What is the most effective first‑line oral iron supplement for low ferritin and iron deficiency?

Best Oral Iron Supplementation for Low Ferritin and Iron

Ferrous sulfate 325 mg (65 mg elemental iron) taken once daily is the first-line oral iron supplement for low ferritin and iron deficiency. 1, 2, 3

Why Ferrous Sulfate is Preferred

• No formulation has proven superiority over others in terms of efficacy, making ferrous sulfate the preferred choice solely because it is the least expensive option while providing known amounts of elemental iron 1
• Ferrous sulfate remains the gold standard with well-established bioavailability, efficacy, and acceptable tolerability demonstrated in large clinical studies 4, 5
• Alternative ferrous salts (ferrous fumarate providing 69-106 mg elemental iron, or ferrous gluconate providing 37-38 mg elemental iron) can be substituted if ferrous sulfate is not tolerated 2

Optimal Dosing Strategy

• Take once daily, not multiple times per day - more frequent dosing increases hepcidin levels, which paradoxically decreases iron absorption while worsening gastrointestinal side effects 1, 6, 2
• Consider every-other-day dosing as an alternative, which may achieve similar iron absorption with better tolerability for some patients 1, 6
• The standard adult dose is 200 mg elemental iron daily in divided doses, though once-daily dosing of 65 mg elemental iron (one 325 mg ferrous sulfate tablet) is now preferred 1

Maximizing Absorption

• Add vitamin C (ascorbic acid) 80-500 mg with each iron dose to enhance absorption by forming a chelate with iron and preventing formation of insoluble compounds 1, 6, 2
• Take on an empty stomach when possible, ideally in the morning when hepcidin levels are lowest 6, 2
• If gastrointestinal intolerance occurs, taking with food is acceptable despite reduced absorption 6
• Avoid tea or coffee within one hour of iron supplementation as these are powerful inhibitors of iron absorption 2

Treatment Duration and Monitoring

• Continue treatment for approximately 3 months after hemoglobin normalizes to adequately replenish marrow iron stores 1, 2
• Monitor hemoglobin response within the first 4 weeks of treatment 6, 2
• Expect hemoglobin to increase by approximately 1 g/dL within 2 weeks in patients responding to therapy 2

When Oral Iron Fails

Switch to intravenous iron if: 1, 6

• Ferritin levels fail to improve after 4 weeks of optimized oral therapy
• Patient cannot tolerate oral iron despite dosing adjustments
• Malabsorption conditions exist (active inflammatory bowel disease, post-bariatric surgery, celiac disease)
• Ongoing blood loss exceeds oral iron replacement capacity

Managing Side Effects

• Common side effects include constipation (12%), diarrhea (8%), and nausea (11%) 2
• If standard doses are not tolerated, reduce dose, take with food, or switch to an alternative ferrous salt formulation 2
• For patients with gastrointestinal sensitivity, limit elemental iron to no more than 100 mg per day 2

Special Considerations

• Ferric maltol may be considered in patients with previous intolerance to traditional ferrous salts, though it has relatively low iron content and is more expensive 2
• Iron polysaccharide is more expensive and no better tolerated than ionic iron salts, with no well-designed studies supporting superior effectiveness 1
• Avoid multivitamin preparations as the sole iron source, as they contain insufficient elemental iron for treating deficiency 2