What is the best approach for iron supplementation in a patient with low ferritin (iron deficiency) but no anemia, oral iron or intravenous (IV) iron?

Management of Iron Deficiency with Low Ferritin (13) but No Anemia

Oral iron supplementation is the first-line treatment for patients with iron deficiency (ferritin <30 ng/mL) without anemia, with intravenous iron reserved for specific situations where oral iron is ineffective or contraindicated. 1

Diagnosis Confirmation

• Serum ferritin <30 μg/L indicates iron deficiency, even without anemia 2
• Transferrin saturation <16% confirms inadequate iron availability for erythropoiesis 2
• Normal hemoglobin with low ferritin represents non-anemic iron deficiency, which still warrants treatment 3

Treatment Algorithm

First-Line Therapy: Oral Iron

1. Initial oral iron regimen:

   • Ferrous sulfate 325 mg (65 mg elemental iron) once daily in the morning 2, 4
   • Alternative: Ferrous gluconate 324 mg (38 mg elemental iron) if sulfate not tolerated 5

2. Optimization strategies:

   • Take on empty stomach (1 hour before or 2 hours after meals)
   • Add vitamin C (orange juice or supplement) to enhance absorption 2
   • Avoid tea, coffee, calcium, and antacids within 2 hours of iron intake
   • Consider alternate-day dosing to improve absorption and reduce side effects 6

3. Monitoring response:

   • Check ferritin and hemoglobin after 8-10 weeks of therapy 3
   • Target ferritin level >30 μg/L 2
   • Expect ferritin to increase within 4-8 weeks of starting therapy

When to Consider IV Iron

Switch to intravenous iron if: 1

• Patient does not tolerate oral iron (significant gastrointestinal side effects)
• Ferritin levels do not improve after 4-8 weeks of oral iron therapy
• Patient has conditions where oral iron absorption is impaired:
  • Inflammatory bowel disease with active inflammation 1
  • Post-bariatric surgery 1
  • Pernicious anemia (where IV iron showed better response than oral iron) 7
  • Celiac disease with ongoing inflammation despite gluten-free diet 1

Special Considerations

• Gastrointestinal side effects: Common with oral iron (10-20% of patients). Try lower doses, alternate-day dosing, or different formulations before switching to IV iron 8
• Inflammatory conditions: Inflammation can falsely elevate ferritin levels; check C-reactive protein to exclude acute phase reaction 3
• Long-term management: For patients with repeatedly low ferritin, consider intermittent oral supplementation and follow-up every 6-12 months 3
• Avoid excessive supplementation: Long-term daily iron supplementation with normal/high ferritin is potentially harmful 3

Clinical Implications of Iron Deficiency Without Anemia

Even without anemia, iron deficiency can cause:

• Fatigue and reduced exercise tolerance
• Impaired cognitive function and concentration
• Restless legs syndrome
• Reduced work capacity and athletic performance 6

Pitfalls to Avoid

1. Ignoring non-anemic iron deficiency: Iron deficiency without anemia still requires treatment as it can cause significant symptoms 3, 6
2. Excessive iron supplementation: Continuing iron therapy despite normal/high ferritin can be harmful 3
3. Missing underlying causes: Always investigate the cause of iron deficiency (menstrual bleeding, gastrointestinal blood loss, malabsorption, dietary insufficiency) 6
4. Overlooking inflammation: Inflammatory conditions can mask iron deficiency by falsely elevating ferritin 2

By following this approach, most patients with non-anemic iron deficiency will achieve normal iron stores and resolution of symptoms with oral supplementation, reserving IV iron for those specific situations where oral therapy is inadequate or inappropriate.