Zinc (Acetate)

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily zinc supplements have been reported to prevent acute lower respiratory tract infection (LRTI) and reduce child mortality. This is an update of a review first published in 2010. OBJECTIVES: To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months. SEARCH METHODS: We searched CENTRAL (Issue 21 October 2016), MEDLINE (1966 to October 2016), Embase (1974 to October 2016), LILACS (1982 to October 2016), CINAHL (1981 to October 2016), Web of Science (1985 to October 2016) and IMSEAR (1980 to October 2016). SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating zinc supplementation for the prevention of pneumonia in children aged from 2 months to 59 months. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We did not identify any new studies for inclusion in this update. We included six studies that involved 5193 participants.Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (fixed-effect risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, six studies, low-quality evidence) and prevalence of pneumonia by 41% (random-effects RR 0.59; 95% CI 0.35 to 0.99, one study, n = 609, low-quality evidence). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (fixed-effect RR 0.79; 95% CI 0.0.71 to 0.88, four studies, n = 3261), but had no effect on lower specificity pneumonia case definition (i.e. age-specific fast breathing with or without lower chest indrawing) (fixed-effect RR 0.95; 95% CI 0.86 to 1.06, four studies, n = 1932). AUTHORS' CONCLUSIONS: Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia.

BACKGROUND: Otitis media is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent otitis media. OBJECTIVES: To evaluate whether zinc supplements prevent otitis media in adults and children of different ages. SEARCH METHODS: We searched CENTRAL (2014, Issue 1), MEDLINE (1950 to February week 4, 2014) and EMBASE (1974 to March 2014). SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing otitis media. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate. MAIN RESULTS: No new trials were identified for inclusion in this update. We identified 12 trials for inclusion, 10 of which contributed outcomes data. There were a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc-supplemented and placebo groups in the numbers of participants experiencing an episode of definite otitis media during follow-up (3191 participants); another trial showed a significantly lower incidence rate of otitis media in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of otitis media (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the

BACKGROUND: Haemoglobinopathies, inherited disorders of haemoglobin synthesis (thalassaemia) or structure (sickle cell disease), are responsible for significant morbidity and mortality throughout the world. The WHO estimates that, globally, 5% of adults are carriers of a haemoglobin condition, 2.9% are carriers of thalassaemia and 2.3% are carriers of sickle cell disease. Carriers are found worldwide as a result of migration of various ethnic groups to different regions of the world. Zinc is an easily available supplement and intervention programs have been carried out to prevent deficiency in people with thalassaemia or sickle cell anaemia. It is important to evaluate the role of zinc supplementation in the treatment of thalassaemia and sickle cell anaemia to reduce deaths due to complications. OBJECTIVES: To assess the effect of zinc supplementation in the treatment of thalassaemia and sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 01 February 2013. SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements for treating thalassaemia or sickle cell disease administered at least once a week for at least a month. DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and wrote the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate. MAIN RESULTS: We identified nine trials for inclusion with all nine contributing outcome data. Two trials reported on people with thalassaemia (n = 152) and seven on sickle cell anaemia (n = 307).In people with thalassaemia, in one trial, the serum zinc level value showed no difference between the zinc supplemented group and the control group, mean difference 47.40 (95% confidence interval -12.95 to 107.99). Regarding anthropometr

BACKGROUND: The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted in high-income countries since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. OBJECTIVES: To assess whether zinc (irrespective of the zinc salt or formulation used) is efficacious in reducing the incidence, severity and duration of common cold symptoms. In addition, we aimed to identify potential sources of heterogeneity in results obtained and to assess their clinical significance. SEARCH METHODS: In this updated review, we searched CENTRAL (2012, Issue 12), MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013), Web of Science (1985 to January 2013), LILACS (1982 to January 2013), WHO ICTRP and clinicaltrials.gov. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. MAIN RESULTS: Five trials were identified in the updated searches in January 2013 and two of them did not meet our inclusion criteria. We included 16 therapeutic trials (1387 participants) and two preventive trials (394 participants). Intake of zinc was associated with a significant reduction in the duration (days) (mean difference (MD) -1.03, 95% confidence interval (CI) -1.72 to -0.34) (P = 0.003) (I(2) statistic = 89%) but not the severity of common cold symptoms (MD -1.06, 95% CI -2.36 to 0.23) (P = 0.11) (I(2) statistic = 84%). The proportion of participants who were symptomatic after seven days of treatment was significantly smaller (odds ratio (OR) 0.45, 95% CI 0.20 to 1.00) (P = 0.05) than those in the control, (I(2 )statistic = 75%). The incidence rate ratio (IRR) of developing a cold (IRR 0.64, 95% CI 0.47 to 0.88) (P = 0.006) (I(2) statistic = 88%), school absence (P = 0.0003)

BACKGROUND: Otitis media (OM) is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent OM. OBJECTIVES: To evaluate whether zinc supplements prevent OM in adults and children of different ages. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 1) which includes the Cochrane Acute Respiratory Infections Groups' Specialised Register, MEDLINE (1950 to February week 1, 2012) and EMBASE (1974 to February 2012). SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing OM. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate. MAIN RESULTS: We identified 12 trials for inclusion, 10 of which contributed outcomes data. There was a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc supplemented and placebo groups in the numbers of participants experiencing an episode of definite OM during follow-up (3191 participants); another trial showed a significantly lower incidence rate of OM in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of OM (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and reduce child mortality. OBJECTIVES: To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January Week 2, 2010), EMBASE (1974 to January 2010) and LILACS (1985 to January 2010). SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating supplementation of zinc for the prevention of pneumonia in children aged 2 to 59 months of age. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included six trials and 7850 participants in the meta-analysis. Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, fixed-effect, six studies) and prevalence of pneumonia by 41% (RR 0.59; 95% CI 0.35 to 0.99, random-effects, one study). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (RR 0.79; 95% CI 0.0.71 to 0.88, fixed-effect, four studies, n = 4591) but had no effect on lower specificity pneumonia case definition (i.e. age specific fast breathing with or without lower chest indrawing) (RR 0.95; 95% CI 0.86 to 1.06, fixed-effect, four studies, n = 3259). AUTHORS' CONCLUSIONS: Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia, the leading cause of death in children.

BACKGROUND: Otitis media (inflammation of the middle ear, usually caused by infection) affects people of all ages, but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. Because zinc supplements prevent pneumonia in disadvantaged children, we wondered whether they prevent otitis media. OBJECTIVES: To evaluate whether zinc supplements prevent otitis media in adults and children of different ages. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2) which includes the Acute Respiratory Infection Groups' Specialised Register; MEDLINE (1950 to June Week 1 2009); and EMBASE (1974 to June 2009). SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing otitis media. DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and methodological quality of the included trials, extracted and analysed data and wrote the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate. MAIN RESULTS: We identified 12 trials for inclusion, 10 of which contributed outcomes data. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc supplemented and placebo groups in the numbers of participants experiencing an episode of definite otitis media during follow up (3191 participants), while another trial showed a significantly lower incidence rate of otitis media in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc on the mean number of episodes of otitis media (mean difference -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events, but a small minority of children were reported to have vomited shortly after ingestion of the sup

Acute watery diarrhoea (AWD) has not been well-treated with 20 mg elemental zinc, primarily because of adverse symptoms like vomiting. In contrast to 20 mg of zinc, this study sought to determine whether a lower dose of zinc, with or without probiotics, is as beneficial as 20 mg of zinc, yet tolerated better. The aim of this study was to compare the acceptability and efficacy of low-dose zinc (10 mg) with or without probiotics to the acceptability and efficacy of standard-dose zinc (20 mg) in children diagnosed with AWD. A prospective comparative study was conducted among children aged 6 months to 5 years with AWD at a tertiary healthcare centre. Eligible children were randomized into three groups: Group Z20 and Z10 were administered zinc acetate 20 mg/day and 10 mg/day, respectively, and Group Z10P with 10 mg/day with probiotics. Caregivers were followed daily via telephonic interviews for 14 days to record symptoms, adverse reactions, and treatment completion. Data were analyzed using Kruskal-Wallis test, one-way ANOVA, and the chi-square test. A total of 147 children were enrolled (49 in each group). The mean duration of AWD at enrollment was 3 ± 1.5 days, and the mean frequency was 5 ± 2 episodes/day. There was no significant difference in the mean duration of diarrhoea among the groups. The most common adverse reactions reported was vomiting (85%). Diarrhoea resolved within 3 days in 22.4% of Group Z10P, 10.2% of Group Z20, and 2% of Group Z10 (P = .03). Low-dose zinc (10 mg/day) was less effective than 20 mg zinc in controlling AWD. However, the combination of 10 mg zinc with probiotics significantly improved efficacy. © The Author(s) [2026]. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

INTRODUCTION: Zinc is a trace element with a key role in immune function and has demonstrated antiviral and anti-inflammatory properties. Low plasma zinc levels have been associated with poor outcomes in COVID-19. This study aims to evaluate the efficacy and safety of zinc supplementation as an adjuvant therapy in hospitalized patients with COVID-19. METHODS: A single-center, randomized, open-label clinical trial between May and December 2021. Adults hospitalized with confirmed COVID-19 requiring hospitalization were randomized 1:1 to receive standard of care (SoC) with or without oral zinc acetate (90 mg/day) for 14 days. The primary endpoint was disease progression, defined as critical care requirement (ICU admission) or death. Secondary outcomes included time to clinical recovery, hospital length of stay, WHO clinical scale improvement, inflammatory markers, antibody response, and safety. RESULTS: Seventy-one patients were randomized (35 zinc versus 34 SoC). Disease progression occurred in 5.7 % of the zinc group versus 23.5 % in the SoC group (OR 0.21, 95 %CI = 0.03-0.96,). Mean recovery time was significantly shorter in the zinc group (7.4 ± 6.1 versus 13.1 ± 9.7 days, p = 0.006) and a trend to a faster recovery was observed in the Cox proportional hazards model in the intervention group HR of 1.670 (95 % CI: 0.948-2.942), p = 0.076. WHO scale improvement attaining a < 1 points at day 14 was greater in the zinc group (74.3 % versus 42.4 %, p = 0.009). Antibody levels were higher in the SoC group at days 14 and 28. No adverse events were attributed to zinc. CONCLUSIONS: Adjunctive zinc supplementation to standard of care reduced disease progression and showed a trend to accelerated clinical recovery in hospitalized COVID-19 patients, supporting the potential role of zinc in managing viral respiratory infections. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05778383.

OBJECTIVE: This study evaluated the efficacy and safety of NPC-25, zinc histidine hydrate, in patients with hypozincemia. This randomized multicenter active-controlled open-label trial aimed to verify the non-inferiority of NPC-25 to NOBELZIN™, zinc acetate dihydrate. METHODS: Participants whose serum zinc concentrations were <70 μg/dL at two points within 8 weeks before the start of treatment were randomized 1:1 into the NPC-25 (active drug) administration group and the NOBELZIN™ (control drug) administration group, using dynamic allocation. The initial daily doses were 50 mg or 100 mg as the baseline serum zinc levels, and administration periods were set at maximum of 24 weeks with the goal of maintaining the target serum zinc concentration (≥80 and <200 μg/dL) for 8 weeks, with extension up to 52 weeks as needed in the NPC-25 group, but not the NOBELZIN group. The primary efficacy endpoint was the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dosage within 24 weeks after the start of administration. The key secondary endpoints were the cumulative achievement percentage for target serum zinc concentration at each observation time point, the cumulative achievement percentage for maintenance of target concentration for 8 weeks at the same dosage at each observation time point, change in mean serum zinc concentration, and comparison of dosage amount. Safety assessments included the incidence of adverse events and adverse drug reactions, as well as changes in clinical laboratory and physical measurements. RESULTS: For the primary endpoint for full analysis (FAS) set (n=103, NPC-25 group; n=107, NOBELZIN group), the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dose was 86.4 % (89/103) in the NPC-25 group and 80.4 % (86/107) in the NOBELZIN group, which confirmed the non-inferiority of NPC-25 to NOBELZIN™. For the secondary endpoint for FAS, at each observation point, although there was no significant difference between the two groups in the proportion of participants who achieved the target serum zinc concentration, there was a tendency that the maintena

BACKGROUND: This study aimed to compare the effects of three mucoadhesive gels containing lidocaine, zinc acetate, and tannic acid on the gag reflex of dental patients. METHODS: This randomized double-blind clinical trial was conducted on 228 dental patients with gag reflex. The patients were randomly assigned to four groups (n = 57) of placebo, 2% lidocaine, 2% tannic acid, and 2% zinc acetate. The severity of the gag reflex of patients was initially scored by stimulating their soft and hard palate with a radiographic film using a 0-5 visual analog scale. After 5 min, mucoadhesive gels containing 2% lidocaine, zinc acetate, or tannic acid were applied on the hard and soft palate for 5-10 min, and the severity of the gag reflex was scored again. Data were analyzed by ANOVA and paired t-test for the single group comparison (alpha = 0.05). RESULTS: The four groups had no significant difference in the baseline mean gag score (p = 0.05). The difference in the mean gag score was significant among the four groups after the intervention (p < 0.00), and the mean score in the experimental groups was significantly lower than that in the placebo group (p < 0.00). The difference in the mean gag score was not significant between the experimental groups (p > 0.05). CONCLUSIONS: The mucoadhesive gels containing 2% lidocaine, tannic acid, or zinc acetate significantly decreased the gag reflex in dental patients, with all three treatments showing comparable efficacy compared to the placebo. These findings suggest that each gel formulation is a viable alternative for managing the gag reflex during dental procedures. © 2024. The Author(s).

BACKGROUND: COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19. METHODS: Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 μg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality. RESULTS: 90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes. INTERPRETATION: In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility. TRIAL REGISTRATION NUMBER: NCT04780061. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

OBJECTIVES: Bad breath is a condition that negatively affects people's social interactions and quality of life. The aim of this study was to evaluate the effect of thyme mouthwash on intraoral halitosis, gingival index (GI) and plaque index (PI) in patients with gingivitis. METHODS: In this retrospective study, 60 gingivitis patients (30 women/30 men) received initial periodontal treatment followed by oral hygiene instructions (OHI) and then were divided into four groups: The control group (C) received only OHI, while chlorhexidine (CHX) mouthwash was prescribed to the CHX group, Zinc acetate and CHX diacetate mouthwash was prescribed to the zinc acetate and CHX diacetate (ZnA) group, and the thyme (T) group was instructed to use thyme mouthwash. GI, PI and volatile sulfur compound (VSC) values were recorded at baseline and at the first week of treatment. RESULTS: The initial values of the recorded parameters did not differ significantly between the groups. In all groups, VSCs, GI and PI decreased after treatment (p = 0.001). There was no significant difference between the PI values of the groups after treatment (p = 0.188). On the contrary, the GI and VSC values after treatment were significantly different between the groups (p = 0.001). GI values were highest in the control group and lowest in the CHX group. In terms of VSCs, a significant difference was found between groups T and C, and between groups T and ZnA (p = 0.001). CONCLUSION: This study showed that the use of thyme mouthwash after periodontal treatment was effective in improving bad breath and gingivitis in gingivitis patients. © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

This single-centre prospective feasibility study (UMIN000030232) evaluated whether zinc supplementation was safe and effective for improving outcomes among patients with acute myocardial infarction (AMI). Within 24 h after successful primary percutaneous coronary intervention, consenting patients with AMI were randomly assigned 1:1 to receive conventional treatment (conventional treatment group) or conventional treatment plus zinc acetate supplementation (zinc supplementation group). The two groups were compared in terms of major adverse cardiovascular events (MACE), and scar size, which was evaluated using cardiac magnetic resonance imaging (CMR) at 4 weeks after discharge. A total of 56 patients underwent randomization (with 26 assigned to the zinc supplementation group and 27 to the conventional treatment group). The two groups had generally similar laboratory findings and clinical characteristics. The two groups also had similar lengths of hospital stay and rates of MACE. Forty of the 53 patients underwent CMR and it revealed that % core zone was numerically lower in the zinc supplementation group than in the conventional treatment group (9.3 ± 6.9% vs. 14.2 ± 9.1%, P = 0.07). This small single-centre study failed to detect a significant reduction in mid-term MACE after AMI among patients who received zinc supplementation. © 2023. Springer Nature Japan KK, part of Springer Nature.

Zinc inhibits intestinal copper uptake, an effect utilized for treating Wilson's disease (WD). We used copper-64 (64Cu) PET/CT to examine how much four weeks of treatment with different zinc regimens reduced the hepatic 64Cu content after oral 64Cu administration and test if alternative regimens were noninferior to the standard regimen of zinc acetate 50 mg × 3 daily. Forty healthy persons were randomized to four different zinc protocols. The WD standard treatment zinc acetate 50 mg × 3 reduced the hepatic 64Cu content from 26.9 ± 7.5% to 13.3 ± 5.6% of the administered 64Cu. Zinc gluconate 50 mg × 3 was noninferior (P = 0.02) (35.8 ± 9.0% to 17.4 ± 7.5%). Zinc acetate 150 mg × 1 (33.1 ± 9.9% to 17.4 ± 7.5%) and zinc gluconate 150 mg × 1 (28.1 ± 6.7% to 22.0 ± 6.7%) were less effective. These effects were intra- and inter-individually highly variable, and 14% had no effect of any zinc regimen, which may explain disparities in zinc treatment efficacy in WD patients. © 2022. The Author(s).

Contrast-induced acute kidney injury (CI-AKI) is a prevalent cause of renal dysfunction among hospitalized patients, yet the precise pathogenesis and effective therapeutic strategies remain elusive. In this study, we investigated the role of tubular ferroptosis in both experimental CI-AKI models and in primary tubular epithelial cells (PTECs) treated with ioversol. Using whole exome sequencing, we identified metallothioneins (MTs) as being among the most significantly downregulated genes following ioversol exposure. Our findings reveal that overexpression of Mt1 mitigates, whereas suppression of Mt-1 exacerbates, ioversol-induced tubular ferroptosis. Interestingly, the level of MTF1 (metal regulatory transcription factor 1), a principal regulator of Mt1, was found to increase in response to ioversol treatment. We further elucidated that ioversol activates LATS1 (Large tumor suppressor homolog 1), a kinase that promotes the phosphorylation and nuclear translocation of MTF1, thereby inhibiting its transcriptional activity for Mt1. Both genetic and pharmacological inhibition of LATS1 reversed the ioversol-induced suppression of Mt-1. From a therapeutic perspective, the LATS1 inhibitor TDI-011536, in combination with zinc acetate, was administered to a rodent model of CI-AKI. Our data indicate that this combination synergistically upregulates Mt1 expression and provides protection against contrast media-induced tubular ferroptosis. In summary, our study demonstrates that the reduction of Mt-1 contributes to tubular ferroptosis associated with CI-AKI. We show that contrast media activate LATS1, which in turn suppresses the transcriptional activity of MTF1 for Mt1. Herein, the combination of zinc acetate and a LATS1 inhibitor emerges as a potential therapeutic approach for the treatment of CI-AKI.

Formation of bacterial biofilms is a major health threat due to their high levels of tolerance to multiple antibiotics and the presence of persisters responsible for infection relapses. We previously showed that a combination of starvation and induction of SOS response in biofilm led to increased levels of persisters and biofilm tolerance to fluoroquinolones. In this study, we hypothesized that inhibition of the SOS response may be an effective strategy to target biofilms and fluoroquinolone persister cells. We tested the survival of Escherichia coli biofilms to different classes of antibiotics in starved and nonstarved conditions and in the presence of zinc acetate, a SOS response inhibitor. We showed that zinc acetate potentiates, albeit moderately, the activity of fluoroquinolones against E. coli persisters in starved biofilms. The efficacy of zinc acetate to increase fluoroquinolone activity, particularly that of tosufloxacin, suggests that such a combination may be a potential strategy for treating biofilm-related bacterial infections.

This study is aimed to develop a long-acting injectable formulation in treatment of type II diabetes. A glucoregulatory polypeptide, exenatide (EXT), was chosen as the model drug, and an aqueous block copolymer system with a sol-gel transition upon the increase of temperature was selected as the delivery matrix of EXT. The thermoreversible hydrogel composed of poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was found to slower the degradation of the polypeptide to a large extent. However, the initial formulation in this study exhibited a significant drug burst effect, which is a common problem to load a hydrophilic small or medium-size polypeptide into a hydrogel. Zinc acetate was then introduced to slow down the EXT release by formation of insoluble Zn-EXT complexes in the thermogel matrix. Yet an incomplete release became another crucial problem, which is also common for peptide and protein delivery. The synergistic effect of three excipients (zinc acetate, PEG, and sucrose) under an appropriate condition overcame these two problems simultaneously, and the sustained release of drug lasted for 1 week. In vivo experiments via mice oral glucose tolerance tests demonstrated an improved glucose tolerance for 1 week after a single subcutaneous injection of the optimal EXT formulation. As a result, a formulation of antidiabetic drugs was set up, and meanwhile a strategy using synergistic excipients to adjust release profiles of peptides from hydrogels was put forward.

Mercury (Hg), widely used in industry, is a great environmental health problem for humans and animals. Despite several reports regarding Hg toxicity, there is scarcity of data on its toxic manifestations on Sprague Dawley rats under realistic exposure conditions. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Hg. The present work was aimed to study the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 2 mmol/kg ip), zinc (Zn; 2 mmol/kg po), and selenium (Se; 0.5 mg/kg po) against dimethylmercury (DMM; 1 mg/kg po)-intoxicated male rats for 12 weeks. Exposure to DMM caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control. The study results conclude that protective intervention of combined treatment of NAC, along with Zn and Se, is beneficial in attenuating DMM-induced systemic toxicity.

140. J Pharm Belg. 2009 Sep;(3):107-8. [Zinc acetate hydrate--oral administration (Wilzin)]. [Article in French] [No authors listed]

BACKGROUND/AIMS: Gingipains, proteolytic enzymes produced by the periodontal pathogen Porphyromonas gingivalis, are regarded as virulence factors in the pathogenesis of periodontitis. Inhibition of gingipain activity therefore may have therapeutic potential, and it has been suggested that chlorhexidine may inhibit the activities of these enzymes. The purposes of the present study were to examine systematically the inhibitory effects of chlorhexidine on three purified gingipains and to determine the effect of Zn(II) on chlorhexidine inhibition. METHODS: The activities of lys-gingipain (Kgp) and two forms of arg-gingipain (RgpB and HRgpA) were measured in the presence of varying concentrations of chlorhexidine and with chlorhexidine supplemented with Zn(II). Inhibition constants (K(i)'s) were determined for chlorhexidine alone and in the presence of Zn(II). Fractional inhibitory constant indices were calculated to assess the synergy of the chlorhexidine-Zn(II) inhibition. RESULTS: RgpB, HRgpA, and Kgp were all inhibited by chlorhexidine with K(i)'s in the micromolar range. For RgpB and HRgpA, the inhibitory effects of chlorhexidine were enhanced 3-30-fold by Zn(II). The chlorhexidine-Zn(II) interaction was synergistic for inhibition of HRgpA and RgpB. For Kgp, the effect of Zn(II) on chlorhexidine inhibition was antagonistic. CONCLUSIONS: Chlorhexidine is an effective inhibitor of gingipains, and the inhibition of R-gingipains is enhanced by Zn(II). A mixture of chlorhexidine and Zn(II) may be useful as an adjunct in the treatment of periodontitis and in the post-treatment maintenance of periodontitis patients.

To gain a better understanding of the mechanism of action of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd), gene expression profiling analyses were conducted on plateau phase human lung cancer (A549) cell cultures treated with MGd. Drug treatment elicited a highly specific response that manifested in elevated levels of metallothionein isoform and zinc transporter 1 (ZnT1) transcripts. A549 cultures incubated with MGd in the presence of exogenous zinc acetate displayed synergistic increases in the levels of intracellular free zinc, metallothionein transcripts, inhibition of thioredoxin reductase activity, and cell death. Similar effects were observed in PC3 prostate cancer and Ramos B-cell lymphoma cell lines. Intracellular free zinc levels increased in response to treatment with MGd in the absence of exogenous zinc, indicating that MGd can mobilize bound intracellular zinc. These findings lead us to suggest that an important component of the anticancer activity of MGd is related to its ability to disrupt zinc metabolism and alter cellular availability of zinc. This class of compounds may provide insight into the development of novel cancer drugs targeting control of intracellular free zinc and the roles that zinc and other metal cations play in biochemical pathways relevant to cancer.

OBJECTIVE: Volatile sulphur compounds (VSC) are major components of oral malodour. As both zinc ions and cationic antibacterial agents inhibit the formation of oral VSC, this study aimed to determine whether these agents combined have synergistic anti-VSC actions. METHODS: Baseline oral VSC measurements of mouth air from 10 volunteers following cysteine rinsing (6mM, pH 7.2) were obtained using gas chromatography (GC). Subjects rinsed for 1 min with 10ml of the test solutions, 0.3% zinc acetate (Zn), 0.025% chlorhexidine (CHX), 0.025% cetyl pyridinium (CPC), and the combinations Zn+CHX and Zn+CPC. Cysteine rinses were repeated at 1h, 2h and 3h and VSC measurements recorded. Three subjects rinsed with the Zn+CHX combination and fasted for 9h, undergoing cysteine rinses and VSC measurements at 3h intervals. 10 microl of the test solutions were also added to 1ml aliquots of human whole saliva (n=8). Following incubation at 37 degrees C for 24h VSC levels in the saliva headspace were measured by GC. Inhibition of VSC formation and the fractional inhibitory index indicating synergy were calculated. RESULTS: Zn+CHX mouthrinse had a synergistic anti-VSC effect, and was effective for at least 9h. Zn+CPC mouthrinse was less effective. Both combinations showed a synergistic inhibiting effect in-vitro. CONCLUSIONS: Synergy between Zn and the antibacterial agents confirms different mechanisms of operation.

OBJECTIVE: To investigate the protective effect of zinc in CCl4-induced hepatotoxicity. METHODS: Rats were treated with zinc acetate for four days. The zinc doses were 5 mg Zn/kg and 10 mg Zn/kg body weight respectively. Two groups of the zinc acetate-treated rats were later challenged with a single dose of CCl4 (1.5 mL/kg body weight). RESULTS: Compared to control animals, the plasma of rats treated with CCl4 showed hyperbilirubinaemia, hypoglycaemia, hypercreatinaemia and hypoproteinaemia. When the animals were however supplemented with zinc in form of zinc acetate before being dosed with CCl4, the 5 mg Zn/kg body weight of zinc acetate reversed the hypoproteinaemia induced by CCl4, whereas the 10 mg Zn/kg body weight of zinc acetate reversed the hypoglycaemia, hyperbilirubinaemia and hypercreatinaemia induced by CCl4. CONCLUSION: The 10 mg Zn/kg body weight of zinc acetate is more consistent in protecting against CCl4 hepatotoxicity. The possible mechanisms of protection are highlighted.

Present study describes the effect of zinc (Zn) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamine depletion in mice brain. MPTP is a known neurotoxicant primarily causing marked depletion of dopamine (DA) levels in nigrostriatal dopaminergic system. Adult Male C57-mice were intraperitonially injected with 25 mg/kg MPTP in the presence or absence of zinc acetate. Twenty-four hours after treatment animals were sacrificed and DA levels were determined by high performance liquid chromatography in caudate nucleus of control and treated mice. The results showed that there was a marked depletion of DA in MPTP treated mice, whereas no change was observed in DA levels in mice treated with Zn when compare to controls. Interestingly, mice receiving MPTP in conjunction with Zn showed significantly lower DA levels in brain when compare to animals receiving MPTP alone. In summary the data suggest that Zn treatment potentiates depletion of dopamine in MPTP treated mice.

BACKGROUND: Halitosis or bad breath is a symptom in which a noticeably unpleasant breath odour is present due to an underlying oral or systemic disease. 50% to 60% of the world population has experienced this problem which can lead to social stigma and loss of self-confidence. Multiple interventions have been tried to control halitosis ranging from mouthwashes and toothpastes to lasers. This new Cochrane Review incorporates Cochrane Reviews previously published on tongue scraping and mouthrinses for halitosis. OBJECTIVES: The objectives of this review were to assess the effects of various interventions used to control halitosis due to oral diseases only. We excluded studies including patients with halitosis secondary to systemic disease and halitosis-masking interventions. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 April 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3) in the Cochrane Library (searched 8 April 2019), MEDLINE Ovid (1946 to 8 April 2019), and Embase Ovid (1980 to 8 April 2019). We also searched LILACS BIREME (1982 to 19 April 2019), the National Database of Indian Medical Journals (1985 to 19 April 2019), OpenGrey (1992 to 19 April 2019), and CINAHL EBSCO (1937 to 19 April 2019). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (8 April 2019), the World Health Organization International Clinical Trials Registry Platform (8 April 2019), the ISRCTN Registry (19 April 2019), the Clinical Trials Registry - India (19 April 2019), were searched for ongoing trials. We also searched the cross-references of included studies and systematic reviews published on the topic. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) which involved adults over the age of 16, and any intervention for managing halitosis compared to another or placebo, or no intervention. The active interventions or controls were administered over a minimum of one week and with no upper time limit. We exclu

This study aimed to analyze the impact of chewing gum on halitosis parameters. Three databases were searched with the following focused question: 'Can chewing gum additionally reduce halitosis parameters, such as organoleptic scores and volatile sulfur compounds (VSC), when compared to a control treatment'? Controlled clinical trials presenting at least two halitosis measurements (organoleptic scores and/or VSC) were included. Ten studies were included, and different active ingredients were used. One study was performed using a chewing gum without any active ingredient. Chewing gum containing probiotic bacterium was shown to significantly reduce the organoleptic scores. Chewing gums containing zinc acetate and magnolia bark extract as well as allylisothiocyanate (AITC) with zinc lactate significantly reduced the levels of VSC in comparison to a placebo chewing gum. Furthermore, a sodium bicarbonate-containing chewing gum significantly reduced the VSC levels in comparison to rinsing with water. Furthermore, eucalyptus-extract chewing gum showed significant reductions in both organoleptic scores and VSC when compared with a control chewing gum. Chewing gum containing sucrose was able to reduce the VSC levels, in comparison to xylitol and zinc citrate chewing gum, but only for 5 min. It was concluded that chewing gums containing probiotics Lactobaccilus, zinc acetate and magnolia bark extract, eucalyptus-extract, and AITC with zinc lactate may be suitable for halitosis management. However, the low number of included studies and the high heterogeneity among the selected studies may limit the clinical applications of these findings.

Update of Cochrane Database Syst Rev. 2013 Jun 18;(6):CD001364. doi: 10.1002/14651858.CD001364.pub4. September 2016 updated withdrawal notice This Cochrane Review was withdrawn in April 2015, and this withdrawal notice was updated in September 2016. The review was withdrawn as result of comments submitted via the Cochrane Library by Harri Hemilä in February 2015. Hemilä identified multiple errors in this Cochrane Review and made allegations of plagiarism of text and data from a previously published systematic review (Hemilä H. Zinc Lozenges may shorten the duration of colds: a systematic review. Open Respiratory Medicine Journal 2011;5:51‐58. dx.doi.org/10.2174/1874306401105010051). The comments referred to the version of this review first published in June 2013 (Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013;(6):CD001364. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001364.pub4/full). The Cochrane Acute Respiratory Infections Group, which maintains the review, withdrew the review in April 2015, pending an assessment of the errors reported, and the group referred the allegations of plagiarism to the Editor in Chief. The Editor in Chief notified the authors of the concerns, and followed the Committee for Publication Ethics (COPE) guidelines. Replication of text was identified in the Cochrane Review. This was limited to copying of short phrases and was acknowledged by the authors. The level of text plagiarism was minor and at a level that would be addressed by a correction. The Editor in Chief carried out further investigation into the alleged plagiarism of data, with the co‐operation of the review authors, who provided supplementary information in support of their work. The allegations related to the derivation of means and standard deviations of data from some of the included studies. Although the authors acknowledge and cite the Hemilä 2011 review, the Editor in Chief considered that the authors’ explanation regarding some similarities in presented data between the two reviews was not conclusive. This version of the review will therefore remain withdrawn. April 2015 withdrawal notice This review was withdrawn d