Total iron binding capacity (TIBC)
Total iron binding capacity is the amount of iron the transferrin in blood can carry. US survey manuals print adult ranges of 250 to 400 and 250 to 450 µg/dL, and an older manual printed higher limits by sex. US recommendations state that it rises when iron stores are low and that inflammation, liver disease and malnutrition can lower it.
- Status
- Part of an iron panel, ordered by a clinician and also sold direct to consumers by some US laboratories. Many laboratories do not measure it directly and report the sum of serum iron and the measured unsaturated iron binding capacity. FDA classifies iron-binding capacity test systems as class I devices exempt from premarket notification [1][2].
- Measures
- The total amount of iron that the transferrin in serum can carry. It is the iron already bound, the serum iron, plus the spare capacity, the unsaturated iron binding capacity [2].
- Also called
- TIBC, total iron binding capacity, total iron-binding capacity, iron binding capacity, iron-binding capacity, IBC, binding capacity, TIBC calculated
- Tested for
- iron deficiency, anemia workup, iron overload, hemochromatosis screening, calculating transferrin saturation, nutrition assessment in kidney disease, checking an iron supplement
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research1
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in µg/dL. Also reported in µmol/L. Where sources differ, each is shown.
US national survey laboratory procedure manual, 2017 to 2018
Adults, as the reference range printed for the calculated result · [2], [3], [4]
| Range | What the source calls it |
|---|---|
| below 250 µg/dL | No name given |
| 250 to 400 µg/dL | "reference range" |
| above 400 µg/dL | No name given |
One range for adults of both sexes, printed by the laboratory that ran the 2017 to 2018 US National Health and Nutrition Examination Survey, with no account of how it was derived. The laboratory measured the unsaturated iron binding capacity (Roche Cobas 6000) and calculated this result by adding serum iron to it. The manual states that the result is elevated in iron deficiency anemia and low in the anemia of chronic disorders, malignant tumors and infections. It prefers a fasting morning sample, and states that the calculation is not valid when ferritin is above 1,200 ng/mL [2]. The 1998 US recommendations state that the result rises when stored iron is low and falls when it is high [3]. The result reflects transferrin, the iron transport protein. Transferrin measured directly is a different quantity, reported as a protein concentration, and a transferrin result is not placed against this page's ranges [4].
US national survey laboratory procedure manual, 2003 to 2004
Adults, as the reference range printed for the assay · [5]
| Range | What the source calls it |
|---|---|
| below 250 µg/dL | No name given |
| 250 to 450 µg/dL | "reference range" |
| above 450 µg/dL | No name given |
From the manual for the method used in the 2003 to 2004 survey (Beckman Synchron LX20, run by Collaborative Laboratory Services), which also obtained the result indirectly from the unsaturated iron binding capacity. The manual states that its reference ranges were established from wellness participants with an age mix similar to the laboratory's patients, and gives one range with no ages or sex. It equates 586 µg/dL of iron with 105 µmol/L, a factor of 0.179. The upper limit is 50 µg/dL above the one printed for the 2017 to 2018 survey [5][2].
US national survey laboratory procedure manual, 1999 to 2000, men
Men older than 18 · [6]
| Range | What the source calls it |
|---|---|
| below 300 µg/dL | No name given |
| 300 to 455 µg/dL | "normal range" |
| above 455 µg/dL | No name given |
The manual describes these as the normal ranges for the US population, based on the second national survey of 1976 to 1980, and does not say which percentiles they are. The line that prints the ranges gives the unit as µL/dL, while the manual's data table labels the result in µg/dL. This laboratory measured the capacity directly, by saturating serum with iron, removing the excess and measuring what stayed bound. The lower limit is 50 µg/dL above the one in the two later manuals. The manual states that after two freeze and thaw cycles results may tend to be reduced [6][2][5].
US national survey laboratory procedure manual, 1999 to 2000, women
Women older than 18 · [6]
| Range | What the source calls it |
|---|---|
| below 285 µg/dL | No name given |
| 285 to 510 µg/dL | "normal range" |
| above 510 µg/dL | No name given |
From the same manual and the same 1976 to 1980 survey data. The upper limit is 110 µg/dL above the one printed for the 2017 to 2018 survey [6][2]. The 1998 US recommendations state that pregnancy and oral contraceptive use can raise the result [3].
US national survey laboratory procedure manual, 1999 to 2000, children aged 3 to 17
Children aged 3 to 17 · [6]
| Range | What the source calls it |
|---|---|
| below 305 µg/dL | No name given |
| 305 to 490 µg/dL | "normal range" |
| above 490 µg/dL | No name given |
From the same manual and the same 1976 to 1980 survey data, as one range for boys and girls [6].
How it compares with the reference method
Matched the reference method1
TIBC against directly measured transferrin
One study of 570 paired samples found TIBC and immunologically measured transferrin tracked each other closely, at about 25 µmol/L of capacity per g/L of transferrin.
The numbers and sources
- Compared with
- Serum transferrin measured by immunoassay
- Effect
- In 570 paired results from five correlation studies at three laboratories, TIBC obtained from serum iron and unsaturated binding capacity correlated with transferrin (r squared 0.941 after three outliers were removed). The scatter was fully accounted for by the imprecision of the two assays. With both tests measured without bias, the ratio of TIBC in µmol/L to transferrin in g/L was close to the theoretically expected 25.0 [4].
- Population
- 570 paired serum results at three US commercial laboratories [4].
- Sources
- [4]
- Caveats
- The study was run by a commercial laboratory company comparing a lower-cost chemical assay with an immunoassay. Transferrin is reported as a protein concentration, in g/L in this study, so its numbers are not interchangeable with TIBC in µg/dL without conversion [4].
Mixed results2
Detecting iron deficiency against ferritin
Limited evidence: in one laboratory study TIBC or transferrin picked out iron deficiency better than serum iron or saturation, 0.94 against 0.77 and 0.87.
The numbers and sources
- Compared with
- Iron deficiency defined by serum ferritin below 12 or below 15 ng/mL
- Effect
- Across inpatients and outpatients and three reagent combinations, the mean area under the curve for identifying iron deficiency was 0.94 for transferrin or TIBC, 0.87 for the saturation index and 0.77 for serum iron. Transferrin and two ways of obtaining TIBC performed the same [10]. The 1998 US recommendations state that TIBC is less sensitive to iron deficiency than ferritin, because it changes only after iron stores are depleted [3].
- Population
- Laboratory requests with serum iron, transferrin or binding capacity, and ferritin measured together [10].
- Sources
- [10], [3]
- Caveats
- One retrospective laboratory study by a single author, which used ferritin and not bone marrow iron as the reference. The abstract gives no patient count and states no threshold for agreement, so the result is given as numbers only [10].
Variation over the day and from one draw to the next
Limited evidence: transferrin, the protein behind TIBC, varied about 3.9% between draws in a pooled estimate, against about 28% for serum iron.
The numbers and sources
- Compared with
- The same person's results on repeated draws
- Effect
- The European Federation of Clinical Chemistry and Laboratory Medicine database gives a pooled within-person variation of 3.9% for transferrin, with lower and upper limits of 3.4% and 5.8%, from 2 included estimates, against 27.6% for serum iron. It has no entry for TIBC itself [11]. The 1998 US recommendations state that day-to-day variation is less for TIBC than for serum iron [3]. In 20 healthy adults sampled at 8 AM, noon and 4 PM, then at 8 AM the next day, mean iron-binding capacity differed significantly between collection times, with no consistent daily pattern, and variation between days was similar to variation within a day [12].
- Population
- Healthy adults in the studies the database pools [11]. 20 healthy adult volunteers [12].
- Sources
- [11], [3], [12]
- Caveats
- The pooled figure is for transferrin, not for TIBC, and rests on 2 estimates. The database states no threshold for agreement, so the result is given as numbers only [11].
Did not match the reference method1
Illness and other states that shift it apart from iron stores
Limited evidence: US recommendations state that inflammation, infection, cancer, liver disease, nephrotic syndrome and malnutrition can lower TIBC, and pregnancy and oral contraceptives can raise it.
The numbers and sources
- Compared with
- Body iron stores
- Effect
- The 1998 US recommendations state that TIBC rises when serum iron and stored iron are low and falls when they are high, and that factors other than iron status affect it. They name inflammation, chronic infection, malignancies, liver disease, nephrotic syndrome and malnutrition as lowering the reading, and oral contraceptive use and pregnancy as raising it [3]. The 2017 to 2018 survey manual describes a low TIBC with low serum iron as the pattern of the anemia of chronic disorders, malignant tumors and infections [2]. In 807 people on hemodialysis, a lower TIBC went with lower body mass index and higher inflammatory markers [7].
- Population
- Sources cited by the 1998 recommendations [3]. 807 people on hemodialysis [7].
- Sources
- [3], [2], [7]
- Caveats
- The recommendations and the manual give no sizes for these shifts. The statements are quoted from them, not from the studies behind them [3][2].
What studies tie it to
Linked in research1
Death in people on hemodialysis
Limited evidence: one cohort of 807 hemodialysis patients linked a lower TIBC, and a fall in TIBC over 6 months, to more deaths.
The numbers and sources
- Effect
- Mortality rose step by step across lower TIBC groups. The adjusted hazard ratio for death was 1.75 (95% CI 1.00 to 3.05) for a TIBC below 150 against 200 to 250, and a fall of more than 20 over 6 months had a hazard ratio of 1.57 (1.04 to 2.36) against a stable result. Patients with a TIBC of 250 or above had a higher body mass index, more arm muscle and fat by skinfold, higher serum iron, and lower ferritin and inflammatory markers [7].
- Population
- 807 people on maintenance hemodialysis in a prospective 5-year cohort [7].
- Sources
- [7]
- Caveats
- One observational cohort in people on dialysis, in whom the authors treat TIBC as a marker of protein and energy wasting, so it does not describe people without kidney failure. The abstract prints the TIBC values in mg/dL, and the figures above are given as printed. The lower limit of the hazard ratio for a low TIBC is 1.00 [7].
Mixed results1
Coronary artery disease and stroke in genetic studies of transferrin
Limited evidence: two genetic studies tied higher transferrin, the protein behind TIBC, to slightly more coronary artery disease and slightly less stroke.
The numbers and sources
- Effect
- In Mendelian randomization studies using three gene variants tied to iron status, the odds ratio per standard deviation higher transferrin was 1.08 for coronary artery disease (95% CI 1.01 to 1.16) and 0.92 for stroke (0.86 to 0.99). The authors read a higher transferrin as a sign of lower iron status. The same studies found higher serum iron associated with less coronary artery disease and more stroke [8][9].
- Population
- Gene associations with iron status from 48,972 people. Coronary artery disease data from 60,801 cases and 123,504 controls combined with a second set of 63,746 cases and 130,681 controls. Stroke data from the MEGASTROKE consortium [8][9].
- Sources
- [8], [9]
- Caveats
- The studies measured transferrin, not TIBC. They estimate a lifelong genetic difference in iron status from three variants and do not show what a single reading means. The two outcomes point in opposite directions [8][9].
Related
Sources
- US Food and Drug Administration. 21 CFR 862.1415, Iron-binding capacity test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1415
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 2017-2018 Laboratory Procedure Manual: Unsaturated Iron-Binding Capacity (UIBC), serum, Roche Cobas 6000. Performed by the University of Minnesota Advanced Research and Diagnostic Laboratory. https://wwwn.cdc.gov/nchs/data/nhanes/public/2017/labmethods/FETIB-J-MET-UIBC-508.pdf
- Centers for Disease Control and Prevention. Recommendations to Prevent and Control Iron Deficiency in the United States. MMWR Recommendations and Reports. 1998;47(RR-3). https://www.cdc.gov/mmwr/preview/mmwrhtml/00051880.htm
- Gambino R, Desvarieux E, Orth M, et al. The relation between chemically measured total iron-binding capacity concentrations and immunologically measured transferrin concentrations in human serum. Clinical Chemistry. 1997. https://doi.org/10.1093/clinchem/43.12.2408
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 2003-2004 Laboratory Procedure Manual: Total Iron Binding Capacity (TIBC), serum, Beckman Synchron LX20. Performed by Collaborative Laboratory Services. https://wwwn.cdc.gov/nchs/data/nhanes/public/2003/labmethods/l40fe_c_met_tibc.pdf
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 1999-2000 Laboratory Procedure Manual: Iron and TIBC, serum. Performed by the Inorganic Toxicology and Nutrition Branch, National Center for Environmental Health. https://wwwn.cdc.gov/nchs/data/nhanes/public/1999/labmethods/lab06_met_-fe_tibc.pdf
- Bross R, Zitterkoph J, Pithia J, et al. Association of Serum Total Iron-Binding Capacity and Its Changes Over Time with Nutritional and Clinical Outcomes in Hemodialysis Patients. American Journal of Nephrology. 2009. https://doi.org/10.1159/000191470
- Gill D, Del Greco M F, Walker AP, et al. The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study. Arteriosclerosis, Thrombosis, and Vascular Biology. 2017. https://doi.org/10.1161/ATVBAHA.117.309757
- Gill D, Monori G, Tzoulaki I, Dehghan A. Iron Status and Risk of Stroke. Stroke. 2018. https://doi.org/10.1161/STROKEAHA.118.022701
- Hawkins RC. Total iron binding capacity or transferrin concentration alone outperforms iron and saturation indices in predicting iron deficiency. Clinica Chimica Acta. 2007. https://doi.org/10.1016/j.cca.2007.02.032
- European Federation of Clinical Chemistry and Laboratory Medicine. EFLM Biological Variation Database, meta-analysis estimates, read 2026-11-13. https://biologicalvariation.eu/
- Dale JC, Burritt MF, Zinsmeister AR. Diurnal Variation of Serum Iron, Iron-Binding Capacity, Transferrin Saturation, and Ferritin Levels. American Journal of Clinical Pathology. 2002. https://doi.org/10.1309/2YT4-CMP3-KYW7-9RK1