Baseline Plasma Zinc Research Articles

Prospective association between baseline plasma zinc concentration and development of proteinuria in Chinese hypertensive patients

ObjectiveWe aimed to evaluate the association between baseline plasma zinc and the development of proteinuria as well as possible effect modifiers in hypertensive patients. MethodsThis is a subset of the China Stroke Primary Prevention Trial (CSPPT) Renal Sub-Study. In the CSPPT, participants were randomized to receive a daily oral dose of 1 tablet containing 10 mg enalapril and 0.8 mg folic acid or 1 tablet containing 10 mg enalapril only. A total of 783 participants with plasma zinc measurements and without proteinuria at baseline were included in the current study. The study outcome was the development of proteinuria during the follow-up, defined as a urine dipstick reading of trace or ≥1+ at the exit visit. ResultsDuring a median follow-up duration of 4.4 years, the development of proteinuria occurred in 93 (11.9 %) participants. There was an inverse relation of baseline plasma zinc with the development of proteinuria (per SD increment; OR, 0.74, 95 % CI: 0.55−0.99), p for trend of quartiles = 0.005. ConclusionsIn Chinese hypertensive patients, there was a significant inverse association between baseline plasma zinc and the development of proteinuria, although plasma zinc remained in the reference range.

Role and effects of zinc supplementation in HIV-infected patients with immunovirological discordance: A randomized, double blind, case control study.

It has been estimated that between 15% and 18% of patients who start antiretroviral therapy (ART) do not achieve a successful immune recovery despite complete virological suppression. In the literature this phenomenom is known as poor immune recovery or immunovirological discordance (IVD). Zinc has an immunomodulatory role associated with T lymphocytes and its supplementation could enhance immune recovery. To determine if zinc supplementation on IVD patients prevents immune failure after 12 months of supplementation. Secondary objectives were to determine serum zinc levels in HIV patients with and without IVD and the frequency of hypozincemia in discordant patients. We reviewed the historical record of patients under care at Arriarán Foundation. Following inclusion criteria were defined: 1) age ≥ 18 years, 2) standard ART (three effective drugs) for at least 18 months, 3) virologically suppressed for 12 months, 3) persistence of CD4 count ≤200 cells/mm3 and/or increase ≤ 80 cells/mm3 after one year of viral undetectability. A control group was assigned paired 1:1 by sex, age (± 2 years) that did achieved an increase of CD4> 350 cells/ mm3. In both groups plasma zinc levels were determined. In a later phase, patients with IVD were randomized to receive zinc (15 mg daily) versus placebo. Patients were followed for 12 months with CD4 count, viral load and zinc levels determinations every 4-6 months. A total of 80 patients, 40 patients with IVD criteria and 40 controls were included. 92.5% were men, and age average was 47.5 years. The median baseline CD4 was 189 cells/mm3 (71-258) in the cases vs. 552.5 cells/ mm3 (317-400) in the control group with a median increase at the end of the study of 39 cell/mm3 and 19 cell/mm3 respectively. There was no difference in baseline plasma zinc levels between both groups (81.7 + 18.1 in cases versus 86.2 + 11.0 in controls). In the 40 patients with IVD, the median absolute increase in CD4 after annual zinc supplementation was 31.5 cells/mm3 in the treated group versus 50 cells/mm3 in the placebo group, this difference being statistically not significant (p = 0.382). Patients with IVD have plasma zinc levels similar to those who achieve adequate immune recovery. Zinc supplementation in IVD patients showed a statistically non-significant difference in in CD4 levels between cases and controls. The results warrant a comparative study with a larger number of patients.

Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial

Background:Zinc deficiency impairs immune function and is common among children in South-East Asia. Objectives:The effect of zinc supplementation on immune function in young Laotian children was investigated. Methods:Children (n = 512) aged 623 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration). Results:T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL,P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL,P = 0.012). Conclusions:Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at http://www.clinicaltrials.gov as NCT02428647.

Renal handling of zinc in chronic kidney disease patients and the role of circulating zinc levels in renal function decline.

Zinc deficiency is commonly encountered in chronic kidney disease (CKD). The aims of this study were to assess whether zinc deficiency was related to increased renal excretion of zinc and to the progression of CKD. Plasma and 24-h urinary zinc levels, urinary electrolytes and uromodulin were measured in 108 CKD patients and 81 individuals without CKD. Serum creatinine values were collected for 3years to calculate the yearly change in estimated glomerular filtration rate (eGFR). Multivariable regression analysis was performed to assess the association between baseline zinc levels and yearly change in eGFR. CKD patients had lower circulating zinc levels and higher 24-h urinary zinc excretion than non-CKD participants (612.4 ± 425.9 versus 479.2 ± 293.0 µg/day; P = 0.02). Fractional excretion (FE) of zinc was higher and it significantly increased at more advanced CKD stages. Zinc FE was correlated negatively with 24-h urinary uromodulin excretion (r=-0.29; P < 0.01). Lower baseline plasma zinc levels were associated with a faster yearly decline of renal function in age, gender, diabetes and hypertension adjusted models, but this relationship was no longer significant when baseline eGFR or proteinuria were included. Zinc levels are lower in CKD, and not compensated by reduced renal zinc excretion. The inverse association between urinary zinc excretion and uromodulin possibly points to an impaired tubular activity, which could partly account for zinc imbalance in CKD. These data suggest that zinc status is associated with renal function decline, but further studies elucidating the underlying mechanisms and the potential role of zinc supplements in CKD are needed.

Zinc Supplementation Does Not Alter Indicators of Insulin Secretion and Sensitivity in Black and White Female Adolescents

Background: Zinc is a micronutrient involved in the production of, and peripheral sensitivity to, pancreatic β cell-derived insulin. To our knowledge, the effect of zinc supplementation on insulin outcomes, and potential risk of diabetes, in otherwise healthy children in the United States has not been investigated.Objective: The objective of this study was to determine the influence of zinc supplementation on insulin outcomes in black and white girls in the early stages of adolescence. A secondary objective was to determine relations between baseline zinc concentrations and insulin outcomes.Methods: Healthy black and white girls aged 9-11 y were randomly assigned to daily supplementation of zinc (9 mg elemental Zn/d; n = 75; blacks: n = 35) or placebo (n = 72; blacks: n = 32) for 4 wk. Fasting serum insulin, glucose, and C-peptide were assessed at baseline and at 4 wk. C-peptide and glucose values were used to calculate the computer model-derived homeostatic model assessment of insulin resistance (HOMA2-IR). Changes in outcome measures were compared by using repeated-measures, mixed-model ANOVA.Results: Baseline plasma zinc was not correlated with C-peptide (r = -0.07), insulin (r = -0.06), or HOMA2-IR (r = -0.09) (all P > 0.05) after controlling for race and age. Treatment × time interactions for C-peptide and HOMA2-IR were not significant (both P > 0.05). Although the treatment × race × time interactions for C-peptide and HOMA2-IR were not significant (both P = 0.08), black girls who received the placebo experienced slight increases in C-peptide (15.7%) and HOMA2-IR (17.7%) (P = 0.06).Conclusions: Four weeks of zinc supplementation had no effect on insulin outcomes in healthy black and white early-adolescent girls, although C-peptide and HOMA2-IR tended to increase in black girls who received placebo. Additional trials that are appropriately powered should further explore the effect of zinc on markers of diabetes risk, and whether race affects this relation. This trial was registered at clinicaltrials.gov as NCT01892098.

Plasma Zinc Concentrations Are Depressed during the Acute Phase Response in Children with Falciparum Malaria

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 micromol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response.

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials

Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials

Objectives: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. Study design: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 “continuous” trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 “short-course” trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. Results: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. Conclusions: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings. (J Pediatr 1999;135:689-97)

Effects of repletion with zinc and other micronutrients on neuropsychologic performance and growth of Chinese children

The knowledge that zinc is essential for growth and neuropsychologic performance and a report of zinc-responsive stunting in Chinese children prompted this project. This article summarizes findings from a 10-wk, double-blind, controlled trial of zinc repletion in 740 urban, 6-9-y-old first graders from low-income families in Chongqing, Qingdao, and Shanghai, People’s Republic of China. Treatments were 20 mg Zn alone (Z), 20 mg Zn with micronutrients (ZM), and micronutrients alone (M). The M mixture was based on National Research Council guidelines. Nutrients that might interfere with zinc retention were excluded or given in lower amounts. Main outcomes were changes in neuropsychologic performance and knee height. Hemoglobin, serum ferritin, plasma and hair zinc, and whole blood and hair lead were also measured. Anemia was not common, and serum ferritin concentrations were usually within the range of normal. Mean baseline plasma zinc concentrations were marginal in children from Chongqing and Qingdao and normal in children from Shanghai. After treatment with ZM or M plasma zinc increased. Hair zinc tended to decrease after all treatments. Mean baseline whole blood lead concentrations were slightly below the limit considered excessive for children by the US Centers for Disease Control and Prevention. Neuropsychologic performance and growth were most improved after treatment with ZM. These findings were consistent with the presence of zinc and other micronutrient deficiencies. Am J Clin Nutr 1998;68(suppl):470S–5S.

Zinc Supplementation Reduces the Incidence of Persistent Diarrhea and Dysentery among Low Socioeconomic Children in India

Persistent diarrhea (PD) and dysentery (DD) account for most diarrhea-associated deaths among children in developing countries. Zinc deficiency can cause stunting and impaired immune function, both of which are risk factors for these diarrheal illnesses. We investigated the effect of zinc supplementation on the incidence of PD and DD in a community-based, double-blind randomized trial in children 6–35 mo of age. Increase over baseline in plasma zinc concentrations in the supplemented group compared with a control group (3.61 vs. 0.009 µmol·L-1) indicated successful supplementation. The overall reductions in the zinc supplemented group of 21% in the incidence of PD (95% CI -6 to 42%) and 14% in the incidence of dysentery (95%CI -15 to 36%) were not significant. There was a significant interaction of treatment effect with baseline plasma zinc concentration and age for PD and with gender for DD. In the zinc-supplemented group compared with the control group, the incidence of PD was reduced by 73% (P < 0.05; 95% CI 34 to 91%) in children with a baseline zinc <7.65 µmol·L-1 and by 49% (P < 0.05; 95%CI 24 to 66%) in children > 11 mo of age. Zinc supplementation resulted in a 38% (P < 0.05 95%CI 8 to 59%) reduction in the incidence of DD in boys. There was no effect on PD among children 6–11 mo old or on DD in girls. In conclusion, zinc supplementation had a significant impact on the incidence of persistent diarrhea in children > 1 y old and in children with low plasma zinc, as well as on dysentery in boys. These findings may have important implications for reducing diarrhea-related morbidity and mortality.

Zinc Intake and Plasma Zinc Level are Maintained in Men Consuming Cholesterol-Lowering Diets

Objective Reduced zinc intake has been reported when cholesterol-lowering diets are adopted. This study examined whether such diets compromise the zinc status of men with hypercholesterolemia. Design Zinc intake on baseline 4-day food records and baseline plasma zinc levels were compared with intake and levels 12 and 24 months after subjects adopted a low-fat, increased-fiber diet. Dietary fiber intake, supplement use, alcohol intake, and exercise were evaluated as possible confounding variables. Subjects Subjects were free-living men (n=365) with baseline cholesterol level above the 75th percentile who were participants in a randomized trial comparing cholesterol-lowering diets with goals of 30%, 26%, 22%, and 18% of energy from fat and 300, 200, 100, and 100 mg cholesterol, respectively. Statistical analyses Data were analyzed using two sample t tests, multiple linear regression, and analysis of variance. Results For all subjects combined, mean fat and cholesterol intakes approached or met the guidelines of the National Cholesterol Education Program step 2 diet, with approximately 30 g fiber per day. Density (mg/1,000 kcal) of zinc intake was unchanged from the baseline value. We found a slightly positive relationship between fiber and zinc intakes; no relationship between fiber intake and plasma zinc level; no effect of supplement use (category included all types of supplements), alcohol use, or level of exercise on plasma zinc levels; and no difference by dietary assignment in zinc intake or plasma zinc levels. Application Zinc status does not appear to be at risk in adult men who adopt cholesterol-lowering diets. These results may not be generalized to higher-risk population groups or situations in which dietary counseling is less comprehensive. J Am Diet Assoc. 1995; 95:1274-1279.