Am J Otolaryngol xxx (xxxx) xxxx

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Am J Otolaryngol
journal homepage: www.elsevier.com/locate/amjoto

Investigation of vitamin D levels in patients with Sudden Sensory-Neural

Hearing Loss and its effect on treatment
⁎
Hossein Ghazavi, Amir-Abbas Kargoshai, Mohammad Jamshidi-koohsari
Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

A R T I C LE I N FO A B S T R A C T

Keywords: Background: Due to high prevalence of vitamin D deficiency and the possible association with Sudden Sensory-
Sudden Sensory-Neural Hearing Loss (SSNHL) Neural Hearing Loss (SSNHL) finding the main causes and appropriate treatments are highly essential. This study
Response to treatment aimed to investigate vitamin D levels in patients suffering SSNHL and its effect on response to treatment.
Vitamin D Materials and methods: This cross-sectional study was performed on two groups of case (34 SSNHL patients) and
control (34 healthy subjects without risk of hearing loss). All patient information such as age, sex, audiogram
illustration of hearing frequency and the level of vitamin D were recorded at baseline. Patients with SSNHL
received routine treatments such as 10 days of 1 mg/kg/day steroid and the response or lack of complete re-
sponse to treatment was recorded and analyzed according to the audiometry.
Results: Vitamin D level in SSNHL group with a mean of 19.28 ± 9.56 ng/ml was significantly less than the
control group (25.71 ± 11.21 ng/ml; P value < 0.001). After treatment, 76.5% were completely recovered and
23.5% did not recover completely. Factors such as age, sex and level of initial hearing loss did not have a
significant effect on the response to treatment, but the level of vitamin D in these patients had a significant
relationship with the response to treatment (P value = 0.004); so that all patients with sufficient vitamin D level
had completely recovered, versus 87.5% of patients with vitamin D deficiency and 12.5% of insufficient vitamin
D had no response to treatment.
Conclusion: According to the results of the present study, the prevalence of vitamin D deficiency in patients with
SSNHL was more than healthy people. SSNHL patients with deficient vitamin D had the highest percentage of no
response to treatment.

1. Introduction
Sudden Sensory-Neural Hearing Loss (SSNHL) refers to hearing loss
above 30 dB (or higher) in three consecutive frequencies occurring
within a 72-h period [1]. The estimated annual incidence of SSNHL is
5–30 cases in every 100,000 with annual report of 15,000 new cases all
over the world and about 4000 new cases in the USA [2].
On the other hand, though the causes of SSNHL are unknown and
the case is classified as idiopathic, the identified causes of the disease
can be trauma, infection, neoplasm, blood vessel diseases, autoimmune
diseases and central nervous system disorders [3].
This disease is one of the most controversial issues in otorhinolar-
yngology. It is the responsibility of physicians to seek out specific
causes, and to identify and investigate effective factors in its prognosis
and to find the appropriate treatment for this agitating and annoying
disease [4–6].
The treatment of SSNHL is based on its cause. In case of SSNHL with
unknown cause, the best and most effective cure is corticosteroids.
Other treatments are intravenous and oral steroids, intratympanic
steroid treatment, hyperbaric oxygen therapy, meglumine, antiviral
drugs, anticoagulants, vasodilators such as papaverine, nicotinic acid
and anti-inflammatory drugs [7,8].
On the other hand, it is estimated that around one billion people
worldwide suffer from vitamin D deficiency. The prevalence of vitamin
D deficiency has been observed in Middle Eastern and Asian countries
(including Iran), which 50.8% of adults with high levels of vitamin D
deficiency [9–11]. Today, vitamin D deficiency in adults is associated
with cases such as autoimmune diseases, increased triglycerides, type 1
and type 2 diabetes and neoplasms, and in children with severe asthma,
bronchiolitis, and decreased or lack of response to corticosteroids
[12,13]. In addition, given the presence of vitamin D receptor in the
inner ear, it seems reasonable that deficiency of this vitamin can cause
problems in this area [14,15]. Moreover, vitamin D deficiencies or its
metabolic derivatives 25-OHD and 1.25(OH)2D may directly lead to

⁎
Corresponding author.
E-mail addresses: Mj.6483@gmail.com, www.mj_6483@yahoo.com (M. Jamshidi-koohsari).

https://doi.org/10.1016/j.amjoto.2019.102327
Received 2 October 2019
0196-0709/ © 2019 Elsevier Inc. All rights reserved.

Please cite this article as: Hossein Ghazavi, Amir-Abbas Kargoshai and Mohammad Jamshidi-koohsari, Am J Otolaryngol,
https://doi.org/10.1016/j.amjoto.2019.102327
H. Ghazavi, et al.
auditory dysfunction or create secondary effects by disturbing the
metabolism of calcium. Such factors may primarily interfere with the
physiological mechanisms of the inner ear. Alternatively, secondary
functional problems can be caused by disrupting the morphology of the
neurosensory epithelium or the supporting bone structure of the otic
capsule. In fact, deficiency of ionized calcium may adversely affect
transmission of the nerve action potentials generated by the cochlea, by
inhibiting the release of transmitter substances at the neural synapse
and impairing neuronal excitability [15,16].
Therefore, researchers believe that vitamin D deficiency may be
directly or indirectly associated with hearing loss [14,15,17,18].
In this regard, it has been reported that vitamin D deficiency is very
common in patients with Ear, Nose and Throat problems (E.N.T).
Several studies have indicated that vitamin D deficiency is associated
with deafness and hearing impairment or SSNHL, as well as its possible
impact on the patient's improvement [14–19]. According to these stu-
dies, the cause is most likely the demineralization of the cochlea re-
sulting in a metabolic type of sensorineural hearing loss [15]. There-
fore, due to the high prevalence of vitamin D deficiency (especially in
the Iranian population) and the lack of evaluation of the effect of this
vitamin on the recovery of these patients, the present study was con-
ducted to determine the prevalence of vitamin D deficiency in patients
with SSNHL and its effect on response to treatment.
2. Materials ad methods
This cross-sectional study was performed on 34 SSNHL patients at
Al-Zahra hospital in Isfahan from May 2018 to April 2019 as the
treatment group and 34 healthy people without hearing loss as the
control group.
The incidence of SSNHL disease was considered to be at least 30 dB
in three consecutive frequencies within 72 h or less. The criteria for
entering the study in the treatment group included consent to partici-
pate in the study, a period of less than or equal to 45 days from the
incidence of hearing loss to the patient's referral to the hospital, failure
to see evidence of acute and chronic otitis media in the patient's ex-
amination and history, no history of ear surgery, absence of Meniere
disease, acoustic trauma, barotrauma, genetic SNHL, or known
anomalies in the inner ear. There was also no evidence of retrocochlear
disease in the control group. It should be noted that during the study,
patients with drug complications (corticosteroids) or those who did not
complete their treatment and not attended to the next follow-up, were
excluded (which in the present study, no one was excluded). After
obtaining the approval of ethical committee of Isfahan University of
Medical Sciences and obtaining the written consent of all participants in
the study (cases and controls), at first, demographic characteristics such
as age, sex and clinical characteristics including hearing frequency il-
lustrated in audiogram were recorded. Then, 5 cm3 of blood sample was
taken from each patient to measure vitamin D level and the results were
recorded. Serum 25(OH)D level < 12 ng/ml (< 30 nmol/L) has been
considered as deficient and serum 25(OH)D level of 12–20 ng/ml
(30–50 nmol/L) has been considered as insufficient and 25(OH)D
level ≥ 20 ng/ml (≥50 nmol/L) has been considered as sufficient [10].
Then, in the case group, routine treatments as 1 mg/kg/day of
corticosteroids were given for 10 days. If partial response (response to
therapy based on audiometry) was found within ten days, treatment
continued for ten more days until further recovery (based on audio-
metry) was not observed. The status of these patients was determined
and documented in two categories: response to treatment (Improved)
and lack of response to treatment (Non-Improved). Finally, the col-
lected information was included in the SPSS (ver. 22) software and it
was analyzed using the Fisher's exact test, chi-square and t-test, and
significance level of < 0.05 was considered for all analyzes.
2
Am J Otolaryngol xxx (xxxx) xxxx
Table 1
Compare the age and gender between the two groups.
Characteristics Control (n = 34) SSNHL (n = 34) P value
Sex Male 14(41.2%) 12(35.3%) 0.803
Female 20(58.8%) 22(64.7%)
Age; year 48.12 ± 15.75 50.26 ± 15.89 0.578
< 30 year 6(17.6%) 4(11.8%) 0.748
30–60 year 18(52.9%) 18(52.9%)
> 60 year 10(29.4%) 12(35.3%)
Pure Tone Audiogram (Mean 15.38 ± 4.97 46.06 ± 13.56 < 0.001
Threshold); dB
3. Results
In this study, of 34 patients with SSNHL, 12 patients (35.3%) were
male and 22 patients (64.7%) were female with the mean age of
50.26 ± 15.89 years, and of 34 healthy subjects in the study, 14 pa-
tients (41.2) were male and 20 cases (58.8%) were female with the
mean age of 48.12 ± 15.75 years (P value > 0.05). The hearing
threshold of people in the SSNHL group with the mean of
46.06 ± 13.56 dB (42.4% mild hearing loss, 57.6% moderate hearing
loss) was significantly elevated than the control group with the mean of
15.38 ± 4.97 dB (P value < 0.001) (Table 1).
On the other hand, vitamin D levels in the SSNHL group with the
mean of 19.28 ± 9.56 ng/ml was significantly less than the control
group with the mean of 25.71 ± 11.21 ng/ml (P value < 0.001); so
that 26.5% of people in the SSNHL group had vitamin D deficiency,
47% had vitamin D insufficiency, and 26.5% had vitamin D sufficiency.
In the control group, deficient, insufficient and sufficient vitamin D
level were reported as 8.8%, 41.2% and 50% respectively (Fig. 1).
Finally, status assessment of patients in the SSNHL group after
treatment showed that 76.5% of patients recovered and 23.5% were not
completely recovered. In addition, the recovery of patients were not
significantly different based on age, sex and level of hearing loss (P
value > 0.05), but vitamin D level in patients with complete recovery
with a mean of 21.79 ± 9.47 ng/ml was significantly higher than pa-
tients without complete recovery with the mean of 11.13 ± 3.31 ng/
ml (P value = 0.004); so that 87.5% of untreated patients had vitamins
D deficiency and 12.5% had insufficient vitamin D and all patients with
sufficient vitamin D had a complete recovery (Improved) (P value <
0.001) (Table 2).
4. Discussion
This study was performed on 34 patients with SSNHL and 34
healthy people (without hearing loss). More than 50% of patients with
SSNHL were women with the mean age of 50.26 ± 15.89 years.
In this regard, some studies on the prevalence of SSNHL reported
the increase of disease rate with age, especially among the men of 50 to
60 years [1]. The relationship of hearing sensitivity loss with age is
caused by peripheral hearing system disorders specially inside the co-
chlea [20,21]. The cochlea is the auditory portion of the inner ear that
is located in the bony spiral canal containing fluid-filled membranous
channels [22]. Although it is well recorded that the nature of hearing
loss is related with age, but the causes are still unknown. It is possible
that increasing the time of exposure to noise and other environmental
factors (such as toxic substances, drugs) with age in the daily life causes
hearing loss in some of the elderly [23,24].
On the other hand, in the present study, in both groups a high
percentage of vitamin D deficiency or insufficiency was observed. This
vitamin D deficiency in patients with SSNHL was far more than healthy
people (without hearing problem), with 47% of these patients having
insufficient vitamin D levels and 26.5% vitamin D deficiency.
In line with the present study, Segana et al. showed a very high
prevalence (79%) of vitamin D deficiency (44.7% insufficient levels of
H. Ghazavi, et al. Am J Otolaryngol xxx (xxxx) xxxx

Fig. 1. Assessment of vitamin level D in the two groups in the study.

Table 2 In this regard, according to the results of some previous studies,

Evaluation of factors associated with patient recovery. 45–65% of patients with SSNHL may gain previous hearing even
Characteristics Improved (n = 26) Non-improved P value without treatment (with the mean increase of 35 dB). Self-healing
(n = 8) without treatment can occur within 2 weeks (in 30 to 80% of cases), but
complete recovery occurs only in 35% of patients [6].
Sex Male 9(34.6%) 3(37.5%) 0.881
Ibrahim et al. (2018) also pointed out to the benefits of anti-anti-
Female 17(65.4%) 5(62.5%)
Age; year 43.75 ± 12.97 52.27 ± 16.39 0.181
oxidants as an adjuvant element (such as Antioxidant vitamins A, C and
< 30 year 2(7.7%) 2(25.0%) 0.194 E) for SSNHL treatment [1]. Recent reports indicate that free radicals,
30–60 year 13(50.0%) 5(62.5%) reactive oxygen species, and nitric oxide have toxic effects on the au-
> 60 year 11(42.3%) 1(12.5%) ditory system (especially outer hair cells). During mitochondrial re-
Pure Tone Audiogram 45.38 ± 13.60 48.25 ± 14.13 0.609
spiration, reactive oxygen species (ROS) are produced, which, if over-
(Mean Threshold); dB
Vitamin D, ng/ml 21.79 ± 9.47 11.13 ± 3.31 0.004 produced, can cause cell damage. The use of antioxidants can protect
Deficiency 2(7.7%) 7(87.5%) < 0.001 the cells by recycling additional ROSs and prevent injury [27,28]. Al-
Insufficiency 15(57.7%) 1(12.5%) though our study did not discuss the above mentioned antioxidants and
Sufficiency 9(34.6%) 0(0.0%) only vitamin D was considered, but this suggests that along with
treatment, there are some underlying factors that can affect the treat-
ment process or even by taking them into account and using regimens
vitamin D and 34.3% vitamin D deficiency) [18]. The prevalence of this
containing them, it is possible to affect the treatment of these patients.
deficiency over the age of 65 in is 14.5%–30% in England, 24.3% in the
Several studies have reported the important role of vitamin D for
United States, 12.5% in Italy, 55% in Ireland, 83% in the United
normal vestibular and auditory function [19,29,30]. A study on ten
Kingdom, and 50.8% in Iran [9,25].
patients with bilateral cochlea hearing loss revealed a relationship be-
Many previous studies also reported high prevalence of vitamin D
tween hearing loss and vitamin D deficiency [15].
deficiency or insufficiency in patients with hearing problems [14–19].
According to another study, sensory-neural hearing loss has been
According to previous studies, vitamin D deficiency causes increased
commonly observed in patients with hypothyroidism.
respiratory infections in patients. It also has a role in pathophysiology
Hypoparathyroidism causes a deficiency of 1,25-dihydroxyvitamin D
of chronic rhinitis and nasal sinusitis [26].
associated with hypocalcemia. Therefore, it is natural to suspect that
In fact, scientists have proven that vitamin D receptors are on the
hypocalcemia and/or vitamin D deficiency are associated with hearing
systems dedicated to the transport of Ca in the inner ear and help reg-
loss pathogenesis. Therefore, impaired inner ear function is probably
ulate the proper calcium balance. This mechanism helps explain the
due to low levels of calcium in the inner ear fluid and/or systemic vi-
role of vitamin D in maintaining good ear performance. The role of
tamin D deficiency [31].
vitamin D deficiency is associated with hearing loss, Menier disease,
Taneja also concluded that serum level of vitamin D (25(OH)D
and otosclerosis, including cochlear otosclerosis [15].
serum) is essential; its deficiency may lead to recurrence of respiratory
In addition, after treatment of patients with SSNHL in this study,
and ear infections that may lead to dramatic illnesses such as hearing
76.5% recovered completely and 23.5% was recovered partially.
loss, poor language communication, and mental health. They stated
Although the age of patients with complete recovery was higher than
that in cases of relapse of otitis/cholesteatoma, estimation and sup-
those with partial recovery, this difference was not statistically sig-
plementation of vitamin D are important in managing these cases [17],
nificant. In addition, gender was not associated with their recovery, but
which may end up with significant morbidity in terms of hearing loss,
the levels of vitamin D was different in these people; so that none of the
poor language, communication, and mental health.
patients without complete recovery had sufficient level of vitamin D
In general, vitamin D deficiency may effect hearing directly and
and only12.5% had vitamins D insufficiency and > 80% of them had
indirectly by altering calcium metabolism, fluids and nerve transmis-
vitamin D deficiency. However, in patients with complete recovery,
sion, and bone structure. Vitamin D deficiency, directly or indirectly,
34.6% had enough level of vitamin D and a small percentage of them
through its role in calcium homeostasis may lead to degeneration of
(7.7%) had vitamin D deficiency. Therefore, it can say that the level of
auditory structures, cochlear sensitivity to chronic ischemic effects,
vitamin D in patients may have a significant role in the course of
imbalance in lysosomal enzymes that lead to cellular degradation,
treatment and response.
deafness and cochlear demineralization and changes in bone

3
H. Ghazavi, et al.
remodeling of the otic capsule [32, 33, 34].
Therefore, considering that dietary factors such as vitamin D defi-
ciency are associated with cochlear disorder and disturbances in cal-
cium homeostasis in the cochlea and the possible impact on the re-
sponse to treatment, it seems that attention to this vitamin is very
important. However, in this study, co-administration of this vitamin
with routine treatment was not used and it only showed higher per-
centage of response to treatment in SSNHL patients with higher vitamin
D levels. It is suggested to evaluate the role of enrichment with sup-
plements such as vitamin D and other nutrients in people with vitamin
D deficiency and hearing loss, and investigate their role in better and
faster response to treatment.
5. Conclusion
According to the results of the present study, the prevalence of vi-
tamin D deficiency/insufficiency in patients with SSNHL was higher
than healthy people. In addition, the high percentage of no response to
treatment in SSNHL patients was seen in the cases with insufficiency or
deficiency of vitamin D.
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