Mercola J. Fatty liver reexamined choline and mitochondrial toxin amelioration. World J Biol Chem 2025; 16(4): 111831 [DOI: 10.4331/wjbc.v16.i4.111831]
Corresponding Author of This Article
Joseph Mercola, Researcher, Independent Researcher, Midwestern University, 555 31 Street, Downers Grove, IL 60515, United States. drm@mercola.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Biol Chem. Dec 5, 2025; 16(4): 111831 Published online Dec 5, 2025. doi: 10.4331/wjbc.v16.i4.111831
Fatty liver reexamined choline and mitochondrial toxin amelioration
Joseph Mercola
Joseph Mercola, Independent Researcher, Midwestern University, Downers Grove, IL 60515, United States
Author contributions: Mercola J was the sole author responsible for study conception and design, data acquisition and interpretation, manuscript preparation and revision, final approval of the version to be published, and agrees to be accountable for the integrity of the work in all respects.
Conflict-of-interest statement: I have no conflicts of interests.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph Mercola, Researcher, Independent Researcher, Midwestern University, 555 31 Street, Downers Grove, IL 60515, United States. drm@mercola.com
Received: July 10, 2025 Revised: July 22, 2025 Accepted: October 27, 2025 Published online: December 5, 2025 Processing time: 147 Days and 12.4 Hours
Abstract
Choline supports phospholipid synthesis, membrane integrity, neurotransmission, verylowdensity lipoprotein export, and one-carbon/epigenetic pathways, yet most United States adults fall short of adequate intake. Fatty liver is now viewed as a mitochondrial-centric metabolic–inflammatory disorder; ethanol and excess linoleic acid (LA) can magnify bioenergetic stress when choline is insufficient to sustain phosphatidylcholine/phosphatidylethanolamine. This narrative review examines whether optimized choline delivery, alongside reduced exposure to mitochondrial toxicants, offers a rational therapeutic approach. Low choline intake associates with higher liver fat and aminotransferases. In rodents, choline deficiency combined with ethanol or LA lowers mitochondrial membrane potential, limits β-oxidation, and promotes steatosis and inflammation. Advanced formulations-especially citicoline-demonstrate favorable absorption and tissue choline delivery and may lessen trimethylamine-N-oxide formation versus free choline salts. Early, small human studies suggest that choline repletion, together with curtailed ethanol or dietary LA, can reduce intrahepatic triglyceride content and improve insulin sensitivity, though large randomized trials are lacking. Framing fatty liver as nutrition-modifiable mitochondrial toxicosis highlights correctable choline insufficiency when the liver is burdened by ethanol or excess LA. A dual strategy—using higher-bioavailability, gutmicrobial trimethylamineNoxide-sparing choline forms and mitigating mitochondrial toxicants-targets core bioenergetic defects, may reverse early steatosis, and warrants testing in adequately powered clinical trials.
Core Tip: This review recasts fatty liver disease as a reversible mitochondrial toxicosis driven by linoleic acid (LA) and ethanol when choline intake is inadequate. It collates pre-clinical and pilot clinical evidence showing that bioavailable, gutmicrobial trimethylamineNoxide-sparing choline carriers (citicoline, αglycerophosphocholine), together with LA restriction or alcohol abstinence, restore phosphatidylcholine/phosphatidylethanolamine balance, revive hepatic respiration and shrink intrahepatic fat. This dual nutrition-first approach targets the root bioenergetic defect, offering a low-risk route to halt steatosis progression and warrants large, randomized trials.
