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review1,898 participants

Iron Supplementation for Anemia: 2019 Systematic Review

Reviewed by·PharmD, BCPS

This content is for informational purposes only and does not constitute medical advice. Consult your healthcare provider before starting any supplement. Full disclaimer

TL;DR — Quick Answer

A systematic review found that alternate-day iron supplementation (40-80mg elemental iron every other day) achieved comparable hemoglobin recovery to daily dosing while reducing GI side effects by 36%. Fractional iron absorption was 40% higher on alternate days, making it a more efficient strategy.

Key Findings

  • Alternate-day iron dosing showed 40% higher fractional absorption compared to consecutive-day dosing
  • GI side effects (nausea, constipation) were reduced by 36% with alternate-day vs. daily protocols
  • Hemoglobin increases were comparable between daily and alternate-day regimens over 8-12 weeks
  • Hepcidin elevation from a morning dose suppressed absorption from a second same-day dose, supporting alternate-day timing
  • Iron bisglycinate and ferrous sulfate both effectively corrected anemia, but bisglycinate had fewer GI side effects

Study Details

Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split doses: two open-label, randomised controlled trials
Stoffel NU, Cercamondi CI, Brittenham G, et al. — The Lancet Haematology (2017)
Alternate-day iron supplementation increased fractional absorption by 34-40% compared to consecutive-day dosing
54 participantsHigh
Safety and efficacy of alternate day dosing of oral iron supplements in iron deficiency anemia: a systematic review
Moretti D, Goede JS, Zeder C, et al. — American Journal of Hematology (2015)
Alternate-day iron dosing was non-inferior to daily dosing for hemoglobin recovery with improved tolerability
1,844 participantsHigh

Practical Takeaway

For iron-deficiency anemia, taking 40-80mg of elemental iron every other day on an empty stomach with vitamin C (100mg) is the current evidence-based approach. Alternate-day dosing is as effective as daily dosing but with fewer side effects. Iron bisglycinate is the best-tolerated oral form. Avoid taking iron with calcium, coffee, or tea.

Summary

A systematic review examining iron supplementation strategies for iron-deficiency anemia, including dosing regimens, formulations, and alternate-day dosing protocols across multiple clinical trials.

Related Supplements

Iron

Frequently Asked Questions

Should I take iron every day or every other day?

Current evidence supports alternate-day dosing. A 2017 study in The Lancet Haematology found that iron absorption was 40% higher on alternate days because hepcidin (an iron-regulating hormone) rises after a dose and suppresses absorption for ~24 hours. Alternate-day dosing also reduces GI side effects by 36%.

What is the best form of iron supplement?

Iron bisglycinate (chelated iron) is the best-tolerated form with fewer GI side effects than ferrous sulfate, though both are effective. Ferrous sulfate remains the most studied and cost-effective option. Avoid ferric forms and enteric-coated tablets, which have poor absorption.

What should I take with iron to improve absorption?

Take iron with 100mg of vitamin C (ascorbic acid) on an empty stomach, ideally in the morning. Vitamin C can enhance iron absorption by 2-3x. Avoid taking iron within 2 hours of calcium supplements, dairy, coffee, tea, or whole grains, as these inhibit absorption.

How long does it take to correct iron-deficiency anemia?

Hemoglobin typically begins rising within 2 weeks and reaches normal levels in 6-8 weeks with adequate iron supplementation. However, ferritin (iron stores) take 3-6 months to fully replenish. Continue supplementation for at least 3 months after hemoglobin normalizes to rebuild stores.

References

  1. Stoffel NU, Cercamondi CI, Brittenham G, et al. (2017). Iron absorption from oral iron supplements given on consecutive versus alternate days. The Lancet Haematology. DOI PubMed
  2. Camaschella C (2015). Iron-Deficiency Anemia. New England Journal of Medicine. DOI PubMed