Iron (Serum)

Iron in blood plasma

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Vitamins &NutrientsCategory

Men:65-175 μg/dL, WReference

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Reference Range

Men:65-175 μg/dL, Women:50-170 μg/dL

What is Iron (Serum)?

Serum iron measures the amount of iron currently circulating in your bloodstream, bound to transferrin (the iron transport protein). Unlike ferritin (which reflects iron stores), serum iron reflects the iron available for immediate use by cells. Serum iron fluctuates significantly throughout the day and is influenced by recent meals, inflammation, and diurnal variation (highest in morning, lowest at night). Because of this variability, serum iron alone is not a reliable marker of iron status—it must be interpreted alongside ferritin, TIBC (total iron-binding capacity), and transferrin saturation.

Here's the critical insight:serum iron, TIBC, and transferrin saturation work together to paint a complete picture of iron status. Low serum iron + high TIBC + low transferrin saturation=iron deficiency (body desperately trying to capture more iron). High serum iron + low TIBC + high transferrin saturation (>45%)=iron overload (hemochromatosis). Normal serum iron + low TIBC=anemia of chronic disease (inflammation sequesters iron). You can't interpret serum iron in isolation—you need the full iron panel.

Transferrin saturation is the most useful calculated value:(Serum Iron / TIBC) × 100. Normal is 20-45%. <20% indicates iron deficiency;>45% suggests iron overload. Transferrin saturation <20% with ferritin <30 ng/mL confirms iron deficiency anemia. Transferrin saturation >45% with ferritin >300 ng/mL (men) or >200 ng/mL (women) suggests hemochromatosis—genetic testing for HFE mutations is warranted.

Why Serum Iron Matters (As Part of Full Iron Panel)

Diagnose iron deficiency vs anemia of chronic disease:Low serum iron can be due to true iron deficiency OR inflammation. TIBC and ferritin differentiate:iron deficiency (high TIBC, low ferritin) vs chronic disease (low TIBC, normal/high ferritin).
Detect iron overload (hemochromatosis):High serum iron + high transferrin saturation (>45%) indicates excessive iron absorption. Hemochromatosis causes cirrhosis, diabetes, heart failure if untreated.
Guide iron supplementation:If transferrin saturation <20% and ferritin <30 ng/mL, iron supplementation is clearly indicated. Monitor transferrin saturation and ferritin to track response.
Evaluate unexplained fatigue or anemia:Serum iron (with TIBC, ferritin, transferrin saturation) identifies the cause:iron deficiency, chronic disease, hemochromatosis, or other.

Optimal vs Standard Ranges

Range Type	Level	Significance
Optimal (with TIBC and Transferrin Saturation)	60-170 mcg/dL (men) 50-150 mcg/dL (women)	Normal range for serum iron. Must interpret with TIBC and transferrin saturation (optimal 25-35%).
Low Serum Iron	<50 mcg/dL	Low serum iron. Check TIBC and ferritin:\| If TIBC high (>400) + ferritin low (<30)=iron deficiency. \| If TIBC low (<250) + ferritin normal/high=anemia of chronic disease (inflammation).
High Serum Iron	>200 mcg/dL	High serum iron. Check TIBC and transferrin saturation:\| If transferrin saturation >45% + ferritin >300 (men) or >200 (women)=possible hemochromatosis. \| If acute, may be from recent iron supplementation, blood transfusion, or hemolysis.
Low Transferrin Saturation	<20%	Iron deficiency. Body can't saturate transferrin with iron. Supplement with iron (ferrous bisglycinate 25-50 mg daily).

Standard lab range: Men:65-175 μg/dL, Women:50-170 μg/dL

How to Optimize Iron (Serum)

1. High Transferrin Saturation

>45%

2. Iron overload (hemochromatosis). Transferrin fully saturated;excess iron deposited in organs. Check ferritin and HFE genetic testing.

TIBC (Total Iron-Binding Capacity)

3. 250-450 mcg/dL

Normal TIBC. High TIBC (>400)=iron deficiency (body makes more transferrin to capture iron). Low TIBC (<250)=chronic inflammation or liver disease.

4. Correct Iron Deficiency (if transferrin saturation <20%)

Serum iron <50 mcg/dL + TIBC >400 + transferrin saturation <20% + ferritin <30 ng/mL=iron deficiency anemia.

Iron supplementation:Ferrous bisglycinate 25-50 mg elemental iron daily (or ferrous sulfate 325 mg once-twice daily). Take with vitamin C, away from calcium/tea/coffee.

Dietary iron:Red meat, organ meats, shellfish (heme iron, highly bioavailable). Vegetarians need 1.8x more iron due to poor non-heme absorption.

Retest in 3 months:Expect ferritin to rise 30-50 ng/mL, transferrin saturation to normalize (>20%).

5. Differentiate Iron Deficiency from Anemia of Chronic Disease

Both cause low serum iron and anemia, but iron studies distinguish them:

Iron deficiency:Low serum iron, HIGH TIBC (>400), low transferrin saturation (<20%), LOW ferritin (<30). Treat with iron.

Anemia of chronic disease:Low serum iron, LOW TIBC (<250), low-normal transferrin saturation (15-30%), NORMAL or HIGH ferritin (>100). Caused by inflammation (infections, autoimmune disease, cancer) sequestering iron. Treat underlying disease, NOT iron supplementation (can worsen inflammation).

Symptoms of Abnormal Iron (Serum)

Low Iron (Serum)

Evaluate for Hemochromatosis (if transferrin saturation >45%)

High Iron (Serum)

Timing of Test (Morning Fasting)

Causes of Abnormal Iron (Serum)

Low Levels

Retest After Treatment

High Levels

If treating iron deficiency:Retest serum iron, TIBC, transferrin saturation, ferritin after 3 months of supplementation. Goal:ferritin >50 ng/mL, transferrin saturation 25-35%.
If treating hemochromatosis:Monitor ferritin and transferrin saturation every 3 months during phlebotomy, then every 6-12 months for maintenance.

When to Retest

Low serum iron causes same symptoms as iron deficiency (see Ferritin section):
Fatigue, weakness, low energy
Shortness of breath, especially with activity
Pale skin, pale conjunctiva
Cold intolerance
Brain fog, poor concentration
Headaches, dizziness
Hair loss, brittle nails
Restless leg syndrome
Pica (craving ice, dirt, starch)

Scientific Evidence

Low serum iron with high TIBC and low ferritin=iron deficiency. Low serum iron with low TIBC and normal/high ferritin=anemia of chronic disease.

Source:High serum iron + high transferrin saturation (>45%) suggests iron overload (hemochromatosis). Requires genetic testing and treatment.

True iron deficiency:Low dietary iron (vegetarian/vegan), heavy menstrual bleeding, GI blood loss, malabsorption (celiac, gastric bypass).|Anemia of chronic disease:Chronic infections (TB, HIV), autoimmune diseases (rheumatoid arthritis, lupus), cancer, chronic kidney disease. Inflammation (high CRP, IL-6) causes hepcidin release, which sequesters iron in macrophages, lowering serum iron.|Pregnancy:Increased iron demand lowers serum iron and ferritin.|Recent blood donation:Acutely lowers serum iron and ferritin.

Hereditary hemochromatosis:HFE gene mutations (C282Y, H63D) cause excessive iron absorption from diet. Most common genetic disorder in Caucasians (1:200-300).|Frequent blood transfusions:Chronic anemia (thalassemia, sickle cell) requiring transfusions → iron overload.|Excessive iron supplementation:Taking high-dose iron without deficiency.|Acute iron ingestion:Iron poisoning (accidental or intentional overdose).|Hemolysis:Red blood cell destruction releases iron into bloodstream (hemolytic anemia, transfusion reaction).|Acute hepatitis or liver necrosis:Damaged hepatocytes release stored iron.

Source:Baseline:Order full iron panel (serum iron, TIBC, transferrin saturation, ferritin) if anemia, fatigue, or risk factors for iron deficiency/overload.|Always test in morning, fasting:Serum iron varies by time of day and recent meals.|If low transferrin saturation (<20%) + low ferritin (<30):Confirms iron deficiency. Start iron supplementation, retest in 3 months.|If high transferrin saturation (>45%) + high ferritin (>300 men, >200 women):Evaluate for hemochromatosis. Order HFE genetic testing.|If low serum iron but normal/high ferritin:Consider anemia of chronic disease. Check CRP, ESR to assess inflammation.|Retest after 3 months of iron supplementation:Ferritin should rise 30-50 ng/mL, transferrin saturation normalize to 25-35%.

Transferrin Saturation as Key Diagnostic

Transferrin saturation (serum iron / TIBC × 100) is more useful than serum iron alone. <20%=iron deficiency;>45%=iron overload. Transferrin saturation <16% in combination with ferritin <30 ng/mL has 90% sensitivity and specificity for iron deficiency anemia.

Source:Guyatt GH, et al. Laboratory diagnosis of iron-deficiency anemia:an overview. J Gen Intern Med. 1992;7(2):145-153.

Anemia of Chronic Disease vs Iron Deficiency

Anemia of chronic disease (ACD) is the second most common anemia after iron deficiency. Inflammation (infections, autoimmune disease, cancer) releases hepcidin, which traps iron in macrophages, lowering serum iron but raising/maintaining ferritin. ACD:low serum iron, low TIBC, normal/high ferritin. Iron deficiency:low serum iron, high TIBC, low ferritin.

Source:Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011-1023.

Hemochromatosis Diagnosis and Treatment

Hereditary hemochromatosis is diagnosed with transferrin saturation >45% (most sensitive early marker), ferritin >300 (men) or >200 (women), and HFE genetic testing (C282Y homozygous most common). Treatment is phlebotomy:remove 500 mL blood weekly until ferritin <50 ng/mL, then maintenance every 2-3 months. Prevents cirrhosis, diabetes, heart disease.

Source:Bacon BR, et al. Diagnosis and management of hemochromatosis:2011 practice guideline by AASLD. Hepatology. 2011;54(1):328-343.

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