The role of nutrition in the formation of hearing disorders: literature review

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Introduction

In recent decades, hearing loss (HL) has become the most common sensory health impairment worldwide, limiting interpersonal communication and negatively affecting psychosocial well-being, professional activity, and quality of life, as well as being the third leading cause of years lived with disability [1; 2]. According to the latest meta-analysis of the prevalence of hearing loss conducted as part of the Global Burden of Disease (GBD) project, in 2019, approximately 20 % of the world's population (1.57 billion people) had hearing impairments of varying severity [3], of which 37.3 million people in Russia were registered with an average hearing threshold of more than 20 dB [4]. According to forecasts by the World Health Organization (WHO), due to the ongoing trend of increasing global prevalence of hearing loss and demographic aging, by 2050, 2.5 billion people worldwide may be affected by hearing loss, of which at least 700 million will have disabling hearing loss [3].

Despite the intensive development of innovative approaches to the prevention and treatment of HL — anti-apoptotic technologies for the regeneration of inner ear structures, methods for the targeted delivery of pharmaceuticals to the cochlea, genomic and cellular (stem cell) correction, there is currently no pathogenetically sound unified strategy for otoprotective clinical interventions [5]. In this regard, one of the most effective measures aimed at reducing the risk of developing HL remains control over modifiable risk factors for HL formation, primarily the level and exposure to noise, stressful biopsychosocial environmental influences, including occupational ones, as well as diet [6].

The aim of the study is to summarize and analyze data from domestic and foreign works devoted to contemporary aspects of the role of nutrition, its individual components, and dietary supplements in the pathogenesis of hearing disorders.

Materials and Methods

The search for scientific information sources was conducted using the RINC, eLibrary, CyberLeninka, PubMed, and Google Scholar databases. Search queries included the following keywords, phrases, and combinations thereof: “hearing impairment,” “age-related hearing loss,” “occupational hearing loss,” “presbycusis,” “sudden hearing loss,” “neurosensory hearing loss,” “pathogenesis,” “oxidative stress,” “systemic inflammation,” “risk factors,” “noise factor,” “lifestyle,” “nutrition,” “diet,” “nutrients,” “food supplements,” “vitamins,” “trace elements,” “prevention,” “treatment,” “medical intervention.” The search covered the period from 2007 to 2024. The paper summarizes data from 60 publications, mainly foreign ones.

Results and Discussion

Balanced nutrition, especially for non-smokers, is a primary modifiable component of a healthy lifestyle, widely used to normalize and maintain physiological activity, slow the progression of age-related dysfunctions, and prevent socially significant chronic non-communicable diseases such as cardiovascular disease, type 2 diabetes mellitus, neoplasms [8]. Recently, there has been an increasing number of epidemiological and experimental studies whose results indicate a significant impact of consumed foods on the development of hearing disorders, which exert their effects through indirect modulation of low-level systemic inflammation and cellular antioxidant defense processes [5; 8; 9].

Products with high fat and cholesterol content. To date, numerous cross-sectional, longitudinal, and interventional studies have verified the close relationship between lipid profile and the incidence and prognosis of HL, which affects microcirculation and cellular metabolism in the structures of the inner ear [10]. It has been shown that long-term consumption of foods high in cholesterol, trans fats, and polyunsaturated fatty acids (fast food, butter, margarine, highly processed foods, etc.), which have an atherogenic effect, increases the incidence and progression of sensorineural hearing loss [11], as well as sudden hearing loss [12].

On the other hand, diets low in saturated fat and cholesterol have a protective effect against HL, and a high content of mono- and polyunsaturated fatty acids (PUFAs) in the diet reduces the incidence of both subjective and audiometric hearing loss [13]. These effects are likely to depend on the amount of these nutrients consumed. Thus, the results of some experimental and population studies show that both deficiency and excessive consumption of omega-3 PUFAs, especially docosahexaenoic acid, can lead to impaired auditory nerve conduction and decreased hearing acuity at all stages of life [14]. In this regard, according to the expert community, it is preferable not to enrich the diet with dietary supplements, but to include fish species (herring, mackerel, sardines, salmon, trout, halibut, tuna) with a high content of natural omega-3 PUFA, whose anti-apoptotic effect on the structures of the inner ear is due to the activation of nitric oxide production—an endothelial regulator of arterial tone as well as a reduction in the production of pro-inflammatory cytokines and oxidative damage to the mitochondria of the cell structures of the cochlea, primarily the stria vascularis [15; 16]. Thus, according to the results of a prospective cohort study of the health status of 65,215 female nurses in the United States aged 27–44 (observation period of 18 years), taking into account intervening factors, a lower risk of hearing loss was found in women who ate fish 2–4 times a week compared to those who consumed it less frequently (less than once a month) [17]. The latter was consistent with the results of an earlier Dutch population study, which found an inverse relationship between higher plasma omega-3 PUFA levels and the three-year risk of hearing loss in adulthood [18].

Products with a high protein content. Although there is currently no established conceptual model of the pathogenetic mechanisms underlying the causal relationship between protein consumption and hearing impairment, the results of epidemiological studies show that low-protein diets can have a negative impact on hearing function [19]. Thus, the results of logistic regression analysis of data from the French observational study of the impact of nutrition on the quality of aging – SU. VI.MAX 2, which included 1,825 men and women aged 45–60 at baseline (follow-up duration 2 years), revealed a statistically significant inverse association between animal protein consumption (red meat, poultry, game, meat by-products) and self-reported hearing loss in women, but not in men [20]. A similar Korean study, supplemented by audiometry, also found an inverse correlation between protein consumption and average hearing threshold, but only at a frequency of 1000 Hz [21]. It should be emphasized that the studies cited took into account the consumption of natural animal protein, which provides the body not only with pure protein, but also with other essential nutrients, essential amino acids, vitamins, and trace elements which made it difficult to assess the direct impact of protein on the development of hearing impairments.

Products with high carbohydrate content. The current public health paradigm considers excessive consumption of certain simple carbohydrates—glucose, fructose, and table sugar to be an independent cardiometabolic risk factor for health problems [16]. The main pathogenetic mechanisms through which permanent hyperglycemia may be associated with structural and functional hearing impairments and the risk of hearing loss are believed to be the activation of free radical and peroxide processes, a decrease in the synthesis of nitric oxide by the endothelium of the inner ear, which is more complementary to excess fructose than to a similar amount of glucose consumption [22; 23], as well as initiated by high consumption of simple carbohydrates, increased formation of glycated derivatives of proteins, amino acids, and lipids, which have pro-oxidant and pro-inflammatory effects [24].

Currently, scientific literature contains numerous data confirming a verified link between diets with a high glycemic index and/or glycemic load [25], containing simple carbohydrates, and the prevalence of sensorineural hearing loss in populations [6; 9; 18; 26–29], as well as an increased risk of sudden hearing loss [30]. The results of epidemiological studies evaluating the relationship between HL and glycemic load, glycemia, and insulin resistance indicate that individuals with hearing loss who do not have type 2 diabetes or obesity and have a background glucose level that is slightly elevated relative to reference values [31], high postprandial glycemia was detected more often than in groups of examinees without HL, which a number of researchers consider to be a predictor of age-related hearing loss [27; 29].

Simple and complex carbohydrates can have diametrically opposite effects on HL. In contrast to the negative effects of mono- and disaccharides, high consumption of dietary polysaccharides, primarily plant-based fiber (whole grains, legumes, vegetables, fruits, mushrooms, etc.), protects against hearing impairment and loss [39]. At the same time, the otoprotective effects of dietary fiber can offset the harmful effects of other carbohydrate components in food [40] by reducing insulin resistance and postprandial glycemia, mediated by the low glycemic index of fiber [19].

A balanced (healthy) diet is characterized by increased consumption of vegetables, fruits, whole grains, legumes, nuts, fish, lean meat, dairy products, olive oil, herbs, spices, moderate alcohol consumption (red wine), and very low consumption of highly processed foods with high levels of sugar, salt, and saturated fats. This diet is a balanced source of antiatherogenic lipids (omega-3 and omega-9 PUFA), fiber, vitamins, polyphenols, and minerals [34].

There are now numerous scientific observations indicating that a balanced diet, such as the Mediterranean diet, has been proven to reduce the risk of developing a number of chronic non-communicable diseases independently associated with age (cardiovascular and neurodegenerative diseases, type 2 diabetes), as well as increasing life expectancy and improving quality of life [19]. At the same time, the impact of this diet on the hearing organ has not been sufficiently studied and is reflected in only a few studies. Thus, the results of an American longitudinal cohort study (1991–2013) of the long-term relationship between diet and the risk of hearing loss in nurses showed that women adhering to a healthy diet, including the Mediterranean diet, had a lower risk of developing both moderate and severe hearing loss compared to nurses with a less balanced diet [35].

It should be noted that the pathogenetic assessment of the protective effect of the Mediterranean diet on cochlear function is difficult due to the complex composition and combined effects of the macro- and micronutrients it contains. However, the presence of large amounts of plant fiber and polyunsaturated fatty acids in this diet suggests that its otoprotective effect is realized through the above-mentioned antioxidant and anti-inflammatory mechanisms that prevent apoptosis of auditory cells.

Food supplements (vitamins and vitamin complexes). It has now been established that the protective effect of vitamins and trace elements can be achieved both by neutralizing the effects of oxidative stress and by normalizing cellular metabolic processes, in which they act as coenzymes (vitamins) or cofactors (metal ions) in enzymatic reactions) [9; 28; 29; 36].

The protective effect mediated by the antioxidant activity of vitamins A, E, and C, which are most widely used as dietary supplements, is determined by their structural and functional properties and can be realized through various biochemical mechanisms [36]. Vitamin A, mainly in the form of β-carotenoids, neutralizes singlet oxygen and peroxyl radicals in the lipid cell environment, thereby preventing free radical damage to PUFAs caused by the conjugation of their double bonds [37]. Fat-soluble vitamin E, mainly in the form of α-tocopherol, which acts as a hydrogen atom donor, interacts with peroxyl radicals, converting them into inert α-tocopherol-phenoxy derivatives, protecting the membrane phospholipids of the cell structures of the hearing organ by limiting oxidative stress [38]. Vitamin C is capable of inhibiting free radical oxidation processes, mainly by neutralizing active forms of oxygen through the glutathione-ascorbate cycle in aqueous cell interfaces [36].

Unlike vitamins A, E, and C, which are used to enrich the diet, water-soluble B vitamins—thiamine (B₁), riboflavin (B₂), niacin (B₃), pantothenic acid (B₅), pyridoxine (B₆), folic acid (Bc, B₉), and cobalamin (B₁₂),which are coenzymes in mitochondrial energy metabolism reactions and have an otoprotective effect by normalizing tissue respiration [9; 36; 39]. At the same time, the different involvement of vitamins in the interrelated mechanisms of energy metabolism and antioxidant cell protection in the complex use of fat-soluble and water-soluble vitamins may be accompanied by a synergistic effect in relation to HL [40], initially established in experiments on laboratory animals [41].

Most epidemiological studies of the effect of vitamins on cochlear function presented in the scientific literature focus on the preventive effect of their use in relation to noise-induced HL, including occupational noise, as well as minimizing the ototoxicity of drugs, heavy metals, and other toxicants [28]. As a rule, various vitamin complexes were used in the therapeutic and prophylactic intake of dietary supplements, including those enhanced with a vasodilator such as magnesium (Mg2+), which protects the inner ear from the development of age-related and/or occupational hearing loss [42]. Thus, B. Gopinath et al., based on the results of a 5-year longitudinal epidemiological study of the relationship between antioxidant vitamins (A, E, C) and the prevalence of HL in a cohort of Australian adults, it was shown that higher intake of vitamins A and E was inversely correlated with the frequency of hearing impairment, but did not affect the risk of sudden hearing loss [43]. A similar study (4 years) of the effects of prolonged intake of an antioxidant complex (A, E, C, Mg) on the threshold level of hearing in the form of a pure tone during speech and at high frequencies, conducted as part of the National Health and Nutrition Examination Survey (NHANES) of the US population, it was also found that consumption of this dietary supplement statistically significantly reduced the risk of HL [44]. In addition, it was found that long-term (daily for more than three years) intake of Mg-enriched antioxidant vitamins prevented the progression of deafness in children with genetically determined HL [45].

The above data were comparable to the results of a regression analysis of the relationship between vitamin intake (A, B₁, B₂, B₃, C) and hearing thresholds in older adults, conducted using data from the Korean National Health and Nutrition Examination Survey (KNHANES), which showed that the use of these vitamin supplements statistically significantly improved hearing acuity at all frequencies [46]. After adjusting for age, gender, smoking, and exposure to occupational noise, a stronger association was found between vitamin C intake and better hearing (lower threshold) at mid-frequencies (2000 and 3000 Hz) [46].

The results of the French randomized placebo-controlled study SU.VI.MAX 2, which analyzed the delayed relationship between daily 8-year intake of therapeutic doses of vitamin supplements (A, E, C, B₆, B₁₂, folic acid) in 6,850 men and women aged 58–73 years of age and hearing acuity (frequencies 0.5, 1, 2, and 4 kHz): 5–7 years after its completion, a significant direct correlation was found only between cobalamin and HL in the women examined [20]. According to the authors, the data obtained may have been influenced by the lack of adjustment for confounding factors, such as the use of ototoxic drugs, exposure to industrial noise, and the presence of cardiovascular and oncological diseases. At the same time, another large prospective study of the relationship between vitamins (A, C, E, folic acid) and the risk of HL in 65,521 women (nurses) from the United States, taking into account a number of important covariates affecting hearing function in a multivariate analysis (physical activity; consumption of alcohol, cobalamin, magnesium, potassium, and omega-3 PUFAs; history of hypertension and type 2 diabetes; use of acetaminophen and ibuprofen), it was shown that higher intake of provitamins A (β-carotene and β-cryptoxanthin) and folic acid (FA) was independently associated with a lower risk of HL, while prolonged intake of high doses of vitamin C was correlated with an increased risk of hearing impairment [47].

It should be noted that cobalamin and folic acid deficiency is the most common vitamin deficiency, indirectly affecting cochlear function through the intermediate metabolism of homocysteine (Hcy), the accumulation of which in the cellular structures of the inner ear leads to the activation of oxidative stress processes and microcirculation disorders, resulting in auditory cell apoptosis and accelerated hearing loss [19; 48]. According to NHANES estimates, the prevalence of HL associated with deficiency of these B vitamins ranged from 2.9 % to 25.7 % in different populations, increased with age, and was generally higher in women than in men [49].

An analysis of the relationship between serum levels of FA, vitamin B₁₂, Hcy, and the risk of age-related hearing loss in older Australians (aged 50+, 4,900 participants), conducted based on the results of the Blue Mountains longitudinal cohort study (1997–1999; 2002–2004), revealed varying degrees of hearing impairment in almost 65.0 % of those examined with hyper-homocysteinemia, whereas in individuals with normal serum Hcy levels, presbycusis occurred in only one-third of cases [50]. It was found that individuals with low FC levels in their blood serum had a 39 % higher risk of age-related HL; while serum vitamin B₁₂ levels had no statistically significant association with hearing loss, and the risk of sudden HL did not correlate with baseline levels of Hcy, folic acid, and/or vitamin B₁₂ determined in serum in 1997–1999. According to the authors, despite the fact that the study adjusted for the impact of occupational noise, the data obtained may contain significant measurement errors due to the failure to take into account a number of confounding factors—alcoholism, low consumption of fiber and grain products, combined with low levels of folic acid and vitamin B₁₂, which could mask the effect of hyperhomocysteinemia on cochlear function.

The results of another large prospective American study (1986–2002), involving more than 26,000 men in various medical professions aged 40–75 at the start of the study, analyzing the relationship between vitamin intake (A, E, C, and FA) and the risk of HL using a questionnaire on diet and nutritional quality, as well as information on diagnosed hearing impairment, found a significant correlation only between folic acid and a 21.0 % reduction in the risk of HL for men aged 60 and older who took more than 800 mcg of folic acid per day, which was twice the therapeutic doses recommended for this age group [51]. The authors considered the main limitation of this study to be the low reliability of information about hearing impairments obtained from respondents, which was not supported by objective audiometry data.

E.K. Kabagambe et al. based on representative NHANES data for 2003–2004, taking into account confounders (age, gender, serum B₁₂ levels, noise exposure, smoking, alcohol
consumption, body mass index, blood pressure, kidney function, socioeconomic status),
a U-shaped relationship was established between the content of FA in erythrocytes and hearing loss [52]. In a fully adjusted model using the lowest quartile of erythrocyte FC (374.0 ± ± 6.1 nmol/L) as a reference, quantitative assessment of the relationship between HL and FA levels showed a significant risk of hearing impairment in those examined with the highest FA content in erythrocytes (986.0 ± 17.9 nmol/L). At the same time, individuals with moderately elevated erythrocyte FA levels (582–741 nmol/L) had a 32% lower probability of hearing loss at low frequencies (0.5–4.0 kHz) on average compared to the subgroup with the lowest FA content. Neither folic acid nor vitamin B₁₂ were significantly associated with hearing loss at higher frequencies (4.0–8.0 kHz).

A possible pathophysiological mechanism linking the increased risk of HL with excessive accumulation of FA in erythrocytes, caused by chronic use of vitamin supplements or folate-enriched foods, may be a disruption of DNA methylation in auditory cells and an imbalance in one-carbon metabolism processes, including FA metabolism, the homocysteine remethylation cycle, and the transsulfuration pathway of amino acids and polypeptides synthesized from Hcy, leading to dysfunction of the nervous and immune systems, insulin resistance, obesity, and type 2 diabetes [28; 53].

Although the side effects of excessive folic acid consumption are considered reversible, the consequences of long-term excessive consumption have not been sufficiently studied and may synergize with low vitamin B₁₂ levels, which are also associated with hearing loss [9; 48]. In this regard, despite the identified otoprotective effect of high doses of FA with respect to HL, their introduction into clinical practice should be approached with caution, taking into account potential side effects, and recommended only to population groups with established folic acid deficiency or insufficiency. According to E. Tavanai et al., this restriction should also apply to antioxidant prevention and treatment of HL, since for individuals who have achieved optimal antioxidant potential through a healthy diet and adequate physical activity, taking antioxidant vitamins and antioxidant supplements does not provide any additional improvement in cochlear function [6]. In addition, it has been experimentally established that extended sets of combined vitamin complexes with antioxidant action and/or the intake of high doses of individual vitamins in some cases can critically disrupt the balance of redox reactions, beyond which antioxidant protection ceases to work, and functional or organic hearing impairments persist or even progress [36].

Conclusions

Nutrition is the most important modifiable lifestyle factor that determines health status and shapes the independent or indirect risk of developing most pathological conditions, including hearing disorders. Currently, epidemiological and experimental studies have established that the nature of nutrition can have a dual effect on the development of hearing disorders. Thus, foods with a high glycemic index and elevated levels of cholesterol, trans fats, and polyunsaturated fatty acids are statistically significantly correlated with a higher risk of developing age-related and/or occupational HL. While balanced diets that include plant-based fiber (whole grains, legumes, vegetables, fruits, mushrooms, etc.) and natural omega-3 polyunsaturated fatty acids (fatty fish, seafood), as well as the intake of antioxidant vitamins (A, E, C) and a number of B vitamins (folic acid, cobalamin) when deficient or insufficient, improve hearing acuity and statistically significantly reduce the risk of hearing impairment caused by presbycusis, exposure to noise, or ototoxic agents.

Thus, the analysis of current scientific literature indicates the high potential of healthy nutrition in the prevention and possible restoration of cochlear dysfunction in the absence of irreversible changes. The latter requires additional large-scale longitudinal studies and in-depth research into the relationship between HL and nutrient intake and the dose-dependent effects of vitamins in order to scientifically substantiate therapeutic, health-promoting, and preventive dietary programs adapted to different population groups, which is especially relevant for the prevention of age-related and occupational hearing loss.

About the authors

V. F. Spirin

Saratov Medical Research Center for Hygiene of Federal Scientific Center for Medical and Preventive Health Risk Management Technologies; Saratov State Medical University named after V.I. Razumovsky

Email: bezrukovagala@yandex.ru
ORCID iD: 0000-0002-2987-0099

DSc (Medicine), Professor, Head of the Department of Occupational Medicine and General Pathology

Russian Federation, Saratov; Saratov

G. A. Bezrukova

Saratov Medical Research Center for Hygiene of Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Author for correspondence.
Email: bezrukovagala@yandex.ru
ORCID iD: 0009-0009-6254-3506

DSc (Medicine), Associate Professor, Chief Researcher of the Department of Occupational Medicine and General Pathology

Russian Federation, Saratov

References

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