Should I start iron supplementation for an otherwise healthy 20-year-old with a transferrin saturation of 15%?

Iron Supplementation for Transferrin Saturation of 15% in a Healthy 20-Year-Old

You should obtain a complete iron panel including ferritin before making any treatment decision, because a transferrin saturation of 15% alone is insufficient to diagnose iron deficiency or determine whether supplementation is needed. 1

Why TSAT Alone Is Inadequate

A transferrin saturation of 15% sits at the diagnostic threshold (TSAT <16% in healthy individuals without inflammation) but requires ferritin measurement to distinguish between absolute iron deficiency, functional iron deficiency, or normal iron status with other causes of low TSAT. 1

• TSAT <16% in adults without inflammation confirms absolute iron deficiency only when combined with ferritin <30 ng/mL. 2, 1
• TSAT is less sensitive than ferritin for detecting early iron depletion—it primarily reflects iron-deficient erythropoiesis rather than depleted iron stores. 1
• In healthy young adults, TSAT <16% has 93% specificity but only 20% sensitivity for true iron deficiency, meaning many patients with low TSAT do not have iron deficiency. 1

Required Diagnostic Work-Up

Before treating, obtain:

• Complete iron panel: serum iron, total iron-binding capacity (TIBC), ferritin, and calculate TSAT. 2, 1
• Complete blood count: hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) to assess for anemia and red cell indices. 2, 1
• C-reactive protein (CRP): to exclude inflammation that could falsely elevate ferritin or alter iron metabolism. 1, 3

Decision Algorithm Based on Results

If Ferritin <30 ng/mL (Absolute Iron Deficiency)

Treat with oral iron supplementation regardless of whether anemia is present. 2, 4

• Dosing: 28-50 mg elemental iron every other day (alternate-day dosing improves absorption and reduces gastrointestinal side effects compared to daily dosing). 3, 4
• Rationale: Ferritin <30 ng/mL indicates depleted iron stores that warrant repletion even without anemia, as iron deficiency impairs cognitive function and physical performance before anemia develops. 3, 5
• Monitoring: Repeat iron studies at 8-10 weeks to assess response; hemoglobin should increase by 1-2 g/dL if anemia was present. 1, 3

If Ferritin 30-45 ng/mL (Borderline Low Stores)

Consider iron supplementation if the patient has risk factors for ongoing iron loss or increased demand. 2, 4

• Risk factors in a 20-year-old include: heavy menstrual bleeding (if female), high-performance athletics, vegetarian/vegan diet, frequent blood donation, or eating disorders. 3, 4
• A ferritin cut-off of 45 ng/mL provides optimal sensitivity and specificity for iron deficiency in otherwise healthy adults. 2
• If risk factors are present, treat with oral iron as above and provide dietary counseling to increase heme iron intake and avoid inhibitors of iron absorption. 3

If Ferritin ≥45 ng/mL and TSAT 15% (No Iron Deficiency)

Do not supplement with iron—the low TSAT likely reflects normal variation or a non-iron cause. 2, 1

• TSAT has significant day-to-day and diurnal variation (rises in morning, falls at night) and increases after meals, so a single value of 15% may not be clinically significant. 1
• Ferritin ≥45 ng/mL indicates adequate iron stores, and iron supplementation in the presence of normal stores is inefficient, causes gastrointestinal side effects, and may be harmful. 3
• Investigate alternative causes if symptoms (fatigue, reduced exercise capacity) are present: thyroid dysfunction, vitamin B12/folate deficiency, sleep disorders, or other medical conditions. 2

Common Pitfalls to Avoid

• Treating based on TSAT alone without ferritin: This leads to unnecessary iron supplementation in patients with adequate stores and misses the opportunity to identify true iron deficiency requiring treatment. 2, 1
• Assuming low TSAT always means iron deficiency: In healthy individuals, TSAT <20% can occur with normal iron stores due to physiologic variation. 1
• Ignoring inflammation: Even in "otherwise healthy" young adults, subclinical inflammation (recent infection, intense exercise, menstruation) can transiently lower TSAT and elevate ferritin; always check CRP. 1, 3
• Over-supplementing: Long-term daily oral or intravenous iron in the presence of normal or high ferritin is not recommended and potentially harmful. 3

Special Considerations for a 20-Year-Old

• If female with menstruation: Heavy or prolonged menstrual bleeding is the most common cause of iron deficiency in this age group; assess menstrual history and consider gynecologic evaluation if bleeding is excessive. 3, 4
• If male or non-menstruating female with confirmed iron deficiency: Gastrointestinal blood loss must be excluded, though in a 20-year-old without alarm symptoms, dietary insufficiency or malabsorption (celiac disease) are more likely than malignancy. 2, 4
• Athletes: High-performance sport causes increased iron losses through hemolysis, gastrointestinal bleeding, and sweat; lower ferritin thresholds may impair performance even without anemia. 3