What Causes Low Ferritin?
Low ferritin results primarily from depleted iron stores due to blood loss, inadequate dietary intake, malabsorption, or increased physiological demands—with gastrointestinal bleeding and menstrual blood loss being the most common culprits in clinical practice. 1
Primary Causes of Iron Depletion
Blood Loss
- Menstrual bleeding is the leading cause in reproductive-age women, with approximately 38% having iron deficiency without anemia and 13% having iron-deficiency anemia 1
- Gastrointestinal bleeding from any source (ulcers, malignancy, angiodysplasia) represents the most common cause in men and postmenopausal women 2, 1
- NSAID use causes occult GI blood loss and is a frequent contributor to iron deficiency 3, 2
- In hemodialysis patients, blood losses approximate 1.6 g/1.73 m² annually from dialysis procedures and blood sampling 4
Malabsorption Disorders
- Celiac disease is present in approximately 5% of patients with iron deficiency and may present with low ferritin before anemia develops 2, 5
- Low ferritin without anemia can be an early and silent sign of celiac disease, with 6% of such patients having biopsy-confirmed disease 5
- Atrophic gastritis impairs iron absorption through reduced gastric acid production 1
- Post-bariatric surgery patients have impaired iron absorption requiring intravenous supplementation 1
- Helicobacter pylori gastritis is significantly more common (24% vs 17.6%) in patients with low ferritin levels without anemia 5
Inadequate Dietary Intake
- Borderline iron-deficient diets are common, particularly in vegetarian and vegan populations where non-heme iron has substantially lower bioavailability than meat-based sources 3
- The RDA for iron is 18 mg (North America) or 14.8 mg (UK) for females, and 8 mg (North America) or 8.7 mg (UK) for males 3
Increased Physiological Demands
- Pregnancy, especially the third trimester, affects up to 84% of pregnant women in high-income countries 1
- Athletes, particularly female athletes, have iron deficiency prevalence of 15-35% (females) and 5-11% (males) due to red cell hemolysis, gastrointestinal bleeding during exercise, and menstruation 3
Chronic Inflammatory Conditions
While these conditions may show low ferritin, they more commonly present with functional iron deficiency (normal or elevated ferritin with low transferrin saturation):
- Chronic kidney disease: 24-85% prevalence of iron deficiency 1
- Heart failure: 37-61% prevalence 1
- Inflammatory bowel disease: 13-90% prevalence 1
- Cancer: 18-82% prevalence 1
Important caveat: Ferritin is an acute-phase reactant and may be falsely elevated during inflammation, potentially masking true iron deficiency 4, 6. In inflammatory states, ferritin ≥100 μg/L is required to exclude iron deficiency, whereas <30 μg/L indicates depleted stores in non-inflammatory conditions 6.
Diagnostic Approach to Low Ferritin
When ferritin is <15 μg/L without inflammation, absolute iron deficiency is confirmed 6. For values between 15-30 μg/L, check transferrin saturation—if <16%, iron deficiency is present 6, 1.
Mandatory investigations include:
- Tissue transglutaminase antibody for celiac disease screening 2
- Upper and lower endoscopy in men and postmenopausal women to identify GI sources 2, 7
- Detailed menstrual history in premenopausal women 1
- Medication review for NSAIDs and aspirin 2
Critical pitfall: In elderly hospitalized patients, ferritin ≤50 μg/L justifies gastrointestinal investigation even without anemia, as most patients lack classic GI symptoms 8. Do not wait for anemia to develop before investigating the cause.