What is more effective for treating iron deficiency anemia, ferric pyrophosphate or heme iron supplements, such as ferrous sulfate?

Ferrous Sulfate is Superior to Ferric Pyrophosphate for Iron Deficiency Anemia

For treating iron deficiency anemia, ferrous sulfate (or other ferrous salts like ferrous fumarate or ferrous gluconate) is the preferred first-line oral iron supplement, not ferric pyrophosphate. The British Society of Gastroenterology strongly recommends starting with one tablet daily of ferrous sulfate, fumarate, or gluconate as initial treatment 1.

Why Ferrous Salts Are Preferred

Evidence-Based Efficacy

• Ferrous sulfate is the most cost-effective and well-established treatment for iron deficiency anemia, providing 65 mg of elemental iron per 200 mg tablet 1
• The optimal oral iron dose is 50-100 mg elemental iron once daily, which ferrous sulfate readily provides 1
• Ferrous salts (sulfate, fumarate, gluconate) are equally effective at correcting hemoglobin and replenishing iron stores 1

Absorption and Dosing Advantages

• Once-daily dosing of 60-100 mg elemental iron is as effective as split dosing due to hepcidin-mediated absorption regulation 1
• Alternate-day dosing with ferrous salts significantly increases fractional iron absorption compared to daily dosing when side effects occur 1
• Lower doses (100 mg ferrous fumarate once daily) are sufficient for symptom-free patients with anemia 2

Ferric Pyrophosphate Limitations

Ferric pyrophosphate is not mentioned in major gastroenterology guidelines as a recommended oral iron formulation 1. The guidelines specifically list ferrous sulfate, ferrous fumarate, and ferrous gluconate as standard preparations, with ferric maltol as an alternative ferric compound for specific situations 1.

When Ferric Compounds May Be Considered

• Ferric maltol (not ferric pyrophosphate) is an alternative for patients with inactive inflammatory bowel disease who have failed or are intolerant to traditional ferrous salts 1
• Ferric maltol normalized hemoglobin in 63-66% of cases with moderate IDA over 12 weeks, with GI side effects comparable to placebo 1
• However, ferric maltol is considerably more expensive (£47.60 per 28 days) compared to ferrous sulfate (£1.00 per 28 days) 1

Practical Treatment Algorithm

Initial Treatment

1. Start with ferrous sulfate 200 mg once daily (65 mg elemental iron) taken on an empty stomach 1
2. Monitor hemoglobin response at 4 weeks—expect at least 10 g/L rise 1
3. Continue for 3 months after hemoglobin normalization to replenish iron stores 1

If Side Effects Occur

1. Switch to alternate-day dosing of the same ferrous salt (improves absorption and reduces GI symptoms) 1
2. Consider ferrous fumarate or ferrous gluconate as alternatives 1
3. Only if intolerant to at least two ferrous preparations, consider ferric maltol or parenteral iron 1

When to Use Parenteral Iron Instead

• Oral iron contraindicated, ineffective, or not tolerated after trying multiple formulations 1
• Severe symptomatic anemia requiring rapid correction 1
• Active inflammatory bowel disease, dialysis-dependent renal insufficiency, or heart failure 1, 2

Common Pitfalls to Avoid

• Don't prescribe modified-release preparations—they are less suitable for prescribing per British National Formulary 1
• Don't use three-times-daily dosing—once-daily or alternate-day dosing is equally effective with better tolerability 1, 2
• Don't switch between ferrous salts for side effects—this is not evidence-based; try alternate-day dosing instead 1
• Don't use parenteral iron as first-line—reserve for specific indications as it's more expensive and carries hypersensitivity risks 1

The evidence overwhelmingly supports ferrous sulfate and other ferrous salts as first-line therapy, with no role for ferric pyrophosphate in current treatment guidelines 1.