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Background: Considering different factors, such as high withdrawal rates in methadone maintenance treatment (MMT) programs alongside mental health (MH) problems appearing in patients with opioid use disorder and the lack of prior research on the effect of zinc supplementation in this respect, the present study aimed to investigate the effect of zinc supplementation on the probability of relapse (PoR) and MH problems in patients with opioid use disorder undergoing MMT. Methods: For this purpose, a randomized controlled trial with a clinical basis was fulfilled on a total of 68 patients with opioid use disorder receiving MMT, allocated to two groups, viz. intervention, and control (each one consisting of 34 individuals). Then, the participants in the intervention group were given zinc supplements combined with methadone for three months, and the controls only took methadone, according to the treatment plan. The data were collected using the Relapse Prediction Scale (RPS) and the Depression, Anxiety, and Stress Scale 21 (DASS-21) before, one month after, and at the end of the intervention program. Findings: Compared to the control group, the likelihood of drug use (p = 0.01), drug craving (p = 0.002), and the RPS total score (p = 0.002) in the intervention group was significantly lower. Moreover, the results revealed a significant decreasing trend in depression (p = 0.01), anxiety (p < 0.001), stress (p = 0.001), and the DASS-21 total score (p = 0.001) in the intervention. Compared to the control group, the DASS-21 total score (p < 0.001) in the intervention group was significantly lower. Conclusion: Accordingly, it was concluded that zinc supplementation could reduce the PoR and improve MH problems in patients with opioid use disorder experiencing MMT. However, further research is recommended to fill the gaps. Trial registration: The research protocol has also been listed on the Iranian Registry of Clinical Trials (IRCT) with code no. IRCT2020050904736N1. [ABSTRACT FROM AUTHOR]

Background: Aging is accompanied by a dramatic decline in the interleukin (IL)-2 production capacity of human immune cells, thus making seniors more susceptible to a variety of age-related diseases. A common cause of impaired cytokine production in advanced age is a deficiency of the essential micronutrient zinc. Nevertheless, the molecular mechanisms underlying a zinc deficiency-induced decrease in IL-2 production have not yet been satisfactorily elucidated. Recent animal and in vitro data suggested that the transcription factor cAMP-responsive element modulator (CREM) α plays a critical role in T cells´ disturbed IL-2 production in suboptimal zinc conditions. However, its role in the human aging process and the possibility of influencing this detrimental process by short-term zinc supplementation have not yet been evaluated. Results: Comparing peripheral lymphocytes of 23 young and 31 elderly subjects with either high, intermediate, or deficient zinc status, we observed zinc-dependent regulation of the IL-2 production mediated by the transcription factor CREM α . For the first time in humans, we report a mutual relationship between low zinc levels, high CREM α expression, subsequent impaired IL-2 production, and vice versa. Remarkably, an average of only 6 days of in vivo zinc supplementation to zinc-deficient seniors was sufficient to rapidly improve zinc status, reverse CREM α overexpression, and counteract subsequent low IL-2 production rates. Conclusions: Our ex vivo and in vivo data identify zinc deficiency-mediated CREM α overexpression as a key cellular mechanism underlying impaired IL-2 production in the elderly and point toward the use of zinc as a rapidly immune-enhancing add-on nutraceutical in geriatric therapy. During the aging process, there is a progressive decrease in zinc status, which in turn leads to overexpression of the transcription factor CREM α in peripheral lymphocytes. CREMα is a negative regulator of the IL-2 gene, the overexpression of which dramatically limits adequate IL-2 production. This deleterious mechanism can be counteracted by short-term oral zinc administration, which can adjust IL-2 production in old, zinc-deficient individuals to a level similar to that of young adults. [ABSTRACT FROM AUTHOR]

Background: The heme group constitutes a major functional form of iron, which plays vital roles in various biological processes including oxygen transport and mitochondrial respiration. Heme is an essential nutrient, but its pro-oxidant nature may have toxic cellular effects if present at high levels, and its synthesis is therefore tightly regulated. Deficiency and excess of heme both lead to pathological processes; however, our current understanding of metazoan heme transport is largely limited to work in mammals and the worm Caenorhabditis elegans, while functional analyses of heme transport in the genetically amenable Drosophila melanogaster and other arthropods have not been explored. Results: We implemented a functional screening in Schneider 2 (S2) cells to identify putative heme transporters of D. melanogaster. A few multidrug resistance-associated protein (MRP) members were found to be induced by hemin and/or involved in heme export. Between the two plasma membrane-resident heme exporters CG4562 and CG7627, the former is responsible for heme transit across the intestinal epithelium. CG4562 knockdown resulted in heme accumulation in the intestine and lethality that could be alleviated by heme synthesis inhibition, human MRP5 (hMRP5) expression, heme oxygenase (HO) expression, or zinc supplement. CG4562 is mainly expressed in the gastric caeca and the anterior part of the midgut, suggesting this is the major site of heme absorption. It thus appears that CG4562 is the functional counterpart of mammalian MRP5. Mutation analyses in the transmembrane and nucleotide binding domains of CG4562 characterized some potential binding sites and conservative ATP binding pockets for the heme transport process. Furthermore, some homologs in Aedes aegypti, including that of CG4562, have also been characterized as heme exporters. Conclusions: Together, our findings suggest a conserved heme homeostasis mechanism within insects, and between insects and mammals. We propose the fly model may be a good complement to the existing platforms of heme studies. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a dyad of behavioural symptoms—social and communication deficits and repetitive behaviours. Multiple aetiological genetic and environmental factors have been identified as causing or increasing the likelihood of ASD, including serum zinc deficiency. Our previous studies revealed that dietary zinc supplementation can normalise impaired social behaviours, excessive grooming, and heightened anxiety in a Shank3 mouse model of ASD, as well as the amelioration of synapse dysfunction. Here, we have examined the efficacy and breadth of dietary zinc supplementation as an effective therapeutic strategy utilising a non-Shank-related mouse model of ASD—mice with Tbr1 haploinsufficiency. Methods: We performed behavioural assays, amygdalar slice whole-cell patch-clamp electrophysiology, and immunohistochemistry to characterise the synaptic mechanisms underlying the ASD-associated behavioural deficits observed in Tbr1+/− mice and the therapeutic potential of dietary zinc supplementation. Two-way analysis of variance (ANOVA) with Šídák's post hoc test and one-way ANOVA with Tukey's post hoc multiple comparisons were performed for statistical analysis. Results: Our data show that dietary zinc supplementation prevents impairments in auditory fear memory and social interaction, but not social novelty, in the Tbr1+/− mice. Tbr1 haploinsufficiency did not induce excessive grooming nor elevate anxiety in mice. At the synaptic level, dietary zinc supplementation reversed α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) hypofunction and normalised presynaptic function at thalamic-lateral amygdala (LA) synapses that are crucial for auditory fear memory. In addition, the zinc supplemented diet significantly restored the synaptic puncta density of the GluN1 subunit essential for functional NMDARs as well as SHANK3 expression in both the basal and lateral amygdala (BLA) of Tbr1+/− mice. Limitations: The therapeutic effect of dietary zinc supplementation observed in rodent models may not reproduce the same effects in human patients. The effect of dietary zinc supplementation on synaptic function in other brain structures affected by Tbr1 haploinsufficiency including olfactory bulb and anterior commissure will also need to be examined. Conclusions: Our data further the understanding of the molecular mechanisms underlying the effect of dietary zinc supplementation and verify the efficacy and breadth of its application as a potential treatment strategy for ASD. [ABSTRACT FROM AUTHOR]

Background: Enteromorpha prolifera (E. prolifera) polysaccharide has become a promising feed additive with a variety of physiological activities, such as anti-oxidant, anti-cancer, anti-diabetic, immunomodulatory, hypolipidemic, and cation chelating ability. However, whether Enteromorpha polysaccharide-trace element complex supplementation regulates amino acid and fatty acid metabolism in chicken is largely unknown. This study was conducted to investigate the effects of E. prolifera polysaccharide (EP)-Zn supplementation on growth performance, amino acid, and fatty acid metabolism in chicken. Methods: A total of 184 one-day-old Ross-308 broiler chickens were randomly divided into two treatment groups with 8 replicates, 12 chickens per replicate, and fed either the basal diet (control group) or basal diet plus E. prolifera polysaccharide-Zinc (400 mg EP-Zn/kg diet). Results: Dietary EP-Zn supplementation significantly increased (P < 0.05) the body weight, average daily gain, muscle antioxidant activity, serum HDL level, and reduced serum TG and LDL concentration. In addition, dietary EP-Zn supplementation could modulate ileal amino acid digestibility and upregulate the mRNA expression of amino acid transporter genes in the jejunum, ileum, breast muscle, and liver tissues (P < 0.05). Compared with the control group, breast meat from chickens fed EP-Zn had higher (P < 0.05) Pro and Asp content, and lower (P < 0.05) Val, Phe, Gly, and Cys free amino acid content. Furthermore, EP-Zn supplementation upregulated (P < 0.05) the mRNA expressions of mTOR and anti-oxidant related genes, while down-regulated protein degradation related genes in the breast muscle. Breast meat from EP-Zn supplemented group had significantly lower (P < 0.05) proportions of Σn-3 PUFA, and a higher percentage of Σn-6 PUFA and the ratio of n-6/n-3 PUFA. Besides, EP-Zn supplementation regulated lipid metabolism by inhibiting the gene expression of key enzymes involved in the fatty acid synthesis and activating genes that participated in fatty acid oxidation in the liver tissue. Conclusions: It is concluded that EP-Zn complex supplementation regulates apparent ileal amino acid digestibility, enhances amino acid metabolism, and decreases oxidative stress-associated protein breakdown, thereby improving the growth performance. Furthermore, it promotes fatty acid oxidation and restrains fat synthesis through modulating lipid metabolism-related gene expression. [ABSTRACT FROM AUTHOR]

Background: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage.Methods: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps.Discussion: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels.Trial Registration: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845. [ABSTRACT FROM AUTHOR]

Background: Zinc is an essential element for normal embryogenesis and embryonic and neonatal development. Therefore, we compared the birth weights of neonates born to mothers who consumed zinc supplement during pregnancy with that of neonates born to mothers who did not.Methods: In a cross-sectional study, we divided 200 pregnant mothers into two groups: case group (mothers receiving zinc supplement during pregnancy) and control group (mothers not receiving zinc supplement during pregnancy) Then, the neonate's cord zinc level and mother's serum level were measured and neonate's growth charts (weight, height and head circumference)were completed.Results: In this study, both groups of mothers were observed to have zinc deficiency; 35% of the mothers who consumed zinc supplements and 81% of the mothers who did not consume zinc supplements (P < 0.001). Based on the results, maternal serum of zinc (P < 0.001), neonatal birth weight (P = 0.008), maternal age (P < 0.001) and parity (P < 0.01) in zinc-supplemented group were higher. Neonatal birth weight was associated moderately with mother's zinc serum levels and poorly with neonatal serum zinc levels.Conclusion: Zinc consumption during pregnancy increases serum zinc level of mother and neonatal weight. Neonatal weight has a higher correlation to maternal serum zinc level. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorders (ASD) are characterised by deficits in social interactions and repetitive behaviours. Multiple ASD-associated mutations have been identified in the Shank family of proteins that play a critical role in the structure and plasticity of glutamatergic synapses, leading to impaired synapse function and the presentation of ASD-associated behavioural deficits in mice. Shank proteins are highly regulated by zinc, where zinc binds the Shank SAM domain to drive synaptic protein recruitment and synaptic maturation. Here we have examined the influence of maternal dietary zinc supplementation during pregnancy and lactation on the development of ASD-associated behavioural and synaptic changes in the offspring Shank3 knockout (Shank3−/−) mice. Behavioural and electrophysiological experiments were performed in juvenile and adult Shank3−/− and wildtype littermate control mice born from mothers fed control (30 ppm, ppm) or supplemented (150 ppm) dietary zinc. We observed that the supplemented maternal zinc diet prevented ASD-associated deficits in social interaction and normalised anxiety behaviours in Shank3−/− offspring mice. These effects were maintained into adulthood. Repetitive grooming was also prevented in adult Shank3−/− offspring mice. At the synaptic level, maternal zinc supplementation altered postsynaptic NMDA receptor-mediated currents and presynaptic function at glutamatergic synapses onto medium spiny neurons in the cortico-striatal pathway of the Shank3−/− offspring mice. These data show that increased maternal dietary zinc during pregnancy and lactation can alter the development of ASD-associated changes at the synaptic and the behavioural levels, and that zinc supplementation from the beginning of brain development can prevent ASD-associated deficits in Shank3−/− mice long term. [ABSTRACT FROM AUTHOR]

Background: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). Methods: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. Results: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β − 9.44 mg/dL, 95% CI, − 18.30, − 0.57; P = 0.03) and insulin levels (β − 1.37 μIU/mL, 95% CI, − 2.57, − 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β − 0.85 mg/L, 95% CI, − 1.26, − 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.003) and total antioxidant capacity (TAC) (β 43.44 mmol/L, 95% CI, 3.39, 83.50; P = 0.03) when compared with placebo. Furthermore, magnesium and zinc significantly reduced the Beck Depression Inventory index (BDI) (β − 1.66; 95% CI, − 3.32, − 0.009; P = 0.04) and Beck Anxiety Inventory (BAI) (β − 1.30; 95% CI, − 2.43, − 0.16; P = 0.02) when compared with the placebo. Conclusions: In patients with T2DM and CHD, the 12-week intake of magnesium plus zinc had beneficial effects on FPG, HDL-cholesterol, CRP, insulin, total nitrite, TAC levels, and BDI and BAI score. This suggests that magnesium and zinc co-supplementation may be beneficial for patients with T2DM and CHD. Further studies on more patients and lasting longer are needed to determine the safety of magnesium and zinc co-supplementation. Trial registration: Current Controlled Trials http://www.irct.ir: IRCT20130211012438N31 at 11 May 2019 of registration. This study retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Taste disorder is a common symptom in the general population. Several studies have shown that patients with neurological disorders, such as amyotrophic lateral sclerosis and Parkinson's disease, develop taste disturbance. Facial onset sensory and motor neuronopathy (FOSMN) is a rare disease characterized by sensory disturbance and weakness spreading from the face to the limbs caudally. We describe a patient with FOSMN who showed taste disorder as the sole initial symptom.Case Presentation: A 49-year-old man who smoked cigarettes developed taste disturbance. Despite using zinc supplements, an herbal medication, and an ointment, his taste disorder worsened. 4 years later, a tingling feeling emerged at the tip of his tongue and gradually spread to his entire lips. At 55 years of age, he showed difficulty in swallowing, followed by facial paresthesia, muscle atrophy, and weakness in the face and upper limbs without apparent upper motor neuron sign. Cessation of smoking did not improve his taste disturbance, and he was unable to discriminate different tastes on the entire tongue. In an electrogustometric study, electrical stimulation did not induce any type of taste sensation. Blink reflex showed delayed or diminished R2 responses. Needle electromyography revealed severe chronic neurogenic changes in the tongue and masseter muscles. Mild chronic neurogenic changes were also observed in the limbs. In the thoracic paraspinal muscles, active neurogenic changes were detected. Findings of hematological and cerebrospinal fluid analyses, and magnetic resonance images of the brain and spinal cord were unremarkable. One cycle of intravenous immunoglobulin therapy did not improve his symptoms. We diagnosed him as having FOSMN with the sole initial symptom of taste disorder. Nine years after the onset of taste disorder, he developed impaired sensation of touch in the right upper limb and required tube feeding and ventilator support.Conclusion: Taste disorder can be the initial manifestation of FOSMN and might involve the solitary nucleus. [ABSTRACT FROM AUTHOR]

Background: Pregnant women and children are the most vulnerable groups to zinc deficiency. Despite the presence of few primary studies, studies that could provide strong evidence that would help policymakers to develop appropriate interventional strategies in addressing zinc deficiency among pregnant women and children are limited in Ethiopia. Therefore, the aim of this systematic review and meta-analysis was to estimate the national pooled prevalence and associated factors of zinc deficiency among pregnant women and children.Methods: We searched Pub Med, Scopus, CINAHL, Google Scholar, and Google for studies reported on zinc deficiency and associated factors among pregnant women and children. Search terms were 'zinc deficiency', 'zinc status', 'associated factors', 'children', 'pregnant women', and 'Ethiopia' using the boolean operators 'OR' or 'AND'. Searches were using English language. A preferred reporting item for systematic reviews and meta-analysis (PRISMA) checklist was used. Two authors independently reviewed the studies. The effect sizes of the meta-analysis were the prevalence of zinc deficiency and adjusted odds ratio (AOR) of the associated factors. Finally, the Comprehensive Meta-Analysis (CMA) version 3.3.07 was used for statistical analysis by applying the random-effects model and publication bias was assessed using funnel plots and Egger's test.Results: Thirteen studies (7 among pregnant women having total participants of 2371 pregnant women and 6 among children with total participants of 5154 children) were included in this systematic review and meta-analysis. Using the random-effects model, the pooled prevalence of zinc deficiency was 59.9% (95%CI: 51.9, 67.7%) and 38.4% (95%CI: 28.6, 49.4) among pregnant women and children, respectively. The associated factors for zinc deficiency among pregnant women were coffee intake (adjusted odds ratio (AOR) =1.76), low intake of animal source foods (AOR = 2.57), and inadequate diet diversity (AOR = 2.12).Conclusion: Overall, zinc deficiency among pregnant women and children is a significant public health concern in Ethiopia. Promoting dietary modification to enhance the bioavailability of zinc, improving diet diversity, and consuming animal source foods would help in alleviating and/or minimizing the problem among the target groups. Zinc supplementation could also be considered for pregnant women and children. [ABSTRACT FROM AUTHOR]

Background: Even though the WHO currently recommends zinc for diarrhea management, no consensus has been reached with respect to routine distribution of zinc for preventive reasons. We reviewed the health impact of preventive zinc interventions, and evaluated the relative cost effectiveness of currently feasible interventions. Methods: Using the latest relative risk estimates reported in the literature, we parameterized a health impact model, and calculated the expected benefits of zinc supplementation in a representative low-income country. We then computed the cost and cost-effectiveness for three delivery mechanisms: the direct distribution of zinc supplements, the distribution of micronutrient biscuits including zinc, and the distribution of zinc through water filtration systems. Results: Combining all health outcomes and impact estimates, we find that systematic zinc supplementation among children of ages one to five would avert 1.423 DALYs per 100 households and year in least developed countries. The estimated cost per DALY is US$ 606 for pill supplementation, US$ 1211 for micronutrient biscuits, and US$ 879 per DALY saved for water filtration systems. Conclusions: Preventive zinc supplementation to children of ages 1-5 appears to be a highly cost-effective intervention in typical developing country settings. More research will be needed to determine the most effective mechanism to deliver zinc to this target population. [ABSTRACT FROM AUTHOR]

Background Zinc supplements can treat or prevent enteric infections and diarrheal disease. Many articles on zinc in bacteria, however, highlight the essential nature of this metal for bacterial growth and virulence, suggesting that zinc should make infections worse, not better. To address this paradox, we tested whether zinc might have protective effects on intestinal epithelium as well as on the pathogen. Results Sing polarized monolayers of T84 cells we found that zinc protected against damage induced by hydrogen peroxide, as measured by trans-epithelial electrical resistance. Zinc also reduced peroxide-induced translocation of Shiga toxin (Stx) across T84 monolayers from the apical to basolateral side. Zinc was superior to other divalent metals to (iron, manganese, and nickel) in protecting against peroxide-induced epithelial damage, while copper also showed a protective effect. The SOS bacterial stress response pathway is a powerful regulator of Stx production in STEC. We examined whether zinc's known inhibitory effects on Stx might be mediated by blocking the SOS response. Zinc reduced expression of recA, a reliable marker of the SOS. Zinc was more potent and more efficacious than other metals tested in inhibiting recA expression induced by hydrogen peroxide, xanthine oxidase, or the antibiotic ciprofloxacin. The close correlation between zinc's effects on recA/SOS and on Stx suggested that inhibition of the SOS response is one mechanism by which zinc protects against STEC infection. Conclusions Zinc's ability to protect against enteric bacterial pathogens may be the result of its combined effects on host tissues as well as inhibition of virulence in some pathogens. Research focused solely on the effects of zinc on pathogenic microbes may give an incomplete picture by failing to account for protective effects of zinc on host epithelia. [ABSTRACT FROM AUTHOR]

Background Zinc is essential for the activities of pancreatic β-cells, especially insulin storage and secretion. Insulin secretion leads to co-release of zinc which contributes to the paracrine communication in the pancreatic islets. Zinc-transporting proteins (zinc-regulated transporter, iron-regulated transporter-like proteins [ZIPs] and zinc transporters [ZnTs]) and metalbuffering proteins (metallothioneins, MTs) tightly regulate intracellular zinc homeostasis. The present study investigated how modulation of cellular zinc availability affects β-cell function using INS-1E cells. Results Using INS-1E cells, we found that zinc supplementation and zinc chelation had significant effects on insulin content and insulin secretion. Supplemental zinc within the physiological concentration range induced insulin secretion. Insulin content was reduced by zinc chelation with N,N,N',N-tektrakis(2-pyridylmethyl)-ethylenediamine. The changes in intracellular insulin content following exposure to various concentrations of zinc were reflected by changes in the expression patterns of MT-1A, ZnT-8, ZnT-5, and ZnT-3. Furthermore, high zinc concentrations induced cell necrosis while zinc chelation induced apoptosis. Finally, cell proliferation was sensitive to changes in zinc the concentration. Conclusion These results indicate that the β-cell-like function and survival of INS-1E cells are dependent on the surrounding zinc concentrations. Our results suggest that regulation of zinc homeostasis could represent a pharmacological target. [ABSTRACT FROM AUTHOR]

Objectives: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine.Trial Design: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial.Participants: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded.Intervention and Comparator: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days.Main Outcomes: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes.Randomisation: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures.Blinding (masking): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial.Numbers To Be Randomised (sample Size): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm.Trial Status: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). [ABSTRACT FROM AUTHOR]

Background: The number of people with diabetes is increasing worldwide, especially in developing South Asian countries. Therefore, preventing diabetes at the early stages has become an important issue. Recent clinical trials, systematic reviews, and meta-analysis have shown that zinc has beneficial effects on glycemic and metabolic control in those with diabetes. The present study is designed to evaluate the effects of zinc supplementation on glycemic control and other metabolic parameters in those with pre-diabetes. Methods/design: The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 12 months at the Faculty of Medicine, University of Colombo, Sri Lanka. The study has been approved by the Ethics Review Committee of Faculty of Medicine, University of Colombo (EC/11/189). A total of 200 adults (age 18-60 years) with pre-diabetes will be recruited for the study. They will be stratified according to age, gender, and body mass index and randomly assigned into the test and placebo groups on a 1:1 ratio. The zinc capsules, each weighing 456 mg, will contain the following ingredients:zinc sulfate monohydrate 55.096 mg (elemental zinc 20 mg), lactose monohydrate 399.504 mg, and stearic acid 1.400 mg. The placebo capsule with the same weight will be comprised of lactose monohydrate 454.600 mg and stearic acid 1.400 mg. The subjects will receive either zinc 20 mg capsules or placebo daily for a period of 12 months. The study drugs will be double blinded to both investigators and subjects. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 3 month (visit 2), 6 month (visit 3), and 12 month (visit 4). The following primary outcome measures will be evaluated:fasting plasma glucose (FPG), post oral glucose tolerance test (OGTT), serum insulin, HbA1c, total/lowdensity lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol, triglycerides, serum zinc, and appetite using a visual analog scale. Secondary outcome measures include: blood pressure, anthropometry, and dietary assessment using a validated food frequency questionnaire. Data will be analyzed using SPSS v16. Discussion: The present protocol will aim to establish the beneficial effects of zinc supplementation on disease progression in those with pre-diabetes and also establish its effectiveness in the prevention of diabetes mellitus. [ABSTRACT FROM AUTHOR]

The article presents a systematic review and meta-analysis on the effects of zinc supplementation on patients with diabetes mellitus. It reviews 25 articles including 22 studies on type-2 diabetes and three studies on type-1 diabetes. It shows that zinc supplementation promotes healthy lipid parameters and has beneficial effects on glycaemic control.

The article presents a research to study zinc adjunct therapy that reduces case fatality in severe childhood pneumonia. In the study, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% for more than 15 minutes.

Background: Dietary zinc supplementation may help to promote growth, boost the immune system, protect against diabetes, and aid recovery from diarrhoea. We exploited the zebrafish (Danio rerio) gill as a unique vertebrate ion transporting epithelium model to study the time-dependent regulatory networks of gene-expression leading to homeostatic control during zinc supplementation. This organ forms a conduit for zinc uptake whilst exhibiting conservation of zinc trafficking components. Results: Fish were maintained with either zinc supplemented water (4.0 μM) and diet (2023 mg zinc kg-1) or water and diet containing Zn2+ at 0.25 μM and 233 mg zinc kg-1, respectively. Gill tissues were harvested at five time points (8 hours to 14 days) and transcriptome changes analysed in quintuplicate using a 16 K microarray with results anchored to gill Zn2+ influx and whole body nutrient composition (protein, carbohydrate, lipid, elements). The number of regulated genes increased up to day 7 but declined as the fish acclimated. In total 525 genes were regulated (having a fold-change more than 1.8 fold change and an adjusted P-value less than 0.1 which is controlling a 10% False discovery rate, FDR) by zinc supplementation, but little overlap was observed between genes regulated at successive time-points. Many genes displayed cyclic expression, typical for homeostatic control mechanisms. Annotation enrichment analysis revealed strong overrepresentation of "transcription factors", with specific association evident with "steroid hormone receptors". A suite of genes linked to "development" were also statistically overrepresented. More specifically, early regulation of genes was linked to a few key transcription factors (e.g. Mtf1, Jun, Stat1, Ppara, Gata3) and was followed by hedgehog and bone morphogenic protein signalling. Conclusions: The results suggest that zinc supplementation reactivated developmental pathways in the gill and stimulated stem cell differentiation, a response likely reflecting gill remodelling in response to its altered environment. This provides insight to the role of zinc during cell differentiation and illustrates the critical nature of maintaining zinc status. The study also highlights the importance of temporal transcriptomics analysis in order resolve the discrete elements of biological processes, such as zinc acclimation. [ABSTRACT FROM AUTHOR]

Background: The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin has not been conducted on many of the studied markers in prediabetic patients.Methods: The purpose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers among 84 prediabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18-50 years old for men and 18 years to before menopause for women) will be followed for 3 months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences.Discussion: A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus.Trial Registration: Iranian Registry of Clinical Trials (IRCT) IRCT20190902044671N1 . Registered on 11 October 2019. [ABSTRACT FROM AUTHOR]

Background: Observational studies have shown a link between zinc deficiency and migraine headaches. We aimed to examine the effect of zinc supplementation on the characteristics of migraine attacks in patients with migraine.Methods: This randomized clinical trial was conducted on 80 patients with migraine. Patients were randomly assigned to receive either zinc sulfate (220 mg/d zinc sulfate) or placebo (lactose) for 8 weeks. Anthropometric measures, serum zinc concentrations, and characteristics of migraine attacks (headache severity, frequency and duration of migraine attacks, and headache daily results) were assessed at baseline and end of the trial.Results: Compared with the placebo, zinc supplementation resulted in a significant reduction in headache severity (- 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01) and migraine attacks frequency (- 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02) in migraine patients. However, the observed reduction for headache severity became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity. Other characteristics of migraine attacks including the duration of attacks and headache daily results were not altered following zinc supplementation either before or after controlling for covariates.Conclusion: Zinc supplementation had a beneficial effect on the frequency of migraine attacks in migraine patients. Additional well-designed clinical trials with a long period of intervention and different dosages of zinc are required.Trial Registration Code: IRCT20121216011763N23 at www.irct.ir . [ABSTRACT FROM AUTHOR]

Objectives: The decline in diarrhoeal disease-related mortality globally has been attributed to the use of oral rehydration solution (ORS) and zinc supplementation. However, data on ORS and zinc supplementation in Sudan are scarce. We aimed to investigate the access to ORS and zinc treatments and the associated factors, through the analysis of the latest available data from Sudan-Multiple Indicator Cluster Survey (MICS)-2014 obtained from the United Nations Children's Fund (UNICEF). Results: A total of 14,081 children were included in this analysis. During the 2 weeks preceding the survey, 29.3% of these children had a diarrhoeal disease. Only 18.9% and 14.8% of these children had received ORS and zinc supplements, respectively. Whereas children from the higher wealth index groups were more likely to receive ORS treatment (fourth group: AOR = 1.301; 95% CI 1.006–1.682), children from rural areas were less likely to receive ORS treatment (AOR = 0.666; 95% CI 0.552–0.803) and zinc supplements (AOR = 0.603; 95% CI 0.500–0.728). The results indicate the existence of unequal access to treatment of childhood diarrhoeal diseases among children under 5 years in Sudan. [ABSTRACT FROM AUTHOR]