Effects of drinking natural hydrogen sulfide (H2S) waters: a systematic review of in vivo animal studies

  • Müfit Zeki KaragülleEmail author
  • Mine Karagülle
Special Issue: Balneology


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.


Sulfur waters Balneology Hydropinic therapy Drinking cure Animal studies Hydrogen sulfide 


  1. Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16:1066–1071CrossRefGoogle Scholar
  2. Ahmed HH, Taha FM, Omar HS, Elwi HM, Abdelnasser M (2019) Hydrogen sulfide modulates SIRT1 and suppresses oxidative stress in diabetic nephropathy. Mol Cell Biochem 457:1–9CrossRefGoogle Scholar
  3. Baschini MT, Pettinari GR, Vallés JM, Aguzzi C, Cerezo P, López-Galindo A, Setti M, Viseras C (2010) Suitability of natural sulphur-rich muds from Copahue (Argentina) for use as semisolid health care products. Applied Clay Science 49:205–212CrossRefGoogle Scholar
  4. Bełtowski J (2015) Hydrogen sulfide in pharmacology and medicine--an update. Pharmacol Rep 67:647–658CrossRefGoogle Scholar
  5. Benedetti S, Benvenuti F, Nappi G, Fortunati NA, Marino L, Aureli T, De Luca S, Pagliarani S, Canestrari F (2009) Antioxidative effects of sulfurous mineral water: protection against lipid and protein oxidation. Eur J Clin Nutr 63:106–112CrossRefGoogle Scholar
  6. Benedetti S, Pagliari S, Benvenuti F, Marini D, Galli T, Oliva F, Lazzari P, Canestrari F (2007) Antioxidative effects of sulphurous water from Macerata Feltria Thermal resort in patients with osteoarthritis. Progress in Nutrition 9:46–52Google Scholar
  7. Bertolo R, Hirata R, Fernandes A (2007) Hidrogeoquímica das águas mine - rais envasadas do Brasil. Rev Bras Geociênc 37:515–529CrossRefGoogle Scholar
  8. Bhatia M (2015) H2S and inflammation: an overview. Handb Exp Pharmacol 230:165–180CrossRefGoogle Scholar
  9. Bothe G, Coh A, Auinger A (2017) Efficacy and safety of a natural mineral water rich in magnesium and sulphate for bowel function: a double-blind, randomized, placebo-controlled study. Eur J Nutr 56:491–499CrossRefGoogle Scholar
  10. Cantalamessa F, Nasutti C (2003) Hypocholesterolemic activity of calcic and magnesic-sulphate-sulphurous spring mineral water in rat. Nutr Res 23:775–789CrossRefGoogle Scholar
  11. Carbajo JM, Maraver F (2017) Sulphurous mineral waters: new applications for health. Evid Based Complement Alternat Med 2017:8034084CrossRefGoogle Scholar
  12. Carbajo JM, Ubogui J, Vela L, Maraver F (2018) Sulphurous minerals waters and psoriasis. Medicina Naturista 12:58–602Google Scholar
  13. Carubbi C, Masselli E, Calabrò E et al (2019) Sulphurous thermal water inhalation impacts respiratory metabolic parameters in heavy smokers. Int J Biometeorol Google Scholar
  14. Contoli M, Gnesini G, Forini G, Marku B, Pauletti A, Padovani A, Casolari P, Taurino L, Ferraro A, Chicca M, Ciaccia A, Papi A, Pinamonti S (2013) Reducing agents decrease the oxidative burst and improve clinical outcomes in COPD patients: a randomized controlled trial on the effects of sulphurous thermal water inhalation. Sci World J 2013:927835CrossRefGoogle Scholar
  15. Coruzzi G, Adami M, Pozzoli C, Solenghi E, Grandi D (2010) Functional and histologic assessment of rat gastric mucosa after chronic treatment with sulphurous thermal water. Pharmacology 85:146–152CrossRefGoogle Scholar
  16. Costantino M, Filippelli A, Giampaolo C, Tiano L, Carlucci DM, Coiro V, Rastrelli L (2012) Hypoglycemic and antioxidant activities of sulphureous mineral water. PharmacologyOnLine 1:220–226Google Scholar
  17. Costantino M, Giuberti G, Caraglia M, Lombardi A, Misso G, Abbruzzese A, Ciani F, Lampa E (2009) Possible antioxidant role of SPA therapy with chlorine-sulphur-bicarbonate mineral water. Amino Acids 36:161–165CrossRefGoogle Scholar
  18. Costantino M, Lampa E, Nappi G (2006) Effectiveness of sulphur spa therapy with politzer in the treatment of rhinogenic deafness. Acta Otorhinolaryngol Ital 26:7–13Google Scholar
  19. Costantino M, Marongiu MG, Iannotti S, Filippelli A (2015) Sulphurous mud-balneotherapy: an possible strategy for the plaque psoriasis. Indian Journal of Research 4.
  20. Costantino M, Nappi G, Contaldi E, Lampa E (2005) Effectiveness of sulphur spa therapy in psoriasis: clinical-experimental study. Med Clin Term 18:127–137Google Scholar
  21. Ekmekcioglu C, Strauss-Blasche G, Holzer F, Marktl W (2002) Effect of sulfur baths on antioxidative defense systems, peroxide concentrations and lipid levels in patients with degenerative osteoarthritis. Forsch Komplementarmed Klass Naturheilkd 9:216–220Google Scholar
  22. El-Seweidy MM, Sadik NA, Shaker OG (2011) Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats. Arch Biochem Biophys 506:48–57CrossRefGoogle Scholar
  23. Fraioli A, Menunni G, Petraccia L, Fontana M, Nocchi S, Grassi M (2010) Sulphate-bicarbonate mineral waters in the treatment of biliary and digestive tract diseases. Clin Ter 161:163–168Google Scholar
  24. Gálvez Galve JJ, Peiró PS, Lucas MO, Torres AH, Gil ES, Pérez MB (2012) Quality of life and assessment after local application of sulphurous water in the home environment in patients with psoriasis vulgaris: a randomized placebo-controlled pilot study. Eur J Integr Med 4:e213–e218CrossRefGoogle Scholar
  25. Gutenbrunner C, Bender T, Cantista P, Karagülle Z (2010) A proposal for a worldwide definition of health resort medicine, balneology, medical hydrology and climatology. Int J Biometeorol 54:495–507CrossRefGoogle Scholar
  26. Hirata I, Naito Y, Takagi T, Mizushima K, Suzuki T, Omatsu T, Handa O, Ichikawa H, Ueda H, Yoshikawa T (2011) Endogenous hydrogen sulfide is an anti-inflammatory molecule in dextran sodium sulfate-induced colitis in mice. Dig Dis Scic 56:1379–1386CrossRefGoogle Scholar
  27. Honorio-França AC, De Oliveira FC, França EL, Ferrari CK (2015) Antioxidant and hypoglycemic effects of sulphurous water on alloxan-induced diabetic rats: a preliminary study. Nutr Clín Diet Hosp 35:50–55Google Scholar
  28. Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14(1):43CrossRefGoogle Scholar
  29. Huang A, Seité S, Adar T (2018) The use of balneotherapy in dermatology. Clin Dermatol 36:363–368CrossRefGoogle Scholar
  30. Jokić A, Sremcević N, Karagülle Z, Pekmezović T, Davidović V (2010) Oxidative stress, hemoglobin content, superoxide dismutase and catalase activity influenced by sulphur baths and mud packs in patients with osteoarthritis. Vojnosanit Pregl. 67:573–578CrossRefGoogle Scholar
  31. Karagülle MZ, Tütüncü ZN, Aslan O, Basak E, Mutlu A (1996) Effects of thermal sulphur bath cure on adjuvant arthritic rats. Phys Rehab Kur Med 6:53–57CrossRefGoogle Scholar
  32. Karagülle Z, Dönmez A (2002) Balneotherapy for fibromyalgia at the Dead Sea. Rheumatol Int 21:210–211CrossRefGoogle Scholar
  33. Leibetseder V, Strauss-Blasche G, Holzer F, Marktl W, Ekmekcioglu C (2004) Improving homocysteine levels through balneotherapy: effects of sulphur baths. Clin Chim Acta 343:105–111CrossRefGoogle Scholar
  34. Lewis RJ, Copley GB (2015) Chronic low-level hydrogen sulfide exposure and potential effects on human health: a review of the epidemiological evidence. Crit Rev Toxicol 45:93–123CrossRefGoogle Scholar
  35. Mennuni G, Petraccia L, Fontana M, Nocchi S, Stortini E, Romoli M, Esposito E, Priori F, Grassi M, Geraci A, Serio A, Fraioli A (2014) The therapeutic activity of sulphate-bicarbonate-calcium-magnesiac mineral water in the functional disorders of the biliary tract. Clin Ter 165:e346–e352Google Scholar
  36. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Plos Medicine 6(7):e1000097CrossRefGoogle Scholar
  37. Motta JP, Flannigan KL, Agbor TA, Beatty JK, Blackler RW, Workentine ML, Da Silva GJ, Wang R, Buret AG, Wallace JL (2015) Hydrogen sulfide protects from colitis and restores intestinal microbiota biofilm and mucus production. Inflamm Bowel Dis 21:1006–1017CrossRefGoogle Scholar
  38. Nasuti C, Gabbianelli R, Cantalamessa F, Falcioni G (2005) Erythrocyte plasma membrane perturbations in rats fed a cholesterol-rich diet: effect of drinking sulphurous mineral water. Ann Nutr Metab 49:9–15CrossRefGoogle Scholar
  39. Nunes S, Tamura BM (2012) A historical review of mineral water. Surg Cosmet Dermatol 4:252–258Google Scholar
  40. Ottaviano G, Marioni G, Staffieri C, Giacomelli L, Marchese-Ragona R, Bertolin A, Staffieri A (2011) Effects of sulfurous, salty, bromic, iodic thermal water nasal irrigations in nonallergic chronic rhinosinusitis: a prospective, randomized, double-blind, clinical, and cytological study. Am J Otolaryngol 32:235–239CrossRefGoogle Scholar
  41. Pagliarani S, Benedetti S, Fortunati NA, Nappi G, Calcaterra P, Mazzone D, De Luca S, Benvenuti F, Francogli S, Canestrari F (2005) Antioxidant prophylactic role of sulphurous water by thermal centre of Saturnia. [article in Italian]. Med Clin Term 58:139–148Google Scholar
  42. Pan LL, Qin M, Liu XH, Zhu YZ (2017) The role of hydrogen sulfide on cardiovascular homeostasis: an overview with update on immunomodulation. Front Pharmacol 8:686. CrossRefGoogle Scholar
  43. Pollock A, Berge E (2018) How to do a systematic review. Int J Stroke 13:138–156CrossRefGoogle Scholar
  44. Pozsgai G, Benkó R, Barthó L, Horváth K, Pintér E (2015) Thermal spring water drinking attenuates dextran-sulfate-sodium-induced colitis in mice. Inflammopharmacology 23:57–64CrossRefGoogle Scholar
  45. Qin M, Long F, Wu W, Yang D, Huang M, Xiao C, Chen X, Liu X, Zhu YZ (2019) Hydrogen sulfide protects against DSS-induced colitis by inhibiting NLRP3 inflammasome. Free Radic Biol Med 137:99–109CrossRefGoogle Scholar
  46. Sadik NA, El-Seweidy MM, Shaker OG (2011) The antiapoptotic effects of sulphurous mineral water and sodium hydrosulphide on diabetic rat testes. Cell Physiol Biochem 28:887–898CrossRefGoogle Scholar
  47. Safar MM, Abdelsalam RM (2015) H2S donors attenuate diabetic nephropathy in rats: Modulation of oxidant status and polyol pathway. Pharmacol Rep 67:17–23CrossRefGoogle Scholar
  48. Scheidleder B, Holzer F, Marktl W (2000) Effect of sulfur administration on lipid levels, antioxidant status and peroxide concentration in health resort patient. Forsch Komplementarmed Klass Naturheilkd 7:75–78Google Scholar
  49. Sukenik S, Buskila D, Neumann L, Kleiner-Baumgarten A, Zimlichman S, Horowitz J (1990) Sulphur bath and mud pack treatment for rheumatoid arthritis at the Dead Sea area. Ann Rheum Dis 49:99–102CrossRefGoogle Scholar
  50. Szabó C (2007) Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 6:917–935CrossRefGoogle Scholar
  51. Szabo C (2012) Roles of hydrogen sulfide in the pathogenesis of diabetes mellitus and its complications. Antioxid Redox Signal 17:68–80CrossRefGoogle Scholar
  52. Wallace JL, Blackler RW, Chan MV, Da Silva GJ, Elsheikh W, Flannigan KL, Gamaniek I, Manko A, Wang L, Motta JP, Buret AG (2015) Anti-inflammatory and cytoprotective actions of hydrogen sulfide: translation to therapeutics. Antioxid Redox Signal 22:398–410CrossRefGoogle Scholar
  53. Wallace JL, Ianaro A, de Nucci G (2017) Gaseous mediators in gastrointestinal mucosal defense and injury. Dig Dis Sci 62:2223–2223CrossRefGoogle Scholar
  54. Wang J, Wang W, Li S, Han Y, Zhang P, Meng G, Xiao Y, Xie L, Wang X, Sha J, Chen Q, Moore PK, Wang R, Xiang W, Ji Y (2018) Hydrogen sulfide ss a potential target in preventing spermatogenic failure and testicular dysfunction. Antioxid Redox Signal 28:1447–1462CrossRefGoogle Scholar
  55. Wang R (2012) Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev 92:791–896CrossRefGoogle Scholar
  56. Watzlawick R, Antonic A, Sena ES, Kopp MA, Rind J, Dirnagl U, Macleod M, Howells DW, Schwab JM (2019) Outcome heterogeneity and bias in acute experimental spinal cord injury: a meta-analysis. Neurology 93:e40–e51CrossRefGoogle Scholar
  57. Wu D, Hu Q, Zhu Y (2016) Therapeutic application of hydrogen sulfide donors: the potential and challenges. Front Med 10:18–27CrossRefGoogle Scholar
  58. Zhang L, Wang Y, Li Y, Li L, Xu S, Feng X, Liu S (2018) Hydrogen sulfide (H2S)-releasing compounds: therapeutic potential in cardiovascular diseases. Front Pharmacol 9:1066. CrossRefGoogle Scholar
  59. Zheng D, Dong S, Li T, Yang F, Yu X, Wu J, Zhong X, Zhao Y, Wang L, Xu C, Lu F, Zhang W (2015) Exogenous hydrogen sulfide attenuates cardiac fibrosis through reactive oxygen species signal pathways in experimental diabetes mellitus models. Cell Physiol Biochem 36:917–929CrossRefGoogle Scholar

Copyright information

© ISB 2019

Authors and Affiliations

  1. 1.Department of Medical Ecology and HydroclimatologyIstanbul Faculty of Medicine, Istanbul UniversityIstanbulTurkey

Personalised recommendations