Iron is an element required for the survival of nearly all organisms. In the human body, it plays a part in processes ranging from oxygen transport to energy production. However, iron’s chemical reactivity also makes it potentially toxic. Unchecked, iron can promote the formation of compounds that damage cellular structures like DNA, proteins, and lipids. To manage this, the body has developed a complex system for regulating iron levels, a process known as iron homeostasis.
This internal balancing act ensures that tissues have enough iron to function without accumulating a harmful surplus. It involves precise control over how iron is absorbed, distributed throughout the body, and stored for future use.
Iron’s Roles in the Body
Iron’s most recognized function is in oxygen transport. It is a central component of hemoglobin, the protein in red blood cells that picks up oxygen in the lungs and delivers it to the rest of the body. A similar protein, myoglobin, uses iron to store oxygen within muscle cells, making it readily available. Without sufficient iron, the body cannot produce enough of these proteins, hindering its ability to supply tissues with oxygen.
Iron is also a part of cellular energy production. It is a component of proteins called cytochromes, which are involved in the electron transport chain, a series of reactions that generate adenosine triphosphate (ATP), the cell’s main energy currency. Iron’s ability to easily accept and donate electrons makes it suited for this role.
Beyond oxygen and energy, iron is needed for the synthesis and repair of DNA, as several enzymes required to build these genetic blueprints depend on it to function correctly. The immune system also relies on iron for the proper development and function of its cells to fight off infections.
The Body’s Iron Balancing Act: Absorption, Storage, and Recycling
The body’s regulation of iron begins in the small intestine, where it is absorbed from food. Dietary iron comes in two forms: heme iron, found in meat, poultry, and fish, and non-heme iron, found in plant-based foods. Heme iron is absorbed more efficiently than non-heme iron. Intestinal cells, called enterocytes, take up iron from the diet.
Once inside the enterocytes, a protein called ferroportin acts as a gateway, allowing iron to pass into the bloodstream. In the blood, iron attaches to a transport protein called transferrin, which carries it to various tissues, such as the bone marrow for the production of new red blood cells.
Excess iron is stored securely within a protein called ferritin, primarily in the liver, spleen, and bone marrow. The body is also highly efficient at recycling iron. When old red blood cells are broken down by macrophages, the iron from their hemoglobin is recovered and released back into circulation for reuse. This recycling provides the majority of the iron needed for daily red blood cell production. The body has very limited means of excreting iron, so the regulation of absorption is a primary control point.
Hepcidin: The Primary Controller of Iron Levels
The central regulator of iron homeostasis is a hormone called hepcidin, produced primarily by the liver. Hepcidin functions as the primary switch that controls the amount of iron entering the bloodstream. It does this by binding to ferroportin, the protein that exports iron from cells. When hepcidin binds to ferroportin, it causes the exporter protein to be pulled into the cell and degraded.
This action traps iron inside cells like the enterocytes in the intestine and macrophages that recycle old red blood cells. By blocking these exit points, hepcidin reduces the amount of iron absorbed from the diet and limits its release from storage and recycling sites.
The production of hepcidin is tightly controlled. When the body’s iron stores are high, the liver produces more hepcidin to prevent further absorption and release of iron. Conversely, when iron levels are low or when there is an increased need to make red blood cells, hepcidin production is suppressed. This allows more iron to be absorbed and mobilized. Inflammation can also increase hepcidin production, a defense mechanism that can lead to anemia in chronic diseases.
Consequences of Disrupted Iron Homeostasis
When the mechanisms of iron homeostasis are disturbed, it can lead to either iron deficiency or iron overload, both with health consequences. Iron deficiency is a common condition that can result from insufficient dietary intake, blood loss, or problems with absorption. As iron stores are depleted, the body’s ability to produce hemoglobin is impaired, leading to iron-deficiency anemia. Symptoms often include fatigue, weakness, pale skin, and shortness of breath due to reduced oxygen delivery to tissues.
Iron overload is where excess iron accumulates in the body. This can be caused by genetic conditions, such as hereditary hemochromatosis, where mutations in genes disrupt the signaling pathways that control hepcidin production. It can also occur from conditions requiring frequent blood transfusions, which introduce large amounts of iron.
This excess iron gets deposited in various organs, including the liver, heart, and pancreas. Over time, the stored iron can cause significant damage by promoting oxidative stress, leading to conditions like liver cirrhosis, heart failure, and diabetes. Doctors assess iron status through blood tests that measure levels of ferritin, transferrin saturation, and hemoglobin to diagnose these conditions.