Every-Other-Day Iron Supplementation Is More Effective Than Daily Dosing
Stoffel NU, et al • American Journal of Clinical Nutrition
Key Finding
Alternate-day iron dosing results in 34% higher fractional absorption compared to daily dosing, due to hepcidin dynamics.
Key Findings
- 1Hepcidin rises 24+ hours after iron supplementation, suppressing subsequent absorption
- 2Alternate-day dosing allows hepcidin to return to baseline, improving next-dose absorption
- 3Single morning doses absorbed better than twice-daily split dosing
- 4This explains why traditional daily high-dose iron often causes GI side effects without proportional benefit
- 5Clinical recommendation: 30-60mg elemental iron every other day may be more effective than daily dosing
Original title: “Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women”
Plain English Summary
This randomized controlled trial studied iron absorption in iron-depleted women, comparing daily vs alternate-day dosing. The key finding is that hepcidin (the iron-regulating hormone) rises after each iron dose and suppresses absorption for 24+ hours. By dosing every other day, total iron absorption was significantly higher than with daily supplementation.
In-Depth Analysis
This landmark RCT changed clinical practice for iron supplementation by revealing the critical role of hepcidin timing in iron absorption.
Study Design
- •54 iron-depleted (ferritin <25 μg/L) but non-anemic women
- •Compared: daily vs alternate-day dosing over 14 days
- •Also compared: single morning dose vs twice-daily split dosing
- •Measured: fractional iron absorption using stable iron isotopes
Key Findings
Hepcidin Dynamics
After each iron dose, serum hepcidin increased significantly and remained elevated for 24+ hours. This elevated hepcidin:
- •Blocks iron absorption from subsequent doses
- •Explains why increasing iron dose doesn't proportionally increase absorption
- •Creates a "refractory period" for iron uptake
Absorption Results
- •Alternate-day dosing: 34% higher fractional absorption
- •Single morning dose: Better absorbed than split dosing
- •Practical implication: Less frequent dosing = more total iron absorbed
Clinical Application
Instead of 325mg ferrous sulfate daily (traditional approach):
- •Consider 30-60mg elemental iron every other day
- •Take in the morning on an empty stomach
- •Pair with vitamin C to enhance absorption
- •Expect fewer GI side effects with improved efficacy
Paradigm Relevance
How this study applies to different clinical perspectives:
Standard Medical
Conventional clinical guidelines used by most doctors
Not directly relevant to this paradigm
Research Consensus
RelevantCurrent scientific understanding, often ahead of guidelines
Metabolic Optimization
RelevantProactive targets for optimal health, not just disease absence
Study Details
- Type
- Randomized Controlled Trial
Related Biomarkers
Calculate & Evaluate on Metabolicum
Original Source
DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.
Related Studies
The effect of low versus high fractional iron absorption on iron absorption and utilization
Stoffel NU, et al • American Journal of Clinical Nutrition • 2020
Alternate-day iron absorption 40-50% higher than consecutive day (p<0.001); 200mg alternate-day yields ~2x total absorption vs 100mg consecutive-day
Iron Status of Vegetarian Adults: A Review of Literature
Pawlak R, et al • American Journal of Lifestyle Medicine • 2016
Female vegetarians: ferritin <12 µg/L prevalence 12-79%; inadequate hemoglobin 6-30.3%. Male vegetarians: ferritin <12 µg/L prevalence 1.7-29%
Iron-Deficiency Anemia: A Comprehensive Clinical Review
Camaschella C • New England Journal of Medicine • 2015
Iron deficiency is the most common nutritional deficiency worldwide, affecting an estimated 2 billion people, with ferritin being the most sensitive early marker.