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original article

Role of vitamin D supplementation in allergic rhinitis


Datt Modh, Ashish Katarkar, Bhaskar Thakkar1, Anil Jain, Pankaj Shah, Krupal Joshi2

Access this article online ABSTRACT


Website: www.ijaai.in

DOI: 10.4103/0972-6691.134223
Background: Allergic rhinitis(AR) is the most common type of chronic rhinitis,
Quick Response Code:
affecting 1020% of the population. Severe AR has been associated with significant
impairments in quality of life, sleep, and work performance. Arole for vitamin D
in the regulation of immune function was first proposed after the identification of
vitamin D receptors in lymphocytes. It has since been recognized that the active
form of vitamin D, 1, 25(OH) 2D3, has direct affects on nave and activated
helper Tcells, regulatory Tcells, activated Bcells and dendritic cells. There is a
growing researches linking vitamin D(serum 25(OH) D, oral intake and surrogate
indicators such as latitude) to various immunerelated conditions, including
allergy, although the pattern of this relationship is still yet to establish. Such
effects of vitamin D can significantly affect the outcome of allergic responses
like in AR. Aims and Objectives: To evaluate nasal symptom scores in patients
of AR, preand posttreatment with and without supplementation of vitamin D.
Materials and Methods: Vitamin D levels were assessed in 21patients with AR
diagnosed clinically and evaluated prospectively during the period of 1year.
Preand posttreatment vitamin D3 serum levels measured and documented.
They received oral vitamin D(cholecalciferol; 1000IU) for a given period. The
results were compared with the patients having ARtreated conventionally
without supplementation of vitamin D. Results: Improvement in the levels of
serum vitamin D levels were significant in posttreatment patients(P=0.0104).
As well as clinical improvement in terms of reduction in the total nasal
symptom score was also significant in the posttreatment patients(P<0.05).
Conclusion:Supplementation of vitamin D in such patients alters natural course
of AR toward significant clinical improvement.

Key words: Allergic rhinitis, vitamin D supplementation, immunemodulation

INTRODUCTION Severe AR has been associated with significant impairments


in quality of life, sleep and work performance.[1] There are
Allergic rhinitis(AR) is the most common type of chronic good treatments available for AR, including antihistamines
rhinitis, affecting 1020% of the population, and evidence and topical corticosteroids.[2] Yet, there is a need for new
suggests that the prevalence of the disorder is increasing. treatment options, particularly aiming at new targets and

Departments of ENT, and 2Community Medicine, C. U. Shah Medical College and Hospital, Surendranagar, 1Department of
Pathology, GMERS Medical College, Gandhinagar, Gujarat, India
Address for correspondence: Dr.Datt Modh, Department of ENT, C. U. Shah Medical College and Hospital, Surendranagar, Gujarat, India.
Email: dattmodh@gmail.com

Indian Journal of Allergy, Asthma and Immunology | Jan-Jun 2014 Volume 28 Issue 1 35
Modh, etal.: Vitamin D in Allergic Rhinitis

associated with reduced side effects. The prevalence varies Another 21patients of lower and middle class between 15
among countries, probably because of geographic and and 50years of age both gender having a history of AR were
aeroallergen differences.[36] In India, AR is considered to be a assessed in the similar way for pretreatment TNSS and
trivial disease, despite the fact that symptoms of rhinitis were treated using similar criteria i.e.fexofenadine(inpatients
present in 75% of children and 80% of asthmatic adults.[7] having TNSS score 10) and fluticasone nasal
spray(inpatients having TNSS score11) for a short
In recent years, the worldwide increase in allergic diseases period but without supplementation of vitamin D and
has been associated with low vitamin D. Schauber etal.[8] followed similarly after given period. Posttreatment
stated that the association between low serum vitamin TNSS assessed and compared.
D levels and an increase in immune disorders is not
coincidental. Growth in populations has resulted in people Measurements
spending more times indoors, leading to less sun exposure Before and after treatment, patients rated their nasal
and less cutaneous vitamin D production.[9] symptoms(i.e.,rhinorrhea, nasal blockage, sneezing,
nasal itching, anosmia) using four point scale as follows:
To investigate the value of vitamin D in the treatment 0=No symptom evident, 1=symptom present but not
of allergic diseases and asthma, several studies have bothersome, 2=definite symptom that is bothersome
been designed up to date. However still the results are but tolerable, 3=symptoms that is hard to tolerate.
controversial.[8,10,11] Vitamin D deficiency can be treated Each patients TNSS were calculated by summing that
and further it can prevent AR occurrence and thus reduce patients nasal symptoms[Table1][12]
morbidity. In the presented study, the vitamin D status of Serum vitamin D3 levels measured using Cobas E
patients with AR was compared preand posttreatment with 411(fully automated) hormoneimmunoassay analyzer.
oral vitamin D supplements(cholecalciferol1000IU) and Enhanced Chemiluminance method used by this
course of AR assessed. instrument for measurement. 25(OH) D levels greater
than 30ng/ml is considered as normal
MATERIALS AND METHODS While vitamin D deficiency is defined as 25(OH) D
levels<20ng/ml, vitamin D insufficiency defined as
Study design and population 25(OH) D levels between 20 and 30ng/ml[Table2].[13]
The study included patients with AR, who were referred to Patients with serum vitamin D levels>30ng/ml were
Department of ENT in our institute during a 1year period considered as normal and excluded from the study. Such
between December 2011 and December 2012. patients were two in number
A total of 21patients between 15 and 50years age both Followup Clinical assessment for nasal symptom
gender having a history of AR were included in the study. score and serum vitamin D levels were obtained
Inclusion criteria were patients having history of AR after 21days during which patients with deficient
(perennial) with eosinophilia on blood smear/nasal smear vitaminD levels were supplemented with oral vitamin
All the patients were thoroughly interviewed and D3 (cholecalciferol; 1000IU).
complete ENT examination were done
Total nasal symptoms score(TNSS) recorded preand Statistical analysis
posttreatment Data were analyzed using SPSSR software(version17.0; SPSS,
Serum vitamin D3 levels were measured preand USA). Descriptive statistical analysis and nonparametric
posttreatment statistical tests were used.
They received tablet fexofenadine(in patients having
TNSS score10) and fluticasone nasal spray(in patients
having TNSS score11) for a short period to relieve Table1: Total nasal symptomes socring system
acute phase without vitamin D3 which was followed Score 03
Rhinorrhea 03
supplementation of oral vitamin D3(cholecalciferol; Obstruction 03
1000IU) in case of deficiency for 21days Sneezing 03
Exclusion criteria concerned patients who had comorbid Itching 03
disease in addition to AR that could affect vitamin D Anosmia 03
TNSS Out of 15
serum levels. Such diseases included rheumatoid arthritis,
0Absent, 1Mild, 2Moderate, 3Severe, TNSSTotal nasal symptoms score
cystic fibrosis, multiple sclerosis, ulcerative colitis,
Crohns disease, celiac disease, rickets, osteomalacia,
sarcoidosis and thyroid dysfunctions, and individuals Table2: Vitamin D status - grading
who had received medications including corticosteroids, Vitamin D status Serum level(ng/ml)
barbiturates, bisphosphonates, sulfasalazine, omega3 Normal >30
and vitamin D components such as calciumD were Insufficient 2030
excluded Deficient <20

36 Indian Journal of Allergy, Asthma and Immunology | Jan-Jun 2014 Volume 28 Issue 1
Modh, etal.: Vitamin D in Allergic Rhinitis

RESULTS Improvement in the levels of serum vitamin D levels


were significant using paired ttest in our study group
Initially there were 23patients. 2 of them were having (P=0.0104). The clinical improvement in terms of reduction
levels>30ng/ml i.e.normal in our study. Hence they in the total nasal symptom score was assessed using Wicoxan
were excluded. Of the 21patients enrolled in the signed rank test for preand posttreatment in our study
study, 11(52.38%) were men and 10(47.61%) were group where value of P=0.0001. Which shows statistically
women[Table3]. The mean age of the patients was significant differences between these two group[Table6].
34.479.25years. Distribution of patients according to
The patients with TNSS>11 were having mean vitamin
age is summarized in Table4.
D level 16.884.65ng/ml. These patients were improved
following treatment suggested by the posttreatment
The mean vitamin D level was 18.035.61ng/ml in 21patients
TNSS(mean)3.77 1.92.The improvement in the
of AR before treatment. Posttreatment mean vitamin D
level of vitamin D were also noted in this group with a
level was 28.926.21ng/ml in 15patients(71.42%) in which
mean level of21.54 9.17 ng/ml which was statistically
vitamin D level was increased following supplementation significant(P<0.05). This observation correlates the link
of oral vitamin D3(cholecalciferol; 1000IU). Rest of the of severity of AR with vitamin D deficiency.
6patients(28.57%) showed decrease in the vitamin D level.
In another control group of patients without supplementation
Of the 21patients evaluated, 8(38.09%) were experiencing vitamin D, the mean pretreatment TNSS score was
severe signs and symptoms of the AR(TNSS>11), 10(47.61%) 11.041.93 which get improved following antiallergic
were considered to be moderate(TNSS: 710) and 1(4.76%) treatment applying same criteria as for study group and mean
were classified as mild(TNSS: 36) and 2(9.42%) were with posttreatment TNSS score was 4.661.99. In the control
TNSS: 02[Table5]. In this group of patients overall mean group, this improvement in TNSS was also significant when
pretreatment TNSS score was 10.62.65 and posttreatment assessed by Wicoxan signed rank test suggested by value of
mean TNSS score was 2.761.6[Table6]. P=0.0001[Table7].

Posttreatment improvement in the TNSS were indicated DISCUSSION


by shifting of patients to a lower TNSS as shown in Table6.
The mean vitamin D levels posttreatment were 22.1; 21.22 In AR, numerous inflammatory cells, including mast cells,
and 25.86 in the group of patients having TNSS 710; 36 CD4positive Tcells, Bcells, macrophages, and eosinophils,
and 02 respectively. infiltrate the nasal lining upon exposure to an inciting
allergen(most commonly airborne dust mite fecal particles,
Table3: Sex distribution of disease cockroach residues, animal dander, molds, and pollens).[14]
Sex No. of patients Percentage During the early phase of an immune response to an inciting
Male 11 52.38 allergen the mediators and cytokines are released which
Female 10 47.61 trigger a further cellular inflammatory response over the
Total 21 100
next 48h(late phase inflammatory response) which
results in recurrent symptoms(usually nasal congestion).[15]
Table4: Age distribution of disease Infiltration of inflammatory cells is evident in both seasonal
Age group(years) No. of patients Percentage
2024 2 9.52 Table6: Pre and post treatment comparison of disease severity
2529 4 19.04 and vitamin D levels
3034 5 23.8 Study group TNSS Vitamin D(21patients)
3539 2 9.52
Pretreatment 10.62.65 185.61
4044 4 19.04
Posttreatment 2.761.6 23.919.73
4550 4 19.04
Difference 7.84 5.91
Total 21 100
TNSSTotal nasal symptoms score

Table5: Distribution of patients according to severity- pre and Table7: Effect of vitamin D supplementation
post treatment
Treatment modality TNSS Difference
TNSS No. of patients (%) Mean Mean
Pretreatment Posttreatment pretreatment posttreatment
>11 8(38.09) 0 Antiallergic treatment followed 10.62.65 2.761.6 7.84
710 10(47.61) 1(4.76) by vitamin D supplementation
36 1(4.76) 8(38.09) Antiallergic treatment only 11.041.93 4.661.99 6.34
02 2(9.42) 12(57.14) without vitamin D supplementation
TNSSTotal nasal symptom score TNSSTotal nasal symptoms score

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Modh, etal.: Vitamin D in Allergic Rhinitis

and perennial form, though the magnitude of these cellular vitamin D into active calcitriol with subsequent paracrine
changes is somehow different in seasonal and perennial AR.[16] and autocrine effects.[21,22]

The Tcells infiltrating the nasal mucosa are predominantly As 25(OH) D serum levels are low in individuals and vitamin
T helper(Th) 2 in nature and release cytokines D influences allergy mediating immune cells such as Tcells
(e.g.interleukin[IL]3, IL4, IL5, and IL13) that promote and immune functions of cells forming the barriers against
immunoglobulin E(IgE) production by plasma cells. IgE allergies such as epithelial cells, one might speculate that
production, in turn, triggers the release of mediators, such as vitamin D plays a role in allergy development. First scientist
histamine and leukotrienes, which leads to arteriolar dilation, who hypothesized a link between nutritional intake of
increased vascular permeability, itching, rhinorrhea(runny vitamin D and allergies wereWjstand Dold in 1999.[23]
nose), mucous secretion, and smooth muscle contraction.[1]
Effect of vitamin D on innate immunity
In our study, patients of AR showed deficiency in vitaminD Innate immune responses comprise all mechanisms that
indicated by mean vitamin D level of 18.035.61ng/ml resist infection, but do not require specific recognition of the
before treatment. This result suggests the importance of pathogen. Several aspects of innate immunity are affected
assessing vitamin D levels in patients of AR. There are by vitamin D.
other studies recently coming in support of this fact as
stated by Arshi etal.[17] The prevalence of severe vitamin D The expression of pattern recognition receptor, which activates
deficiency was significantly higher in patients with AR than innate immune responses such as Tolllike receptors(TLRs)
the normal population. In a study performed by Moradzadeh on monocytes are inhibited by Vitamin D, which leads to
etal.[18] the prevalence of severe vitamin D deficiency was suppression of TLRmediated inflammation.[24] Vitamin D
significantly greater in patients with AR than the normal induces autophagy in human macrophages, which helps in the
population(30% vs. 5.1%; P=0.03) demonstrating that defense against opportunistic infections.[25] The endogenous
there is an association between serum vitamin D levels and antimicrobial peptide in resident epithelial cells in the skin
AR status. These results may indicate subtle differences and lung are induced by Vitamin D, thereby strengthening
in terms of vitamin D metabolism or sensitivity in allergic the innate barriers against environmental allergens.[26,27]
patients, as hypothesized by Wjst and Hyppnen.[19]
Effect of vitamin D on adaptive immunity
Lymphocytes such as Tcell with Th1 and Th2 polarization
In presented study, we supplemented the patients of AR
are major players in adaptive immunity and vitamin D
having deficient serum vitamin D levels with oral vitamin
modulates their functions.
D supplements(cholecalciferol1000IU) and such patients
were followed to evaluate their clinical status regarding AR. Proinflammatory cytokine release from peripheral
There was an improvement in the total nasal symptom score mononuclear blood cells in general and from Tcells in
and serum vitamin D level in such patients as it is concluded particular are decreased by vitamin D.[28,29] In addition, Tcell
from the presented study. When the clinical improvement proliferation is suppressed by vitamin D through decreased
compared in the control group in which vitamin D Th1 cytokine production.[30,31] Vitamin D increases IL10 and
supplements were not given, they showed a difference of decreases IL2 production, thereby promoting the state of
6.34 in TNSS score which is lower than our study group hypo responsiveness in T regulatory cellsan effect which is
which showed a difference of 7.84 in TNSS score. When also seen with antiallergic therapies such as corticosteroids
both groups compared statistically using MannWhitney or allergen immunotherapy.[28,30]
Utest, P=0.0001, which shows a significant difference
between study group and control group. Effect of vitamin D on IgE secretion, mast cells and
eosinophils
As per internet medical database there is no similar study Vitamin D also affects B lymphocytes functions and
done previously. Our study and its result are more important modulates the humoral immune response including
than other studies mentioned above suggesting a correlation secretion of IgE.[31]
between AR and vitamin D as they did not compare the
preand posttreatment levels and its clinical correlation. Allergymediating cells such as mast cells and eosinophils
are also vitamin D targets: Increased cutaneous vitamin D
The improvement in the allergic status can be attributed synthesis increases IL10 production in mast cells, which
to the immunomodulator effects of vitamin D on the leads to suppression of skin inflammation[32] also vitamin D
immune system: Vitamin D regulates the activity of various treated mice showed reduced airway hyperresponsivenes and
immune cells, including monocytes, dendritic cells, T and decreased infiltration of eosinophils in the lung.[33]
B lymphocytes, as well as immune functions of epithelial
cells.[20] Furthermore, some immune cells express vitamin As chronic AR is a decays old problem, management of
Dactivating enzymes facilitating local conversion of inactive which is a difficult task for most of clinicians including
38 Indian Journal of Allergy, Asthma and Immunology | Jan-Jun 2014 Volume 28 Issue 1
Modh, etal.: Vitamin D in Allergic Rhinitis

physicians and otolaryngologists in the current scenario, 14. SmallP, FrenkielS, BeckerA, BoisvertP, BouchardJ, CarrS,
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RajabianR, NabipourI, etal. Normative values of vitamin D
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ACKNOWLEDGMENT Vitam Horm 2011;86:2362.
21. BaekeF, TakiishiT, KorfH, GysemansC, MathieuC. VitaminD:
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2011;125:102832. Joshi K. Role of vitamin D supplementation in allergic rhinitis. Indian J
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