Understanding What Diseases Cause Iron-Deficiency Without Anemia?

October 9, 2025 •

4 min read

Chronic iron deficiency is the most common nutritional deficiency worldwide, and it can exist even with normal hemoglobin levels. This is known as iron-deficiency without anemia (IDWA), and it is often caused by underlying health conditions rather than a simple dietary lack. Identifying what diseases cause iron-deficiency without anemia is crucial for accurate diagnosis and effective treatment.

Quick Summary

Several medical conditions, including chronic inflammation, gastrointestinal disorders, and kidney disease, can cause iron deficiency even when blood counts remain normal. Functional iron deficiency, driven by the hormone hepcidin, impairs iron transport. Specific diseases like celiac disease and H. pylori infection also disrupt iron absorption.

Key Points

Chronic Inflammation Traps Iron: Diseases like CKD and IBD can cause functional iron deficiency by increasing hepcidin, a hormone that blocks iron transport, leading to low iron availability despite stored iron.
Malabsorption from GI Disorders: Conditions such as celiac disease, H. pylori infection, and bariatric surgery interfere with the gut's ability to absorb iron from food.
Normal Hemoglobin is Not Enough: IDWA can cause symptoms like fatigue, restless legs, and poor concentration even when routine blood tests show normal hemoglobin levels.
Iron Studies are Key for Diagnosis: Diagnosing IDWA requires specific iron studies, including serum ferritin and transferrin saturation, to assess the body's iron stores and transport.
Treat the Root Cause: Effective treatment for IDWA involves not only dietary changes or supplements but also addressing the underlying inflammatory or gastrointestinal condition responsible for the iron imbalance.

The Role of Chronic Inflammation in Non-Anemic Iron Deficiency

Chronic inflammation is a leading cause of iron-deficiency without anemia (IDWA), a state also referred to as functional iron deficiency. In this condition, the body has sufficient iron stores but is unable to effectively transport and utilize the iron. The root cause is a regulatory hormone called hepcidin, which is produced in response to inflammatory signals from diseases like chronic kidney disease (CKD), inflammatory bowel disease (IBD), and chronic heart failure (CHF).

Hepcidin blocks the iron transporter ferroportin, trapping iron inside storage cells like macrophages and liver cells. This reduces the amount of iron available for red blood cell production and for crucial cellular processes throughout the body, leading to symptoms of iron deficiency even if hemoglobin levels haven't dropped enough to trigger a diagnosis of anemia. Conditions that can trigger this response include:

Chronic Kidney Disease (CKD): The kidneys' inability to clear hepcidin, combined with ongoing inflammation, contributes significantly to functional iron deficiency in CKD patients.
Inflammatory Bowel Disease (IBD): Active inflammation in Crohn's disease or ulcerative colitis can increase hepcidin levels and impair iron absorption.
Chronic Heart Failure (CHF): Iron deficiency, with or without anemia, is an independent risk factor for worse outcomes in CHF patients.
Rheumatoid Arthritis: This and other chronic inflammatory diseases can elevate hepcidin and contribute to IDWA.

Gastrointestinal Disorders and Malabsorption

Many diseases affecting the gastrointestinal (GI) tract interfere with the body's ability to absorb iron, which is predominantly absorbed in the small intestine. Unlike inflammatory causes that trap existing iron, these conditions prevent sufficient dietary iron from entering the bloodstream in the first place. Common GI culprits include:

Celiac Disease: This autoimmune disorder damages the lining of the small intestine (villous atrophy), impairing the absorption of many nutrients, including iron. Iron deficiency is a common extra-intestinal manifestation of celiac disease, and it can be present even without classic GI symptoms or anemia.
Helicobacter pylori Infection: This bacterial infection in the stomach can lead to chronic inflammation (atrophic gastritis), which reduces stomach acid needed for iron absorption. H. pylori can also increase hepcidin levels.
Bariatric Surgery: Procedures like gastric bypass alter the digestive tract, limiting the area available for iron absorption.
Chronic Occult Blood Loss: Slow, persistent bleeding from sources like peptic ulcers, colon polyps, or inflammatory lesions can deplete iron stores over time without obvious signs of blood loss.
Chronic Use of Medications: Long-term use of proton pump inhibitors (PPIs) and other antacids can reduce stomach acid, impairing iron absorption.

Other Factors Contributing to Non-Anemic Iron Deficiency

Besides chronic inflammation and GI disease, other medical and lifestyle factors can contribute to IDWA:

Increased Blood Loss: Conditions that cause chronic blood loss can lead to iron depletion. Heavy menstrual bleeding (menorrhagia) is a very common cause of IDWA in premenopausal women. Frequent blood donation also depletes iron stores.
Vegan and Vegetarian Diets: While not a disease, following a strictly plant-based diet can lead to low iron stores due to the lower bioavailability of non-heme iron found in plant foods. If not carefully managed with enhancers like vitamin C, this can cause IDWA.
Athletic Activity: Endurance athletes are at a higher risk of iron depletion due to increased iron turnover and losses through sweat and the GI tract.

The Importance of Correct Diagnosis

Because the symptoms of IDWA, such as fatigue, poor concentration, and restless legs syndrome, are non-specific and overlap with many other conditions, it is often missed or misattributed. A proper diagnosis relies on blood tests, specifically iron studies. A key diagnostic challenge in inflammatory states is that ferritin, the primary storage protein for iron, can be falsely elevated as an acute-phase reactant. Therefore, clinicians must consider the overall clinical picture and other markers when assessing for IDWA in patients with chronic diseases.

Comparison of Iron-Deficiency Anemia (IDA) and Iron-Deficiency Without Anemia (IDWA)

To clarify the distinction, here's a comparison of the key indicators:


Indicator	Iron-Deficiency Anemia (IDA)	Iron-Deficiency Without Anemia (IDWA)
Hemoglobin	Low	Normal
Serum Ferritin	Low	Low (or normal/high due to inflammation)
Transferrin Saturation	Low	Low
Symptoms	Often more pronounced; fatigue, pallor, shortness of breath	Can be milder, or similar but non-specific; fatigue, restless legs
Mean Cell Volume (MCV)	Low (Microcytic)	Normal (or can fall later)
Underlying Cause	Inadequate intake, blood loss, malabsorption	Often chronic inflammation causing functional iron deficiency

Conclusion

While iron deficiency is commonly associated with anemia, many diseases can cause iron levels to drop to a symptomatic level before hemoglobin is affected. This can cause a range of non-specific and debilitating symptoms, impacting a person's overall quality of life. Chronic inflammatory conditions like CKD, IBD, and CHF, as well as gastrointestinal disorders such as celiac disease and H. pylori infection, are key culprits. By understanding the causes of IDWA, clinicians can better interpret lab results, investigate the underlying condition, and provide targeted treatment to replenish iron stores and alleviate symptoms. Early diagnosis and management of the root cause are vital for improving patient outcomes and overall well-being. For more in-depth information, consider this resource: Iron deficiency without anaemia: a diagnosis that matters.

Frequently Asked Questions

The main difference is hemoglobin level. In IDWA, the body’s iron stores are depleted, but hemoglobin remains within the normal range. In IDA, the iron depletion is severe enough to cause a drop in hemoglobin, leading to anemia.

Yes, chronic kidney disease (CKD) can cause IDWA. The chronic inflammation associated with CKD increases hepcidin levels, which traps iron in storage cells and prevents its proper use, leading to functional iron deficiency even with normal hemoglobin.

Celiac disease, an autoimmune condition triggered by gluten, damages the small intestine lining where most iron is absorbed. This malabsorption can cause iron deficiency and other nutritional deficiencies, often before anemia develops.

H. pylori can cause chronic gastritis, which reduces stomach acid levels. The acidic environment is necessary for iron absorption, so a lack of it can lead to iron deficiency. The infection can also increase hepcidin levels.

Vegetarians and vegans consume non-heme iron from plant sources, which is less bioavailable than heme iron from meat. Without careful dietary planning to include vitamin C and other absorption enhancers, they can develop IDWA.

Diagnosis involves blood tests beyond a standard complete blood count. Key indicators include low serum ferritin (representing low iron stores) and low transferrin saturation, even with a normal hemoglobin level.

Treatment involves addressing the underlying cause. Options may include dietary counseling, oral iron supplements (often taken on alternate days for better absorption), or intravenous iron in cases of malabsorption or poor response to oral therapy.