How to treat iron deficiency without anemia?

Treatment of Iron Deficiency Without Anemia

The decision to treat iron deficiency without anemia is controversial and should be individualized based on patient symptoms, underlying conditions, and clinical context, as there is insufficient evidence to recommend universal iron supplementation in this population. 1, 2

Current Evidence and Guideline Recommendations

The available guidelines explicitly acknowledge the lack of consensus on treating iron deficiency without anemia:

• The European Crohn's and Colitis Organisation states that "the decision to supplement iron in patients without anaemia is more controversial and will depend on the patients' history, symptoms and individual preferences." 1
• Although evidence supports treating iron deficiency without anemia in conditions like chronic fatigue and heart failure, such evidence is not yet available for most clinical contexts. 1
• The British Society of Gastroenterology identified "the need to investigate iron deficiency without anaemia" as a priority research topic, highlighting the evidence gap. 1

When to Consider Treatment

Treat iron deficiency without anemia when patients have:

Symptomatic Iron Deficiency

• Fatigue, irritability, or difficulty concentrating attributable to iron deficiency 3
• Restless legs syndrome (affects 32-40% of iron deficient patients) 3
• Pica (affects 40-50% of iron deficient patients) 3
• Exercise intolerance or dyspnea 3

Specific High-Risk Populations

• Inflammatory bowel disease patients: Consider treatment even without anemia, particularly if ferritin <30 ng/mL or transferrin saturation <20% 1
• Pregnant women: Treat iron deficiency during second and third trimesters regardless of anemia status 4, 3
• Heart failure patients: Evidence supports treatment of iron deficiency without anemia in this population 1
• Patients with ongoing blood loss: Treat to prevent progression to anemia 3

Treatment Approach When Indicated

First-Line Oral Iron Therapy

Start with ferrous sulfate 200 mg (65 mg elemental iron) once daily, which is the most cost-effective option. 4

• Once-daily dosing improves tolerance while maintaining effectiveness compared to multiple daily doses 4
• Alternative formulations (ferrous gluconate, ferrous fumarate) are equally effective if ferrous sulfate is not tolerated 1, 4
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption 1, 4

Dosing for Iron Deficiency Without Anemia

• A minimum of 500-1000 mg total iron should be considered for replenishing stores 1
• Continue therapy for 3 months to adequately replenish iron stores 4
• Monitor ferritin levels every 3 months during treatment 1

When to Use Intravenous Iron

Consider IV iron in non-anemic iron deficiency for:

• Intolerance to at least two different oral iron preparations 1, 4
• Conditions affecting iron absorption (active IBD, celiac disease with ongoing gluten exposure, post-bariatric surgery) 1, 4
• Pregnancy during second and third trimesters if oral iron fails 4, 3
• Heart failure patients with documented iron deficiency 1, 3

Diagnostic Criteria for Iron Deficiency Without Anemia

In patients without inflammation:

• Serum ferritin <30 ng/mL confirms iron deficiency 1

In patients with inflammation or chronic disease:

• Ferritin 30-100 ng/mL with transferrin saturation <20% suggests combined iron deficiency and anemia of chronic disease 1
• Ferritin >100 ng/mL with transferrin saturation <20% suggests anemia of chronic disease alone 1

Critical Pitfalls to Avoid

• Do not treat asymptomatic iron deficiency without anemia in otherwise healthy individuals outside of high-risk populations, as evidence for benefit is lacking 1, 2
• Do not prescribe multiple daily doses of oral iron, as this increases side effects without improving efficacy 4
• Do not fail to identify and treat the underlying cause of iron deficiency 4, 2
• Avoid excessive iron supplementation, which can cause iron overload, especially in patients with hereditary hemochromatosis 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1, 4

Monitoring and Follow-Up

• Recheck ferritin at 3-month intervals during treatment 1, 4
• If ferritin fails to improve after 3 months of compliant oral therapy, reassess for malabsorption, ongoing blood loss, or consider switching to IV iron 4
• Continue treatment until ferritin normalizes (typically >30 ng/mL in non-inflammatory states) 1