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

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.

In order to study the reliability of urinary zinc levels as an index of zinc metabolism and status in Crohn's disease, we evaluated plasma and urinary zinc concentrations, urinary 3-methylhistidine excretion, and Crohn's disease activity index (CDAI) in 42 patients affected by Crohn's disease. Plasma zinc correlated directly with albuminemia (P = 0.01) and inversely with CDAI (P = 0.001). Urinary zinc excretion correlated with urinary 3-methylhistidine (P = 0.001) and plasma zinc levels (P = 0.01), and inversely with CDAI (P = 0.05). However, from multiple regression analysis, it was found that zincemia is influenced by CDAI and not by albumin, whereas zincuria is related to urinary 3-methylhistidine and plasma zinc, and not to CDAI. Our conclusion is that, in Crohn's disease, zincuria can be an index of zinc status when used together with measurements of lean body mass and turnover and factors influencing plasma ultrafiltrable zinc fraction.

Plasma and red blood cell zinc in cystic fibrosis.

Zinc status, pregnancy complications, and labor abnormalities

The role of zinc deficiency as an important cause of morbidity and impaired linear growth has prompted the need to identify indicators of population zinc status. Three indicators have been recommended - prevalence of zinc intakes below the estimated average requirement (EAR), percentage with low serum zinc concentrations, and percentage of children aged < 5 years who are stunted. This review outlines steps to estimate the prevalence of inadequate intakes, and confirm their validity based on the EARs set by International Zinc Nutrition Collaborative Group. Next, the appropriateness of serum zinc as a biochemical marker for population zinc status is confirmed by a summary of: (a) the response of serum zinc concentrations to zinc intakes; (b) usefulness of serum zinc concentrations to predict functional responses to zinc interventions; (c) relationship between initial serum zinc and change in serum zinc in response to interventions. Height- or length-for-age was chosen as the best functional outcome after considering the responses of growth, infectious diseases (diarrhoea, pneumonia), and developmental outcomes in zinc supplementation trials and correlation studies. The potential of other zinc biomarkers such as zinc concentrations in hair, cells, zinc-metalloenzymes, and zinc-binding proteins, such as metallothionein, is also discussed. Molecular techniques employing reverse transcriptase (RT)-polymerase chain reaction to measure mRNA in metallothionein and ZIP1 transporter hold promise, as do kinetic markers such as exchangeable zinc pools (EZP) and plasma zinc turnover rates. More research is needed to establish the validity, specificity, sensitivity, and feasibility of these new biomarkers, especially in community-settings.

Patient zinc stores are quantified with plasma or red blood cell (RBC) measures. The relationship between these 2 measures of zinc status has not been determined in a broad population of hospitalized patients. Both plasma zinc and RBC zinc were prospectively collected and measured in 252 consenting patients admitted urgently to hospital. Plasma and RBC zinc levels were measured within 48 h of admission. We collected demographic, vitals, and laboratory data for use in multivariate regression models that included markers of acute disease severity and systemic inflammation. Plasma zinc and RBC zinc levels were low in 63% and 10% of hospitalized patients, respectively. Categorized zinc levels based on normal intervals for plasma and RBC zinc values were not related (χ2 0.47 [2 df] P = 0.79). The Pearson correlation coefficient between plasma zinc and RBC zinc was -0.09 (P = 0.15). After adjustments for multiple clinical covariates, the correlation coefficient remained insignificant (r = -0.11, P = 0.08). Plasma zinc was inversely associated with markers of inflammation including the neutrophil-to-lymphocyte ratio and temperature. Patient-specific plasma and RBC zinc are unrelated in hospitalized patients, possibly due to decreased values with acute illness seen in the former but not the latter. Future studies are required to determine which of these measures best predicts outcomes in hospitalized patients.

The loss of body weight due to suppressed appetite at high altitude is very common. The hormone leptin and trace metal zinc have key roles in appetite regulation. In the present study, changes in leptin and zinc status of female mountaineers with and without supplementation with zinc have been investigated. Plasma leptin, zinc and enzyme activities of alkaline phosphatase (EC 3.1.3.5) and 5' nucleotidase (EC 3.1.3.1) of 25 women mountaineers between age group 17-25 yr were studied. The women mountaineers were divided into two groups, i.e., placebo control (n = 7) and supplemented with zinc at dose 15 mg/day for 21 days (n = 18) and all variables were analysed initially at 1981 m, at high altitude (4572-5182 m) and on return to initial altitude. The basal leptin level for both the groups combined was 3.12 ± 0.57 ng/ml (mean ± SD). Plasma leptin levels were found increased by 24 per cent and 58 per cent, respectively at high altitude and after return in case of control group, whereas in case of zinc-supplemented group, there was a statistically non-significant decrease of 20 per cent at high altitude in comparison to basal values. Thereafter, levels were maintained at baseline. There was no significant change in zinc status of control group as indicated by plasma zinc as well as maintained activities of alkaline phosphatase and 5' nucleotidase in the present study. On the other hand, zinc-supplemented group showed increase in zinc status at high altitude, which was evident by increased plasma zinc levels. On return from high altitude, plasma zinc levels were low in comparison to high altitude but still higher than that of basal. Results indicate beneficial effects of zinc supplementation by decreasing leptin levels at high altitude

Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries

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

Methods for the measurement of the zinc content of blood components (plasma, erythrocytes, platelets, mononuclear leukocytes, and polymorphonuclear neutrophils) as indicators of the zinc status of animals have been reviewed and evaluated. The values of plasma or serum zinc concentrations as indicators of zinc status in experimental animals or humans is questionable. Consequently, the zinc content of blood cellular components has been suggested as better indicators of zinc status. Methodological problems, such as incomplete cellular separation or zinc contamination, occur in some of the procedures applied to the quantitation of blood cellular component zinc. Specialized microprobe procedures involving, for example, proton-induced X-ray fluorescence, scanning ion technology, mass spectrometery, or laser microprobe mass analysis might be used to measure the absolute zinc level in individual cells subjected to minimal handling. Then, more conventional methods can be tested against the true standard. Nevertheless, there appears to be species differences in regard to the response of blood cellular zinc concentrations to dietary zinc deficiency. Blood cellular component zinc is conserved during severe zinc deficiency in the rat. In contrast, the zinc content of blood cellular components in humans may reflect the whole body zinc status.

The aim of the study was to determine the effect of weaning and the effect of increasing dietary zinc concentrations on the zinc and copper status of weaned piglets (study 1) and to study the effect of high concentrations of dietary zinc and/or copper on zinc and copper status of weaned piglets (study 2). Study 1 included 54 piglets (six litters of nine piglets). One piglet from every litter was killed 1 day before weaning. The remaining 48 piglets were allocated at weaning (28 days) to four dietary zinc treatments (100, 250, 1000 or 2500 ppm) and subsequently killed 1-2, 5-6 or 14-15 days after weaning. Study 2 included 48 piglets (six litters of eight piglets) allocated to four dietary treatments, consisting of low or high dietary zinc (100 or 2500 ppm) in combination with low or high dietary copper (20 or 175 ppm). All piglets in study 2 were killed 5-7 days after weaning. In both studies, the trace mineral status was assessed by zinc and copper concentrations and alkaline phosphatase (AP) activity in plasma and mucosal tissue. In study 2, lymphocyte metallothionein (MT) mRNA and intestinal mucosa MT mRNA concentrations were included as zinc status markers. The results showed that the zinc status, measured as zinc in plasma and mucosa, was not affected by weaning of the piglets. Plasma copper concentrations decreased during the first 2 weeks after weaning. High dietary copper concentrations did not affect the concentration of copper in plasma, but increased the concentration of copper in mucosa and the concentration of zinc in plasma. The dietary zinc treatments increased the zinc concentration in plasma as well as the zinc and MT mRNA concentration in mucosa. Lymphocyte MT mRNA concentrations did not reflect the differences in dietary zinc supplementation.

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

Several authors have shown that lowered zinc is related to risk factors during pregnancy and labor complications.1 The best index of zinc status is unclear. The purpose of the present study was to test the hypothesis that certain complications during the course of pregnancy and delivery would be related to one or more lowered indices of zinc status. Plasma zinc, erythrocyte zinc and serum alkaline phosphatase activity were used as indices of zinc status and were compared to the incidence of complications and major dysfunctional labor patterns.

Zinc deficiency continues to be a major concern of international nutrition, yet there are still few sensitive and reliable biomarkers for identifying moderate zinc deficiency or monitoring changes in zinc status. Plasma zinc content is used most frequently, but it is influenced by conditions other than zinc intake and, therefore, is not reliable except when zinc intake is very low. In this study, the sensitivity of leukocytic zinc transporter gene expression and genomic integrity were evaluated in a moderate depletion/repletion study. Eighteen healthy men were provided a low zinc (6 mg/day) diet with added phytate for two weeks followed by an adequate zinc (10 mg/day) diet for four weeks. They then consumed an ad libitum diet while taking a 25mg zinc supplement for three weeks. Leukocyte DNA damage increased (p&lt;0.0001) during the depletion phase, as detected by the Comet Assay. ZIP1, ZIP4, and ZnT1 zinc transporter gene expression was evaluated in isolated leukocytes and measured using qPCR. ZnT1 gene expression increased (p=0.02) during the depletion phase, although total plasma and leukocyte zinc levels did not change. These results suggest that a short‐term, low zinc intake alters genomic integrity and zinc transporter expression, but not plasma zinc. These potential biomarkers may be useful to evaluate zinc deficiency and the effectiveness of zinc interventions in conditions where plasma zinc remains unchanged.Grant Funding Source: This study was funded by a grant from HarvestPlus.

Background: Adjustments in zinc losses and absorption are thought to maintain zinc homeostasis with changes in intake, but the capacity to make these adjustments appears to be affected by aging. Zinc status of the individual may also influence adjustments in fractional zinc absorption.Objective: The purpose of this study was to compare the effects of changes in zinc status due to zinc supplementation on fractional zinc absorption in young and elderly Korean women.Design: Zinc status and absorption were measured initially in 15 young (20–24 yr) and 15 elderly women (64–75 yr) confined to a metabolic unit and consuming a typical Korean diet. Upon discharge from the unit the women were supplemented with 22 mg zinc/d for 28 days. On d 20, the women returned to the unit for measurement of zinc status and absorption. Fractional zinc absorption (FZA) was estimated from the same typical Korean breakfast at both time points using the dual isotopic tracer method. Zinc stable isotopic ratios were measured in urine samples collected for 3 days following isotope administration.Results: Plasma and urinary zinc concentrations increased significantly with zinc supplementation in the young but not the elderly women. FZA decreased following zinc supplementation in the young women from 22 to 8% (p < 0.0001) and in the elderly women from 19 to 10% (p < 0.0001). The decline in young women was greater than that in elderly women (p < 0.05).Conclusions: Both young and elderly women reduced their efficiency of zinc absorption with zinc supplementation. But, plasma and urinary zinc concentrations did not increase in the elderly following zinc supplementation suggesting that age altered the use of the additional zinc.