What is the best oral iron supplementation for iron replacement therapy?

From the Guidelines

Ferrous sulfate is the best oral iron replacement for most patients with iron deficiency anemia. This is based on the most recent and highest quality study, which states that no single formulation of oral iron has any advantages over any other, and ferrous sulfate is preferred as the least expensive iron formulation 1.

Key Considerations

• The dose of ferrous sulfate is typically 325 mg (containing 65 mg elemental iron) taken 1-3 times daily.
• For optimal absorption, it should be taken on an empty stomach with vitamin C-containing foods or drinks, as adding vitamin C to oral iron supplementation improves absorption 1.
• If stomach upset occurs, it can be taken with food.
• Treatment should continue for 3-6 months after hemoglobin normalizes to replenish iron stores.

Alternative Formulations

• Alternative formulations include ferrous gluconate and ferrous fumarate, which may cause less gastrointestinal side effects in sensitive individuals.
• The British Society of Gastroenterology guidelines recommend that the initial treatment of IDA should be with one tablet per day of ferrous sulphate, fumarate or gluconate, and if not tolerated, a reduced dose or alternative oral preparations or parenteral iron should be considered 1.

Important Notes

• Common side effects include constipation, nausea, and black stools.
• Slow-release formulations are available but generally not recommended as they release iron beyond the duodenum where absorption is poor.
• Ferrous sulfate is preferred because it provides good bioavailability at a reasonable cost, making it the most efficient way to correct iron deficiency in most patients.
• For those who cannot tolerate oral iron, intravenous iron may be necessary.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Oral Iron Replacement Options

The following oral iron supplements are commonly used for iron replacement:

• Ferrous sulfate: a widely prescribed and inexpensive option 2
• Ferrous gluconate: an alternative to ferrous sulfate, with some studies suggesting it may be more effective in certain populations 3, 4
• Ferric citrate: an oral medication approved for the treatment of iron deficiency anemia in patients with chronic kidney disease (CKD) 5
• Ferrous glycinate chelate: a form of iron that may be more bioavailable than ferrous sulfate, with minimal gastrointestinal symptoms 6
• Ferric maltol: a novel iron formulation with potential benefits for patients with iron deficiency anemia 2
• Sucrosomial® iron: a nanoparticle-encapsulated form of iron that may offer improved efficacy and tolerability 2

Efficacy and Tolerability

Studies have compared the efficacy and tolerability of different oral iron supplements, including:

• Ferrous sulfate vs. ferrous gluconate: ferrous gluconate may be more effective in certain populations, such as toddlers 4 and patients with gastrectomy 3
• Ferrous sulfate vs. ferric citrate: ferric citrate may be more effective in patients with CKD 5
• Ferrous sulfate vs. ferrous glycinate chelate: ferrous sulfate may be more effective in patients with iron deficiency anemia after gastrectomy 6

Special Considerations

Certain populations may require special consideration when selecting an oral iron supplement, including:

• Patients with CKD: ferric citrate may be a suitable option 5
• Patients with gastrectomy: ferrous sulfate may be more effective than ferrous gluconate 3
• Toddlers: both ferrous gluconate and ferrous sulfate may be effective for prophylaxis, but ferrous gluconate may be more effective 4