Hydrogen sulfide (H2S) - therapeutic relevance in rehabilitation and balneotherapy Systematic literature review and meta-analysis based on the PRISMA paradigm

Background. An active molecule in sulfurous mineral - therapeutic waters and also in sapropelic mud is H2S, a hormetic gaseous molecule that can actively penetrate the skin. While high levels of H2S are extremely toxic, low levels are tolerated and have potential cytoprotective effects, with anti-inflammatory and antioxidant applications. Objective. This systematic review aims to rigorously select related articles and identify within their content the main possible uses of hydrogen sulfide from balneary sources and to explain its physiological mechanisms and therapeutic properties. Methods. To elaborate our systematic review, we have searched for relevant open access articles in 6 international databases: Cochrane , Elsevier , NCBI/PubMed , NCBI/PMC , PEDro , and ISI Web of Knowledge/Science , published from January 2016 until July 2021. The contextually quested keywords combinations,syntaxes used are specified on this page. The eligible articles were analyzed in detail regarding pathologies addressed by hydrogen sulfide. All articles with any design (reviews, randomized controlled trials, non-randomized controlled trials, case-control studies, cross-sectional studies), if eligible according to the above-mentioned selection methodology, containing in the title the selected combinations, were included in the analysis. Articles were excluded in the second phase if they did not reach the relevance criterion. Results. Our search identified, first, 291 articles. After eliminating the duplicates and non-ISI articles, remained 121 papers. In the second phase, we applied a PEDro selection filter, resulting in 108 articles that passed the relevance criterion and were included in this systematic review. Conclusions. H2S biology and medical relevance are not fully understood and used adequately for sanogenic or medical purposes. More research is needed to fully understand the mechanisms and importance of this therapeutic gase. The link between balneotherapy and medical rehabilitation regarding the usage of hydrogen sulfide emphasises the unity for this medical speciality