In order to document specific effects of zinc deficiency in humans, we established an experimental human model of zinc deficiency. Adult healthy human volunteers received restricted zinc intake for several weeks under strict metabolic conditions. We monitored zinc levels in plasma, red blood cells, lymphocytes, granulocytes and platelets. We assayed several zinc dependent enzymes including deoxythymidine kinese in rapidly regenerating collagen connective tissue and 5' ectonucleotidase in lymphocytes, a marker of cell maturity. Both of these enzymes turned out to be very sensitive biomarkers of mild human zinc deficiency. Most importantly we observed that cell medicated immune function was affected adversely as a result of dietary zinc restriction.
Serum active thymulin (a thymic hormone responsible for differentiation and proliferation of thymic dependent lymphocytes (TH) and generation of Th1 cytokines such as 1L-2 and 1FN-Y were down regulated within eight to twelve weeks of institution of zinc restricted diet. Decreased 1L-2 activity decreased the activation of NK cell and T cytolytic cells activities. Decreased 1FN-Y and 1L-12 generated by macrophages-monocytes which is also zinc dependent, together activate macrophages-monocytes to kill parasites, viruses and bacteria. Thus as a result of zinc deficiency the macrophages-monocytes function is also affected adversely. Th2 cytokines were not affected by zinc deficiency. Macrophage monocytes were activated by zinc deficiency and these cells generated inflammatory cytokine such as 1L-1β and TNF-α and upregulation of inflammatory cytokines resulted in increased oxidative stress. Thus in our human experimental model studies, we showed that cell medicated immune function was affected adversely and there was an upregulation of inflammatory cytokines and increased oxidative stress. The earliest effect of zinc restricted diet was on active thymulin andIL-2 generation from TH1 cells.
These effects were seen after eight to ten weeks of zinc restriction. At this time the zinc levels in plasma, lymphocytes, granulocytes and platelets were not decreased. We observed decreased levels in lymphocytes after sixteen to twenty weeks of zinc restriction and the plasma zinc decreased after 24 weeks of zinc restricted diet. Thus we concluded that sensitive biomarkers were immune functions and assays of TK and 5' ectonucleotidase activities.