What are the causes of ferritin deficiency?

Causes of Ferritin Deficiency

Low serum ferritin is primarily caused by iron deficiency, which can result from blood loss, inadequate dietary intake, malabsorption, or increased iron requirements. 1

Primary Causes of Low Ferritin

1. Blood Loss

• Gastrointestinal bleeding

  • Colonic cancer/polyps
  • Gastric cancer
  • Peptic ulcer disease
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
  • NSAID use causing GI erosions
  • Angiodysplasia
  • Esophageal varices 1

• Gynecological causes

  • Menstrual bleeding (most common cause in pre-menopausal women)
  • Childbirth
  • Postpartum hemorrhage 1, 2

2. Malabsorption

• Celiac disease
• Atrophic gastritis
• Post-gastrectomy (partial or total)
• Bacterial overgrowth
• Inflammatory bowel disease
• Whipple's disease
• Intestinal resection or bypass 1, 2

3. Dietary Factors

• Inadequate iron intake
  • Vegetarian/vegan diets (lower bioavailability of non-heme iron)
  • Poor dietary intake in general
• Consumption of iron absorption inhibitors
  • Polyphenols (certain vegetables)
  • Tannins (tea)
  • Phytates (bran)
  • Calcium (dairy products) 1

4. Increased Iron Requirements

• Pregnancy (especially third trimester)
• Rapid growth (infancy, adolescence)
• Regular blood donation
• Athletic training (especially in female athletes) 1, 2

Special Considerations

Inflammatory Conditions

It's important to note that ferritin is an acute-phase reactant, and its levels can be elevated in inflammatory states even when iron stores are low. In patients with inflammation:

• Serum ferritin up to 100 μg/L may still be consistent with iron deficiency
• Transferrin saturation <16% with ferritin between 30-100 μg/L suggests iron deficiency with concurrent inflammation 1

Obesity

Obesity can cause elevated ferritin levels due to low-grade inflammation, potentially masking iron deficiency:

• In overweight and obese individuals, ferritin correlates more strongly with inflammatory markers than with iron status
• Complete iron profile including transferrin saturation is more reliable than ferritin alone in these populations 3

Diagnostic Approach

When evaluating low ferritin:

• Serum ferritin <30 μg/L in non-inflammatory states indicates iron deficiency
• In inflammatory conditions, consider iron deficiency when ferritin <100 μg/L with transferrin saturation <16%
• Evaluate for occult blood loss in all adult men and post-menopausal women with iron deficiency
• Consider menstrual blood loss as the primary cause in pre-menopausal women, but investigate for GI causes if menstrual loss doesn't explain the severity 4

Clinical Pitfalls

1. Relying solely on ferritin in inflammatory states: Inflammation can elevate ferritin levels, potentially masking iron deficiency. Always check inflammatory markers (CRP) and transferrin saturation when evaluating ferritin levels 1, 5.

2. Overlooking non-GI causes: While GI blood loss is a common cause, particularly in men and post-menopausal women, don't overlook other causes like dietary factors, malabsorption, or physiological blood loss 1.

3. Assuming normal ferritin excludes iron deficiency: In inflammatory conditions, "normal" ferritin levels (up to 100 μg/L) may still represent iron deficiency 1.

4. Failing to investigate the underlying cause: Identifying and treating the root cause is essential for long-term resolution of iron deficiency 4.