Erythrocyte metallothionein as an index of zinc status in humans.

Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins

Metallothionein Expression Is Increased in Monocytes and Erythrocytes of Young Men during Zinc Supplementation , ,

Zinc: An Essential Trace Element for Parenteral Nutrition

Red blood cell metallothionein as an indicator of zinc status during pregnancy

Investigation of Lymphocyte Gene Expression for Use as Biomarkers for Zinc Status in Humans

Erythrocyte metallothionein (E-MT) is considered a promising index of zinc status in humans, since it may be more sensitive than other biochemical indices to changes in dietary zinc. However, conditions of high zinc demand with substantial redistribution of tissue zinc and specific changes in hormone profile, such as pregnancy, may have an influence on E-MT levels in addition to dietary zinc. In this study, we compared E-MT concentrations in relation to other biochemical zinc indices in healthy pregnant women at delivery (n = 40) and non-pregnant women (n = 22) with similar habitual dietary zinc intakes (average 13.3 mg/d). Pregnant women had lower serum zinc and albumin-bound serum zinc, but higher levels of alpha 2-macroglobulin-bound serum zinc than the nonpregnant women. Erythrocyte zinc (E-Zn) was similar in both groups, but E-MT (mean +/- SE) was slightly but significantly (p < 0.05) higher in the pregnant women (2.9 +/- 0.09 nmol/g protein) compared to nonpregnant women (2.6 +/- 0.06 nmol/g protein). A significant correlation was observed between E-MT and E-Zn in the nonpregnant women (r = 0.70; p < 0.001), consistent with the role of intracellular zinc in the regulation of metallothionein synthesis. However, such correlation was not observed in the pregnant women, suggesting that E-MT levels in pregnancy may be influenced by factors related to the pregnant state.

Assessment of Marginal Zinc Status in Humans

The effect of zinc on the outcome of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials

We have previously reported a trapping of zinc in the placenta directly related to circulating cadmium that comes from cigarette smoke. The purpose of this study was to examine in detail the effect of smoking on (a) the relationship between maternal and fetal zinc status and (b) the relationship between zinc status and birth weight. One hundred and eighteen smokers and 172 nonsmokers without any medical complications during pregnancy were studied. Atomic absorption spectroscopy was used to assess zinc status in maternal and cord vein plasma and red blood cells. Plasma alkaline phosphatase was also determined as an index of zinc status. Thiocyanate was used as an index of smoking status. The data were analyzed using univariate correlations and repeated measures analysis of variance. Infants of smokers had a statistically significant decrease in plasma zinc (5%), alkaline phosphatase (13%), and in cord vein RBC zinc (12%). Furthermore, the results showed an altered relationship between maternal and fetal indices of zinc status and zinc status and birth weight due to maternal smoking. The infant of the nonsmoking mother appears to be able to maintain adequate zinc status due to depletion of maternal zinc. However, it appears that the infant of the smoking mother may be marginally zinc deficient. These findings support studies of zinc supplementation in the pregnancy complicated by smoking.

Assessing the prevalence and severity of zinc deficiency in populations is critical to determine the need for and appropriate targeting of zinc intervention programs and to assess their effectiveness for improving the health and well-being of high-risk populations. However, there is very little information on the zinc status of populations worldwide due to the lack of consensus on appropriate biochemical indicators of zinc status. The objective of this review was to evaluate the use of serum zinc concentration as an indicator of population zinc status. We have reviewed the response of serum zinc concentration to dietary zinc restriction and zinc supplementation. In addition, we completed pooled analyses of nine zinc intervention trials in young children to assess the relations between serum zinc concentration of individuals before treatment and their responses to zinc supplementation. Also, in updated combined analyses of previously published data, we investigated the relation between the mean initial serum zinc concentration of a study population and their mean growth responses to zinc supplementation in randomized intervention trials among children. The results from depletion/repletion studies indicate that serum zinc concentrations respond appreciably to severe dietary zinc restriction, although there is considerable interindividual variation in these responses. There is also clear evidence that both individual and population mean serum zinc concentrations increase consistently during zinc supplementation, regardless of the initial level of serum zinc concentration. By contrast, an individual's serum zinc concentration does not reliably predict that person's response to zinc supplementation. Serum zinc concentration can be considered a useful biomarker of a population's risk of zinc deficiency and response to zinc interventions, although it may not be a reliable indicator of individual zinc status.

Metallothioneins (MTs) constitute a family of evolutionary conserved low molecular weight proteins with small variations in their amino acid sequences. They play a role in the regulation of trace metals metabolism, in the detoxification of heavy metal ions and in mechanisms controlling growth, differentiation and proliferation of cells. The aim of this study was to evaluate the human and rabbit MTs purity and characterization using advanced analytical approaches. Due to the common use of MT from rabbit liver as a model protein, the properties of the rabbit and human MTs were compared. Capillary electrophoresis (CE), matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and Brdicka reaction were used for human and rabbit MTs characterization. In chip CE analysis, changes in the range of 5-8 kDa corresponding to the MT monomer, as well as some peaks of 13-14 kDa corresponding to dimers in both species, were observed. Using MALDI-MS, rabbit (MT-2D) and human (MT-1A, MT-1G, MT-1G + Cd and MT-2A) MTs were identified. In the Brdicka reaction analysis, a lower concentration of MTs from both organisms coincided with a decrease in the signal corresponding to MT level (Cat2). However, human MT gave higher Cat2 peak than the same concentration (0.025 mg/mL) of rabbit MT. The applied methods allowed for the characterization of MTs and gave complementary information about MT isoforms. Altered electrochemical activity of human and rabbit MTs, despite the same number of -sulfhydryl (-SH) groups, was observed, which may be due to different availability of MT cysteinyl groups.

Suspicions that mild zinc deficiency is common among the elderly cannot be confirmed or refuted because definitive indicators of zinc status are lacking. The goal of this study was to document the clinical responsiveness of parameters of zinc status in a group of older adults consuming a carefully controlled diet: first moderately low in zinc (3.97 mg/day for 15 days) and then high in zinc (28.19 mg/day for 6 days). Fifteen older adults (mean age = 66.6 yrs) volunteered to consume a marginally zinc-deficient diet for 15 days followed by 6 days of zinc repletion. Plasma concentrations of erythrocyte metallothionein and the enzyme 5'-nucleotidase, as well as levels of zinc, alkaline phosphatase, copper and ceruloplasmin were measured before and after zinc depletion and repletion. Plasma zinc levels were not altered during the study. Alkaline phosphatase (AP) values did not change in the expected direction, although a small decrease in AP following zinc repletion was statistically significant. Erythrocyte metallothionein results followed a pattern similar to that of alkaline phosphatase, little change, but a small, statistically significant drop after zinc repletion. As expected, there were no diet-associated changes in plasma copper and ceruloplasmin levels. In contrast, plasma concentrations of the enzyme 5'-nucleotidase decreased (p < 0.01) from 2.7 +/- 0.5 to 1.1 +/- 0.5 U during zinc depletion and increased (p < 0.05) to 2.2 +/- 0.4 U after 6 days of repletion. Mild zinc deficiency is difficult to detect. In this study, traditional indicators such as plasma zinc and alkaline phosphatase did not change as would be expected in response to alterations in zinc intake. Likewise, erythrocyte metallothionein did not respond to altered zinc intakes as expected but this factor may reflect long-standing or more severe zinc depletion and thus requires additional study. Activity of the enzyme 5'-nucleotidase appears responsive to acute changes in zinc intake; however, more work is needed to define how well these activities will reflect zinc intake in other types of subjects.

Replacement of zinc sulphate by microbial phytase for piglets given a maize-soya-bean meal diet

There is need for a reliable index of zinc status in humans. Considering the importance of zinc in membrane function, activities of erythrocyte membrane enzymes have been measured in animals of low and normal zinc status as possible indices. Immature rats and neonatal pigs were fed low and adequate zinc diets; the latter was fed both ad libitum and restricted so as to control for food intake effects. Low rates of gain and plasma zinc concentrations demonstrated that animals fed the low zinc diets were of low zinc status. Erythrocyte membranes were prepared and assayed for Na,K-ATPase, 5'-nucleotidase, and calcium-ATPase activities. Na,K-ATPase activity was not affected by zinc status, but 5'-nucleotidase was significantly lower in deficient animals of both species than in controls, whose food intake was restricted to maintain comparable weight (2.76 vs 3.94 nmol/hr/mg of protein in rats and 60.5 vs 119 in pigs). The basal calcium-ATPase activities were also decreased by low zinc status in both species. Addition of calmodulin in vitro stimulated activity two-fold to four-fold and resulted in the same maximal activities for all treatments. The results show that erythrocyte membrane 5'-nucleotidase activity is an index of zinc status in these species. It is suggested that the decreased membrane calcium-ATPase activity in zinc deficiency is caused by a defect in calmodulin metabolism.

Aging impacts immunity, zinc status, and overall health, with these factors being closely interconnected. Zinc is known to modulate protein expression and cytokine production, with new molecular mechanisms continuing to be identified. ZIP8 facilitates IFN-γ production by increasing the intracellular zinc levels; how zinc status in humans affects ZIP8 expression remains unclear. We assessed serum zinc, dietary zinc intake, proton pump inhibitor (PPI) use, phytohemagglutinin (PHA)-stimulated IFN-γ production, and ZIP8 protein expression in elderly hospitalized patients and young healthy controls. Compared to young adults, elderly participants exhibited lower zinc status and IFN-γ levels, with PPI use among the elderly correlating with zinc deficiency. Zinc-deficient elderly participants received zinc aspartate supplementation for approximately 7 days, resulting in increased serum zinc levels, IFN-γ production, and a trend toward increased ZIP8 expression; in participants taking PPIs, this increase reached statistical significance. Although we found no clear correlation between ZIP8 expression and zinc status, the observed response to supplementation warrants further investigation. These findings reinforce the relevance of zinc supplementation in the elderly, although further studies are needed to elucidate the precise mechanisms linking zinc status to IFN-γ production, particularly regarding the role of ZIP8 expression levels.