{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:55:24Z","timestamp":1791489324111,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alcoholic fatty liver disease (AFLD), a prevalent yet reversible stage of alcoholic liver pathology, is often associated with folate deficiency. This study investigated the association between folate status and AFLD risk and explored the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from NHANES 2011\u20132020 (<jats:italic>n<\/jats:italic>\u202f=\u202f10,452; 259 with AFLD) were analyzed. Associations between dietary folate equivalent (DFE), serum folate, 5-methyltetrahydrofolate (5-MTHF), red blood cell (RBC) folate, and AFLD were evaluated using multivariable logistic regression, adjusting for demographic and clinical variables. In parallel, ethanol-fed C57BL\/6J mice, with or without folic acid supplementation, and L02 hepatocyte models were used to assess biochemical markers, hepatic histology, and lipogenesis-related protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher serum folate levels were significantly associated with reduced AFLD risk across all adjusted models (Model 3 Q4 vs. Q1, OR\u202f=\u202f0.35, 95% CI: 0.22\u20130.54). Serum 5-MTHF levels were inversely associated with the severity of steatosis (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.01). In contrast, elevated RBC folate was a risk factor in specific subgroups. Folic acid intervention <jats:italic>in vivo\/in vitro<\/jats:italic> reduced ethanol-induced increases in hepatic enzymes, TG, hepatic lipid accumulation, and expression of lipogenic proteins (SREBP-1c, FASN, ACC1; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05), but not SCD-1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serum folate and 5-MTHF are protective factors against AFLD. Furthermore, folic acid can ameliorate hepatic steatosis by inhibiting SREBP-1c-mediated lipogenesis, highlighting its potential in AFLD prevention and therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1668430","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T13:59:03Z","timestamp":1758722343000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Folic acid supplementation ameliorates alcohol-induced hepatic steatosis by inhibiting SREBP-1c-mediated lipogenesis"],"prefix":"10.3389","volume":"12","author":[{"given":"Chen","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlei","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huichao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1001\/jama.2021.7683","article-title":"Diagnosis and treatment of alcohol-associated liver disease: a 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