Serum selenium as well as serum zinc, copper, magnesium, calcium and manganese were investigated in a control group of adult males and in 11 groups of patients in various disease states. Not only the change of each trace element but also the possible association between elements was studied in the various groups. All patients were fasting when sampled and studied only after the acute phase of the disease was corrected. Trace metal determinations were performed by atomic absorption spectrophometry (Mg, Ca, Cu, Zn) and by neutron activation analysis (Se, Mn). All patients showed low serum zinc when compared to controls. Cirrhotic patients had a low serum selenium level as well as low calcium, magnesium and zinc. Emphysemia and cancer patients had an elevated serum copper concentration while copper and manganese levels were elevated in congestive heart failure, infection and pschoses. To our knowledge this is the first time low serum selenium values have been demonstrated to be associated with the low serum zinc, calcium and magnesium levels found in cirrhotic patients.

Advances in knowledge of the trace elements zinc, manganese, and copper are reviewed (151 references), particularly as related to human metabolism and disorders. The literature reviewed, with few exceptions, is that published by December 1973.

The clinical association of decreased serum and hepatic zinc in patients with cirrhosis of the liver presumably arising from excess ethanol ingestion prompted a study of the activities of zinc and alcohol in experimental animals. The purpose of this study was to determine the effect of zinc deficiency upon lipid peroxidation in the liver. The effect of ethanol and zinc deficiency on lipid peroxidation was also evaluated. Rats were used in the experimental design, one group received a control diet, and one was maintained on a zinc-deficient diet. One-half of each group also received 3.85 g ethanol per kilogram body weight daily. Lipid peroxidation in vivo was determined by estimation of diene conjugation of microsomal lipids. The in vitro lipid peroxidation potential was measured by the generation of malonic dialdehyde by enzymatic as well as nonenzymatic reactions. Analysis of this data indicated that increased hepatic microsomal lipid peroxidation was associated with zinc deficiency whether using in vivo or in vitro indices of measurement. Review of the data from individual animals indicated that the lowest levels of serum zinc were associated with increased hepatic content of phospholipids. The degree of lipid peroxidation in the zinc deficient animals was not increased by ingestion of alcohol.

Ethanol metabolism as a function of age was assessed in male Sprague-Dawley rats. The ethanol metabolic rates decreased linearly with advancing age. It was also observed that a linear decrease in hepatic alcohol dehydrogenase activity occurred as a function of age. The decreased enzyme activity could be the biochemical mechanism underlying changes in ethanol metabolism. Impaired ethanol metabolism may produce increased pharmacologic effects in older subjects due to increased blood ethanol levels.

Zinc deficiency is associated with poor growth and development. It has been postulated that a deficiency of the various zinc metalloenzymes results from the lack of dietary zinc. From present study, an examination of some aspects of this postulate, we conclude the following about zinc deficiency in pigs: (1) Of the tissues studied, it results in diminished zinc content only in liver, kidney, and pancreas. (2) It is associated with tissue ab normalities of various trace elements other than zinc. (3) Histochemical enzyme assays are satisfactory for qualitative but not quantitative determination of zinc me talloenzymes. (4) Deficiency of various tissue zinc metalloenzymes is difficult to demonstrate, even in severezinc deficiency. (5) It is associated with decreased activity of hepatic leucine aminopeptidase and ornithine transcarbamylase, and decreased serum cholesterol concentrations. Our findings are consistent with the postulate that alterations in a number of trace elements may occur in the entity called zinc deficiency.