Difference Between Ferrous Sulfate and Ferrous Gluconate
Both ferrous sulfate and ferrous gluconate are equally effective first-line oral iron supplements for treating iron deficiency anemia, with no substantial evidence that one is superior to the other in effectiveness, though they differ in elemental iron content, cost, and potentially in tolerability. 1
Key Differences
Elemental Iron Content
- Ferrous sulfate: Contains approximately 65 mg of elemental iron per tablet 1
- Ferrous gluconate: Contains 27-38 mg of elemental iron per tablet 1, with FDA labeling indicating 324 mg ferrous gluconate provides 38 mg elemental iron 2
This means patients need fewer ferrous sulfate tablets to achieve the same elemental iron dose.
Cost
Ferrous sulfate is typically the least expensive option, making it a reasonable first choice. 1
Absorption and Efficacy
Current guidelines state there is no substantial evidence that any one ferrous salt product is better than another in effectiveness. 1 However, research evidence shows some nuanced differences:
- One study in peritoneal dialysis patients found ferrous gluconate was better absorbed than ferrous sulfate, with maximal serum iron increases of 183.87% versus 113.51% respectively (p<0.05) 3
- In gastrectomized patients, ferrous sulfate showed significant iron absorption (148-168% increase at 120-180 minutes), while ferric gluconate showed no significant change 4
- Both preparations showed equivalent therapeutic efficacy in pregnancy-related iron deficiency anemia, with similar improvements in hemoglobin, hematocrit, and serum iron 5
Tolerability and Side Effects
Ferrous gluconate may be better tolerated than ferrous sulfate in some populations, though guideline-level evidence does not establish clear superiority. 1
Research findings on tolerability:
- In peritoneal dialysis patients, side effects occurred more frequently with ferrous sulfate than ferrous gluconate 3
- In pregnancy, liquid ferrous gluconate produced zero side effects and no dropouts, while ferrous sulfate caused gastrointestinal side effects and dropouts 5
- Overall, oral iron causes constipation in 12%, diarrhea in 8%, and nausea in 11% of patients 1
Clinical Recommendations
First-Line Choice
Start with ferrous sulfate 200 mg once daily (not twice or three times daily as previously recommended) because hepcidin elevation blocks further iron absorption for up to 48 hours after a single dose. 1 This approach maximizes absorption while minimizing side effects.
Alternative Options
- If ferrous sulfate is not tolerated, switch to ferrous gluconate or other ferrous salts 1
- Lower doses may be as effective and better tolerated 1
- Taking iron with meals improves tolerance but reduces absorption; taking with meat protein and 500 mg vitamin C can improve absorption even with food 1
Common Pitfalls to Avoid
- Do not prescribe iron more than once daily - this increases side effects without improving absorption due to hepcidin upregulation 1
- Avoid tea and coffee within one hour of iron intake - these are powerful inhibitors of iron absorption 1
- Do not assume poor response means the formulation is ineffective - check adherence first, as hemoglobin should increase by 1 g/dL within 2 weeks and ferritin should increase within a month 1
When to Switch to IV Iron
Consider intravenous iron if: 1
- Oral iron is not tolerated despite trying at least two different formulations 1
- Blood counts or iron stores do not improve with oral supplementation
- Conditions exist where oral iron absorption is impaired (post-bariatric surgery, active inflammatory bowel disease)
- Iron loss exceeds oral iron absorption capacity