The physiological absorption of iron is a complex, multi-step process primarily occurring in the duodenum and upper jejunum of the small intestine. This intricate system is vital for maintaining iron homeostasis, as the body has no regulated excretory pathway for excess iron, making absorption the key regulatory point. Iron from food comes in two main forms, each with its own distinct absorption mechanism.
The two forms of dietary iron: Heme and Non-Heme
Dietary iron is categorized into two main types: heme and non-heme iron.
- Heme Iron: This form of iron is found exclusively in animal products, including meat, poultry, and seafood, as part of the hemoglobin and myoglobin proteins. It is highly bioavailable, meaning the body absorbs it efficiently, with absorption rates ranging from 15% to 35%. Heme iron is less affected by other dietary components than non-heme iron.
- Non-Heme Iron: Predominantly found in plant-based foods like grains, nuts, legumes, and vegetables, non-heme iron is also present in fortified foods and animal products such as eggs. It accounts for the majority of dietary iron but is absorbed far less efficiently and its absorption rate can be significantly influenced by other food components.
The process of non-heme iron absorption
The absorption of non-heme iron is a finely tuned process that relies on specific transport proteins on the enterocytes, the cells lining the small intestine.
1. Luminal processing and reduction
The first step occurs in the intestinal lumen, where dietary non-heme iron, mostly in its oxidized ferric ($Fe^{3+}$) state, must be reduced to the ferrous ($Fe^{2+}$) state. This conversion is critical because the primary transporter can only handle ferrous iron. An enzyme on the brush border membrane of the enterocytes, called duodenal cytochrome B (Dcytb), facilitates this reduction. This process is enhanced by the low pH of the stomach and the presence of ascorbic acid (Vitamin C), which acts as a reducing agent.
2. Apical uptake by DMT1
After reduction, the now-soluble ferrous iron is transported across the apical membrane (the side facing the intestinal lumen) into the enterocyte via the Divalent Metal Transporter 1 (DMT1). The expression of DMT1 is increased during iron deficiency to maximize absorption.
3. Intracellular fate and basolateral transfer
Once inside the enterocyte, the iron faces a decision based on the body's needs.
- Storage: If the body's iron stores are sufficient, the absorbed iron is stored within the enterocyte bound to a protein called ferritin. When the enterocyte naturally dies and is sloughed off, this stored iron is excreted in the feces.
- Export: If iron is needed elsewhere in the body, it is transported across the basolateral membrane (the side facing the bloodstream) by the iron exporter protein ferroportin (FPN1).
4. Oxidization and systemic transport
As the ferrous iron leaves the enterocyte via ferroportin, it is immediately oxidized back to ferric iron ($Fe^{3+}$) by the copper-containing enzyme hephaestin. This allows the iron to bind to the transport protein transferrin in the bloodstream, which then carries it to various tissues, such as the bone marrow for red blood cell production.
The simpler route of heme iron absorption
Heme iron, found in meat, has a more direct and efficient route. After being released from myoglobin or hemoglobin by digestive enzymes, the intact heme molecule is absorbed across the enterocyte's apical membrane by a yet-to-be-fully-elucidated mechanism, potentially involving a heme carrier protein (HCP1) or heme-responsive gene 1 (HRG1). Once inside the cell, an enzyme called heme oxygenase-1 (HO-1) releases the iron from the heme ring. This released iron then enters the same intracellular iron pool as non-heme iron and follows the same pathways of storage or export via ferroportin.
Regulation by the hepcidin-ferroportin axis
At the core of iron homeostasis is the hepcidin-ferroportin axis. Hepcidin is a peptide hormone produced primarily in the liver that serves as the body's master regulator of iron.
- High Iron Levels: When iron stores are high, hepcidin production increases. Hepcidin circulates in the blood and binds to ferroportin on the surface of enterocytes and other iron-releasing cells (like macrophages), causing the internalization and degradation of ferroportin. This effectively closes the export gate, trapping iron inside the cells and preventing further absorption or release into the bloodstream.
- Low Iron Levels: When iron levels are low or there is increased demand (e.g., during rapid erythropoiesis or blood loss), hepcidin production is suppressed. This allows ferroportin to remain on the cell surface, increasing iron release and enhancing absorption from the intestine.
Factors influencing iron absorption
Several dietary and physiological factors can dramatically alter the efficiency of iron absorption.
Enhancers of absorption
- Ascorbic Acid (Vitamin C): The most potent enhancer of non-heme iron absorption. It keeps iron in its more soluble ferrous ($Fe^{2+}$) state and forms a soluble chelate with iron, improving its uptake.
- Meat, Fish, and Poultry: These foods not only provide highly bioavailable heme iron but also contain a 'meat factor' that enhances the absorption of non-heme iron from other foods in the same meal.
Inhibitors of absorption
- Phytates: Found in legumes, whole grains, nuts, and seeds, phytates can bind to non-heme iron and inhibit its absorption.
- Polyphenols: Present in tea, coffee, wine, and certain vegetables, these compounds can form complexes with non-heme iron, reducing its bioavailability.
- Calcium: Found in dairy and supplements, calcium can inhibit the absorption of both heme and non-heme iron.
- Other Metals: High concentrations of other divalent metals, such as zinc or manganese, can compete with iron for absorption via the DMT1 transporter.
Comparison of Heme vs. Non-Heme Iron Absorption
| Feature | Heme Iron Absorption | Non-Heme Iron Absorption |
|---|---|---|
| Source | Animal products (meat, poultry, fish) | Plants, fortified foods, eggs, dairy |
| Bioavailability | High (15-35% absorbed) | Low and variable (0.1% to >35% absorbed) |
| Absorption Mechanism | Absorbed intact by enterocytes via a dedicated transporter (e.g., HCP1/HRG1) | Absorbed as ferrous ($Fe^{2+}$) iron via DMT1 after reduction by Dcytb |
| Dietary Influences | Minimally affected by other foods | Highly influenced by enhancers (vitamin C, meat) and inhibitors (phytates, polyphenols, calcium) |
| Intracellular Processing | Iron is released from the heme ring by heme oxygenase-1 (HO-1) | Iron remains in the ferrous state ($Fe^{2+}$) or is stored as ferritin |
| Efflux into Bloodstream | Shares the ferroportin pathway with non-heme iron | Exported via ferroportin |
Conclusion
The physiological absorption of iron is a tightly controlled process vital for life. While the absorption pathways for heme and non-heme iron differ significantly, their ultimate fate is governed by the hepcidin-ferroportin axis, ensuring the body maintains a delicate iron balance. A complex interplay of hormonal signals, dietary factors, and the body's iron status determines how much iron is absorbed at any given time. This sophisticated regulatory system prevents the damaging effects of both iron deficiency and toxic overload, underscoring the critical importance of a balanced diet for optimal health. For those with specific iron concerns, dietary modification, guided by an understanding of these mechanisms, can be a powerful tool for improving iron status..
