Date Published: 
Wednesday, 22 May, 2013

Why do patients with gastrointestinal disorders become iron deficient?

The cause of iron deficiency in gastrointestinal disease can be multifactorial and the aetiology in individual patients may result from one or more of these factors (see figure below)1.

Figure 1. Why patients with gastrointestinal disease become iron deficient2,3 

Chronic blood loss

Blood loss from the gastrointestinal tract is the principle cause of iron deficiency in men and postmenopausal women3. Blood loss greater than 5–10 mL per day exceeds the amount of iron that can be absorbed from a normal diet. However, this level of bleeding may go undetected, particularly from lesions of the upper gastrointestinal tract, given that blood loss of up to 100 mL per day may still result in stools that appear normal4. The most common sources of blood loss in the upper gastrointestinal tract are benign erosive lesions including gastric and duodenal ulcers4. Colon carcinomas are the most common lesions associated with bleeding in the lower gastrointestinal tract4.

Deficient diet or malabsorption

Iron deficiency can occur in the absence of bleeding due to failure to take up sufficient dietary iron to replace normal iron loss. Anorexia or a low iron diet can be one such cause5. Conditions associated with hypochlorhydria, including atrophic gastritis or H. pylori infection, may also reduce iron absorption, since gastric acid is needed to maintain iron in its more readily absorbed ferric state6. Injury to the duodenum or upper jejunum, which are responsible for iron absorption, or surgical bypass of this region may also result in iron malabsorption3. Iron absorption can also be impaired by inflammation-associated rises in the level of liver-derived hepcidin, the major regulator of iron homeostasis2.


Iron deficiency can occur as a result of inflammation of chronic disease, most notably in inflammatory bowel disease3. Inflammatory cytokines stimulate an increase in levels of hepcidin, an iron homeostasis peptide responsible for controlling the absorption of iron from the intestine, as well as the release of iron from stores within the body7. In the short term, pathological increases in hepcidin also impair the release of iron from iron stores, resulting in functional iron deficiency, a condition with iron deficiency in the blood circulation and in the bone marrow despite rich iron stores2. Over the longer term, absorption of iron from the intestine is also blocked by hepcidin, preventing stores from being replenished and leading to absolute iron deficiency.

Erythropoietin stimulating agents for anaemia

ESA therapy may be used to treat various forms of anaemia but the sudden demand for iron stimulated by ESA-induced erythropoiesis can cause a rapid depletion of iron in the circulation and result in functional iron deficiency8.