Treatment for Low Iron Saturation
Start with oral ferrous sulfate 200 mg twice daily (or 325 mg daily/alternate days) as first-line treatment when low iron saturation is accompanied by anemia (hemoglobin <110 g/L). 1, 2
Initial Assessment Required
Before treating low iron saturation, you must determine:
- Hemoglobin level: Treatment is indicated only when Hb <110 g/L (anemia is present) 1
- Ferritin level: Helps distinguish absolute iron deficiency (ferritin <30 ng/mL in non-inflammatory conditions, <100 ng/mL in cancer/inflammation) from functional iron deficiency 3
- Transferrin saturation <16-20% confirms iron-deficient erythropoiesis but warrants treatment only with concurrent anemia 1
Critical pitfall: Do not treat isolated low transferrin saturation without anemia or low ferritin—this can lead to iron overload and organ damage. 1
Oral Iron Therapy (First-Line)
Ferrous sulfate remains the gold standard due to proven efficacy, low cost, and extensive clinical evidence. 3, 1, 4
Dosing Options:
- Standard dose: Ferrous sulfate 200 mg twice daily (provides ~65 mg elemental iron per dose) 3, 1, 5
- Alternative lower dose: 325 mg daily or every other day—equally effective with better tolerability 1, 2
- Duration: Continue for 3 months after anemia correction to replenish iron stores 3, 1
Enhancing Absorption:
- Consider adding ascorbic acid 250-500 mg twice daily with iron to enhance absorption 3
- Alternative ferrous salts (ferrous fumarate, ferrous gluconate) may be better tolerated if ferrous sulfate causes side effects 3
Expected Response:
- Hemoglobin should rise by 2 g/dL after 3-4 weeks 3
- Recheck hemoglobin, ferritin, and transferrin saturation at 8-12 weeks 1
Intravenous Iron Therapy (Second-Line)
Switch to IV iron when oral iron fails or specific conditions exist. 1, 2
Indications for IV Iron:
- Intolerance to at least two oral iron preparations 3
- Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease) 1, 2
- Chronic inflammatory conditions (chronic kidney disease, heart failure, cancer) 1, 2
- Ongoing blood loss 1
- Pregnancy (second and third trimesters) 2
- Need for rapid correction 4
Preferred IV Formulation:
Ferric carboxymaltose (Ferinject) is first-line for IV iron: 1000 mg over 15 minutes, can be repeated weekly up to 20 mg/kg body weight. 3, 1, 4
Alternative IV Formulations:
- Iron isomaltoside: Up to 1000 mg over 15 minutes 3
- Iron dextran (low molecular weight): Up to 20 mg/kg over 6 hours, but higher risk of anaphylaxis (0.6-0.7%) 3
- Iron sucrose: 200 mg over 10 minutes (requires multiple doses, less convenient) 3
Important safety consideration: All IV iron must be administered in facilities with resuscitation equipment available due to rare but serious anaphylaxis risk. 3, 4
Monitoring for IV Iron:
- Monitor phosphate levels—ferric carboxymaltose carries increased risk of hypophosphatemia 4
Special Population Considerations
Restless Legs Syndrome:
- IV ferric carboxymaltose receives strong recommendation for RLS patients with low iron saturation, as brain iron deficiency is central to RLS pathophysiology 3
- Oral iron (ferrous sulfate) is conditionally recommended but poorly absorbed when ferritin >50-75 ng/mL 3
Chronic Kidney Disease:
- Target ferritin >200 ng/mL and transferrin saturation >20% to minimize erythropoiesis-stimulating agent requirements 1
- Iron supplementation indicated regardless of ferritin levels up to 800 ng/mL if hemoglobin <110 g/L 1
Cancer Patients:
- Use higher ferritin threshold (<100 ng/mL) to diagnose iron deficiency due to inflammatory state 3
- IV iron significantly improves response to erythropoiesis-stimulating agents (total doses ~1000 mg) 3
Premenopausal Women:
- Women >45 years require full investigation (endoscopy, colonoscopy) regardless of menstrual history 3
- Women <45 years with upper GI symptoms should have endoscopy and celiac screening; colonic investigation only if indicated 3