Effect of acute zinc depletion on zinc homeostasis and plasma zinc kinetics in men.

BACKGROUND: Zinc homeostasis and normal plasma zinc concentrations are maintained over a wide range of intakes. OBJECTIVE: The objective was to identify the homeostatic response to severe zinc depletion by using compartmental analysis. DESIGN: Stable zinc isotope tracers were administered intravenously to 5 men at baseline (12.2 mg dietary Zn/d) and after 5 wk of acute zinc depletion (0.23 mg/d). Compartmental modeling of zinc metabolism was performed by using tracer and mass data in plasma, urine, and feces collected over 6-14 d. RESULTS: The plasma zinc concentration fell 65% on average after 5 wk of zinc depletion. The model predicted that fractional zinc absorption increased from 26% to essentially 100%. The rate constants for zinc excretion in the urine and gastrointestinal tract decreased 96% and 74%, respectively. The rate constants describing the distribution kinetics of plasma zinc did not change significantly. When zinc depletion was simulated by using an average mass model of zinc metabolism at baseline, the only change that accounted for the observed fall in plasma zinc concentration was a 60% reduction in the rate constant for zinc release from the most slowly turning over zinc pool. The large changes in zinc intake, excretion, and absorption-even when considered together-only explained modest reductions in plasma zinc mass. CONCLUSION: The kinetic analysis with a compartmental model suggests that the profound decrease in plasma zinc concentrations after 5 wk of severe zinc depletion was mainly due to a decrease in the rate of zinc release from the most slowly turning over body zinc pool.     

Gastrointestinal factors influencing zinc absorption and homeostasis

Diet-derived luminal factors have a major influence on zinc available for uptake across the apical membrane of enterocytes. Malabsorption and possibly intestinal microbiota limit this zinc availability. The transporter ZIP4 is expressed along the entire gastrointestinal tract and acts as a major processor of dietary zinc for loading into enterocytes from the apical membrane. Zip4 and other Zip family genes expressed in the gastrointestinal tract are up-regulated in periods of dietary zinc restriction. This provides for powerful homeostatic control. The transporter ZIP14 is up-regulated along the entire gastrointestinal tract by proinflammatory conditions. Intracellular transporters such as ZnT7, influence the transcellular movement of zinc across the enterocyte. Metallothionein, an intracellular metal buffer, and the transporter ZnT1 at the basolateral membrane, regulate the amount of zinc released to the portal circulation for systemic distribution. Pancreatic release of zinc by acinar cells is through the secretory process and apical membrane and involves transporters ZnT2 and ZnT1, respectively. Expression of both transporters is zinc-responsive. Enterocytes and acinar cells constitutively express Zip5 at the basolateral membrane, where it may serve as a monitor of zinc status.     

Growth and zinc homeostasis in the severely Zn-deficient rat

Male weanling rats were fed on diets either adequate (55 mg/kg), or severely deficient (0.4 mg/kg) in zinc, either ad lib. or in restricted amounts in four experiments. Measurements were made of growth rates and Zn contents of muscle and several individual tissues. Zn-deficient rats exhibited the expected symptoms of deficiency including growth retardation, cyclic changes in food intake and body-weight. Zn deficiency specifically reduced whole body and muscle growth rates as indicated by the fact that (a) growth rates were lower in ad lib.-fed Zn-deficient rats compared with rats pair-fed on the control diet in two experiments, (b) Zn supplementation increased body-weights of Zn-deficient rats given a restricted amount of diet at a level at which they maintained weight if unsupplemented, (c) Zn supplementation maintained body-weights of Zn-deficient rats fed a restricted amount of diet at a level at which they lost weight if unsupplemented (d) since the ratio, muscle mass: body-weight was lower in the Zn-deficient rats than in the pair-fed control groups, the reduction in muscle mass was greater than the reduction in body-weight. Zn concentrations were maintained in muscle, spleen and thymus, reduced in comparison to some but not all control groups in liver, kidney, testis and intestine, and markedly reduced in plasma and bone. In plasma, Zn concentrations varied inversely with the rate of change of body-weight during the cyclic changes in body-weight. Calculation of the total Zn in the tissues examined showed a marked increase in muscle Zn with a similar loss from bone, indicating that Zn can be redistributed from bone to allow the growth of other tissues. The magnitude of the increase in muscle Zn in the severely Zn-deficient rat, together with the magnitude of the total losses of muscle tissue during the catabolic phases of the cycling, indicate that in the Zn-deficient rat Zn may be highly conserved in catabolic states.     

Dysprosium as a nonabsorbable fecal marker in studies of zinc homeostasis

BACKGROUND: Dysprosium is a nonabsorbable rare earth element that has had successful application as a marker for fecal excretion of unabsorbed zinc. OBJECTIVE: Our goals were 1) to evaluate the efficacy of administering dysprosium with all meals over several days as a method of determining the completeness of fecal collections, 2) to determine the similarity of gastrointestinal transit kinetics and excretion patterns of dysprosium and zinc tracer administered simultaneously over several days, and 3) to evaluate alternative methods of using the data for fecal excretion of orally administered zinc tracer and dysprosium to measure the fractional absorption of zinc. DESIGN: 70Zn and dysprosium were administered orally with all meals for 5 consecutive days to 7 healthy, free-living adults consuming a constant diet based on habitual intake. Additional tracers, 67Zn and 68Zn, were administered intravenously. Urine and fecal samples were collected during tracer administration and for 8 d after the last dose. Isotope ratios were measured in urine and feces, and total zinc and dysprosium were measured in fecal samples. RESULTS: The mean recovery of dysprosium was 101.3 +/- 2.4%. The zinc oral tracer and dysprosium had similar fecal excretory patterns; the correlation coefficient for 70Zn and dysprosium in fecal samples exceeded 0.99 (P < 0.0001) for each subject. Fractional zinc absorption measurements using various dysprosium methods correlated well (r > 0.95) with those from the fecal monitoring and dual-isotope-tracer ratio methods. CONCLUSION: Administration of dysprosium is a useful means of determining the completeness of fecal collections and of measuring zinc absorption.     

Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages

Purpose

Polarization of macrophages by environmental stimuli leads to the characteristic of different phenotypes that exhibit distinct functions, ranging in a continuous spectrum from pro-inflammatory M1 up to immunoregulatory and wound-healing M2 macrophages. Diseases like cancer, allergic asthma or diabetes are associated with an M1/M2 imbalance. Owing to the importance of the essential trace element zinc for the immune system and its involvement in signal transduction as a second messenger, we investigated the impact of zinc on M1 and M2 polarization of macrophages in vitro.

Methods

A polarization model with human THP-1 cells was established and validated with previously described markers using quantitative real-time PCR, Western blot and flow cytometry. Intracellular free Zn²⁺ was determined with FluoZin-3-AM.

Results

Whereas pSTAT1 and HLA-DR or pSTAT6 and Dectin-1 distinguish between M1 and M2 macrophages, respectively, CD86 and CD206 failed. Depending on the used markers, both zinc supplementation in physiological dose (50 µM) and zinc deficiency promote M1 polarization of THP-1-derived macrophages. Furthermore, zinc supplementation strongly inhibits M2 polarization.

Conclusion

For the first time, we show a modulating effect of zinc for the polarization of human macrophages. The strong inhibitory effect of zinc supplementation on M2 polarization indicates a relevance regarding M2-dominated diseases like allergic asthma or cancer. All in all, zinc achieves a great potential for modulating macrophage polarization.

     

Red meat and a fortified manufactured toddler milk drink increase dietary zinc intakes without affecting zinc status of New Zealand toddlers

Evidence suggests that New Zealand (NZ) children are mildly zinc deficient and may respond to dietary change. A 20-wk randomized intervention trial was therefore conducted to determine whether an increased intake of red meat or consumption of a fortified manufactured toddler milk drink (FTMD, fortified with zinc and other micronutrients) would increase dietary zinc intakes and improve the biochemical zinc status of 12- to 20-mo-old NZ toddlers. Toddlers were randomized to a red meat intervention (n = 90), FTMD intervention (n = 45), or nonfortified milk placebo (n = 90). Study foods were provided. Adherence was assessed via monthly 7-d meat or milk recording diaries. Hair and serum zinc concentrations, and length and weight were measured at baseline and postintervention. Nutrient intakes were assessed via 3-d weighed food records at baseline, wk 4, and wk 18. At baseline, 38% of participants had low serum zinc concentrations despite seemingly adequate dietary zinc intakes (<4% below the Estimated Average Requirement). Dietary zinc intakes significantly increased by 0.8 mg/d (95% CI: 0.5, 1.1) in the meat group and 0.7 mg/d (95% CI: 0.2, 1.1) in the FTMD group compared with a decrease of -0.5 (95% CI: -0.8, -0.2) mg/d in the placebo group. No corresponding increases in serum or hair zinc concentrations were observed. Dietary zinc intakes achievable via interventions based on red meat or a FTMD are unlikely to improve biochemical zinc status in NZ toddlers. These results also question cutoffs used to define zinc deficiency in toddlers.     

Effect of dietary phytate on zinc homeostasis in young and elderly Korean women

BACKGROUND: Previous studies suggest that consumption of predominantly plant-based diets with high phytate content contribute to zinc deficiency by inhibiting zinc absorption. Age of the individual may also affect the ability to maintain zinc homeostasis. OBJECTIVE: This study was designed to determine the effect of dietary phytate on zinc homeostasis and to evaluate the effect of age on the capacity to maintain the zinc homeostasis with changes in dietary phytate in young and elderly Korean women. DESIGN AND METHODS: Seven healthy young women (22-24 yr) and 10 healthy elderly women (66-75 yr) were studied consecutively for 3 months in 2 metabolic periods (MP) in two different metabolic units. During MP1 the women consumed a high phytate (HP) diet (P:Zn molar ratio = 23) for 9 days. After a 10 d wash-out period at home eating their usual diets, a lower phytate diet (LP) (P:Zn molar ratio = 10) was fed in MP2 for 9 d. Phytase was added to selected foods in the high phytate diet to reduce the phytate content of the meals in the LP period. The zinc content of both diets was about 6.5 mg/d. Stable isotopes of Zn ((70)Zn) were administered intravenously on d 5 of MP 1 and 2 for measuring endogenous fecal zinc excretion. Plasma samples were also collected on d 5 for measuring plasma zinc concentrations by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). 24 hr urine samples were collected for 5 d and complete fecal samples were collected for 9 d after isotope administration. Fractional zinc absorption (FZA) was calculated from mass balance corrected for endogenous fecal zinc (EFZ) excretion and EFZ was determined by using an isotopic dilution technique. Isotopic ratios for FZA and EFZ were measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Statistical analyses were done using ANOVA. RESULTS: Both the young and elderly women were in negative zinc balance during the HP period. This was due to a significant decrease in FZA and total absorbed zinc (TAZ) with a HP diet (43 vs 22% in young women, 34 vs 20% in elderly women, p < 0.001). EFZ excretion did not differ in the young and elderly women during the LP and HP periods. Dietary phytate did not alter plasma zinc concentrations or and urinary zinc excretion in either group. CONCLUSIONS: Adjustments in zinc homeostasis with an increase in dietary phytate did not differ between young and elderly women in this study.     

Zinc homeostasis during lactation in a population with a low zinc intake.

BACKGROUND: There is a major increase in endogenous zinc excretion, specifically via the mammary gland, in early human lactation. Whereas fractional absorption of dietary zinc has been reported to increase in early human lactation, it is not known to what extent adaptive mechanisms may maintain zinc homeostasis, especially when dietary zinc intake is relatively low. OBJECTIVE: The objective of this study was to quantitate major variables of zinc homeostasis during early lactation in subjects from a population whose habitual dietary zinc intake is low. DESIGN: We studied 18 free-living lactating women from a rural community of northeast China whose infants were exclusively breast-fed. The subjects were studied at approximately 2 mo of lactation with use of stable isotopes of zinc and metabolic collection techniques. Milk volume was measured with use of a deuterium enrichment method. RESULTS: The mean (+/-SD) secretion of zinc in milk was 2.01 +/- 0.97 mg/d, the intake of zinc was 7.64 +/- 1.61 mg/d, and the fractional absorption of zinc was 0.53 +/- 0.09, for a total daily zinc absorption of 4.00 +/- 0.71 mg/d. Endogenous zinc excretion in urine and feces was 0.30 +/- 0.10 and 1.66 +/- 0.97 mg/d, respectively. CONCLUSIONS: Zinc balance, including zinc secreted in breast milk, was maintained at approximately 2 mo of lactation in women whose habitual diet was low in zinc. Homeostasis was achieved by high fractional absorption of zinc and intestinal conservation of endogenous fecal zinc.     

Accumulation and regulation of zinc in Daphnia magna: links with homeostasis and toxicity

Zinc accumulation in Daphnia magna was investigated, and the results were linked to the previously established optimal concentration range for zinc and D. magna. It was observed that organisms cultured in this optimal range (300-600 microg Zn/L) contained 212 +/- 57 to 254 +/- 79 microg Zn/g dry weight. Lower and higher zinc contents were obtained after acclimation to previously established culture concentrations inducing deficiency and toxicity, respectively. The calculation of bioconcentration factors indicated that zinc was actively regulated, at least up to a concentration of 600 microg Zn/L. Zinc uptake and elimination are rapid processes; major increases and decreases in body content occurred within 1 day. Zinc concentrations in daphnids exposed to 600 microg Zn/L fluctuated with 2- to 3-day intervals, suggesting a role of molting in the regulation and elimination of zinc.     

Effect of experimental zinc deficiency and repletion on some immunological variables in guinea-pigs

1. Cellular and humoral immune responses were studied in guinea-pigs fed on zinc-deficient (ZnD), Zn-adequate (control) and Zn-replete diets containing 1.25, 50 and 100 mg Zn/kg diet respectively. 2. It was found that the ZnD guinea-pigs had significantly decreased ability to elicit delayed-type hypersensitivity (DTH) response against sheep erythrocytes as compared with controls on the 9th day of immunization. This was further substantiated by histological examination of DTH-positive skin sections. 3. A significant reduction in direct splenic plaque-forming-cell response and haemagglutinating-antibody titre was also observed in ZnD guinea-pigs. 4. Serum electrophoretic studies revealed a highly disordered protein profile with a significantly depressed value for gamma-globulin. 5. Zn repletion of the previously ZnD group resulted in marked, though incomplete, restoration of immunological responses.     

Plasma zinc in hypertension/toxemia and other reproductive variables in adolescent pregnancy

A study was conducted at Charity Hospital, New Orleans, among 272 adolescent pregnant women to ascertain the relationship of pregnancy outcome to plasma zinc level measured once at the time of enrollment. Regression analyses were performed on zinc status versus parameters concerning success of pregnancy corrected for gestational stage at specimen collection. Analysis of variance was performed on groups according to presence or absence of complications, with analyses of covariance used to analyze dichotomous groups. Low, though widely variable, plasma zinc levels were found (mean = 58 +/- 12.6 micrograms/dl). Zinc values differed significantly by gestational stage at collection, the regression coefficient indicating a decline of 0.07 micrograms/dl/day. Plasma zinc level correlated significantly with Hb, red blood cells, ferritin, and folic acid. As to course of pregnancy, women experiencing hypertension/toxemia were found to have significantly lower plasma zinc level. Among infants displaying congenital defects at birth those with undescended testes and metatarsus varus were delivered by mothers whose plasma zinc was well below the mean for the group. These findings indicate the need to investigate the influence of dietary patterns and zinc intake on maternal plasma zinc level and pregnancy outcome, further delineating the role of zinc in human reproduction, particularly hypertension of pregnancy.     

Psychosocial variables and obesity-risk-reduction behaviors in Chinese Americans

The objective of this study was to utilize social-psychological theories to explain obesity-risk-reduction behaviors. A questionnaire based on the health belief model and theory of planned behavior was administered to a convenience sample of 300 Chinese Americans in the New York metropolitan area. Psychosocial variables accounted for 40.4% of the variance of obesity-risk-reduction behaviors. Self-efficacy, behavioral intention, and perceived benefits emerged as most influential variables. Forty-eight percent of the variance of behavioral intention was accounted with self-efficacy predominating. Health professionals targeting Chinese Americans need to address self-efficacy, behavioral intention, and perceived benefits of adopting obesity-risk-reduction behaviors.     

Fortifying milk with ferrous gluconate and zinc oxide in a public nutrition program reduced the prevalence of anemia in toddlers

We aimed to assess the efficacy of whole cow's milk fortified with ferrous gluconate and zinc oxide, along with ascorbic acid, in reducing the prevalence of anemia and improving iron status of low income children 10-30 mo of age. Healthy children were randomly assigned to drink 400 mL/d of cow's whole milk, either fortified milk (FM) with 5.8 mg/400 mL of iron as ferrous gluconate, 5.28 mg/400 mL of zinc as zinc oxide, and 48 mg/400 mL of ascorbic acid, or nonfortified milk (NFM) with 0.2 mg iron/400 mL, 1.9 mg zinc/400 mL, and 6.8 mg ascorbic acid/400 mL. Hemoglobin, serum ferritin, soluble transferrin receptors (TfR), and C-reactive protein concentrations were measured at baseline and 6 mo after intervention. The prevalence of anemia declined from 41.4 to 12.1% (P < 0.001), or 29 percentage points, in the FM group; there was no change in the NFM group. Hemoglobin (coefficient = 0.22, P < 0.01) was positively and TfR (coefficient = -0.29, P < 0.001) negatively associated with treatment, controlling for their respective baseline values, age, and gender. Treatment with FM was negatively associated with the likelihood of being anemic (pseudo R(2) = 0.085, P < 0.03) after 6 mo of intervention. Ferrous gluconate added to whole cow's milk as a fortificant along with ascorbic acid is efficacious in reducing the prevalence of anemia and in improving iron status of Mexican toddlers. The results of this study lead to broadening a subsidized FM distribution program to 4.2 million beneficiary children 1-11 y of age in Mexico.     

Effects of zinc and iron supplementation fail to improve motor and language milestone scores of infants and toddlers

ObjectiveTo assess the effects of zinc and iron–folic acid supplementation on motor and language milestones in Nepali children.MethodsFive hundred forty-four children 4 to 17 mo old residing in Ishwarpur, Nepal were randomized to receive placebo, iron–folic acid, zinc, or zinc plus iron–folic acid daily. Data were collected at baseline and at 3-mo intervals for 1 y. The main effects of zinc and iron folic–acid supplementation were estimated for motor and language milestones. Crude and adjusted mean cumulative changes in scores from visits 1 to 5 and adjusted rates of change were modeled.ResultsAdjusted differences in motor milestone scores from visits 1 to 5 and rates of change were not significantly different for the zinc and non-zinc groups (adjusted β = ?0.7, 95% confidence interval [CI] ?1.4 to 0.01; adjusted β = ?0.1, 95% CI ?0.5 to 0.3, respectively). Motor milestones in children receiving and not receiving iron supplements were not significantly different (adjusted β = 0.1, 95% CI ?0.7 to 0.8, from visits 1 to 5; adjusted β = 0.1, 95% CI ?0.3 to 0.5, for rate of change). Children receiving zinc had a 0.8 lower mean crude change in language score from visits 1 to 5 compared with children not receiving zinc (95% CI ?1.3 to ?0.3), but the significance was lost after adjustment (adjusted β = ?0.2, 95% CI ?0.6 to 0.2, for visits 1 to 5; β = ?0.1, 95% CI ?0.3 to 0.2, for rate of change). No significant difference in motor or language milestone scores from iron supplementation was observed.ConclusionAfter 1 y, neither zinc nor iron–folic acid supplementation in Nepali children improved the attainment of motor or language milestones.     

Accidents of toddlers and youngsters

The Public Health Department in Biberach an der Riss developed a questionnaire to investigate the incidence of accidents in children under school-starting age (6 years). This questionnaire was presented to the parents of more than 2,300 prospective first-graders from the town and rural district on the occasion of the pre-school medical examination 2000. As this examination is mandatory for all children starting school, and as the questions were answered by all the parents with very few exceptions (language reasons), a complete survey can be assumed. The investigation confirmed the results of last year: The incidence of children who suffered an accident requiring medical attention before reaching school age is approximately 33 %; boys are predominantly involved. The scene of accidents also changes with increasing age from living quarters to outside areas. The most frequent type of accidents are, of course, falls, resulting especially in injuries to the head and face. Scalds and burns, in particular at the age of 2, occur more frequently in the Biberach district than described in other up-to-date investigations in Germany. For this reason efforts have to be made to reduce this number over the next years. About 11 % of accidents occur in the streets or involve traffic, a result which is also higher in comparison to other investigations. According to the statement of parents, more than two-thirds of accidents are caused by the children themselves, including babies and toddlers. At the time of the accident 40 % of the children were without parental control, and 20 % completely alone.A great number of the accidents could certainly have been prevented. That is why the results of the study should be made available to all those responsible for the care and wellbeing of this age group. The last section of the paper deals with the most urgent needs of action to be implemented in the long run for the sake of the health of our children.     

Nutrient intake of Swiss toddlers

European Journal of Nutrition - During the first years of life, food preferences are shaped that might last throughout a person’s entire life affecting his/her health in the long term....