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Abstract

Background: Vitamin B12 is an essential nutrient crucial for overall health, and deficiencies can lead to hearing loss. Objective: The aim of the systematic review was to explore the intricate connection between vitamin B12 deficiency and hearing loss using a systematic literature review. Methods: A systematic literature search was carried out to identify the articles exploring the connection between vitamin B12 deficiency and hearing loss. Electronic databases such as PubMed, Scopus, and Cochrane databases were used to identify the relevant studies. Results: A total of 612 studies were identified from 3 databases, and after stepwise screening, 9 articles were found eligible for the data extraction and inclusion in the review. Most of the studies had observed statistically-significant differences in the hearing thresholds with low vitamin B12 levels. However, few studies found hearing loss in the low frequencies (250 and 500 Hz), and others have found elevated thresholds above 4 KHz. Factors such as age, gender, and treatment for vitamin B12 did not show any significant changes in the hearing thresholds. Conclusion: The systematic review revealed that individuals with lower vitamin B12 levels tended to have a higher prevalence of hearing impairment than those with normal or elevated levels. Vitamin B12 deficiency, coupled with high homocysteine levels and low folate concentrations, may contribute to different degrees of hearing loss, particularly in the elderly. Lower serum levels of vitamin B12 have been associated with slight to mild hearing loss, while cochlear dysfunction and poorer hearing thresholds have also been observed in individuals with vitamin B12 deficiency. These findings highlight the importance of maintaining optimal levels of vitamin B12 for preserving hearing health and warrant further investigation into potential interventions.

Keywords

vitamin B12 deficiency cobalamine hearing loss vitamin deficiency

Introduction

The B vitamins, namely, B1, B2, B3, B5, B6, B7, B9, and B12, also known as thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folate, and cobalamin respectively, are group of essential nutrients with diverse chemical properties that fulfill various functions in the human body.¹ Most of these vitamins are produced by plants, except for vitamin B12. The neurotropic vitamins B1, B6, and B12 each plays unique roles in the nervous system. Vitamin B12 (cobalamin) is a micronutrient that serves an important function in maintaining metabolic function of the body. It also has a role in DNA synthesis and maintaining blood level.² Myelination, which refers to synthesis of myelin sheath, is another important function of vitamin B12(2). Due to its involvement in numerous critical pathways, a deficiency in vitamin B12 poses a significant health issue.^3,4

Insufficient intake or impaired absorption of vitamin B12 leads to vitamin B12 deficiency.⁵ A vitamin B12 deficiency is commonly diagnosed based on the measurement of vitamin B12 in serum or plasma. A vitamin B12 deficiency is considered as having a concentration below 148 pmol/L (200 pg/mL) and marginal status defined as a concentration of 148 to 221 pmol/L.⁶

The source of vitamin B12 is mainly from animal-based food products⁷ and very few plant based foods, such as shiitake mushrooms, dried purple laver (nori), and tempe.⁸ One of the studies shows that consuming meat, milk, and fish is associated with higher vitamin B12 levels, particularly in Western countries.⁹ Different types of animal meats such as beef, veal, mutton, and lamb, which come from ruminant animals such as cattle and sheep, are rich sources of B12. Additionally, pork and poultry, which come from omnivorous animals such as pigs and chickens, also serve as good sources of vitamin B12.^7,10 Vegans, who exclude all animal-derived foods from their diet, need to fulfil their vitamin B12 needs through fortified foods or supplement³ diet, thus having a significant impact on the vitamin B12 levels

The process of making vitamin B12 from food usable by our cells is complicated and has several steps. First, vitamin B12 binds to different proteins as it moves through the intestine and blood. These proteins include haptocorrin, intrinsic factor, and transcobalamin II.¹¹ Finally, the vitamin B12, now part of the holotranscobalamin complex, is absorbed by the target cell after it binds to the transcobalamin receptor.¹²

Apart from vitamin B12 deficiency, other nutritional deficiencies such as iron, folic acid, and vitamin D are also known to affect the auditory system.^9,13,14 Vitamin D is crucial for maintaining calcium balance and is essential for transmitting electrical impulses between nerve fibers and hair cells. Few studies have reported that low levels of vitamin D can lead to sensorineural hearing loss (SNHL) and may also increase the risk of age-related hearing loss (ARHL).^15,16 Iron deficiency can reduce oxygen supply to cells, potentially damaging them and impairing the brain's ability to process sound signals. This can lead to hearing loss and reduced auditory perception.¹⁷ The formation of free radicals in the inner ear is a key factor in hearing loss, and vitamins A, C, and E, in synergy with magnesium, reduce changes in hearing thresholds more reliably than any single agent.^18,19

Deficiency of vitamin B12 has been linked to impaired myelination of neurons in cochlear nerve, impaired cellular metabolism affecting nervous system and vascular system affecting hearing loss.^20,21 Adequate vitamin B12 levels are essential for optimal functioning of the nervous and vascular systems. The deficiency in these levels and its impact on the auditory system has been explored in isolated studies, and a systematic review is warranted to consolidate these findings. The present systematic review explores the connection between vitamin B12 deficiency and hearing loss.

Method

The review was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.²² The review aimed to answer the research question “What is the relationship between vitamin B12 deficiency and hearing loss as evidenced in literature?” Thus, a systematic search was conducted to find the relevant articles examining the link.

The inclusion criteria for including studies in the review were as follows: studies exploring link between vitamin B12 deficiency and hearing loss and studies published in English language up to Match 2024. Animal and in vitro studies and studies on other micronutrients that did not discuss vitamin B12 deficiency and published in languages other than English were excluded. Case reports or case series and letter to editor were excluded.

The PubMed, Scopus, and Cochrane databases were searched using search terms and suitable Boolean operators “AND” and “OR.” A broad search was carried out using search terms “hearing loss” OR “hearing impairment” AND “Vitamin B12.” The search results were compiled using the Mendeley desktop reference manager, and duplicate studies were eliminated. Title and abstract screening were carried out independently by the first and second authors. The articles that met the inclusion criteria were included at this stage. Any discrepancies in inclusion were resolved through discussion among all the authors. The full-text articles corresponding to the shortlisted abstracts were retrieved. A predefined data-extraction template was used for this study. The data extracted from the final articles included details such as author details, year of publication, study design, population, inclusion and exclusion criteria, serum vitamin levels, audiological findings, and intervention used and outcomes. The quality of the included studies were assessed using the Mixed Methods Appraisal Tool (MMAT) version 2018.²³

Results

The Figure 1 illustrates the process followed based on the PRISMA statement.

Figure 1.

Prisma flowchart.

A total of 612 articles were identified across different databases of which 69 were duplicates. After duplicates removal, 547 studies were screened for the title. Eleven articles underwent abstracts screening. A total of 10 studies were included for full-length review of which 9 article were finally included in review for data-extraction.

The characteristics of the included studies are discussed in Table 1.

Table 1.

Characteristics of included studies.

Study ID	Study design	Aim	Population	Inclusion and exclusion criteria	Serum vitamin levels	Audiological evaluation	Intervention	Outcome
Akyay et al.²⁴	Case-control	To investigate the effects of vitamin B12 deficiency on hearing in school-aged children by pure-tone audiometry	80 children (2 groups): Case: 43 vitamin B12-deficient children, control: 37 normal vitamin B12 levels	The inclusion criteria included vitamin B12 levels <200 pg/mL; normal iron, ferritin, folic acid, and biochemical values; intact ear drums; and normal middle ear function as indicated by tympanometry. The exclusion criteria included frequent middle ear infections (>4 times a year), ototoxic medications, genetic hearing loss, head trauma, ear surgery and presence of structural or mechanical occlusive problems leading to hearing loss, tympanic membrane perforation, unilateral hearing loss, conductive hearing loss, folic acid or iron deficiencies, and air–bone gap greater than 10 decibel (dB) hearing level at any frequency	Vit B12 deficiency present if plasma vitamin B12 < 200 pg/mL. Mean vitamin B12 level: group 1-141.39 ± 32.49 pg/mL. group 2—328.02 ± 8.5 pg/mL	Pure-tone threshold at frequencies 0.25–16 kHz; tympanometric evaluation	8 patients in group 1 were repeated after vitamin B12 supplementation followed by audiologic measurements (repeated) – (100 µg daily for 1 week, 100 μg weekly for 3 weeks and 500 µg monthly thereafter)	• The vitamin B12 level was statistically significantly lower in group 1 than in the controls • No differences between boys and girls at any PTHTs • FFPTA (four-frequency pure-tone average; 0.5, 1, 2, and 4 kHz) values and PTHTs at 0.25–4 kHz were worse and slight, and mild hearing losses were more likely in the vitamin B12-deficient group than in the control group in school-aged children • Vitamin B12 supplementation did not cause any changes in hearing tests in 8 patients in group 1
Berkiten et al.²⁵		To determine vitamin B12 levels in patients with nonpulsatile tinnitus and to assess the efficacy of replacement treatment in tinnitus and hearing in patients with vitamin B12 deficiency	100 patients (mean age, 43.87, SD 10.12; 62 females, 38 males) and 20 healthy volunteers (9 females, 11 males)	Exclusion criteria: after a detailed medical history, patients who had suffered head trauma, who had a history of chronic otitis media or a family history of hearing loss and who had a noise induced hearing loss	Patients whose blood serum vitamin B12 levels were below 180 pg/mL were deemed to be vitamin B12-deicient	Audiometry and high-frequency audiometry (250-20 000 Hz)	63 patients with low vitamin B12 levels received parenteral vitamin B12 therapy. Vitamin B12 (1 g/mL) was injected intramuscularly once a day for 5 days and then once a month for one year. Serum vitamin B12 concentrations increased significantly after this vitamin B12 treatment	Patients with normal vitamin B12 had experienced tinnitus for an average of 15.10 (SD 13.51) months, and those with vitamin B12 deficiency had experienced tinnitus for an average of 19.61 (SD 25.12) months. Of the patients with tinnitus, 63% had low vitamin B12 levels, and 37% had normal levels. In subjects with vitamin B12 deficiency, the mean VAS values were 6.40 ± 1.58 before vitamin B12 therapy and 6.24 ± 3.05 after vitamin B12 therapy. However, the difference in the severity of tinnitus after vitamin B12 therapy was not significant. Hearing loss was higher in ears with tinnitus
Gocer et al.²⁶	Retrospective study	To investigate a possible association between hearing impairment and homocysteine, folate and vitamin B12 concentrations in subjects presenting with sensorineural hearing loss before the geriatric age, namely, before the age of 60	Two groups of patients. group 1 (n = 78) with hearing impairment. Group 2, control group (n = 53) without hearing impairment	The inclusion criteria: middle-aged adults (40-60 years) with sensorineural hearing loss. Exclusion criteria: recent consumption of vitamin B12 and/or folate supplements. Ototoxic drug usage, noise exposure, ear surgery, perforated tympanic membrane, Meniere’s disease, cranial trauma, metabolic and systemic diseases, a family history of ischemic heart disease, and a personal history of cardiovascular disease	The reference ranges for vitamin B12 were 145-980 pg/mL and >2.7 ng/mL for folate. Mean vitamin B12 level: group 1—251.7 ± 158.6 pg/mL. Group 2—304.9 ± 152.0 pg/mL. Grouped into 3 categories based on HL	Otoscopy, tympanometry, and a complete audiologic evaluation. Pure-tone air and bone conduction audiometry (250-8 kHz) and speech audiometry	NA	In both groups, no correlation between the age and the blood concentrations of vitamin B12, folate, and homo cysteine could be found. Pure-tone averages were inversely correlated (Spearman’s rank-order correlation coefficient) with serum vitamin B12. Compared with women with impaired hearing, those with normal hearing were 3 times more likely to meet the RDA-recommended dietary allowance for vitamin B12 (not a significant difference). But the associations of auditory function with dietary intake of folate and vitamin B12 remained significant. Compared with participants with normal hearing, participants with impaired hearing had 38% lower mean serum vitamin B12. The findings suggest that elevated homocysteine and decreased folate and vitamin B12 concentrations accompany to hearing loss before the geriatric age. Poor auditory function was consistently associated with low concentrations of serum vitamin B12
Gok et al.²⁷	Cross-sectional study	To determine the levels of homocysteine, folic acid, and vitamin B12 in subjects with noise-induced hearing loss. Furthermore, possible links between these parameters and NIHL were aimed to be evaluated	Study group: 28 male patients with noise-induced hearing loss (mean age 37 ± 5 year). Control group: 32 healthy male volunteers (mean age 36 ± 4 year)	Exclusion criteria: History of using ototoxic drugs, previous ear diseases, trauma to head and the ear, and familial history of hearing diseases	Mean vitamin B12 level: NIHL group: 199.87 ± 75.25 pg/mL. Control Group: 323.62 ± 121.91 pg/mL	PTA—Air conduction (250-16 kHz); bone conduction (500-4000 Hz), questionnaire	NA	Vitamin B12 levels were significantly lower in patients with NHIL than in controls. In study group the hearing loss was started at 4000 Hz and reached to maximum at 6000 Hz
Houston et al.²¹		To test the hypothesis that age-related hearing loss may be associated with poor vitamin B12 and folate status	55 healthy women aged 60-71 years. Categorized into 2 groups for logistic regression analyses: normal hearing (<20 dB hearing level	Exclusion criteria: H/o diabetes, stroke, ear diseases, noise induced hearing loss, or unilateral hearing loss, and use of fluorides, bisphosphonates such as Fosamax (Merck & Co Inc, Whitehouse Station, NJ), or calcitonin. Potential participants with conductive hearing loss (air-bone gaps > 10 dB) were also excluded. The study also excluded age-related hearing loss, or presbycusis, that were identified based on hearing loss that might have been due to other causes (ear infections, ototoxic medications, genetics, trauma, ear surgery, Meniere disease, or otosclerosis) or who had hearing loss before the age of 50 years	Normal (<20 dBHL, n = 38-44): Serum vitamin B12 (pmol/L)— 380 ± 1544 [380] < 148 pmol/L (%)- 3 < 185 pmol/L (%)- 5 < 221 pmol/L (%)- 13 HI (≥20 dBHL, n = 10-11). Serum vitamin B12 (pmol/L)—236 ± 150 [206] < 148 pmol/L (%)- 30 < 185 pmol/L (%)—30 < 221 pmol/L (%)- 60	PTA (0.5, 1, 2, and 4 kHz). Otoscopic examinations acoustic immittance otoacoustic emissions. Speech audiometry tests. Questionnaire	NA	Mean age was the same (65 years) for the normal hearing and impaired hearing groups. Pure-tone averages were inversely correlated with serum vitamin B12 and red cell folate. Women with impaired hearing had 38% lower serum vitamin B12 (236 compared with 380 pmol/L, respectively) and 31% lower red cell folate (425 compared with 619 nmol/L, respectively) than women with normal hearing. Among participants who did not take supplements containing vitamin B12 or folate, women with impaired hearing had 48% lower serum vitamin B12 (156 compared with 302 pmol/L, respectively) and 43% lower red cell folate (288 compared with 502 nmol/L, respectively) than women with normal hearing
Karaer et al.²⁸	Prospective case-control study	To examine the association between low serum vitamin B12 levels and low serum vitamin D levels and cochlear health in women	30 patients with vitamin B12 deficiency (a mean age of 32.5 ± 1.7 years women). 30 patients with vitamin D deficiency (a mean age of 32.3 ± 1.58 years women) and 30 controls (a mean age of 27.8 ± 1.48 years women)			Distortion product otoacoustic emissions (DPOAEs), transient evoked otoacoustic emissions (TEOAEs)	NA	Signal-to-noise ratio for TEOAE 1, 2, 3, 4 kHz and DPOAE 1, 2, 6 kHz was somewhat lower in patients with vitamin B12-deficient group than in the controls. Moreover, TEOAE 3, 4 kHz and DPOAE 1, 2, 6 kHz was lower in the vitamin D deficiency group compared with the controls. There was a significant association between both vitamin B12 deficiency and vitamin D deficiency and cochlear health
Lasisi et al.²⁹	Cross-sectional study	To determine the correlation between the hearing threshold and the serum levels of vitamin B12 (cobalamin) and folic acid among elderly subjects (60 years) with age-related hearing loss (ARHL)	The subjects included 126 elderly subjects (males and females), and the ages ranged from 60 to 98 years (mean SD 66.9 ± 0.77)	Inclusion criteria: all elderly men and women above 60 years of age who had no known medical condition. Exclusion criteria: those with history of diabetes, stroke, hypertension, ear diseases, exposure to noise and ototoxic drugs such as aminoglycoside antibiotics or diuretics, ear infections, ear trauma, or ear surgery	The levels of vitamin B12 were between 26.2 and 70.2 pmol/L.	The pure-tone audiometry was done for frequency 250-8000 Hz. The average for the 4 frequencies, 250, 500, 1000, and 2000 Hz was recorded as pure-tone average (PTA) for speech frequency, while the average for the 3000, 4000, 6000, and 8000 Hz was recorded as the PTA for the high frequencies	NA	In the high frequencies, the mean SD values among the subjects with normal PTA was 426.3, 17.6 nmol/L, while among those with HL, it was 279.14 nmol/L 171.2 nmol/L. The serum cobalamin among the subjects with normal PTA within the speech frequencies was 49.7, 9.4 pmol/L, while among those with speech-frequency HL, it was 42.6, 10.2 pmol/L. However, for high frequencies, the mean SD values among the subjects with normal PTA was 47.4, 7.3 pmol/L, while among those with HL, it was 41.3, 9.2 pmol/L. Spearman’s correlation revealed that low folate and cyanocobalamin were significantly associated with increasing hearing threshold in the high frequencies. In addition, our findings revealed that increasing age had significant effect on hearing threshold in the speech frequencies and the serum levels of vitamin B12
Shemesh et al.³⁰		To examine the incidence of vitamin B12 deficiency in three groups of noise-exposed subjects	A group of 113 army personnel exposed to military noise was studied. The mean age was 39.4 years. Chronic tinnitus and NIHL existed in 57 subjects. NIHL alone was observed in 29 subjects, and 27 subjects had normal audiograms	Inclusion criteria: those having NIHL. Those having tinnitus lasting more than 6 months with frequent and or permanent occurrence and sufficiently severe	Serum cobalamin levels below 250 pg/mL were considered as deficiency, levels of 180 to 250 pg/mL suboptimal or borderline deficiency, and levels below 180 pg/mL as abnormal or definite low levels	Conventional audiological examination—pure-tone threshold for 0.25 to 8 kHz range and speech tests. Auditory brainstem evoked response (ABR) to exclude retro cochlear lesions. Tinnitus assessment consisting of tinnitus localization, tinnitus pitch, tinnitus loudness in dB sensation level at his tinnitus pitch frequency, and a self-report on a tinnitus questionnaire (TQ)		Patients with tinnitus and NIHL exhibited vitamin B12 deficiency in 47% of cases (blood levels < or = 250 pg/mL). This was significantly more compared with NIHL and normal subjects who exhibited vitamin B12 deficiency in 27% and 19%, respectively
Taha et al.²⁶		To evaluate the role of vitamin B12 and folate blood concentrations in children suffering from moderate, severe, and severe-to-profound sensorineural hearing loss (SNHL)	The study was conducted on 95 children: 30 children with severe-to-profound SNHL who were scheduled for cochlear implantation, 25 children who are hearing aid users for moderate and severe SNHL, and another 40 healthy volunteers considered as the control group	Exclusion criteria: included syndromic HL, history of intake of ototoxic drugs, noise-induced HL, ear surgery, perforated tympanic membrane, Meniere’s disease, cranial trauma, metabolic and systemic diseases, a family history of ischemic heart disease, and a personal history of cardiovascular disease or history of vitamin B12 or folic acid intake	The normal level of Vitamin B12 ranges from 240 to 1100 pg/mL, whereas that for folic acid is at least 3.6 ng/mL	Play audiometry or voluntary threshold estimation according to their age using air conduction thresholds (0.25-8 kHz), bone conduction thresholds (0.5-4 kHz), and speech audiometry. Aided sound field hearing threshold in double-walled sound-treated booth IAC 1602, using two-channel audiometer Orbiter 922 (GN Otometrics, Taastrup, Denmark), warble tones were used to estimate aided thresholds. Immittance including tympanometry and acoustic reflex thresholds. Auditory brainstem response was performed to infants who were unable to perform play audiometry using biologic navigator		Median vitamin B12 and folic acid levels were significantly higher in the control group 3 than in the SNHL groups 1 and 2 patients. There was no significant correlation between vitamin B12 and folic acid levels and the other parameters. There was no significant difference between groups 1 and 2 with respect to median vitamin B12 and folic acid level

MMAT was used to appraise the quality of the included study, and the results are tabulated in Table 2.

Table 2.

Quality Appraisal of the Included Study.

Study ID	Is the sampling strategy relevant to address the research question?	Is the sample representative of the target population?	Are the measurements appropriate?	Is the statistical analysis appropriate to answer the research question?
Akyay et al.²⁴	Yes	Yes	Yes	Yes
Berkiten et al.²⁵	Yes	Yes	Can’t say	Yes
Gocer et al.³¹	Yes	Yes	Yes	Yes
Gok et al.²⁷	Yes	Yes	No	Yes
Houston et al.²¹	Yes	Yes	Yes	Yes
Karaer et al.²⁸	Yes	Yes	Yes	Can’t say
Lasisi et al.³²	Yes	Yes	Yes	Yes
Shemesh et al.³⁰	Yes	Yes	Yes	Yes
Taha et al.²⁶	Yes	Yes	Yes	Yes

Discussion

The systematic review examined the association between vitamin B12 levels and hearing loss across multiple studies. The review examined the relationship between vitamin B12 levels and hearing loss across diverse populations, considering factors such as noise-induced hearing loss (NIHL), age-related hearing decline, and elderly participants. Based on our findings several studies reported that individuals with lower vitamin B12 levels had a higher prevalence of hearing impairment than those with normal or elevated levels.^{24-26,29,31,32}

Homocysteine, Folate, and B12 Deficiency: Links to Sensorineural Hearing Loss

Vitamin B12 and folic acid play a crucial role in homocysteine metabolism, and a deficiency in either of these vitamins leads to elevated homocysteine levels.³² Gocer et al.³¹ and Gok et al.²⁷ aimed to investigate the association between hearing impairment and the levels of homocysteine, folate, and vitamin B12 in individuals with SNHL under the age of 60, and to determine these levels in subjects with NIHL and evaluate their potential links to NIHL respectively. Gok et al.²⁷ aimed to assess the levels of homocysteine, folic acid, and vitamin B12 in individuals with NIHL and explore potential connections between these factors and NIHL. Results indicated that folate and vitamin B12 levels were notably reduced in patients with NIHL. Additionally, the hearing loss in the study group predominantly began at 4000 Hz and peaked at 6000 Hz. Gocer et al.³¹ conducted a retrospective study investigating the potential association between SNHL before the age of 60 and levels of homocysteine, folate, and vitamin B12. They analyzed 2 groups: group 1, comprising 78 participants with hearing impairment, and group 2, a control group of 53 individuals without hearing impairment. The study included middle-aged adults (40-60 years) with SNHL and excluded those with recent vitamin B12 or folate supplement intake, ototoxic drug usage, noise exposure, ear surgery, and various medical conditions. The study found significant associations between auditory function and dietary intake of folate and vitamin B12, with participants with impaired hearing having lower mean serum vitamin B12 levels, suggesting a potential link between elevated homocysteine and decreased folate and vitamin B12 concentrations and hearing loss before old age. The findings underscored a consistent association between poor auditory function and low serum vitamin B12 concentrations.

Vitamin B12 Deficiency in Children and Hearing Loss

Hearing loss due to vitamin B12 deficiency manifests differently across the lifespan. In children, it can disrupt the development of the auditory system, leading to notable developmental issues if untreated, while in adults, particularly the elderly, it accelerates age-related hearing decline due to neurodegenerative effects.^24,26 Akyay et al.²⁴ provided critical insights into the effect of vitamin B12 supplementation on hearing outcomes. This study reported that among 8 patients with severe B12 deficiency (levels less than 100 pg/mL) supplementation did not result in significant changes in their hearing test results. Additionally, they observed that mild hearing loss was more common among school-aged children with vitamin B12 deficiency than those in the control group. Another study by Taha et al.²⁶ assessed the impact of blood concentrations of vitamin B12 and folate in children experiencing varying degrees of SNHL, ranging from moderate to severe and severe to profound. The control group had significantly higher median levels of vitamin B12 than the groups with SNHL. However, there was no significant difference between the 2 groups with SNHL moderate to severe and severe to profound with respect to median vitamin B12 level.

Influence of Vitamin B12 Deficiency on Elderly Population and Hearing Loss

Seven studies address the connection between vitamin B12 deficiency and hearing loss in adults and older people. Two studies^21,29 investigated the possible relationship between vitamin B12 levels and ARHL in older adults. Based on pure-tone air conduction threshold, Houston et al.²¹ performed a comprehensive audiometric evaluation on 55 healthy women aged 60 to 71 years, classifying their hearing function into the normal and impaired groups. They discovered that compared to women with normal hearing those with hearing impairments had far lower serum vitamin B12 levels. Serum vitamin B12 levels were found to be 38% lower in women with hearing impairments and 48% lower in those who did not take vitamin B12 supplements. It is interesting to note that there was a dose-response pattern in the link between serum vitamin B12 levels and auditory function at various hearing levels. This investigation was expanded to a more extensive and diversified group of 126 senior citizens, aged 60 to 98, who were both male and female. They evaluated hearing thresholds at different frequencies and compared the results to serum levels of folate and vitamin B12. They reported that there was a substantial correlation between growing older and declining vitamin B12 levels and that higher hearing thresholds in the high frequencies were significantly correlated with lower vitamin B12 levels. The results of these investigations emphasize the significance of keeping elderly people’s vitamin B12 levels at optimal levels as a potentially modifiable risk factor for ARHL. Since vitamin B12 deficiency can have a substantial negative influence on quality of life, early detection of and treatment for the deficiency could be a preventive intervention.²¹ Lasisi et al.²⁹ conducted a cross-sectional study aiming to determine the relationship between hearing thresholds and serum levels of vitamin B12 and folic acid among elderly individuals (aged 60 years and above) with ARHL. The study included 126 elderly subjects, both males and females, with an age range of 60 to 98 years. The study found that lower serum levels of folate and vitamin B12 were significantly associated with increased hearing thresholds in high frequencies. Additionally, advancing age was found to have a significant impact on hearing thresholds in speech frequencies and serum levels of vitamin B12. However, the correlation between vitamin B12 and ARHL does not appear to be significant after adjusting for age.

Interaction of Noise Induced Hearing Loss and Vitamin B12 Deficiency

Two investigations found a link between vitamin B12 deficiency and noise exposure. In one study, Gok et al.²⁷ examined vitamin B12 levels in those who had NIHL. The research group’s hearing loss peaked at 6000 Hz, having begun at 4000 Hz. Patients with NHIL have considerably reduced mean levels of vitamin B12. The control group in this study consisted exclusively of men, influencing the generalizability of the findings across genders. Shemesh et al.³⁰ investigated the relationship between vitamin B12 deficiency and chronic tinnitus, which is often associated with hearing loss. They examined the prevalence of vitamin B12 deficiency in 3 groups of noise-exposed people: individuals with NIHL only, individuals with chronic tinnitus and NHIL, and subjects with normal hearing. One hundred thirteen military members who were subjected to noise were among the subjects. Ninety percent of the participants in the audiological testing and questionnaire used to estimate tinnitus stated having tinnitus pitch in the 4 to 8 kHz range. Supplements of vitamin B12 were given to each subject and kept up until levels were steady. While there was some improvement, the 3 symptoms of tinnitus, loudness, disruption in noisy surroundings, and general feeling showed significant improvement. The findings showed that vitamin B12 deficiency was much more common (47%) in patients with tinnitus and NIHL.

Vitamin B12 Deficiency and Tinnitus

Two of the studies also addressed tinnitus in those who are vitamin B12 deficient. In addition to reporting the vitamin B12 levels in individuals with nonpulsatile tinnitus, Berkiten et al.²⁵ also investigated the outcomes of vitamin B12 therapy. The study group and the control group had tinnitus for slightly different lengths of time. Thirty-seven percent of the tinnitus patients had normal vitamin B12 levels, while 63% had low level pure-tone audiometry revealed that ears experiencing tinnitus exhibited higher levels of hearing loss than those without tinnitus. An observational study by Shemesh et al.³⁰ found that supplementation with vitamin B12 led to an improvement in tinnitus symptoms for some of the patients, suggesting a potential therapeutic role for B12 in managing tinnitus associated with deficiency.

Limitations and Future Recommendations

Only studies in peer-reviewed English language articles were included, and grey literature and articles published in other languages were not considered. Differing reference ranges for vitamin B12 levels across studies and inconsistent categorization of participants based on hearing loss severity make the comparison of findings difficult. Additionally, understanding the relationship between auditory pathways and vitamin B12 deficiency is complex, considering factors such as the duration of deficiency and its impact on hearing sensitivity.

The present review included studies conducted in humans only, further studies and reviews can explore the relation between vitamin B12 deficiency based on laboratory-based or animal studies. There is also a lack of longitudinal data among individuals with vitamin B12 deficiency and the benefits on the auditory system (if any) associated with food and medical supplements to overcome the deficiency.

Conclusion

The current study contributes to the growing body of evidence suggesting a potential role for vitamin B12 in maintaining auditory health. Findings demonstrate that vitamin B12 deficiencies cause hearing impairment, particularly in cases of ARHL, NIHL, and SNHL. DPOAE responses in vitamin B12-deficient individuals were decreased, suggesting cochlear dysfunction. While some studies found that taking B12 supplements led to minor improvements in the severity of tinnitus and hearing thresholds, these results were often not statistically significant, suggesting that the therapeutic value of B12 is still unknown and needs more research. These results emphasize the need for additional study to completely comprehend the connection between vitamin B12 levels and hearing health, as well as the possible advantages of focused therapies for controlling and preventing hearing loss.

Footnotes

Contributors

KK, DRG, and RR proposed the search strategy, and SA and JR independently searched the database and extracted relevant data from the included literature. DRG arbitrate questions or disagreements arising from data retrieval and analysis. The final version of the manuscript has been reviewed by all authors and approved for publication.

CRediT Authorship Contribution Statement

Joyline Rodrigues and Shubhangi Anand: Conceptualization, investigation, methodology, project administration, and writing—original draft. Dhanshree R. Gunjawate: Supervision, validation, writing, and review and editing. Kaushlendra Kumar: Supervision, validation, and review and editing. Rohit Ravi: Conceptualization, methodology, data curation, and review and editing, and supervision.

Consent for Publication

All authors consent to the publication of this work.

Data Availability

The present study is a secondary data analysis, and all the information is embedded in the manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Kaushlendra Kumar

Rohit Ravi

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Exploring the Intricate Connection Between Vitamin B12 Deficiency and Hearing Loss: A Systematic Literature Review