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.