Association of Antioxidants With Allergic Rhinitis in Children From Seoul

Abstract

The prevalence of allergic diseases has risen over the last few decades. Many factors, including environmental factors such as those related to diet, have been considered. Among dietary factors, intake of antioxidant-related nutrients has been associated with the risk of allergic disease. We investigated the association of antioxidant nutritional status with allergic rhinitis (AR) in Korean schoolchildren aged 6-12 years.
Subjects were 4,554 children in Seoul, Korea. The risk of allergic disease was measured using the Korean version of the International Study of Asthma and Allergies in Childhood, and dietary intake was measured by a semi-quantitative food frequency questionnaire. Intake of vitamins A (including retinol and β-carotene), C, and E was used in the analysis.
Vitamin C intake was negatively associated with an increased risk of current symptoms (adjusted odds ratio, 0.886; 95% confidence interval, 0.806-0.973). There was no association between AR and intake of vitamin A, retinol, β-carotene, or vitamin E. Total serum IgE level and sensitization to allergen did not differ according to nutrient intake.
The group of children with increased vitamin C consumption had fewer AR symptoms, despite the lack of a difference in total serum IgE level or allergen sensitization. These findings suggest that nutrient intake, especially that of vitamin C, influences AR symptoms.

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© Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease http://e-aair.org
INTRODUCTION
e prevalence of allergic diseases, including allergic rhinitis
(AR), has risen markedly in recent years,1,2 including in Korea.3
is increasing prevalence is thought to be due to lifestyle and
environmental changes rather than genetic factors. Coincident
with the increased prevalence of allergic disease, there has been
a signicant change in diet in many countries, such as decreased
consumption of fresh fruit, vegetables, and sh and increased
intake of high-fat foods. is has led to the hypothesis that chang-
es in the prevalence of allergic disease are associated with re-
Association of Antioxidants With Allergic Rhinitis in Children
From Seoul
Ju-Hee Seo,1 Sung-Ok Kwon,2 So-Yeon Lee,3 Hyung Young Kim,4,5 Ji-Won Kwon,6 Byoung-Ju Kim,7 Jinho Yu,4
Hyo-Bin Kim,8 Woo Kyung Kim,9 Gwang Cheon Jang,10 Dae Jin Song,11 Jung Yeon Shim,12 Se-Young Oh,2*
Soo-Jong Hong4,5*
1Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
2Department of Food and Nutrition, College of Human Ecology, Kyung Hee University, Seoul, Korea
3Department of Pediatrics, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang, Korea
4Department of Pediatrics, Childhood Asthma Atopy Center, 5Research Center for Standization of Allergic Diseases, Asan Medical Center, University of Ulsan
College of Medicine, Seoul, Korea
6Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea
7Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan, Korea
8Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea
9Department of Pediatrics, Inje University Seoul Paik Hospital, Seoul, Korea
10Department of Pediatrics, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
11Department of Pediatrics, College of Medicine, Korea University, Seoul, Korea
12Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
Original Article
Allergy Asthma Immunol Res. 2013 March;5(2):81-87.
http://dx.doi.org/10.4168/aair.2013.5.2.81
pISSN 2092-7355 • eISSN 2092-7363
Purpose: The prevalence of allergic diseases has risen over the last few decades. Many factors, including environmental factors such as those re-
lated to diet, have been considered. Among dietary factors, intake of antioxidant-related nutrients has been associated with the risk of allergic dis-
ease. We investigated the association of antioxidant nutritional status with allergic rhinitis (AR) in Korean schoolchildren aged 6-12 years. Meth-
ods: Subjects were 4,554 children in Seoul, Korea. The risk of allergic disease was measured using the Korean version of the International Study of
Asthma and Allergies in Childhood, and dietary intake was measured by a semi-quantitative food frequency questionnaire. Intake of vitamins A (in-
cluding retinol and β-carotene), C, and E was used in the analysis. Results: Vitamin C intake was negatively associated with an increased risk of
current symptoms (adjusted odds ratio, 0.886; 95% condence interval, 0.806-0.973). There was no association between AR and intake of vitamin A,
retinol, β-carotene, or vitamin E. Total serum IgE level and sensitization to allergen did not differ according to nutrient intake. Conclusions: The
group of children with increased vitamin C consumption had fewer AR symptoms, despite the lack of a difference in total serum IgE level or allergen
sensitization. These ndings suggest that nutrient intake, especially that of vitamin C, inuences AR symptoms.
Key Words: Allergic rhinitis; antioxidant; vitamin C
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Correspondence to: Soo-Jong Hong, MD, PhD, Department of Pediatrics,
Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan
College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea.
Tel: +82-2-3010-3379; Fax: +82-2-473-3725; E-mail: sjhong@amc.seoul.kr
Co-corresponding author: Se-Young Oh, PhD, Department of Food and
Nutrition, College of Human Ecology, Kyung Hee University,
26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Korea.
Tel: +82-2-961-0649; Fax: +82-2-959-0649; E-mail: seyoung@khu.ac.kr
Received: October 17, 2011; Revised: May 11, 2012; Accepted: June 26, 2012
• Ju-Hee Seo and Sung-Ok Kwon contributed equally to this work and should
be considered co-first authors.
•There are no financial or other issues that might lead to conflict of interest.

Allergy Asthma Immunol Res. 2013 March;5(2):81-87. http://dx.doi.org/10.4168/aair.2013.5.2.81
Seo et al. Volume 5, Number 2, March 2013
82 http://e-aair.org
duced intake of the antioxidant vitamins C, E, and β-carotene,
which is the result of lower dietary intake of fresh green vegeta-
bles.4
A number of studies have investigated the relationship be-
tween dietary antioxidants and allergic disease in adults. Total
plasma carotenoids were negatively associated with prevalence
of AR in one study,5 and vitamin E supplementation did not de-
crease the percentage of days with serious symptoms or on
which medications were used to control allergic symptoms.6
However, there is considerably less data relating to children.4
Some studies have reported that fruit and vegetable intake pro-
vides a protective eect against wheezing, current asthma symp-
toms, and rhinoconjuctivitis in children.7-9 Similarly, intake of
vegetables and vitamin E protected against the development of
atopy and wheezing in young children, although fruit intake and
vitamin C had no eect on current wheezing.10
e above studies focused on wheezing, asthma, and atopic
dermatitis in children, and there have been few studies on AR
and antioxidant intake. A negative association between AR and
intake of dietary antioxidants and milk has been reported in 6
to 7-year-old children, and a positive association with consump-
tion of nuts and butter has been reported.11 However, it is di-
cult to draw conclusions about the importance of specic anti-
oxidants from this latter study, since it focused on foods and
not nutrients. In the vitamin E (400 IU/day) supplement study
of 63 AR patients aged 12-19 years, there was no eect of vita-
min E on the severity of nasal symptoms or on the concentra-
tion of allergen-specic serum IgE.12
No epidemiologic data of an association between AR and an-
tioxidant nutrients in children are currently available. In the
present study, we addressed this deciency by focusing on the
association between dietary antioxidant nutrients and AR and
allergic sensitization in Korean schoolchildren.
MATERIALS AND METHODS
Study population
is study included 5,036 students (enrolled in rst through
sixth grade) from ve elementary schools that were randomly
selected from ve areas of Seoul City (downtown, northeastern,
northwestern, southeastern, and southwestern) in Korea.
A total of 4,731 children responded to the questionnaire (re-
sponse rate, 93.9%). Of the responders, 4,554 (2,317 [50.9%]
boys and 2,237 [49.1%] girls) were included in this study. e
remaining 177 children, who did not answer the age or sex ques-
tions, were excluded because of insufficient responses to the
questionnaire. e mean age of the enrolled children was 9.50±
1.73 years (Table 1). e parents or guardians of all participants
signed a written informed consent form. is study was approved
by the International Review Board of Asan Medical Center, Uni-
versity of Ulsan, Seoul, Korea.
Methods
Questionnaire survey
A modified International Study of Asthma and Allergies in
Childhood (ISAAC) questionnaire was used in this study.13 e
questionnaire consisted of three main sections: (1) general
characteristics, including name, sex, date of birth, height, and
weight, (2) histories of symptoms related to asthma, AR, atopic
dermatitis, allergic conjunctivitis, and food allergy, and (3) ex-
posure to environmental factors associated with allergic diseas-
es. Our ISAAC questionnaire was the same as the original ISAAC
questionnaire14 except that the core question about disease was
modied with regard to environmental risk factors. e ques-
tions regarding AR were as follows:
• Have you ever had a problem with sneezing or a runny or
blocked nose when you did not have a cold or the u?
• In the past 12 months, have you had a problem with sneez-
ing or a runny or blocked nose when you did not have a cold
or the u?
• Have you ever been diagnosed with AR by a doctor?
• In the past 12 months, have you been treated for AR?
We dened current AR when the child was diagnosed with AR
by doctors and had AR symptoms during the last 12 months.
e questionnaire was explained to the parents or guardians of
the students, and written consent was obtained. e parents or
guardians completed the questionnaires.
Dietary intake was assessed by the semi-quantitative food fre-
Table 1. General characteristics of the study participants
Variable N (%) or Mean (±SD)
Sex (M) 2,317/4,554 (50.9%)
Age (yr) 9.50 (±1.73)
Height (cm) 137.81 (±12.13)
Weight (kg) 34.36 (±10.40)
Body mass index (kg/m2) 17.91 (±3.14)
Family history of allergic disease
Parental history of asthma 125/4,025 (3.1%)
Parental history of AR 1,279/4,025 (31.8%)
Parental history of allergic disease* 1,458/4,025 (36.2%)
Family income (Korean Won/month)
Low ( < 2 million) 554/4,382 (12.6%)
Middle (2-5 million) 3,209/4,382 (73.2%)
High (≥ 5 million) 619/4,382 (14.1%)
AR
Symptom ever 1,604/4,076 (39.4%)
Current symptoms 1,526/4,264 (35.8%)
Current AR 980/4,408 (22.2%)
Diagnosis ever 1,440/4,225 (34.1%)
Treatment 1,097/4,198 (26.1%)
*Allergic diseases: asthma, allergic rhinitis, or atopic dermatitis.
AR, allergic rhinitis.

Allergy Asthma Immunol Res. 2013 March;5(2):81-87. http://dx.doi.org/10.4168/aair.2013.5.2.81
Vitamin C and Allergic RhinitisAAIR
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quency questionnaire (FFQ), which assesses the portion size
and frequency of consumption of 86 dierent food items dur-
ing the previous year. e FFQ was answered by the parents or
guardians. Using the Computer Aided Nutritional Analysis Pro-
gram III (CAN PRO III) developed by the Korean Nutrition So-
ciety the amount of each food item included in the FFQ was
converted into grams, from which daily nutrient intake was cal-
culated.
Skin prick and blood tests
Skin prick and blood tests were conducted on 1,376 students
from one of the ve elementary schools in the study. e skin
prick test measured the responses to 18 allergens (Derma-
tophagoides pteronyssinus, Dermatophagoides farinae, cock-
roach, dog dander, cat dander, tree 1, tree 2, grasses, alder, oak,
mugwort, ragweed, Alternaria, Aspergillus, peanut, milk, egg
white, and soyabean), together with a positive and a negative
control. A positive result for each allergen was defined as a
wheal diameter for the allergen, plus the positive control, of
greater than 3 mm. Total serum IgE was measured using the
uniform capitalization method.
Statistical analysis
Statistical analyses were conducted with the PASW software,
version 18 (SPSS Inc., Chicago, IL, USA). e children were di-
vided evenly into four groups based on the levels of nutrient re-
siduals, which were obtained by adjusting for total calories us-
ing a linear regression model. Multiple logistic regression anal-
ysis was performed by adjusting key covariates such as age, sex,
body mass index, parental history of allergic disease, and month-
ly household income. The odds ratios (ORs) and 95% confi-
dence intervals (CIs) were obtained, and a P value of <0.05 was
considered to indicate statistical signicance.
RESULTS
Baseline characteristics
A parental history of AR was noted in 31.8% of the subjects.
e prevalence of AR diagnosis ever was 33.9%, and 21.1% of
children had current AR (AR symptoms during the last 12
months together with previous diagnosis of AR) (Table 1). Daily
nutrient intake is described in Table 2. e average vitamin C
intake was within the dietary reference intake (DRI) for Kore-
ans. e average intakes of total calories and vitamins A and E
were slightly above the DRI for Koreans.
Relationship between nutrient intake and AR
Vitamin C intake was negatively associated with current AR
symptoms (P for trend=0.003, OR=0.904, 95% CI=0.847-0.966)
and current AR (P for trend=0.007, OR=0.901, 95% CI=0.835-
0.972) by univariate analysis. No association between intake of
vitamin A or E and AR was found (data not shown).
In multiple logistic regression analysis, after adjusting for age,
sex, body mass index, parental history of allergic disease, and
monthly household income, there was an inverse relationship
between vitamin C intake and the risk of current AR symptoms
(P for trend=0.011, adjusted OR=0.886, 95% CI=0.806-0.973)
(Table 3).
Relationship between nutrient intake and serum total IgE or
allergic sensitization
Children from one of the five schools also underwent skin
prick testing and blood sampling. Intake of vitamins A and C
and β-carotene protected from sensitization as measured by
skin prick testing in univariate analysis. However, there was no
association between sensitization and intake of any of the mea-
sured nutrients after adjusting for age, sex, body mass index,
parental history of allergic disease, and monthly household in-
come (Table 4). We also analyzed AR according to allergic sen-
sitization, but there was no significant association. Similarly,
there was no association between total serum IgE level and in-
take of antioxidant-related nutrients by univariate analysis (Ta-
ble 5).
DISCUSSION
We investigated the association between antioxidant-related
nutrient intake and AR in Korean schoolchildren aged 6-12 years.
A higher vitamin C intake was negatively associated with AR
symptoms. However, there was no association between dietary
antioxidants and sensitization measured by skin prick test or
serum total IgE after adjusting for confounding factors. ese
results suggested that nutritional factors, such as vitamin C, in-
uenced the symptoms of AR, but had no eect on atopy.
Inammatory disorders, such as asthma and AR, may be me-
diated by oxidative stress and the failure of antioxidant defens-
es.15 Antioxidants may prevent the free radical-induced chain
Table 2. Daily nutrient intake distribution
Nutrient Mean (±SD) DRIs for Koreans
(6-14 year-old children)
Total calories (kJ) 1,958.675 (±1,271.203) 1,500-1,900
Carbohydrate (g) 275.911 (±165.953) -
Vegetable protein (g) 32.874 (±21.180) -
Animal protein (g) 41.006 (±38.643) -
Vegetable fat (g) 27.947 (±24.101) -
Animal fat (g) 36.798 (±32.190) -
Vitamin A (μg) 824.803 (±702.189) 400-700
Retinol (μg) 228.625 (±172.424) -
β-carotene (μg) 3,351.850 (±3,484.160) -
Vitamin C (mg) 88.218 (±86.980) 60-100
Vitamin E (mg) 15.520 (±14.837) 7-10
DRIs, dietary reference intakes.

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Seo et al. Volume 5, Number 2, March 2013
84 http://e-aair.org
reactions that lead to lipid peroxidation and damage to cell
membranes or DNA, both of which may be involved in the
pathogenesis of allergic disease.16
Associations between antioxidants and allergic disease have
been reported in numerous epidemiological and immunologi-
cal studies. Most observational studies report potentially bene-
ficial associations between dietary antioxidants and allergic
disease. For example, low consumption of fruit and vegetables,
which are rich sources of antioxidants, and low intake of dietary
antioxidants such as vitamin C, vitamin E, and selenium are as-
Table 3. Association between antioxidant nutrient intake and AR in school children aged 6-12 years by multiple logistic regression analysis
AR symptom ever*
970/2,379
Current AR symptom†
926/2,480
Current AR‡
622/2,539
AR diagnosis§
910/2,432
AR treatmentII
678/2,417
Variable aOR¶ (95% CI) aOR¶ (95% CI) aOR¶ (95% CI) aOR¶ (95% CI) aOR¶ (95% CI)
Vitamin A
Q1 1.000 1.000 1.000 1.000 1.000
Q2 0.924 (0.728-1.173) 0.823 (0.649-1.043) 0.883 (0.676-1.153) 0.939 (0.735-1.199) 0.914 (0.704-1.187)
Q3 0.742 (0.582-0.945) 0.666 (0.523-0.847) 0.726 (0.553-0.954) 0.958 (0.749-1.224) 0.824 (0.632-1.074)
Q4 0.970 (0.749-1.256) 0.910 (0.704-1.176) 1.168 (0.879-1.151) 1.219 (0.937-1.587) 1.273 (0.964-1.680)
P for trend 0.935 0.512 0.701 0.265 0.186
Total OR** (95% CI) 1.004 (0.920-1.095) 0.971 (0.889-1.061) 1.019 (0.924-1.125) 1.051 (0.963-1.146) 1.064 (0.970-1.168)
Retinol
Q1 1.000 1.000 1.000 1.000 1.000
Q2 1.024 (0.807-1.300) 0.895 (0.706-1.135) 0.896 (0.686-1.170) 1.149 (0.902-1.464) 0.983 (0.759-1.273)
Q3 1.010 (0.793-1.286) 0.946 (0.745-1.202) 0.945 (0.723-1.234) 1.098 (0.859-1.404) 0.952 (0.732-1.238)
Q4 0.900 (0.705-1.148) 0.894 (0.703-1.138) 0.877 (0.668-1.150) 0.991 (0.771-1.272) 0.909 (0.697-1.187)
P for trend 0.915 0.336 0.550 0.894 0.431
Total OR** (95% CI) 0.995 (0.912-1.086) 0.957 (0.876-1.046) 0.969 (0.876-1.073) 0.994 (0.907-1.089) 0.961 (0.870-1.061)
β-carotene
Q1 1.000 1.000 1.000 1.000 1.000
Q2 1.136 (0.896-1.440) 1.002 (0.791-1.269) 0.958 (0.734-1.250) 1.027 (0.806-1.309) 0.949 (0.731-1.231)
Q3 0.923 (0.723-1.177) 0.885 (0.695-1.127) 0.864 (0.658-1.135) 0.979 (0.764-1.253) 0.944 (0.724-1.229)
Q4 1.016 (0.802-1.287) 0.972 (0.769-1.230) 1.085 (0.834-1.410) 1.141 (0.897-1.451) 1.163 (0.900-1.501)
P for trend 0.773 0.735 0.528 0.223 0.113
Total OR** (95% CI) 1.013 (0.929-1.104) 0.985 (0.903-1.075) 1.032 (0.937-1.136) 1.055 (0.968-1.150) 1.076 (0.983-1.179)
Vitamin C
Q1 1.000 1.000 1.000 1.000 1.000
Q2 1.079 (0.854-1.364) 0.973 (0.771-1.229) 0.937 (0.721-1.216) 0.871 (0.684-1.109) 0.864 (0.668-1.118)
Q3 0.981 (0.769-1.252) 0.923 (0.725-1.175) 0.961 (0.735-1.256) 0.943 (0.738-1.207) 0.902 (0.694-1.173)
Q4 0.861 (0.676-1.097) 0.797 (0.626-1.015) 0.788 (0.599-1.036) 0.845 (0.661-1.080) 0.858 (0.660-1.116)
P for trend 0.086 0.011 0.103 0.581 0.103
Total OR** (95% CI) 0.923 (0.842-1.011) 0.886 (0.806-0.973) 0.915 (0.823-1.018) 0.975 (0.890-1.067) 0.915 (0.823-1.018)
Vitamin E
Q1 1.000 1.000 1.000 1.000 1.000
Q2 0.981 (0.773-1.245) 1.071 (0.845-1.357) 1.076 (0.825-1.403) 0.888 (0.697-1.132) 0.829 (0.638-1.076)
Q3 1.085 (0.852-1.383) 1.039 (0.816-1.323) 1.076 (0.821-1.411) 0.985 (0.770-1.261) 0.956 (0.735-1.243)
Q4 1.095 (0.858-1.397) 1.087 (0.853-1.386) 1.051 (0.798-1.383) 1.046 (0.818-1.338) 1.063 (0.818-1.380)
P for trend 0.238 0.662 0.303 0.098 0.303
Total OR** (95% CI) 1.056 (0.965-1.156) 1.019 (0.937-1.109) 1.050 (0.956-1.154) 1.073 (0.987-1.167) 1.050 (0.956-1.154)
*AR symptoms ever: sneezing or rhinorrhea or nasal obstruction without respiratory infection; †Current AR symptoms: allergic rhinitis symptoms without cold during
last 12 months; ‡Current AR: allergic rhinitis symptoms during last 12 months plus previous diagnosis by a doctor; §AR diagnosis: diagnosed by a doctor ever in their
lifetime; IIAR treatment: treated during the previous 12 months; ¶Adjusted for age, sex, BMI, family income, parental allergic disease, and total calories; **Total OR:
the odds ratio between mean data of each nutrient intake and allergic rhinitis.
AR, allergic rhinitis; OR, odds ratio; CI, condence interval; aOR, adjusted odds ratio; BMI, body mass index.

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sociated with respiratory symptoms and reduced lung func-
tion.8,9,17-20 However, the precise nature of these associations and
the potential for therapeutic intervention remain unclear.17
e role of oxidative stress in AR has not been well-studied,
but may be similar to that in asthma.21 Few epidemiologic stud-
ies have focused on the relationship between antioxidant in-
take and AR, particularly in children. e Mediterranean diet,
which has a high antioxidant content due to its high content of
fruit, vegetables, legumes, nuts, and wholegrain cereals, is asso-
ciated with a decreased incidence of AR.7,22,23 However, it is dif-
cult to draw rm conclusions about the role of antioxidants
from these studies because they did not focus on specic nutri-
ents within the Mediterranean diet.
Vitamin C has intracellular and extracellular aqueous-phase
antioxidant capacity primarily by scavenging oxygen free radi-
cals and suppressing macrophage secretion of superoxide an-
ions.24 Most studies of dietary vitamin C and asthma have re-
ported that consumption of the former is associated with im-
proved ventilator function. In contrast, no association was re-
ported between serum vitamin C and diagnosis of AR.5 ere
was also no association in our study between dietary vitamin C
and diagnosis of AR and atopic sensitization or total serum IgE.
is result was consistent with others of sensitization and vita-
min C.5,25,26 In our study, vitamin C consumption was associat-
ed with reduced symptoms of AR. is result was consistent with
an animal study, which showed that administered vitamin C
exerted a moderate anti-inflammatory effect, although it did
not show any 1/2 shifting eect.27 e anti-inammatory
eect of vitamin C was ascribed to its antioxidant property, and
some investigators insist that vitamin C directly inhibited IkB
kinase phosphorylation leading to eventual inhibition of NF-kB
activation, which plays a critical role in inammation.27,28 We
conclude that higher consumption of vitamin C may improve
the symptoms of AR despite having little eect on allergic sensi-
tization.
Vitamin A comprises retinol and more than 600 carotenoids,
many of which (β-carotene, β-cryptoxanthin, lutein-zeaxan-
thin, and lycopene) have strong antioxidant activity.24 e role
of vitamin A in asthma is not clear. Two analyses of children
aged 4-17 years from National Health and Nutrition Examina-
tion Survey III demonstrated negative associations between
asthma and serum levels of α-carotene and β-carotene,29,30 while
the Dutch MORGEN cross-sectional intervention study of 5,744
adults aged 20-59 reported that dietary β-carotene intake was
positively associated with the 12-month prevalence of wheez-
ing in the absence of respiratory infection.31 Our results are con-
sistent with a previous study showing no association between
Table 4. Association between antioxidant nutrient intake and sensitization by
skin prick test
Univariate analysis Multiple logistic
regression analysis
Variable Crude OR (95% CI) Adjusted OR* (95% CI)
Vitamin A
Q1 1.000 1.000
Q2 0.904 (0.646-1.266) 0.864 (0.553-1.350)
Q3 0.649 (0.464-0.906) 0.564 (0.356-0.895)
Q4 0.677 (0.485-0.946) 0.891 (0.559-1.421)
P for trend 0.005 0.271
Total OR (95% CI) 0.861 (0.774-0. 987) 0.921 (0.795-1.066)
Retinol
Q1 1.000 1.000
Q2 1.062 (0.761-1.483) 1.513 (0.962-2.380)
Q3 1.002 (0.719-1.395) 1.353 (0.857-2.136)
Q4 1.246 (0.889-1.747) 1.371 (0.859-2.187)
P for trend 0.275 0.241
Total OR (95% CI) 1.061 (0.954-1.180) 1.093 (0.942-1.268)
β-carotene
Q1 1.000 1.000
Q2 0.901 (0.644-1.259) 0.836 (0.534-1.310)
Q3 0.709 (0.507-0.991) 0.693 (0.434-1.105)
Q4 0.684 (0.488-0.957) 0.843 (0.530-1.342)
P for trend 0.011 0.348
Total OR (95% CI) 0.871 (0.783-0.968) 0.932 (0.805-1.079)
Vitamin C
Q1 1.000 1.000
Q2 0.966 (0.693-1.346) 0.981 (0.620-1.551)
Q3 0.919 (0.659-1.281) 0.954 (0.598-1.524)
Q4 0.693 (0.496-0.969) 0.911 (0.576-1.441)
P for trend 0.034 0.679
Total OR (95% CI) 0.892 (0.802-0.992) 0.970 (0.838-1.122)
Vitamin E
Q1 1.000 1.000
Q2 1.084 (0.776-1.515) 1.323 (0.835-2.095)
Q3 0.845 (0.606-1.178) 1.123 (0.707-1.782)
Q4 0.962 (0.688-1.346) 1.123 (0.707-1.782)
P for trend 0.493 0.850
Total OR (95% CI) 0.964 (0.867-1.071) 1.014 (0.876-1.174)
*Adjusted for age, sex, BMI, family income, parental allergic disease, and total
calories.
OR, odds ratio; CI, condence interval; BMI, body mass index.
Table 5. Association between antioxidant nutrient intake and total serum IgE
by univariate analysis
Total serum IgE (kU/L)
Nutrient Vitamin A Retinol β-carotene Vitamin C Vitamin E
Q1 139.59 142.16 130.30 143.10 137.78
Q2 149.67 158.48 148.62 150.19 171.63
Q3 152.62 127.53 164.37 145.67 138.87
Q4 151.15 165.22 149.60 154.35 144.40
P for trend 0.956 0.444 0.614 0.974 0.502

Allergy Asthma Immunol Res. 2013 March;5(2):81-87. http://dx.doi.org/10.4168/aair.2013.5.2.81
Seo et al. Volume 5, Number 2, March 2013
86 http://e-aair.org
AR and α-carotene or β-carotene.5
Vitamin E is the principal defense against oxidant-induced
membrane injury and has additional eects on immune func-
tion that might account for dierences reported in epidemio-
logic studies of its associations with allergic disease and asth-
ma.24 ere are several reports of an eect of vitamin E in AR. In
a randomized, double-blind, placebo-controlled study, vitamin
E supplementation in 112 patients with seasonal AR who re-
ceived conventional treatment to control symptoms led to an
improvement in the symptoms reported by the patient but not
by the investigators.6 In contrast, another double blind, place-
bo-controlled study, which evaluated the effect of vitamin E
supplementation in 63 patients with perennial AR, showed no
signicant eect on nasal symptoms or on the serum concen-
tration of specic IgE.12 ese two studies did not investigate di-
etary consumption of vitamin E in addition to the supplement,
making it dicult to assess total vitamin E intake. Our study did
not distinguish between seasonal or perennial AR, and we con-
clude only that vitamin E was not associated with symptoms of
AR.
ere were several drawbacks to this study, including the di-
agnosis of AR by way of questionnaire and not by a medical ex-
amination. In addition, recall bias could have aected the FFQ,
as it recorded dietary habits from the past year, and parents may
have underreported bad and overreported good foods. In addi-
tion, we did not record the use of other supplements, such as
multivitamins, and we could not conrm the correlation of di-
etary nutrient intake to serum levels because we did not mea-
sure serum antioxidant level.
e strengths of the present study include the large number of
participants, the detailed assessment of AR, and the compre-
hensive assessment of dietary intake of antioxidants using a
semi-quantitative FFQ focusing on 86 dierent foods especially
in schoolchildren. e ISAAC questionnaire has been validated
in a number of Korean studies.13,32 Sensitization was evaluated
by skin prick test, and total IgE was measured, although these
were not correlated with nutrient intake.
In conclusion, our data suggest that a higher vitamin C intake
may be benecial in AR, although it is not associated with aller-
gen sensitization.
ACKNOWLEDGMENTS
is study was supported by a grant from the Korea Health-
care Technology R&D Project, Ministry for Health, Welfare Af-
fairs, Republic of Korea (A092076). e authors would like to
thank all of the study participants, their parents, and their school
teachers, all joint research workers.
REFERENCES
1. Schatz M. A survey of the burden of allergic rhinitis in the USA. Al-
lergy 2007;62 Suppl 85:9-16.
2. Sly RM. Changing prevalence of allergic rhinitis and asthma. Ann
Allergy Asthma Immunol 1999;82:233-48; quiz 248-52.
3. Jee HM, Kim KW, Kim CS, Sohn MH, Shin DC, Kim KE. Prevalence
of asthma, rhinitis and eczema in Korean children using the Inter-
national Study of Asthma and Allergies in Childhood (ISAAC)
questionnaires. Pediatr Allergy Respir Dis 2009;19:165-72.
4. Patel S, Murray CS, Woodcock A, Simpson A, Custovic A. Dietary
antioxidant intake, allergic sensitization and allergic diseases in
young children. Allergy 2009;64:1766-72.
5. Kompauer I, Heinrich J, Wolfram G, Linseisen J. Association of ca-
rotenoids, tocopherols and vitamin C in plasma with allergic rhini-
tis and allergic sensitisation in adults. Public Health Nutr 2006;9:
472-9.
6. Shahar E, Hassoun G, Pollack S. Eect of vitamin E supplementa-
tion on the regular treatment of seasonal allergic rhinitis. Ann Al-
lergy Asthma Immunol 2004;92:654-8.
7. Garcia-Marcos L, Canflanca IM, Garrido JB, Varela AL, Garcia-
Hernandez G, Guillen Grima F, Gonzalez-Diaz C, Carvajal-Urueña
I, Arnedo-Pena A, Busquets-Monge RM, Morales Suarez-Varela M,
Blanco-Quiros A. Relationship of asthma and rhinoconjunctivitis
with obesity, exercise and Mediterranean diet in Spanish school-
children. orax 2007;62:503-8.
8. Hong SJ, Lee MS, Lee SY, Ahn KM, Oh JW, Kim KE, Lee JS, Lee HB;
for the Korean ISAAC Study Group, Korean Academy of Pediatric
Allergy and Respiratory Disease, Seoul, Korea. High body mass in-
dex and dietary pattern are associated with childhood asthma. Pe-
diatr Pulmonol 2006;41:1118-24.
9. Lee SI. Prevalence of childhood asthma in Korea: international
study of asthma and allergies in childhood. Allergy Asthma Immu-
nol Res 2010;2:61-4.
10. Hijazi N, Abalkhail B, Seaton A. Diet and childhood asthma in a so-
ciety in transition: a study in urban and rural Saudi Arabia. orax
2000;55:775-9.
11. Farchi S, Forastiere F, Agabiti N, Corbo G, Pistelli R, Fortes C,
Dell’Orco V, Perucci CA. Dietary factors associated with wheezing
and allergic rhinitis in children. Eur Respir J 2003;22:772-80.
12. Montaño Velázquez BB, Jáuregui-Renaud K, Bañuelos Arias Adel C,
Ayala JC, Martínez MD, Campillo Navarrete R, Rosalia IS, Salazar
Mdel R, Serrano HA, Mondragón AO, Perez RL. Vitamin E eects
on nasal symptoms and serum specic IgE levels in patients with
perennial allergic rhinitis. Ann Allergy Asthma Immunol 2006;96:
45-50.
13. Hong SJ, Lee MS, Sohn MH, Shim JY, Han YS, Park KS, Ahn YM, Son
BK, Lee HB; Korean ISAAC Study Group. Self-reported prevalence
and risk factors of asthma among Korean adolescents: 5-year fol-
low-up study, 1995-2000. Clin Exp Allergy 2004;34:1556-62.
14. Worldwide variation in prevalence of symptoms of asthma, allergic
rhinoconjunctivitis, and atopic eczema: ISAAC. e International
Study of Asthma and Allergies in Childhood (ISAAC) Steering
Committee. Lancet 1998;351:1225-32.
15. Bakkeheim E, Mowinckel P, Carlsen KH, Burney P, Carlsen KC. Al-
tered oxidative state in schoolchildren with asthma and allergic
rhinitis. Pediatr Allergy Immunol 2011;22:178-85.
16. Marmsjö K, Rosenlund H, Kull I, Håkansson N, Wickman M, Per-
shagen G, Bergström A. Use of multivitamin supplements in rela-
tion to allergic disease in 8-y-old children. Am J Clin Nutr 2009;90:
1693-8.
17. Allan K, Kelly FJ, Devereux G. Antioxidants and allergic disease: a

Allergy Asthma Immunol Res. 2013 March;5(2):81-87. http://dx.doi.org/10.4168/aair.2013.5.2.81
Vitamin C and Allergic RhinitisAAIR
87
http://e-aair.org
case of too little or too much? Clin Exp Allergy 2010;40:370-80.
18. Cook DG, Carey IM, Whincup PH, Papacosta O, Chirico S, Bruck-
dorfer KR, Walker M. Effect of fresh fruit consumption on lung
function and wheeze in children. orax 1997;52:628-33.
19. Shaheen SO, Sterne JA, Thompson RL, Songhurst CE, Margetts
BM, Burney PG. Dietary antioxidants and asthma in adults: popu-
lation-based case-control study. Am J Respir Crit Care Med 2001;
164:1823-8.
20. Tabak C, Smit HA, Räsänen L, Fidanza F, Menotti A, Nissinen A,
Feskens EJ, Heederik D, Kromhout D. Dietary factors and pulmo-
nary function: a cross sectional study in middle aged men from
three European countries. orax 1999;54:1021-6.
21. Bowler RP, Crapo JD. Oxidative stress in allergic respiratory diseas-
es. J Allergy Clin Immunol 2002;110:349-56.
22. Chatzi L, Apostolaki G, Bibakis I, Skypala I, Bibaki-Liakou V, Tzana-
kis N, Kogevinas M, Cullinan P. Protective eect of fruits, vegetables
and the Mediterranean diet on asthma and allergies among chil-
dren in Crete. orax 2007;62:677-83.
23. de Batlle J, Garcia-Aymerich J, Barraza-Villarreal A, Antó JM, Ro-
mieu I. Mediterranean diet is associated with reduced asthma and
rhinitis in Mexican children. Allergy 2008;63:1310-6.
24. Devereux G, Seaton A. Diet as a risk factor for atopy and asthma. J
Allergy Clin Immunol 2005;115:1109-17; quiz 1118.
25. McKeever TM, Lewis SA, Smit H, Burney P, Britton J, Cassano PA.
Serum nutrient markers and skin prick testing using data from the
ird National Health and Nutrition Examination Survey. J Allergy
Clin Immunol 2004;114:1398-402.
26. Forastiere F, Pistelli R, Sestini P, Fortes C, Renzoni E, Rusconi F,
Dell’Orco V, Ciccone G, Bisanti L. Consumption of fresh fruit rich
in vitamin C and wheezing symptoms in children. SIDRIA Collab-
orative Group, Italy (Italian Studies on Respiratory Disorders in
Children and the Environment). orax 2000;55:283-8.
27. Jeong YJ, Kim JH, Kang JS, Lee WJ, Hwang YI. Mega-dose vitamin C
attenuated lung inammation in mouse asthma model. Anat Cell
Biol 2010;43:294-302.
28. Cárcamo JM, Pedraza A, Bórquez-Ojeda O, Golde DW. Vitamin C
suppresses TNF alpha-induced NF kappa B activation by inhibiting
I kappa B alpha phosphorylation. Biochemistry 2002;41:12995-3002.
29. Rubin RN, Navon L, Cassano PA. Relationship of serum antioxi-
dants to asthma prevalence in youth. Am J Respir Crit Care Med
2004;169:393-8.
30. Harik-Khan RI, Muller DC, Wise RA. Serum vitamin levels and the
risk of asthma in children. Am J Epidemiol 2004;159:351-7.
31. Grievink L, Smit HA, Ocké MC, van ‘t Veer P, Kromhout D. Dietary
intake of antioxidant (pro)-vitamins, respiratory symptoms and
pulmonary function: the MORGEN study. orax 1998;53:166-71.
32. Kim WK, Kwon JW, Seo JH, Kim HY, Yu J, Kim BJ, Kim HB, Lee SY,
Kim KW, Kang MJ, Shin YJ, Hong SJ. Interaction between IL13 gen-
otype and environmental factors in the risk for allergic rhinitis in
Korean children. J Allergy Clin Immunol 2012;130:421-6.e5.