Zinc is among the most important of the trace elements in human nutrition. The remarkable ability of this metal to participate in flexible and easily exchangeable ligand binding with organic molecules underlies the extraordinary extend to which zinc has been incorporated into an impressive range of biological systems. This has undoubtedly been assisted by the relative safety of this element, especially its lack of oxidant properties (in sharp contrast to iron and copper), which facilitates its transport within the body and its metabolism in individual cells as well as its utilization biologically. It is, indeed, ubiquitous in sub-cellular metabolism. Zinc is essential for gene expression and nucleic acid metabolism which accounts in part for its importance for cellular growth and differentiation, in which it may actually have a regulatory role. Its ligand binding properties are utilized effectively at the catalytic site of a wide range of enzymes. Zinc also has many structural roles in biological membranes, cell receptors (for example, for hormones including testosterone), enzymes and other proteins. One much-quoted example is the "zinc finger" that is present in certain transcription proteins that are vital for gene expression.

Because of zinc's vital roles in cellular growth and differentiation, and probably for several other reasons, zinc is especially important at times of the human life cycle, for example early childhood and during the reproductive cycle, that are associated with rapid prenatal of postnatal growth. It is also needed especially by tissues that turnover rapidly such as the immune system and bone marrow, which is likely to go a long way towards explaining in general terms why a salient feature of zinc deficiency is gross and multifaceted impairment of normal host defence mechanisms. These disturbances of immune function are likely to underlie some of the most serious consequences of zinc deficiency, which are of special concern in infants and young children, specifically the susceptibility to infections, notably infections of the respiratory system, diarrheal disease and parasitic infections. Similarly, the rapidly turning over mucosal lining of the gut is compromised by zinc deficiency which, by several putative mechanisms, leads to or/and aggravates diarreal disease.

At one or, more likely, several levels, the zinc requirement for normal cellular growth and differentiation may underlie the impairment of physical growth that is a hallmark of zinc deficiency in childhood and may also contribute to impaired function of the developing brain of the zinc-deprived young child for which evidence continues to accumulate. In general, though, the biochemical correlates of the clinical features of zinc deficiency still lack adequate definition. Better ability to link clinical features of zinc deficiency with progressive advances in knowledge of the biology of zinc is one factor that will accelerate optimal treatment and prevention of human zinc deficiency.

Other factors that have and continue to hamper progress include the non-specific nature of the deleterious effects of zinc deficiency on human health and development. For example, though zinc deficiency is now recognized as a major factor contributing to diarrheal disease and its associated morbidity and mortality, it is clearly only one of numerous etiologic factors. Hence, clinical features of zinc deficiency do not give the same strong clue to the existence of this deficiency as, for example does hypochromic anemia to iron deficiency. As a further major challenge to the detection of zinc deficiency, laboratory assays only give limited help. Though careful recent data analysis has shown that relatively low circulating levels of zinc in blood plasma do help to identify populations who are likely to benefit from zinc supplements, no index has been identified that is sufficiently sensitive and reproducible to reliably detect individuals who are suffering from mild to moderate zinc deficiency. As the global extent of zinc deficiency becomes increasingly apparent, these problems become more vexing. Though zinc is regarded quite correctly as a relatively "safe" metal, it is also becoming increasingly apparent that the optimal physiologic range of intake and body content is not so broad as had been thought and the adverse consequences of excess can be of much greater concern than had been appreciated. Hence, it is important not only to be able to identify those individuals or populations who are likely to benefit from increasing intakes of bioavailable zinc but to achieve a better idea of optimal intervention strategies.

In order to achieve this, it is necessary to gain better insights into the regulation of zinc metabolism at a molecular and sub-cellular as well as a whole body level. In particular, it would be helpful to know much more about how whole body zinc homeostasis is maintained, and the "cost" of this, in terms of zinc "status", under a variety of different dietary and host circumstances. The advent and refinement of zinc stable isotope techniques, which allow us to trace the progress of zinc, from the time it is taken through the gut and the body, now offers one important tool for addressing these questions. It has been found to be feasible to combine these sophisticated and quite complex scientific techniques with intervention studies even in remote communities, though cost and funding restrictions continue to hamper progress. These techniques can provide quantitative information on how and to what extend zinc homeostasis is adjusted in communities/individuals in which/whom the intake of bioavailable zinc is habitually low.

They can be of outstanding assistance in evaluating the quantitative effects of different intervention strategies for the prevention/treatment of zinc deficiency, hence contributing to the ultimate selection of the safest, simplest and optimal strategies.