What is the difference between iron and ferritin?

The Difference Between Iron and Ferritin

Iron is a mineral essential for oxygen transport and cellular metabolism, while ferritin is the primary storage protein for iron in the body that reflects iron reserves.

Key Differences Between Iron and Ferritin

Fundamental Differences

• Iron (Fe): An essential mineral needed for hemoglobin production and oxygen transport
• Ferritin: A protein complex that stores iron in a soluble, non-toxic form, primarily in liver, spleen, and bone marrow reticuloendothelial cells 1

Physiological Roles

• Iron:

  • Component of hemoglobin in red blood cells
  • Essential for oxygen transport throughout the body
  • Required for cellular metabolism and enzyme function
  • Transported in blood bound to transferrin

• Ferritin:

  • Storage protein that can hold thousands of iron atoms inside a protein cage 2
  • Protects cells from toxic effects of free iron
  • Serves as a reservoir for iron when body needs increase
  • Acts as an acute phase reactant that increases during inflammation 1

Laboratory Assessment

• Serum Iron:

  • Measures circulating iron bound to transferrin
  • Subject to diurnal variation
  • Part of transferrin saturation calculation (serum iron ÷ TIBC × 100)
  • Low in iron deficiency and inflammation

• Serum Ferritin:

  • Reflects iron storage levels in the body
  • Most accurate predictor of iron deficiency when extremely low 1
  • Affected by inflammation (increases as acute phase reactant)
  • Normal range typically 30-300 ng/mL, but varies by laboratory

Clinical Significance

• Transferrin Saturation (TSAT):

  • Reflects iron readily available for erythropoiesis
  • Calculated as: serum iron ÷ total iron binding capacity × 100
  • TSAT <20% suggests iron deficiency 1
  • More reliable when combined with ferritin assessment

• Ferritin Interpretation:

  • Without inflammation: ferritin <30 μg/L indicates iron deficiency 1, 3
  • With inflammation: ferritin up to 100 μg/L may still indicate iron deficiency 1
  • Values >100 μg/L with TSAT <20% suggest anemia of chronic disease 1
  • Values between 30-100 μg/L suggest combined iron deficiency and anemia of chronic disease 1

Diagnostic Challenges

Confounding Factors

• Inflammation's Impact:

  • Ferritin increases as an acute phase reactant during inflammation
  • Can mask underlying iron deficiency 4
  • C-reactive protein (CRP) should be measured alongside ferritin to assess inflammation

• Obesity:

  • Ferritin may be elevated due to low-grade inflammation in obesity
  • May not accurately reflect iron stores in overweight/obese individuals 4
  • Complete iron profile including transferrin is more reliable in these cases

Diagnostic Algorithm

1. Measure serum ferritin, iron, TIBC, and TSAT
2. Assess inflammatory status (CRP, clinical symptoms)
3. Interpret results:
   • Ferritin <30 μg/L without inflammation = iron deficiency 1, 3
   • Ferritin <100 μg/L with inflammation = possible iron deficiency 1
   • Ferritin >100 μg/L with TSAT <20% = anemia of chronic disease 1
   • Ferritin 30-100 μg/L = possible mixed picture 1

Common Pitfalls in Interpretation

1. Relying solely on ferritin: Ferritin alone can be misleading, especially in inflammatory states
2. Using outdated cutoffs: Some laboratories still use ferritin <12-15 μg/L as cutoff, which has low sensitivity 5, 6
3. Ignoring inflammation: Failing to consider inflammatory status when interpreting ferritin results
4. Overlooking functional iron deficiency: Normal ferritin but low TSAT can indicate functional iron deficiency 1
5. Gender differences: Women may have physiologically lower ferritin levels, requiring different reference ranges 6

Clinical Applications

• Iron deficiency diagnosis: Requires assessment of both iron availability (TSAT) and iron stores (ferritin)
• Monitoring iron therapy: Ferritin is useful for monitoring response to iron supplementation
• Chronic disease management: Understanding the relationship between iron and ferritin helps distinguish between absolute and functional iron deficiency in chronic conditions like kidney disease 1 and inflammatory bowel disease 1

By understanding the relationship between iron and ferritin, clinicians can more accurately diagnose and treat iron-related disorders, recognizing that these parameters must be interpreted in the context of the patient's overall clinical and inflammatory status.