Iron and Other Metal Ions in Human Health and Disease.

Abstract

Iron is the most abundant trace element, driving both the commonest deficiency and ferroptosis. This review takes iron as the central theme and extends to copper, zinc, and calcium, spanning physiological functions, pathological mechanisms, risk factors, diagnostics, and therapeutics. We classify these ions into redox-active (iron, copper), which engage in catalytic electron transfer, and redox-inert (zinc, calcium), which serve structural and signaling roles without redox cycling. Iron deficiency remains the global leading micronutrient deficit, whereas iron overload triggers ferroptosis-mediated organ damage. Copper deficiency manifests as hematological and neurological syndromes, while copper excess induces cuproptosis. Zinc deficiency impairs growth and immunity, yet chronic zinc toxicity primarily causes secondary copper deficiency. Calcium dysregulation underpins hypoparathyroidism, osteoporosis, cardiovascular diseases, and crystal deposition disorders. Diagnosis integrates clinical assessment, biochemical profiling, imaging, and genetic analysis; risk factors encompass dietary insufficiency, environmental exposure, genetic variants, and demographic variables. Given the narrow therapeutic window between deficiency and toxicity, vigilant monitoring is mandatory. Treatment strategies are metal-specific and include chelation, hormone replacement, source removal, and channel modulation. Future directions emphasize validated biomarkers, tissue-targeted delivery, and metallo-genomics to enable precision medicine, with iron metabolism as a pivotal entry point for understanding and managing systemic metal homeostasis.