Iron is an indispensable element for human health, playing a central role in oxygen transport throughout the body as a component of hemoglobin. It is also required for numerous enzyme functions involved in energy production and DNA synthesis. Since the body has no active mechanism for iron excretion, the small intestine acts as the gatekeeper, controlling the amount of dietary iron that enters the circulation. This strict regulation of absorption is necessary to maintain iron balance, preventing both deficiency and toxic overload.
Anatomy of Iron Absorption Location
Dietary iron absorption occurs predominantly in the proximal section of the small intestine, specifically the duodenum and the very beginning of the jejunum. The duodenum is uniquely suited for iron uptake due to its anatomical position and specialized cellular environment. Consequently, the vast majority of iron transfer into the body is completed in the duodenum.
This section benefits from the highly acidic contents arriving directly from the stomach. The low pH environment helps keep the iron soluble, a prerequisite for absorption. Specialized cells lining the intestine, called enterocytes, are highly concentrated here and express the specific transport proteins needed for iron uptake.
As contents move further along the small intestine, the environment becomes progressively less acidic, decreasing iron solubility. This shift causes remaining iron to precipitate, making it less available for absorption in the jejunum and ileum.
The Molecular Mechanisms of Uptake
Iron is absorbed through two distinct pathways depending on its chemical form: heme iron and non-heme iron. Heme iron, derived from animal sources like meat and fish, is absorbed more efficiently and is less affected by other dietary components. The exact transporter for intact heme remains under investigation, but once inside the enterocyte, the iron is released by an enzyme called heme oxygenase.
Non-heme iron, found in both plant and animal foods, makes up the majority of dietary intake. This iron is often in the ferric state (\(\text{Fe}^{3+}\)), which must first be reduced to the ferrous state (\(\text{Fe}^{2+}\)) to be absorbed. An enzyme on the surface of the enterocyte, duodenal cytochrome B (Dcytb), facilitates this chemical reduction.
The resulting ferrous iron (\(\text{Fe}^{2+}\)) is then transported across the cell membrane into the enterocyte cytoplasm by the Divalent Metal Transporter 1 (DMT1). Once inside the cell, if the body’s iron stores are sufficient, the iron is sequestered and stored within a protein cage called ferritin. Conversely, if the body needs iron, it is promptly moved toward the bloodstream.
Systemic Regulation and Distribution
The body tightly controls the amount of iron that leaves the enterocyte and enters the circulation to prevent toxicity. The hormone hepcidin, primarily produced by the liver, regulates this systemic process. Hepcidin acts as a negative regulator of iron flow, setting the body’s iron thermostat.
When iron stores are high, the liver increases hepcidin production. This hormone circulates to the enterocytes and binds to Ferroportin, the only known protein channel responsible for exporting iron out of the enterocyte and into the plasma. The binding of hepcidin triggers the internalization and degradation of the Ferroportin channel.
By destroying the export channel, hepcidin effectively traps the iron inside the intestinal cell. This trapped iron, stored within ferritin, is eventually lost when the enterocyte is shed. This mechanism ensures that only the necessary amount of iron is transferred into the bloodstream, where it is immediately bound to the transport protein transferrin for distribution to tissues like the bone marrow for red blood cell production.
Dietary Factors Influencing Absorption Efficiency
The efficiency of non-heme iron absorption is sensitive to other substances consumed simultaneously during a meal. Certain dietary components enhance the absorption process. Ascorbic acid (Vitamin C) is a powerful enhancer because it helps reduce ferric iron (\(\text{Fe}^{3+}\)) to the more absorbable ferrous iron (\(\text{Fe}^{2+}\)) in the gut lumen.
Meat, fish, and poultry also boost non-heme iron absorption, an effect often attributed to muscle proteins that aid the transfer process. Conversely, several compounds inhibit iron uptake. Phytates, found in grains, legumes, and nuts, bind to non-heme iron, creating an insoluble complex that cannot be taken up by the enterocytes.
Tannins and polyphenols, present in tea, coffee, and certain wines, similarly interfere by chelating the iron. Additionally, calcium, particularly when consumed in high amounts from dairy or supplements, can inhibit the absorption of both heme and non-heme iron. Strategic pairing of iron-rich foods with enhancers like Vitamin C can help overcome these inhibitory effects.