Transferrin saturation
Transferrin saturation is serum iron divided by total iron binding capacity. A US survey laboratory lists 14% to 50% for adults. Bodies use below 16% or below 20% to flag iron deficiency and 45% or above to prompt testing for iron overload. A saturation of 50% or more was linked to more deaths. Results vary between draws.
- Status
- Part of an iron panel, ordered by a clinician and also sold direct to consumers by some US laboratories. It is calculated from two measured results. FDA classifies iron test systems and iron-binding capacity test systems as class I devices exempt from premarket notification [1][2].
- Measures
- The share of the blood's iron-carrying capacity that is occupied by iron, calculated as serum iron divided by total iron binding capacity, times 100 [3].
- Also called
- TSAT, TS, transferrin saturation, iron saturation, percent saturation, % saturation, iron sat, Fe sat, iron panel, iron studies
- Tested for
- iron deficiency, iron overload, hemochromatosis screening, anemia workup, fatigue, checking an iron supplement, iron testing in heart failure, iron testing in kidney disease
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 research3
- StrongShown in trials: intravenous iron cut heart failure hospital stays in iron-deficient patients, possibly more when saturation was below 20%, with no clear effect on deaths.
- ModerateLinked to more deaths at a saturation of 50% or above, about 40% more than below 50% in two Danish population studies.
- LimitedLimited evidence: one cohort linked higher transferrin saturation to more cancer and cancer deaths in women, with no such link for ferritin.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in %. 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 · [4]
| Range | What the source calls it |
|---|---|
| below 14 % | No name given |
| 14 to 50 % | "reference range" |
| above 50 % | No name given |
One range for adults of both sexes, printed by the laboratory that runs the US national survey, with no account of how it was derived. The manual lists total iron binding capacity and iron saturation as calculated results. The same manuals print reference ranges of 250 to 400 µg/dL for total iron binding capacity and, for serum iron, 59 to 158 µg/dL in men and 37 to 145 µg/dL in women. Those are separate quantities and a result for them is not placed against this page's ranges. The manual states that a fasting morning sample is preferred [4][5].
US Centers for Disease Control and Prevention recommendations, 1998, iron deficiency
People being assessed for iron deficiency · [3]
| Range | What the source calls it |
|---|---|
| below 16 % | "iron deficiency" |
| 16 or above % | No name given |
A cutoff for iron deficiency, listed with a ferritin cutoff of 15 ng/mL or below. The source describes transferrin saturation as a sign of iron-deficient red cell production, less sensitive to changes in iron stores than ferritin. It gives no upper cutoff, so this block does not classify high results [3].
International expert consensus on iron deficiency in chronic inflammatory conditions, 2017
People with chronic heart failure, chronic kidney disease or inflammatory bowel disease · [6]
| Range | What the source calls it |
|---|---|
| below 20 % | "iron deficiency" |
| 20 or above % | No name given |
A consensus cut-off for people with these three conditions. The panel proposes ferritin below 100 ng/mL or transferrin saturation below 20%, and states that when ferritin is between 100 and 300 ng/mL a transferrin saturation test is needed to confirm iron deficiency. No upper cutoff is given [6].
American Association for the Study of Liver Diseases hemochromatosis guideline, 2011
Adults with symptoms, physical findings or a family history that suggest hemochromatosis · [7]
| Range | What the source calls it |
|---|---|
| below 45 % | No name given |
| 45 or above % | "abnormal" |
A threshold for going on to gene testing for hemochromatosis, used together with ferritin, not a diagnosis of iron overload. The guideline states that 45% is often chosen for its high sensitivity for the hemochromatosis genotype, that it has lower specificity than higher cutoffs, and that it will also pick up people with minor iron overload from other causes and some carriers of one gene copy. It advises confirming a raised result with a second test. No lower cutoff is given [7].
Asian Pacific Association for the Study of the Liver hemochromatosis guideline, 2023
Men and women being assessed for iron overload · [8]
| Range | What the source calls it |
|---|---|
| 45 or below % | No name given |
| above 45 % | "elevated" |
The guideline states that a transferrin saturation over 45% in both males and females is considered elevated, and that people with suspected iron overload are identified by a raised ferritin together with a saturation above 45%, followed by gene testing. No lower cutoff is given [8].
European Association for the Study of the Liver haemochromatosis guideline, 2022, as summarized in a 2023 guideline review, women
Women being assessed for hemochromatosis · [9]
| Range | What the source calls it |
|---|---|
| 45 or below % | No name given |
| above 45 % | "elevated" |
Taken from a published review of the guideline, not from the guideline itself. The review reports that people with a raised ferritin (above 200 ng/mL in women) and a transferrin saturation above this threshold, and people with an unexplained saturation that stays raised, are to be gene tested for hemochromatosis. No lower cutoff is given [9].
European Association for the Study of the Liver haemochromatosis guideline, 2022, as summarized in a 2023 guideline review, men
Men being assessed for hemochromatosis · [9]
| Range | What the source calls it |
|---|---|
| 50 or below % | No name given |
| above 50 % | "elevated" |
Taken from a published review of the guideline, not from the guideline itself. The threshold for men is 5 points above the one for women, paired with a ferritin above 300 ng/mL. No lower cutoff is given [9].
What has been shown to move it
Shown to lower it1
Iron status during training
One small trial found transferrin saturation fell 24% on chromium picolinate against 10% to 13% on chromium chloride or placebo in 36 men.
How it compares with the reference method
Mixed results3
Detecting iron deficiency against bone marrow iron
Limited evidence: US recommendations cite a saturation below 16% as picking up 20% of women with no bone marrow iron, with 93% specificity.
The numbers and sources
- Compared with
- Iron seen on staining of a bone marrow sample
- Effect
- Among nonpregnant women of childbearing age, the sensitivity of a transferrin saturation below 16% for iron deficiency, defined as no stainable bone marrow iron, was 20%, and the specificity was 93% [3].
- Population
- Nonpregnant women of childbearing age, as cited in the 1998 US recommendations [3].
- Sources
- [3]
- Caveats
- The figures are quoted by the recommendations from an earlier study, which was not read for this page. The source states no threshold for agreement, so the result is given as numbers only [3].
Time of day and fasting
Mixed results: one small study found no consistent change in iron results across the day, while laboratory manuals and US recommendations describe a daily rhythm.
The numbers and sources
- Compared with
- The same person's morning sample
- Effect
- In 20 healthy adults sampled at 8 AM, noon and 4 PM, then at 8 AM the next day, no consistent daily pattern was seen in serum iron, iron-binding capacity or transferrin saturation. Morning iron was higher than afternoon iron in only half of them, and variation between days was similar to variation within a day [16]. In a screening study of 101,168 people, fasting samples gave no advantage in finding the hemochromatosis genotype [15]. The US survey manual prefers a fasting morning sample because of daily variation [4], and the 1998 US recommendations state that serum iron rises after each meal, rises in the morning and falls at night [3].
- Population
- 20 healthy adult volunteers [16]. 101,168 primary care participants [15].
- Sources
- [16], [15], [4], [3]
- Caveats
- The direct comparison is one study of 20 people. A US liver society guideline no longer treats a fasting sample as strictly necessary and advises confirming a raised result with a second test [7].
Variation in serum iron from one draw to the next in one person
Shown to vary about 28% from one draw to the next for serum iron, the top half of the calculation, in a pooled estimate from a European laboratory federation.
The numbers and sources
- Compared with
- The same person's serum iron on repeated draws
- Effect
- The European Federation of Clinical Chemistry and Laboratory Medicine database gives a pooled within-person variation of 27.6% for serum iron, with lower and upper limits of 19.8% and 30.4%, from 4 included estimates. For transferrin, the protein behind the binding capacity, the figure is 3.9%. The database has no pooled entry for transferrin saturation itself [17].
- Population
- Healthy adults in the studies the database pools [17].
- Sources
- [17]
- Caveats
- These figures are for serum iron and transferrin, not for the calculated saturation. Because saturation is iron divided by binding capacity, it moves with iron. The database states no threshold for agreement, so the result is given as numbers only [17].
Did not match the reference method1
Detecting the hemochromatosis genotype
Limited evidence: in one large screening study, saturation cut points of 45% for women and 50% for men missed 33% of people with the hemochromatosis genotype.
The numbers and sources
- Compared with
- Gene testing for two copies of the HFE C282Y variant
- Effect
- Among 209 people found to carry two copies of the variant, 68 (33%) had a transferrin saturation below the cut point at the first screening test, at a second test several months later, or both. Their median ferritin was 170 ng/mL. Fasting samples gave no advantage. The authors conclude that variation within a person limits the test as a first screen for this genotype [15]. A US liver society guideline states that a 45% cutoff has high sensitivity for the genotype and lower specificity than higher cutoffs [7].
- Population
- 101,168 primary care participants screened in the Hemochromatosis and Iron Overload Screening Study, 209 with previously undiagnosed genotype and repeat testing [15].
- Sources
- [15], [7]
- Caveats
- One screening study. A person was counted as missed if either of two tests fell under the cut point, so the share missed by a single test is lower than 33% [15].
What studies tie it to
Linked in research3
Death from any cause at high levels
Linked to more deaths at a saturation of 50% or above, about 40% more than below 50% in two Danish population studies.
The numbers and sources
- Effect
- In two Danish general population studies combined, a transferrin saturation of 50% or above had an adjusted hazard ratio for death of 1.4 (95% CI 1.2 to 1.6) against below 50%, 1.3 in men and 1.5 in women. Risk rose stepwise, and 80% or above against below 20% had a hazard ratio of 2.2 (1.4 to 3.3). Adding a third population study, the pooled odds ratio for death at 50% or above was 1.3 (1.2 to 1.5) [10]. In a US national cohort, a saturation above 55% had a hazard ratio of 1.60 (1.17 to 2.21) against lower values. No death certificate listed hemochromatosis, and people above 55% were more likely to have died of cirrhosis or diabetes [11].
- Population
- 45,159 Danish adults, 4,568 deaths over up to 18 years [10]. 10,714 US adults aged 25 to 74 at baseline, followed from the early 1970s to 1992 [11].
- Sources
- [10], [11]
- Caveats
- Observational. The share of all deaths in the Danish studies attributable to a saturation of 50% or above was 0.8% [10]. Neither source shows that lowering saturation changes the risk of death.
Cancer
Limited evidence: one cohort linked higher transferrin saturation to more cancer and cancer deaths in women, with no such link for ferritin.
The numbers and sources
- Effect
- In women, higher transferrin saturation had a hazard ratio of 1.68 (95% CI 1.18 to 2.38) for a new cancer other than skin cancer, 1.90 (1.02 to 3.56) for breast cancer and 2.48 (1.28 to 4.82) for death from cancer. In men, higher serum iron went with fewer new cancers (hazard ratio 0.65, 95% CI 0.42 to 0.99). Ferritin was not associated with cancer risk or cancer death [12].
- Population
- 1,597 men and 1,795 women aged 25 to 79 in the Busselton Health Survey, without cancer at the start and with ferritin of 20 ng/mL or above, followed from 1994 or 1995 to 2010 [12].
- Sources
- [12]
- Caveats
- One observational cohort, with opposite directions in women and men. The abstract does not state which saturation levels were compared, and the authors call the basis for the sex difference unclear [12].
Heart failure hospital stays in trials of intravenous iron
Shown in trials: intravenous iron cut heart failure hospital stays in iron-deficient patients, possibly more when saturation was below 20%, with no clear effect on deaths.
The numbers and sources
- Effect
- In a meta-analysis of 10 trials, intravenous iron lowered the combined rate of repeat heart failure hospital stays and cardiovascular death (rate ratio 0.75, 95% CI 0.61 to 0.93). Effects on cardiovascular death (odds ratio 0.86, 0.70 to 1.05) and death from any cause (0.93, 0.78 to 1.12) were inconclusive. Patients with a transferrin saturation below 20% had an odds ratio of 0.67 (0.49 to 0.92) for the main outcome, against 0.99 (0.74 to 1.30) at 20% or above (P for difference 0.07) [13]. In pooled patient-level data from 3 trials of one iron product, the rate ratio for cardiovascular hospital stays and cardiovascular death was 0.86 (0.75 to 0.98), with no apparent effect on death. That analysis reported a lower risk of cardiovascular death in the subgroup with saturation below 15% and possibly unfavorable effects at 24% or above [14].
- Population
- 3,373 people with heart failure and iron deficiency in 10 randomized trials [13]. 4,501 people in 3 placebo-controlled trials of ferric carboxymaltose with at least 52 weeks of follow-up [14].
- Sources
- [13], [14]
- Caveats
- The findings by saturation come from subgroup analyses, and the test for a difference between subgroups did not reach significance [13]. The trials enrolled people with heart failure who met a definition of iron deficiency, so they say nothing about iron given to other people with a low saturation.
Related
Sources
- US Food and Drug Administration. 21 CFR 862.1410, Iron (non-heme) test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1410
- 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. 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
- 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, National Center for Health Statistics. National Health and Nutrition Examination Survey 2017-2018 Laboratory Procedure Manual: Iron (Frozen), 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-Iron-(Frozen)-508.pdf
- Cappellini MD, Comin-Colet J, de Francisco A, et al. Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management. American Journal of Hematology. 2017. https://doi.org/10.1002/ajh.24820
- Bacon BR, Adams PC, Kowdley KV, et al. Diagnosis and management of hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011. https://doi.org/10.1002/hep.24330
- Crawford DHG, Ramm GA, Bridle KR, et al. Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver. Hepatology International. 2023. https://doi.org/10.1007/s12072-023-10510-3
- Liu Yin J, Cussen C, Harrington C, et al. Guideline Review: European Association for the Study of Liver (EASL) Clinical Practice Guidelines on Haemochromatosis. Journal of Clinical and Experimental Hepatology. 2023. https://doi.org/10.1016/j.jceh.2022.11.003
- Ellervik C, Tybjærg-Hansen A, Nordestgaard BG. Total Mortality by Transferrin Saturation Levels: Two General Population Studies and a Metaanalysis. Clinical Chemistry. 2011. https://doi.org/10.1373/clinchem.2010.156802
- Mainous AG, Gill JM, Carek PJ. Elevated Serum Transferrin Saturation and Mortality. The Annals of Family Medicine. 2004. https://doi.org/10.1370/afm.25
- Chua AC, Knuiman MW, Trinder D, et al. Higher concentrations of serum iron and transferrin saturation but not serum ferritin are associated with cancer outcomes. The American Journal of Clinical Nutrition. 2016. https://doi.org/10.3945/ajcn.115.129411
- Graham FJ, Pellicori P, Kalra PR, et al. Intravenous Iron in Patients with Heart Failure and Iron Deficiency: An Updated Meta-Analysis. European Journal of Heart Failure. 2023. https://doi.org/10.1002/ejhf.2810
- Ponikowski P, Mentz RJ, Hernandez AF, et al. Efficacy of ferric carboxymaltose in heart failure with iron deficiency: an individual patient data meta-analysis. European Heart Journal. 2023. https://doi.org/10.1093/eurheartj/ehad586
- Adams PC, Reboussin DM, Press RD, et al. Biological Variability of Transferrin Saturation and Unsaturated Iron-Binding Capacity. The American Journal of Medicine. 2007. https://doi.org/10.1016/j.amjmed.2007.02.027
- 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
- European Federation of Clinical Chemistry and Laboratory Medicine. EFLM Biological Variation Database, meta-analysis estimates, read 2026-11-13. https://biologicalvariation.eu/