Zinc for prevention and treatment of the common cold.

BACKGROUND: The common cold is an acute, self-limiting viral respiratory illness. Symptoms include nasal congestion and mucus discharge, sneezing, sore throat, cough, and general malaise. Given the frequency of colds, they are a public health burden and a significant cause of lost work productivity and school absenteeism. There are no established interventions to prevent colds or shorten their duration. However, zinc supplements are commonly recommended and taken for this purpose. OBJECTIVES: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS to 22 May 2023, and searched Web of Science Core Collection and two trials registries to 14 June 2023. We also used reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children or adults that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI). We excluded zinc interventions in which zinc was combined with other minerals, vitamins, or herbs (e.g. a multivitamin, or mineral supplement containing zinc). DATA COLLECTION AND ANALYSIS: We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We independently extracted data. When necessary, we contacted study authors for additional information. We assessed zinc (type and route) with placebo in the prevention and treatment of the common cold. Primary outcomes included the proportion of participants developing colds (for analyses of prevention trials only), duration of cold (measured in days from start to resolution of the cold), adverse events potentially due to zinc supplements (e.g. unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhoea), and adverse events considered to be potential complications of the common cold (e.g. respiratory bacterial infections). MAIN RESULTS: We included 34 studies (15 prevention, 19 treatment) involving 8526 participants. Twenty-two studies were conducted on adults and 12 studies were conducted on children. Most trials were conducted in the USA (n = 18), followed by India, Indonesia, Iran, and Turkey (two studies each), and Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, and the UK (one study each). The 15 prevention studies identified the condition as either common cold (n = 8) or URTI (n = 7). However, almost all therapeutic studies (17/19) focused on the common cold. Most studies (17/34) evaluated the effectiveness of zinc administered as lozenges (3 prevention; 14 treatment) in acetate, gluconate, and orotate forms; gluconate lozenges were the most common (9/17). Zinc gluconate was given at doses between 45 and 276 mg/day for between 4.5 and 21 days. Five (5/17) lozenge studies gave acetate lozenges and two (2/17) gave both acetate and gluconate lozenges. One (1/17) lozenge study administered intranasal (gluconate) and lozenge (orotate) zinc in tandem for cold treatment. Of the 17/34 studies that did not use lozenges, 1/17 gave capsules, 3/17 administered dissolved powders, 5/17 gave tablets, 4/17 used syrups, and 4/17 used intranasal administration. Most studies were at unclear or high risk of bias in at least one domain. There may be little or no reduction in the risk of developing a cold with zinc compared to placebo (risk ratio (RR) 0.93, 95% CI 0.85 to 1.01; I2 = 20%; 9 studies, 1449 participants; low-certainty evidence). There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow-up (mean difference (MD) -0.90, 95% CI -1.93 to 0.12; I2 = 96%; 2 studies, 1284 participants; low-certainty evidence). When colds occur, there is probably little or no difference in the duration of colds in days (MD -0.63, 95% CI -1.29 to 0.04; I² = 77%; 3 studies, 740 participants; moderate-certainty evidence), and there may be little or no difference in global symptom severity (standardised mean difference (SMD) 0.04, 95% CI -0.35 to 0.43; I² = 0%; 2 studies, 101 participants; low-certainty evidence). When zinc is used for cold treatment, there may be a reduction in the mean duration of the cold in days (MD -2.37, 95% CI -4.21 to -0.53; I² = 97%; 8 studies, 972 participants; low-certainty evidence), although it is uncertain whether there is a reduction in the risk of having an ongoing cold at the end of follow-up (RR 0.52, 95% CI 0.21 to 1.27; I² = 65%; 5 studies, 357 participants; very low-certainty evidence), or global symptom severity (SMD -0.03, 95% CI -0.56 to 0.50; I² = 78%; 2 studies, 261 participants; very low-certainty evidence), and there may be little or no difference in the risk of a change in global symptom severity (RR 1.02, 95% CI 0.85 to 1.23; 1 study, 114 participants; low-certainty evidence). Thirty-one studies reported non-serious adverse events (2422 participants). It is uncertain whether there is a difference in the risk of adverse events with zinc used for cold prevention (RR 1.11, 95% CI 0.84 to 1.47; I2 = 0%; 7 studies, 1517 participants; very low-certainty evidence) or an increase in the risk of serious adverse events (RR 1.67, 95% CI 0.78 to 3.57; I2 = 0%; 3 studies, 1563 participants; low-certainty evidence). There is probably an increase in the risk of non-serious adverse events when zinc is used for cold treatment (RR 1.34, 95% CI 1.15 to 1.55; I2 = 44%; 2084 participants, 16 studies; moderate-certainty evidence); no treatment study provided information on serious adverse events. No study provided clear information about adverse events considered to be potential complications of the common cold. AUTHORS' CONCLUSIONS: The findings suggest that zinc supplementation may have little or no effect on the prevention of colds but may reduce the duration of ongoing colds, with an increase in non-serious adverse events. Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold.

Differential Protective Effect of Zinc and Magnesium for the Hepatic and Renal Toxicity Induced by Acetaminophen and Potentiated with Ciprofloxacin in Rats.

Background and Objectives: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. Material and Methods: The experiment was performed on five animal groups: group 1-control, treated for 6 weeks with normal saline, 1 mL/kg; group 2-AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3-AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4-AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl2 10 mg/ kg/day was added; and group 5-AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (p < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < p < 0.01 and 0.01 < p < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < p < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < p < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < p < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < p < 0.05 group 5 vs. group 4). Conclusions: This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney's function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.

Eficacia del apósito de gluconato de clorhexidina sobre las infecciones relacionadas con el catéter de hemodiálisis / Efficacy of Chlorhexidine Gluconate Dressing on Catheter-Related Infections in Hemodialysis

Introducción: El uso de catéteres venosos centrales para hemodiálisis se relaciona con un mayor desarrollo de complicaciones infecciosas, por lo que las Guías de Práctica Clínica recomiendan diferentes estrategias para disminuir dichas complicaciones, sin indicación clara sobre el apósito a utilizar en la cura del orificio de salida. Objetivo: Comparar la tasa de infecciones relacionadas con el catéter de dos pautas de cura del orificio de salida del catéter venoso central de hemodiálisis: apósito con gluconato de clorhexidina al 2% frente a clorhexidina en solución al 2%, cubierta con apósito de poliuretano semipermeable autoadhesivo. Material y Método: Estudio experimental, controlado, aleatorizado en pacientes en hemodiálisis a través de catéter venoso central para comparar dos pautas de cura, grupo control: clorhexidina en solución al 2% cubierta con apósito de poliuretano semipermeable autoadhesivo y grupo intervención: apósito con gluconato de clorhexidina al 2%. Se recogieron datos socioclínicos y relacionados con las complicaciones infecciosas. Se realizó un análisis descriptivo e inferencial.. Resultados: Se estudiaron 50 pacientes, 25 en cada grupo. El grupo intervención presentó dos infecciones del orificio de salida y el grupo control, presentó doce casos (OR: 0,176, IC 95%: 0,039-0,790; p=0,013). El grupo intervención presentó un caso de bacteriemia frente a dos episodios del grupo control (OR: 0,533, IC 95%: 0,048-5,892; p=ns). Conclusión: La cura con apósito con gluconato de clorhexidina al 2% es una medida protectora frente a la infección del orificio de salida en comparación con la cura con clorhexidina en solución al 2% y apósito de poliuretano. (AU)

Introduction: The use of central venous catheters for hemodialysis is associated with a higher incidence of infectious complications, leading Clinical Practice Guidelines to recommend various strategies to reduce such complications, with no clear indication of the dressing to use for catheter exit site care. Objectives: To compare the infection rate related to the catheter exit site using two different protocols: dressing with 2% chlorhexidine gluconate versus 2% chlorhexidine solution, both covered with self-adhesive semi-permeable polyurethane dressing for central venous catheters used in hemodialysis. Material and Method: An experimental, controlled, randomized study was conducted in hemodialysis patients with central venous catheters to compare two care protocols. The control group received a 2% chlorhexidine solution covered with a self-adhesive semi-permeable polyurethane dressing, while the intervention group received a dressing with 2% chlorhexidine gluconate. Socio-clinical and infection-related data were collected, and descriptive and inferential analyses were performed. Results: A total of 50 patients were studied, with 25 in each group. The intervention group had two exit site infections, while the control group had twelve cases (OR: 0.176, 95% CI: 0.039-0.790; p=0.013). The intervention group had one case of bacteremia compared to two cases in the control group (OR: 0.533, 95% CI: 0.048-5.892; p=ns). Conclusion: Dressing with 2% chlorhexidine gluconate is a protective measure against exit site infection compared to dressing with 2% chlorhexidine solution and polyurethane dressing. (AU)

Effect of Saline vs Gluconate/Acetate-Buffered Solution vs Lactate-Buffered Solution on Serum Chloride Among Children in the Pediatric Intensive Care Unit: The SPLYT-P Randomized Clinical Trial.

Importance: Most children admitted to pediatric intensive care units (PICUs) receive intravenous fluids. A recent systematic review suggested mortality benefit in critically ill adults treated with balanced solutions compared with sodium chloride, 0.9% (saline). There is a lack of clinically directive data on optimal fluid choice in critically ill children. Objective: To determine if balanced solutions decrease the rise of plasma chloride compared with saline, 0.9%, in critically ill children. Design, Setting, and Participants: This single-center, 3-arm, open-label randomized clinical trial took place in a 36-bed PICU. Children younger than 16 years admitted to the PICU and considered to require intravenous fluid therapy by the treating clinician were eligible. Children were screened from November 2019 to April 2021. Interventions: Enrolled children were 1:1:1 allocated to gluconate/acetate-buffered solution, lactate-buffered solution, or saline as intravenous fluids. Main Outcomes and Measures: The primary outcome was an increase in serum chloride of 5 mEq/L or more within 48 hours from randomization. New-onset acute kidney injury, length of hospital and intensive care stay, and intensive care-free survival were secondary outcomes. Results: A total of 516 patients with a median (IQR) age of 3.8 (1.0-10.4) years were randomized with 178, 171, and 167 allocated to gluconate/acetate-buffered solution, lactate-buffered solution, and saline, respectively. The serum chloride level increased 5 mEq/L or more in 37 patients (25.2%), 34 patients (23.9%), and 58 patients (40.0%) in the gluconate/acetate-buffered solution, lactate-buffered solution, and saline groups. The odds of a rise in plasma chloride 5 mEq/L or more was halved with the use of gluconate/acetate-buffered solution compared with saline (odds ratio, 0.50 [95% CI, 0.31-0.83]; P = .007) and with the use of lactate-buffered solution compared with saline (odds ratio, 0.47 [95% CI, 0.28-0.79]; P = .004). New-onset acute kidney injury was observed in 10 patients (6.1%), 6 patients (3.7%), and 5 patients (3.2%) in the gluconate/acetate-buffered solution, lactate-buffered solution, and saline groups, respectively. Conclusions and Relevance: Balanced solutions (gluconate/acetate-buffered solution and lactate-buffered solution) administered as intravenous fluid therapy reduced the incidence of rise in plasma chloride compared with saline in children in PICU. Trial Registration: anzctr.org.au Identifier: ACTRN12619001244190.

Immunomodulatory and clinical responses to zinc gluconate supplementation in patients with Behçet's disease: A double-blind, randomized placebo-controlled clinical trial.

BACKGROUND & AIMS: Toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of Behçet's disease (BD). The current study aimed to investigate the effect of zinc supplementation on TLR-2/4 expression and the clinical manifestations of BD. METHODS: In this double-blind placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day) or placebo groups for 12 weeks. Before and after the intervention, the surface and mRNA expression level of TLR-2 and TLR-4 in the leukocytes, serum level of zinc and tumor necrosis factor-α (TNF-α), quality of life, anthropometric measures, and blood pressure of patients were collected. BD activity was studied using the nonocular Iranian Behçet's disease dynamic activity measure (IBDDAM), Behçet's disease current activity form (BDCAF), and total inflammatory activity index (TIAI) at the pre-and post-intervention phases. The effect sizes were compared between two groups using analysis of covariance. RESULTS: There were significant decrease in TLR-2 mRNA (P = 0.038) and protein expression (P = 0.034) and nonocular IBDDAM score (P = 0.046) in the zinc group compared to placebo at the endpoint. The serum level of zinc was increased in the zinc group (P < 0.001). Zinc supplementation significantly decreased the TLR-4 surface (P = 0.012) and mRNA expression (P = 0.028) within the group. However, this decrease was not significant compared to the placebo group. There was no significant difference between the two groups regarding the serum level of TNF-α, BDCAF, TIAI, quality of life, anthropometric measures, and blood pressure (P > 0.05). CONCLUSIONS: The present study revealed that zinc supplementation significantly improved nonocular IBDDAM score and TLR-2 expression in BD patients. GOV REGISTRATION NUMBER: NCT05098678.

Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults.

BACKGROUND: Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute kidney injury or death is uncertain. METHODS: In a double-blind, randomized, controlled trial, we assigned critically ill patients to receive BMES (Plasma-Lyte 148) or saline as fluid therapy in the intensive care unit (ICU) for 90 days. The primary outcome was death from any cause within 90 days after randomization. Secondary outcomes were receipt of new renal-replacement therapy and the maximum increase in the creatinine level during ICU stay. RESULTS: A total of 5037 patients were recruited from 53 ICUs in Australia and New Zealand - 2515 patients were assigned to the BMES group and 2522 to the saline group. Death within 90 days after randomization occurred in 530 of 2433 patients (21.8%) in the BMES group and in 530 of 2413 patients (22.0%) in the saline group, for a difference of -0.15 percentage points (95% confidence interval [CI], -3.60 to 3.30; P = 0.90). New renal-replacement therapy was initiated in 306 of 2403 patients (12.7%) in the BMES group and in 310 of 2394 patients (12.9%) in the saline group, for a difference of -0.20 percentage points (95% CI, -2.96 to 2.56). The mean (±SD) maximum increase in serum creatinine level was 0.41±1.06 mg per deciliter (36.6±94.0 µmol per liter) in the BMES group and 0.41±1.02 mg per deciliter (36.1±90.0 µmol per liter) in the saline group, for a difference of 0.01 mg per deciliter (95% CI, -0.05 to 0.06) (0.5 µmol per liter [95% CI, -4.7 to 5.7]). The number of adverse and serious adverse events did not differ meaningfully between the groups. CONCLUSIONS: We found no evidence that the risk of death or acute kidney injury among critically ill adults in the ICU was lower with the use of BMES than with saline. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; PLUS ClinicalTrials.gov number, NCT02721654.).

Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial.

Importance: There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. Objective: To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. Design, Setting, and Participants: This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Intervention: Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. Outcomes: The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. Results: A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. Conclusions and Relevance: In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342728.

Effect of zinc on oropharyngeal mucositis in children with acute leukemia undergoing chemotherapy

BACKGROUND: Oropharyngeal mucositis (OM) is one of the main side-effects of oncological therapy. There is no treatment to prevent its occurrence, but some zinc-based therapies have been proven to help in decreasing its in-tensity. The objective of this study was to determine the effect of zinc in OM in children with acute leukemia in the early stages of oncological treatment. MATERIAL AND METHODS: This quasi-experimental study evaluated OM in 2 groups (control group: conventional hospital management, and experimental group: administration of 50 mg of zinc gluconate daily plus conventional hospital management). OM severity was recorded at a two-month follow-up. RESULTS: Forty-nine patients (26 in the control group and 23 in the experimental group) were included. The mean age of the patients was 11.1 ± 2.7 years; 65.3% had a diagnosis of pre-B acute lymphoblastic leukemia. The incidences of OM in the control group and the experimental group were 46.2% and 26.1%, respectively, but the difference was not significant. Based on a negative binomial regression model, females had, on average, 1.5 more days with OM (p = 0.002), and patients assigned to the experimental group had, on average, 2 less days with OM than the control group (p = 0.001). The pain score was higher in the control group (p = 0.0009), as was the mean score on the WHO scale (p = 0.0012). CONCLUSIONS: Zinc facilitated a reduction in the severity and duration of OM; further studies focusing on children are needed to confirm the effects of this trace element

No disponible

A pilot study on secondary anemia in "frailty" patients treated with Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine: safety of treatment explored by HRV non-linear analysis as predictive factor of cardiovascular tolerability.

OBJECTIVE: Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. PATIENTS AND METHODS: In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. RESULTS: Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. CONCLUSIONS: Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.

Effects of zinc supplementation on lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Findings on the effects of zinc supplementation on the lipid profile in patients with type 2 diabetes mellitus (T2DM) are conflicting. The current comprehensive systematic review and meta-analysis aimed to summarize available evidence in this regard. METHODS AND RESULTS: After a systematic search in the online databases, we included the randomized controlled trials (RCTs) investigating the effect of zinc supplementation on lipid profile [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)] in patients with T2DM. Altogether, 9 studies with a total sample size of 424 patients with T2DM were included in the analysis. Combining 9 effect sizes from 9 RCTs, we found a significant lowering effect of zinc supplementation on serum levels of TG (weighted mean difference (WMD): -17.08, 95% CI: -30.59, -3.58 mg/dL, P = 0.01) and TC (WMD: -26.16, 95% CI: -49.69, -2.62 mg/dL, P = 0.02). Although the overall effect of zinc supplementation on LDL-C levels was not significant, a beneficial effect was seen in studies that administered <100 mg/d zinc. Based on the non-linear dose-response analysis, a greater reduction in serum levels of TC and LDL-C following zinc supplementation was seen at <12 weeks' duration of intervention. Unlike the overall effect size, we found a significant increasing effect of zinc supplementation on serum HDL-C concentrations in most subgroups of RCTs according to the subgroup analyses. CONCLUSION: We found that zinc supplementation may beneficially influence lipid profile in patients with T2DM.

Zinc gluconate supplementation impacts the clinical improvement in patients with ulcerative colitis.

Ulcerative colitis is an inflammatory bowel disease that affects the mucous membrane of the colon. The pathogenesis is not clear, but there is evidence of a complex interaction between genetic, environmental, and immunological factors. In this regard, we highlight the role of zinc in the immune system and probable control of the disease. This study evaluated the effect of zinc supplementation on the inflammatory response in patients with ulcerative colitis. A blind interventional study involving 41 patients of both sexes, who underwent either zinc gluconate supplementation (n = 23), or treatment with a placebo (corn starch) (n = 18). Patients were evaluated for dietary zinc intake, plasma and erythrocyte zinc concentrations, and serum levels of Th1/Th2/Th17 type cytokines at baseline (T0) and 30 (T1) and 60 (T2) days after intervention. Patients in the zinc supplementation group had a lower probability of having an adequate zinc intake than placebo. In this same group, there was a significant difference between plasma zinc concentrations (T1 in relation to T0, T2 in relation to T1, and T2 in relation to T0) and erythrocyte zinc (T1 in relation to T0 and T2 in relation to T1). Zinc supplementation resulted in significant changes in the concentrations of IL-2 and IL-10 without differences in the other interleukins. Zinc gluconate intervention in patients with ulcerative colitis improves the nutritional status of this mineral in these patients and positively influences their clinical outcome, reinforcing the role of zinc as an important dietary component in disease control.

0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) is an important complication encountered during the course of diabetic ketoacidosis (DKA). Plasma-Lyte with lower chloride concentration than saline has been shown to be associated with reduced incidence of AKI in adults with septic shock. No study has compared this in DKA. METHODS: This double-blind, parallel-arm, investigator-initiated, randomized controlled trial compared 0.9% saline with Plasma-Lyte-A as initial fluid in pediatric DKA. The study was done in a tertiary care, teaching, and referral hospital in India in children (> 1 month-12 years) with DKA as defined by ISPAD. Children with cerebral edema or known chronic kidney/liver disease or who had received pre-referral fluids and/or insulin were excluded. Sixty-six children were randomized to receive either Plasma-Lyte (n = 34) or 0.9% saline (n = 32). MAIN OUTCOMES: Primary outcome was incidence of new or progressive AKI, defined as a composite outcome of change in creatinine (defined by KDIGO), estimated creatinine clearance (defined by p-RIFLE), and NGAL levels. The secondary outcomes were resolution of AKI, time to resolution of DKA (pH > 7.3, bicarbonate> 15 mEq/L & normal sensorium), change in chloride, pH and bicarbonate levels, proportion of in-hospital all-cause mortality, need for renal replacement therapy (RRT), and length of ICU and hospital stay. RESULTS: Baseline characteristics were similar in both groups. The incidence of new or progressive AKI was similar in both [Plasma-Lyte 13 (38.2%) versus 0.9% saline 15 (46.9%); adjusted OR 1.22; 95% CI 0.43-3.43, p = 0.70]. The median (IQR) time to resolution of DKA in Plasma-Lyte-A and 0.9% saline were 14.5 (12 to 20) and 16 (8 to 20) h respectively. Time to resolution of AKI was similar in both [Plasma-Lyte 22.1 versus 0.9% saline 18.8 h (adjusted HR 1.72; 95% CI 0.83-3.57; p = 0.14)]. Length of hospital stay was also similar in both [Plasma-Lyte 9 (8 to 12) versus 0.9% saline 10 (8.25 to 11) days; p = 0.39]. CONCLUSIONS: The incidence of new or progressive AKI and resolution of AKI were similar in both groups. Plasma-Lyte-A was similar to 0.9% Saline in time to resolution of DKA, need for RRT, mortality, and lengths of PICU and hospital stay. TRIAL REGISTRATION: Clinical trial registry of India, CTRI/2018/05/014042 (ctri.nic.in) (Retrospectively registered).

Brief Report: Zinc Supplementation and Inflammation in Treated HIV.

OBJECTIVE: In this study, we explored the effect of zinc supplementation on markers of inflammation and monocyte activation in antiretroviral therapy-treated HIV infection. METHODS: This is a phase I open-labeled randomized double-arm study, exploring the efficacy and safety of zinc supplementation on inflammation in ≥18-year-old people living with HIV in the US, on stable antiretroviral therapy and with zinc levels ≤75 µg/dL in the last 60 days. Patients were randomized 1:1 to zinc gluconate capsules at a dose of 45 mg (low-dose), or 90 mg (high-dose) elemental zinc daily for 16 weeks. We assessed inflammatory and gut integrity biomarkers at baseline and 16 weeks. RESULTS: Overall, a total of 52 participants were enrolled (25 participants in the low-dose arm and 27 participants in the high-dose arm). Median (Interquartile range) age was 49 (38, 60) years, 77% were men and 73% were African Americans. At baseline, median zinc levels were 73 (64, 86) µg/dL. Median circulating zinc levels increased to 91 µg/dL in the low-dose arm and to 100 µg/dL in the high-dose arm. Overall, 48%-60% of participants experienced a reduction in biomarkers levels. The margin of reduction ranged between 8% and 21%. This change was meaningful with large effect size (Cohen D ranging from 5 to 19). CONCLUSIONS: In this pilot study, we found that zinc supplementation is effective at increasing circulating zinc levels. In addition, our findings provide novel data suggesting that zinc can affect a biological signature in people living with HIV and modulate biomarkers associated with clinical comorbidities.

Gluconate suppresses seizure activity in developing brains by inhibiting CLC-3 chloride channels.

Neonatal seizures are different from adult seizures, and many antiepileptic drugs that are effective in adults often fail to treat neonates. Here, we report that gluconate inhibits neonatal seizure by inhibiting CLC-3 chloride channels. We detect a voltage-dependent outward rectifying Cl- current mediated by CLC-3 Cl- channels in early developing brains but not adult mouse brains. Blocking CLC-3 Cl- channels by gluconate inhibits seizure activity both in neonatal brain slices and in neonatal animals with in vivo EEG recordings. Consistently, neonatal neurons of CLC-3 knockout mice lack the outward rectifying Cl- current and show reduced epileptiform activity upon stimulation. Mechanistically, we demonstrate that activation of CLC-3 Cl- channels alters intracellular Cl- homeostasis and enhances GABA excitatory activity. Our studies suggest that gluconate can suppress neonatal seizure activities through inhibiting CLC-3 Cl- channels in developing brains.

The Effect of Zinc Gluconate Supplementation on Symptoms and Tongue Epithelium Regeneration in Non-psoriatic Patients with Migratory Glossitis.

The aim of this study was to evaluate zinc gluconate as a treatment option in patients with symptomatic migratory glossitis (MG). Using simple random sampling, 28 non-psoriatic patients with symptomatic MG were divided into a test and control group. The test group took 20 mg/day of chelated zinc gluconate for one month, and was put on a diet rich in zinc. The control group was only put on a diet rich in zinc. Changes in the size of red atrophied areas (width and length) and the intensity of symptoms were evaluated as primary and secondary outcomes, respectively, at baseline, after therapy, and one month later. In the test group, the mean value of the red atrophy area width and length displayed some significant reduction as a primary outcome. There were no significant changes in the size of red patches in the control group. Secondary outcome showed that the intensity of subjective symptoms in the test group significantly decreased (P=0.042) compared with controls. The filiform papillae had partially or completely regenerated in 85.7% of cases in the test group and in 23.1% of the controls (P=0.001). Red patches with raised keratotic rims may have healed spontaneously and reappeared in constantly changing patterns that are typical for MG. This phenomenon was not observed in patients supplemented with zinc, and new atrophy areas occurred in only one case. Low-dose zinc gluconate.

Plasma-Lyte 148 vs. Hartmann's solution for cardiopulmonary bypass pump prime: a prospective double-blind randomized trial.

BACKGROUND: The mechanisms of acid-base changes during cardiopulmonary bypass (CPB) remain unclear. We tested the hypothesis that, when used as CPB pump prime solutions, Plasma-Lyte 148 (PL) and Hartmann's solution (HS) have differential mechanisms of action in their contribution to acid-base changes. METHODS: We performed a prospective, double-blind, randomized trial in adult patients undergoing elective cardiac surgery with CPB. Participants received a CPB prime solution of 2000 mL, with either PL or HS. The primary endpoint was the standard base excess (SBE) value measured at 60 minutes after full CPB flows (SBE60min). Secondary outcomes included changes in SBE, pH, chloride, sodium, lactate, gluconate, acetate, strong ion difference and strong ion gap at two (T2min), five (T5min), ten (T10min), thirty (T30min) and sixty (T60min) minutes on CPB. The primary outcome was measured using a two-tailed Welch's t-test. Repeated measures ANOVA was used to test for differences between time points. RESULTS: Twenty-five participants were randomized to PL and 25 to HS. Baseline characteristics, EURO and APACHE scores, biochemistry, hematology and volumes of cardioplegia were similar. Mean (SD) SBE at T60min was -1.3 (1.4) in the PL group and -0.1 (2.7) in the HS group; p=0.55. No significant differences in SBE between the groups was observed during the first 60 minutes (p=0.48). During CPB, there was hyperacetatemia and hypergluconatemia in the PL group and hyperlactatemia and hyperchloremia in the HS group. No significant difference between the groups in plasma bicarbonate levels and total weak acid levels were found. Complications and intensive care unit and hospital length of stays were similar. CONCLUSIONS: During CPB, PL and HS did not cause a significant metabolic acidosis. There was hyperacetatemia and hypergluconatemia with PL and hyperchloremia and hyperlactatemia with HS. These physiochemical effects appear clinically innocuous.

Atividade in vitro do extrato etanólico de própolis e do digluconato de clorexidina sobre as espécies de Candida isoladas da mucosa bucal de pacientes internados em Unidade de Terapia Intensiva (UTI) / In vitro activity of ethanolic extract of propolis and chlorhexidine digluconate on Candida species isolated from the oral mucosa of patients hospitalized in the Intensive Care Unit (ICU)

Avaliou-se a atividade dos extratos de própolis e digluconato de clorexidina em Candida sp isoladas da mucosa bucal de pacientes em UTI. Foram determinadas as concentrações fungicidas mínimas (CFM) e comparadas, nas doses sub-inibitórias, à produção de exoenzimas proteinase e fosfolipase e formação de franjas. Em 72 isolados foram avaliadas a atividade antifúngica pela técnica de microdiluição em série, na “base 2”, a produção das exoenzimas proteinase e fosfolipase, e a formação de franjas, antes e após a exposição às própolis e clorexidina. Dos 72 isolados, 53 eram C. albicans, 11 C. tropicalis, quatro C. guilhermondii e quatro sugestivas de C. dubliniensis. CFM 90% do extrato de própolis foi de 5% para C. albicans, 20% C. tropicalis, 0,625% C. guilhermondii e 0,312% sugestivas de C. dubliniensis. CFM 90% da clorexidina foi de 0,0018% para C. albicans, 0,012% C. tropicalis, de 0,0018% C. guilhermondii e de 0,00375% sugestivas de C. dubliniensis. Ocorreu inibição das exoenzimas e franjas, em ambos os produtos. Apesar da inibição da clorexidina ser menor que a da própolis, seu uso diário não causa efeitos colaterais indesejáveis como manchas nos dentes e na língua, perda do paladar e sensação de queimação na mucosa bucal.

The activity of propolis extract and chlorhexidine digluconate on Candida sp isolated from oral mucosa of patients in ICU was evaluated. The minimum fungicidal concentrations (MFC) were determined, and also the production of proteinase and phospholipase exoenzymes and the fringe formation. Seventy-two isolates were used and identified by the API 20C AUX® System. The antifungal activity was evaluated by “at base 2” serial microdilution technique. Also the exoenzymes production (proteinase and phospholipase), the fringes formation, before and after being exposed to propolis and chlorhexidine, were analysed. Of 72 isolates, 53 were C. albicans, 11 C. tropicalis, four C. guilhermondii and four suggestive C. dubliniensis. The MFC 90% of propolis extract was 5% C. albicans, 20% C. tropicalis, 0.625% C. guilhermondii; and 0.312% suggestive of C. dubliniensis. MFC 90% of chlorhexidine was 0.0018% C. albicans, 0.012% C. tropicalis, 0.0018% C. guilhermondii and 0.00375% suggestive of C. dubliniensis. The inhibition of exoenzymes and fringes occurred in the both products. Although the inhibition of chlorhexidine is lower than that showed by propolis, its daily use neither cause undesirable side effects as blemishes on the teeth and tongue, nor the loss of the taste and the burning sensation in the oral mucosa.