Meniere’s disease (MD) remains a challenging clinical entity characterized by the triad of recurrent vertigo, fluctuating hearing loss, and tinnitus, often accompanied by aural fullness (1). Although endolymphatic hydrops represents the pathological hallmark, its precise etiopathogenesis involves multifactorial interactions, including autoimmune dysregulation, genetic predisposition, viral infection, and neurovascular compromise. Of particular interest, displaced otoconia may disrupt inner ear homeostasis, potentially triggering MD symptoms (2, 3). Current therapeutic options for MD remain limited and include sodium restriction, intratympanic gentamicin or steroids administration, and endolymphatic sac decompression (3).

Vitamin D modulates immunity and vascular integrity beyond calcium regulation (4). Notably, vitamin D receptors (VDRs) are abundantly expressed in the inner ear, particularly in hair cells, spiral ganglion neurons, and stria vascularis. VDR-knockout (VDR−/−) mice develop hearing loss and vestibular dysfunction, with histopathological evidence of hair cell apoptosis and otoconia demineralization (5). Clinical studies link vitamin D deficiency to higher recurrence rates in benign paroxysmal positional vertigo (BPPV), as well as poorer recovery outcomes in idiopathic sudden sensorineural hearing loss (SSNHL) (6, 7).

Prior study by Bakhshaee et al. (8), first demonstrated significantly lower serum 25-hydroxyvitamin D (25(OH)D) levels in patients with MD compared to matched controls, but did not examine links to symptom severity/frequency or therapeutic implications. While Buki et al. (9) theorized vitamin D deficiency might exacerbate MD symptoms via immune dysregulation or otolithic instability, their suggested symptomatic benefits of supplementation relied solely on unvalidated clinical observations. Consequently, direct evidence linking vitamin D status to MD phenotype remains limited.

Given the anatomical concordance between vitamin D target tissues and sites of MD pathology, we hypothesized that serum 25(OH)D levels might be associated with MD. This study was designed to address this knowledge gap with two primary objectives: (1) to compare 25(OH)D status between patients with MD and healthy controls, and (2) to evaluate potential dose–response relationships between 25(OH)D concentrations and auditory parameters.

Serum 25(OH)D in patients with MD were significantly lower than matched controls (p = 0.006). Notably, 63.3% of MD patients met criteria for vitamin D deficiency, a prevalence 1.45-fold higher than in controls (43.6%). Moreover, a dose-dependent inverse correlation existed between 25(OH)D and hearing thresholds (ρ = −0.440, p = 0.002), suggesting a potential dose–response relationship. These findings align with emerging evidence linking hypovitaminosis D to inner ear disorders, including BPPV and SSNHL. While prior studies have implicated vitamin D in otolith metabolism and cochlear function, our study provides the first clinical evidence of its association with both MD prevalence and auditory dysfunction severity in a well-phenotype cohort.

Accumulating clinical evidence demonstrates a consistent association between hypovitaminosis D and various otologic conditions. Epidemiological studies have established that patients with BPPV, vestibular neuritis (VN), and SSNHL exhibit significantly reduced serum 25(OH)D concentrations compared to healthy controls. Importantly, correcting vitamin D deficiency was beneficial for alleviating clinical symptoms and reducing BPPV recurrence by 40% in randomized controlled trial (7, 13, 14), and for reducing high-frequency hearing loss risk in SSNHL. Objective vestibular testing demonstrates that vitamin D deficiency significantly alters otolith-vestibular reflexes, with abnormal oVEMP responses observed in 68% of deficient individuals versus only 22% of those with sufficient levels (15).

While these findings strongly implicate vitamin D in peripheral vestibular function, its specific role in MD remains understudied. Preliminary investigation by Bakhshaee et al. (8) in a small MD cohort (n = 28) reported serum 25(OH)D levels lower than controls (15.2 vs. 19.8 ng/mL, p = 0.03). Critically, our finding advances prior work by establishing a novel inverse correlation between serum 25(OH)D levels and objective hearing loss severity (ρ = −0.440, p = 0.002). This dose-dependent relationship with audiometric outcomes distinct from earlier studies linking vitamin D solely to MD prevalence. More compellingly, a prospective intervention showed 55% lower intratympanic gentamicin use in MD patients with supplementation vitamin D (9).

Vitamin D levels are influenced by multiple factors, such as season, geographic location, skin color, lifestyle, supplement use, nutritional status, and measurement methodology (16). To mitigate seasonal and geographic effects, healthy controls were recruited from our hospital’s health check-up center at a 1:5 ratio to cases, matched by local community and recruitment timeframe. We also compared potential confounders (age, sex, BMI, comorbidities) between groups. Furthermore, the mean vitamin D level (21.1 ± 6.2 ng/mL) and frequency of deficiency (43.6%) in our control group closely mirrored the Zhejiang Province epidemiological survey values (21.26 ± 7.72 ng/mL and 48.2%, respectively) (17). These methodological measures strengthen the reliability of our findings.

Physiologically, endolymphatic calcium concentrations (~20–30 μM) are critical for normal hair cell function. It proposes that vitamin D deficiency elevates endolymphatic Ca²⁺ via three putative mechanisms: (1) dissolution of displaced otoconia; (2) impaired calcium buffering by vitamin D-dependent binding proteins; and (3) dysregulated VDR-mediated ion channel function. Resultant calcium overload disrupts stereocilia transduction and promotes endolymphatic hydrops via ductus reuniens obstruction by otolithic debris (3, 5, 18). VDR−/− mice exhibit a pathological triad: disorganized otoconia mineralization, cochlear-vestibular ganglion degeneration, and premature hair cell loss with stereocilia defects (4, 19). Collectively, these findings implicate vitamin D deficiency as a potential predisposing factor for MD, simultaneously affecting labyrinthine structures, the otic capsule, and neural elements. The confluence of these pathologies likely contributes to the characteristic MD symptomatology (1, 20).

Growing evidence implicates viral triggers (e.g., HSV-1 DNA detected in MD temporal bones) and immune dysregulation in MD pathogenesis, characterized by sensory neuron invasion, otolithic membrane degeneration, and perivascular inflammation (21, 22). These processes disrupt the blood-labyrinth barrier via cytokine-mediated increases in vascular permeability (TNF-α, IL-6) (23). Vitamin D exhibits multimodal immunomodulation, downregulating NF-κB signaling, suppressing pro-inflammatory cytokine production, and stabilizing endothelial junctions (5, 24, 25), potentially counteracting these effects. Genetic studies further identify vitamin-D-responsive risk alleles affecting cell adhesion molecules (e.g., PCDH15) in MD. Critically, emerging immunophenotyping classifies MD into: autoinflammatory (13%, NLRP3 inflammasome activation, elevated IL-1β), autoimmune (20%, high TNF-α), allergic (25%, type 2 cytokines, IgE), and low cytokine levels (42%) (26). Vitamin D exerts subtype-specific immunomodulation: suppressing NLRP3 inflammasome activation and IL-1β maturation (relevant to autoinflammatory subtype); downregulating Th2 responses, IgE production, and mast cell degranulation (relevant to allergic subtype); and enhancing Treg function and attenuates TNF-α-mediated inflammation (relevant to autoimmune subtype) (5, 27). Clinically, adequate serum 25(OH)D correlates with attenuated inner ear inflammation and preserved barrier integrity (28, 29). Thus, deficiency may permit unchecked immune-mediated damage across immunophenotypes, highlighting its therapeutic potential-particularly in IL-1β/IgE-dominant subtypes.

This study has several limitations. First, the cross-sectional design precludes causal inference regarding serum vitamin D levels and MD. Second, residual confounding may persist despite covariate adjustment, including unquantified dietary vitamin D/calcium intake, UV exposure patterns, sunscreen use, and genetic variants VDR/CYP2R1 /GC polymorphisms, which were hard to control. Third, biological interpretability is constrained by: (a) lack of objective audiometry in controls, and (b) absence of serum calcium, phosphate, and parathyroid hormone measurements. Finally, although described as well-phenotype regarding core diagnostic criteria, key clinical variables: including disease duration, vertigo attack frequency, bilateral involvement, and vestibular suppressant use-were not analyzed. These factors may potentially influence both vitamin D status (through behavioral modifications like reduced outdoor activity) and hearing outcomes. While the difference in mean 25(OH)D levels between MD patients and controls (2.7 ng/mL) is modest, its clinical relevance is underscored by the strong independent association of vitamin D deficiency with MD (adjusted OR = 2.21) and significant inverse correlation with hearing loss severity (ρ = −0.440). Future multicenter studies with expanded cohorts should integrate genetic profiling, lifestyle factors, advanced imaging, and animal models to elucidate the mechanistic links between vitamin D metabolism and the pathogenesis of MD.

This cross-sectional study demonstrates a significant association between vitamin D deficiency and both MD prevalence and hearing loss severity, suggesting that hypovitaminosis D may associated with MD pathogenesis.