Are over‑the‑counter oral iron preparations appropriate first‑line treatment for mild‑to‑moderate iron‑deficiency anemia?

Yes, OTC Oral Iron Supplements Are Appropriate First-Line Treatment for Mild-to-Moderate Iron Deficiency Anemia

Over-the-counter oral iron supplements, specifically ferrous sulfate 200-325 mg once daily, are the recommended first-line treatment for mild-to-moderate iron deficiency anemia in patients without active inflammation, malabsorption, or prior intolerance to oral iron. 1, 2, 3

When OTC Oral Iron Is Appropriate

Use oral iron as first-line therapy when ALL of the following criteria are met:

• Hemoglobin >100 g/L (>10 g/dL) indicating mild anemia 2
• No clinically active inflammatory disease (IBD, active infection) 4, 2
• No previous intolerance to oral iron preparations 2
• No malabsorption conditions (celiac disease, post-bariatric surgery) 3
• Not in second or third trimester of pregnancy 3

Specific Dosing Recommendations

The optimal regimen is ferrous sulfate 200-325 mg once daily, taken as a single morning dose on an empty stomach. 1 This once-daily approach is superior to multiple daily dosing due to better tolerability with similar or better efficacy. 1

• Add vitamin C 500 mg with each dose to enhance absorption, particularly if response is suboptimal 1
• If gastrointestinal side effects occur, taking with food is acceptable despite reduced absorption 1
• Consider alternate-day dosing (every other day) to improve tolerability, as this allows hepcidin levels to decrease between doses 1

Monitoring Response

Check hemoglobin after 4 weeks of treatment—an acceptable response is ≥2 g/dL increase. 2 If this target is not met, switch to intravenous iron rather than continuing ineffective oral therapy. 1

• Continue monitoring hemoglobin and red cell indices at 3-month intervals for the first year 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores—this is a critical pitfall to avoid, as stopping too early leads to recurrence 1, 2

When to Switch to Intravenous Iron Instead

Intravenous iron should be first-line (not oral) in the following situations:

• Hemoglobin <100 g/L (<10 g/dL) indicating moderate-to-severe anemia 4, 2
• Clinically active inflammatory bowel disease or other inflammatory conditions 4, 2, 3
• Previous intolerance to oral iron 4, 2
• Malabsorption conditions (celiac disease, post-gastric bypass) 3
• Ongoing blood loss that cannot be controlled 3
• Second or third trimester of pregnancy 3
• Chronic kidney disease or heart failure 3

The evidence from inflammatory bowel disease studies demonstrates that IV iron achieves hemoglobin rise of 2.0 g/dL more effectively than oral iron (OR: 1.57), with lower treatment discontinuation rates (OR: 0.27) and fewer gastrointestinal adverse events. 4

Diagnostic Confirmation Before Treatment

Confirm iron deficiency with serum ferritin <30 μg/L in patients without inflammation, or transferrin saturation <20% in those with inflammation. 1, 3

• In the presence of inflammation, ferritin between 30-100 μg/L suggests combined iron deficiency and anemia of chronic disease 4
• Exclude acute phase reaction by checking C-reactive protein to avoid false-negative results (falsely elevated ferritin despite true iron deficiency) 5

Critical Pitfalls to Avoid

• Never prescribe multiple daily doses—once-daily or alternate-day dosing improves compliance without sacrificing efficacy 1
• Never stop iron when hemoglobin normalizes—continue for 3 months to replenish stores 1
• Never use oral iron in active inflammation—absorption is compromised and IV iron is more effective 2
• Never check ferritin immediately after IV iron—wait 8-10 weeks as levels are falsely elevated 1
• Never continue oral iron beyond 4 weeks without documented response—switch to IV iron if hemoglobin fails to rise ≥2 g/dL 1, 2