Association between serum α-Klotho levels and tinnitus stratified by sex and depression: A cross-sectional study from NHANES

Tinnitus is a prevalent condition that can impair quality of life, particularly among older adults. The antiaging protein α-Klotho may influence auditory health by reducing oxidative stress and inflammation within the cochlea and central auditory pathways. Given the established associations of α-Klotho with sex and depression, this study examined whether sex and depression modify the relationship between serum α-Klotho levels and tinnitus. This cross-sectional analysis included 4,244 participants aged 40 to 69 years from the 2011 to 2012 and 2015 to 2016 cycles of the National Health and Nutrition Examination Survey. Tinnitus was defined as self-reported ringing, roaring, or buzzing in the ears or head lasting at least 5 minutes in the past year. Serum α-Klotho concentrations were measured using an enzyme-linked immunosorbent assay. Multivariable logistic regression models were used to evaluate the association between α-Klotho and tinnitus, adjusting for potential confounders. Subgroup analyses stratified by sex and depression status and sensitivity analyses were performed. In fully adjusted models, higher serum α-Klotho levels were associated with lower odds of tinnitus (odds ratio [OR] = 0.79; 95% confidence interval [CI]: 0.65-0.97). Stronger inverse associations were observed among females (OR = 0.75; 95% CI: 0.56-0.99) and participants without depression (OR = 0.74; 95% CI: 0.59-0.93). Serum α-Klotho levels were inversely associated with tinnitus prevalence, particularly among females and individuals without depression. These findings are derived from a cross-sectional observational analysis and should not be interpreted as causal.