Hepcidin

What is hepcidin?

Hepcidin is a hormone that controls how your body uses iron, an important mineral your body needs. Iron is an essential building block of a protein called hemoglobin. Hemoglobin is the most important component of your red blood cells. Hemoglobin binds to oxygen, enabling your red blood cells to transport oxygen to tissues and organs throughout your body.

Iron is also a building block of myoglobin, a protein that provides oxygen to your muscles and heart.

Hepcidin is sometimes called the “master iron regulator” because it controls how much iron is available for your cells to perform essential processes, like making hemoglobin and red blood cells. Too little iron can lead to conditions like iron-deficiency anemia, where your body doesn’t make enough red blood cells. Too much iron can be toxic (poisonous) and even life-threatening.

Where is hepcidin found in my body?

Hepcidin gets made in your liver and secreted into your bloodstream.

What is the role of hepcidin?

As your body’s “master iron regulator,” hepcidin maintains iron homeostasis (balance) by helping control how your body uses its iron supply. You get iron from your diet, from foods like meat, nuts, green vegetables, etc. Unlike with most minerals, your body doesn’t have a standard process for removing unused iron. For example, your body eliminates excess sodium when you pee. In contrast, you lose small amounts of iron incidentally through blood loss and cell shedding.

Instead, your body stores iron until it’s needed. You have iron stores in your bone marrow, spleen and liver. About 70% of your body’s iron is in the hemoglobin that powers your red blood cells.

Hepcidin plays a crucial role in processes that allow your body to store iron, relocate it and reuse it. It regulates your iron so that your body’s cells have iron when needed, but not so much that you experience iron overload.

Hepcidin plays a role in:

• Regulating iron absorption: Iron absorption is when iron gets relocated from your small intestine to your bloodstream. Once iron is in your blood, it’s available for use in your body. Hepcidin controls how much iron gets absorbed in your bloodstream and how much remains in storage.
• Recycling the iron in macrophages: White blood cells called macrophages destroy old red blood cells to make way for your body’s new red blood cells. Your bone marrow makes new red blood cells approximately every 120 days. The macrophages capture iron from the hemoglobin in dying red blood cells during the destruction process. Hepcidin controls whether the iron remains stored in macrophages or if it gets released into your body.
• Releasing stored iron: Your body stores iron in liver cells (hepatocytes) and cells in your small intestine (enterocytes). Hepcidin controls whether iron remains in these cells or if it gets released for use.

How does hepcidin regulate iron absorption?

Hepcidin doesn’t regulate iron absorption by setting processes into motion. Instead, it prevents the processes that allow your body to absorb iron. Hepcidin acts on a protein called ferroportin. Ferroportin is your body’s iron exporter. Its job is to release iron from storage (from macrophages, hepatocytes and enterocytes) and move iron among your body’s cells. Ferroportin transports iron from your small intestine to your bloodstream so your body can use it.

Hepcidin binds to ferroportin, causing it to break down. When this happens, the iron that ferroportin would’ve moved to your bloodstream remains in storage.

Think of it this way:

• More hepcidin makes it harder for ferroportin to transport iron to your bloodstream, preventing iron absorption.
• Less hepcidin makes it easier for ferroportin to transport iron to your bloodstream, enabling iron absorption.

What factors influence how much hepcidin you have?

Your hepcidin levels depend on the signals your body sends. Various factors prompt your body to make more or less hepcidin.

Factors that control hepcidin levels in your body include:

• The total amount of iron in your body:Low iron levels signal your body to make less hepcidin, while high iron signals your body to produce more hepcidin.
• The production of red blood cells: Hepcidin levels decrease when your body needs more hemoglobin for red blood cell production. The decrease allows ferroportin to transport iron so new cells get made.
• Low oxygen levels (hypoxia):Hypoxia occurs when you don’t have enough oxygen in your tissues. Low oxygen signals your body to decrease hepcidin, freeing up ferroportin to release the iron needed to make hemoglobin, which helps transport oxygen via red blood cells.
• Inflammation in response to an injury or an infection:Hepcidin levels increase to prevent iron from being released into your body. Many harmful germs, like bacteria, use iron to thrive. The increase in hepcidin and the decrease in iron prevent these germs from accessing it.

What conditions are associated with abnormal hepcidin levels?

Too much hepcidin can lead to problems like iron deficiency, where your body doesn’t absorb enough iron. Too little hepcidin can cause iron overload, where your body absorbs too much.

Low hepcidin levels

Conditions associated with low hepcidin levels include:

• Iron-deficiency anemia: The most common type of anemia associated with low hepcidin. Hepcidin levels may be so low that they’re undetectable. The low levels reflect your body’s attempt to free up ferroportin so it can transport to your blood.
• Hereditary hemochromatosis: A genetic condition where cell mutations (errors) cause your liver to secrete too little hepcidin. As a result, your body absorbs too much iron. Most of the iron gets stored in your heart, liver and pancreas.
• Iron-loading anemias:A group of anemias that involve having too much iron instead of too little of it. Problems during red blood cell production cause too little hepcidin to get made. As a result, ferroportin exports too much iron.
• Hepatitis C: A liver infection caused by a virus (HCV). The virus suppresses your body’s ability to make hepcidin.
• Type 2 diabetes: Some studies have shown that people with Type 2 diabetes have decreased hepcidin levels, causing iron overload. Insulin, a standard diabetes treatment, is a potential cause.

High hepcidin levels

High hepcidin levels are associated with non-iron deficiency anemia. Non-iron deficiency anemia is a genetic condition that results in too much hepcidin. Anemias of inflammation, or anemia of chronic disease (ACD), also cause high hepcidin levels. With ACD, inflammation causes your body to release a protein called cytokine. This protein increases your hepcidin levels.

Conditions associated with ACD include:

• Chronic infections.
• Crohn’s disease.
• Cancer.
• Chronic kidney disease.

A note from Cleveland Clinic

Hepcidin plays an essential role in regulating how your body uses iron. By preventing iron export, hepcidin controls your body’s ability to make hemoglobin and red blood cells. In doing so, hepcidin plays an indirect role in determining the availability of oxygen throughout your entire body. Hepcidin prevents your body from absorbing too much iron. Too much iron can cause serious long-term complications.