Iron
The role of iron in immunonutrition has been widely discussed and confirmed by many studies [133]. Iron is required for a number of different cellular functions and there is a constant balance between iron uptake, transport, storage, and utilization required to maintain iron homeostasis [134, 135]. As the body lacks a defined mechanism for the active excretion of iron, iron balance is mainly regulated at the point of absorption. Iron deficiency induces thymus atrophy and has multiple effects on immune function in human subjects [133, 136].
The effects of this micronutrient in modulating the immune system include the regulation of T cell differentiation and proliferation [85], also helping to regulate the interplay between helper T cells and cytotoxic T cells [95, 137]. It also play a role in IFN-γ production and participates in the production of cytokines, in fact it is involved in the regulation of the production and action of cytokines. It forms highly toxic hydroxyl radicals, involved in the killing of bacteria by neutrophils and it is a component of enzymes critical for the functioning of immune cells (e.g. ribonucleotide reductase involved in DNA synthesis) [95]. The iron-rich state promotes the M2-like macrophage phenotype and negatively regulates the M1 pro-inflammatory response [138]. This nutrient is necessary for the generation of ROS, that kill pathogens (by neutrophils) during the oxidative burst [85]. Finally, it appears to be essential for the differentiation and growth of epithelial tissue [95].
Iron at doses above the upper threshold has been associated with increased risk of malaria and other infections, including pneumonia [139]. Obviously it should be noted that treatment for anemia in a malarious area must be preceded by an effective anti-malarial therapy. Notably, iron rich status promotes M2-like macrophage phenotype and negatively regulates M1 pro-inflammatory response [65]. On the other hand, iron overload causes impairment of immune function [140]. Iron excess increases the harmfulness of inflammation and the microorganisms themselves require iron as it can contribute to the growth of the pathogen. RDA for iron reports a range of 8–18 mg/day [138].