Which type of iron supplement is most effective for treating iron‑deficiency anemia?

Which Type of Iron Supplement is Most Effective?

Ferrous sulfate is the most effective and cost-effective oral iron supplement for treating iron-deficiency anemia, and should be taken as a single daily dose of 50-100 mg elemental iron (one 200 mg tablet containing 65 mg elemental iron) on an empty stomach in the morning. 1, 2

First-Line Iron Formulation

• Ferrous sulfate remains the gold standard for oral iron therapy, providing 65 mg of elemental iron per 200 mg tablet at a cost of approximately £1.00 for a 28-day supply 1, 3
• No single oral iron formulation has proven superiority over others in terms of efficacy or tolerability when comparing ferrous salts (ferrous sulfate, ferrous fumarate, ferrous gluconate) 1, 2
• Ferrous sulfate conventional-release tablets demonstrate the highest iron absorption compared to other preparations in laboratory studies 4
• Alternative ferrous salts (ferrous fumarate providing 69-106 mg elemental iron, or ferrous gluconate providing 37 mg elemental iron) can be considered if ferrous sulfate is not tolerated, though there is no evidence they are better tolerated 1, 2

Optimal Dosing Strategy

• Once-daily dosing of 50-100 mg elemental iron is superior to multiple daily doses because iron doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours, reducing absorption of subsequent doses by 35-45% 1, 2
• Take iron on an empty stomach in the morning, 1-2 hours before meals, to maximize absorption 2, 5
• Alternate-day dosing (every other day) significantly increases fractional iron absorption compared to daily dosing and may reduce gastrointestinal side effects while maintaining efficacy 1, 2

Formulations to Avoid

• Modified-release preparations are less suitable for prescribing according to the British National Formulary, as they demonstrate uniformly low iron absorption compared to conventional-release tablets 1, 4
• Multivitamin preparations contain insufficient elemental iron (up to 14 mg) for treating iron deficiency anemia and should not be used as the sole source of supplementation 1, 2

Enhancing Absorption and Tolerability

• Taking iron with vitamin C (250-500 mg) enhances absorption, especially if taking with meals 2, 5
• Avoid consuming tea or coffee within 1 hour after taking iron, as both are powerful inhibitors of iron absorption 2, 5
• Avoid taking iron with calcium-containing foods or aluminum-based antacids, which significantly reduce absorption 2, 5

Alternative Oral Formulations

• 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, with normalization of hemoglobin in 63-66% of cases after 12 weeks 1
• However, ferric maltol costs £47.60 versus £1.00 for ferrous sulfate per 28 days, and produces slower iron loading due to relatively low iron content 1, 2
• Gastrointestinal side effects with ferric maltol are comparable to placebo, but the rate of iron loading is comparatively slow 1

Monitoring Response

• Hemoglobin should rise by at least 10 g/L within 2 weeks of starting daily oral iron therapy; failure to achieve this strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%) 2
• Monitor hemoglobin within the first 4 weeks to confirm adequate response 2, 5
• Continue treatment for approximately 3 months after hemoglobin normalizes to ensure adequate repletion of iron stores 2, 5

When to Switch to Intravenous Iron

• Consider parenteral iron when oral iron causes intolerable side effects despite dosing adjustments, or when hemoglobin fails to rise after 2-4 weeks of adherent oral therapy 2, 5
• Intravenous iron produces a clinically meaningful hemoglobin response within one week and should be considered as an alternative to blood transfusion 1
• Modern formulations like ferric carboxymaltose and ferric derisomaltose can replenish total body iron stores in one or two infusions of 500-1000 mg 1, 3
• Intravenous iron is preferred for patients with inflammatory bowel disease, post-bariatric surgery, chronic kidney disease, or conditions where oral iron absorption is impaired 2, 5

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses of iron, as this increases side effects without improving absorption due to hepcidin-mediated blockade 1, 2
• Do not switch between different ferrous salts expecting better tolerability, as this is not supported by evidence 2, 5
• Do not discontinue iron therapy prematurely when hemoglobin normalizes—continue for 3 months to replenish iron stores 2, 5
• Gastrointestinal side effects are significantly more common with oral ferrous sulfate than placebo (OR 2.32,95% CI 1.74-3.08) or parenteral iron (OR 3.05,95% CI 2.07-4.48), but discontinuation rates in clinical trials are relatively low (0-24%) 1