What hormone causes iron deficiency? An in-depth look at hepcidin

January 2, 2026 •

4 min read

Worldwide, iron deficiency is the most common nutritional deficiency, and at the core of its pathology is a powerful regulator: the hormone hepcidin. While low iron intake is a primary cause, surprisingly, high levels of this specific hormone can also cause iron deficiency by blocking the body's ability to utilize stored and dietary iron.

Quick Summary

The hormone hepcidin controls the body's iron supply by regulating absorption and release from stores. When hepcidin levels are inappropriately high due to inflammation or genetic factors, it can cause iron deficiency by trapping iron inside cells.

Key Points

Hepcidin is the master iron regulator: This liver-produced hormone controls the body's iron supply by regulating absorption and release from stores.
High hepcidin causes iron deficiency: Excess hepcidin blocks iron from being absorbed from the diet and prevents its release from cellular storage, leading to iron-restricted anemia.
Inflammation is a primary trigger: In inflammatory states, the body produces high levels of hepcidin to sequester iron from pathogens, often leading to anemia of chronic disease.
Hepcidin acts on ferroportin: The hormone works by binding to and causing the degradation of ferroportin, the only protein that exports iron out of cells.
Genetic defects can cause high hepcidin: A rare condition called Iron-Refractory Iron Deficiency Anemia (IRIDA) is caused by mutations that result in inappropriately high hepcidin levels, preventing iron absorption.
Therapies may target hepcidin: Understanding hepcidin's role allows for the development of new diagnostic tools and targeted therapies, such as hepcidin agonists or antagonists, for managing iron disorders.

The Master Regulator: Understanding Hepcidin's Function

Iron is an essential mineral vital for producing hemoglobin, which transports oxygen throughout the body. The management of iron is a finely tuned process controlled by the liver-produced peptide hormone, hepcidin. Hepcidin acts as the body’s master iron regulator, balancing iron absorption and release to prevent both deficiency and toxic overload. It accomplishes this by targeting a protein called ferroportin. Ferroportin is the only known iron exporter in vertebrates and is found on the surface of cells that handle iron, including intestinal cells (enterocytes), liver cells (hepatocytes), and iron-recycling macrophages. When hepcidin levels are high, it binds to ferroportin, causing the iron exporter to be internalized and degraded inside the cell. This action effectively locks iron away, limiting its entry into the bloodstream.

The Hepcidin-Ferroportin Axis: A Closer Look

Normal Regulation: In a healthy body, hepcidin levels are suppressed when iron stores are low or when there is an increased demand for red blood cell production (erythropoiesis). This allows ferroportin to remain on the cell surface, increasing dietary iron absorption and releasing stored iron into the plasma. Conversely, when iron is abundant, hepcidin production increases, reducing iron availability to prevent overload.
Dysfunctional Regulation: Problems arise when hepcidin levels are dysregulated, either remaining too high or too low for the body’s needs. Pathologically high hepcidin levels lead to iron-restrictive disorders, while pathologically low levels can cause iron overload conditions like hereditary hemochromatosis.

How Elevated Hepcidin Leads to Iron Deficiency

High hepcidin levels can cause functional iron deficiency by restricting the delivery of iron to the bone marrow for hemoglobin synthesis, even if there are ample iron stores within the body’s cells. This happens in several contexts:

Anemia of Inflammation (AI) or Chronic Disease (ACD): Inflammation and infection stimulate the liver to produce more hepcidin, largely driven by the cytokine interleukin-6 (IL-6). The body does this as a defense mechanism to sequester iron from pathogens that need it to thrive. However, this response can become chronic in long-term inflammatory conditions like autoimmune diseases, cancer, and chronic kidney disease, leading to a persistent block on iron release and restricted erythropoiesis.
Genetic Disorders: A rare, inherited disorder called Iron-Refractory Iron Deficiency Anemia (IRIDA) is caused by mutations in a gene called TMPRSS6. This gene normally suppresses hepcidin production, especially when iron is low. When TMPRSS6 is mutated, hepcidin is inappropriately high, causing severe microcytic, hypochromic anemia that does not respond to oral iron supplements because intestinal absorption is blocked.
Other Conditions: In very rare cases, tumors that autonomously produce hepcidin have been reported to cause severe anemia, which can be cured by surgical removal of the growth.

Comparing Anemia of Inflammation and True Iron Deficiency


Feature	Anemia of Inflammation (AI)	True Iron Deficiency Anemia (IDA)
Hepcidin Levels	High or inappropriately normal	Very low or undetectable
Ferritin Levels	Normal or elevated, as iron is trapped in stores	Low, indicating depleted iron stores
Transferrin Saturation	Low	Low
Cause	Inflammation and high hepcidin production limit iron availability	Insufficient iron in the body due to poor intake or blood loss
Response to Oral Iron	Poor response, as absorption is blocked	Responds well to treatment

The Delicate Balance: Factors That Suppress Hepcidin

Just as high hepcidin levels can cause iron deficiency, the body has mechanisms to lower hepcidin when more iron is needed. Several factors can suppress hepcidin production:

Low Iron Levels: The body's own iron stores provide a powerful negative feedback loop. When iron levels are low, hepcidin production is suppressed to maximize absorption and release of any available iron.
Erythropoietic Activity: The bone marrow’s demand for iron to produce red blood cells is a strong inhibitor of hepcidin. The hormone erythropoietin (EPO), which stimulates red blood cell production, also triggers the release of another hormone called erythroferrone (ERFE). ERFE suppresses hepcidin, freeing up iron for erythropoiesis.
Hypoxia: Low oxygen levels also trigger a decrease in hepcidin production. This frees up iron for hemoglobin production, improving oxygen transport.

Therapeutic Implications of Hepcidin Research

Understanding hepcidin’s role has opened up new avenues for diagnosing and treating iron disorders. Measuring hepcidin levels can help differentiate between anemia of inflammation and true iron deficiency, which is crucial for determining the correct treatment strategy. For example, in cases of anemia of inflammation, oral iron is often ineffective because high hepcidin levels prevent its absorption. In these instances, targeting the inflammation or using hepcidin antagonists could be more effective. Conversely, conditions like hereditary hemochromatosis are caused by low hepcidin, and therapies that increase hepcidin expression or mimic its action (agonists) are being explored to help regulate iron levels.

Conclusion: Hepcidin's Central Role in Iron Homeostasis

Hepcidin is the central regulatory hormone for systemic iron balance. While its primary function is to prevent iron overload, its pathological overproduction, particularly in inflammatory conditions and rare genetic disorders, is a direct cause of functional iron deficiency by blocking iron absorption and sequestration. Future diagnostic and therapeutic approaches for iron disorders will increasingly rely on understanding and manipulating the hepcidin-ferroportin axis to restore proper iron availability. Continued research is vital for developing effective treatments for the millions affected by these complex conditions. The discovery of hepcidin has fundamentally changed our understanding of iron metabolism and its associated diseases, paving the way for more targeted and personalized medicine.

For more detailed scientific information on hepcidin regulation, see this comprehensive review from the National Institutes of Health: PMC5227985.

Frequently Asked Questions

Hepcidin is a hormone primarily produced by the liver that controls the body's iron levels. It regulates how iron is absorbed from food and released from storage by binding to a protein called ferroportin, essentially blocking iron from entering the bloodstream.

When hepcidin levels are too high, it prevents dietary iron from being absorbed in the intestine and locks away stored iron within cells. This causes a functional iron deficiency, where the body cannot access the iron it needs, even if stores exist.

AI is an iron-restricted anemia caused by a chronic inflammatory state. The inflammation triggers the overproduction of hepcidin, which traps iron in macrophages and reduces its availability for red blood cell production.

Yes, in conditions like anemia of inflammation, the body’s iron stores (measured by ferritin) can be normal or high. However, high hepcidin levels prevent this stored iron from being released and utilized, leading to functional iron deficiency.

Doctors may look at a combination of tests. While both conditions can show low circulating iron, anemia of inflammation typically has normal or high ferritin (the storage protein), whereas true iron deficiency has low ferritin. Hepcidin levels can also be measured, although this is not a routine test.

Yes, Iron-Refractory Iron Deficiency Anemia (IRIDA) is a rare genetic disorder caused by mutations that lead to persistently high hepcidin levels. This blocks iron absorption and makes the anemia resistant to oral iron supplements.

In addition to low iron levels, hepcidin is suppressed by increased erythropoietic activity (red blood cell production, mediated by erythroferrone) and low oxygen levels (hypoxia).