Numerous studies have explored serum lipid levels or the presence/absence of hyperlipidemia as related to hearing loss (Jones and Davis 2000, 2001; Suzuki et al. 2000; Lee et al. 1998; Evans et al. 2006; Dullemeijer et al. 2010; Simpson et al. 2013). However, findings have been inconsistent. For example, Jones and Davis (2000) found in a retrospective study that subjects with hyperlipidemia (as measured by fasting total cholesterol) had better hearing thresholds. On the other hand, Evans et al. (2006) demonstrated that subjects with dyslipidemia (i.e., abnormal lipid profile) as indicated by elevated triglycerides had elevated hearing thresholds compared to matched controls.

The variability may be explained by the blood serum measure used to define lipid status. Cholesterol is a sterol, a vital component of our cells, and the basic building block of hormones. Triglycerides are esters derived from glycerol and three fatty acids, and their primary function is energy supply. Excess calories are repackaged and stored as triglycerides. Cholesterol and triglycerides, both lacking solubility in the blood, are chaperoned in the bloodstream by proteins, thus, as lipoproteins, i.e., lipid + protein. There are several types of lipoproteins based on the order of density from chylomicrons up to high-density lipoproteins (HDL). The lower-density variants have a larger lipid component. The cholesterol component is essentially the same in the different low- to high-density lipoproteins. The density of the lipoprotein has been associated with its relative effect on cardiovascular health, where lower-density lipoproteins (LDL) are associated with poorer cardiovascular outcomes. It is not the cholesterol that represents the risk factor; rather it is the density (molecular weight and saturation) of the associated fatty acids. Triglycerides are a major component of very low-density lipoproteins (VLDL) and when elevated can be indicative of a poor diet and risk for cardiovascular health problems. Cholesterol is usually measured as total cholesterol and two subcomponents: HDL and LDL cholesterol. However, the cholesterol as previously described is essentially the same for these two subcomponents; what differs is the ratio of protein and triglycerides. Therefore, elevated triglycerides (related to higher amount of stored fat and higher VLDL) may be associated with poorer hearing (as in Evans et al. 2006), but total cholesterol may not (Jones and Davis 2000), depending on what constitutes the majority of the lipoprotein transporting that cholesterol (LDL vs. HDL). This may explain why total cholesterol may lack sensitivity, as it comprises both HDL and LDL sources.

Suzuki et al. (2000) performed a cross-sectional study of serum total cholesterol including comparison of LDL and HDL. They demonstrated that total cholesterol and total triglycerides had no relationship to hearing thresholds. However, when subjects with higher HDL were compared to those with lower LDL, a significant relationship was found, where higher HDL was associated with better hearing thresholds and lower LDL with poorer hearing thresholds. In a longitudinal study, Dullemeijer et al. (2010) found that persons with highest levels of serum n-3 polyunsaturated fatty acids had better lower-frequency hearing thresholds. Two studies out of the Medical University of South Carolina (MUSC) found a significant relationship between hearing and ratio of LDL/HDL in a cross-sectional study (Lee et al. 1998), but a follow-up longitudinal study found no significant relationship (Simpson et al. 2013).

A variety of factors can influence serum lipid measures including but not limited to how measured, patient posture, stress, medications, and etc. These factors and recognized acute changes in blood serum lipid measures limit their application for determining the relationship and risk of hearing loss. The application of serum measures of lipids and relationship to hearing loss remains unclear.

Gopinath et al. (2010a, b, 2011a, b) and Spankovich et al. (2011), studies from the Blue Mountains Hearing Study (BMHS), explored the relationship between dietary lipid intake and auditory function. The BMHS is a population-based longitudinal survey of ARHL in the Blue Mountains of Sydney, Australia, conducted through the years 1997–2004. During 1997–1999, over 3,000 participants 49 years or older were examined; surviving baseline participants were invited to participate in the 5-year follow-up examination between 2000 and 2004; 75 % of the original sample participated in the 5-year follow-up. [The dietary intake of participants was measured via food frequency questionnaires (FFQ). An FFQ is a self-reported inventory of the usual participant consumption of different food items over a length of time (in the case of BMHS over the past year) including portion sizes and frequency of consumption. The FFQ data is entered into a database to estimate the nutrient composition of the reported food intake. The FFQ used in the BMHS studies was validated using weighed food records (Smith et al. 1998).] Audiometric data collected included transient-evoked otoacoustic emissions (TEOAEs), pure-tone threshold sensitivity, immittance measures, and hearing handicap inventory. Information on potential confounders was obtained via a comprehensive medical history. In addition other health data were collected including an evaluation of vision, quality of life, cognitive function, and blood labs (e.g., fasting blood glucose, cholesterol, kidney function, homocysteine, and various serum levels of vitamins).

One of the earliest publications from the BMHS group on diet and hearing was the (Gopinath et al. 2010a) cross-sectional and prospective analysis of dietary intake of polyunsaturated fats and hearing loss. They found that long-chained omega-3 fatty acids were significantly associated with better hearing thresholds (cross-sectional) and reduced 5-year incidence of hearing loss (prospective). In addition, higher intake of fish was associated with reduced risk and progression of hearing loss.

Gopinath et al. (2011a, b) in a second cross-sectional and prospective analysis found that higher dietary intake of cholesterol was associated with increased odds of hearing loss. Conversely, serum lipid levels were not associated with odds of hearing loss. In addition, dietary intake of monounsaturated fats was associated with reduced risk of progression of hearing loss over a 5-year period. However, neither total fat intake nor serum lipid levels were associated with 5-year incidence of hearing loss.

Finally, Spankovich et al. (2011) showed that higher total fat and cholesterol intake were associated with poorer TEOAEs. In addition, higher cholesterol intake was associated with poorer high-frequency (3,000, 4,000, 6,000, 8,000 Hz) and low-frequency (500, 1,000, 2,000 Hz) pure-tone averages (PTAs). No further assessments of lipid components or serum measures were analyzed.

In summary, serum levels of lipids have limitations as makers of hearing health and health in general. The overall findings do support a relationship between dietary intake of lipids and hearing (e.g., higher omega-3 fatty acid intake associated with better hearing). However, the effect size may be small.

In addition to lipids, antioxidants and other macro- and micronutrients have been a major area of investigation. For example, interest in vitamin B12 and folate (B9) with hearing was based in the common inadequacies of these two nutrients in the elderly population, as well as their respective roles in cellular metabolism, neural integrity, and vascular function.

Increased prevalence of hearing loss was found in older women with low serum levels of vitamin B12 and folate (Houston et al. 1999). On the contrary, another study showed no relationship between serum B12 and folate in elderly subjects (Berner et al. 2000). Gok et al. (2004) found that young adult subjects with evidence of NIHL had higher serum levels of homocysteine and reduced serum levels of B12 and folic acid compared to matched controls. In addition, a significant relationship between ARHL and serum folate was also reported by Lasisi et al. (2010). Gopinath et al. (2010b) examined serum levels of folate, B12, and homocysteine with hearing loss. Higher levels of folate were associated with better hearing and higher levels of homocysteine with poorer hearing prevalence, but no relationship was found prospectively over a 5-year period. Also, no significant relationship was found for B12 serum levels and hearing sensitivity.

Shargorodsky et al. (2010) performed a prospective analysis (n > 26,000) of vitamin intake and risk of hearing loss in men. The data were collected as part of the Health Professionals Follow-up Study over a period from 1986 to 2004. Based on reported dietary intake and reported diagnosed hearing loss, they found no relationship between intake of vitamins C and E, beta-carotene, and hearing loss. However, dietary folate intake was associated with reduced risk of hearing loss. Dietary B12 was also associated with reduced risk of hearing loss, but only in men with higher alcohol intake. Unfortunately, this study had at least one major limitation; no objective auditory function data was available. Hearing status was based on participant-reported diagnosed hearing loss.

Spankovich et al. (2011) examined 25 total dietary nutrients and relationship to TEOAEs and pure-tone threshold hearing sensitivity (high- and low-frequency PTA). The motivation of the analysis was to determine if associations found in animal-based literature were present in a human population and to identify novel relationships that may inform future directions for otoprotection strategies. All major macro- and micronutrients available in the database were considered including caloric intake, total carbohydrates, protein, total fat, total cholesterol, carotenoids, vitamin A, vitamin C, vitamin E, B vitamins, and trace minerals. Both dietary- and supplement-based sources were included. Prior to adjustment for confounding variables, 19 nutrients showed significant correlations to at least one of three auditory outcomes. After adjusting for significant covariates (age, sex, noise exposure), the findings revealed that better pure-tone threshold sensitivity was associated with higher lycopene, vitamin E, vitamin C, riboflavin (B2), and magnesium intake. Higher intake of lipids, as described above, was associated with poorer auditory outcomes. The major shortcoming of the study was the limitation to cross-sectional analysis. As a follow-up, Gopinath et al. (2011a, b) examined intake of dietary antioxidants prospectively in the same population. The findings showed that dietary intake of antioxidants was not associated with the 5-year incidence of hearing loss. The lack of significant findings in prospective analysis was attributed to the relatively short time between testings.

Choi et al. (2014) studied the relationship between antioxidant and magnesium intake and hearing in 2,592 participants using the National Health and Nutrition Examination Study (NHANES) database. The NHANES is an ongoing cross-sectional survey of the civilian noninstitutionalized population of the United States. Every 2 years, approximately 10,000 individuals are selected at random within specific demographic distributions so as to be representatives of the US population. The results demonstrated a significant association between higher intake of antioxidants (daily beta-carotene and vitamins C and E) and magnesium with better hearing thresholds.

Gopinath et al. (2010a, b) evaluated the relationship between carbohydrate intake and hearing loss. The results indicated that higher glycemic load (GL) foods (i.e., high carbohydrate and efficiency in raising blood glucose levels) were associated with higher incidence of hearing loss, and higher fiber intake may reduce this risk.

In summary, there are inconsistent findings when examining single-nutrient relationships with hearing. Study design is likely a critical factor (e.g., cross-sectional vs. longitudinal, auditory function measures vs. reported hearing loss). The literature overall suggests there is a relationship between higher intake of nutrients with antioxidant properties and B vitamins for better auditory function. However, longitudinal studies with appropriate controls and measures of auditory function are needed to further understand this relationship.

Somewhat similar to Rosen and Olin (1965) and Rosen et al. (1970), a low-cholesterol diet and anti-lipid therapy were administered to hyperlipidemic patients with tinnitus and hearing loss. The findings indicated reduced subjective tinnitus severity and improved high-frequency thresholds over a 2-year period (Sutbas et al. 2007).

Durga et al. (2007) followed 728 men on folic acid supplementation (800 μg daily) over a 3-year period to assess its influence on hearing. The study was performed in the Netherlands where at that time folic acid fortification of foods was prohibited and baseline folate levels in participants were about half of those found in the US population. The results showed a decreased progression of hearing loss in speech frequencies in participants on the supplement compared to controls. A third case–control study assessed the efficacy of B12 treatment on tinnitus and hearing in 100 patients with B12 deficiency. The treatment showed no effect in ameliorating tinnitus or effect on hearing compared to controls (Berkiten et al. 2013). Takumida and Anniko (2009) assessed the effects of supplementation with rebamipide (300 mg/day), alpha-lipoic acid (60 mg/day), and vitamin C (600 mg/day) on hearing over an 8-week period. The results showed significant improvement in hearing thresholds after treatment primarily limited to low frequencies. The study however had many design limitations including lack of a placebo-control group.

Weijl et al. (1998) showed that cisplatin-combination chemotherapy resulted in reduced plasma concentrations of vitamins C and E, uric acid, and ceruloplasmin, despite no significant change in diet. The results provided evidence of reduced antioxidant levels during treatment with cisplatin. In a follow-up study, Weijl and colleagues performed a randomized, double-blind, placebo-controlled study of antioxidant supplementation for cisplatin-induced ototoxicity (Weijl et al. 2004). Participants were supplemented with vitamins C and E and selenium and compared to controls on placebo. No significant difference was found between the supplemented group and placebo in regard to hearing thresholds. However, participants with highest plasma concentrations of the three antioxidants (regardless if on supplement or not) had significantly less loss of higher-frequency hearing. Unfortunately, dietary intake of the participants was not monitored or considered in the analysis. Recent evidence suggests potential limitations of antioxidant supplementation for patients with some forms of cancer; Sayin et al. (2014) found that mice with lung tumors supplemented with antioxidants were seen with an accelerated growth in tumor size and increased mortality.

Based on the evidence of the Weijl et al. (1998) findings, Joachims et al. (2003) performed a prospective, double-blind study of vitamin E in treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). The patients were all treated with steroids, magnesium, and carbogen inhalation. The experimental group received the additional vitamin E (d-α-tocopherol, 400 mg twice daily). The group receiving vitamin E showed greatest success with nearly 80 % showing at least 75 % recovery of thresholds compared to only 45 % of the control treatment. Similar benefits were described by Hatano et al. (2008). In this study a group of patients received vitamin E (tocopherol nicotinate, 600 mg/day) and vitamin C (1,200 mg/day) in addition to control treatment with steroids. The patients treated with the antioxidant regimen showed an average of 30 dB recovery in thresholds compared to the control’s 18 dB recovery.

The application of micronutrient supplement strategies has also been applied to NIHL. Supraphysiological levels of B12 injections (cyanocobalamin, 1 mg/day for 7 days, 5 mg on eighth day) were shown to protect against temporary threshold shift (TTS) in 20 young adult subjects (Quaranta et al. 2004). Two double-blind placebo-controlled studies have reported that Mg can reduce NIHL in humans (Joachims et al. 1993; Attias et al. 1994, 2004). However, it does not appear that individual variation in dietary Mg, in the absence of high-level supplements, is adequate to confer protection against NIHL. In contrast to positive outcomes with higher-level supplements, Walden et al. (2000) reported that plasma Mg was not reliably correlated with NIHL measured in male US Army soldiers with long-term (8–18 years) exposure to high-level weapon noise in a single combat unit.