What is the best iron supplement for patients with iron deficiency?

Best Iron Supplement for Iron Deficiency

Ferrous sulfate is the preferred oral iron supplement because no formulation has proven superior to any other, and ferrous sulfate is the least expensive option. 1

Oral Iron Supplementation

First-Line Formulation

• Ferrous sulfate 200 mg is the recommended first-line treatment due to its cost-effectiveness and equivalent efficacy to other iron formulations 1
• Other ferrous salts (ferrous gluconate, ferrous fumarate) are equally effective alternatives if ferrous sulfate is not tolerated 1
• Liquid preparations may be better tolerated when tablets cause side effects 1

Optimal Dosing Strategy

• Give oral iron once daily at most—more frequent dosing increases side effects without improving absorption due to hepcidin elevation 1
• Every-other-day dosing may be equally effective with better tolerability for some patients, as iron absorption rates remain similar 1
• Lower doses (e.g., 200 mg once or twice daily rather than three times daily) may be as effective and better tolerated 1

Enhancing Absorption

• Add vitamin C (250-500 mg) to oral iron supplementation to improve absorption, as vitamin C is the most potent enhancer of non-heme iron absorption 1, 2
• Take iron on an empty stomach when possible, as absorption is better away from meals 2
• Morning dosing is preferable to afternoon dosing because hepcidin levels are lower in the morning 2

Duration of Treatment

• Continue oral iron for 3 months after correction of anemia to replenish iron stores 1
• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 1

When to Use Intravenous Iron

Switch to intravenous iron if: 1

• The patient does not tolerate oral iron despite trying at least two different formulations
• Ferritin levels do not improve with a trial of oral iron
• The patient has a condition where oral iron is unlikely to be absorbed (e.g., inflammatory bowel disease with active inflammation, post-bariatric surgery, celiac disease)

IV Iron Formulations

• Prefer IV iron formulations that can replace iron deficits with 1 or 2 infusions over those requiring more than 2 infusions 1
• All IV iron formulations have similar safety profiles; true anaphylaxis is very rare (most reactions are complement activation-related pseudo-allergy) 1
• Available options include iron sucrose (Venofer), ferric carboxymaltose (Ferinject), and iron dextran (Cosmofer) 1, 3

Common Pitfalls to Avoid

Absorption Inhibitors

• Avoid taking iron with calcium-containing foods (dairy products), tea, or coffee, as these significantly decrease iron absorption 2
• Polyphenols (in certain vegetables) and phytates (in bran) also inhibit absorption 2
• Coffee decreases iron absorption by 54% and should not be consumed within an hour of taking iron 2

Contraindications for Vitamin C

• Never give vitamin C supplements to patients with hemochromatosis or iron overload, as vitamin C accelerates iron mobilization and can cause cardiac complications 2
• If vitamin C is needed for other reasons in iron-overloaded patients, limit to 500 mg daily only after physician discussion 2

Failure to Respond

If hemoglobin does not rise by 2 g/dL after 3-4 weeks, consider: 1

• Poor compliance with medication
• Continued blood loss
• Malabsorption
• Misdiagnosis
• Need for IV iron therapy

Special Populations

Post-Bariatric Surgery

• Use IV iron therapy in patients who have undergone bariatric procedures that disrupt duodenal iron absorption, particularly if they have iron-deficiency anemia without identifiable GI blood loss 1

Inflammatory Bowel Disease

• Use IV iron therapy in IBD patients with active inflammation and compromised absorption 1
• Treat active inflammation effectively to enhance iron absorption or reduce iron depletion 1