Effects of drinking natural hydrogen sulfide (H 2 S) waters: a systematic review of in vivo animal studies.

Natural waters containing originally hydrogen sulfide (H2S) gas with an S2-level at least 1 mg/L are classified as "sulfur waters" or "hydrogen sulfide waters." This systematic review aimed to evaluate in vivo experimental studies investigating the biological effects of natural H2S water drinking in healthy or with disease model laboratory animals. A comprehensive databases search (PubMed, Embase, Web of Science, and Google Scholar) was performed and PICOS criteria were used to assess eligibility. All relevant studies were identified, screened, and examined. The qualitative assessment was performed with the help of the SYRCLE Risk of Bias tool. A total of nine articles were included. The extracted data showed that ad libitum drinking of such waters by rats and mice exert beneficial effects on animal model of diabetes and glucose metabolism plus protective effects on diabetic cardiac, testicular, and nephrological complications as shown biochemically, histopathologically, and bio-molecularly. Additional effects were gastroprotection, antioxidant effects and improvement of intestinal physiology in healthy animals, reduction in general signs of murine model of colitis in mice, improvement in lipid metabolism and lipid-lowering effect, and positive interference with the enterohepatic cycle of the bile acids and biliary functions in hyperlipidemic rats. This systematic review provides preliminary insights into the "biological truth" about natural H2S waters and partly elucidates their potential therapeutic role in balneology and health resort medicine. However, it should be kept in mind that the retrieved preclinical data cannot be directly extrapolated to humans. Additionally, most of the included studies were rated for unclear risk of bias across all categories except random allocation, reflecting very poor reporting of methodological details. These limitations should be addressed when planning similar studies in the future. The question "can traditional hydropinic therapies or drinking cures with H2S waters at natural sulfur water spas/health resorts or natural (even artificial) H2S water consumption at home exert similar effects in humans?" remains to be clarified by clinical trials.