Critical Importance of Iron Saturation in Lactoferrin: Effects on Biological Activity, Nutritional Functions, and Applications

Lactoferrin (LF), a multifunctional glycoprotein with high iron-binding affinity, plays a critical role in modulating physiological processes through its ability to reversibly bind and release iron ions, existing in two distinct states: iron-saturated (holo-LF, > 85% saturation) and iron-deficient (apo-LF, < 5% saturation). However, the importance of iron saturation has been largely overlooked in LF production and research due to the lack of standardized protocols. The iron saturation level of LF dictates its functional specificity: apo-LF exhibits potent antimicrobial properties by chelating iron and disrupting membrane integrity, while also significantly inhibiting oxidative stress, thereby alleviating neurological disorders and modulating immune responses. In contrast, holo-LF participates in iron metabolism and transport, influencing tumor cell proliferation and systemic iron uptake. This review systematically evaluates the interplay between iron saturation levels and LF's biological functions, emphasizing its dual roles in human iron homeostasis and disease modulation. Future research should prioritize elucidating the mechanisms underlying iron saturation-dependent bioactivity and metabolic differences, while incorporating emerging technologies to enhance LF stability and refine iron saturation measurement accuracy.