Biomarkers of Iron Status: Transferrin

Optimal Takeaways

Transferrin is the main transport protein that carries iron in the blood. Transferrin reduces the risk of iron creating dangerous free radicals by keeping it bound. Transferrin also reduces iron availability to bacteria that can use it for their growth. Transferrin will decrease when iron availability is high and increase when iron availability is low.

Standard Range: 200 - 390 mg/dL (2.0 - 3.9 g/L)

The ODX Range: 200 - 360 mg/dL (2.0 - 3.6 g/L)

Low transferrin is associated with inflammation, chronic illness, malignancy, collagen vascular disease, cirrhosis, hypoproteinemia, hemolytic, pernicious, and sickle cell anemias (Pagana 2021), liver dysfunction, and a protein-deficient diet (Kotze 2009).

High transferrin levels are associated with iron deficiency anemia, oral contraceptive use, pregnancy, and polycythemia vera (Pagana 2021).

Overview

Serum transferrin is a hepatic protein that transports iron through the blood. Under normal circumstances, approximately one-third of circulating transferrin will be saturated with iron, leaving additional binding capacity available when needed. Transferrin picks up iron from the GI tract but receives most of it from the recycling of hemoglobin. Transferrin levels decrease when iron availability is high and increase when availability is low. Its utilization in diagnosing iron deficiency is limited as it is a negative acute-phase reactant that can decrease during inflammation and chronic illness (Pagana 2021).

Each transferrin molecule can carry 1-2 atoms of iron and maintain a normal plasma pool of 3-4 milligrams of transferrin-bound iron. Transferrin delivers iron to three main storage sites: the liver, spleen, and bone marrow. Maintaining iron in bound form is an essential protective mechanism, as unbound iron can generate harmful free radicals. Maintaining iron in its bound form is also critical to keeping it away from bacteria that can use free iron for their proliferation. Although transferrin has a high affinity for iron, it can also bind other nutrients, including chromium, copper, manganese, zinc, nickel, and cadmium, a toxin (Gropper 2021).

Monitoring transferrin over time may be prudent in several chronic conditions. A retrospective study of cirrhosis patients found that those with transferrin below 180 mg/dL had significantly lower transplant-free survival than those at 180 mg/dL or above. Transferrin was inversely correlated with CRP, decreasing as CRP increased (Viveiros 2018).

In a retrospective study of type 2 diabetics, a transferrin of 115 mg/dL or below was significantly associated with progression to end-stage renal disease versus a transferrin of 165 mg/dL or above (Zhao 2020). Low transferrin may indicate protein malnutrition, and in one study of chronic hemodialysis patients, transferrin increased significantly from 169.4 mg/dL to 180.9 mg/dL with nutrition intervention that increased dietary protein (Lim 2012).

References

Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P. Advanced Nutrition and Human Metabolism. 8^th edition. Wadsworth Publishing Co Inc. 2021.

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

Lim, Su-Lin, and Jamie Lye. “Nutritional Intervention Incorporating Expedited 10 g Protein Counter (EP-10) to Improve the Albumin and Transferrin of Chronic Hemodialysis Patients.” ISRN nutrition vol. 2013 396570. 22 Oct. 2012, doi:10.5402/2013/396570

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

Viveiros, André et al. “Transferrin as a predictor of survival in cirrhosis.” Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society vol. 24,3 (2018): 343-351. doi:10.1002/lt.24981

Zhao, Lijun et al. “Serum transferrin predicts end-stage Renal Disease in Type 2 Diabetes Mellitus patients.” International journal of medical sciences vol. 17,14 2113-2124. 29 Jul. 2020, doi:10.7150/ijms.46259