Treatment for Low Ferritin with Normal Iron Levels
Treat low ferritin with oral iron supplementation even when iron saturation is normal, because low ferritin indicates depleted iron stores that require replenishment regardless of functional iron status. 1
Understanding the Clinical Situation
Low ferritin with normal iron saturation represents early-stage iron deficiency where body iron stores are depleted but functional iron remains adequate—ferritin is the earliest and most specific indicator of depleted iron stores. 1 Normal transferrin saturation does not exclude the need for treatment when ferritin is low, as this pattern indicates iron stores are exhausted before functional iron becomes compromised. 1 Each unit of serum ferritin represents approximately 10 mg of stored iron, making it the gold standard for assessing iron stores. 1
First-Line Treatment Protocol
Start ferrous sulfate 325 mg (containing 65 mg elemental iron) three times daily as the most cost-effective and evidence-based first-line therapy. 1 Alternative dosing includes 100-200 mg elemental iron daily in divided doses if the standard regimen is not tolerated. 1 Recent evidence supports alternate-day dosing (every other day) for better absorption and fewer gastrointestinal side effects, though this approach is still being validated. 1, 2
Enhancing Absorption
Add vitamin C 500 mg with each iron dose to enhance absorption, particularly if initial response is suboptimal. 1 Take iron on an empty stomach when possible to enhance absorption, though this may increase gastrointestinal side effects. 1 Avoid taking iron with calcium supplements, antacids, or tea/coffee as these inhibit absorption. 1
Treatment Duration
Continue oral iron supplementation for 3 months after ferritin normalizes to adequately replenish body iron stores. 1 Total treatment duration typically ranges from 3-6 months depending on baseline ferritin levels and response. 1
Monitoring Response
Recheck ferritin and complete blood count after 8-10 weeks of treatment, not earlier, as ferritin levels may be falsely elevated immediately after iron supplementation. 1, 2 Expected ferritin rise is a gradual increase over 2-3 months with adequate supplementation. 1 After normalization, monitor ferritin every 3 months for one year, then annually, to detect recurrence. 1
When Oral Iron Fails
Consider intravenous iron if intolerance to at least two different oral iron preparations occurs, or if malabsorption conditions (celiac disease, post-bariatric surgery) or chronic inflammatory conditions are present. 1, 3 Ferric carboxymaltose 1000 mg infused over 15 minutes is a well-studied option for intravenous iron supplementation, with a low risk of serious reactions (<1:250,000). 1
Investigating Underlying Causes
Identify and address the source of iron depletion, including menstrual blood loss, gastrointestinal blood loss, dietary insufficiency, and malabsorption disorders. 1, 3 NSAID use commonly causes occult gastrointestinal bleeding and should be investigated as a potential underlying cause. 1 In reproductive-age women, heavy menstrual bleeding is the most common cause, affecting 38% with iron deficiency without anemia. 3
Critical Pitfalls to Avoid
Do not withhold iron supplementation based on normal iron saturation alone when ferritin is low, as this represents true iron deficiency requiring treatment. 1 Do not supplement iron if ferritin is normal or elevated, as this provides no benefit and may be harmful. 1, 2 Do not confuse this scenario with anemia of chronic disease, where ferritin may be normal or elevated due to inflammation despite functional iron deficiency. 1 Do not recheck ferritin too early after starting treatment (wait 8-10 weeks minimum), as levels may be misleadingly elevated. 1, 2
Diagnostic Thresholds
For healthy males and females aged >15 years, a ferritin cut-off of 30 µg/L is appropriate for diagnosing iron deficiency. 2, 3 For children from 6-12 years and younger adolescents from 12-15 years, cut-offs of 15 and 20 µg/L, respectively, are recommended. 2