What is the best treatment for an adult with no significant medical history and low ferritin levels?

Treatment of Low Ferritin in Adults Without Significant Medical History

For an otherwise healthy adult with low ferritin, oral iron supplementation is the first-line treatment, with the goal of restoring iron stores and preventing progression to iron deficiency anemia. 1, 2, 3

Initial Diagnostic Confirmation

Before initiating treatment, confirm true iron deficiency:

• Serum ferritin <30 ng/mL (or <45 ng/mL) is diagnostic of iron deficiency in adults without inflammation 2, 3
• If ferritin is 30-100 ng/mL, check transferrin saturation—values <20% confirm iron deficiency 2, 3
• Measure C-reactive protein to exclude inflammation, which can falsely elevate ferritin levels 4
• Obtain complete blood count to assess for anemia (hemoglobin <130 g/L in men, <120 g/L in non-pregnant women) 1

Identify and Address Underlying Cause

Investigation for the source of iron deficiency is essential, as recurrent blood loss accounts for 94% of cases 2:

• In premenopausal women with heavy menstrual bleeding: treat the bleeding source and provide iron supplementation 2
• In men and postmenopausal women: bidirectional endoscopy (gastroscopy and colonoscopy) should be performed to exclude gastrointestinal malignancy 1
• Screen for celiac disease with tissue transglutaminase antibodies, as it's found in 3-5% of iron deficiency cases 1
• Test for Helicobacter pylori infection, a common reversible cause 2
• Assess dietary history for inadequate intake (vegetarian/vegan diet, eating disorders) 4, 3
• Check urinalysis to exclude urinary blood loss 1

First-Line Treatment: Oral Iron Supplementation

Oral iron is the preferred initial therapy for most patients without contraindications 2, 3:

• Dose: Ferrous sulfate 325 mg daily OR every-other-day dosing (which improves absorption and reduces side effects) 2, 3
• Alternative preparations with 28-50 mg elemental iron content may improve tolerability 4
• Take on an empty stomach when possible to maximize absorption, though taking with food is acceptable if gastrointestinal side effects occur 3
• Avoid taking with calcium, tea, coffee, or antacids which inhibit absorption 4

Important caveat: Approximately 50% of patients experience gastrointestinal side effects (nausea, constipation, abdominal discomfort) leading to decreased adherence 2. Every-other-day dosing significantly reduces these effects while maintaining efficacy 2, 3.

Monitoring Response to Treatment

Reassess iron studies and hemoglobin 2-4 weeks after initiating oral iron to confirm response 2:

• Hemoglobin should rise ≥10 g/L within 2 weeks if anemia was present 1
• Repeat complete iron studies at 8-10 weeks 4
• Target ferritin levels should reach normal range (>30 ng/mL, ideally >50 ng/mL) 4

When to Use Intravenous Iron

Intravenous iron is indicated when oral iron fails or is inappropriate 2, 3:

• Intolerance to oral iron with significant gastrointestinal side effects 2, 3
• Inadequate response to oral iron after 2-4 weeks 2
• Malabsorption conditions (celiac disease, inflammatory bowel disease, post-bariatric surgery) 3
• Ongoing blood loss that exceeds oral replacement capacity 3
• Chronic inflammatory conditions where hepcidin blocks intestinal iron absorption 5

Hypersensitivity reactions to modern intravenous iron formulations are rare (<1%) 2.

Long-Term Management

For patients with recurrent iron deficiency despite treatment:

• Intermittent oral iron supplementation may be needed to maintain iron stores 4
• Monitor ferritin every 6-12 months in at-risk populations 4
• Re-investigate if iron deficiency recurs, as this may indicate subclinical disease activity or undiagnosed pathology 1

Critical warning: Do not provide long-term iron supplementation when ferritin is normal or elevated, as this is inefficient, causes side effects, and may be harmful 4. Iron therapy should only continue until stores are replenished.

Special Considerations

Even without anemia, iron deficiency can cause significant symptoms including fatigue, cognitive impairment, reduced physical performance, restless legs syndrome (32-40% of cases), headache, and pica (40-50% of cases) 1, 3. These symptoms often improve with iron replacement even before hemoglobin normalizes 1.