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Understanding Iron Saturation and Its Clinical Implications
Iron Saturation and Osteogenic Activity
Iron saturation levels significantly impact the osteogenic activity of lactoferrin (LF). Research indicates that as the iron saturation level of LF increases, its ability to stimulate osteoblast proliferation decreases both in vitro and in vivo. Specifically, LF with lower iron saturation (apo-LF) promotes more robust new bone formation compared to LF with higher iron saturation (holo-LF) 1. This suggests that the conformational changes in LF due to varying iron saturation levels play a crucial role in its osteogenic activity.
Total Iron-Binding Capacity (TIBC) and Transferrin Saturation
Total iron-binding capacity (TIBC) is a critical measure used to determine the maximum amount of iron that can be bound by plasma or serum transferrin, the primary iron-transport protein. TIBC is closely correlated with transferrin concentration, and it is often used alongside serum iron and transferrin saturation (TS) to diagnose iron-deficiency anemia and other iron-related disorders 2. The calculation of TIBC can be done directly or through automated methods, which have shown strong correlation with transferrin concentrations 2.
Diagnostic Methods for Iron Saturation
Different methods are employed to determine iron saturation levels in clinical settings. A survey of clinical laboratories revealed that transferrin saturation is commonly calculated using either the ratio of serum iron to TIBC or the ratio of serum iron to transferrin concentration 3. Both methods are effective in screening for conditions like genetic hemochromatosis, although the transferrin index (TI) has been recommended as a more precise alternative due to its lower false-positive rate 3.
Transferrin Saturation in Diagnosing Iron Deficiency
Transferrin saturation is a valuable diagnostic criterion for iron deficiency, especially when used in conjunction with ferritin levels. This combination is particularly beneficial for diagnosing iron deficiency in patients with chronic inflammatory diseases, where traditional markers may be less reliable 4. The systematic review highlights the importance of using transferrin saturation as part of a comprehensive diagnostic approach to iron deficiency.
Iron Absorption and Transferrin Saturation
The relationship between iron absorption and transferrin saturation is complex. Studies show that dietary iron absorption correlates more strongly with a reference dose of iron than with serum ferritin levels, particularly in subjects with transferrin saturation below 25% 8. This indicates that while both serum ferritin and transferrin saturation reflect iron status, the control of iron absorption in iron-replete individuals is more dependent on iron stores as indicated by serum ferritin.
Iron Therapy in Hemodialysis Patients
In anemic hemodialysis patients with high ferritin and low transferrin saturation, intravenous iron therapy has been shown to be effective. The DRIVE study demonstrated that administering ferric gluconate significantly increased hemoglobin levels and transferrin saturation compared to no iron therapy, even in patients with high baseline ferritin levels 10. This suggests that intravenous iron can be beneficial in managing anemia in hemodialysis patients, regardless of their initial ferritin levels.
Conclusion
Iron saturation plays a crucial role in various physiological and clinical contexts, from bone formation to the management of anemia. Understanding the methods for measuring and interpreting iron saturation, as well as its implications for iron therapy, is essential for effective diagnosis and treatment of iron-related disorders. The research underscores the importance of using a combination of diagnostic markers to accurately assess and manage iron status in different patient populations.
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Most relevant research papers on this topic
Effect of iron saturation level of lactoferrin on osteogenic activity in vitro and in vivo.
Lactoferrin's osteogenic activity decreases with increasing iron saturation level in vitro and in vivo, potentially due to conformational changes in lactoferrin.
RCT
Animal StudyTotal iron-binding capacity calculated from serum transferrin concentration or serum iron concentration and unsaturated iron-binding capacity.
The DTIBC assay accurately measures total iron-binding capacity, aiding in the diagnosis of iron-deficiency anemia and chronic inflammatory disorders.
Highly CitedTransferrin index: an alternative method for calculating the iron saturation of transferrin.
Calculated transferrin index (TI = Fe/TRF) is a more precise and sensitive method for screening iron overload than total iron-binding capacity (TIBC).
Observational StudyHighly CitedUsing transferrin saturation as a diagnostic criterion for iron deficiency: A systematic review
Using transferrin saturation in addition to ferritin is beneficial in diagnosing iron deficiency and aiding in first-line analysis for patients with chronic inflammatory diseases.
Systematic ReviewSome Quantitative Considerations in Iron Nutrition of Higher Plants.
The minimum concentration of iron ions required for adequate plant growth should not exceed the saturation concentration given by the solubility product, as iron is thermodynamically unstable in aqueous solutions and may be taken up through exchange phenomena or complex formation.
Evaluation of different methods for determination of the iron saturation level in bovine lactoferrin.
Chromametry, Differential Scanning Calorimetry, and Circular roism spectropolarimetry are reliable methods for estimating iron saturation levels in bovine lactoferrin up to 75% iron saturation.
Assessing iron status: beyond serum ferritin and transferrin saturation.
Newer markers for iron status, such as reticulocyte hemoglobin content and soluble transferrin receptor, may be useful in diagnosing iron deficiency in chronic kidney disease patients.
Highly CitedRelationships among iron absorption, percent saturation of plasma transferrin and serum ferritin concentration in humans.
Serum ferritin concentration is more important for controlling iron absorption in iron-replete subjects than transferrin saturation, as both indicators reflect iron status in iron-depleted subjects.
Observational StudyHighly CitedTransferrin saturation, plasma iron turnover, and transferrin uptake in normal humans.
Increased plasma iron and transferrin saturation lead to increased iron delivery to tissues, but the number of iron-bearing transferrin molecules leaving the plasma to bind to tissue receptors remains relatively constant.
In Vitro StudyFerric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study.
Intravenous ferric gluconate is highly effective in anemic hemodialysis patients with high ferritin and low transferrin saturation, improving hemoglobin levels and reducing iron deficiency.
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