Association of Nutritional Factors with Hearing Loss

Hearing loss (HL) is a major public health problem. Nutritional factors can affect a variety of diseases, such as HL, in humans. Thus far, several studies have evaluated the association between nutrition and hearing. These studies found that the incidence of HL was increased with the lack of single micro-nutrients such as vitamins A, B, C, D and E, and zinc, magnesium, selenium, iron and iodine. Higher carbohydrate, fat, and cholesterol intake, or lower protein intake, by individuals corresponded to poorer hearing status. However, higher consumption of polyunsaturated fatty acids corresponded to better hearing status of studied subjects. In addition to malnutrition, obesity was reported as a risk factor for HL. In studies of the relationship between middle ear infection and nutrition in children, it was reported that lack of vitamins A, C and E, and zinc and iron, resulted in poorer healing status due to vulnerability to infection. These studies indicate that various nutritional factors can affect hearing. Therefore, considering that multifactorial nutritional causes are responsible, in part, for HL, provision of proper guidelines for maintaining a proper nutritional status is expected to prevent some of the causes and burden of HL.


Introduction
Hearing loss (HL), caused by partial or complete dysfunction of the auditory pathway from the external ear to the cerebral auditory cortex, is the most important and frequent symptom of ear disorders [1]. HL is a major public health problem and has been recently ranked as the fifth leading cause of years lived with disability, even higher than many other chronic diseases such as diabetes, dementia, and chronic obstructive pulmonary disease. Moreover, according to the World Health Organization (WHO), the incidence of auditory disorders is increasing at an alarming rate without much concern or perception by society and public health officials [2][3][4][5]. Because HL affects the quality of life and communication and relationships with others, it is related to the social costs as well as economic costs of medical treatment [6]. In particular, HL affects talking and has been associated with depression and anxiety [7]. Affected children are likely to experience delays in development of speech, language and cognition, and poor school performance [8], whereas adults face higher risks of unemployment or low earnings [9]. Recently, it has been reported that hearing impairment is associated with increased cognitive dysfunction and dementia in the elderly [10][11][12] and that social isolation accompanies the daily life of those with impaired hearing [13].
HL is most often a sensorineural origin due to irreversible loss of hair cells and/or spiral ganglion neurons. Causes of sensorineural HL (SNHL) are multifactorial factors, including genetic and environmental factors such as noise, toxicity and aging [14]. Sex has commonly been a statistically significant factor, with males having worse hearing thresholds than females [15]. Other to cell membranes, cytoplasm and mitochondria. In particular, excess free radicals in the cells of the cochlear sensory epithelium, spiral ganglion neurons and cochlear blood vessels can play an important role in the onset of HL. Excess ROS, induced by intense noise exposure and toxic drugs, is a key factor in the pathogenesis of HL, along with other stresses and aging [33,[35][36][37]44,45]. Several studies have shown that loud noise induces unnecessary ROS production and the overproduction of certain cells in the cochlea resulting in cell damage and noise-induced HL. Under these conditions, high blood concentrations of antioxidants could inhibit the production of ROS, suggesting that antioxidants reduce cell damage by suppressing ROS production in hair cells exposed to noise [31][32][33].
In contrast to vitamins and minerals, higher carbohydrate intake [49], fat intake [36,[50][51][52][53], and cholesterol intake [54][55][56] have been reported to have a negative effect on hearing outcome. Damage to the blood supply to the cochlea can contribute to a decrease in auditory sensitivity, and thus vascular factors are known to play a key role in the development and progression of HL [57]. Excessive consumption of carbohydrates, fats and cholesterol can increase the risk of cardiovascular [58] and cerebrovascular disease [59], and similar mechanisms can damage cochlea blood flow [60]. In contrast, consumption of fish and higher intakes of long-chain omega-3 polyunsaturated fatty acids (PUFAs) have been reported to have a positive impact on auditory sensitivity by improving blood supply to the cochlea [61]. Taken together, these results suggest that micronutrients and macronutrients can interact in a variety of forms on the hearing outcome.
In another study, a Healthy Eating Index (HEI) was used as a measure of total dietary value to utilize dietary patterns as an alternative method to investigate the relationship between nutrition and hearing considering the limitations of single nutritional analysis [30,62]. Other studies have also used biomarkers (such as serum albumin levels) or anthropometric indices to assess general nutritional status [63]. All reported that the general nutritional status was a factor that could affect HL and that the risk of HL was increased with poorer general nutritional status.
There are also studies on the relationship between pediatric HL and nutrition [64][65][66][67][68]. According to these studies, certain nutritional deficiencies associated with iodine and thiamine can increase the risk of HL, even with only limited data and an unquantified threshold of interest. In children, in particular, the most common cause of HL is related to middle ear infections. Therefore, studies on the effect of nutrition on middle ear infections have been reported, and these studies suggest that micronutrient status and vitamin deficiency (such as vitamin A or zinc) may cause more frequent inflammation in the middle ear, leading to increased frequency of otitis media, which increases the risk of HL [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83].
Most of these studies on the association between nutrition and HL have reported an increased risk of HL in certain nutritional deficiencies. However, recent studies have also shown that obesity, an excessively increased state of nutrition, increases the risk of HL [84][85][86][87][88][89][90][91][92][93]. A key hypothesis for the mechanism of the relationship between obesity and HL is that deformation of the capillary wall due to excessive fat tissue damaging the delicate inner ear system, resulting in vasoconstriction of the inner ear [94]. (Table 1) To date, various data have supported the possibility that the intake of certain nutrients has a particular relevance to hearing outcomes ( Table 1). Some of the nutrients suggested to play a role in human hearing are vitamins, including vitamin A, B (specifically B2, B9 and B12), C and E [33][34][35][36][37][38][39][40]46,47]. Some of the minerals suggested to play a role in hearing include Mg and Se [33,36,[41][42][43][44][45], although there are also studies reporting no statistically significant association between HL and Mg [95]. In another recent study, women had better hearing when retinol and vitamin B12 levels were elevated, or the intake of meat, red meat, and organ meat increased [39]. In contrast to the result in women, there was no correlation between meat intake and hearing outcomes in males, and the association between increased seafood and shellfish intake was statistically significant. The authors point out that red meat is a good source of retinol and B12. However, it is difficult to determine a definite relationship because meat provides protein or other essential nutrients. Thus, these results highlight potential interactions between nutrients, gender, possibly unknown environmental factors, genetic factors, or other individual risk factors and hearing. In some studies, iodine and iron deficiency have been reported as risk factors for HL although the exact pathophysiologic mechanism associated with them has not yet been determined [26,27]. Vitamin D deficiency can induce HL by affecting calcium metabolism and microcirculation in the cochlea or by affecting bone mineralization of the ossicles [96].   Intakes of retinol (p = 0.058) tended to be associated with better HL in women.

Impact of Single Nutrition on Hearing
Intake of retinol and Vit. B12 tended to be associated with a better HL in women. Vit. B12 Intakes of Vit. B12 (p = 0.068) tended to be associated with better HL in women. NIPTS was significantly more frequent and more severe in the placebo group than in the magnesium group, especially in bilateral damages.
A significant natural agent for the reduction of hearing damages in noise-exposed population.  A higher mean dietary GI was associated with an increased prevalence of any hearing loss, comparing quintiles 1 (lowest) and 5 (highest), (multivariable-adjusted odds ratio = 1.41 (95% CI = 1.01-1.97)).
Higher carbohydrate and sugar intakes were associated with incident hearing loss (p-trend = 0.03 and p-trend = 0.05, respectively).
high-GL diet was a predictor of incident hearing loss, as was a higher intake of total carbohydrate.  Some previous studies have shown that excessive nutrient intake is associated with hearing in humans, especially with high levels of carbohydrate, fat and cholesterol intake associated with poor hearing outcomes. It has been reported that the risk of HL may be increased in adults with a higher glycemic index (index of carbohydrate quality) and higher glycemic load (index of both quality and quantity), as well as higher total carbohydrate intake [49]. The first association between dietary fat and HL was proposed in the Mabaan tribe in Sudan where a better-than-expected cardiovascular function and hearing sensitivity were observed [50]. It was also shown that when an institutionalized patient diet was manipulated by replacing saturated fat with unsaturated fat, low hearing thresholds were observed [51]. PUFAs have been implicated in hearing results in more recent studies [36,52,53,61]. Regular fish consumption and higher intake of long-chain omega-3 PUFAs are associated with lower risk of HL in women [39]. In addition, high-density lipoprotein depletion and elevated triglycerides are associated with HL [54,55] although the relationship between HL and total cholesterol is unclear [54,56]. On the contrary, in a 2015 report in which 36,067 subjects were surveyed, an association of low fat (and low protein) diets with hearing discomfort (mean hearing thresholds), after adjustments for confounding variables such as BMI, smoking, and economic status were made, was observed [97]. In addition, it has been reported that dietary carotenoids lutein (L) and zeaxanthin (Z) play a role in maintaining optimal auditory function [98].

Impact of General Nutritional Status on Hearing (Table 2)
One of the most critical limitations of the single nutrition study is the inability to fully control the effect of other nutrients. This is because humans are omnivorous animals who ingest various nutrients at the same meal. Therefore, in order to overcome this, many researchers have been trying to clarify the relationship between the generalized nutrition status and various diseases by analyzing the subject's overall eating habits, such as via the HEI [30,62]. The HEI assesses the overall quality of a person's diet by assessing how well a person's diet conforms to the U.S. Dietary Guidelines for Americans [99]. The use of dietary patterns allows parallel lines that better match the "real" diet, and nutrients are ingested as a combination of foods rather than individually. In other studies, dietary diversity scores were used to assess nutritional status [100]. In a Japanese community-based prospective cohort study, serum albumin and three anthropometric indices, such as body mass index (BMI), midarm circumference (MAC), and calf circumference (CC), were used to assess general nutritional status [63]. These studies suggested that lower marker values of overall nutritional status were associated with greater incidence of HL. However, the relationship between obesity and hearing status is reported in contrast to these previous studies. The current literature suggests that obesity is associated with age-related HL and sudden SNHL (SSNHL) [84][85][86][87][88][89][90][91][92]. In addition, underweight and severe obesity have been associated with an increased prevalence of HL in a cross-sectional study in a Korean population [93]. Therefore, from a review of the literature, it can be seen that various data support the possibility that dietary patterns affect hearing status and the relationship between total dietary patterns and hearing has been established in some cases ( Table 2). WC is independently associated with HL, but this differs by age and gender.
Central obesity was more important than BMI as a risk factor for ARHL.   (Tables 3 and 4) HL is the most common communication disorder that may potentiate delays in language, social, and behavioral developments in children [101]. Even children who are not severely affected may face increased risks of grade failure, behavioral problems, and interpersonal interactions, and require significant financial investment [101,102]. In addition, the specific needs for special education, amplification devices, and missed parental work have inevitable ramifications beyond the directly affected family unit, and the expected lifetime cost for a single prelingually deafened child exceeds $1,000,000 [102]. There have been many studies to identify the risk factors of pediatric HL because of its great impact both on social and economic aspects, one of which is the relationship between nutrition and HL. These studies can be divided into two major categories: (1) the study of the overall hearing status and (2) the study of HL that occurs in relation to middle ear infections.

Impact of Nutrition on Pediatric Hearing
Like adults, the relationship between general hearing status and nutrition in children can be divided into studies about single and general nutritional statuses (Table 3). One cross-sectional study assessed the HL of 0-3-month-old infants (n = 3386) in Nigeria. In this study, the authors defined infant malnutrition as an infant with Z scores less than two standard deviations below one of three indices (age-specific weight, age-specific BMI or BMI) and one of the hearing thresholds greater than 30 dB of at least one ear. Infants with poor nutritional status were significantly more likely to have severe sensory nerve impairment than infants without nutritional deficiencies [64]. Based on these results, the researchers added the weight for the length as a fourth index and could still demonstrate, using the entire study population (n = 6585), that early-onset hearing loss was much more prevalent among malnourished infants [65]. Single nutrition studies in pediatric populations include studies of iodine and thiamine deficiencies. One cross-sectional study showed that hearing thresholds were worse among children at risk for mild and moderate iodine deficiency and had a statistically significant correlation between hearing and urinary iodine levels at 4 kHz [66]. One randomized, placebo-controlled intervention trial (n = 197) with an observation period of 11 months, reported that the mildly iodine-deficient child population with higher serum thyroglobulin concentrations had significantly higher hearing thresholds in the higher frequency range (≥2 kHz) than children with lower serum thyroglobulin concentrations. Therefore, this study suggested that even if the iodine deficiency was "mild", it was still important to promote adequate iodine intake through the salt iodination program and other methods [67]. In another study, a small case series (n = 11), which examined infants with thiamine deficiency resulting in pediatric intensive care unit admission, found a prevalence of HL and auditory neuropathy of between 27.3% to 45.5% among affected infants [68]. After thiamine supplementation, postintervention hearing evaluation showed improvement in 5 of 11 cases.
The most common cause of HL in the pediatric population is middle ear infections such as otitis media. Therefore, many studies concerning middle ear infection related to HL in children have been reported (Table 4). To summarize these studies, deficiencies of single micronutrients and vitamins (such as zinc, vitamin A, iron, and retinol) are associated with mild ear pathologies such as acute or chronic otitis media [69][70][71][72][73][74][75][76]. In addition, multi-micronutrient supplementation studies have reported that the frequency of HL is significantly reduced when these nutrients are supplied sufficiently [77][78][79][80][81][82][83]. In a large, well-controlled trial in Bangladeshi children, zinc supplementation showed a significant protective effect in reducing otitis media and indicates a significant importance in reducing the infection pathology of middle ear disease [76]. The precise mechanism for these is yet to be elucidated, but it is assumed that the deficiency of these nutrients affects the mucosa of the middle ear or Eustachian tube, thereby increasing the infection by increasing the inflammatory response.   The beneficial effect in SOM.

Limitations of Previous Studies
The most frequent limitation of studies assessing the relationship between HL and nutrition is the lack of clarity about the mechanisms by which specific nutrients or general nutritional status affect HL. This is probably due to most studies to date being retrospective or cross-sectional in design. Additional studies, including animal testing, may be required to determine the mechanisms by which HL is affected by individual nutrients or nutritional status. Because the cochlea is sensitive to blood flow, the mechanisms by which nutrients affect cochlear function are likely similar to the mechanisms by which they affect various cardiovascular and neurologic diseases [58][59][60]. Systematic prospective studies and studies in animals are needed to evaluate these mechanisms.
Another limitation was that studies to date have been limited to patients with HL in a narrow sense. For example, cochlear implantation (CI) is the most successful neural prosthesis to date, with more than 220,000 implanted individuals worldwide in 2011 [103]. Education about nutritional aspects can play a significant role in the rehabilitation of patients who have undergone CI. However, no studies to date have assessed the relationship between nutrition and HL in patients who have undergone CI, suggesting the need for future research on this relationship.

Summary of Clinical Relevance
Studies on the relationship between HL and nutrition have reported that the incidence of HL was increased by a lack of single micro-nutrients, such as vitamins A, B, C, D and E, zinc, Mg, Se, iron and iodine. Higher intake of carbohydrates, fats, and cholesterol, and lower protein intake, corresponded to poorer hearing status, whereas higher consumption of PUFAs corresponded to better hearing status. In addition to malnutrition, obesity was reported to be a risk factor for HL. The mechanisms by which various nutritional factors influence HL have not been clearly elucidated. However, the physiological characteristics of the cochlea, which is highly influenced by blood flow and ROS, indicate that these nutritional factors may protect against HL by affecting cochlear blood flow or exhibiting antioxidative effects. Studies of the relationship between middle ear infection and nutrition in children found that lack of vitamins A, C and E, and of Zn and iron, resulted in poorer healing status due to greater vulnerability to infection.

Conclusions
We have summarized the current knowledge about the factors associated with nutrition and hearing status. The review showed that (1) various nutritional factors (such as single nutrients (vitamin A, B, C, D and E, and zinc, Mg, Se, iodine, iron, fatty acid, carbohydrate, and protein) and the generalized nutritional status) are associated with hearing status; (2) the effect of each nutritional factor may depend on other factors (such as age or gender); and (3) various nutritional factors play roles in middle ear infection (such as otitis media) in pediatric subjects. Further studies will be needed to clarify the pathophysiological mechanism of each nutrition-related factor affecting hearing. In addition, it is expected that guidelines to control nutritional factors with the aim of preventing HL can be suggested after these studies are completed.

Conflicts of Interest:
The authors have no conflicts of interest to report. The authors have no funding or financial relationships to disclose.