Abstract
Although polyunsaturated fatty acids (PUFAs) are recognized for their beneficial impact on human health, evidence regarding their association with high-frequency hearing loss (HFHL) remains limited. This study aimed to examine the association between the dietary intake of n − 3 and n − 6 PUFAs, dietary n − 6/n − 3 PUFA ratio, and HFHL. In this cross-sectional study, data were obtained from 2 cycles of the National Health and Nutrition Examination Survey 2011 to 2012 and 2015 to 2016. Multivariable logistic regression models were used to assess the associations of dietary n − 3 and n − 6 PUFA intake and the dietary n − 6/n − 3 PUFA ratio with HFHL. Restricted cubic spline (RCS) analyses were performed to evaluate potential dose–response relationships. Stratification and sensitivity analyses were conducted to evaluate the robustness of the findings. A total of 6454 adults aged 30 to 69 years were included (mean [standard deviation age, 49.2 [11.4] years; 50.9% women), among whom 44.7% had HFHL. After full adjustment, higher dietary intake of both n − 3 and n − 6 PUFAs was associated with lower odds of HFHL (adjusted odds ratio, 0.93; 95% confidence interval [CI], 0.87–0.99 for n − 3 PUFAs; and 0.90; 95% CI, 0.81–0.99 for n − 6 PUFAs). RCS analyses demonstrated a linear inverse dose–response relationship (all P for nonlinearity > 0.05). Subgroup and sensitivity analyses generally supported the robustness of these associations; no significant interactions were observed for n − 3 PUFAs. For n − 6 PUFAs, a significant interaction was detected in the race/ethnicity subgroup (interaction P < .001), whereas interactions were not significant in other subgroups. Dietary n − 3 and n − 6 PUFA intake and HFHL among adults in the United States aged 30–69 years were negatively associated. This finding could have significant implications for further research on modifying dietary patterns to address HFHL.
Keywords: audiometry, cross-sectional, dietary, hearing loss, n-3 polyunsaturated fatty acid, n-6 polyunsaturated fatty acid, NHANES
1. Introduction
Hearing loss has emerged as a major public health concern that poses a threat to human well-being. Approximately 1.4 billion people worldwide, accounting for 18.7% of the global population, experience varying degrees of hearing impairment.[1,2] Hearing loss is significantly linked to cognitive impairment, anxiety, depression, and the onset of dementia.[3–6] Certainly, the prevalence of high-frequency hearing loss (HFHL) is notably higher than that of speech-frequency hearing loss among individuals aged 20 to 69 years in the United States. Moreover, the risk of HFHL increases with age.[7] High-frequency hearing is significantly correlated with abstraction and verbal functioning. Moreover, high-frequency hearing plays a crucial role in speech discrimination, particularly in noisy environments.[5,8] Severe HFHL significantly affects communication and can reduce quality of life and jeopardize overall human health.
Hence, exploring the factors influencing HFHL is an area of active importance. Adhering to the Mediterranean dietary pattern and increasing dietary potassium intake can potentially reduce the risk of developing HFHL.[9,10] However, n − 3 and n − 6 PUFAs are 2 important components of polyunsaturated fatty acids (PUFAs). Biological roles of n − 3 and n − 6 PUFAs are wide-ranging and are associated with various conditions such as HIV infection, nonalcoholic fatty liver disease, diabetic retinopathy, cardiovascular diseases, and major depressive disorder, among others.[11–15] However, few studies have simultaneously examined the association of dietary n − 3 PUFAs and n − 6 PUFAs with HFHL. The results from these studies are inconsistent, with one study suggesting no significant correlation between n − 3 PUFAs and HFHL in individuals aged 50 to 70 years.[16] In addition, another study has indicated no significant correlation between n − 3 PUFAs and HFHL in individuals aged 20 to 40 years.[17] using data from the National Health and Nutrition Examination Survey (NHANES), the present study was conducted to further investigate the relationship between dietary intake of n − 3 PUFAs and n − 6 PUFAs and the odds of HFHL. This study aimed to provide a reference basis for the early prevention and treatment of HFHL by adjusting dietary factors.
2. Methods
2.1. Data sources
NHANES is a national survey that collects data on the health and nutritional status of the noninstitutionalized population in the United States. It employs a stratified, multistage probability sampling approach to ensure the representativeness of the sample.[18] The survey was authorized by the National Center for Health Statistics Research Ethics Review Board, and all participants provided written informed consent. Data were de-identified to ensure additional ethical approvals were met. All data are publicly available on https://wwwn.cdc.gov/nchs/nhanes/Default.aspx.
2.2. Study design and population
This cross-sectional study utilized NHANES data from 2 cycles, 2011 to 2012 and 2015 to 2016. Excluding dietary n − 3 and n − 6 PUFAs (missing data n = 202) and audiometry (missing data n = 2655), a total of 6454 adults aged 30–69 years were ultimately included in the current study analysis. Missing covariate data, including body mass index (BMI) (0.67% missing data), coronary heart disease (0.40% missing data), diabetes mellitus (0.06% missing data), alcohol consumption (7.19% missing data), hypertension (0.08% missing data), ear infections (3.42% missing data), dietary energy intake (5.87% missing data), marital status (0.06% missing data), 24-hour noise exposure (0.02% missing data), household income (8.06% missing data), hearing protection (0.06% missing data), smoking status (0.11% missing data), stroke (0.03% missing data), tinnitus (0.05% missing data), dietary vitamin A intake (5.87% missing data), dietary vitamin B12 (5.87% missing data), dietary supplement use (0.03% missing data), and ototoxic drug use (29.49% missing data), were handled using multiple imputation.[19] We did not conduct a priori statistical power estimation as the sample size was determined solely using the available data. Data were analyzed from July to November 2023. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
2.3. Audiometry
Participants underwent binaural audiometry at frequencies of 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz, conducted by professional examiners in a specialized soundproof room at the screening center (MEC). The outcome variable for this study was HFHL, with pure tones at 3000, 4000, 6000, and 8000 Hz in both ears being defined as indicative of HFHL. HFHL was further defined as an average pure tone audiometry of > 25 dB HL.[20]
2.4. Dietary n − 3 and n − 6 PUFA intake and n − 6/n − 3 ratio
Intake data on dietary n − 3 PUFAs and dietary n − 6 PUFAs were collected through the 24-hour Dietary Recall Interview method, which involved professionals assessing participants’ dietary information according to the Dietary Recall Interview Measurement Guidelines on 2 occasions. The first assessment was conducted in person at the Mobile Screening Center, and the second assessment was conducted via phone 3 to 10 days later.[21] This dietary assessment methodology has been extensively discussed in workshops on NHANES data collection procedures and has garnered expert consensus.[22] We classified octadecatrienoic acid (18:3), octadecatetraenoic acid (18:4), eicosapentaenoic acid (20:5), docosapentaenoic acid (22:5), and docosahexaenoic acid (22:6) as n − 3 PUFAs, whereas octadeca-2-enoic acid (18:2) and eicosatetraenoic acid (20:4) were classified as n − 6 PUFAs.[23,24] The dietary data for this study were averaged over 2 measurements. Additionally, the dietary n − 6/n − 3 PUFA ratio was calculated for each participant by dividing total dietary n − 6 PUFA intake by total dietary n − 3 PUFA intake.
2.5. Other covariates
Based on prior research,[23,25,26] we evaluated demographic factors including age, sex, race/ethnicity, marital status, household income, and education attainment. We also considered comorbidities such as tinnitus, ear infections, hypertension, diabetes mellitus, stroke, and coronary artery disease, along with potential covariates such as smoking, alcohol consumption, BMI, 24-hour noise exposure, hearing preservation, dietary supplement use, dietary energy intake, dietary vitamin A intake, dietary vitamin B12 intake, and ototoxic medication use.
2.6. Statistical analysis
Continuous variables are presented as means ± standard deviations or medians (interquartile ranges, whereas categorical variables are expressed as percentages (n%). Differences between groups were compared using analysis of variance for normal distribution, the Kruskal–Wallis test for skewed distribution, and the chi-square test for categorical variables. Multifactorial logistic regression analysis was employed to ascertain the odds ratios (OR) and 95% confidence intervals (95% CIs) for the association between the intake of dietary n − 3 and n − 6 PUFA and between the dietary n − 6/n − 3 PUFA ratio and HFHL. Dietary intake of n − 3 and n − 6 PUFA and the dietary n − 6/n − 3 PUFA ratio were analyzed as continuous and categorical variables, respectively. The categorical variables were divided into quintiles, with the lowest quintile serving as the reference group. Additionally, the intake of n − 6 PUFAs was transformed by a factor of 10. Model 1 was adjusted for sex and age. Model 2 was adjusted for complications, including tinnitus, ear infections, hypertension, diabetes, stroke, and coronary heart disease, building upon the adjustments made in model 1. Model 3 was adjusted for all covariates including age, sex, race/ethnicity, marital status, household income, education attainment, tinnitus, ear infections, hypertension, diabetes, stroke, coronary heart disease, smoking, alcohol consumption, BMI, 24-hour noise exposure, hearing protection, dietary supplement use, dietary energy intake, dietary vitamin A intake, dietary vitamin B12 intake, and ototoxic drug use.
Furthermore, we employed RCS to evaluate the linear relationship between dietary n − 3 and n − 6 PUFA intake, and the dietary n − 6/n − 3 PUFA ratio and HFHL, after adjusting for the variables in model 3. We stratified our analysis by sex, age, race/ethnicity, education attainment, marital status, household income, and BMI to evaluate potential variations in the relationship between dietary n − 3 and n − 6 PUFA intake and HFHL. We assessed heterogeneity between subgroups using multivariate logistic regression and examined interactions between subgroups and dietary n − 3 and n − 6 PUFA intake through likelihood ratio tests. Multiplicative interaction terms between dietary n − 3 PUFA intake and noise exposure, dietary n − 6 PUFA intake and noise exposure, and the dietary n − 6/n − 3 PUFA ratio and noise exposure were included in multivariable logistic regression models to evaluate potential effect modification. Additive interactions were assessed by calculating the relative excess odds due to interaction and the attributable proportion.
To further evaluate the robustness of our findings, we conducted sensitivity analyses by comparing the inclusion and exclusion of demographic characteristics and by excluding participants of other races. This was performed in consideration of potential differences in the ability to synthesize and metabolize PUFA due to genetic predispositions among various racial groups in the United States.[27,28] To assess potential multicollinearity among dietary n − 3 PUFA intake, dietary n − 6 PUFA intake, and the dietary n − 6/n − 3 PUFA ratio, generalized variance inflation factors (GVIFs) were calculated. Given the differing degrees of freedom across variables, GVIFs were scaled as GVIF^(1/(2 × df)). Values < 5 indicate acceptable collinearity, and all variables meet this criterion.
Statistical analyses were performed using R 4.2.2 (https://www.r-project.org/, The R Foundation) and Free Statistics software version 2.0.[29] A 2-sided value of P < .05 was considered to indicate statistical significance.
3. Results
3.1. Baseline characteristics of the study population
The study utilized NHANES data from 2011 to 2012 and 2015 to 2016. Missing data from participants with dietary n − 3 and n − 6 PUFA intake (n = 185) and hearing tests (n = 1110) were excluded. A total of 6454 participants were ultimately included in the analysis. Figure 1 illustrates the inclusion and exclusion process.
Figure 1.
Flow diagram of participant selection.
In Table 1, participant characteristics are presented based on whether they had HFHL. Among the study population, 50.9% were women, with a mean age of 49.2 ± 11.4 years, and 44.7% had HFHL. Individuals with HFHL were generally male, non-Hispanic White, married or in a partnership, with higher levels of education, lower household income, higher BMI, and nonsmokers but alcohol drinkers. They were less likely to have a history of ear infections, tinnitus, diabetes, hypertension, coronary heart disease, or stroke. Additionally, they were not exposed to noise for 24 hours, did not use ototoxic medications or dietary supplements, and had low dietary total energy, dietary vitamin A, dietary vitamin B12, dietary n − 3 PUFA intake, and dietary n − 6 PUFA intake. A comparison of the characteristics of participants included and excluded is presented in Table S1, Supplemental Digital Content, https://links.lww.com/MD/R401.
Table 1.
Characteristics of NHANES 2011–2012 and 2015–2016 Participants.
| Variables | Total (n = 6454) | Without high-frequency hearing loss | With high-frequency hearing loss | P |
|---|---|---|---|---|
| (n = 3566) | (n = 2888) | |||
| Sex, n (%) | <.001 | |||
| Male | 3172 (49.1) | 1426 (40.0) | 1746 (60.5) | |
| Female | 3282 (50.9) | 2140 (60.0) | 1142 (39.5) | |
| Age (yr), Mean ± SD | 49.2 ± 11.4 | 44.0 ± 9.9 | 55.7 ± 9.6 | <.001 |
| Race/ethnicity, n (%) | <.001 | |||
| Non-Hispanic White | 2100 (32.5) | 1097 (30.8) | 1003 (34.7) | |
| Non-Hispanic Black | 1606 (24.9) | 964 (27.0) | 642 (22.2) | |
| Mexican American | 941 (14.6) | 474 (13.3) | 467 (16.2) | |
| Others | 1807 (28.0) | 1031 (28.9) | 776 (26.9) | |
| Education attainment (yr), n (%) | <.001 | |||
| <9 | 621 (9.6) | 238 (6.7) | 383 (13.3) | |
| 9–12 | 845 (13.1) | 390 (10.9) | 455 (15.8) | |
| >12 | 4988 (77.3) | 2938 (82.4) | 2050 (71) | |
| Marital status, n (%) | .01 | |||
| Married or living with a partner | 4195 (65.0) | 2367 (66.4) | 1828 (63.3) | |
| Living alone | 2259 (35.0) | 1199 (33.6) | 1060 (36.7) | |
| Family income, n (%) | <.001 | |||
| Low((<<1.5)) | 2059 (31.9) | 1004 (28.2) | 1055 (36.5) | |
| Medium((1.5-3.5)) | 2326 (36.0) | 1301 (36.5) | 1025 (35.5) | |
| High((>>3.5)) | 2069 (32.1) | 1261 (35.4) | 808 (28.0) | |
| BMI (kg/m2), Mean ± SD | 29.9 ± 7.2 | 29.8 ± 7.4 | 30.0 ± 6.8 | .306 |
| Smoking status,n (%) | <.001 | |||
| Never | 3585 (55.5) | 2226 (62.4) | 1359 (47.1) | |
| Current | 1410 (21.8) | 700 (19.6) | 710 (24.6) | |
| Former | 1459 (22.6) | 640 (17.9) | 819 (28.4) | |
| Alcohol consumption, n (%) | .574 | |||
| Yes | 4610 (71.4) | 2537 (71.1) | 2073 (71.8) | |
| No | 1844 (28.6) | 1029 (28.9) | 815 (28.2) | |
| Diabetes, n (%) | <.001 | |||
| Yes | 907 (14.1) | 302 (8.5) | 605 (20.9) | |
| No | 5547 (85.9) | 3264 (91.5) | 2283 (79.1) | |
| Hypertension, n (%) | <.001 | |||
| Yes | 2386 (37.0) | 1033 (29) | 1353 (46.8) | |
| No | 4068 (63.0) | 2533 (71) | 1535 (53.2) | |
| Coronary heart disease, n (%) | <.001 | |||
| Yes | 401 (6.2) | 119 (3.3) | 282 (9.8) | |
| No | 6053 (93.8) | 3447 (96.7) | 2606 (90.2) | |
| Stroke, n (%) | <.001 | |||
| Yes | 193 (3.0) | 53 (1.5) | 140 (4.8) | |
| No | 6261 (97.0) | 3513 (98.5) | 2748 (95.2) | |
| Ear infections, n (%) | .048 | |||
| Yes | 1523 (23.6) | 808 (22.7) | 715 (24.8) | |
| No | 4931 (76.4) | 2758 (77.3) | 2173 (75.2) | |
| Tinnitus, n (%) | <.001 | |||
| Yes | 1088 (16.9) | 366 (10.3) | 722 (25) | |
| No | 5366 (83.1) | 3200 (89.7) | 2166 (75) | |
| Hearing protection, n (%) | .497 | |||
| Always | 487 (7.5) | 260 (7.3) | 227 (7.9) | |
| About half the time | 440 (6.8) | 231 (6.5) | 209 (7.2) | |
| Seldom | 360 (5.6) | 199 (5.6) | 161 (5.6) | |
| Never | 5167 (80.1) | 2876 (80.7) | 2291 (79.3) | |
| Loud noise exposure in past 24 hours, n (%) |
<.001 | |||
| Yes | 672 (10.4) | 429 (12) | 243 (8.4) | |
| No | 5782 (89.6) | 3137 (88) | 2645 (91.6) | |
| Ototoxic medication use, n(%) | .688 | |||
| No | 6281 (97.3) | 3473 (97.4) | 2808 (97.2) | |
| Yes | 173 (2.7) | 93 (2.6) | 80 (2.8) | |
| Dietary supplements,n (%) | .402 | |||
| Yes | 3279 (50.8) | 1795 (50.3) | 1484 (51.4) | |
| No | 3175 (49.2) | 1771 (49.7) | 1404 (48.6) | |
| Dietary energy intake (kcal/day), Median (IQR) | 1907.2 (1420.8, 2462.4) | 1910.8 (1437.0, 2448.6) | 1900.2 (1394.5, 2482.6) | .699 |
| Dietary vitamin A intake (mg/day), Median (IQR) | 477.2 (282.5, 741.4) | 491.5 (292.0, 753.9) | 463.8 (273.0, 733.0) | .028 |
| Dietary vitamin B12 intake (mg/day), Median (IQR) | 3.7 (2.3, 5.8) | 3.7 (2.4, 5.9) | 3.7 (2.3, 5.8) | .311 |
| Dietary n-3 PUFA intake (g/day), Median (IQR) | 1.6 (1.0, 2.3) | 1.6 (1.0, 2.3) | 1.5 (1.0, 2.3) | .033 |
| Dietary n-6 PUFA intake (g/day), Median (IQR) | 14.2 (9.1, 20.6) | 14.5 (9.4, 20.7) | 13.9 (8.7, 20.4) | .014 |
| Dietary n-6:n-3 PUFA ratio Median (IQR) | 8.8 (7.5, 10.5) | 8.8 (7.5, 10.6) | 8.8 (7.5, 10.5) | .303 |
3.2. Associations between dietary n − 3 and n − 6 PUFA intake, the dietary n − 6/n − 3 PUFA ratio, and HFHL
For the univariate analyses (Table S2, Supplemental Digital Content, https://links.lww.com/MD/R401), we conducted multivariate logistic regression analyses to examine the associations between dietary intake of n − 3 PUFA, n − 6 PUFA, and HFHL (Tables 2–3). After controlling for all potential confounders, dietary n − 3 PUFA intake was negatively associated with the odds of HFHL when used as a continuous variable. The adjusted OR was 0.93 (95% CI: 0.87–0.99, P = .023) for the intake of dietary n − 3 PUFAs and HFHL. When used as a quintile categorical variable, compared to individuals with the lowest intake (Q1 ≤ 0.86 g/day) of dietary n − 3 PUFAs, the adjusted OR for intake and HFHL in Q2 (0.87–1.34 g/day), Q3 (1.35–1.83 g/day), Q4 (1.84–2.53 g/day), and Q5 (2.54–16.1 g/day) were 0.94 (95% CI: 0.77–1.15, P = .558), 0.73 (95% CI: 0.59–0.91, P = .004), 0.79 (95% CI: 0.63–1.00, P = .048), and 0.76 (95% CI: 0.59–0.98, P = .036), respectively. When a negative association was observed between dietary n − 6 PUFA intake and the odds of HFHL for every 10 units of change in dietary n − 6 PUFA intake as a continuous variable, the adjusted OR for dietary n − 6 PUFA intake in relation to HFHL was 0.90 (95% CI: 0.81–0.99, P = .033). When dietary n − 6 PUFA intake was used as a quintile categorical variable and compared to individuals with the lowest intake (Q1, ≤7.82 g/day), the adjusted OR to HFHL in Q2 (7.83–12.27 g/day), Q3 (12.28–16.33 g/day), Q4 (16.34–22.41 g/day), and Q5 (22.43–80.64 g/day) were 0.84 (95% CI: 0.68–1.02, P = .084), 0.84 (95% CI: 0.67–1.04, P = .105), 0.77 (95% CI: 0.61–0.97, P = .027), and 0.77 (95% CI: 0.58–1.02, P = .064), respectively. Furthermore, we examined the association between the dietary n − 6/n − 3 PUFA ratio and HFHL using fully adjusted multivariate models, treating the ratio both as a continuous variable and in quintiles. In both analyses, no statistically significant association with HFHL was observed (all P > .05). A detailed overview of these results is provided in Supplementary Table 4, Supplemental Digital Content, https://links.lww.com/MD/R401.
Table 2.
Association between dietary n-3 polyunsaturated fatty acid intake and high-frequency hearing loss.
| Variable | n.total | Unadjusted | Model 1 | Model 2 | Model 3 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR (95%CI) | P-value | OR (95%CI) | P-value | OR (95%CI) | P-value | OR (95%CI) | P-value | ||||||
| Dietary n-3 PUFA intake (g/day) | 6454 | 0.98 (0.94–1.02) | .283 | 0.93 (0.89–0.98) | .005 | 0.93 (0.88–0.98) | .003 | 0.93 (0.87–0.99) | .023 | ||||
| Quintiles | |||||||||||||
| Q1 (≤0.86) | 1291 | 1 (Reference) | 1 (Reference) | 1 (Reference) | 1 (Ref) | ||||||||
| Q2 (0.87–1.34) | 1290 | 0.98 (0.84–1.14) | .796 | 0.95 (0.79–1.15) | .624 | 0.96 (0.79–1.16) | .667 | 0.94 (0.77–1.15) | .558 | ||||
| Q3 (1.35–1.83) | 1291 | 0.88 (0.75–1.02) | .097 | 0.74 (0.61–0.89) | .001 | 0.74 (0.61–0.9) | .002 | 0.73 (0.59–0.91) | .004 | ||||
| Q4 (1.84–2.53) | 1290 | 0.86 (0.74–1.01) | .066 | 0.8 (0.66–0.97) | .021 | 0.79 (0.65–0.96) | .017 | 0.79 (0.63–1) | .048 | ||||
| Q5 (2.54–16.1) | 1292 | 0.91 (0.78–1.06) | .214 | 0.77 (0.64–0.92) | .005 | 0.77 (0.63–0.93) | .006 | 0.76 (0.59–0.98) | .036 | ||||
| P for trend | .069 | .001 | .001 | .018 | |||||||||
Model 1: Adjusted for sex and age.
Model 2: Adjusted for sex, age, tinnitus, ear infection, hypertension, diabetes, stroke, and coronary heart disease.
Model 3: Adjusted for sex, age, race/ethnicity, education attainment, household income, marital status, tinnitus, ear infection, hypertension, diabetes, stroke, coronary heart disease, body mass index, smoking status, alcohol consumption, noise exposure, hearing protection, ototoxic medication use, dietary energy intake, dietary vitamin A intake, dietary vitamin B12 intake, and dietary supplements.
Table 3.
Association between dietary n-6 polyunsaturated fatty acid intake and high-frequency hearing loss.
| Variable | n.total | Unadjusted | Model 1 | Model 2 | Model 3 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR (95%CI) | P-value | OR (95%CI) | P-value | OR (95%CI) | P-value | OR (95%CI) | P-value | |||||
| Dietary n-6 PUFA intake,(g/day) per10 | 6454 | 0.95 (0.90–1.00) | .045 | 0.93 (0.88–0.99) | .03 | 0.92 (0.87–0.98) | .011 | 0.90 (0.81–0.99) | .033 | |||
| Quintiles | ||||||||||||
| Q1 (≤7.82) | 1291 | 1 (Reference) | 1 (Reference) | 1 (Reference) | 1 (Reference) | |||||||
| Q2 (7.83–12.27) | 1291 | 0.86 (0.74–1.01) | .058 | 0.82 (0.68–0.99) | .038 | 0.82 (0.68–1.00) | .046 | 0.84 (0.68–1.02) | .084 | |||
| Q3 (12.28–16.33) | 1290 | 0.88 (0.75–1.02) | .093 | 0.84 (0.70–1.01) | .066 | 0.82 (0.68–0.99) | .039 | 0.84 (0.67–1.04) | .105 | |||
| Q4 (16.34–22.41) | 1291 | 0.79 (0.68–0.93) | .003 | 0.75 (0.62–0.91) | .003 | 0.74 (0.61–0.9) | .002 | 0.77 (0.61–0.97) | .027 | |||
| Q5 (22.43–80.64) | 1291 | 0.85 (0.73–0.99) | .04 | 0.79 (0.65–0.95) | .015 | 0.77 (0.63–0.93) | .008 | 0.77 (0.58–1.02) | .064 | |||
| P for trend | .021 | .01 | .004 | .06 | ||||||||
Model 1: Adjusted for sex and age.
Model 2: Adjusted for sex, age, tinnitus, ear infection, hypertension, diabetes, stroke, and coronary heart disease.
Model 3: Adjusted for sex, age, race/ethnicity, education attainment, household income, marital status, tinnitus, ear infection, hypertension, diabetes, stroke, coronary heart disease, body mass index, smoking status, alcohol consumption, noise exposure, hearing protection, ototoxic medication use, dietary energy intake, dietary vitamin A intake, dietary vitamin B12 intake, and dietary supplements.
RCS analysis demonstrated a negative linear association between dietary n − 3 and n − 6 PUFA intake and HFHL (all P for nonlinearity > 0.05; Fig. 2). In contrast, no significant association, either linear or nonlinear, was observed between the dietary n − 6/n − 3 PUFA ratio and HFHL (all P for nonlinearity > 0.05; Supplementary Table 4 and Figure S1, Supplemental Digital Content, https://links.lww.com/MD/R401).
Figure 2.
Associations between dietary n-3 and n-6 PUFA intake and high-frequency hearing loss.
Adjusted odds ratios for HFHL were estimated using restricted cubic spline (RCS) logistic regression models with knots at the 5th, 35th, 65th, and 95th percentiles. Models were adjusted for sex, age, race/ethnicity, education attainment, household income, marital status, tinnitus, ear infection, hypertension, diabetes, stroke, coronary heart disease, body mass index, smoking status, alcohol consumption, noise exposure, hearing protection, ototoxic medication use, dietary energy intake, dietary vitamin A intake, dietary vitamin B12 intake, and dietary supplement use.
3.3. Stratified analyses based on additional variables
We analyzed the data by stratifying based on sex, age, race/ethnicity, education attainment, marital status, household income, and BMI (Fig. 3). We determined no significant interaction between dietary n − 3 PUFA intake and the odds of HFHL in any subgroup, as indicated by interaction P > .05. However, a significant interaction (interaction P < .001) was observed between dietary n − 6 PUFA intake and the odds of HFHL in the race/ethnicity subgroup. In all other subgroups, the interaction P > .05.
Figure 3.
Stratified analyses of the associations between dietary n-3 and n-6 pufa intake and high-frequency hearing loss.
Except for the stratification factor itself, each analysis was adjusted for all other covariates, including sex, age, race/ethnicity, education attainment, household income, marital status, tinnitus, ear infection, hypertension, diabetes, stroke, coronary heart disease, body mass index, smoking status, alcohol consumption, noise exposure, hearing protection, ototoxic medication use, dietary energy intake, dietary vitamin A intake, dietary vitamin B12 intake, and dietary supplement use. Squares represent odds ratios (ORs), and horizontal lines indicate 95% confidence intervals (CIs).
In addition, we formally tested multiplicative interactions between loud noise exposure in the past 24 hours and dietary n − 3 PUFA intake, n − 6 PUFA intake, and the dietary n − 6/n − 3 PUFA ratio. No significant interactions were observed (all P for interaction > .05; Tables S5–S7, Supplemental Digital Content, https://links.lww.com/MD/R401).
3.4. Sensitivity analysis
After excluding participants from other racial/ethnic groups (Table S3, Supplemental Digital Content, https://links.lww.com/MD/R401), we performed multivariable logistic regression analyses with full covariate adjustment. The results remained robust, demonstrating significant inverse associations between dietary n − 3 and n − 6 PUFA intake and HFHL. The adjusted odds ratios were 0.90 (95% CI, 0.83–0.97; P = .009) for n − 3 PUFAs and 0.89 (95% CI, 0.79–0.99; P = .04) for n − 6 PUFAs.
3.5. Collinearity diagnostics
Assessment of multicollinearity among dietary n − 3 PUFAs, n − 6 PUFAs, and the n − 6/n − 3 ratio showed no evidence of problematic collinearity, with all GVIF^(1/(2 × df)) values below 5 (Tables S8–S10, Supplemental Digital Content, https://links.lww.com/MD/R401).
4. Discussion
This cross-sectional study examining data from 6454 participants across 2 NHANES cycles (2011–2012 and 2015–2016) revealed a negative association between dietary intake of n − 3 and n − 6 PUFAs and the odds of HLHL. After adjusting the full model, the findings remained consistent. The prevalence of HFHL decreased by 7% with every 1-unit increment in dietary n − 3 PUFA intake and by 10% with every 10-unit increase in dietary n − 6 PUFA intake. This negative association persisted across categorical variables, subgroup analyses, and sensitivity analyses. However, a notable interaction was observed between the intake of dietary n − 6 PUFAs and the relationship with HLHL odds in the race/ethnicity subgroup analyses.
An epidemiologic survey of hearing loss among adults in the United States aged 20 to 69 years has reported that approximately 31% (approximately 60.98 million individuals) were affected by HFHL in 2011 to 2012.[7] Assuming a causal relationship, we generated preliminary estimates of the potential public health implications of the effect sizes observed in our study. A 1-unit increment in dietary n − 3 polyunsaturated fatty acid intake was associated with an approximately 7% lower prevalence of HFHL, corresponding to an estimated 4.26 million potentially affected individuals. Similarly, a 10-unit increment in dietary n − 6 polyunsaturated fatty acid intake was associated with an approximately 10% lower HFHL prevalence, representing a potential benefit for roughly 6.09 million individuals. Although these estimates cannot establish causality, they illustrate the possible magnitude of public health benefit associated with higher intake of dietary polyunsaturated fatty acids.
In a study conducted on mice, dietary omega-3 supplementation demonstrated long-term protective effects on cochlear metabolism and the progression of hearing loss.[30] In another prospective cohort study involving 65,215 women, a higher intake of long-chain omega-3 PUFAs reduced the risk of hearing loss in women.[25] However, this study did not focus on the male population and the effect of dietary n − 6 PUFAs on hearing loss. These studies align with our findings regarding the consumption of dietary n − 3 PUFAs and HFHL. Our study considered sex variables and concurrently investigated the relationship between dietary n − 6 PUFAs and HLHL.
Owing to the linear increase in plasma concentrations of PUFAs with higher dietary intake, some studies have examined the use of plasma PUFA concentration as a measurement index. In a Dutch cohort study involving 720 older adults aged 50 to 70 years, no significant correlation was identified between plasma very long-chain n − 3 polyunsaturated fatty acids and HFHL.[16] In a study involving 534 participants aged 19 years, plasma n − 3 PUFAs, n − 6 PUFAs, and the n − 6/n − 3 ratio were found to have non-significant associations with HL.[17] The findings of these studies were inconsistent with ours, and their studies did not include the 30 to 49 year old population. Furthermore, no stratified analysis to further explore potential correlations was performed. In a cross-sectional survey conducted in the United States involving 913 individuals aged 20 to 69 years, serum n − 3 PUFAs and serum n − 6 PUFAs had no correlation with HFHL in individuals aged 20 to 40 years, but showed a positive correlation in individuals aged 40 to 60 years.[31] Although this study does not entirely align with our findings, it suggests the effect of polyunsaturated fatty acids on HFHL may have different mechanisms of action in different age groups. The differences in study populations and various methods used for reporting HL examinations and assessing blood and dietary content could account for the variability observed in the abovementioned studies. This study encompassed 6454 participants aged 30 to 69 years, representing a broad age range and a substantial sample size. The researchers utilized logistic regression and RCS to investigate the relationship between dietary n − 3 and n − 6 PUFA intake and HFHL. Additionally, they conducted stratified and sensitivity analyses, which contributed to high statistical certainty and reliable results. Furthermore, our study identified a noteworthy interaction between dietary n − 6 PUFA intake and the prevalence of HFHL in subgroup analyses based on race/ethnicity. Previous research has indicated variations in the synthesis and metabolism of PUFAs due to genetically inherited factors among different ethnic groups in the United States.[27,28] These findings provide additional support for our results.
PUFAs have physiological functions that include lowering cholesterol levels, preventing platelet aggregation, reducing blood viscosity, enhancing blood microcirculation, and exhibiting anti-inflammatory effects through some of their metabolites.[32–34] Both n − 3 and n − 6 PUFAs serve as substrates for cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes, generating a wide array of bioactive lipid mediators, including prostaglandins, leukotrienes, cycloepoxyeicosatrienoic acids, anti-inflammatory mediators, and other specialized pro-resolution molecules. These mediators regulate vascular tone, support endothelial function, and facilitate inflammation resolution, thereby helping to maintain microvascular homeostasis.[35,36] The stria vascularis is a highly vascularized and specialized epithelial structure that is essential for preserving the endolymphatic potential and ion homeostasis and represents a central component of the cochlear microcirculation.[37] Previous studies have demonstrated that microcirculatory dysfunction is closely associated with several forms of hearing loss.[38–40] The hypothesis that PUFAs may mitigate hearing loss by modulating eicosanoid metabolic pathways within the stria vascularis warrants further investigation, given their potential to influence local blood flow and endothelial function.[36,41] Furthermore, the inflammatory response represents a key pathological pathway contributing to the development of hearing loss.[42,43] PUFAs also exert anti-inflammatory effects and promote the resolution of inflammation through their derived lipid mediators.[35,44] In summary, PUFAs may mitigate the risk of hearing loss through multiple mechanisms, including preservation of cochlear blood flow, reduction of ischemic injury, stabilization of microcirculatory homeostasis, enhancement of endothelium-dependent vasodilation, and suppression of inflammation and its sustained activation.[14,45] PUFAs are essential fatty acids, as humans cannot synthesize them endogenously and must obtain them from dietary sources. Dietary n − 6 PUFAs are primarily derived from vegetable oils and nuts, whereas n − 3 PUFAs are obtained from various types of fish. The biological effects of PUFAs, particularly n − 3 types, have been extensively studied, with their metabolites demonstrating anti-inflammatory properties.[32,33] The inverse association observed for n − 6 PUFAs was unexpected, given the ongoing debate regarding their biological effects and the limited mechanistic evidence supporting a protective role in auditory function. Although classical pathways identify n − 6 PUFAs as precursors of arachidonic acid-derived proinflammatory lipids, growing evidence indicates that n − 6 PUFAs are not universally pro-inflammatory and may confer anti-inflammatory or cardiometabolic benefits comparable to those of n − 3 PUFAs.[46–49] Population-based studies have also reported inverse associations between circulating n − 6 PUFA levels and inflammatory markers, such as C-reactive protein,[50] suggesting a more complex physiological profile. In our additional diagnostic analyses, the GVIF^[1/(2 × Df)] values for n-3 PUFA, n − 6 PUFA, and the n − 6/n − 3 ratio were all below 5, indicating no evidence of substantial multicollinearity. Nonetheless, the potential influence of residual nutrient co-correlation and shared dietary patterns cannot be fully excluded and may partially account for the associations observed. Therefore, the protective signal identified for n − 6 PUFA should be interpreted with caution. Future longitudinal and experimental studies are warranted to determine whether this association reflects true biological activity or underlying dietary patterns within the population.
In contrast to the associations observed for absolute intakes of dietary n − 3 and n − 6 PUFAs, the dietary n − 6/n − 3 PUFA ratio was not independently associated with HFHL in this study. The simple ratio may not fully reflect the complex and potentially independent biological effects of these fatty acids on cochlear microvascular function, oxidative stress, and inflammatory pathways. Further studies are warranted to explore whether specific populations or dietary ranges of n − 6/n − 3 PUFA ratios may exhibit differential associations with auditory outcomes.
This study has several strengths. Our sample size is large and nationally representative. Additionally, to the best of our knowledge, this study is the first to simultaneously explore the association of dietary n − 3 and n − 6 PUFA intake with HFHL. However, this study has some limitations. First, owing to the constraints of a cross-sectional design, a causal relationship between the intake of n − 3 and n − 6 PUFAs and HFHL could not be established. Second, even after considering several potential confounders, the possibility of residual confounding effects cannot be completely ruled out. Lastly, the intake of dietary n − 3 and n − 6 PUFAs was obtained through a 24-hour recall, which may introduce recall bias. However, the likelihood of such bias is very low because this survey methodology obtains detailed information on food type and quantity, which is superior to food frequency surveys.[51,52] Therefore, prospective cohort studies should be conducted to further validate the relationship between the intake of dietary n − 3 and n − 6 PUFAs and HFHL.
5. Conclusions
Higher dietary intake of PUFAs was associated with a lower likelihood of HFHL in adults in the United States. These findings support the potential role of dietary fatty acid composition in hearing health and highlight the need for prospective studies to clarify causality and inform evidence-based nutritional prevention strategies.
Acknowledgments
We gratefully thank Jinbao Ma, Department of Drug-Resistant Tuberculosis, Xi’an Chest Hospital, China, and Jie Liu, Department of Vascular and Endovascular Surgery, General Hospital of the Chinese People’s Liberation Army, China, for contributing to the statistical support, study design consultation, and comments on the manuscript.
Author contributions
Conceptualization: Zhaocha Gao, Qiufang Zhang, Yunbing Dai, Jianmin Qu, Yungang Wu, Xue Zhang.
Data curation: Zhaocha Gao, Qiufang Zhang, Congcong Lv, Jianmin Qu, Yungang Wu, Xue Zhang.
Formal analysis: Zhaocha Gao, Qiufang Zhang, Yunbing Dai, Congcong Lv, Xue Zhang.
Funding acquisition: Zhaocha Gao, Yungang Wu.
Writing – original draft: Zhaocha Gao, Qiufang Zhang, Congcong Lv, Xue Zhang.
Writing – review & editing: Zhaocha Gao, Qiufang Zhang, Yunbing Dai, Yungang Wu, Xue Zhang.
Methodology: Jianmin Qu.
Supplementary Material
Abbreviations:
- CI
- confidence interval
- GVIF
- generalized variance inflation factor
- HFHL
- high-frequency hearing loss
- n-3 PUFAs
- n-3 polyunsaturated fatty acid
- n-6 PUFAs
- n-6 polyunsaturated fatty acid
- NHANES
- National Health and Nutrition Survey,
- OR
- odds ratio
This study was supported by the Jining Key Research and Development Program of the Jining Science and Technology Bureau (No. 2023YXNS208); the Research Fund of the Academician Helin New Medical Clinical Transformation Workstation (No. JYHL2022FMS11); and the Special Research Program of the Attending Physician Team at the Affiliated Hospital of Jining Medical University (No. ZZTD-2022-007).
The NHANES was authorized by the National Center for Health Statistics Ethics Review Committee, and all participants completed written informed consent forms before participation.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are publicly available.
Supplemental Digital Content is available for this article.
The NHANES study protocols were approved by the National Center for Health Statistics Research Ethics Review Board, and this approval covers all survey cycles analyzed in the present study, including the 2011–2012 and 2015–2016 cycles. As the present study was a secondary analysis of publicly available, de-identified data, no additional institutional review board approval was required.
How to cite this article: Gao Z, Zhang Q, Dai Y, Lv C, Qu J, Wu Y, Zhang X. Association of dietary n−3 and n−6 polyunsaturated fatty acid intake and n−6/n−3 ratio with high-frequency hearing loss: A cross-sectional study. Medicine 2026;105:8(e47745).
ZG, QZ, and YD contributed equally to this work.
Contributor Information
Zhaocha Gao, Email: gaocha87@163.com.
Qiufang Zhang, Email: zxent_jyfy@163.com.
Yunbing Dai, Email: 519993373@qq.com.
Congcong Lv, Email: lvcongcong@ihcams.ac.cn.
Jianmin Qu, Email: txqujmicu@sina.com.
Yungang Wu, Email: wyg0607@163.com.
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