Hydrogen Sulfide Delivery in Sulfurous Thermal Waters: Saturnia as a Translational Model for Gasotransmitter Pharmacology—A Narrative Review
Elisabetta Ferrara, Manela Scaramuzzino, Davide Ciaramellano, Luigi Brunetti, Giuseppe Balice, Giovanna Murmura, Bruna SinjariABSTRACT
Background
Hydrogen sulfide (H2S) is an endogenous gasotransmitter regulating redox balance, inflammation, and vascular tone, but reproducing the spatial and kinetic features of endogenous production remains challenging. We examine sulfurous thermal waters as natural contexts of sustained H2S exposure, using the Saturnia springs (Tuscany, Italy) as a representative natural analog to discuss geochemical determinants of sulfide stability, the bioglea microbial interface, and the clinical evidence base.
Methods
We conducted a structured, non‐systematic literature search of PubMed, Scopus, and Web of Science (inception to March 2026) using predefined sulfide‐, balneology‐, and Saturnia‐related terms. Experimental, observational, geochemical, and review sources were narratively synthesized and critically appraised; no meta‐analysis or formal quality scoring was performed, consistent with the hypothesis‐generating scope.
Results
Saturnia waters show elevated, relatively stable sulfide (≈14 mg/L; historical range ≈13–20 mg/L) within a buffered carbonate matrix. At pH ~6.85, a transparent Henderson–Hasselbalch calculation indicates that roughly 45%–55% of total dissolved sulfide is present as undissociated molecular H 2 S, depending on temperature and ionic strength. Controlled hydropinotherapy studies and sulfurous insufflation protocols suggest measurable effects on surrogate outcomes related to oxidative stress and to auditory and respiratory function, but the literature is limited by small sample sizes, heterogeneous exposure modalities, and a scarcity of trials with standardized clinical endpoints.
Conclusions
Rather than a validated translational model, Saturnia offers an informative, hypothesis‐generating natural analog for sustained H2S exposure in complex aqueous matrices, from which generalizable design principles and translational priorities—including route‐specific pharmacokinetics and standardized exposure reporting—can be abstracted for gasotransmitter delivery.