# A plasma metabolomic fingerprint of moderate or severe hearing loss

## TL;DR

This study finds that certain blood metabolites are linked to moderate or severe hearing loss in women, suggesting metabolic changes may play a role in hearing decline.

## Contribution

The study identifies a plasma metabolomic fingerprint associated with adult-onset hearing loss in a large population-based cohort.

## Key findings

- Ten metabolites were significantly associated with moderate or severe hearing loss.
- Triglycerides showed positive associations, while steroid esters were inversely associated with hearing loss.
- Triglycerides with fewer double bonds were particularly linked to hearing loss.

## Abstract

Disabling hearing loss affects millions of adults world-wide. Metabolomics investigations are comprehensive assessments of an individual’s metabolic processes that could provide insight into biological pathways underlying auditory dysfunction, yet data are limited.

We conducted a cross-sectional investigation of the association of plasma metabolite profiles and self-reported adult-onset moderate or severe hearing loss among 3925 women, including 1167 hearing loss cases and 2758 controls in the Nurses’ Health Study. Information on hearing status at the time of the blood collection and on relevant risk factors was collected on biennial questionnaires. Metabolic profiling was conducted by liquid chromatography-mass spectrometry. The independent associations of 278 metabolites with hearing loss was assessed in logistic regression models adjusted for age, fasting status, race/ethnicity, co-morbidities, medication use and biobehavioral factors. The false discovery rate was controlled at 5% through the q-value approach. Metabolite Set Enrichment Analysis was conducted to identify metabolite classes that are enriched for concordant associations with hearing loss.

We identified 10 metabolites that were significantly associated (q value < 0.05) with moderate or severe hearing loss in multivariable-adjusted models. Steroid esters were enriched for negative associations, while triglycerides were enriched for positive associations. Triglycerides with fewer double bonds were enriched for significant, positive associations with hearing loss (p = 0.04).

In this population-based investigation, we identified that triglycerides were enriched for positive associations, while steroid esters were inversely associated with adult-onset moderate or severe hearing loss. This study indicates that metabolic perturbations may contribute to the pathoetiology underlying adult-onset hearing loss.

The online version contains supplementary material available at 10.1007/s11306-026-02395-8.