Obesity and Iron Metabolism: Mechanisms, Status Assessment, and Clinical Implications

Obesity reshapes systemic iron handling, yet the resulting iron phenotype is frequently misclassified at the bedside and in population studies. This review examines how excess adiposity disturbs iron metabolism and complicates iron-status assessment, with balanced attention to biology and measurement problems across adults and children.

Adipose tissue is an endocrine, inflammatory, and iron-handling organ. In obesity, interleukin-6 drives hepatic hepcidin through JAK/STAT3 signaling, while leptin, adipose hypoxia, and adipose hepcidin expression may contribute additional signals. Hepcidin degrades ferroportin, reducing duodenal iron export and limiting macrophage iron release, producing hypoferremia and iron-restricted erythropoiesis despite normal or elevated ferritin. We and others have shown that women with obesity may have higher hepcidin, ferritin, and inflammatory markers but lower serum iron. Stable-isotope and intervention studies suggest weight loss reduces inflammation and hepcidin and improves iron absorption, whereas the World Health Organization and Biomarkers of Nutrition for Development frameworks recommend interpreting ferritin relative to inflammation. Iron status in obesity spans a continuum from absolute or functional iron deficiency to sufficiency and, in some individuals, hyperferritinemia with possible dysmetabolic iron overload. Reliable assessment requires a multi-marker strategy: ferritin interpreted alongside an inflammation marker such as C-reactive protein and supported by transferrin saturation, soluble transferrin receptor, reticulocyte hemoglobin, or other context-appropriate indices. Management should address reversible inflammation through weight loss and metabolic risk reduction, use oral or intravenous iron according to the likelihood of true deficiency and hepcidin-mediated oral refractoriness, and avoid reflexive phlebotomy for dysmetabolic hyperferritinemia without confirmed overload.