Is EzFer Easier to Absorb Than Standard Ferrous Sulfate?
No, polysaccharide-iron complex (PIC) formulations like EzFer are not easier to absorb than standard ferrous sulfate—in fact, ferrous sulfate demonstrates superior absorption and efficacy for treating iron-deficiency anemia. 1, 2, 3
Evidence Supporting Ferrous Sulfate Superiority
Ferrous sulfate remains the gold-standard oral iron formulation because it provides the most bioavailable form of iron at the lowest cost (approximately £1.00 for a 28-day supply versus significantly higher costs for alternative formulations). 4 The ferrous (Fe²⁺) form is directly absorbed by enterocytes, whereas ferric (Fe³⁺) complexes like polysaccharide-iron must first be reduced to ferrous iron before absorption, creating an additional rate-limiting step. 3
Direct Comparative Evidence
A head-to-head randomized trial comparing ferrous fumarate (with vitamin C) versus polysaccharide-iron complex demonstrated that the ferrous product was significantly more effective at increasing both hemoglobin and serum ferritin levels over 12 weeks. 2 While both formulations were well-tolerated with no withdrawals due to side effects, the ferrous preparation achieved superior therapeutic endpoints. 2
A systematic review comparing ferrous sulfate with ferric iron polymaltose complex concluded that slow-release ferrous sulfate preparations remain the established standard treatment given their superior bioavailability, efficacy, and acceptable tolerability demonstrated across multiple large clinical studies. 3
The Vitamin C Advantage in EzFer May Not Overcome Absorption Limitations
While EzFer contains vitamin C (which enhances non-heme iron absorption by forming a chelate with iron and reducing ferric to ferrous iron 1), this advantage does not compensate for the inherently lower bioavailability of the polysaccharide-iron complex itself.
The evidence for vitamin C co-administration improving clinical outcomes is surprisingly weak. A 2023 systematic review and meta-analysis found that adding vitamin C to oral iron supplementation did not produce statistically significant improvements in hemoglobin or ferritin levels, with very low quality of evidence. 5 The American Gastroenterological Association acknowledges that while vitamin C co-administration is commonly recommended, the supporting evidence is limited. 1
Optimal Iron Supplementation Strategy
For maximum absorption and efficacy, take standard ferrous sulfate (200 mg tablet providing 65 mg elemental iron) once daily in the morning on an empty stomach with 100-500 mg vitamin C. 1, 4 This approach:
- Provides the most bioavailable iron form at lowest cost 4
- Maximizes absorption through fasting administration 1
- Leverages vitamin C's enhancement effect 1
- Avoids hepcidin-mediated absorption blockade from multiple daily doses 4
Dosing Frequency Matters More Than Formulation
Once-daily dosing is superior to multiple daily doses because iron doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours, reducing absorption of subsequent doses by 35-45%. 4 If daily dosing causes intolerable gastrointestinal side effects, alternate-day dosing (every other day) significantly increases fractional iron absorption while reducing side effects. 4
When to Consider Alternative Formulations
Polysaccharide-iron complexes may be considered only if:
- Standard ferrous sulfate causes intolerable gastrointestinal side effects despite dosing adjustments 4
- The patient has failed multiple ferrous salt formulations 4
However, switching between different iron formulations expecting better tolerability is not supported by evidence, as gastrointestinal side effects are similar across formulations. 4
Monitoring Treatment Success
Hemoglobin should increase by at least 10 g/L within 2 weeks of starting therapy; failure to achieve this strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%) and warrants investigation for non-compliance, continued blood loss, malabsorption, or consideration of intravenous iron. 4 Continue treatment for approximately 3 months after hemoglobin normalizes to adequately replenish iron stores. 4
Critical Caveat
Patients with hemochromatosis or iron overload must completely avoid vitamin C supplements with iron, as vitamin C accelerates iron mobilization and can cause cardiac arrhythmias, cardiomyopathy, and sudden death. 1