Biomarkers of Iron Status: Transferrin Saturation

Optimal Takeaways

The transferrin saturation (TSAT) percentage indicates how much transferrin in the bloodstream is bound to iron. Low TSAT is linked to conditions like iron deficiency anemia, chronic illness, malignancy, insulin resistance, and inflammation. Conversely, high TSAT can signal iron overload conditions, various anemias, and an increased risk of cardiovascular disease and diabetes. Both low and high TSAT may be associated with cardiovascular disease and all-cause mortality.

Standard Range: 20 - 48%

The ODX Range: 24 - 35%                   

Low transferrin saturation is associated with iron deficiency anemia, chronic illness, malignancy (Pagana 2021), insulin resistance, diabesity, inflammation, and possibly impaired erythropoiesis (Pilar Vaquero 2021). Both low and high %transferrin saturation may be associated with CVD and all-cause mortality (Stack 2014).

High transferrin saturation is associated with iron overload or overdose, hemochromatosis, hemosiderosis, and hemolytic, sideroblastic, and megaloblastic anemias (Pagana 2021). Elevated %transferrin saturation may also be associated with increased risk of cardiovascular disease mortality (Stack 2014), and type 1 and 2 diabetes (Ellervic 2011).

Overview

Transferrin saturation (TSAT) is derived by dividing the serum iron level by TIBC and multiplying by 100. A value below 15% is associated with iron-deficiency anemia (Pagana 2021).

Cardiovascular and all-cause mortality displays a J-shaped curve with regard to transferrin saturation. A review of data from 15,823 subjects in the Third NHANES III study found significantly greater mortality in those with TSAT below 23.7% or above 31.3% compared to the reference group of 23.7-31.3%. The association with cardiovascular mortality specifically was even more robust. Researchers note that the greatest survival was observed at a TSAT of 24-40% (Stack 2014). Fasting transferrin saturation above 60% in men or 50% in women suggests hemochromatosis (Kotze 2009).

Data from three large population studies determined that a transferrin saturation of 50% or above was associated with significantly greater (2-3-fold) risk for type 1 and type 2 diabetes. Researchers note that iron overload, particularly hemochromatosis, is a risk factor for developing diabetes (Ellervic 2011). However, a low TSAT of 20% or less was associated with obese diabetics (diabesity), inflammation, insulin resistance, and possibly impaired erythropoiesis (Pilar Vaquero 2021).

Elevated transferrin saturation is also associated with all-cause mortality. Evaluation of research from NHANE studies indicates a level of 55% or above increased the risk of all-cause mortality despite controlling for diabetes, hypertension, smoking, elevated cholesterol, and cancer. Individuals with 45% or less transferrin saturation had the lowest all-cause mortality rate (Mainous 2004).

References

Ellervik, Christina et al. “Elevated transferrin saturation and risk of diabetes: three population-based studies.” Diabetes care vol. 34,10 (2011): 2256-8. doi:10.2337/dc11-0416

Kotze, M J et al. “Pathogenic Mechanisms Underlying Iron Deficiency and Iron Overload: New Insights for Clinical Application.” EJIFCC vol. 20,2 108-23. 25 Aug. 2009

Mainous, Arch G 3rd et al. “Elevated serum transferrin saturation and mortality.” Annals of family medicine vol. 2,2 (2004): 133-8. doi:10.1370/afm.25

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Pilar Vaquero, M et al. “Diabesity negatively affects transferrin saturation and iron status. The DICARIVA study.” Diabetes research and clinical practice vol. 172 (2021): 108653. doi:10.1016/j.diabres.2021.108653

Stack, A G et al. “Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.” QJM : monthly journal of the Association of Physicians vol. 107,8 (2014): 623-33. doi:10.1093/qjmed/hcu045