What is the most effective oral iron supplement with optimal absorption and tolerance?

Best Oral Iron Supplement for Absorption and Tolerance

Prescribe ferrous sulfate 200 mg once daily (providing 65 mg elemental iron) as first-line therapy, as it is the most cost-effective formulation with equivalent efficacy and tolerability to other preparations. 1, 2

Recommended First-Line Iron Formulation

• Ferrous sulfate remains the gold standard for oral iron replacement, recommended by both the American College of Gastroenterology and British Society of Gastroenterology as the most cost-effective option with no proven advantages of alternative formulations in terms of tolerability 2

• Standard ferrous sulfate 200 mg tablets provide 65 mg elemental iron per tablet and cost approximately £1.00 for a 28-day supply, making them significantly less expensive than alternatives 1, 2

• If ferrous sulfate is not tolerated, switch to alternative ferrous salts rather than assuming all iron preparations will cause similar side effects 2:

  • Ferrous fumarate (69-106 mg elemental iron per tablet) 1, 2
  • Ferrous gluconate (37 mg elemental iron per tablet) 1, 2

Optimal Dosing Strategy for Maximum Absorption

Prescribe 50-100 mg elemental iron once daily, not multiple times per day. 1, 2

• Once-daily dosing achieves similar total iron absorption compared to twice-daily dosing because oral iron stimulates hepcidin levels, which remain elevated for up to 48 hours and reduce subsequent iron absorption by 35-45% 1, 3

• Alternate-day dosing leads to significantly increased fractional iron absorption compared to daily dosing and may be considered if daily dosing causes intolerable side effects 1, 2

• Taking iron more frequently than once daily increases side effects without improving absorption due to hepcidin-mediated blockade 2, 3

Strategies to Maximize Absorption

• Take iron on an empty stomach (1-2 hours before or after meals) to maximize absorption, though this may increase gastrointestinal side effects 2, 4

• Add vitamin C 250-500 mg with each iron dose to enhance absorption by forming a chelate with iron 2, 3, 4

• If taking with food is necessary for tolerability, consume with meat protein to improve absorption 3, 4

Critical Substances to Avoid

• Do not take iron with tea or coffee within 1 hour of dosing, as these are powerful inhibitors of iron absorption 2, 3

• Avoid calcium-containing foods or supplements at the time of iron administration 3, 4

• Do not take with aluminum-based antacids or phosphate binders, as these significantly reduce absorption 3, 4

• Avoid fiber-containing foods at the time of iron dosing 3, 4

Formulations to Avoid

• Modified-release preparations are "less suitable for prescribing" according to the British National Formulary, as they release iron beyond the duodenum where absorption is optimal 1, 2

• Multivitamin preparations should not be used as the sole source of iron supplementation, as they typically contain insufficient elemental iron (up to 14 mg) for treating iron deficiency 2, 4

Alternative for Intolerant Patients

• Ferric maltol (30 mg twice daily) may be considered for patients with previous intolerance to traditional iron salts, particularly those with inactive inflammatory bowel disease 1, 2

• Ferric maltol normalized hemoglobin in 63-66% of cases after 12 weeks in patients with moderate iron deficiency anemia (Hb >95 g/L), with gastrointestinal side effects comparable to placebo 1

• However, ferric maltol costs £47.60 versus £1.00 for ferrous sulfate per 28-day supply, making it considerably more expensive 1, 2

Monitoring Response to Confirm Efficacy

• Check hemoglobin within 2 weeks of starting therapy—expect an increase of at least 10 g/L (1 g/dL) in responders 2, 3

• The absence of a hemoglobin rise of at least 10 g/L after 2 weeks strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%) and should prompt consideration of intravenous iron 2, 3

• Continue treatment for 3 months after hemoglobin normalizes to ensure adequate repletion of iron stores 2, 3, 4

• Monitor blood counts every 6 months after completing treatment to detect recurrent iron deficiency 1

When to Switch to Intravenous Iron

• Consider intravenous iron when 2, 3:

  • Oral iron is not tolerated despite dosing modifications
  • Ferritin levels do not improve after an adequate trial of oral iron
  • Patient has conditions impairing oral iron absorption (inflammatory bowel disease, post-bariatric surgery, chronic kidney disease)
  • Blood loss exceeds the ability to replete iron orally

• Parenteral iron produces a clinically meaningful hemoglobin response within one week and should be considered as an alternative to blood transfusion in most cases 1, 2

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses, as this increases side effects without improving absorption due to hepcidin elevation 2, 3, 4

• Do not discontinue therapy prematurely—improvement in hemoglobin occurs within 2-4 weeks, but complete iron store repletion requires 3 months of continued therapy after normalization 2, 3, 4

• Do not assume all gastrointestinal symptoms are due to iron—persistent symptoms warrant evaluation for other causes 3

• Do not use enteric-coated formulations, as they may improve tolerability but decrease absorption by releasing iron beyond the optimal absorption site 3