Abstract
Zinc is an essential element for humans, and its deficiency was documented in 1963. Nutritional zinc deficiency is now known to affect over two billion subjects in the developing world. Conditioned deficiency of zinc in many diseases has also been observed. In zinc-deficient dwarfs from the Middle East, we reported growth retardation, delayed sexual development, susceptibility to infections, poor appetite, and mental lethargy. We never found a zinc-deficient dwarf who survived beyond the age of 25 y. In an experimental model of human mild zinc deficiency, we reported decreased thymulin (a thymopoietic hormone) activity in Th1 cells, decreased mRNAs of IL-2 and IFN-gamma genes, and decreased activity of natural killer cells (NK) and T cytotoxic T cells. The effect of zinc deficiency on thymulin activity and IL-2 mRNA was seen within eight to twelve weeks of the institution of zinc-deficient diet in human volunteers, whereas lymphocyte zinc decreased in 20 weeks and plasma zinc decreased in 24 weeks after instituting zinc-deficient diet. We hypothesized that decreased thymulin activity, which is known to proliferate Th1 cells, decreased the proliferation differentiation of Th1 cells. This resulted in decreased generation of IL-2 and IFN-gamma. We observed no effect in Th2 cell function; thus, zinc deficiency resulted in an imbalance of Th1 to Th2 function resulting in decreased cell-mediated immunity. Zinc therapy may be very useful in many chronic diseases. Zinc supplementation improves cell-mediated immunity, decreases oxidative stress, and decreases generation of chronic inflammatory cytokines in humans. Development of sensitive immunological biomarkers may be more sensitive than an assay of zinc in plasma and peripheral blood cells for diagnosis of marginal zinc deficiency in human.
Highlights
Raulin in 1869 [1] showed for the first time that zinc was required for the growth of Aspergillus niger
Hypogonadism, skin changes, poor appetite, mental lethargy, abnormal dark adaptation, and delayed wound healing are some of the manifestations of moderate zinc deficiency in human subjects
Bach et al [20] described the biochemical characteristics of a thymic hormone protein called facteur thymique serique (FTS)
Summary
Raulin in 1869 [1] showed for the first time that zinc was required for the growth of Aspergillus niger. Within three weeks of my arrival in Shiraz, my Chief Resident showed me a 21 yr old male who was extremely growth retarded, had no secondary sexual characteristics, and had hypogonadism, hepatosplenomegaly, rough skin, and mental lethargy [7] He was severely anemic, and the anemia was due to iron deficiency. Genitalia size increased to normal size, and secondary sexual characteristics developed within 12-24 wk in all subjects following zinc supplementation No such changes were observed in a comparable length of time in the iron-supplemented group or in the group on an animal protein diet alone [10]. There was a highly significant effect of zinc supplementation on increase in height [13] These studies indicate that zinc deficiency is a global health problem, which affects growth and development in children. It is evident that nutritional as well as conditioned deficiency of zinc may complicate many diseases in human subjects
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