What is the treatment for low ferritin levels?

Low Ferritin Differential and Treatment

Primary Approach to Low Ferritin

Low ferritin (<30-45 μg/L) indicates depleted iron stores and requires iron supplementation to prevent progression to iron deficiency anemia and improve quality of life. 1, 2

The most recent AGA guidelines (2024) recommend using a ferritin cutoff of 45 μg/L for diagnosing iron deficiency in individuals with anemia, as this threshold optimizes sensitivity and specificity 1. However, ferritin <30 μg/L remains the most specific indicator of depleted iron stores in otherwise healthy individuals 2.

Differential Diagnosis Considerations

When Ferritin May Be Falsely Normal or Elevated

• Inflammatory conditions can mask true iron deficiency by falsely elevating ferritin levels, even when iron stores are depleted 1, 2
• In patients with chronic inflammation, infection, or tissue damage, iron deficiency may exist with ferritin levels between 45-100 μg/L 1
• Confirmatory testing should include transferrin saturation (<20% suggests iron deficiency), soluble transferrin receptor, or reticulocyte hemoglobin equivalent when inflammation is suspected 1

Underlying Causes to Investigate

• Gastrointestinal blood loss: peptic ulcers, colonic disease, angioectasias 1
• Malabsorption disorders: celiac disease, atrophic gastritis (autoimmune or H. pylori-related), post-gastrectomy 1, 3
• Increased demand: pregnancy, rapid growth, frequent blood donation 3, 4
• Inadequate dietary intake: particularly in premenopausal women and vegetarians 1, 5
• Medication effects: proton pump inhibitors reduce iron absorption 1
• Rare genetic causes: TMPRSS6 mutations causing iron-refractory iron deficiency anemia 3

Treatment Algorithm

First-Line: Oral Iron Supplementation

Initiate oral ferrous iron salts (ferrous sulfate, ferrous fumarate, or ferrous gluconate) as first-line therapy for most patients with low ferritin. 1

Dosing Strategies

• Standard dosing: 65 mg elemental iron daily (e.g., ferrous sulfate 324 mg tablet) 6
• Alternate-day dosing: 30-60 mg elemental iron every other day may improve absorption and reduce gastrointestinal side effects compared to daily dosing 1, 2
• The most recent high-quality evidence (2025) from blood donors showed that 60 mg daily was most effective at preventing iron deficiency (OR 0.60) and low ferritin (OR 0.52) compared to placebo 4

Optimization of Absorption

• Take on empty stomach when possible for maximum absorption 1
• Add 500 mg vitamin C to enhance absorption, especially if taken with meals 1
• Take with meat protein if consuming with food 1
• Avoid concurrent calcium or high-fiber foods unless vitamin C is added 1

Duration

• Minimum 56 days (8 weeks) of treatment before reassessing 2, 4
• Optimal duration is ≥3 months for complete iron store repletion 5

Second-Line: Intravenous Iron Therapy

Consider IV iron when oral iron fails, is not tolerated, malabsorption is present, or rapid repletion is needed. 1, 2

Indications for IV Iron

• Severe iron deficiency requiring rapid correction 1, 3
• Gastrointestinal intolerance to oral iron (nausea, constipation, diarrhea) 1, 2
• Malabsorption disorders (celiac disease, inflammatory bowel disease) 1
• Chronic kidney disease or heart failure with iron deficiency 3

Available Formulations

• Iron sucrose, ferric gluconate, ferric carboxymaltose, and other high-dose formulations 2, 3
• Calculate total dose based on body iron deficit formulas 2

Monitoring After IV Iron

• Wait at least 8-10 weeks before checking ferritin, as levels may be falsely elevated immediately post-infusion 2

Monitoring During Treatment

Oral Iron Therapy

• Repeat ferritin and hemoglobin after 8-10 weeks of oral supplementation 2
• More frequent monitoring as ferritin approaches normal range 1

Maintenance Phase

• Monitor ferritin every 6 months once iron stores are repleted 2
• Target ferritin maintenance range: 50-100 μg/L 1

Critical Pitfalls to Avoid

Do Not Treat Based on Ferritin Alone

• Always consider clinical context and other iron status markers (transferrin saturation, hemoglobin) 2
• In inflammatory states, use transferrin saturation and additional markers to confirm true iron deficiency 1

Avoid Iron Supplementation When Inappropriate

• Never supplement when ferritin is normal or high (can cause iron overload and toxicity) 2
• In hemochromatosis patients who develop low ferritin, extend phlebotomy intervals rather than supplementing 2

Investigate Unexpected Changes

• If ferritin fails to rise appropriately with treatment, investigate for ongoing blood loss, malabsorption, or non-compliance 1
• In older patients with unexplained iron loss, evaluate for peptic ulcers, colonic disease, and hematuria 1

Special Populations

Celiac Disease

• Ensure strict gluten-free diet adherence to improve iron absorption before supplementation 1
• Start with oral iron based on severity and tolerance, then escalate to IV iron if stores don't improve 1

Premenopausal Women

• This population has highest risk: 39% have iron deficiency and 4-17% have iron deficiency anemia 1
• Review menstrual blood losses as part of evaluation 1

Blood Donors

• Screen ferritin routinely in regular donors (every 10th donation or when hemoglobin is low-normal) 7
• Supplement when ferritin <15-30 μg/L to prevent progression to anemia 7

Pediatric Patients

• Monitor ferritin closely and keep levels <500 μg/L to avoid iron overload toxicity 2