How is low iron saturation treated?

Treatment of Low Iron Saturation

Direct Answer

Oral ferrous sulfate 200 mg twice daily (or 325 mg daily/alternate days) is the first-line treatment for low iron saturation when accompanied by anemia (hemoglobin <110 g/L), while isolated low transferrin saturation without anemia or low ferritin should NOT be treated with iron supplementation. 1, 2, 3

Clinical Decision Algorithm

Step 1: Determine if Treatment is Indicated

Check hemoglobin and ferritin levels alongside transferrin saturation:

• If hemoglobin <110 g/L: Iron supplementation is indicated regardless of ferritin levels (up to 800 ng/mL) 1, 2
• If hemoglobin normal AND ferritin normal/elevated: Do NOT treat isolated low transferrin saturation—this is potentially harmful and can lead to iron overload 2
• If transferrin saturation <16-20%: This confirms iron-deficient erythropoiesis and warrants treatment only when accompanied by anemia 1

Step 2: Choose Oral vs. Intravenous Iron

Start with oral iron unless specific contraindications exist:

Oral Iron (First-Line)

• Ferrous sulfate 200 mg twice daily is the gold standard—cheapest and most effective 1, 4
• Alternative: Ferrous sulfate 325 mg daily or on alternate days for better tolerability with similar efficacy 3, 5
• Continue for 3 months after correction to replenish iron stores 1
• Lower doses (80-100 mg elemental iron daily) may be equally effective with better tolerability 1, 6

Intravenous Iron (Reserved for Specific Situations)

Use IV iron when: 1, 3, 5

• Oral iron intolerance or gastrointestinal side effects
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease)
• Chronic inflammatory conditions (chronic kidney disease, heart failure, cancer)
• Ongoing blood loss
• Pregnancy (second and third trimesters)
• Need for rapid correction (e.g., pre-surgery)

IV formulations in order of preference:

• Ferric carboxymaltose (Ferinject): 1000 mg over 15 minutes—highest single dose, no anaphylaxis reported to date 1, 5
• Iron sucrose (Venofer): 200 mg over 10 minutes 1
• Iron dextran (Cosmofer): 20 mg/kg over 6 hours—can replenish in single infusion but carries 0.6-0.7% risk of serious reactions including fatalities 1

Step 3: Enhance Absorption (Optional)

• Vitamin C 250-500 mg twice daily with oral iron may enhance absorption, though evidence for clinical effectiveness is limited 1
• Heme iron from meat sources is better absorbed than plant-based non-heme iron 1

Special Populations

Chronic Kidney Disease/Hemodialysis Patients

• Target ferritin >200 ng/mL and transferrin saturation >20% to minimize erythropoiesis-stimulating agent (ESA) requirements 1
• Even with ferritin 500-1200 ng/mL, IV iron may be beneficial if transferrin saturation <25% and hemoglobin remains low despite high ESA doses 1

Female Athletes

• Higher daily iron requirements: 22 mg/day minimum (vs. 18 mg/day for general population) 1
• Risk factors include vegetarian/vegan diets, high-impact sports, endurance training, and heavy menstrual bleeding 1

Restless Legs Syndrome

• IV ferric carboxymaltose receives strong recommendation for RLS patients with low iron saturation 1
• Brain iron deficiency is central to RLS pathophysiology; oral iron is poorly absorbed when ferritin >50-75 ng/mL 1

Critical Pitfalls to Avoid

Do not treat isolated low transferrin saturation in healthy individuals:

• Without anemia or low ferritin, iron supplementation risks iron overload and organ damage 2
• Transferrin saturation has significant diurnal and day-to-day variation (larger than hemoglobin), making isolated measurements unreliable 1

Do not rely on transferrin saturation alone for diagnosis:

• Sensitivity for iron deficiency is only 20% in nonpregnant women of childbearing age 1
• Inflammation, infection, malignancies, liver disease, and oral contraceptives all affect results 1

Resuscitation facilities must be available when administering IV iron:

• Anaphylaxis can occur with any IV formulation 1
• Monitor phosphate levels with IV iron, especially ferric carboxymaltose, due to hypophosphatemia risk 5

Follow-Up

• Repeat hemoglobin, ferritin, and transferrin saturation after 8-12 weeks of oral iron therapy 1, 2
• If no response to oral iron, consider IV iron or investigate for ongoing blood loss/malabsorption 1, 3
• The initial hemoglobin rise is faster with IV iron, but at 12 weeks, oral and IV iron achieve similar results 1