Association between Serum Vitamin D Levels and Risk of Sudden Sensorineural Hearing Loss: A cross-sectional Study

Abstract

Background

Sudden sensorineural hearing loss (SSNHL) is an autoimmune diseases of the inner ear which is usually defined by acute onset of hearing loss in one or both ears, of 30 dB or more on at least three contiguous audiometric frequencies within 3 days or less. This study aimed to compare the serum levels of 25-hydroxyvitamin D (VitD) between patients with SSNHL and healthy controls.

Methods

A total of 50 patients with SSNHL and 50 healthy individuals without hearing loss as control group were enrolled in this study. Serum levels of VitD and other related laboratory tests such as calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) were measured and compared between two study groups.

Results

Serum level of VitD was significantly lower in patients suffering from SSNHL compared to the healthy controls (26.55 ± 14.44 vs. 33.51 ± 14.21, P = 0.017, respectively). VitD insufficiency was observed in 70% (n = 35) of the patients with SSNHL as compared to 44% (n = 22) of healthy individuals, demonstrating a significant difference between two study groups. However, no statistically difference was observed for serum levels of Ca, P, and PTH.

Conclusion

This study indicated an increased prevalence of VitD insufficiency in subjects with SSNHL, suggesting a possible association between serum VitD levels and the development of SSNHL. VitD may protect the hearing loss through its antioxidant role.

Introduction

Sudden sensorineural hearing loss (SSNHL) is an autoimmune disease of the inner ear that is unilateral in almost 90% of cases. It is a relatively common controversial condition in otological and audiological practices [1]. SSNHL is typically characterized by an abrupt onset of hearing loss in one or both ears, with a decline of at least 30 decibels on three or more contiguous audiometric frequencies within a period of three days or less [2].

SSNHL is diagnosed in almost 5–20 cases per 100,000 individuals annually. The incidence is positively associated with age, and it is more prevalent, especially in men and women between 50 and 60 years old [3]. SSNHL is a medical emergency that should be diagnosed and treated immediately to prevent permanent hearing loss and devastating consequences; the sooner treatment might lead to more significant recovery [4, 5]. Despite the extensive research, much controversy remains about the etiology and appropriate care of these patients. SSNHL is usually idiopathic; however, viral infection, vascular impairment, autoimmune disorder, impaired blood flow to the cochlea, otologic disease, retro-cochlear pathologies, obesity, and diabetes are among the possible risk factors of the disease [6, 7]. High-dose oral administration of corticosteroids is the current standard treatment for idiopathic SSNHL to improve the inflammation and edema (swelling) in the hearing organs. Evaluating the benefits of applying different antioxidants, minerals, or metabolic materials as adjuvant therapy to the current standard treatment is of great interest to investigators.

Vitamin D (VitD) produced photochemically in the skin from 7-dehydrocholesterol as a steroid hormone, is mainly involved in calcium homeostasis and mineralization of collagen matrix that lead to normal bone growth. VitD deficiency or insufficiency is a common global issue that affects infants, children, and adults [8]. Deficiency of VitD has been detected in different conditions, such as parathyroid hormone secretion disorders, osteoporosis, various cancers, cardiovascular diseases, type I diabetes, and obesity [9, 10]. VitD can also maintain the oxidant-antioxidant equilibrium as an antioxidant. Few studies have shown the association between antioxidant nutrients and hearing loss with inconsistent results. According to the literature, dietary intake of antioxidant vitamins (A, C, and E), magnesium, vitamin B12, folic acid, and NAC might be potentially influential in improving the SSNHL along with the main treatment strategy [11–14].

Despite the considerable effect of using antioxidant vitamins in combination with standard treatment in complete recovery of SSNHL patients, more research is needed to come up with conclusive evidence. The role of VitD in the human auditory system has been extensively studied, with research indicating that VitD deficiency is linked to both bilateral hearing impairment and bilateral sensorineural hearing loss in older adults [15–19]. The aim of this study was to investigate the difference in serum VitD levels between patients with SSNHL and healthy controls.

Materials and methods

This cross-sectional study was conducted in the otolaryngology clinic of Ghaem and Imam-Reza hospitals of Mashhad, Iran, on all the patients who were referred with complaints of acute hearing loss within the last 72 h. A total of 50 patients with SSNHL as the case group and 50 healthy individuals without hearing loss as the control group were enrolled in this study. The control group consisted of individuals who accompanied the patients to the clinic and were deemed healthy.

The inclusion criteria for entering the study were patient’s age between 18 and 65 years old and consent for participating in the study, loss of hearing due to SSNHL in the last 72 h, not using VitD supplements for at least three months before the investigation or having any underlying medical condition. Individuals taking VitD supplements during the last months, having underlying disease, and those with gradual hearing loss were excluded from the study.

All the patients were examined by otolaryngology specialists and SSNHL was diagnosed based on patients’ description, physical examination, and laboratory and radiologic evaluations. All the included participants signed the written constant form. The ethics committee of Mashhad University of Medical Sciences approved this study with ethics code of IR.MUMS.MEDICAL.REC.1401.156.

All the data regarding the age, sex, and severity of the hearing loss of the patients was gathered. Laboratory tests were then conducted to measure the levels of calcium, phosphorus (P), parathyroid hormone (PTH), and plasma (25-hydroxy) vitamin D3, in order to compare their levels between the two groups. Patients in case group were compared with the healthy controls regarding the VitD level. VitD insufficiency was defined as having a serum VitD levels of less than 20 ng/ml.

Comparisons were made using Fisher’s exact test, chi-square, and t-test, and a significance level of < 0.05 were considered for all analyses. Statistical analyses were performed using SPSS version 21.

Results

In total, 50 patients with confirmed SSNHL were included in the case group consisting of 28 males and 22 females aged 50 years or older (with the mean age of 50.66 ± 16.43 years old). In the control group, 50 healthy individuals including 27 males and 23 females, with the mean age of 44.22 ± 15.11 were included. Groups were matched regarding sex; however, they showed significant differences when compared by age (Table 1).

Table 1.

Comparing groups regarding the vitamin D, calcium, phosphorus (P), parathyroid hormone (PTH).

Groups		Case (mean ± SD)	Control (mean ± SD)	P-value
Age (year)		50.66 ± 16.43	44.22 ± 15.11	0.044
Gender	Male	56	54	0.841
	Female	44	46
VitD (ng/mL)		26.55 ± 14.44	33.51 ± 14.21	0.017
Ca (mg/dL)		9.37 ± 0.67	9.06 ± 0.67	0.025
P (mg/dL)		3.65 ± 0.65	3.89 ± 0.42	0.032
PTH (pg/mL)		37.44 ± 16.07	37.97 ± 12.56	0.854

VitD: Vitamin D, Ca: Calcium, P, Phosphate, PTH: parathyroid hormone, SD: Standard deviation

Results of the plasma levels of calcium, phosphate, PTH, and VitD in the case group compared with the control group are presented in Table 1. Evaluating the mean VitD serum level showed that patients with SSNHL had significantly lower VitD levels compared with healthy controls; mean ± sd: 26.55 ± 14.44 vs. 33.51 ± 14.21, P = 0.017, respectively (Fig. 1). VitD insufficiency was detected in 70% (35 patients with SSNHL) of the case group compared with 44% (22 healthy individuals) of the controls (Fig. 2), which was significantly higher in the case group.

Fig. 1.

Difference between case and control groups regarding the vitamin D level

Fig. 2.

Difference between case and control groups regarding the prevalence of vitamin D insufficiency

Results showed that patients did not have any statistically significant difference with the control group regarding the serum level of calcium. The mean calcium level was 9.37 ± 0.68 in the case group and 9.06 ± 0.09 in healthy controls (P = 0.025) (Table 1).

Comparing case vs. controls did not show any significant difference on P level; mean ± SD: 3.6 ± 0.7 vs. 3.8 ± 0.8 (P = 0.032), respectively. Comparing the PTH level revealed no significant difference between case and control groups: mean ± sd: 37.44 ± 16.07 vs. 37.97 ± 12.56 (P = 0.854).

Discussion

We compared 50 SSNHL patients with healthy controls regarding the difference in their VitD, P, PTH, and calcium levels. Results showed that VitD insufficiency was more prevalent in patients with SSNHL compared with healthy controls. In total, 70% of the SSNHL patients had VitD insufficiency; however, only 44% of the healthy controls had VitD insufficiency. Patients with SSNHL also had a lower levels of serum VitD level compared with healthy controls (Table 1). Serum level of 25-OHD (the major circulating form of VitD) was used as a standard index of VitD nutritional status in individuals and an accepted clinical indicator of VitD insufficiency. VitD insufficiency leads to neuropathological adverse effects as it is a neurosteroid hormone; the deficiency might results in neurological decline of the cranial nerves related to the auditory vestibular nerve. According to our result, VitD status could affect the hearing threshold and might be involved in SSNHL incidence.

The association between VitD level and SSNHL has been examined in several previous studies that revealed conflicting results. The study of Brooks et al. showed the link between bilateral cochlear hearing loss and decreased VitD level for the first time as a new metabolic type of sensorineural deafness [17]. Our findings were in line with studies which confirmed the significant role of VitD in the typical human auditory system, and revealed the involvement of VitD deficiency directly in hearing problems and auditory dysfunction, or indirectly in exerting secondary effects as an antioxidant or by disturbances of calcium metabolism [15–17, 20].

By comparing the case group with controls in the current study, no association was found between PTH, Ca, and P levels with SSNHL in case group. Hypothyroidism is another predisposing factor for the incidence of SSNHL. Hypothyroidism is significantly related to decreased VitD and calcium levels and increased incidence of SSNHL; however, we did not find any differences between patients and healthy controls regarding the Ca, P, and PTH levels, which roll out the effect of hyperthyroidism on the incidence of SSNHL in our patients [21, 22].

The potential of antioxidants as an adjuvant treatment of SSNHL has attracted a special interest currently. According to the literature, the auditory system is influenced by of antioxidant and reactive oxygen species (ROS) [20]. VitD, as an antioxidant might be able to prevent ROS production and manage oxidative stress by reducing the main biomarkers. It has shown antioxidant effects by maintaining the oxidant-antioxidant equilibrium through reducing malondialdehyde (MDA) which is lipid peroxidation marker [23]. It has been shown that VitD has a protective role against oxidative stress by inhibiting the iron-dependent liposomal lipid peroxidation in erythrocytes, oxidative stress-related protein oxidation, and DNA damage [24]. Lipid peroxidation is responsible for cell damage. The imbalance between ROS production and degradation (oxidative stress) in the auditory sensory organ, results in excessive production of ROS which is proposed as another cause of SSNHL. Hair cells of the auditory pathway that contain sensory epithelium in the cochlea are the main target of ROS and are prone to oxidative-related hearing loss. In study of Paprocki et al., the effect of VitD was evaluated in patients with SSNHL undergoing hyperbaric oxygen (HBO) therapy. According to their results, VitD could increase the total antioxidant capacity in blood serum of patients and decrease lipid peroxidation [20].

Other epidemiological studies in this field of research also showed the implication of VitD in cochlear diseases, such as Menier disease, tinnitus, vertigo, and cochlear otosclerosis [25, 26]. The role of VitD insufficiency might be based on several biological explanations for the underlying mechanism, such as regulation of vascular cell function, angiogenesis, immunomodulatory properties, and inflammation [27].

The biological role of VitD is mediated through its binding receptors and regulating target gene expression in variety of cells and tissues. Dysfunction of the VitD receptor (VDR) also has been implicated in ear disorders as the proper activity of the VDR is crucial for reducing oxidative stress and DNA damage [28]. VitD and binding receptors also might be involved in enhancing the antioxidant defense system through upregulating cellular glutathione (GSH), glutathione peroxidase, and superoxide dismutase to reduce reduces nitrite production and ROS secretion [24].

VitD is a key regulator of calcium absorption and bone metabolism, and its low concentration could be linked with low Ca level and proposed as risk factor for SSNHL disease. Although VitD decline might lead to calcium demineralization, data on the relation between VitD level and calcium concentration is contentious; in our study no significant difference was observed between groups regarding the serum Ca level. In study of Szeto et al. on hearing loss risk factors in the elderly, altering calcium homeostasis within the inner ear and demineralization of the cochlea were suggested as the consequences of low VitD level and responsible mechanisms of hearing loss. They also did not find any association between PTH and hearing loss, which was consistent with our results [19].

The prevalence of SSNHL has shown no sex preference; however, it has been associated with higher age, and Vit D deficiency and low bone mineral density are risk factors for age-related hearing loss [16, 18].

In conclusion, the considerably high prevalence of VitD insufficiently in patients with SSNHL, increased the likelihood of VitD being a significant risk factor for SSNHL pathogenesis. VitD might affect hearing loss through its antioxidant role.

Author Contributions

Study concept and design: MRA, HMM, Acquisition of data: AZ, BR, ZMK Statistical analysis: HMM, Drafting of the manuscript: AZ, HMM, Study supervision: MRA.

Data Availability

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Declarations

Competing Interests

The authors declare no conflicts of interest regarding the publication of this paper.