Serum homocysteine is a biomarker for hearing loss associated with or without cardiovascular risk: a cross-sectional study in men

Abstract

Purpose: Hearing loss (HL) represents a major health problem worldwide, and increasingly so due to population ageing and new leisure activities, such as video gaming or virtual reality experiences. HL has a multifactorial origin including both genetic and environmental issues with nutrition status emerging as a new contributing factor. In fact, certain micronutrient deficiencies, along with excessive consumption of specific macronutrients, have been related to HL This study aimed to examine the association of HL with dietary fat intake, nutritional status biomarkers, and serum metabolic signature in aviation pilots and controls.

Methods: A cohort of aviation pilots, chronically exposed to noise pollution at work, was compared to a cohort of non-exposed university workers (controls). Hearing function was determined by tonal audiometry and dietary fat intake was assessed by three 24-h recalls. In addition, lipoprotein profiles as well as serum homocysteine (Hcy), folate, vitamins B₁₂ and D were analysed. Two multiple linear regression models adjusted for age were constructed to explain HL variability.

Results: HL prevalence was similar and elevated in both cohorts (controls: 64% vs. noise-exposed: 65%), when compared to the American Speech-Language-Hearing Association (ASHA) classification. When comparing both cohorts, although no significant differences were found in Hcy and folate levels, controls had significantly lower vitamins B₁₂ and D concentrations and, conversely, higher serum lipids and lipoprotein values (triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol subfractions), suggesting the possible involvement of CV risk in HL in the control cohort. In the noise-exposed cohort, HL was associated with flight hours, Hcy, and folate (r² = 0.439), while in controls, HL was associated with Hcy and vitamin D (r² = 0.474). After adjusting for CV profile, the positive association between HL and Hcy was maintained (β = 0.444; p < 0.001), evidencing the strong involvement of this metabolite not only in CV risk, but also in HL.

Conclusion: Folate insufficiency together with hyperhomocysteinemia increased susceptibility to noise-induced HL. However, the role of Hcy in HL without noise exposure at work seems to be partially masked by an altered CV profile.

Keywords: Cardiovascular risk; Folate; Hearing loss; Homocysteine; Lipoproteins; Vitamin D.

Fig. 1

Volunteer eligibility flowchart. CON: control, NE: noise-exposed

Fig. 2

Experimental procedure scheme

Fig. 3

Classification of hearing loss in a, the control cohort and b, the noise-exposed cohort, according to the American Speech-Language-Hearing Association (ASHA) [35]

Fig. 4

Audiometry of the sample sorted by exposure and ear: a, control cohort and b, noise-exposed cohort. *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001 indicate significant differences between cohorts (Student´s T test)

Fig. 5

Monte Carlo Cross Validation - Partial Least Squares Discriminant Analysis (MCCV-PLSDA). MCCV-PLSDA score plot derived from 1D ¹H‐NMR spectra of serum samples, indicating the differentiation between noise-exposed (purple) vs. control (green) cohort. The model is comprised of Kernel Density Estimate (KDE) of the predicted scores (Tpred) for both groups. Dots represent the metabolic profile of each volunteer from the study cohort when its corresponding NMR spectrum was available. The fit and predictability of the model were obtained and expressed as R²_Y (explained variance) and Q²_Y (capability of prediction) values