How is iron deficiency without anemia treated?

Treatment of Iron Deficiency Without Anemia

Iron supplementation is recommended for patients with iron deficiency without anemia when symptoms are present, with oral iron being the first-line treatment option for most patients. 1

Diagnosis and Symptoms of Non-Anemic Iron Deficiency

Iron deficiency without anemia is characterized by:

• Normal hemoglobin levels (≥12 g/dL for women, ≥13 g/dL for men)
• Low ferritin (<30 μg/L)
• Low transferrin saturation (<16%)

Patients may experience significant symptoms despite normal hemoglobin levels, including:

• Reduced physical performance and cognitive function
• Fatigue
• Headache
• Sleeping disorders
• Loss of libido
• Restless-legs syndrome
• Impaired nail growth and skin health
• Impaired mucosal regeneration 2

Treatment Algorithm

Step 1: Oral Iron Supplementation

• First-line treatment: Ferrous sulfate 324 mg (65 mg elemental iron) once daily 1, 3
• Alternative options:
  • Ferrous gluconate 324 mg (38 mg elemental iron) once daily 4
  • Ferrous fumarate 100-200 mg once daily 5

Step 2: Optimize Absorption

• Administer iron in the morning on an empty stomach 6
• Add vitamin C 250-500 mg with iron doses to enhance absorption 1
• Consider alternate-day dosing if GI side effects occur (improves absorption and reduces side effects) 6

Step 3: Monitor Response

• Assess response after 4 weeks by checking ferritin and transferrin saturation 1
• Target values: ferritin >30 μg/L and transferrin saturation >16% 1
• Continue treatment for 3 months after normalization of iron parameters 1

Step 4: Consider IV Iron if Oral Treatment Fails

• Indications for IV iron:
  • Intolerance to at least two oral preparations
  • Poor compliance with oral therapy
  • Need for rapid iron repletion
  • Conditions with impaired absorption (celiac disease, IBD, post-bariatric surgery) 2, 1
• Recommended IV dosing: 500-1000 mg (up to 20 mg/kg body weight) of ferric carboxymaltose 2, 1

Special Considerations

Monitoring

• Monitor iron parameters every 3 months for at least a year after correction, then every 6-12 months thereafter 2
• Re-treatment with iron should be initiated as soon as serum ferritin drops below 100 μg/L 2

Underlying Causes

• Always investigate and treat the underlying cause of iron deficiency 2
• Common causes include:
  • Gastrointestinal blood loss
  • Malabsorption (celiac disease, post-gastrectomy)
  • Inadequate dietary intake
  • Increased requirements (pregnancy, heavy menstruation) 7

Pitfalls and Caveats

1. Don't miss underlying pathology: Iron deficiency without anemia may be the only sign of disease activity in conditions like IBD 2

2. Avoid excessive iron: Excessive supplementation can cause iron overload, especially in high-risk patients with hereditary hemochromatosis 8

3. Consider alternate-day dosing: Daily high-dose iron stimulates hepcidin, which reduces subsequent iron absorption; alternate-day dosing may be more effective 6

4. Don't ignore persistent deficiency: Rapid recurrence of iron deficiency in asymptomatic patients should raise suspicion for subclinical inflammatory activity or ongoing blood loss 2

5. Remember that ferritin is an acute phase reactant: In inflammatory conditions, ferritin may be falsely elevated despite iron deficiency; in these cases, transferrin saturation is a more reliable marker 2