{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:41:58Z","timestamp":1792806118188,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Precision Medicine of the University of Campania \u201cLuigi Vanvitelli\u201d","award":["390-01583577-30059"],"award-info":[{"award-number":["390-01583577-30059"]}],"id":[{"id":"https:\/\/ror.org\/02kqnpp86","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Fonte Essenziale\u00ae, a mineral water rich in bicarbonate, sulfate, calcium, and magnesium, has shown potential in modulating the gut\u2013liver axis and microbiota in hepatic steatosis. However, its long-term effects on intestinal permeability (IP), systemic inflammation (SI), and oxidative stress\u2014key factors in Metabolic dysfunction-associated steatotic liver disease (MASLD)\u2014remain unexplored. Methods: Eighty-seven MASLD patients were randomized into two groups: group A received Fonte Essenziale\u00ae (400 mL\/day, fasting) plus a controlled nutritional regimen for 12 months, followed by a 6-month water washout; group B followed only the controlled nutritional regimen. IP markers, SI (IL-1\u03b2, IL-6, TNF-\u03b1), oxidative stress (dROMs\/BAP), and clinical data (including Controlled Attenuation Parameter\u2014CAP) were assessed at baseline (T0), 12 months (T12), and post-washout (T18). Baseline increased IP (in-IP) was defined by fecal zonulin &gt; 110 ng\/mL and serum LBPp &gt; 10 \u00b5g\/mL; improvement (im-IP) required normalization of both. A \u226530% CAP reduction indicated steatosis improvement. Results: Thirty-eight patients in group A and thirty-nine in group B completed the study. At T12, group A showed significant reductions in fecal zonulin (p: 0.0163) and serum LBPp (p &lt; 0.0001), with increased occludin and claudin 1 (all p &lt; 0.0001). Im-IP prevalence was higher in group A (p: 0.0037). Group A also showed significant reductions in IL-1\u03b2, TNF-\u03b1, IL-6, LPS, and dROM\/BAP (all p &lt; 0.05), especially among those with im-IP. CAP, insulin, and HDL levels improved significantly (all p &lt; 0.0001). Multivariate analysis confirmed water intake (aOR: 2.185, p: 0.001) and im-IP achievement (aHR: 1.267, p: 0.021) as predictors of steatosis improvement. Benefits persisted at T18. Conclusions: Prolonged Fonte Essenziale\u00ae intake improved hepatic steatosis and MASLD outcomes by modulating IP, SI, and oxidative stress. This trial has been registered on clinicaltrials.gov (NCT07211113).<\/jats:p>","DOI":"10.3390\/nu17213452","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:00:33Z","timestamp":1762178433000},"page":"3452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Beneficial Effects of Long-Lasting Bicarbonate\u2013Sulfate\u2013Calcium\u2013Magnesium Water Intake on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Related Outcomes via Impacting Intestinal Permeability (IP), IP-Related Systemic Inflammation, and Oxidative Stress"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4153-815X","authenticated-orcid":false,"given":"Marcello","family":"Dallio","sequence":"first","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-9019","authenticated-orcid":false,"given":"Mario","family":"Romeo","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0519-3049","authenticated-orcid":false,"given":"Fiammetta","family":"Di Nardo","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Senese","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5428-4407","authenticated-orcid":false,"given":"Alessia","family":"Silvestrin","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annachiara","family":"Coppola","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2392-3539","authenticated-orcid":false,"given":"Carmine","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Vaia","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5473-3440","authenticated-orcid":false,"given":"Claudio","family":"Basile","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia De","family":"Gregorio","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-0793","authenticated-orcid":false,"given":"Alessandro","family":"Federico","sequence":"additional","affiliation":[{"name":"Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Palma, R., Pronio, A., Romeo, M., Scognamiglio, F., Ventriglia, L., Ormando, V.M., Lamazza, A., Pontone, S., Federico, A., and Dallio, M. 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