What causes low ferritin levels?

Causes of Low Ferritin Levels

Low ferritin levels are primarily caused by iron deficiency, which can result from blood loss, inadequate dietary iron intake, impaired iron absorption, or increased iron requirements. 1, 2

Primary Causes of Low Ferritin

• Blood Loss: The most common cause of iron deficiency in adults, particularly:

  • Menstrual blood loss in premenopausal women 2
  • Gastrointestinal bleeding (ulcers, inflammatory bowel disease, colorectal cancer) 2, 3
  • Chronic use of NSAIDs leading to GI blood loss 2

• Impaired Iron Absorption:

  • Celiac disease 2, 3
  • Atrophic gastritis 2
  • Post-bariatric surgery 2
  • Inflammatory bowel disease (affects 13-90% of IBD patients) 2

• Inadequate Dietary Iron Intake:

  • Poor nutrition or restrictive diets 2
  • Vegetarian/vegan diets without proper iron supplementation 2

• Increased Iron Requirements:

  • Pregnancy (affects up to 84% of women in third trimester) 2
  • Periods of rapid growth (infancy, adolescence) 4

Special Populations with High Risk

• Women of Reproductive Age:

  • Approximately 38% of non-pregnant women have iron deficiency without anemia 2
  • About 13% have iron-deficiency anemia 2

• Patients with Chronic Inflammatory Conditions:

  • Chronic kidney disease (24-85% affected) 2
  • Heart failure (37-61% affected) 2
  • Cancer (18-82% affected) 2
  • Inflammatory bowel disease (13-90% affected) 2

Diagnostic Considerations

• Absolute Iron Deficiency: Defined as serum ferritin <30 ng/mL in individuals without inflammation 1, 2

• Functional Iron Deficiency: May occur despite normal or elevated ferritin levels due to:

  • Inflammation blocking iron utilization 1
  • Chronic disease states 1

• Impact of Inflammation: Ferritin is an acute-phase reactant that increases during inflammation, potentially masking iron deficiency 1, 5

  • In patients with inflammation, ferritin levels between 30-100 ng/mL may still indicate iron deficiency 1
  • Transferrin saturation <16% with ferritin >100 ng/mL suggests anemia of chronic disease 1

Clinical Manifestations of Low Ferritin

• Asymptomatic: Many patients with low ferritin without anemia may have no symptoms 2

• Symptomatic Presentations:

  • Fatigue and exercise intolerance 2
  • Irritability and difficulty concentrating 2
  • Restless legs syndrome (affects 32-40% of iron deficient patients) 2
  • Pica (unusual cravings for non-food items, affects 40-50%) 2
  • Hair loss (controversial association) 6

Evaluation Algorithm

1. Assess ferritin level and transferrin saturation:

   • Ferritin <15 μg/L confirms absolute iron deficiency (98% specificity) 1, 7
   • Transferrin saturation <16% suggests inadequate iron availability 1, 7

2. Consider inflammatory markers (CRP, ESR) to interpret ferritin levels accurately 1

   • With inflammation: ferritin <100 μg/L may indicate iron deficiency
   • Without inflammation: ferritin <30 μg/L indicates iron deficiency

3. Investigate underlying cause:

   • In men and postmenopausal women: Always investigate for gastrointestinal blood loss 6, 3
   • In premenopausal women: Assess menstrual blood loss and pregnancy status 2
   • In all patients: Evaluate for malabsorption disorders 3

Clinical Pitfalls to Avoid

• Misinterpreting normal ferritin in inflammatory states: Inflammation can elevate ferritin levels, masking iron deficiency 1, 5

• Overlooking serious underlying causes: Low ferritin may be the first sign of gastrointestinal malignancy, especially in men and postmenopausal women 3

• Focusing only on ferritin: A comprehensive iron panel including transferrin saturation provides better diagnostic accuracy 1

• Ignoring functional iron deficiency: Patients with chronic inflammatory conditions may have iron deficiency despite normal ferritin levels 1