What is the preferred choice between ferrous (iron) sulphate and ferrous (iron) ascorbate for treating iron deficiency?

Ferrous Sulphate vs Ferrous Ascorbate for Iron Deficiency

Ferrous sulphate is the preferred first-line oral iron formulation for treating iron deficiency, as it is the most cost-effective option with no proven advantages of other formulations in terms of efficacy or tolerability. 1, 2

Primary Recommendation

• Ferrous sulphate 200 mg tablets (providing 65 mg elemental iron) should be prescribed as the standard treatment, costing approximately £1.00 for a 28-day supply compared to significantly more expensive alternatives 1, 2, 3
• The American College of Gastroenterology explicitly states that no single iron formulation has proven advantages over others in terms of tolerability 2
• Standard ferrous sulphate provides 65 mg of elemental iron per 200 mg tablet, which is adequate for therapeutic dosing 1, 3

Optimal Dosing Strategy

• Once-daily dosing of 50-100 mg elemental iron is recommended rather than multiple daily doses, as more frequent dosing increases side effects without improving absorption due to hepcidin elevation 2, 4
• Ferrous sulphate 200 mg (65 mg elemental iron) taken once daily or on alternate days is the evidence-based approach 2, 5
• Taking iron on an empty stomach maximizes absorption, though this may increase gastrointestinal side effects 2

Enhancing Absorption with Vitamin C

• Adding vitamin C (250-500 mg) with ferrous sulphate significantly enhances iron absorption by forming a chelate with iron and reducing ferric to ferrous iron 1, 2, 6
• This combination is particularly important for patients following plant-based diets or those with impaired absorption 6
• The British Society of Gastroenterology notes that while ascorbic acid may enhance absorption, there are limited data for its effectiveness specifically in treating iron deficiency anemia 1

Ferrous Ascorbate: Limited Evidence

• Ferrous ascorbate is marketed as a combination product containing both iron and vitamin C 7, 8
• One study in pregnant women showed ferrous ascorbate had comparable efficacy to ferrous sulphate, with slightly higher hemoglobin levels at day 90 (though this difference was marginal) 8
• There is no high-quality evidence demonstrating superior efficacy or tolerability of ferrous ascorbate over ferrous sulphate plus separate vitamin C supplementation 8
• The cost-effectiveness of ferrous ascorbate has not been established in guidelines 1, 2

Alternative Formulations When Ferrous Sulphate Not Tolerated

• If ferrous sulphate is not tolerated, consider ferrous fumarate (69-106 mg elemental iron per tablet) or ferrous gluconate (37 mg elemental iron per tablet) 1, 2
• Lower doses of ferrous sulphate may be as effective and better tolerated in patients not tolerating traditional doses 1
• Taking iron with food improves tolerability but decreases absorption—this trade-off may be necessary for adherence 2, 6

Monitoring Response

• Expect hemoglobin to increase by approximately 1 g/dL within 2 weeks in patients responding to therapy 2, 9
• The absence of a hemoglobin rise of at least 10 g/L after 2 weeks of daily oral iron strongly predicts subsequent treatment failure (sensitivity 90.1%, specificity 79.3%) 2
• Continue treatment for approximately 3 months after hemoglobin normalizes to ensure adequate repletion of iron stores 1, 2, 9

When to Consider Intravenous Iron

• Intravenous iron should be considered when oral iron is not tolerated despite modifications, ferritin levels do not improve with oral iron trial, or the patient has conditions where oral iron absorption is impaired (inflammatory bowel disease, post-bariatric surgery, chronic kidney disease, heart failure) 2, 9
• Parenteral iron can produce a clinically meaningful hemoglobin response within a week 2

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 lasting up to 48 hours 2, 4
• Avoid taking iron with tea, coffee, or calcium-containing foods, which significantly inhibit absorption 2, 6
• Do not use modified-release preparations, as they are considered "less suitable for prescribing" by the British National Formulary 2
• Avoid multivitamin preparations as the sole source of iron supplementation, as they typically contain insufficient elemental iron (up to 14 mg) for treating iron deficiency anemia 2