Iron dysregulation in chronic diseases: Mechanistic links between oxidative stress, inflammation, and ferroptosis: A narrative review

Iron is essential for cellular metabolism, oxygen transport, and redox homeostasis; however, disturbances in iron handling, rather than absolute iron excess alone, are increasingly recognized as contributors to tissue injury in chronic disease. Expansion of the labile iron pool promotes oxidative stress, mitochondrial dysfunction, inflammation, and ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, thereby linking iron dysregulation to multisystem pathology. This narrative review integrates experimental, clinical, and epidemiological evidence examining the role of iron dysregulation in colorectal cancer, metabolic dysfunction, cardiovascular, pulmonary, renal, hepatic, neurodegenerative, and reproductive disorders. Emphasis is placed on ferroptosis, whose biological effects vary according to tissue environment and disease type. In neoplastic conditions such as colorectal cancer, ferroptosis may represent a therapeutic vulnerability that can be exploited to induce tumor cell death. In contrast, in non-neoplastic chronic diseases, ferroptosis predominantly acts as a mediator of oxidative injury, inflammation, fibrosis, and progressive organ dysfunction. These observations support a systems-level model in which iron functions not as a uniformly toxic or protective factor, but as a selective amplifier of redox imbalance and tissue susceptibility. At the population level, current evidence highlights the complexity of defining safe iron exposure and the limitations of indiscriminate supplementation, particularly in iron-replete individuals. These findings support a shift from exposure-based interpretations of iron excess toward mechanism-based, tissue-specific, and risk-stratified approaches integrating biomarkers of iron metabolism, oxidative stress, and inflammation.