Treatment of Normal Iron with Low Ferritin
For individuals with normal serum iron but low ferritin levels, oral iron supplementation is the first-line treatment, with typical doses of 100-200 mg/day of elemental iron, preferably given on alternate days to optimize absorption and minimize gastrointestinal side effects. 1
Diagnostic Thresholds
The definition of "low ferritin" depends critically on the clinical context:
- Without inflammation: Ferritin <30 ng/mL indicates absolute iron deficiency 1, 2
- With inflammation or cancer: The threshold should be raised to ferritin <100 ng/mL, as ferritin behaves as an acute phase reactant and can be falsely elevated 1
- Symptomatic patients: Treatment should be considered even at ferritin levels <50 ng/mL, as this represents the body's physiologic threshold 3, and symptoms can occur at levels <100 ng/mL 4
Always measure C-reactive protein to exclude inflammation before interpreting ferritin levels, as this prevents false-negative results where ferritin appears normal despite true iron deficiency 5.
Treatment Algorithm
First-Line: Oral Iron Supplementation
Oral iron is recommended as initial therapy for most patients with low ferritin 1, 5, 2:
- Dosing: 100-200 mg elemental iron daily (e.g., ferrous sulfate 325 mg daily or on alternate days) 1, 2
- Alternate-day dosing: Recent evidence shows better absorption and fewer adverse effects compared to daily dosing 1
- Duration: Continue for 8-10 weeks before reassessing 1, 5
- Co-administration: Take with vitamin C to enhance absorption of non-heme iron 1
- Avoidance: Separate from tea, coffee, and calcium-containing foods that inhibit absorption 1
Dietary Optimization
Concurrent dietary counseling should emphasize heme iron sources 5:
- Prioritize red meat and seafood as highly bioavailable sources 1
- This is particularly important for vegetarians/vegans who have substantially lower iron bioavailability 1
When to Use Intravenous Iron
Intravenous iron is indicated when oral iron fails or specific conditions exist 1, 2:
- Intolerance to oral iron (gastrointestinal side effects occur in ~50% of patients) 1, 6
- Malabsorption conditions (celiac disease, post-bariatric surgery, atrophic gastritis) 2, 6
- Chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure, cancer) 1, 2
- Pregnancy (second and third trimesters) 2, 6
- Ongoing blood loss requiring rapid repletion 1, 2
- Repeated failure of oral therapy 5
IV iron formulations: Ferric carboxymaltose and iron isomaltoside allow rapid administration of large single doses (up to 1000 mg over 15 minutes), with hypersensitivity reactions occurring in <1:250,000 administrations 1, 6
Monitoring Response
Reassess iron parameters after 8-10 weeks of treatment 1, 5:
- Do not recheck earlier after IV iron, as ferritin levels will be falsely elevated 1
- If oral iron fails after 2-4 weeks, consider switching to IV iron 6
- For patients with recurrent deficiency, intermittent oral supplementation maintains stores 5
- Long-term monitoring every 6-12 months is appropriate for at-risk patients 5
Critical Safety Considerations
Iron supplementation in the presence of normal or high ferritin values is not recommended and potentially harmful 1, 5. This is a common pitfall—always confirm true deficiency before treating.
Monitor ferritin levels during treatment to avoid toxicity, particularly keeping levels below 500 ng/mL in most patients 1. In dialysis populations, upper limits of 500-800 ng/mL are used, but this does not apply to otherwise healthy individuals 1.
Special Populations
For athletes with low ferritin (<35 μg/L) but normal hemoglobin, dietary optimization with iron-rich foods is recommended first, with supplementation considered after consultation with practitioners 1. Parenteral iron is rarely indicated unless malabsorption is documented 1.
For women with heavy menstrual bleeding, address the underlying bleeding source while providing iron supplementation 4, 2.