Oral Iron Supplementation for Iron Deficiency: Every Other Day vs Daily Dosing

Every-other-day iron dosing may be better tolerated for patients with similar or equal rates of iron absorption compared to daily dosing. 1

Physiological Basis for Alternate-Day Dosing

When oral iron is taken, serum hepcidin levels increase in response and remain elevated for up to 48 hours, blocking further iron absorption 1
Taking iron more frequently than once daily will not improve absorption but will increase side effects due to this hepcidin-mediated regulatory mechanism 1
Alternate-day dosing leads to significantly increased fractional iron absorption in iron-depleted individuals compared with daily dosing 1, 2

For most patients with iron deficiency, a single morning dose of 50-100 mg elemental iron is sufficient 1, 3
If standard doses are not tolerated, consider:
- Reduced dose of one tablet every other day 1
- Taking iron with 250-500mg vitamin C to enhance absorption 1, 3
- Avoiding tea or coffee within an hour of taking iron 1, 3

Studies using serum hepcidin profiles and stable iron isotopes have shown that oral iron doses ≥60 mg stimulate an acute increase in hepcidin that persists 24 hours but subsides by 48 hours 2
To maximize fractional iron absorption, oral doses ≥60 mg should be given on alternate days 2
A randomized controlled trial comparing alternate-day dosing (120 mg elemental iron) versus daily dosing (60 mg) found no significant difference in hemoglobin improvement after 8 weeks 4

Monitor hemoglobin response within the first 4 weeks of treatment 1, 3
Expect hemoglobin to increase by approximately 1 g/dL within 2 weeks in patients responding to therapy 1
Absence of a hemoglobin rise of at least 10 g/L after 2 weeks strongly predicts subsequent treatment failure 3
Treatment should continue for approximately 3 months after hemoglobin normalizes to ensure adequate repletion of marrow iron stores 1, 3

If oral iron is not tolerated despite modifications, consider:
- Alternative oral iron preparations 1, 3
- Intravenous iron therapy 1
Intravenous iron should be considered when:
- Oral iron is contraindicated, ineffective, or not tolerated 1
- Patient has conditions where oral iron absorption is impaired (e.g., inflammatory bowel disease, post-bariatric surgery) 1

Prescribing multiple daily doses of iron, which increases side effects without improving absorption 1
Using modified-release preparations, which are indicated as "less suitable for prescribing" 3
Relying on multivitamin preparations as the sole source of iron supplementation, as they typically contain insufficient elemental iron (up to 14 mg) 1, 3
Taking iron with calcium-containing foods or medications, which can significantly reduce absorption 1, 3