Iron Metabolism and Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Review on Implications of Iron Supplementation in Disease Progression and Management

Abstract

Iron is an essential micronutrient involved in key biological functions such as oxygen transport, energy production, and cellular metabolism. The liver plays a central role in maintaining iron balance by regulating its absorption and storage through the hormone hepcidin. However, consuming high doses of iron—either through diet or supplements—can cause iron to build up in the liver. This overload triggers oxidative stress, damages fats in cells (lipid peroxidation), and promotes chronic inflammation. Research shows that when iron metabolism is disrupted, particularly with a high-fat diet, it can contribute to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into a more severe form called metabolic dysfunction-associated steatohepatitis (MASH). Animal studies reveal that excess iron in liver immune cells like Kupffer cells and macrophages increases inflammation, worsens metabolic problems, and accelerates fibrosis, raising the risk of cirrhosis and liver cancer. Population studies also suggest that high iron intake can damage the liver, particularly in individuals with genetic tendencies toward abnormal iron handling. Despite this growing body of evidence, many overlook the effects of excessive iron intake on liver health. This review discusses how excess supplemental iron harms the liver and emphasizes the need for more research to determine safe intake levels and explore treatments to reduce iron-related liver injury.