Can Inflammation Reduce Iron Absorption? The Surprising Connection

October 13, 2025 •

4 min read

Anemia affects a significant portion of the global population, and while a simple iron deficiency is often blamed, chronic inflammation is a common yet overlooked culprit. Many people with inflammatory conditions repeatedly ask, "Can inflammation reduce iron absorption?" The answer is a clear yes, and the underlying mechanism involves a sophisticated immune response that actively disrupts the body's iron metabolism, often leading to a challenging condition known as functional iron deficiency.

Quick Summary

The inflammatory process releases cytokines that stimulate hepcidin, a hormone preventing iron transport into the bloodstream. This leads to iron being trapped within cells, limiting its availability for red blood cell production.

Key Points

Hepcidin is key: Inflammation triggers the release of the hormone hepcidin, which is the primary cause of reduced iron absorption.
Iron is trapped: High hepcidin levels degrade ferroportin, the protein that exports iron from cells, effectively trapping iron in intestinal cells and macrophages.
Functional iron deficiency: This mechanism leads to a state where iron stores exist but are unavailable for producing red blood cells, a condition distinct from true iron-deficiency anemia.
Inflammatory diseases are linked: Chronic conditions like IBD, CKD, obesity, and autoimmune disorders are well-known causes of inflammation that impair iron metabolism.
Oral iron may not work: During active inflammation, oral iron supplements are often poorly absorbed and can sometimes exacerbate gut inflammation, necessitating alternative options like intravenous iron.

The Master Regulator: How Inflammation Increases Hepcidin

At the heart of the connection between inflammation and reduced iron absorption is the hormone hepcidin. Produced primarily by the liver, hepcidin is the master regulator of iron homeostasis. During an inflammatory state, the immune system releases pro-inflammatory cytokines, most notably interleukin-6 (IL-6), which acts on the liver to ramp up hepcidin production. Increased hepcidin then orchestrates a systematic reduction of iron in the bloodstream.

The Hepcidin-Ferroportin Mechanism

Hepcidin exerts its effect by targeting a protein called ferroportin. Ferroportin is the only known cellular iron exporter and is found on the surface of cells that transport iron, such as duodenal enterocytes (in the small intestine) and macrophages (immune cells that recycle iron from old red blood cells). When hepcidin binds to ferroportin, it triggers the internalization and degradation of the ferroportin protein. This has two critical consequences for iron metabolism:

Blocks Intestinal Absorption: By destroying ferroportin on duodenal enterocytes, hepcidin prevents newly absorbed dietary iron from entering the bloodstream from the digestive tract.
Traps Recycled Iron: Hepcidin also traps iron inside macrophages by degrading their ferroportin. This prevents the recycling of iron from senescent red blood cells, a process that normally supplies a large portion of the body's daily iron needs.

This process leads to a state known as "functional iron deficiency" or anemia of inflammation (AI), where there may be plenty of iron stored in the body's cells, but it is not accessible for the production of new red blood cells.

Anemia of Inflammation vs. Iron-Deficiency Anemia

It is crucial to differentiate between Anemia of Inflammation (AI) and Iron-Deficiency Anemia (IDA), as their treatments differ significantly. The standard approach for IDA, which is iron supplementation, is often ineffective for AI and can sometimes worsen inflammation.


Feature	Iron-Deficiency Anemia (IDA)	Anemia of Inflammation (AI)
Cause	Low body iron stores due to poor intake, malabsorption, or blood loss.	Chronic disease causing inflammation, leading to impaired iron utilization.
Iron Stores	Depleted iron stores; serum ferritin is low.	Retained iron stores; serum ferritin is normal or high.
Inflammatory Markers	Typically normal, unless another process is at play.	Elevated markers, such as C-reactive protein (CRP) and IL-6.
Iron Status	Low serum iron and low transferrin saturation (TSAT).	Low serum iron and low TSAT (hypoferremia).
Hepcidin Levels	Low, as the body tries to increase iron absorption.	High, actively inhibiting iron release into the bloodstream.
Supplementation	Oral iron is the standard treatment.	Often requires treatment of the underlying condition or intravenous iron.

Chronic Inflammatory Conditions that Impact Iron

Many long-term health issues can trigger the inflammatory response that hinders iron absorption. Patients suffering from these conditions are at a higher risk of developing anemia of inflammation:

Inflammatory Bowel Disease (IBD): Conditions like Crohn's disease and ulcerative colitis cause chronic gut inflammation, directly affecting intestinal absorption and often leading to blood loss. The inflammation also raises hepcidin levels, compounding the issue.
Chronic Kidney Disease (CKD): Renal dysfunction can lead to reduced erythropoietin production and decreased hepcidin clearance, resulting in its accumulation and persistent iron sequestration.
Autoimmune Diseases: Rheumatoid arthritis, lupus, and other autoimmune conditions involve systemic inflammation that elevates cytokines like IL-6, driving hepcidin production.
Obesity: Adipose tissue secretes pro-inflammatory cytokines, and higher body mass index (BMI) is associated with increased hepcidin and lower iron absorption, even in the absence of other inflammatory conditions.
Infections and Cancer: Chronic infections like HIV/AIDS and various types of cancer can cause a sustained inflammatory response that results in AI.

Dietary Strategies to Counteract Impaired Absorption

While inflammation is active, dietary and supplemental strategies must be carefully considered to maximize the absorption of available iron. Some dietary components can either enhance or inhibit non-heme iron absorption.

Enhancers of Non-Heme Iron Absorption: To help increase the bioavailability of non-heme iron from plant sources, incorporate these foods into your meals:
- Vitamin C-rich foods: Citrus fruits, bell peppers, broccoli, and strawberries. Vitamin C captures non-heme iron, making it more easily absorbed.
- Vitamin A and Beta-Carotene: Carrots, sweet potatoes, spinach, and kale. These help mobilize stored iron.
- Heme Iron-Containing Foods: Pairing plant-based iron sources with small amounts of meat, fish, or poultry can boost non-heme iron uptake.
Inhibitors of Non-Heme Iron Absorption: These can interfere with iron absorption and should be consumed separately from iron-rich meals:
- Phytates: Found in whole grains, legumes, nuts, and seeds. Soaking beans and grains can help reduce phytate content.
- Polyphenols: Present in coffee, tea, and wine. Have these beverages between meals instead of with them.
- Calcium: High amounts of calcium, particularly from dairy products and supplements, can hinder absorption.

Conclusion: A Nuanced Approach to Iron Management

In summary, inflammation significantly reduces iron absorption through the hepcidin-ferroportin axis, resulting in functional iron deficiency even when the body's iron stores are sufficient. This condition, known as anemia of inflammation, is common in patients with chronic diseases like IBD, CKD, and obesity. Effective management requires a two-pronged approach: treating the underlying inflammatory condition to lower hepcidin and improve iron utilization, and implementing strategic dietary choices to maximize absorption of dietary iron. Unlike simple iron deficiency, blindly supplementing with oral iron is often ineffective and can have unintended side effects. For many patients, intravenous iron proves a more reliable and efficient route for replenishing iron stores. The complex relationship between inflammation and iron metabolism underscores the importance of a comprehensive diagnosis to ensure the correct and most effective treatment is provided. To read more about the role of hepcidin and iron homeostasis in chronic inflammation, consult this review [https://pmc.ncbi.nlm.nih.gov/articles/PMC4993159/].

Frequently Asked Questions

The main mechanism is the inflammation-induced increase of the hormone hepcidin. Hepcidin blocks ferroportin, the protein responsible for exporting iron into the bloodstream from intestinal cells and macrophages, thereby trapping iron within these cells.

In classic iron-deficiency anemia, the body's iron stores are low. In anemia of inflammation, the body has normal or high iron stores, but the iron is trapped and unavailable for red blood cell production due to high hepcidin levels.

While diet can help, it is often not enough to fully overcome the effects of significant inflammation. Certain foods rich in Vitamin C can enhance the absorption of non-heme iron, but the underlying inflammation must be managed to restore normal iron metabolism.

Common examples include inflammatory bowel disease (IBD), chronic kidney disease (CKD), autoimmune diseases like rheumatoid arthritis, certain cancers, and obesity. All of these conditions can trigger the release of inflammatory cytokines that lead to high hepcidin levels.

Oral iron is less effective because the high levels of hepcidin present during inflammation prevent the iron from being absorbed from the intestines into the bloodstream. The unabsorbed iron can also potentially worsen gut inflammation.

Pro-inflammatory cytokines, especially interleukin-6 (IL-6), are signaling molecules released by immune cells during inflammation. IL-6 directly stimulates the liver to produce more hepcidin, initiating the cascade that blocks iron absorption and release.

The main treatment for anemia of inflammation is to address the underlying chronic condition. If this is not fully effective, intravenous (IV) iron can be administered, bypassing the intestinal absorption block. In some cases, erythropoiesis-stimulating agents may also be used.