The isolation of two forms of hepatic zinc-thioneins after either zinc injection into rats or partial restriction of their food intake is described. The proteins differed slightly in their amino acid composition and electrophoretic mobilities. Increases in liver zinc content after both treatments were synchronous with, and associated almost completely with, increased zinc-binding to these proteins. The time-course for the appearance and disappearance of the zinc proteins is shown. It is suggested that metallothionein is involved in the normal metabolism of zinc, perhaps in some temporary storage or detoxication capacity.

The effect of administration of large amounts of zinc on immune response and serum lipoproteins was examined. Eleven healthy adult men ingested 150 mg of elemental zinc twice a day for six weeks. This was associated with a reduction in lymphocyte stimulation response to phytohemagglutinin as well as chemotaxis and phagocytosis of bacteria by polymorphonuclear leukocytes. Serum high-density lipoprotein concentration decreased significantly and low-density lipoprotein level increased slightly. The common food fad of zinc supplementation with resultant excessive intake could have deleterious effects in healthy persons.

BACKGROUND: Multiple studies have been carried out to assess the effect of zinc supplementation on children's growth. The results of these studies are inconsistent, and the factors responsible for these varied outcomes are unknown. OBJECTIVE: Meta-analyses of randomized controlled intervention trials were therefore completed to assess the effect of zinc supplementation on the physical growth and serum zinc concentrations of prepubertal children. DESIGN: A total of 33 acceptable studies with appropriate data were identified by MEDLINE (National Library of Medicine, Bethesda, MD) searches and other methods. Weighted mean effect sizes (expressed in SD units) were calculated for changes in height, weight, weight-for-height, and serum zinc concentration by using random-effects models; factors associated with effect sizes were explored by meta-regression techniques. RESULTS: Zinc supplementation produced highly significant, positive responses in height and weight increments, with effect sizes of 0.350 (95% CI: 0.189, 0.511) and 0.309 (0.178, 0.439), respectively. There was no significant effect of zinc on weight-for-height indexes [weighted mean effect size:-0.018 (-0.132, 0.097)]. Zinc supplementation caused a large increase in the children's serum zinc concentrations, with an effect size of 0.820 (0.499, 1.14). Growth responses were greater in children with low initial weight-for-age z scores and in those aged >6 mo with low initial height-for-age z scores. CONCLUSIONS: Interventions to improve children's zinc nutriture should be considered in populations at risk of zinc deficiency, especially where there are elevated rates of underweight or stunting. The population mean serum zinc concentration is a useful indicator of the successful delivery and absorption of zinc supplements in children.

OBJECTIVE--To evaluate whether zinc supplementation during pregnancy is associated with an increase in birth weight. DESIGN--A randomized double-blind placebo-controlled trial. SETTING--Outpatient clinic and delivery service at the University of Alabama at Birmingham. PATIENTS--Five hundred eighty medically indigent but otherwise healthy African-American pregnant women with plasma zinc levels below the median at enrollment in prenatal care, randomized at 19 weeks' gestational age. Women were subdivided by the population median body mass index of 26 kg/m2 into two groups for additional analyses. INTERVENTION--Women who were taking a non-zinc-containing prenatal multivitamin/mineral tablet were randomized to receive either a daily dose of 25 mg of zinc or a placebo until delivery. MAIN OUTCOME MEASURES--Birth weight, gestational age at birth, and head circumference at birth. RESULTS--In all women, infants in the zinc supplement group had a significantly greater birth weight (126 g, P =.03) and head circumference (0.4 cm, P =.02) than infants in the placebo group. In women with a body mass index less than 26 kg/m2, zinc supplementation was associated with a 248-g higher infant birth weight (P =.005) and a 0.7-cm larger infant head circumference (P =.007). Plasma zinc concentrations were significantly higher in the zinc supplement group. CONCLUSIONS--Daily zinc supplementation in women with relatively low plasma zinc concentrations in early pregnancy is associated with greater infant birth weights and head circumferences, with the effect occurring predominantly in women with a body mass index less than 26 kg/m2.

An integration of knowledge concerning regulation of metallothionein expression with research on metallothionein's proposed functions is necessary to delineate how this metalloprotein affects cellular processes, especially zinc metabolism. Metallothionein expression is driven by a number of physiological mediators through several response elements in the metallothionein gene promoter. Cellular accumulation of metallothionein depends on both gene expression and protein degradation. Both depend largely on availability of cellular zinc derived from the dietary zinc supply. Metallothionein expression is related to zinc accumulation in certain organs. Evidence has been produced, which suggests that metallothionein could act in a number of biochemical processes. It may act in zinc trafficking and/or zinc donation to apoproteins, including zinc finger proteins that act in cellular signaling and transcriptional regulation. As a result, metallothionein expression may affect a number of cellular processes including gene expression, apoptosis, proliferation and differentiation. The ability of metallothionein to exchange other metals with zinc in these proteins may explain a role in metal toxicity. Similarly, mobilization of zinc from metallothionein by oxidative stresses may explain its proposed antioxidant function. Apparent good health of metallothionein-deficient mice argues against a critical biological role for metallothionein; however, expression may be critical in times of stress.

A total of 452 cases of prostatic cancer identified through the population-based Hawaii Tumor Registry during the period 1977-1983 and 899 age-matched population controls were interviewed on the island of Oahu from 1981 to 1983. All interviews of the subjects, who comprised five different ethnic groups, were conducted in the home by use of a quantitative dietary history method. Usual weekly intake of fat, zinc, and vitamins A and C, including supplements, was determined for each subject. Among men 70 years or older, but not among younger men, and mean weekly consumption of saturated fat, carotenes, and zinc, adjusted for age and ethnicity, was greater for cases than for controls. In a multiple logistic regression analysis, the odds ratio for the highest quartile of fat intake among the older men was 1.7 (95% confidence interval (CI) 1.0-2.8). The corresponding odds ratios were 1.6 (95% CI 1.0-2.5) for carotenes, 1.4 (95% CI 0.9-2.3) for total vitamin C, and 1.7 (95% CI 1.1-2.7) for total zinc. There were significant linear trends in the odds ratios for saturated fat and zinc, but no synergistic interactions among the nutrients. The findings suggest that several different components of the diet may contribute independently to the risk of prostatic cancer in elderly men.

The therapeutic effect of orally administered zinc was evaluated in an adult woman with acrodermatitis enteropathica. When she was off therapy and in clinical relapse the plasma zinc concentration (10 mug per 100 ml), serum alkaline phosphatase (3 1U per liter) and urine zinc excretion rate (39 mug per 24 hours) were extremely low. Di-iodohydroxyquin therapy was accompanied by a modest increase in plasma zinc concentrations. Oral zinc sulfate (220 mg three times a day or 50 mg twice a day) resulted in rapid and complete clinical remission, and in a return of plasma zinc, serum alkaline phosphatase and urinary zinc excretion to normal. These data are compatible with a severe zinc deficiency state and indicate that the inherited defect in this disease is either in or closely related to zinc metabolism. The beneficial effects of zinc therapy in this patient provide further confirmation of the efficacy of oral zinc in the treatment of acrodermatitis enteropathica.

Hypocupremia occurred in an adult with sickle cell anemia who received zinc as an antisickling agent for two years. The hypocupremia was associated with microcytosis and relative neutropenia. Administration of copper resulted in an increase in RBC size and leukocyte counts. We have since observed hypoceruloplasminemia of varying degrees in several other sickle cell anemia patients who were receiving oral zinc therapy. This complication was easily corrected by copper supplementation.