.0 33.2 6 0.6 30.5 6 1.2
Income (log US $) 7.0 6 0.9 7.0 6 0.9 7.0 6 1.1 .26 7.0 6 0.9 6.8 6 0.9 <.001 7.0 6 0.9 7.2 6 0.8 <.001
Education <.001 <.001 <.001
Elementary school or less 17.6 6 0.5 17.9 6 0.5 9.1 6 1.5 17.2 6 0.5 32.1 6 2.7 19.3 6 0.6 6.8 6 0.6
Middle school 10.2 6 0.3 10.3 6 0.3 6.1 6 1.4 10.1 6 0.3 11.6 6 1.6 10.7 6 0.3 6.6 6 0.6
High school 40.2 6 0.6 40.0 6 0.6 45.4 6 2.9 40.5 6 0.6 29.9 6 2.9 39.6 6 0.7 44.4 6 1.5
College or above 32.0 6 0.7 31.8 6 0.7 39.4 6 2.8 32.2 6 0.7 26.4 6 2.6 30.4 6 0.7 42.2 6 1.5
Smoking .17 .07 <.001
No 54.9 6 0.4 54.8 6 0.4 58.8 6 2.8 54.8 6 0.4 60.0 6 2.8 54.2 6 0.5 59.9 6 1.3
Yes 45.1 6 0.4 45.2 6 0.4 41.2 6 2.8 45.2 6 0.4 40.0 6 2.8 45.8 6 0.5 40.1 6 1.3
BMI (kg/m2) .25 .06 <.001
Normal or less (<23) 45.1 6 0.5 45.0 6 0.5 49.8 6 2.8 45.3 6 0.5 39.1 6 2.8 44.4 6 0.5 49.6 6 1.4
Overweight (23-<25) 23.1 6 0.4 23.2 6 0.4 20.2 6 2.5 23.1 6 0.4 23.6 6 2.5 23.2 6 0.4 22.8 6 1.1
Obese (>_25) 31.8 6 0.5 31.8 6 0.5 30.0 6 2.8 31.6 6 0.5 37.3 6 2.6 32.4 6 0.5 27.6 6 1.3
Serum 25(OH)D level (ng/mL) <.001 .38 <.001
Adequate (>_20) 34.2 6 1.0 34.6 6 1.0 21.9 6 2.6 34.3 6 1.0 31.1 6 2.6 35.1 6 1.0 28.6 6 1.5
Inadequate (12-<20) 48.2 6 0.7 47.9 6 0.7 56.1 6 3.0 48.2 6 0.7 49.4 6 2.7 47.5 6 0.7 52.6 6 1.5
Deficient (<12) 17.6 6 0.7 17.4 6 0.7 22.0 6 2.4 17.5 6 0.7 19.6 6 2.4 17.4 6 0.7 18.8 6 1.3

Data are expressed as mean 6 SD or % 6 SE.

P values were calculated by design-based Wilcoxon rank-sum test for complex sample survey data or Pearson x2 test with Rao-Scott adjustment.

are well recognized as defective in patients with AD.26 Mice null
for 25(OH)D 1a-hydroxylase exhibit decreased filaggrin expres-
sion in their epidermis,29 which is known to increase the risk of
allergen penetration and AD development.31 Vitamin D enhances
the expression of the antimicrobial peptide, cathelicidin,30 which
has broad-spectrum antimicrobial activity against bacteria,
viruses, and fungi.32 Because colonization or infection by patho-
gens, including Staphylococcus aureus, weakens the permeability
barrier and exacerbates AD,26 the antimicrobial effects of vitamin
D can potentially play beneficial roles in AD.
The association between vitamin D and asthma has been
studied extensively in recent years and has been observed by
many, if not all, studies among children.10,33 In contrast, this as-
sociation has not been observed in many adult studies.25,34-36
A significant proportion of childhood wheezing is associated
with respiratory viral agents, particularly respiratory syncytial
virus (RSV).37 While RSV infection produces only cold-like
symptoms in healthy adults, it can involve the lower respiratory
tract in infants and young children.38 RSV infection, including
bronchiolitis, has been suggested to increase respiratory mucosal
permeability, enhance allergic sensitization to aeroallergens, and
contribute to asthma development.37 Because vitamin D can
decrease the predisposition of children to respiratory viral infec-
tions (RSV in particular)39 and can also decrease the inflamma-
tory response to RSV infection,40 adequate vitamin D levels
may be associated with reduced wheezing or asthma development
in children. In adults, however, many studies found no association
between vitamin D and asthma,25,34-36 consistent with the results
of the present study.
In contrast to AD and asthma, relatively few studies have
investigated the role of vitamin D in AR,41 but many clinicians
now subscribe to the united airways disease hypothesis, which
1052 CHENG ET AL J ALLERGY CLIN IMMUNOL
APRIL 2014

TABLE II. General characteristics of participants with total and allergen-specific serum IgE measurements
Sensitization to
Increased serum Dermatophagoides Sensitization Sensitization
total IgE P farinae P to cockroaches P to dogs P
Characteristic Total No Yes value No Yes value No Yes value No Yes value

Total
n 1588 1044 544 978 610 1277 311 1505 83
% 100.0 64.5 6 1.7 35.5 6 1.7 60.9 6 1.5 39.1 6 1.5 78.5 6 1.5 21.5 6 1.5 93.6 6 0.9 6.4 6 0.9
Age (y) 44.8 6 15.4 43.7 6 15.0 46.9 6 15.9 .004 46.1 6 15.4 42.8 6 15.1 .003 44.7 6 15.3 45.3 6 15.6 .66 45.2 6 15.3 38.4 6 15.3 .002
Sex <.001 <.001 <.001 <.001
Male 49.4 6 1.1 40.9 6 1.5 65.0 6 2.2 43.1 6 1.5 59.3 6 2.3 43.7 6 1.3 70.5 6 3.3 48.1 6 1.1 68.5 6 5.1
Female 50.6 6 1.1 59.1 6 1.5 35.0 6 2.2 56.9 6 1.5 40.7 6 2.3 56.3 6 1.3 29.5 6 3.3 51.9 6 1.1 31.5 6 5.1
Season at blood .04 .06 .13 .01
sampling
Spring 24.7 6 3.9 22.1 6 3.7 29.3 6 4.9 24.2 6 4.1 25.4 6 4.2 23.5 6 3.9 28.9 6 5.7 24.4 6 3.9 28.2 6 7.6
Summer 27.5 6 4.0 29.7 6 4.4 23.6 6 4.1 30.3 6 4.3 23.2 6 3.9 29.4 6 4.2 20.6 6 4.5 28.7 6 4.2 10.6 6 4.5
Autumn 20.4 6 3.2 19.9 6 3.2 21.4 6 4.0 19.1 6 3.2 22.4 6 3.8 19.9 6 3.2 22.4 6 4.3 20.5 6 3.2 19.1 6 5.6
Winter 27.4 6 4.1 28.3 6 4.3 25.7 6 4.5 26.4 6 4.1 29.0 6 4.6 27.2 6 4.1 28.1 6 5.1 26.4 6 4.0 42.0 6 8.4
Region of .002 .03 .09 .20
residence
Urban 70.0 6 2.5 73.7 6 2.6 63.3 6 3.4 72.4 6 2.7 66.2 6 3.0 71.5 6 2.6 64.4 6 4.2 69.5 6 2.5 77.9 6 5.8
Rural 30.0 6 2.5 26.3 6 2.6 36.7 6 3.4 27.6 6 2.7 33.8 6 3.0 28.5 6 2.6 35.6 6 4.2 30.5 6 2.5 22.1 6 5.8
Occupation <.001 .01 .001 .69
Groups 1, 2, 71.8 6 1.9 77.2 6 1.9 62.0 6 3.1 74.5 6 2.1 67.7 6 2.6 74.2 6 2.0 63.1 6 3.4 72.0 6 2.0 69.7 6 5.6
3, and 7
Groups 4, 5, 28.2 6 1.9 22.8 6 1.9 38.0 6 3.1 25.5 6 2.1 32.3 6 2.6 25.8 6 2.0 36.9 6 3.4 28.0 6 2.0 30.3 6 5.6
and 6
Regular exercise .02 .12 .42 .43
No 85.2 6 1.2 87.4 6 1.2 81.1 6 2.5 86.8 6 1.5 82.7 6 2.1 85.7 6 1.3 83.3 6 2.8 84.9 6 1.3 88.9 6 4.2
Yes 14.8 6 1.2 12.6 6 1.2 18.9 6 2.5 13.2 6 1.5 17.3 6 2.1 14.3 6 1.3 16.7 6 2.8 15.1 6 1.3 11.1 6 4.2
Regular walking .12 .67 .51 .13
No 71.2 6 1.4 73.0 6 1.6 67.9 6 2.8 71.7 6 1.7 70.4 6 2.5 71.7 6 1.5 69.3 6 3.3 71.7 6 1.4 63.1 6 6.0
Yes 28.8 6 1.4 27.0 6 1.6 32.1 6 2.8 28.3 6 1.7 29.6 6 2.5 28.3 6 1.5 30.7 6 3.3 28.3 6 1.4 36.9 6 6.0
Income (log US $) 7.2 6 0.9 7.2 6 0.9 7.1 6 0.9 .01 7.1 6 0.9 7.2 6 0.9 .50 7.2 6 0.9 7.1 6 0.9 .11 7.2 6 0.9 7.2 6 0.6 .62
Education .01 .04 .87 .35
Elementary 19.2 6 1.5 16.8 6 1.5 23.6 6 3.0 21.0 6 1.9 16.5 6 2.1 19.0 6 1.7 19.9 6 2.9 19.8 6 1.6 10.9 6 4.2
school or
less
Middle school 11.0 6 0.9 10.2 6 1.1 12.4 6 1.7 11.8 6 1.2 9.7 6 1.5 11.4 6 1.0 9.3 6 2.4 11.1 6 1.0 9.9 6 4.0
High school 39.2 6 1.5 42.2 6 1.8 33.7 6 2.3 39.5 6 1.9 38.6 6 2.4 39.0 6 1.8 39.7 6 3.1 39.0 6 1.6 41.7 6 6.4
College or 30.6 6 1.6 30.8 6 1.8 30.3 6 2.5 27.7 6 1.8 35.2 6 2.2 30.5 6 1.9 31.1 6 3.5 30.2 6 1.6 37.5 6 5.7
above
Smoking <.001 <.001 <.001 .005
No 54.9 6 1.3 62.8 6 1.7 40.5 6 2.3 60.3 6 1.7 46.5 6 2.3 58.7 6 1.5 41.3 6 3.6 56.2 6 1.3 36.4 6 6.6
Yes 45.1 6 1.3 37.2 6 1.7 59.5 6 2.3 39.7 6 1.7 53.5 6 2.3 41.3 6 1.5 58.7 6 3.6 43.8 6 1.3 63.6 6 6.6
BMI (kg/m2) .09 .53 .03 .54
Normal or 46.0 6 1.5 48.6 6 2.1 41.2 6 2.6 47.2 6 2.0 44.1 6 2.4 48.3 6 1.7 37.6 6 3.2 46.3 6 1.6 41.8 6 6.7
less (<23)
Overweight 20.2 6 1.2 19.9 6 1.5 20.9 6 2.3 20.4 6 1.6 20.0 6 1.9 19.3 6 1.3 23.7 6 3.1 19.9 6 1.2 25.7 6 5.7
(23-<25)
Obese (>_25) 33.8 6 1.5 31.5 6 1.9 37.9 6 2.6 32.4 6 2.0 35.9 6 2.6 32.4 6 1.6 38.7 6 3.4 33.9 6 1.6 32.4 6 5.8
Serum 25(OH)D .03 .02 .69 .21
level
(ng/mL)
Adequate 32.4 6 2.1 29.5 6 2.3 37.8 6 2.9 29.5 6 2.3 36.9 6 2.7 31.7 6 2.3 34.9 6 3.5 32.5 6 2.1 31.5 6 5.7
_20)
(>
Inadequate 51.5 6 1.8 53.4 6 2.1 48.2 6 3.0 54.5 6 2.0 47.0 6 2.7 52.2 6 1.9 49.1 6 4.2 52.0 6 1.9 44.5 6 6.6
(12-<20)
Deficient 16.0 6 1.5 17.2 6 1.9 14.0 6 2.0 16.0 6 1.9 16.1 6 1.9 16.1 6 1.6 16.0 6 3.1 15.5 6 1.5 24.0 6 5.9
(<12)

Data are expressed as mean 6 SD or % 6 SE.

P values were calculated by design-based Wilcoxon rank-sum test for complex sample survey data or Pearson x2 test with Rao-Scott adjustment.

posits that AR and asthma are the result of a single inflammatory the association between vitamin D deficiency and AR in adults
process.42 On the basis of this concept, we can extrapolate the is weak based on current evidence. While an Iranian study, which
pathophysiology of asthma to that of AR.43 Similar to asthma, did not account for any confounders, showed a strong association
J ALLERGY CLIN IMMUNOL CHENG ET AL 1053
VOLUME 133, NUMBER 4

TABLE III. The estimated mean serum 25(OH)D levels (ng/mL) and their differences according to each condition
Mean 6 SE
Condition Without disease With disease Difference, mean (95% CI) P value

AD
Unadjusted 18.27 6 0.16 16.54 6 0.35 21.73 (22.39 to 21.07) <.001
Model 1* 18.23 6 0.16 17.31 6 0.34 20.92 (21.56 to 20.28) .005
Model 2 19.20 6 0.15 18.58 6 0.29 20.62 (21.15 to 20.08) .02
Asthma
Unadjusted 18.23 6 0.16 17.94 6 0.37 20.29 (20.96 to 0.38) .39
Model 1* 18.22 6 0.16 17.72 6 0.37 20.50 (21.17 to 0.17) .14
Model 2 19.19 6 0.15 18.90 6 0.35 20.29 (20.91 to 0.33) .35
AR
Unadjusted 18.34 6 0.17 17.42 6 0.22 20.92 (21.31 to 20.54) <.001
Model 1* 18.24 6 0.16 18.00 6 0.23 20.23 (20.61 to 0.15) .23
Model 2 19.18 6 0.15 19.17 6 0.20 20.01 (20.34 to 0.33) .96
Increased total serum IgE
Unadjusted 17.53 6 0.36 18.85 6 0.44 1.32 (0.40-2.24) .005
Model 1* 17.85 6 0.36 18.30 6 0.43 0.45 (20.44 to 1.34) .32
Model 2 18.88 6 0.39 19.31 6 0.48 0.43 (20.41 to 1.26) .32
Sensitization to Dermatophagoides farinae
Unadjusted 17.69 6 0.37 18.48 6 0.41 0.79 (20.09 to 1.67) .08
Model 1* 17.78 6 0.36 18.38 6 0.40 0.60 (20.23 to 1.43) .15
Model 2 18.79 6 0.39 19.41 6 0.47 0.61 (20.19 to 1.42) .14
Sensitization to cockroaches
Unadjusted 17.78 6 0.34 18.79 6 0.52 1.01 (20.01 to 2.04) .053
Model 1* 17.96 6 0.34 18.20 6 0.53 0.23 (20.82 to 1.29) .66
Model 2 18.96 6 0.38 19.37 6 0.57 0.40 (20.62 to 1.42) .44
Sensitization to dogs
Unadjusted 18.01 6 0.32 17.83 6 0.97 20.17 (22.06 to 1.72) .86
Model 1* 18.03 6 0.32 17.78 6 0.89 20.25 (21.99 to 1.48) .78
Model 2 19.02 6 0.37 19.66 6 0.93 0.65 (21.01 to 2.30) .44
*Model 1: adjusted for age and sex.
Model 2: adjusted for age, sex, season at blood sampling, region of residence, occupation, regular exercise, and regular walking.

between them,44 a large cohort study found that higher vitamin D
levels were associated with an increased prevalence of AR.45 The
prevalence of AR in adulthood was also higher in participants
who received vitamin D supplements as infants.15 The present
study found no association between vitamin D and AR in an adult
Korean population, and further studies are needed to determine
the precise role of vitamin D in the pathogenesis of AR.
Consistent with our results showing that low vitamin D levels
did not associate with IgE sensitization to allergens, large
cross-sectional studies of adults in the United States also
showed no association.12,45 In children and adolescents, howev-
er, low serum vitamin D levels were significantly associated
with allergic sensitization to most allergens.12 A study of
asthma patients also demonstrated that serum vitamin D levels
inversely correlated with serum IgE levels in the pediatric, but
not adult, group.46 Furthermore, the association in the pediatric
group was stronger in younger (6-12 years old) than in older
(13-17 years old) children, where the association became statis-
tically insignificant in the older children.46 The mechanism
underlying the age-related difference for this association, how-
ever, remains to be elucidated. Because vitamin D contributes
to maintaining the epidermal permeability barrier and mucosal
integrity as well as protecting against pathogenic microorgan-
isms,29,30,47 vitamin D deficiency may increase the chances
of allergen exposure in childhood. However, because most
allergies are initiated in childhood, serum vitamin D levels in
adults may not closely correlate to their allergic sensitization
status.46
A cross-sectional study showed that serum vitamin D levels
inversely associated with the prevalence of asthma in white, but
not African American, women.48 In addition, specific genotypes
for several genes could modify the association between vitamin
D and allergy risk.49 Furthermore, a recent study reported the
association between vitamin D receptor gene polymorphisms
and severe AD in adults.50 Therefore, the role of vitamin D in
allergic diseases was speculated to differ on the basis of race.
However, an insufficient number of investigations have been con-
ducted from which to draw any firm conclusions regarding
whether differences in ethnicity affect the association between
serum vitamin D levels and allergic conditions. To our knowl-
edge, the present study is the first large-scale, population-based
study describing the associations between serum vitamin D levels
and several allergic conditions in an adult East Asian population.
Additional studies will be needed to clarify the effect of ethnicity
on the relationship between vitamin D and allergy.
Owing to the overall design of this study, several limitations
exist. Because of the cross-sectional nature of the collected data,
temporal relationships among the conditions cannot be
established. In addition, the method for absorbing vitamin D
was also not accounted for, because the information about sun
exposure and the use of oral vitamin D supplements was not fully
collected as part of the study. The study is also subjected to recall
bias because diagnoses of the conditions were self-reported.
In summary, we found an increased likelihood of AD among
vitamin Ddeficient individuals in the general adult Korean
population, but no apparent association of vitamin D status with
1054 CHENG ET AL J ALLERGY CLIN IMMUNOL
APRIL 2014

TABLE IV. ORs and 95% CIs of AD, asthma, AR, and allergic sensitization according to serum 25(OH)D levels
Serum 25(OH)D level
Condition _20 ng/mL)
Adequate (> Inadequate (12-<20 ng/mL) Deficient (<12 ng/mL) P for trend

AD
Unadjusted 1 (reference) 1.85 (1.37-2.51) 2.00 (1.42-2.82) <.001
Model 1* 1 (reference) 1.50 (1.10-2.06) 1.48 (1.04-2.12) .02
Model 2 1 (reference) 1.50 (1.10-2.06) 1.48 (1.04-2.12) .02
Asthma
Unadjusted 1 (reference) 1.13 (0.89-1.44) 1.23 (0.90-1.70) .18
Model 1* 1 (reference) 1.21 (0.94-1.55) 1.32 (0.94-1.87) .08
Model 2 1 (reference) 1.19 (0.92-1.53) 1.29 (0.91-1.82) .12
AR
Unadjusted 1 (reference) 1.36 (1.19-1.56) 1.33 (1.12-1.59) <.001
Model 1* 1 (reference) 1.14 (0.98-1.31) 1.03 (0.85-1.24) .59
Model 2 1 (reference) 1.11 (0.96-1.29) 1.01 (0.84-1.23) .71
Increased total serum IgE
Unadjusted 1 (reference) 0.71 (0.53-0.94) 0.64 (0.43-0.95) .01
Model 1* 1 (reference) 0.90 (0.66-1.23) 0.87 (0.58-1.31) .44
Model 2 1 (reference) 0.91 (0.66-1.24) 0.88 (0.58-1.33) .47
Sensitization to Dermatophagoides farinae
Unadjusted 1 (reference) 0.69 (0.53-0.89) 0.80 (0.56-1.15) .07
Model 1* 1 (reference) 0.72 (0.54-0.96) 0.83 (0.59-1.18) .13
Model 2 1 (reference) 0.74 (0.55-0.98) 0.86 (0.61-1.21) .19
Sensitization to cockroaches
Unadjusted 1 (reference) 0.85 (0.59-1.23) 0.91 (0.57-1.45) .54
Model 1* 1 (reference) 1.08 (0.72-1.62) 1.22 (0.73-2.04) .44
Model 2 1 (reference) 1.09 (0.72-1.63) 1.25 (0.75-2.06) .40
Sensitization to dogs
Unadjusted 1 (reference) 0.88 (0.48-1.62) 1.60 (0.80-3.20) .32
Model 1* 1 (reference) 0.91 (0.49-1.71) 1.61 (0.83-3.12) .26
Model 2 1 (reference) 0.89 (0.48-1.67) 1.58 (0.80-3.11) .29
*Model 1: adjusted for age and sex.
Model 2: adjusted for age, sex, region of residence, income, education, smoking, and body mass index.

asthma, AR, or IgE sensitization. Further cohort studies will be
needed to establish whether vitamin D has a possible therapeu-
tic effect to reduce the incidence and disease progression of AD
in adults.
Key messages
d Vitamin D insufficiency is associated with an increased
risk of atopic dermatitis, but not asthma, allergic rhinitis,
or IgE sensitization, in the general adult Korean
population.
d The role of vitamin D in the pathogenesis and manage-
ment of atopic dermatitis in adults warrants further
investigation.
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