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If melatonin at \u201cphysiological\u201d doses achievable through the intake of foods and beverages affects the development of liver diseases, it has not yet been clarified; therefore, we assessed whether supplementing \u201cdietary doses\u201d of melatonin affects the development of ALD in mice. Female 6\u20138-week-old C57BL\/6J mice were either pair-fed a liquid alcohol-enriched Lieber DeCarli diet or a control diet\u2009\u00b1\u2009melatonin (50 ng\/kg BW\/day) for 6 weeks. Markers of liver damage and intestinal barrier function were assessed. Moreover, the effects of melatonin on intestinal barrier function were assessed in an ex vivo model. Supplementing melatonin significantly attenuated the development of ALD being related to lower interleukin-6 protein, NOx, and 4-hydroxynonenal protein adduct levels in liver tissue. Impairments of intestinal barrier function in small intestine in ethanol-fed mice were significantly attenuated in ethanol-fed mice treated with melatonin being associated with lower NOx and higher phosphorylation levels of AMPK. In summary, our results suggest that an oral supplementation of \u201cdietary\u201d doses of melatonin may dampen the development of ALD in mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key messages<\/jats:title>\n            <jats:p>\n              <jats:list list-type=\"bullet\">\n                <jats:list-item>\n                  <jats:p>Supplementation of \u201cdietary\u201d doses of melatonin dampens the development of ALD.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Melatonin attenuates alcohol-induced small intestinal barrier dysfunction.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Protective role of melatonin is related to alterations of AMPK activity.<\/jats:p>\n                <\/jats:list-item>\n              <\/jats:list>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00109-025-02583-4","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T17:53:08Z","timestamp":1754589188000},"page":"1219-1230","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral supplementation of melatonin attenuates the onset of alcohol-related liver disease"],"prefix":"10.1007","volume":"103","author":[{"given":"Franziska","family":"Kromm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphaela","family":"Staltner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3356-4115","authenticated-orcid":false,"given":"Ina","family":"Bergheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"issue":"6","key":"2583_CR1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1093\/alcalc\/agz063","volume":"54","author":"N Pruckner","year":"2019","unstructured":"Pruckner N, Hinterbuchinger B, Fellinger M et al (2019) Alcohol-related mortality in the WHO European Region: sex-specific trends and predictions. 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