A general summary of typical results involving animal studies is shown in TABLE 7. A consistent and established finding is a reduction of plasma vitamin A concentration in zinc-deficient animals despite diets adequate in vitamin A. However, it appears that the depressed plasma vitamin A is not a result of zinc deficiency per se but rather is nonspecific, resulting from food- and growth-restriction factors associated with zinc deficiency. Food restriction apparently is the critical factor, since both immature and mature nongrowing zinc-deficient animals have exhibited the decreased plasma vitamin A concentration. However, this point needs clarification. Liver vitamin A concentration is usually unaltered by the zinc deficiency, suggesting no defect in absorption or transport to the liver. In regard to retinol-binding protein, it appears from the animal studies that zinc deficiency per se has an effect on both the plasma and liver RBP concentrations. We have hypothesized that zinc deficiency impairs RBP synthesis. It is speculated that only severe zinc deficiency results in a deficit of a sufficient magnitude for impairment of vitamin A metabolism at the cellular level. For example, retinene reductase, an apparent zinc-metallo alcohol dehydrogenase of the retina, appears to be sensitive to a severe zinc deficiency in animal studies. In humans, impaired dark adaptation may be a result of inadequate supplies of the metabolizable zinc necessary to maintain the activity of the enzyme system. Thus, the conversion (dehydrogenation) of vitamin A alcohol to vitamin A aldehyde is impaired, with a resulting abnormality in dark adaptation, i.e., night blindness. Indeed, the limited number of human studies suggest that zinc supplementation may be beneficial to vitamin A metabolism only in conditions where zinc deficiency is prevalent as indicated by low (less than 70 micrograms/100 ml) plasma zinc. Conversely, zinc supplementation is of little benefit in conditions where vitamin A metabolism is altered but zinc status is normal. Therefore, definitive clinical studies involving primary zinc deficiency must be conducted before final conclusions can be made regarding the interrelationships of zinc and vitamin A in health and disease.