Higher serum ferritin associated with reduced risk of hearing loss: a cross-sectional analysis of NHANES and causal inference

BACKGROUND: Ferritin, a key iron-storage and antioxidant protein, is integral to iron metabolism. Its association with hearing loss remains unclear. OBJECTIVES: This study aimed to investigate the association between serum ferritin levels and hearing loss in U.S. adults and explore potential causal relationships using Mendelian Randomization (MR). METHODS: We analyzed 2,971 participants from NHANES 1999-2002 using weighted multivariable logistic regression to assess associations between serum ferritin levels (high, normal, and low) and different frequencies of hearing loss. Stratified analyses were conducted. Bidirectional MR was performed using GWAS summary statistics to infer causal associations for sensorineural/conductive hearing loss. RESULTS: After full adjustment, high serum ferritin was associated with a significantly lower risk of high-frequency hearing loss (HFHL) (OR = 0.600 [0.390, 0.922]), especially in younger participants (20-44 years) and males. MR analysis supported a causal protective role of ferritin against sensorineural hearing loss (OR = 0.860 [0.765, 0.968]). CONCLUSIONS: Higher serum ferritin levels are observationally associated with a reduced risk of HFHL. Genetic analyses further suggest a protective causal relationship between ferritin and sensorineural hearing loss. SIGNIFICANCE: These findings suggest ferritin may be a biomarker or potential intervention target for hearing preservation. Further prospective and experimental validation of these associations is warranted.