Iron deficiency or iron toxicity?

This page explains why iron is essential but potentially toxic, how its absorption and transport are regulated by hepcidin and transferrin, why ferritin levels can be misleading, and why an accurate diagnosis of iron imbalance requires a comprehensive evaluation.

Iron metabolism and its importance for health

Iron is one of the essential trace elements for the proper functioning of the human body. It plays a central role in the production of red blood cells, oxygen transport, mitochondrial function, the cellular energy supply, as well as in the synthesis and activation of many enzymes. However, free iron is highly reactive and can be toxic, causing cellular damage. That’s why iron is always bound to proteins that control its transport and storage.

To better understand, imagine iron atoms as VIP guests arriving at a luxury hotel in Venice. They move through "canals"—the blood vessels—aboard gondolas piloted by a "gondolier" called transferrin. At the entrance and exit, the guests are greeted by a "doorman"—the hormone hepcidin, which decides how much iron can be released into the bloodstream.

Hepcidin, synthesized in the liver, is the main regulator of the absorption of iron from foods: in case of deficiency, it increases absorption; in case of excess or inflammation, it reduces it. Transferrin plays the role of a "gondola" with a limited number of seats. To build a sufficient number of these "boats," magnesium, amino acids and insulin are needed. Vitamin A, magnesium and copper help to "load" iron onto transferrin, while ceruloplasmin, an antioxidant protein, coordinates this process.

In case of deficiency in these auxiliary substances, iron does not reach the cells, even if its total reserves in the body are sufficient. This leads to a decrease in the production of red blood cells and hemoglobin, a reduction in transferrin iron saturation, and the appearance of symptoms similar to iron-deficiency anemia. Thus, the causes of anemia can be related not only to iron deficiency but also to disorders of its distribution.

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Ferritin: a reliable indicator of iron status?

Ferritin is a protein that acts as an iron store, but it is also a marker of acute inflammation, autoimmune diseases and certain cancers. This makes its interpretation difficult: a high level can be related to sufficient iron stores or to an inflammatory process.

During inflammation, hepcidin activity increases, which limits the access of iron to the bloodstream. It is “imprisoned” in ferritin, whose level increases, while transferrin iron saturation decreases. Although ferritin is able to store up to 4,500 iron atoms, when saturated, the excess iron can enter cells, causing oxidative damage to DNA, cell membranes and mitochondria.

A very low ferritin level (less than 10 ng/mL) clearly indicates iron deficiency, but a high level does not guarantee sufficient quantity. To diagnose, it is necessary to perform a comprehensive evaluation of iron metabolism, exclude any chronic anemia, and identify the primary cause of the disorders.

The restoration of iron balance requires considering all nutrients involved in its assimilation and transport. The prescription of iron-based preparations should be carried out exclusively by a physician to avoid any risk of iron overload in the body.

Essential facts about iron and ferritin

• Iron is essential for life, but in its free form it can be toxic.
• Hepcidin regulates iron absorption and its passage into the blood.
• Transferrin transports iron to cells and organs.
• Vitamin A, magnesium, copper, amino acids and insulin ensure efficient iron absorption.
• In case of inflammation, the body limits access to iron in order to deprive pathogens of a resource necessary for their reproduction.
• Ferritin is an iron reservoir and a marker of inflammatory processes.
• An excess of free iron damages cells and tissues, increasing oxidative stress.

Thus, understanding the subtleties of iron metabolism and correct evaluation of blood parameters not only allows proper diagnosis of an iron deficiency or overload, but also helps avoid treatment errors that can lead to serious complications.