High-precision iron isotope analysis of whole blood, erythrocytes, and serum in adults.

Background: Iron isotopic composition serves as a biological indicator of Fe metabolism in humans. In the process of Fe metabolism, essential carriers of Fe circulate in the blood and pass through storage organs and intestinal absorptive tissues. This study aimed to establish an analytical method for high-precision Fe isotopic measurement, investigate Fe concentration and isotopic composition in different parts of whole blood, and explore the potential of Fe isotopic composition as an indicator for Fe status within individuals.

Analytical Methods: A total of 23 clinically healthy Taiwanese adults of Han descent were enrolled randomly and Fe isotopic compositions of their whole blood, erythrocytes, and serum were measured. The Fe isotopic analysis was performed by Neptune Plus multiple-collector inductively coupled plasma mass spectrometry with double-spike technique. The precision and reproducibility of the Fe isotopic analysis were monitored by international biological and geological reference materials.

Main Findings: High-precision Fe isotopic measurements were achieved alongside with high consistency in the isotopic data for well-characterized reference materials. The Fe isotopic signatures of whole blood and erythrocytes were resolvable from that of serum, where both whole blood and erythrocytes contained significantly lighter Fe isotopic compositions compared to the case of serum (P = 0.0296 and P = 0.0004, respectively). The δFe value of the serum sample was 0.2‰ heavier on an average than those of whole blood or erythrocytes. This isotopic fractionation observed in different parts of whole blood may indicate redox processes involved in Fe cycling, e.g. erythrocyte production and Fe transportation. Moreover, the δFe values of whole blood and serum significantly correlated with the hemoglobin level (P = 0.0126 and P = 0.0020, respectively), erythrocyte count (P = 0.0014 and P = 0.0005, respectively), and Mentzer index (P = 0.0055 and P = 0.0011, respectively), suggesting the Fe isotopic composition as an indicator of functional Fe status in healthy adults. The relationships between blood Fe isotopic compositions and relevant biodemographic variables were also examined. While the average Fe concentration of whole blood was significantly higher in males than in females (P = 0.0028), females exhibited a heavier Fe isotopic composition compared to that of males in whole blood (P = 0.0010) and serum (P < 0.0001). A significantly inverse correlation of the whole blood δFe value with body mass index of individuals (P = 0.0095) was also observed.

Conclusion: The results presented herein reveal that blood Fe isotopic signature is consequentially linked to baseline erythrocyte parameters in individuals and is significantly affected by the gender and body mass index in the adult population. These findings support the role of Fe isotopic composition as an indicator for the variance of Fe metabolism among adult individuals and populations and warrant further study to elucidate the underlying mechanisms.