What is the most appropriate first‑line oral iron supplement for an adult with low ferritin?

Best Iron Supplement for Low Ferritin

Ferrous sulfate 200 mg (providing 65 mg elemental iron) taken once daily in the morning on an empty stomach is the optimal first-line oral iron supplement for adults with low ferritin. 1, 2, 3

Why Ferrous Sulfate is the Gold Standard

• Ferrous sulfate remains the most cost-effective and evidence-based choice, costing approximately £1.00 for a 28-day supply compared to £47.60 for newer alternatives like ferric maltol. 1, 2
• No oral iron formulation has demonstrated superior efficacy or tolerability compared to ferrous sulfate in clinical trials—all ferrous salts (sulfate, fumarate, gluconate) are considered therapeutically equivalent. 1, 2, 4
• A single 200 mg ferrous sulfate tablet delivers 65 mg elemental iron, which falls perfectly within the recommended therapeutic range of 50–100 mg elemental iron daily. 1, 3

Optimal Dosing Strategy

• Take 50–100 mg elemental iron once daily in the morning, 1–2 hours before meals to maximize absorption while minimizing gastrointestinal side effects. 1, 2
• Never prescribe multiple daily doses—doses ≥60 mg elemental iron trigger hepcidin elevation that persists for 24 hours, reducing absorption of subsequent doses by 35–45%. 1, 2, 5
• If daily dosing causes intolerable gastrointestinal symptoms, switch to alternate-day dosing (every other day) with 100–200 mg elemental iron, which markedly increases fractional absorption and reduces side effects. 1, 2, 5

Monitoring Response

• Check hemoglobin at 2 weeks after starting therapy—an increase of ≥10 g/L predicts treatment success with 90% sensitivity and 79% specificity. 1, 2, 4
• Failure to achieve a ≥10 g/L hemoglobin rise at 2 weeks strongly predicts treatment failure and warrants investigation for non-adherence, ongoing blood loss, malabsorption, or concurrent B12/folate deficiency. 1, 2
• Continue oral iron for approximately 3 months after hemoglobin normalizes to fully replenish bone marrow iron stores. 1, 2, 4
• Monitor hemoglobin every 6 months during the first year after treatment completion to detect recurrent iron deficiency. 1

Strategies to Enhance Absorption

• Co-administer 250–500 mg vitamin C with the iron dose to enhance absorption, especially if the tablet must be taken with food due to intolerance. 2, 4
• Avoid coffee, tea, or calcium-containing foods/supplements within 1–2 hours of the iron dose, as these significantly inhibit absorption. 2, 4
• Discontinue proton-pump inhibitors and H₂-blockers if possible, as they reduce iron absorption. 1, 2

Alternative Oral Formulations (If Ferrous Sulfate Not Tolerated)

• Ferrous fumarate (210–325 mg tablets providing 69–106 mg elemental iron) or ferrous gluconate (300 mg tablets providing 37 mg elemental iron) are acceptable alternatives, though evidence does not support improved tolerability. 1, 2, 4
• Ferric maltol (30 mg twice daily) may be considered for patients with prior intolerance to traditional ferrous salts, particularly those with inactive inflammatory bowel disease, but it is substantially more expensive (£47.60 vs £1.00 per 28 days) and produces slower iron loading. 1, 2
• Gastrointestinal side effects with ferric maltol are comparable to placebo, making it a reasonable option when ferrous salts are genuinely not tolerated. 1

Formulations to Avoid

• Never prescribe modified-release or enteric-coated iron preparations—they release iron beyond the duodenum (the primary absorption site) and are classified as "less suitable for prescribing" by the British National Formulary. 1, 2, 4
• Do not rely on multivitamin preparations as the sole iron source, as they typically contain ≤14 mg elemental iron—insufficient for treating iron deficiency. 1, 2, 4

When to Escalate to Intravenous Iron

• Consider IV iron if hemoglobin does not rise after 2–4 weeks of adherent oral therapy—early oral non-responders have only a 21% chance of later response with continued oral iron versus 65% with IV iron. 1
• Switch to IV iron when gastrointestinal side effects remain intolerable despite dosing adjustments (alternate-day dosing, taking with food, vitamin C co-administration). 1, 6
• IV iron is indicated in malabsorption syndromes (inflammatory bowel disease, celiac disease, post-bariatric surgery), chronic kidney disease, heart failure, ongoing blood loss exceeding oral replacement capacity, and during the second and third trimesters of pregnancy. 1, 6
• Intravenous ferric carboxymaltose can replenish total body iron stores in one or two infusions (500–1000 mg per dose) and produces a clinically meaningful hemoglobin increase within one week. 1, 7

Common Pitfalls to Avoid

• Do not prescribe twice-daily or three-times-daily dosing—this increases gastrointestinal side effects (odds ratio 2.32 vs placebo) without improving absorption due to hepcidin-mediated blockade. 1, 2
• Do not switch between different ferrous salts expecting better tolerability—evidence does not support this practice. 1, 2, 4
• Do not discontinue oral iron when hemoglobin normalizes—continue for an additional 3 months to restore iron stores. 1, 2, 4
• Do not continue oral iron indefinitely without monitoring—failure to respond may indicate non-compliance, malabsorption, continued bleeding, or concurrent vitamin deficiency. 1, 2