Quality-of-life improvements following balneotherapy with hydrogen sulfide-rich thermal waters: A retrospective analysis with exploratory assessment of mineral contributions

Background Saturnia thermal waters contain distinctive calcium-sulfate-hydrogen sulfide (H₂S) composition with documented therapeutic applications. However, which specific mineral components contribute to clinical benefits remains unknown. We examined quality-of-life improvements under different exposure protocols and conducted exploratory assessment to identify potentially active mineral constituents. Methods: Retrospective analysis of 190 adult patients undergoing balneotherapy at Saturnia Thermal Center (2016–2023), stratified into acute (single 2–3-hour session, n = 114) and sustained exposure (3–14 days, n = 76) groups. Primary outcomes were SF-36 Physical Component Summary and WHOQOL-BREF physical domain. Secondary outcomes were pain (VAS) and dermatological quality (DLQI). Geochemical composition was characterized using published analytical data (H₂S: 14.0 ± 1.2 mg/L; SO₄²⁻: 1475 ± 5 mg/L; Ca²⁺: 561 ± 39 mg/L). Given that all participants received water from the same stable source, we employed literature-based exploratory analysis combining mechanistic plausibility, clinical evidence at comparable concentrations, and cross-study comparisons to identify which mineral components warrant priority investigation as potential therapeutic mediators. Results: Both groups showed significant improvements in SF-36 PCS (overall Δ=11.7 points, 95% CI: 9.8–13.6, d=0.67) and WHOQOL-BREF physical domain (Δ=18.4 points, 95% CI: 15.2–21.6, d=0.85). Sustained exposure demonstrated superior outcomes compared to acute exposure (mean difference: 4.4 points, 95% CI: 2.1–6.7, p < 0.001). Exploratory assessment identified hydrogen sulfide as the mineral component with strongest theoretical basis for observed therapeutic effects (priority score: 10/10), based on well-established anti-inflammatory mechanisms, therapeutic concentration range (Saturnia: 14.0 mg/L; literature therapeutic range: 5–50 mg/L), and suggestive cross-study patterns linking higher H₂S concentrations with larger effect sizes. No serious adverse events occurred. Conclusions: Exploratory mechanistic analysis identified hydrogen sulfide as the most biologically plausible active component and highest-priority target for future controlled studies. However, our single-source design cannot establish causality or component-specific effects. Prospective trials comparing thermal waters with systematically varied H₂S concentrations are needed to validate this hypothesis and establish optimal therapeutic parameters.