Higher Serum Zinc Concentrations Research Articles

Does the Protective Effect of Zinc on Telomere Length Depend on the Presence of Hypertension or Type 2 Diabetes? Results from the Iwaki Health Promotion Project, Japan.

Telomeres, repeated TTAGGG sequences at chromosomal ends, shorten with age and indicate cellular lifespan. Zinc can protect against telomere damage through its anti-oxidative effect. Meanwhile, telomere shortening was correlated with metabolic diseases of hypertension and type 2 diabetes. The objective of this study was to investigate whether the association between zinc and telomere length differs by the presence or absence of hypertension/type 2 diabetes. This is a cross-sectional study with 1064 participants of the Iwaki area, Japan. Multiple linear regression models were performed to test the hypothesis. A higher serum zinc concentration was significantly associated with a longer G-tail length (β = 48.11, 95% confidence intervals [CI]: 25.69, 70.54, p < 0.001). By multivariate linear regression analysis, there was a significant positive association between zinc and G-tail length in both hypertensive (β = 46.84, 95%CI: 9.69, 84.0, p = 0.014) and non-hypertensive groups (β = 49.47, 95%CI: 20.75, 78.18, p = 0.001), while the association was significant only in the non-diabetes group (β = 50.82, 95%CI: 27.54, 74.11, p < 0.001). In conclusion, higher zinc concentration was significantly associated with longer G-tail length. The protective effect of zinc on G-tail did not differ by hypertension status; however, it disappeared in individuals with type 2 diabetes.

Zinc Intakes and Health Outcomes: An Umbrella Review.

It is widely accepted that the zinc element is crucial in human beings. Zinc has gained more attention during the COVID-19 pandemic due to its utilization for the treatment and prevention of respiratory tract infections. However, some studies also pointed out that zinc intake might cause unwanted side effects and even be dangerous when overdosed. To reveal the relationship between zinc intake and health outcomes, we performed an umbrella review from human studies. In total, the umbrella review included 43 articles and identified 11 outcomes for dietary zinc intake and 86 outcomes for supplementary zinc intake. Dietary zinc intake in the highest dose would decrease the risk of overall and specific digestive tract cancers, depression, and type 2 diabetes mellitus (T2DM) in adults. Supplementary zinc consumption in adults was linked to an improvement of depression, antioxidant capacity and sperm quality, higher serum zinc concentration, and lower concentration of inflammatory markers. Zinc supplementation in children would reduce the incidence of diarrhea and pneumonia, improve zinc deficiency and boost growth. However, zinc might not decrease all-cause mortality in adults or the in-hospital mortality of COVID-19. And better maternal and neonatal outcomes may not derive from pregnant women who consumed higher or lower doses of zinc supplementation (>20 mg/day and <20 mg/day, respectively). Dose-response analyses revealed that a daily 5 mg increment of zinc would lower the risk of colorectal and esophageal cancer, whereas a large dose of zinc supplementation (daily 100 mg) showed no benefit in reducing prostate cancer risk.

P0940CLINICAL ASSOCIATION BETWEEN SEVERE INFECTION AND HYPOZINCEMIA IN INCIDENT PATIENTS ON HEMODIALYSIS

Abstract Background and Aims Hypozincemia can arise in patients with advanced chronic kidney disease (CKD) due to low protein intake and urinary or dialytic loss. Several studies have confirmed an association between hypozincemia and infection. Because infections comprise a major complication in patients with advanced CKD, we investigated whether hypozincemia is associated with infection risk in incident patients on dialysis. Method We prospectively analyzed 380 consecutive patients aged 20 years old or more who started hemodialysis between January 2013 and December 2018. Six patients who were receiving zinc supplementation at the time of the study were excluded. Serum zinc values were obtained at the time of dialysis initiation. We followed up the remaining patients after enrollment. The endpoint was severe infection defined as infection-related death or bacteremia confirmed by the detection of microorganisms in two sets of culture bottles. The patients were equally divided into groups with low, middle or high serum zinc concentrations. Data were analyzed using Kaplan-Meier curves and Cox hazards models. The local ethics committee approved this research. Informed consent was obtained from each individual participant included in the study. Results The rate of severe infection events over a follow-up of one year was the highest in the group with low zinc (p = 0.030). Cox hazards models adjusted for age, sex, diabetes mellitus, serum albumin and serum zinc, selected hypozincemia as an independent risk factor for severe infection events (HR, 10.76; 95% CI, 1.28–90.41; p = 0.029). Conclusion Hypozincemia is associated with risk of subsequent severe infection in incident patients on dialysis.

Association between serum zinc and copper concentrations and copper/zinc ratio with the prevalence of knee chondrocalcinosis: a cross-sectional study

BackgroundPatients with chondrocalcinosis may suffer from a series of symptoms resembling acute gouty arthritis or septic arthritis, but the aetiology and pathogenesis of chondrocalcinosis have not been fully elucidated yet. This study was aimed to assess serum zinc and copper concentrations, as well as the ratio of serum copper to zinc concentrations (Cu/Zn ratio), in relation to the prevalence of knee chondrocalcinosis.MethodsData included in this analysis were retrieved from a large population-based cross-sectional study. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was diagnosed if definite linear cartilage calcification was detected. Serum zinc and copper concentrations were measured using the spectrophotometric flow injection methods by Roche modular P800. The relations of serum zinc and copper concentrations and Cu/Zn ratio to the prevalence of knee chondrocalcinosis were examined using generalized estimating equations, respectively.ResultsThe prevalence of knee chondrocalcinosis was 1.2% in the sample of this study (n = 12,362). In comparison with the lowest tertile, the odds ratios (ORs) of knee chondrocalcinosis adjusted by age, sex and body mass index were 0.74 (95% CI 0.50–1.09) in the second and 0.56 (95% CI 0.36–0.86) in the third tertiles of serum zinc concentrations (P for trend = 0.009), were 1.26 (95% CI 0.77–2.05) in the second and 2.01 (95% CI 1.25–3.24) in the third tertile of serum copper concentrations (P for trend = 0.003), and were 1.02 (95% CI 0.61–1.69) in the second and 2.23 (95% CI 1.38–3.59) in the third tertile of Cu/Zn ratio (P for trend < 0.001) respectively. These findings were not materially altered by adjustment for potential confounders.ConclusionsThe present study observed that higher serum zinc concentrations, lower serum copper concentrations or lower Cu/Zn ratio are associated with a lower prevalence of knee chondrocalcinosis in a dose-response relationship manner.

Effects of Zinc Acetate on Serum Zinc Concentrations in Chronic Liver Diseases: a Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial and a Dose Adjustment Trial

The essential trace element zinc maintains liver functions. Liver diseases can alter overall zinc concentrations, and hypozincemia is associated with various hepatic pathologies. Modulating systemic zinc through dietary supplementation is potentially useful for liver diseases. We evaluated the usefulness of zinc (NPC-02; acetate formulation) supplementation. We conducted two NPC-02 studies on zinc-deficient patients (serum zinc < 70 μg/dL). Study 1: double-blind, randomized, placebo-controlled trial on 57 subjects with chronic liver diseases comparing serum zinc in patients given NPC-02 (NPC-02 group) versus placebo (Placebo group). Study 2: dose adjustment study on 43 subjects with/without liver diseases to determine proportions maintaining serum zinc target (≥ 80 μg/dL but < 200 μg/dL). In study 1, NPC-02 subjects had higher serum zinc concentrations at week 8 than Placebo subjects (83.2 ± 20.2 and 61.3 ± 12.0, respectively; P < 0.0001), and more NPC-02 than Placebo subjects achieved the serum zinc target (15/27 vs. 1/26). In study 2, the NPC-02-induced serum zinc increase was dose-dependent in subjects both with and without liver diseases (r = 0.5143, P = 0.0022 and r = 0.5753, P = 0.0005, respectively). Interestingly, there was a marginally positive correlation between serum zinc and albumin levels in subjects with but not in those without liver diseases (r = 0.4028, P = 0.0631 and r = 0.1360, P = 0.5567, respectively). NPC-02 dose-dependently increases serum zinc in hypozincemic patients, regardless of liver disease. NPC-02 is a potentially effective therapy for liver cirrhosis, in which zinc deficiency is common. Clinical trial registry number: NCT02337569, NCT02321865.

The Association Between Renal Tubular Dysfunction and Zinc Level in a Chinese Population Environmentally Exposed to Cadmium.

Studies in vivo and in vitro have shown a protective effect of zinc against renal dysfunction caused by cadmium exposure. However, limited human data is available. In this study, we evaluated the association between renal tubular dysfunction and body zinc burden in a Chinese population exposed to cadmium. A total of 331 subjects (170 women and 161 men) living in control and cadmium-polluted area were included. Blood cadmium (BCd), urinary cadmium (UCd), serum zinc (SZn), zinc in hair (HZn), Zn/Cd ratio, and urinary β2Microglobulin (UBMG) were measured. The median UCd, BCd, SZn, and HZn were 2.8 and 13.6μg/g cr, 1.3 and 12.2μg/L, 1.31 and 1.12mg/L, and 0.14 and 0.12mg/g in subjects living in control and polluted areas. The UBMG level of subjects living in the polluted area was significantly higher than that of the control (0.27 vs 0.11mg/g cr, p < 0.01). SZn, HZn, and Zn/Cd ratios were negatively correlated with UBMG (p < 0.05 or 0.01). Subjects with high SZn concentrations (≥ 1.62mg/L) had reduced risks of elevated UBMG [(odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.07-0.99)] after controlling for multiple covariates compared with those with lower zinc levels. A similar result was observed in subjects with high HZn (OR = 0.09, 95% CI 0.02-0.48). The ORs of the second, third, and fourth quartiles of Zn/Cd ratio were 0.40 (95% CI 0.19-0.84), 0.14 (95% CI 0.06-0.37), and 0.01 (95% CI 0.02-0.18) for renal dysfunction compared with those of the first quartile, respectively. For those subjects with high level of UCd, high level of SZn and HZn also had reduced risks of elevated UBMG. The results of the present study show that high zinc body burden is associated with a decrease risk of renal tubular dysfunction induced by cadmium. Zinc nutritional status should be considered in evaluating cadmium-induced renal damage.

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, Ptrend < 0.001]. Inverse associations were also observed for linoleic acid, arachidonic acid and D5D activity. By contrast, men in the highest tertile of D6D activity had an 84% higher risk (OR = 1.84; 95% CI = 1.15-2.94, Ptrend = 0.008). Similar associations were observed with many of the metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations.

Is Serum Zinc Associated with Pancreatic Beta Cell Function and Insulin Sensitivity in Pre-Diabetic and Normal Individuals? Findings from the Hunter Community Study

AimTo determine if there is a difference in serum zinc concentration between normoglycaemic, pre-diabetic and type-2 diabetic groups and if this is associated with pancreatic beta cell function and insulin sensitivity in the former 2 groups.MethodCross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2) calculator.ResultA total of 452 participants were recruited for this study. Approximately 33% (N = 149) had diabetes, 33% (N = 151) had prediabetes and 34% (N = 152) were normoglycaemic. Homeostasis Model Assessment (HOMA) parameters were found to be significantly different between normoglycaemic and prediabetes groups (p<0.001). In adjusted linear regression, higher serum zinc concentration was associated with increased insulin sensitivity (p = 0.01) in the prediabetic group. There was also a significant association between smoking and worse insulin sensitivity.ConclusionHigher serum zinc concentration is associated with increased insulin sensitivity. Longitudinal studies are required to determine if low serum zinc concentration plays a role in progression from pre-diabetes to diabetes.

Supplementation with Zinc Affects Serum MicroRNA (miRNA) Levels in Early Pubertal Females

The purpose of this research was to determine whether supplementation with oral zinc near the RDA for 4 wks would alter serum miRNA levels among females in the early stages of puberty. Black and white females, 9 to 13 years of age, were given either 9 mg elemental zinc (Zn; n=75) or placebo (PL; n=71) for 4 wks. Sera were collected from subjects at baseline and 4 wks, and analyzed for zinc by atomic absorption. There were no differences in baseline characteristics between Zn and PL groups. Blacks had higher serum zinc concentrations at baseline and 4 wks. Following supplementation serum Zn increased more in the Zn group vs PL (p &lt; 0.05). There was no difference in the serum zinc response to zinc supplementation between blacks and whites. Sera from subjects that were most responsive to zinc supplementation (n = 5) or exhibited the least change in serum Zn (n = 5) were pooled. Serum exosomes from each sample were purified using a magnetic‐bead based isolation procedure. The RNAs were analyzed using the Affymetrix GeneChip miRNA 3.0 microarrays. Thirteen and 12 miRNAs changed at least 1.75‐fold in response to zinc supplementation in blacks and whites, respectively; however, there was no overlap in miRNAs species between blacks and whites. These miRNAs may ultimately serve as serum biomarkers for assessing zinc status in young girls. However, zinc biomarkers associated with race may need to be considered.

Hypocupremia associated cytopenia and myelopathy: a national retrospective review

Copper is an essential trace element that is involved in a number of important enzymatic processes throughout the body. Recent single case reports and small studies have shown that deficiency of copper can cause reversible haematological changes and irreversible neurological injury. We chose to undertake a national study, looking at all cases of copper deficiency in Scotland over a 5-yr period using information from a national reference laboratory. From 16 identified patients, we determined that 86% had both haematological and neurological features of copper deficiency, while 18% had haematological features only at presentation. Twelve of the sixteen patients had high serum zinc concentrations (>18 μm/L) nine patients were using zinc-containing dental fixatives at time of diagnosis. 94% of patients had haematological features as an initial manifestation of copper deficiency, which included anaemia, thrombocytopenia and neutropenia. Patients who underwent later bone marrow testing had appearances in keeping with refractory cytopenia with multilineage dysplasia, refractory anaemia with excess of blasts, unclassified marrow dysplasia or probable myelodysplasia (MDS). 75% of patients had neurological symptoms or signs, including progressive walking difficulties and paraesthesia, or gait difficulties without sensory signs. Clinical examination was in keeping with spastic paraparesis (either with or without sensory neuropathy). Magnetic resonance imaging (MRI) showed multifocal T2 hyper intense foci in the subcortical white matter, and atrophy of the cerebrum and cerebellum was also seen on computerised tomography (CT). MRI of the spinal cord showed signal change in the dorsal columns in either the cervical or thoracic cord. 93% of cytopenias responded to copper replacement and addressing the original cause of the copper deficiency, but only 25% of patients had improvement in their neurological function, while 33% deteriorated and 42% remained unchanged. Our study demonstrates that copper deficiency is an under-recognised cause of several types of cytopenia, which are reversible but can progress to significant neurological injury if left untreated. We illustrate the importance of identifying these patients early to prevent irreversible neurological injury.

Blood values of adult captive cheetahs (Acinonyx jubatus) fed either supplemented beef or whole rabbit carcasses

This study evaluated nutrient intake and relevant blood parameters of 14 captive cheetahs, randomly assigned to a meat-only diet (supplemented beef, SB) or a whole prey diet (whole rabbit, WR) for 4 weeks each. Despite a higher food intake, daily metabolizable energy intake was lower when fed WR (308 kJ BW(-1) ) compared with SB (347 kJ BW(-1) ) (P = 0.002). The ratio of protein to fat was markedly lower for WR (2.3:1) compared with SB (8.8:1), which was reflected in higher serum urea levels when fed SB (P = 0.033), and a tendency for elevated cholesterol levels when fed WR (P = 0.055). Taurine intake of cheetahs fed WR was low (0.06% on DM basis); however, analytical error during taurine analysis cannot be ruled out. Feeding WR resulted in a well-balanced mineral intake, in contrast to SB. The latter provided a low calcium:phosphorus ratio (1:2.3), thereby increasing the risk of metabolic bone disease. The high zinc content of SB (200 mg/kg DM), compared with WR (94 mg/kg DM), was reflected in higher serum zinc concentrations (P = 0.011). Feeding WR resulted in an increase in serum vitamin A (P = 0.011). Therefore, the risk of hypervitaminosis A in captive cheetahs when fed WR exclusively on a long-term basis should be evaluated. Our findings suggest that neither diet is likely to provide appropriate nutrition to captive cheetahs when fed exclusively.

Adding zinc to prenatal iron and folate supplements improves maternal and neonatal zinc status in a Peruvian population

Maternal zinc deficiency during pregnancy may be widespread among women in developing countries, but few data are available on whether prenatal zinc supplementation improves maternal and neonatal zinc status. We studied whether maternal zinc supplementation improved the zinc status of mothers and neonates participating in a supplementation trial in a shantytown in Lima, Peru. Beginning at gestation week 10-24, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg Fe and 250 microg folate, with or without 15 mg Zn. Venous blood and urine samples were collected at enrollment, at gestation week 28-30, and at gestation week 37-38. At birth, a sample of cord vein blood was collected. We measured serum zinc concentrations in 538 women, urinary zinc concentrations in 521 women, and cord zinc concentrations in 252 neonates. At 28-30 and 37-38 wk, mothers receiving zinc supplements had higher serum zinc concentrations than mothers who did not receive zinc (8.8 +/- 1.9 compared with 8.4 +/- 1.5 micromol/L and 8.6 +/- 1.5 compared with 8.3 +/- 1.4 micromol/L, respectively). Urinary zinc concentrations were also higher in mothers who received supplemental zinc (P < 0.05). After adjustment for covariates and confounding factors, neonates of mothers receiving zinc supplements had higher cord zinc concentrations than neonates of mothers who did not receive zinc (12.7 +/- 2.3 compared with 12.1 +/- 2.1 micromol/L). Despite supplementation, maternal and neonatal zinc concentrations remained lower than values reported for well-nourished populations. Adding zinc to prenatal iron and folate tablets improved maternal and neonatal zinc status, but higher doses of zinc are likely needed to further improve maternal and neonatal zinc status in this population.

The effect of alcohol on zinc absorption

Two methods of intestinal perfusion are described and used to study the effecs of alcohol on zinc absorption in the rat small intestine. The first method used perfusion of the lumen of the rat small intestinein situ without interruption of the vascular supply. During perfusion with a zinc-containing medium (with and without alcohol), alcohol was found to have no effect on net zinc uptake from the lumen of the intestine. However, there were significantly higher serum zinc concentrations recorded in the rats perfused wih the zinc and alcohol, 28.8 μmol/L, when compared with a group perfused without alcohol, 19.1 μmol/L (P < 0.01). The second method used simultaneous perfusion of the lumen of the rat small intestine, with constant-rate perfusion of the vascular bed with an artificial blood supply. In this experiment with a zinc-containing medium, with and without alcohol, there was no difference noted in zinc absorption from the lumen of the intestine, or release into the artificial blood supply. Therefore, in conclusion, alcohol does not appear to directly influence zinc absorption by the mucosal cells of the small intestine.