HEP

Regulates the body's iron absorption

Hepcidin

Hepcidin is a hormone produced in the liver that regulates how much iron the body absorbs from the intestine and releases from its iron stores. The marker is important for understanding iron deficiency, functional iron deficiency, inflammation, anemia, and some forms of iron overload.

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Contents

What is hepcidin?

Hepcidin is a hormone-like peptide hormone that is produced primarily in the liver and has a central role in the body's iron metabolism. The hormone functions as the body's most important regulator of how much iron is absorbed from the diet, how much iron is released from the body's stores and how much iron is available in the blood.

Iron is needed, among other things, to form hemoglobin, the oxygen-carrying protein in red blood cells. At the same time, too much free iron can be harmful to the body. Hepcidin therefore helps to keep iron balance within a reasonable range.

The marker has become particularly interesting in modern research and specialist medicine because hepcidin can help explain why some people develop iron deficiency, anemia or functional iron deficiency even though ferritin is sometimes normal or elevated.

The function of hepcidin in the body

Hepcidin regulates iron metabolism by affecting the protein ferroportin. Ferroportin functions as a transport channel that releases iron from cells into the bloodstream.

Ferroportin is found in, among other things:

  • intestinal cells, where iron is absorbed from the diet.
  • macrophages, which recycle iron from old red blood cells.
  • liver cells, where iron can be stored.

When hepcidin levels rise, hepcidin binds to ferroportin, which causes ferroportin to break down. This reduces the amount of iron that can be transported into the blood.

This leads to:

  • less iron being absorbed from the intestine.
  • less iron is released from the body's iron stores.
  • less iron becomes available to the bone marrow.
  • red blood cell production may be affected.

When hepcidin is low, ferroportin becomes more active, allowing more iron to be absorbed and released into the blood.

Why is hepcidin analyzed?

Analysis of hepcidin may be relevant in more advanced investigations of iron metabolism, especially when standard iron tests do not provide a clear picture. The test is primarily used in research and specialist care, but interest is increasing because the marker can provide information about why the body is not using iron in a normal way.

The analysis may be relevant in the following conditions:

  • difficult-to-interpret iron deficiency.
  • suspected functional iron deficiency.
  • anemia in chronic inflammation.
  • chronic kidney disease.
  • inflammatory bowel disease.
  • rheumatic or other chronic inflammatory disease.
  • iron overload or suspected hemochromatosis.
  • lack of effect of iron therapy.

Hepcidin can sometimes provide complementary information together with traditional tests such as Ferritin, iron, transferrin, transferrin saturation, HS-CRP and blood status.

Reference values ​​for hepcidin

There are currently no internationally standardized reference ranges for hepcidin. The concentration is affected by the analysis method, biological variations and the laboratory's calibration, which means that reference values ​​may differ between different laboratories.

In studies where hepcidin has been analyzed with standardized LC-MS/MS, healthy adults have approximately the following levels:

  • men: median approximately 4.7 nM (reference range <0.5–15.5 nM).
  • women: median approximately 3.8 nM (reference range <0.5–15.4 nM).
  • premenopausal women generally have lower levels than postmenopausal women.

Like many other hormones, Hepcidin also varies over the day and is affected by, among other things, the body's iron stores, inflammation, infection, kidney function and blood formation. The result should therefore always be interpreted together with ferritin, transferrin saturation, blood status and other clinical findings.

High levels of hepcidin

High levels of hepcidin mean that the body slows down iron absorption and retains iron in its stores. This can be a normal protective mechanism during infection or inflammation, but can also contribute to anemia if the condition becomes long-term.

High levels of hepcidin can be seen in:

  • inflammation.
  • infection.
  • chronic kidney disease.
  • autoimmune diseases.
  • inflammatory bowel disease.
  • cancer.
  • high iron stores.
  • certain forms of anemia in chronic disease.

With high hepcidin, the body may have stored iron, but the iron is not available to the bone marrow to a sufficient extent. This is often called functional iron deficiency or iron restriction.

Hepcidin and functional iron deficiency

Functional iron deficiency means that the body has iron in its stores, but that the iron cannot be used effectively. This differs from absolute iron deficiency, where the body's iron stores are actually depleted.

With functional iron deficiency, ferritin may be normal or elevated, while iron and transferrin saturation are low. A common cause is inflammation that drives up hepcidin.

This can lead to:

  • fatigue
  • reduced energy
  • anemia
  • impaired physical performance
  • poorer response to iron therapy via tablet

With high hepcidin activity, the absorption of iron from the intestine can be reduced, which sometimes means that oral iron therapy works less well.

Low levels of hepcidin

Low levels of hepcidin mean that the body increases the absorption of iron and releases more iron from its stores. This is often a normal reaction to iron deficiency or increased need for blood formation.

Low hepcidin can be seen in:

  • absolute iron deficiency
  • blood loss
  • heavy menstruation
  • pregnancy
  • increased red blood cell production
  • certain forms of hemochromatosis

In hereditary hemochromatosis, hepcidin may be insufficiently low in relation to the body's iron stores. This can lead to increased iron absorption and gradual storage of iron in organs such as the liver, heart, joints and pancreas.

Hepcidin and inflammation

Inflammation is one of the strongest factors that increases the production of hepcidin. During inflammation, signaling substances are released, especially interleukin-6, which stimulates the liver to produce more hepcidin.

This is part of the body's immune defense. By reducing the amount of available iron in the blood, the body tries to limit the availability of iron to bacteria and other microorganisms.

The problem arises when inflammation is prolonged. Then hepcidin can remain elevated for a long time, which can contribute to anemia in chronic disease.

Hepcidin and ferritin

Ferritin is one of the most common blood tests to assess the body's iron stores. A low ferritin often indicates iron deficiency. However, ferritin is also an acute phase protein and can rise during inflammation.

This means that a person may have:

  • normal or high ferritin.
  • low iron in the blood.
  • low transferrin saturation.
  • elevated CRP or other inflammatory activity.
  • high hepcidin.

In such cases, the iron deficiency may be functional rather than absolute. Hepcidin can then help to understand why iron is not available even though ferritin is not low.

Hepcidin and anemia

Hepcidin is closely linked to anemia, as iron is needed to form hemoglobin. When hepcidin is elevated, iron availability to the bone marrow decreases, which can impair the formation of red blood cells.

This is particularly relevant in:

  • anemia in chronic inflammation.
  • anemia in chronic kidney disease.
  • inflammatory bowel disease.
  • cancer-related anemia.
  • iron deficiency that does not respond to standard treatment.

Hepcidin can therefore be an important piece of the puzzle in cases of difficult-to-interpret anemia where ferritin, iron status and inflammation markers need to be assessed together.

How is hepcidin analyzed?

Hepcidin is analyzed via blood test, usually in serum or plasma. The analysis is not yet a routine test in broad primary care and is used primarily in research, specialist medicine and for more complex questions about iron metabolism.

The interpretation is affected by several factors, including:

  • iron stores.
  • inflammation.
  • kidney function.
  • blood loss.
  • erythropoiesis, i.e. the production of red blood cells.
  • analysis method.
  • time of sampling.

Since analytical methods and reference intervals may vary between laboratories, the result should always be interpreted together with other samples and the clinical picture.

Hepcidin in healthcare

Despite hepcidin being a central biomarker for iron metabolism, its use in routine healthcare is still relatively limited. The most common reasons are that the analysis is not as accessible as traditional iron tests and that there is still variation between different analytical methods.

In practice, the following tests are therefore often used first:

  • hemoglobin
  • MCV and MCH
  • ferritin
  • iron
  • transferrin
  • transferrin saturation
  • CRP
  • creatinine and eGFR in cases of suspected kidney damage

Hepcidin can be particularly valuable when these tests are not sufficient to distinguish between absolute iron deficiency, functional iron deficiency and inflammation-driven anemia.

Hepcidin and iron therapy

Hepcidin can also be important for how the body responds to iron therapy. If hepcidin is high, the absorption of iron from the intestine decreases, which can make iron tablets less effective.

In absolute iron deficiency, however, hepcidin is often low, which makes it easier for the body to absorb iron from the diet or supplements.

This is one of the reasons why iron deficiency treatment needs to be adapted to the underlying cause. The same ferritin value can have different meanings depending on whether there is inflammation, kidney disease or other chronic disease at the same time.