Iron (Fe) is essential for life but can be harmful in excess. It, along with calcium (Ca), magnesium (Mg), and trace elements like copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), mercury (Hg), and nickel (Ni), plays a critical role in biological processes. These elements share proteins involved in Fe absorption and transport. Cu and Cd can inhibit Fe absorption, while excess Fe may interfere with Cu metabolism and reduce ceruloplasmin. Excess Fe can hinder Zn absorption, and transferrin can bind to both Zn and Ni. Ca inhibits Fe absorption by affecting DMT1, and low Mg can worsen Fe deficiency. Pb and Cd affect Fe distribution and uptake. Exposure to Hg is linked to higher ferritin levels, and Ni alters intracellular Fe metabolism. Phlebotomy in hemochromatosis patients increases Cd and Pb levels and affects trace elements in anemia. The effects of chronic exposure to trace elements are not well understood. Fe is abundant in the human body and vital for life, involved in oxygen transport, DNA synthesis, and many biological processes. Maintaining Fe balance is crucial, regulated by proteins like DMT1, FPN1, transferrin, and hepcidin. Fe metabolism is closely linked to Ca, Mg, and trace elements. These elements interact during absorption and distribution, affecting various organs. Understanding these interactions is important for health strategies. Fe, Ca, Mg, and trace elements are essential for health, supporting physiological functions and providing insights into disease states. Non-essential elements like Pb, Cd, Hg, and Ni can pose health risks by interfering with Fe regulation. These elements enter the body through occupational exposure or environmental factors. Understanding their impact on Fe metabolism and health is crucial for developing mitigation strategies. Historical evidence shows Fe's significance in human health, with conditions like chlorosis treated with Fe supplements. Fe's role in hemoglobin synthesis and oxygen transport was recognized in the early 20th century. Hemochromatosis was described in the 19th century, linking Fe overload to health issues. This review evaluates the interactions between Fe, Ca, Mg, and trace elements, and their roles in diseases. Understanding these interactions can enhance knowledge of their effects on human health.Iron (Fe) is essential for life but can be harmful in excess. It, along with calcium (Ca), magnesium (Mg), and trace elements like copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), mercury (Hg), and nickel (Ni), plays a critical role in biological processes. These elements share proteins involved in Fe absorption and transport. Cu and Cd can inhibit Fe absorption, while excess Fe may interfere with Cu metabolism and reduce ceruloplasmin. Excess Fe can hinder Zn absorption, and transferrin can bind to both Zn and Ni. Ca inhibits Fe absorption by affecting DMT1, and low Mg can worsen Fe deficiency. Pb and Cd affect Fe distribution and uptake. Exposure to Hg is linked to higher ferritin levels, and Ni alters intracellular Fe metabolism. Phlebotomy in hemochromatosis patients increases Cd and Pb levels and affects trace elements in anemia. The effects of chronic exposure to trace elements are not well understood. Fe is abundant in the human body and vital for life, involved in oxygen transport, DNA synthesis, and many biological processes. Maintaining Fe balance is crucial, regulated by proteins like DMT1, FPN1, transferrin, and hepcidin. Fe metabolism is closely linked to Ca, Mg, and trace elements. These elements interact during absorption and distribution, affecting various organs. Understanding these interactions is important for health strategies. Fe, Ca, Mg, and trace elements are essential for health, supporting physiological functions and providing insights into disease states. Non-essential elements like Pb, Cd, Hg, and Ni can pose health risks by interfering with Fe regulation. These elements enter the body through occupational exposure or environmental factors. Understanding their impact on Fe metabolism and health is crucial for developing mitigation strategies. Historical evidence shows Fe's significance in human health, with conditions like chlorosis treated with Fe supplements. Fe's role in hemoglobin synthesis and oxygen transport was recognized in the early 20th century. Hemochromatosis was described in the 19th century, linking Fe overload to health issues. This review evaluates the interactions between Fe, Ca, Mg, and trace elements, and their roles in diseases. Understanding these interactions can enhance knowledge of their effects on human health.