What is the best oral prescribed iron supplement?

Best Oral Prescribed Iron Supplement

For most patients requiring prescription oral iron supplementation, ferrous sulfate 325 mg (65 mg elemental iron) taken once daily or on alternate days is the optimal choice, as it is the most cost-effective, provides known amounts of elemental iron, and has equivalent efficacy to more expensive formulations. 1

Traditional Iron Salts: The Evidence-Based First Choice

Ferrous Sulfate as the Gold Standard

• Ferrous sulfate 325 mg provides 65 mg elemental iron per tablet and costs approximately $2.29 per month for standard dosing, making it the most economical option 1
• The British Society of Gastroenterology confirms there is no convincing evidence for the superiority of any readily available traditional iron salts over ferrous sulfate 1
• All traditional ferrous salts (sulfate, fumarate, gluconate) have similar gastrointestinal side effect profiles, with no dose-effect relationship over the range of 50-400 mg elemental iron per day 1

Comparative Analysis of Traditional Salts

• Ferrous fumarate (325 mg tablet = 108 mg elemental iron, $1.63/month) provides the highest elemental iron content but offers no clinical advantage 1
• Ferrous gluconate (325 mg tablet = 38 mg elemental iron, $5.08/month) requires more tablets to achieve target dosing and is more expensive 1, 2, 3
• The National Kidney Foundation explicitly recommends using ionic iron salts (sulfate, fumarate, or gluconate) because they are the cheapest and provide known amounts of elemental iron 1

Optimal Dosing Strategy

Single Daily or Alternate-Day Dosing

• Recent evidence supports 50-100 mg elemental iron once daily (one ferrous sulfate 200-325 mg tablet) taken in the fasting state as the best compromise for initial treatment 1
• Alternate-day dosing with 60-120 mg elemental iron may maximize fractional absorption by allowing hepcidin levels to subside between doses 4
• The traditional recommendation of 200 mg elemental iron daily in divided doses is being reconsidered, as lower doses have comparable efficacy with fewer side effects 1, 5

Administration Guidelines

• Take oral iron on an empty stomach (at least 1 hour before or 2 hours after meals) for optimal absorption 1, 6
• Food consumed within 2 hours before or 1 hour after iron supplementation reduces absorption by up to 50% 1
• Avoid concurrent use with aluminum-based phosphate binders, which reduce iron absorption 1
• Morning dosing is preferred over afternoon/evening administration due to circadian hepcidin patterns 4

When NOT to Use Traditional Oral Iron

Consider Newer Formulations or IV Iron When:

• Chronic kidney disease patients may benefit from ferric citrate (210 mg elemental iron per tablet), which also functions as a phosphate binder and can lower FGF23 levels 1
• Ferric maltol (30 mg elemental iron, twice daily) is an option for patients requiring alternatives, though more expensive 1
• Intolerance to traditional salts: Switching between ferrous salts is not evidence-based; consider alternate-day dosing, lower doses, or IV iron instead 1
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease with active inflammation) warrant IV iron 1, 7
• Ongoing blood loss or chronic inflammatory conditions (CKD, heart failure, IBD, cancer) respond better to IV iron 1, 7

What to Avoid

Iron Polysaccharide: Not Recommended

• Iron polysaccharide is more expensive and provides no advantage over traditional iron salts 1, 6
• It is no better tolerated than ionic iron salts in terms of gastrointestinal side effects 1, 6
• One study showed iron polysaccharide was associated with the smallest rise in hematocrit among four oral preparations in hemodialysis patients 1, 6
• Despite marketing claims, there are no well-designed clinical studies supporting superior effectiveness 1

Monitoring Response

Early Assessment is Critical

• Hemoglobin should increase by at least 10 g/L (1 g/dL) after 2 weeks of daily oral iron therapy; failure to achieve this predicts subsequent treatment failure (sensitivity 90.1%, specificity 79.3%) 1, 6
• Check hemoglobin every 4 weeks until normalized 1
• After hemoglobin normalization, continue oral iron for 2-3 months to replenish stores 1
• Monitor blood counts every 3 months for 12 months, then every 6 months for 2-3 years to detect recurrent deficiency 1

Common Pitfalls to Avoid

• Do not switch between different ferrous salts for intolerance—this is not evidence-based; instead, try lower doses, alternate-day dosing, or IV iron 1
• Do not prescribe divided doses throughout the day—single morning doses on daily or alternate-day schedules optimize absorption 1, 4
• Do not assume ascorbic acid improves absorption—evidence does not support this for ferrous iron 1
• Do not continue oral iron indefinitely without monitoring response—early failure to respond requires investigation and alternative therapy 1