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PubMed2005

Measurements of zinc absorption: application and interpretation in research designed to improve human zinc nutriture.

The focus of this paper is on the application of measurements of zinc absorption in human research, especially studies designed to assess the efficacy of intervention strategies to prevent and manage zinc deficiency in populations. Emphasis is given to the measurement of quantities of zinc absorbed rather than restricting investigations to measurements of fractional absorption of zinc. This is especially important when determining absorption of zinc from the diet, whether it be the habitual diet or an intervention diet under evaluation. Moreover, measurements should encompass all meals for a minimum of one day with the exception of some pilot studies. Zinc absorption is primarily via an active saturable transport process into the enterocytes of the proximal small intestine. The relationship between quantity of zinc absorbed and the quantity ingested is best characterized by saturable binding models. When applied to human studies that have sufficient data to examine dose-response relationships, efficiency of absorption is high until approximately 50-60% maximal absorption is achieved, even with moderate phytate intakes. This also coincides approximately with the quantity of absorbed zinc necessary to meet physiologic requirements. Efficiency of absorption with intakes that exceed this level is low or very low. These observations have important practical implications for the design and interpretation of intervention studies to prevent zinc deficiency. They also suggest the potential utility of measurements of the quantity of zinc absorbed when evaluating the zinc status of populations.

Biological Availability↗

PubMed1982

Lymphocyte and granulocyte function in zinc-treated and zinc-deficient hemodialysis patients.

Lymphocyte blast transformation and granulocyte motility were studied in 20 clinically stable hemodialysis patients, 10 of whom were receiving 50 mg of zinc (as zinc acetate) per day and 10 of whom were not. Plasma zinc concentration was significantly higher in zinc-treated than in untreated patients (108 +/- 5 vs. 82 +/- 2 micrograms/dl). Mononuclear cell subpopulation analysis showed equivalent proportions of T lymphocytes and monocytes in both groups, but B lymphocytes were reduced in untreated patients (10 +/- 0.7 vs 14 +/- 0.5%). Lymphocyte blast transformations in response to nonspecific mitogens, soluble antigen and mixed lymphocyte culture were not significantly different in the two groups, nor was lymphocyte zinc concentration. Zinc-treated patients showed significantly greater granulocyte responsiveness to zymosan-activated serum (21 +/- 1 vs. 14 +/- 2 mean), greater chemokinetic activity (50 +/- 4 vs. 27 +/- 3 mean) and higher granulocyte zinc concentration (114 +/- 6 vs. 47 +/- 2 micrograms/10(6) cells) than untreated patients. Granulocyte zinc correlated significantly with plasma zinc (r = 0.81, P less than 0.001) and with granulocyte motility (r = 0.63, P = 0.001). Moderate zinc deficiency in hemodialysis patients does not result in abnormal lymphocyte blast transformation in vitro, but it does result in granulocyte zinc depletion and impaired granulocyte motility.

Acetates↗

PubMed1988

Zinc balance in combined zinc deficiency and uremia.

In order to evaluate whether the hypozincemia associated with chronic renal failure represents true negative zinc balance, male Lewis rats were randomized and pair-fed zinc replete (+Zn) or deplete (-Zn) diets. Subsequently, each animal underwent one- and two-thirds nephrectomy, or a sham operation. Complete balances for zinc, calcium, and magnesium were determined weekly before and after nephrectomy. At sacrifice, -Zn animals had significantly lower (P less than 0.005) plasma zinc levels compared to controls. Nephrectomized (N) animals had significantly elevated plasma creatinine (P less than 0.005), diminished creatinine clearances (P less than 0.005), and increased urinary flows (P less than 0.005) and protein excretion (P less than 0.01) compared to sham-operated (S) controls. Zinc nutritional status had no effect on these parameters in animals with comparable renal function. -Zn/N animals had consistently significantly elevated (P less than 0.005) urinary zinc excretion compared with -Zn/S with similar plasma zinc concentrations. Urinary zinc excretion correlated with urinary flow (r = 0.739, P less than 0.005), urinary protein (r = 0.635, P less than 0.01) and urinary calcium excretion (r = 0.855, P less than 0.005) in -Zn groups. -Zn/N rats had a significantly larger fecal zinc excretion for the first week post-nephrectomy, compared to -Zn/N controls (P less than 0.005). This resulted in negative zinc balance in -Zn/N animals, compared to their pre-nephrectomy balance (P less than 0.05) or to -Zn/S controls for the first (P less than 0.005) and second (P less than 0.05) weeks. -Zn/N rats had lower (P less than 0.02) hepatic zinc concentrations compared to the -Zn/S group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1998

Regulation of zinc homeostasis in yeast by binding of the ZAP1 transcriptional activator to zinc-responsive promoter elements.

Zinc homeostasis in yeast is controlled primarily through the regulation of zinc uptake. Transcription of the ZRT1 and ZRT2 zinc transporters increases in zinc-limited cells, and this induction is dependent on the ZAP1 gene. We hypothesized previously that ZAP1 encodes a zinc-responsive transcriptional activator. Expression of ZAP1 itself increases in zinc-limited cells. This response is also dependent on ZAP1 function through a potential positive autoregulatory mechanism. In this report, we describe the characterization of zinc-responsive elements (ZREs) in the promoters of the ZRT1, ZRT2, and ZAP1 genes. A ZRE consensus sequence, 5'-ACCYYNAAGGT-3', was identified and found to be both necessary and sufficient for zinc-responsive transcriptional regulation. We also demonstrate that ZREs are DNA binding sites for ZAP1. First, a dominant ZAP1 mutation, ZAP1-1(up), which causes increased expression of ZAP1-regulated genes in zinc-replete cells, exerted its effects specifically through the ZREs. Second, electrophoretic mobility shift assays and in vitro DNase I footprint analyses indicated that ZAP1 binds to ZREs in a sequence-specific fashion. These studies demonstrate that ZAP1 plays a direct role in controlling zinc-responsive gene expression in yeast by binding to zinc-responsive elements in the promoters of genes that it regulates.

Alleles↗

PubMed1998

Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial.

OBJECTIVE: to evaluate whether oral supplementation with zinc or zinc/arginine increases the antibody response to influenza vaccine or modulates the lymphocyte phenotype in elderly subjects. DESIGN: a randomized controlled trial with two supplemented groups and one control group. SETTING: a community nursing home. PARTICIPANTS: 384 subjects aged 64-100 (mean age 82 years) examined in three separate studies. INTERVENTION: oral supplementation with zinc (400 mg/day) or zinc plus arginine (4 g/day) for 60 days starting 15 days before influenza vaccination. The control groups received vaccine only. MEASUREMENTS: haematological and nutritional indices, antibody titre against influenza viral antigens, lymphocyte phenotype. RESULTS: supplementation with zinc or zinc plus arginine increased zinc plasma concentrations restoring the age-related impairment in zinc concentrations to values found in younger people. The antibody titre against influenza viral antigens was not increased in zinc or zinc/arginine supplemented groups in comparison with subjects receiving vaccine alone. The number of CD3, CD4 or CD8 lymphocytes was not affected by zinc or zinc/arginine supplementation. CONCLUSION: prolonged supplementation with zinc or zinc/arginine restores zinc plasma concentrations but is ineffective in inducing or ameliorating the antibody response after influenza vaccination in elderly subjects.

Aged↗

PubMed1993

Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases.

The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects. Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn (as gluconate)/d or a placebo, while control subjects received the zinc supplement. Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated, suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state. Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects, which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process. On the contrary, erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined. No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes.

Adult↗

PubMed1997

Zinc supplementation reduced morbidity, but neither zinc nor iron supplementation affected growth or body composition of Mexican preschoolers.

In rural Mexico and in many developing countries micronutrient deficiencies, growth stunting, and morbidity from infectious diseases are highly prevalent in young children. We assessed the extent to which growth stunting could be reversed and the number of infectious disease episodes reduced by zinc and/or iron supplementation. In a double-blind, randomized community trial 219 Mexican preschoolers were supplemented with either 20 mg Zn as zinc methionine, 20 mg Fe as ferrous sulfate, 20 mg Zn + 20 mg Fe, or a placebo. After 12 mo, plasma zinc increased significantly in the two zinc-treated groups, and plasma ferritin was significantly higher in the two iron-treated groups. There was no effect of treatments on growth velocity or body composition. Children in both zinc-supplemented groups had fewer episodes of disease (zinc alone, 3.9 +/- 0.3; zinc+iron, 3.7 +/- 0.4; placebo, 4.6 +/- 0.5; P < 0.03), including diarrhea (zinc alone, 0.7 +/- 0.1; zinc+iron, 0.8 +/- 0.1; placebo, 1.1 +/- 0.2; P < 0.01). Zinc and zinc+iron supplements reduced morbidity but had no effect on growth or body composition.

Body Composition↗

PubMed2000

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

BACKGROUND: Zinc is an essential trace element for human health and well-being; however, methods currently available for the assessment of zinc status in humans are unsatisfactory. OBJECTIVE: The objective was to critically evaluate the use of various indicators of zinc status in humans in a controlled metabolic ward study. DESIGN: Indicators of zinc status were measured in 25 healthy postmenopausal women aged 64.9 +/- 6.7 y. After a 10-d equilibration period, volunteers consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90-d period, and the diet supplemented with 50 mg Zn/d for another 90-d period. RESULTS: Zinc supplementation significantly increased (P < 0.0001) extracellular but not erythrocyte superoxide dismutase activity. This increase was more apparent when subjects were fed the low-copper diet. Zinc supplementation in combination with the low-copper diet significantly decreased (P < 0.01) amyloid precursor protein expression in platelets. Other indicators of zinc status that were significantly elevated after zinc supplementation were as follows: plasma zinc and free thyroxine concentrations and mononuclear 5'-nucleotidase activity. CONCLUSION: The measurement of serum extracellular superoxide dismutase activity may be useful as a marker for the functional assessment of zinc status in humans.

5'-Nucleotidase↗

PubMed1977

Effects of oxalic acid on availability of zinc from spinach leaves and zinc sulfate to rats.

Some effects of dietary oxalic acid on availability of zinc from organic and inorganic sources were assessed. Male rats fed zinc-deficient diets with and without added sodium oxalate were orally dosed once with either 65Zn-labeled spinach leaves or 65Zn-labeled zinc sulfate. Spinach plants (Spinacia oleracea, var. "Winter Bloomsdale") were grown in 65Zn-labeled nutrient solutions that contained 0.033, 0.131 or 0.262 ppm zinc. Increasing zinc supply to the plants increased zinc concentration in the leaves. Oxalic acid content in all leaves was about 7% dry weight. Dietary oxalate enhanced the availability of 65Zn from zinc sulfate, but had no effect on absorption and retention of 65Zn from spinach leaves. Regardless of dietary oxalate levels, absorption and retention of 65Zn was greater from spinach leaves than from zinc sulfate. We concluded that endogenous zinc in spinach leaves was readily available to zinc-deficient rats, and that dietary oxalate was not deleterious to zinc availability.

Absorption↗

PubMed1982

The effect of severe protein deficiency on serum zinc concentration of mice fed a requirement level or a very high level of dietary zinc.

The objective of the present study was to determine the effect of severe dietary protein deficiency on serum zinc concentration in weanling animals fed either a requirement level or a very high level of dietary zinc. Weanling (21-day-old) male and female CBA/J mice were randomly assigned to be fed one of four diets containing either 1.7% or approximately 18.5% protein and either 7 micrograms (predetermined requirement level) or about 200 micrograms zinc per gram of formulation. Serum zinc levels were measured after a 14-day feeding period. Dietary zinc content, over the range tested, did not influence the serum zinc level of protein deficient mice, and these animals exhibited serum zinc concentrations which were much lower than the levels found in adequately nourished mice fed the requirement level of zinc (7 micrograms/g diet). These results indicate that dietary zinc supplementation is unable to restore to normal the zinc status of severely protein-deficient animals. This may be an important factor to consider when studying the effect of protein deficiency on zinc-sensitive physiological processes.

Animals↗

PubMed2000

Zinc transport in the brain: routes of zinc influx and efflux in neurons.

Studies of the routes of entry and exit for zinc in different tissues and cell types have shown that zinc can use several pathways of exit or entry. In neurons, known pathways include (1) presynaptic release along with glutamate when synaptic vesicles empty their contents into the synaptic cleft, (2) voltage-gated L-type Ca(2+) channels and glutamate-gated channels that provide an entry route when cells are depolarized and that mediate extracellular zinc toxicity and (3) a plasma membrane transporter potentially present in all neurons important for cellular zinc homeostasis. The least understood of these pathways, in terms of mechanism, is the transporter pathway. The kinetics of zinc uptake in cultured neurons under resting conditions are consistent with and suggest the existence of a saturable transporter in the plasma membrane. The proteins responsible for plasma membrane zinc transport have not yet been definitely identified. Likely candidates include two proteins identified by molecular cloning termed zinc transporter 1 and divalent cation transporter DCT1. Both proteins have been shown to be expressed in the brain, but only DCT1 is clearly demonstrated to be a transport protein, whereas zinc transporter 1 may only modulate zinc transport in association with as-yet-unidentified proteins. Understanding the mechanism and neuromodulation of plasma membrane zinc transport will be an important first step toward a complete understanding of neuronal zinc homeostasis.

Animals↗

PubMed2005

Weekly iron supplementation does not block increases in serum zinc due to weekly zinc supplementation in Bangladeshi infants.

Because infants and young children in many developing countries are deficient in both iron and zinc, and zinc can affect iron metabolism, evaluation of optimum strategies to simultaneously supplement iron and zinc is an important public health priority. This study evaluated the efficacy of weekly supplementation of iron or zinc or both on iron, zinc, and copper status in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 6-mo-old infants were assigned to receive weekly supplements of 1 mg riboflavin (control, n = 82) or 1 mg riboflavin + 20 mg iron (n = 83), 20 mg zinc (n = 83), or both (n = 85) for 6 mo. Hemoglobin, serum ferritin, transferrin receptor, zinc, and copper concentrations were measured at baseline and at the end of intervention. Serum Zn increased in both groups receiving zinc; the increase was greatest among children with low baseline serum zinc concentration. Iron status indicators did not differ among the groups before or after 6 mo of supplementation. Supplementation with either zinc or iron decreased serum copper after 6 mo. Joint supplementation did not alter the individual effects of iron or zinc supplementation in these Bangladeshi children. However, the dosing regimen may not have been adequate to achieve the desired biochemical effects.

Bangladesh↗

PubMed2001

Plasma zinc, copper, copper:zinc ratio, and survival in a cohort of HIV-1-infected homosexual men.

A prospective cohort study of 121 HIV-1-positive homosexual men was conducted in Miami, Florida, U.S.A. to evaluate the associations between plasma zinc and copper levels and mortality. Plasma zinc and copper levels were measured at baseline and then at semiannual visits. Zinc inadequacy and copper inadequacy were defined as plasma zinc levels <75 (microg/dl) and plasma copper levels <85 (microg/dl), respectively. HIV-1-related deaths were confirmed by review of death certificates. Cox proportional hazards regression models with time-dependent covariates were used to estimate the relative risks of zinc and copper inadequacy on mortality. Over the average course of the 3.3-year follow-up, 19 participants (16%) died of HIV-1-related causes. After adjustment for potential confounders, including low CD4+ cell counts and antiretroviral therapy, zinc inadequacy and copper:zinc ratio >1 (i.e., plasma copper level greater than plasma zinc level) were associated with increased mortality (relative risks [RRs]; 95% confidence intervals [CIs], 4.98, 1.30-19.00 and 8.28, 1.03-66.58, respectively). A negative association was also observed between plasma zinc levels and mortality (RR 0.94; 95% CI, 0.91-0.98). Plasma levels of copper were not significantly associated with mortality. These results suggest that plasma zinc inadequacy or the plasma copper:zinc ratio may be useful predictors of survival in HIV-1 infection. The latter appears to be a stronger predictor.

Adult↗

PubMed1986

The effect of dentifrices containing zinc citrate on plaque growth and oral zinc levels.

Zinc salts have previously been shown to possess antiplaque activity in solution but this activity has as yet not been reported for dentifrices. The purpose of the present investigation was to establish the effect of dentifrices containing zinc citrate (ZCT) on plaque growth and on the concentration of zinc in saliva and plaque. Plaque growth inhibition was studied over periods of time approximating to intervals for normal oral hygiene procedures. Zinc in saliva and plaque was measured by atomic absorption spectroscopy. Elevated zinc levels in saliva were observed for 3-4 h after brushing with the zinc citrate dentifrice. Similarly, raised levels of zinc were encountered in plaque 1 h following contact with a slurry of a dentifrice containing ZCT. Increased concentrations of zinc were observed in plaque fluid and plaque residue. The plaque growth data from 88 participants in 5 studies revealed that plaque regrowth over 16 h or 22 h was reduced by dentifrices containing 0.5% ZCT, compared to placebo dentifrices. Dentifrices which contained 0.5% ZCT or 0.4% stannous fluoride, had similar inhibitory effects on plaque. Further analysis of the data showed that subjects with high rates of plaque growth benefited more from the zinc dentifrices than those with low rates of plaque growth. It is suggested that the effect on plaque was related to zinc concentration in the dentifrice rather than total dose applied, and that the main effect of zinc was to inhibit the extension of existing plaque.

Adolescent↗

PubMed2006

Aldehydes release zinc from proteins. A pathway from oxidative stress/lipid peroxidation to cellular functions of zinc.

Oxidative stress, lipid peroxidation, hyperglycemia-induced glycations and environmental exposures increase the cellular concentrations of aldehydes. A novel aspect of the molecular actions of aldehydes, e.g. acetaldehyde and acrolein, is their reaction with the cysteine ligands of zinc sites in proteins and concomitant zinc release. Stoichiometric amounts of acrolein release zinc from zinc-thiolate coordination sites in proteins such as metallothionein and alcohol dehydrogenase. Aldehydes also release zinc intracellularly in cultured human hepatoma (HepG2) cells and interfere with zinc-dependent signaling processes such as gene expression and phosphorylation. Thus both acetaldehyde and acrolein induce the expression of metallothionein and modulate protein tyrosine phosphatase activity in a zinc-dependent way. Since minute changes in the availability of cellular zinc have potent effects, zinc release is a mechanism of amplification that may account for many of the biological effects of aldehydes. The zinc-releasing activity of aldehydes establishes relationships among cellular zinc, the functions of endogenous and xenobiotic aldehydes, and redox stress, with implications for pathobiochemical and toxicologic mechanisms.

Alcohol Dehydrogenase↗

PubMed1998

Effect of training on zinc metabolism: changes in serum and sweat zinc concentrations in sportsmen.

The purpose of this research was to determine the effects of daily physical training on serum and sweat zinc concentrations in professional sportsmen between October and December, during the competing season. Twelve volleyball players and another 12 control subjects have participated in this study. Tests were made in October and December which consisted of a progressive bicycle ergometer test (increasing 30 W every 3 min to reach maximum tolerated power). Blood samples were obtained at rest and immediately after exercise. Total serum zinc increased significantly after maximal exercise in both sportsmen and control subjects. In athletes, the change after exercise was significantly higher in December than in October. The percentage of ultrafiltrable zinc (ZnUf) in October was similar in sportsmen and in controls. In December, however, after exercise, the percentage of ZnUf was higher in athletes. With respect to sweat zinc, it was in the same range both in controls and in sportsmen in October. In December, however, sweat zinc was significantly higher in athletes as compared with the situation in October and with respect to the control group. In October, the zinc concentration of urine was similar for sportsmen and controls. In December, the sportsmen showed an increase in urinary zinc excretion with respect to control subjects. Cortisol in athletes increased significantly after exercise in December. In conclusion, a daily and maintained practice of exercise is probably responsible for an alteration of zinc metabolism. The results suggest that ZnUf control, zinc supplementation and/or stress control appear to be indicated in athletes to prevent the diminution of active ZnUf. In our practical opinion we think that alterations in zinc metabolism with increases in zinc excretion and stress levels lead to a situation of latent fatigue with a decreased endurance.

Adult↗

PubMed1993

Effect of the severity of maternal zinc deficiency on pregnancy outcome and infant zinc status in rhesus monkeys.

To investigate the effects of the severity of maternal zinc deficiency on early development, rhesus monkeys were fed diets that were either moderately zinc-deficient (MZD) (2 micrograms Zn/g) or marginal in zinc (M) (4 micrograms Zn/g) throughout pregnancy and lactation. Dams in the MZD group developed overt signs of zinc deficiency. Compared with control dams fed diets adequate in zinc (C) (50 or 100 micrograms Zn/g), both M and MZD dams showed low mitogen response. Pregnancy outcome was similar in all groups, and infants were considered healthy at delivery. From birth until d 30, infants were closely monitored for signs of zinc deficiency. On d 30, infants were killed and tissues were analyzed for several parameters reported to be affected by zinc status. MZD infants tended to have lower plasma zinc concentrations than C infants, although the difference was only significant at d 14. M infants tended to have lower plasma zinc concentrations than C infants. Mitogen response was lower in MZD and M infants than in C infants. However, mitogen responses were similar in MZD and M infants. Liver zinc concentrations were similar among the three groups of infants; however, zinc and metallothionein concentrations in (10,000 x g) liver supernatant fractions were lower in the MZD and M groups than in the C group. 65Zn absorption/retention was higher in MZD and M mothers and infants than in C mothers and infants; there were no marked differences between MZD and M mothers or infants. In contrast to whole-body absorption, 65Zn uptake/retention by isolated hepatocytes was similar among the three infant groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2000

Dietary molar ratios of phytate:zinc and millimolar ratios of phytate x calcium:zinc in South Koreans.

The zinc nutritional status in south Koreans was established by evaluation of zinc, calcium and phytate intakes, the molar ratio of phytate:zinc, and the millimolar ratio of phytate x calcium:zinc. The intakes of iron and magnesium were also estimated. Sampling was designed so that it was representative of the national population. Two-day food records were used for the calculation of nutrient intakes, using food consumption data from the 1995 National Nutrition Survey ('95NNS) for South Korea. Daily intakes of zinc and calcium were estimated to be 10.1 mg/d and 426.5 mg/d, respectively, and those of iron and magnesium were 15.2 mg/d and 268.0 mg/d, respectively. The estimated daily phytate intake was 1676.6 mg/d. The ratio of phytate:zinc was 15.9 mol/d and that of phytate x calcium:zinc was 168.9 mmol/d. The ratio in millimoles per 4.2 MJ (1000 kcal) of phytate x calcium:zinc was 91.8. The major food groups for zinc intake were meat, poultry and their products (43%), and cereals and grain products (18%). Sixty-two percent of zinc was from animal food sources. Cereal and grain products supplied most of the phytate intake (46%) followed by seasonings, fruits, and legumes and their products. The major food source of phytate was rice (39%). The results of the study raise concern about the suboptimal zinc status in relation to the Western diet.

Calcium↗