What is the recommended regimen for oral iron supplementation in individuals with iron deficiency?

Oral Iron Supplementation for Iron Deficiency

The recommended regimen is ferrous sulfate 200 mg once daily, taken as a single morning dose on an empty stomach, continued for 3 months after hemoglobin normalizes to fully replenish iron stores. 1

First-Line Oral Iron Regimen

Ferrous sulfate 200 mg once daily is the gold standard due to superior effectiveness, low cost, and better tolerability compared to multiple daily dosing. 1, 2, 3

Dosing Strategy

• Take as a single morning dose rather than divided throughout the day 1
• On an empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur 1
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly when response is suboptimal 1
• Alternate-day dosing (every other day) may improve tolerability with similar or better efficacy by allowing hepcidin levels to decrease between doses 4, 5

Duration and Expected Response

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 1, 6
• Continue oral iron for 3 months after anemia correction to fully replenish iron stores 1, 2
• If no hemoglobin rise occurs within 4 weeks, assess for non-adherence, ongoing blood loss, or malabsorption and consider switching to intravenous iron 1, 6

Monitoring Schedule

• Check hemoglobin and red cell indices at 3-month intervals for the first year, then again after another year 1
• Do not check ferritin levels immediately after iron infusion as levels are falsely elevated; wait 8-10 weeks 4

Alternative Oral Formulations

While ferrous sulfate is preferred, other options include:

• Ferrous gluconate: 324 mg tablets contain 38 mg elemental iron; typical dosing is 1 tablet three to four times daily 7
• Ferric maltol and sucrosomial iron: Newer formulations developed to reduce gastrointestinal side effects, though ferrous sulfate remains the gold standard 8, 2

When Oral Iron is Appropriate vs. Intravenous Iron

Oral Iron is First-Line For:

• Patients with mild anemia (hemoglobin >10 g/dL) 4, 1, 6
• Clinically inactive disease without active inflammation 4, 1, 6
• No previous intolerance to oral iron 4, 1, 6
• Portal hypertensive gastropathy (no malabsorptive defect present) 4

Intravenous Iron is First-Line For:

• Clinically active inflammatory bowel disease 4, 1, 6
• Hemoglobin <10 g/dL 4, 1, 6
• Previous oral iron intolerance 4, 1, 6
• Post-bariatric surgery patients due to disrupted duodenal absorption 1
• Celiac disease with ongoing malabsorption 1
• Patients requiring erythropoiesis-stimulating agents 4, 6
• Second and third trimesters of pregnancy 3
• Chronic kidney disease, heart failure, or cancer with ongoing inflammation 3

Special Population Considerations

Inflammatory Bowel Disease

• Treat active inflammation first to enhance iron absorption and reduce iron depletion 4, 1
• Intravenous iron is superior to oral iron in IBD patients, with greater efficacy (odds ratio 1.57 for achieving 2 g/dL hemoglobin increase) and better tolerability (odds ratio 0.27 for treatment discontinuation) 4
• Oral iron may be used only in carefully selected patients with mild anemia and clinically inactive disease, requiring close follow-up 4

Pregnancy

• 30 mg/day elemental iron at first prenatal visit for primary prevention 1
• 60-120 mg/day elemental iron for treatment of anemia 1
• Decrease to 30 mg/day when hemoglobin normalizes for gestational stage 1

Diagnostic Criteria for Iron Deficiency

• Without inflammation: Serum ferritin <30 μg/L indicates iron deficiency 4, 6, 3
• With inflammation: Serum ferritin up to 100 μg/L may still be consistent with iron deficiency 4, 6
• Transferrin saturation <20% is an alternative diagnostic criterion 3
• Hepcidin is more reliable than transferrin saturation in critically ill patients with variable inflammation 4

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses – once-daily or alternate-day dosing improves tolerability with similar or better efficacy 1
• Do not stop iron when hemoglobin normalizes – continue for 3 months to replenish stores 1, 2
• Do not continue oral iron indefinitely without response – reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise 1
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1
• Do not supplement iron when ferritin is normal or high – this is potentially harmful 4

Physiologic Rationale for Once-Daily Dosing

The hepcidin-ferroportin regulatory pathway creates an inherent limit on gastrointestinal iron uptake. 5 Hepcidin rises in response to oral iron and blocks further absorption for approximately 24 hours. 5 Multiple daily doses lead to elevated hepcidin levels that prevent absorption of subsequent doses, while unabsorbed iron accumulates in the intestinal lumen causing constipation and other gastrointestinal side effects. 5, 2 Once-daily or alternate-day dosing allows hepcidin levels to decrease between doses, optimizing fractional iron absorption. 4, 5

Treatment Failure Management

If anemia does not resolve within 6 months despite appropriate iron therapy, reassess for: 1

• Ongoing blood loss
• Malabsorption syndromes (celiac disease, post-bariatric surgery)
• Non-adherence to therapy
• Misdiagnosis
• Consider small bowel evaluation and hematology consultation 1