Elevated blood lead and cadmium levels could be associated with a higher risk of tinnitus in US adults, according to a cross-sectional analysis.
Investigators drew on data from the National Health and Nutrition Examination Survey and analyzed three survey cycles from 2012 to 2018, yielding a final sample of 4,950 adult patients after excluding those with incomplete tinnitus status, missing blood heavy metal measurements, or missing covariate data. Tinnitus was defined by self-report as being troubled by ringing, roaring, or buzzing in the ears or head for at least 5 minutes during the prior 12 months. Overall, about 16% (n = 776) of the patients met this definition.
Primary Findings
In a fully adjusted model accounting for demographic and clinical factors, the patients in the highest quartile of blood lead concentration had 1.63 times the odds of experiencing tinnitus compared with those in the lowest quartile. The association showed a graded pattern, with statistically significant increases in odds across quartiles 2 through 4.
For blood cadmium, a statistically significant increase in the risk of tinnitus was observed only in the highest quartile, where patients had 1.32 times the odds of tinnitus compared with those in the lowest quartile. Intermediate quartiles were not associated with statistically significant differences.
In continuous-variable models, higher blood mercury and selenium concentrations were associated with higher tinnitus prevalence; however, these associations weren't statistically significant in quartile-based analyses. Blood manganese levels weren't associated with tinnitus in any model.
Dose–Response Relationships
Nonlinear dose–response relationships were observed for several metals. The likelihood of experiencing tinnitus increased sharply with rising blood lead levels at lower concentrations and then increased more gradually at higher levels. Cadmium showed a threshold effect, with the risk rising more rapidly above about 0.3 µg/dL.
Mercury demonstrated a U-shaped relationship, with relatively stable odds at lower concentrations and increasing risk at higher levels. Selenium also showed a nonlinear pattern, with a lower risk in a midrange of concentrations and a higher risk at both lower and higher levels. No statistically significant nonlinear relationship was observed for manganese.
Subgroup Analyses
The association between blood lead levels and tinnitus was generally consistent across the subgroups, although ethnicity modified the strength of the association, with larger effect sizes observed in certain racial and ethnic groups.
For blood cadmium, sex and ethnicity were significant effect modifiers. The association was stronger among female patients compared with male patients and was most pronounced among Mexican American patients.
No statistically significant subgroup interactions were identified for mercury or manganese, suggesting consistent associations across demographic and clinical groups.
For selenium, a statistically significant positive association with tinnitus was observed in male patients, non-Hispanic White patients, and patients aged 40 to 60 years, with no statistically significant interactions for other subgroup variables.
Potential Mechanisms
The investigators noted that the observed associations were consistent with known biological mechanisms. Lead and cadmium have been linked to oxidative stress and neurotoxicity, which may impair auditory function. Lead exposure may increase the permeability of the cochlea-bloodstream barrier and disrupt auditory processing, while cadmium may induce reactive oxygen species and cell death, which may interfere with intracellular signaling.
Mercury can accumulate in the central and peripheral nervous systems and has been linked to damage in auditory pathways. Selenium appears to have a dual role, acting as an antioxidant at optimal levels but contributing to oxidative stress and cellular damage at excessive concentrations, which may explain its nonlinear association with tinnitus.
Limitations
The cross-sectional design precluded causal inference, and the findings reflected associations rather than cause-and-effect relationships. Residual confounding from unmeasured variables is possible. In addition, because all the data were derived from a US population, the findings may not be generalizable to other regions.
Conclusions
“Future longitudinal studies are needed to elucidate the causal pathways and determine whether reducing body burdens of these metals can alleviate tinnitus symptoms,” wrote lead study author XueTong Jin, of the Department of Otorhinolaryngology, Head and Neck Surgery at Yanbian University Hospital, and colleagues.
The study authors reported no funding sources or conflicts of interest.
Source: Medicine
