{"publication_id":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","content_hash":"sha256:2a7885d755b4f0ccb60c38169a3785c0c88092d462d620836fbfdf0cd6c18410","nodes":[{"id":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","type":"publication","title":"Adjacent Evidence Brief: Zinc Supplementation Effects — full paper"},{"id":"claim_1","type":"claim","text":"This paper synthesizes evidence on zinc supplementation effects across 32 accepted source papers and 1454 high-confidence extracted claims. The evidence profile contains 4 direct clinical sources, 28 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base. Positive study-level signals are summarized in the immune and inflammation, longevity outcome classes, null signals in the contextual adjacent evidence, deficiency prevalence, immune and inflammation outcome classes, and negative signals in the immune and inflammation, contextual adjacent evidence outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that zinc supplementation effects remains a bounded evidence hypothesis: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any over-broad aging-related claim. For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint."},{"id":"claim_2","type":"claim","text":"This paper synthesizes evidence on zinc supplementation effects across 32 accepted source papers and 1454 high-confidence extracted claims."},{"id":"claim_3","type":"claim","text":"The evidence profile contains 4 direct clinical sources, 28 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base."},{"id":"claim_4","type":"claim","text":"Positive study-level signals are summarized in the immune and inflammation, longevity outcome classes, null signals in the contextual adjacent evidence, deficiency prevalence, immune and inflammation outcome classes, and negative signals in the immune and inflammation, contextual adjacent evidence outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect."},{"id":"claim_5","type":"claim","text":"The conclusion is that zinc supplementation effects remains a bounded evidence hypothesis: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any over-broad aging-related claim."},{"id":"claim_6","type":"claim","text":"For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint."},{"id":"claim_7","type":"claim","text":"This synthesis evaluates evidence on zinc supplementation effects across 32 included source papers and 1454 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty."},{"id":"claim_8","type":"claim","text":"The corpus contains 4 direct clinical sources, 28 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence."},{"id":"claim_9","type":"claim","text":"The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation."},{"id":"claim_10","type":"claim","text":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance."},{"id":"claim_11","type":"claim","text":"The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof."},{"id":"claim_12","type":"claim","text":"Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection."},{"id":"claim_13","type":"claim","text":"Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints."},{"id":"claim_14","type":"claim","text":"The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific."},{"id":"claim_15","type":"claim","text":"The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge."},{"id":"claim_16","type":"claim","text":"The background evidence for zinc supplementation effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Barffour 2020, Baissary 2025, Wessells 2019 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation."},{"id":"claim_17","type":"claim","text":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect."},{"id":"claim_18","type":"claim","text":"Across the retained sources, positive signals cluster around the immune and inflammation, longevity outcome classes; null signals around the contextual adjacent evidence, deficiency prevalence, immune and inflammation outcome classes; and negative or adverse signals around the immune and inflammation, contextual adjacent evidence outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation."},{"id":"claim_19","type":"claim","text":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty."},{"id":"claim_20","type":"claim","text":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support."},{"id":"claim_21","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text."},{"id":"claim_22","type":"claim","text":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification."},{"id":"claim_23","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, immune and inflammation, longevity, mortality and survival); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_24","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_25","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_26","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_27","type":"claim","text":"| Zinc Supplementation Effects / Contextual Adjacent Evidence | n=9; claims=404 | significant source statistic in 8/9 sources; receipt-level direction coded unclear | 1 direct; 4 indirect; 4 review | limited corpus depth in this outcome class |"},{"id":"claim_28","type":"claim","text":"Aging and geroscience context: 1 sources; significant source statistic in 1/1 sources; receipt-level direction coded null."},{"id":"claim_29","type":"claim","text":"Contextual Adjacent Evidence: n=9; claims=404; mixed signal in 6/9 sources | directness: 1 direct; 4 indirect; 4 review; main limitation: directionally heterogeneous."},{"id":"claim_30","type":"claim","text":"Two systematic reviews anchor the cardiometabolic evidence base for zinc supplementation, each pooling randomized controlled trials across heterogeneous populations. Jayawardena 2022 synthesized studies in prediabetes mellitus, while Khazdouz 2020 aggregated randomized controlled trials evaluating cardiometabolic risk factors more broadly. Both reviews summarize zinc delivered as an oral supplement, alone or in combination with other micronutrients, against comparators that varied across the included primary trials. The principal endpoints assessed were fasting and post-load glucose, glycated hemoglobin, and related metabolic indices. The two reviews together provide the principal human-evidence substrate for the cardiometabolic class within this corpus."},{"id":"source_1","type":"source","study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL)."},{"id":"source_2","type":"source","study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point."},{"id":"source_3","type":"source","study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included."},{"id":"source_4","type":"source","study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"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."},{"id":"source_5","type":"source","study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo."},{"id":"source_6","type":"source","study":"Zinc Deficiency and Therapeutic Value of Zinc Supplementation in Pediatric Gastrointestinal Diseases","year":2023,"doi":"10.3390/nu15194093","url":"https://doi.org/10.3390/nu15194093","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chao 2023","excerpt":"The benefits of zinc in treating certain gastrointestinal (GI) diseases have been recognized for over two decades. This review aims to explore zinc deficiency (ZD) and the potential therapeutic value and safety of zinc supplementation in pediatric GI diseases. A systematic review of published articles on ZD and zinc as adjuvant treatments for GI diseases was conducted using various databases. Children with inflammatory bowel disease (IBD), celiac disease, and those receiving long-term proton pump inhibitor treatments are particularly susceptible to ZD. ZD in children with celiac disease and IBD is attributed to insufficient intake, reduced absorption, and increased intestinal loss as a result of the inflammatory process. Zinc plays a crucial role in maintaining the integrity of the gastric mucosa and exerts a gastroprotective action against gastric lesions. Although considerable evidence supports the use of zinc as adjuvant therapy for certain GI diseases in adults, its use is unspecified in children except for infectious diarrhea."},{"id":"source_7","type":"source","study":"Zinc Supplementation, Inflammation, and Gut Integrity Markers in HIV Infection: A Randomized Placebo-Controlled Trial","year":2025,"doi":"10.3390/nu17101671","url":"https://doi.org/10.3390/nu17101671","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Baissary 2025","excerpt":"Background: Low levels of zinc are prevalent in patients living with HIV and are associated with higher morbidity. Zinc has major immunomodulatory effects. This study aimed to assess the effect of zinc supplementation on inflammatory and gut integrity markers and on zinc levels among HIV patients with zinc deficiency. Methods: This was a double-blind randomized placebo-controlled trial assessing the efficacy and safety of zinc supplementation on inflammation and gut markers in people with HIV (PWH) ≥ 18 years old, on stable antiretroviral therapy (ART) with undetectable HIV-1 viral load, and with zinc levels of ≤0.75 mg/L. Participants were randomized 2:1 to zinc gluconate tablets at a dose of 90 mg of elemental zinc or a matching placebo daily for 24 weeks. At baseline and at week 24, we measured plasma levels of zinc and markers of inflammation and gut barrier integrity. Results: Among the 95 participants enrolled in this study, 74% were male, and 65% were non-white, with a median CD4 count of 722 cells/μL. The primary analysis showed an increase in zinc levels in the active group."},{"id":"source_8","type":"source","study":"High-Dose Zinc Supplementation Therapy Does Not Improve Survival Rates in Severe Trauma Patients: A Single-Center Retrospective Observational Study","year":2026,"doi":"10.3390/nu18030541","url":"https://doi.org/10.3390/nu18030541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Tsushima 2026","excerpt":"Background/Objectives: Hypozincemia associated with severe trauma contributes to immune dysfunction and poor prognosis; however, the clinical utility and optimal dosage of zinc supplementation remain unclear. In particular, it is unclear whether high-dose administration exceeding standard recommendations improves prognosis. Thus, we aimed to verify this in patients with severe trauma requiring mechanical ventilation. Methods: This single-center retrospective observational study included patients with severe trauma (Injury Severity Score [ISS] > 15) requiring mechanical ventilation admitted to our emergency intensive care unit (ICU) between April 2015 and March 2023. Patients were classified into three groups based on their mean daily zinc supplementation dose: low (<15 mg), medium (15-50 mg), and high (>50 mg). The primary outcome was the 30-day survival rate. Secondary outcomes included the 90-day survival rate, length of ICU stay, and hospital-acquired pneumonia. Multivariable regression evaluated the association between high-dose zinc supplementation and clinical outcomes after adjusting for confounding factors."},{"id":"source_9","type":"source","study":"Effectiveness of Zinc Supplementation for Sepsis Treatment: A Single-Center Retrospective Observational Study","year":2024,"doi":"10.3390/nu16172841","url":"https://doi.org/10.3390/nu16172841","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kim 2024","excerpt":"BACKGROUND: Zinc plays an important role in sepsis; however, the effectiveness of zinc supplementation and the appropriate dose remain unclear. This study aimed to verify the effectiveness of zinc supplementation and the appropriate dose in patients with sepsis. METHODS: This single-center retrospective observational study included 247 patients with sepsis from 1 April 2015 to 31 March 2023 who were receiving ventilatory management. The patients were divided into three groups according to the zinc supplementation dose: <15 mg, 15-50 mg, and ≥50 mg. RESULTS: The <15 mg, 15-50 mg, and ≥50 mg groups had 28 (19%), six (21%), and 16 deaths (22%) at discharge, with no statistically significant difference ( p = 0.36). No statistically significant differences were observed in the length of intensive care unit (ICU) stay ( p = 0.06). A higher supplementation dose corresponded with a statistically significant increase in blood zinc concentration in the first week (38.5 ± 16.6 µg/dL, 58.8 ± 19.7 µg/dL, 74.2 ± 22.5 µg/dL, respectively; p < 0.01) but not in the second or third weeks ( p = 0.08, 0.19, respectively)."},{"id":"source_10","type":"source","study":"Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis","year":2024,"doi":"10.3390/nu16234116","url":"https://doi.org/10.3390/nu16234116","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Hsu 2024","excerpt":"BACKGROUND/OBJECTIVES: Primary dysmenorrhea (PD) is a common condition affecting up to 90% of menstruating women, which often results in significant pain without an underlying pathology. Zinc, recognized for its anti-inflammatory and antioxidant effects through inhibiting prostaglandin production and superoxide dismutase 1 (SOD1) upregulation, alleviates menstrual pain by preventing uterine spasms and enhancing microcirculation in the endometrium, suggesting its potential as an alternative treatment for primary dysmenorrhea. The goal of this systematic review and meta-analysis was to assess the efficacy and safety of zinc supplementation in reducing pain severity among women with PD and to explore the influence of dosage and treatment duration. METHODS: Following the PRISMA 2020 guidelines, we conducted an extensive search across databases such as PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar, up to May 2024. Randomized controlled trials assessing the effects of zinc supplementation on pain severity in women with PD were included. Pain severity was evaluated with established tools, such as the Visual Analog Scale (VAS)."},{"id":"source_11","type":"source","study":"Effects of Dose and Duration of Zinc Interventions on Risk Factors for Type 2 Diabetes and Cardiovascular Disease: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.1093/advances/nmaa087","url":"https://doi.org/10.1093/advances/nmaa087","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Pompano 2020","excerpt":"No meta-analysis has examined the effect of dose and duration of zinc interventions on their impact on risk factors for type 2 diabetes (T2D) or cardiovascular disease (CVD). This study aimed first to compare the effects of zinc interventions dichotomized as low versus high dose (<25 mg/d and ≥25 mg/d, respectively) and short versus long duration (<12 wk and ≥12 wk, respectively) on risk factors for T2D and CVD. Second, it discusses the results from the low-dose and long-duration meta-analyses as a foundation for understanding what impact a zinc-biofortification intervention could have on these risk factors. The PubMed and Cochrane Review databases were searched through January 2020 for full-text, human studies providing zinc supplements (alone) at doses ≤75 mg/d and a placebo. Data on study and sample characteristics and several T2D and CVD risk factors were extracted. There were 1042 and 974 participants receiving zinc and placebo, respectively, from 27 studies. Low-dose zinc supplementation (<25 mg/d) significantly benefited fasting blood glucose, insulin resistance, triglycerides, total cholesterol, and LDL cholesterol."},{"id":"source_12","type":"source","study":"Exchangeable Zinc Pool Size Reflects Form of Zinc Supplementation in Young Children and Is Not Associated with Markers of Inflammation","year":2022,"doi":"10.3390/nu14030481","url":"https://doi.org/10.3390/nu14030481","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Long 2022","excerpt":"A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation."},{"id":"source_13","type":"source","study":"Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.","year":2021,"doi":"10.1016/j.cyto.2020.155396","url":"https://doi.org/10.1016/j.cyto.2020.155396","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Hosseini 2021","excerpt":"BACKGROUND: Zinc (Zn) is a trace metal that is considered to have an impact on chronic inflammation. However, findings of clinical trials have been inconsistent. The present systematic review and meta-analysis aimed to provide a more robust examination of the evidence on the effectiveness of Zn supplements on markers of inflammation and oxidative stress. METHODS: A systematic search in PubMed, Scopus, Web of Science and Cochrane Library was undertaken to identify relevant randomized controlled trials (RCTs) assessing the impact of Zn on inflammation and oxidative stress until 17 August 2020. We applied a random-effects method to obtain effect sizes (ES) and 95% confidence intervals (CIs). Meta-regression was used to detect the potential source of between-study heterogeneity. RESULTS: Twenty-one eligible RCTs comprising 1321 participants were included in the meta-analysis. In comparison with the control groups, serum C-reactive protein (CRP) (ES = -0.92 mg/L, 95% CI = [-1.36, -0.48], P < 0.001, I 2 = 90.2%), tumor necrosis factor-alpha (TNF-α) (ES = -0.49 pg/mL, 95% CI = [-084, -0.14], P = 0.006, I 2 = 34.6%) and malondialdehyde (MDA) (ES = -0.42, 95% CI = [-083, -0.01], P = 0."},{"id":"source_14","type":"source","study":"Zinc supplementation and COVID-19 mortality: a meta-analysis","year":2022,"doi":"10.1186/s40001-022-00694-z","url":"https://doi.org/10.1186/s40001-022-00694-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Tabatabaeizadeh 2022","excerpt":"BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a pneumonia outbreak and was called 2019 novel coronavirus disease (COVID-19). COVID-19 emerged in December 2019 and now considered a pandemic. Zinc supplementation can reduce mortality in patients with severe pneumonia. This study aimed at meta-analysis of the results of related studies and evaluate the effect of zinc supplementation on COVID-19 mortality. METHODS: A systematic search has conducted for manuscripts through PUBMED/Medline and Google Scholar (Cochrane guideline has considered it as the gray literature) up to September 2021. This meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Guideline for evaluation of the effect zinc supplementation on COVID-19 mortality. Based on the heterogeneity a fixed-effect or random-effect model, the OR and 95% CI were used to assess the combined risk. RESULTS: After assessment, five studies with 1506 participants in case and control groups were included in meta-analysis. The OR for one study was not estimable, and the pool OR was estimated for other studies with 1398 participants."},{"id":"source_15","type":"source","study":"Enteral Zinc Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis.","year":2022,"doi":"10.1542/peds.2022-057092j","url":"https://doi.org/10.1542/peds.2022-057092j","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Sinha 2022","excerpt":"BACKGROUND AND OBJECTIVES: Evidence on the effect of zinc supplementation on health outcomes in preterm or low birth weight (LBW) infants is unclear. We estimated the effect of enteral zinc versus no zinc supplementation in human milk fed preterm or LBW infants on mortality, growth, morbidities, and neurodevelopment. METHODS: Data sources include PubMed, Cochrane Central and Embase databases through March 24, 2021. Study selection was randomized or quazi-experimental trials. Two reviewers independently screened, extracted data, and assessed quality. We reported pooled relative risks (RR) for categorical outcomes, and mean differences (MD) for continuous outcomes. RESULTS: Fourteen trials with 9940 preterm or LBW infants were included. Moderate to low certainty evidence showed that enteral zinc supplementation had little or no effect on mortality (risk ratio 0.73, 95% confidence interval [CI] 0.46 to 1.16), but increased weight (MD 378.57, 95% CI 275.26 to 481.88), length (MD 2.92, 95% CI 1.53 to 4.31), head growth (MD 0.56, 95% CI 0.23 to 0.90), and decreased diarrhea (RR 0.81; 95% CI 0.68 to 0.97)."},{"id":"source_16","type":"source","study":"Effect of zinc supplementation on mortality in under 5-year children: a systematic review and meta-analysis of randomized clinical trials.","year":2022,"doi":"10.1007/s00394-021-02604-1","url":"https://doi.org/10.1007/s00394-021-02604-1","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Rouhani 2022","excerpt":"BACKGROUND: Several clinical trials evaluated the effect of zinc supplementation on mortality in children, but the results were inconsistent. We aimed to conduct a systematic review and meta-analysis on the impact of zinc supplementation on mortality in under 5-year children. METHODS: A comprehensive search was conducted using the electronic (PubMed, Scopus, Web of Science) databases, and Google Scholar, up to June 2020. Randomized clinical trials (RCTs) that reported the effect of zinc supplementation on death incidence in under 5-year children were included in the analysis. Screening was performed based on title/abstract and full-text. A random effects model was applied to calculate the summary relative risk (SRR). Risk of Bias 2.0 tool was used to rate the quality of trials. The body of evidence was assessed by the GRADE approach. RESULTS: Combining 30 RRs from 28 RCTs including 237,068 participants revealed that zinc supplementation has significantly reduced the risk of all-causes mortality by 16% in children (SRR: 0.84, 95% CI: 0.74, 0.96). A follow-up duration of less than 1 year after supplementation resulted in 54% reduced risk of mortality (0.46; 0.33, 0."},{"id":"source_17","type":"source","study":"Zinc supplementation in prediabetes mellitus.","year":2022,"doi":"10.23736/s2724-6507.21.03234-x","url":"https://doi.org/10.23736/s2724-6507.21.03234-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Jayawardena 2022","excerpt":"INTRODUCTION: Certain pharmacological and lifestyle interventions have been shown to reduce progression of prediabetes. We aimed to perform a systematic review and meta-analyses of studies assessing the outcomes of zinc supplementation in individuals with prediabetes. EVIDENCE ACQUISITION: A comprehensive search was conducted in PubMed, SciVerse Scopus and Web of Science databases. Controlled clinical trials in prediabetics individuals, on zinc supplementation with or without other nutrients, assessing at least one accepted glycemic parameter as an outcome were deemed eligible. EVIDENCE SYNTHESIS: Three papers were included in the systematic review and meta-analysis, with a total of 265 participants. Duration of zinc supplementation ranged from 6-12 months. The zinc dose ranged from 20-30 mg/day. In the pooled analysis, zinc supplementation significantly reduced FBG both when given alone (-10.86 mg/dL; 95% CI, -14.74 to -6.98; P<0.001) and with other micronutrients (-11.77 mg/dL; P<0.001). Similarly, 2hr-OGTT blood glucose was reduced by 21.08 mg/dL (95% CI, -40.05 to -2.11; P=0.03) in the pooled analysis of studies using zinc alone and in combination with other micronutrients."},{"id":"source_18","type":"source","study":"Effects of Zinc Supplementation on Cardiometabolic Risk Factors: a Systematic Review and Meta-analysis of Randomized Controlled Trials.","year":2020,"doi":"10.1007/s12011-019-01870-9","url":"https://doi.org/10.1007/s12011-019-01870-9","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Khazdouz 2020","excerpt":"The prevalence of cardiometabolic risk factors has been increasing worldwide. The results of reported studies on the effects of zinc supplementation on cardiometabolic risk factors are unequivocal. This systematic review and meta-analysis of randomized controlled trials was conducted to evaluate the effects of zinc supplementation on cardiometabolic risk factors. A systematic search was conducted through international databases (PubMed/Medline, Institute of Scientific Information, and Scopus) until December 2018 to include all randomized controlled trials (RCT), quasi-RCT, and controlled clinical trials which assessed the effect of zinc supplementation on cardiometabolic risk factors including lipid profile, glycemic indices, blood pressure, and anthropometric indices. Random- or fixed-effects meta-analysis method was used to estimate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies were included in the meta-analysis, which included a total of 1141 participants in the intervention group. Meta-analysis showed that zinc supplementation significantly decreased plasma levels of triglyceride (SMD - 0.66, 95% CI - 1.27, - 0."},{"id":"source_19","type":"source","study":"Antioxidant effect of zinc supplementation on both plasma and cellular red-ox status markers in a group of elderly Italian population","year":2014,"doi":"10.1007/s12603-014-0005-7","url":"https://doi.org/10.1007/s12603-014-0005-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Venneria 2014","excerpt":"OBJECTIVES: The aim of this work was to evaluate the effect of long term supplementation with two moderate dose of Zn on plasma and cellular red-ox status markers in elderly volunteers. DESIGN, SETTING AND SUBJECTS: In a double blind study 108 healthy volunteers, aged 70-85 years, were enrolled. They were randomly divided in 3 groups of treatment, receiving placebo, 15 mg/day and 30 mg/day of Zn for 6 months. Red-ox status markers were assessed at baseline and after 6 months evaluating carotenoids, vitamin A and E in plasma; glutathione (GSH), thiol groups (RSH), malondialdehyde (MDA), percentage of haemolysis and methemoglobin in erythrocytes. RESULTS: Zn supplementation had no significant effects on red-ox status markers except for vitamin A levels (from 1.94±0.44 to 2.18±0.48 μM in volunteers receiving 15 mg of Zn and from 1.95±0.46 to 2.26±0.56 μM in volunteers receiving 30 mg of Zn), which increased proportionally to zinc dose."},{"id":"source_20","type":"source","study":"Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria","year":2011,"doi":"10.1186/1471-2458-11-S3-S23","url":"https://doi.org/10.1186/1471-2458-11-S3-S23","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Yakoob 2011","excerpt":"BACKGROUND: Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation. DATA SOURCES/ REVIEW METHODS: A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 years of age in developing countries and its effect on mortality was analyzed. RESULTS: The effect of preventive zinc supplementation on mortality was given in eight trials, while cause specific mortality data was given in five of these eight trials. Zinc supplementation alone was associated with a statistically insignificant 9% (RR = 0.91; 95% CI: 0.82, 1.01) reduction in all cause mortality in the intervention group as compared to controls using a random effect model."},{"id":"source_21","type":"source","study":"What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis","year":2011,"doi":"10.1186/1471-2334-11-122","url":"https://doi.org/10.1186/1471-2334-11-122","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Patel 2011","excerpt":"BACKGROUND: Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea. METHODS: EMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality."},{"id":"source_22","type":"source","study":"Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial","year":2019,"doi":"10.4269/ajtmh.19-0584","url":"https://doi.org/10.4269/ajtmh.19-0584","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Wessells 2019","excerpt":"Environmental enteric dysfunction (EED) may be ameliorated by zinc supplementation. The objective of this study was to investigate the impact of different forms of zinc supplementation on biomarkers of EED (i.e., plasma citrulline, kynurenine, and tryptophan concentrations and the kynurenine:tryptophan [KT] ratio) among young Laotian children. In a double-blind randomized controlled trial, 3,407 children aged 6-23 months were randomized into one of four groups: daily preventive zinc dispersible tablets (PZ; 7 mg zinc), daily multiple micronutrient powders (MNP; 10 mg zinc, 6 mg iron, and 13 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/day for 10 days), or daily placebo powder, and followed up for ∼36 weeks. Plasma samples at baseline and endline for 359 children were analyzed for citrulline, kynurenine, and tryptophan concentrations. At baseline, the prevalence of stunting and zinc deficiency was 37% and 76.5%, respectively. The mean plasma citrulline, kynurenine, and tryptophan concentrations were 24.6 ± 5.4 µmol/L, 3.27 ± 0.83 µmol/L, and 72.3 ± 12.9 µmol/L, respectively; the mean KT ratio (×1,000) was 45.9 ± 12.0."},{"id":"source_23","type":"source","study":"Effects of Zinc Supplementation on the Incidence of Mortality in Preschool Children: A Meta-Analysis of Randomized Controlled Trials","year":2013,"doi":"10.1371/journal.pone.0079998","url":"https://doi.org/10.1371/journal.pone.0079998","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Fu 2013","excerpt":"BACKGROUND: Previous trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56-1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53-1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11-2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77-1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67-1.44; P = 0.917)."},{"id":"source_24","type":"source","study":"Impact of vitamin A with zinc supplementation on malaria morbidity in Ghana","year":2013,"doi":"10.1186/1475-2891-12-131","url":"https://doi.org/10.1186/1475-2891-12-131","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Owusu-Agyei 2013","excerpt":"BACKGROUND: Malaria is a leading cause of morbidity and mortality among young children and is estimated to cause at least 1 million deaths each year especially among pregnant women and young children under the age of five years. Vitamin A supplementation is known to reduce morbidity and mortality in young children. Zinc is required for growth and immunity and we sought to replicate the study by Zeba et al. which showed 30% lower cases of clinical malaria in children on a combination of zinc and a large dose of vitamin A compared with children on vitamin A alone based on the hypothesis that combined vitamin A and zinc reduced symptomatic malaria compared to vitamin A alone. OBJECTIVES: The primary objective was to determine the effect of vitamin A alone vs. vitamin A and zinc supplements on the incidence of clinical malaria and other anthropometric indices. It also sought to assess the effects on the incidence of anaemia, diarrhoea and pneumonia."},{"id":"source_25","type":"source","study":"From guidelines to local realities: evaluation of oral rehydration therapy and zinc supplementation in Guatemala","year":2017,"doi":"10.26633/RPSP.2017.8","url":"https://doi.org/10.26633/RPSP.2017.8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hall-Clifford 2017","excerpt":"OBJECTIVE: Diarrhea remains a leading cause of morbidity and mortality for children in low- and middle-income countries throughout the Americas. The World Health Organization (WHO) has developed guidelines on incorporating zinc supplementation (ZS) with traditional oral rehydration therapy (ORT) in order to shorten the duration of diarrheal episodes and to reduce poor health outcomes. Guatemala adopted these guidelines in 2011, but they have not yet been fully implemented at the community level. The objectives of this study were: (1) to co-design an ORT/ZS training program for community members with local health promoters that is appropriate to the local context and (2) to understand how attitudes and behaviors of community members changed after receiving training from the study promoters. METHODS: In an observational study, community health promoters in rural Guatemala were trained according to WHO guidelines, and they worked collaboratively with the study team to develop a training curriculum to implement in their community."},{"id":"source_26","type":"source","study":"Zinc Supplementation Inhibits Complement Activation in Age-Related Macular Degeneration","year":2014,"doi":"10.1371/journal.pone.0112682","url":"https://doi.org/10.1371/journal.pone.0112682","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Smailhodzic 2014","excerpt":"UNLABELLED: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a."},{"id":"source_27","type":"source","study":"High 15-F 2t -Isoprostane Levels in Patients with a Previous History of Nonmelanoma Skin Cancer: The Effects of Supplementary Antioxidant Therapy","year":2015,"doi":"10.1155/2015/963569","url":"https://doi.org/10.1155/2015/963569","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freitas 2015","excerpt":"BACKGROUND: Phase I of this study was aimed at comparing the profiles of oxidative stress biomarkers in patients with history of nonmelanoma skin cancer (NMSC), previously treated with surgery, to the healthy subjects. Phase II aimed to evaluate the effects of supplementary antioxidant therapy on the levels of biomarkers in the case group. MATERIALS AND METHODS: In Phase I, oxidative stress biomarkers were measured in blood samples obtained from 24 healthy subjects and 60 patients with history of NMSC previously treated with surgery. In Phase II, the 60 patients with history of NMSC were randomized into two subgroups, one receiving placebo (n = 34) and the other (n = 26) receiving vitamin C, vitamin E, and zinc supplementation for 8 weeks, followed by reevaluation of biomarkers. RESULTS: In Phase I, patients with history of NMSC showed increased plasma concentrations of all biomarkers, but only 15-F2t-isoprostane was significantly higher than in the healthy subjects. Risk of NMSC increased by 4% for each additional 1 pg/mL increase in 15-F2t-isoprostane. In Phase II, supplementation did not significantly reduce levels of oxidative stress biomarkers."},{"id":"source_28","type":"source","study":"A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy","year":2013,"doi":"10.1186/1475-2891-12-74","url":"https://doi.org/10.1186/1475-2891-12-74","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Chavez-Tapia 2013","excerpt":"BACKGROUND AND AIM: Because low serum zinc levels precipitate hepatic encephalopathy, zinc supplementation is considered a potential therapeutic option. The aim of this study was to assess the effects of oral zinc supplementation in the treatment of hepatic encephalopathy. METHODS: For this systematic review and meta-analysis, data sources included electronic databases (CENTRAL, MEDLINE, EMBASE) and manual searching. Randomized clinical trials of adult patients diagnosed with liver cirrhosis and hepatic encephalopathy were included. The types of interventions considered were any oral zinc supplementation versus no intervention, placebo, or other interventions for the management of hepatic encephalopathy. The data were analyzed by calculating the RR for each trial and expressing the uncertainty as 95% CI. Continuous data were analyzed by calculating the standard mean differences (SMD) between groups within each trial and their 95% CI. Statistical heterogeneity was defined as a P-value > 0.10 (χ2) or I2 > 25%. RESULTS: Four trials with a total of 233 patients were included."},{"id":"source_29","type":"source","study":"Effects of Zinc Supplementation on Plasma Copper/Zinc Ratios, Oxidative Stress, and Immunological Status in Hemodialysis Patients","year":2012,"doi":"10.7150/ijms.5291","url":"https://doi.org/10.7150/ijms.5291","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Guo 2012","excerpt":"BACKGROUND: Patients undergoing hemodialysis (HD) have low plasma levels of zinc (Zn), high plasma levels of copper (Cu), and exhibit increased oxidative stress, inflammation, and immune abnormalities. We evaluated the effects of Zn supplementation on abnormal plasma Cu/Zn ratios and clinical outcomes in HD patients. DESIGN AND METHODS: Patients on long-term HD with lower than normal plasma concentrations of Zn (< 80 mg/dL) were randomized to receive daily oral Zn supplements (n = 40) or no supplements (n = 25) for eight weeks. Age- and sex-matched healthy individuals served as a control group (n = 38). A number of clinical parameters were measured before and after the supplementation period. RESULTS: Compared with healthy subjects, patients had significantly elevated plasma Cu concentrations and Cu/Zn ratios, as well as higher levels of oxidative stress and pro-inflammatory cytokines. Patients who received Zn supplements for eight weeks had higher plasma concentrations of Zn and lower concentrations of Cu, along with reduced Cu/Zn ratios, oxidative stress status, and inflammatory responses compared to patients who did not receive Zn."},{"id":"source_30","type":"source","study":"Preventive zinc supplementation for children, and the effect of additional iron: a systematic review and meta-analysis","year":2014,"doi":"10.1136/bmjopen-2013-004647","url":"https://doi.org/10.1136/bmjopen-2013-004647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Mayo-Wilson 2014","excerpt":"OBJECTIVE: Zinc deficiency is widespread, and preventive supplementation may have benefits in young children. Effects for children over 5 years of age, and effects when coadministered with other micronutrients are uncertain. These are obstacles to scale-up. This review seeks to determine if preventive supplementation reduces mortality and morbidity for children aged 6 months to 12 years. DESIGN: Systematic review conducted with the Cochrane Developmental, Psychosocial and Learning Problems Group. Two reviewers independently assessed studies. Meta-analyses were performed for mortality, illness and side effects. DATA SOURCES: We searched multiple databases, including CENTRAL and MEDLINE in January 2013. Authors were contacted for missing information. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials of preventive zinc supplementation. Hospitalised children and children with chronic diseases were excluded. RESULTS: 80 randomised trials with 205 401 participants were included. There was a small but non-significant effect on all-cause mortality (risk ratio (RR) 0.95 (95% CI 0.86 to 1.05)). Supplementation may reduce incidence of all-cause diarrhoea (RR 0.87 (0.85 to 0."},{"id":"source_31","type":"source","study":"Effect of zinc supplementation on inflammatory markers and adipokines in young obese women.","year":2014,"doi":"10.1007/s12011-013-9885-3","url":"https://doi.org/10.1007/s12011-013-9885-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Kim 2014","excerpt":"Obesity is a chronic inflammatory state characterized by altered adipokine production and increased levels of inflammatory cytokines. The study explored the effect of zinc supplementation on inflammatory markers and adipocyte hormones in young obese women. Twenty five non-obese women and forty obese women (body mass index ≥25 kg/m(2)) aged 19-28 years were recruited for this study. Twenty obese women of the study group took 30 mg/day of supplemental zinc as zinc gluconate for 8 weeks and 20 obese women of control group took placebo. Usual dietary zinc intake was estimated from 3-day diet records. Serum zinc and urinary zinc concentration were measured by Atomic Absorption Spectrophotometry. Inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 and adipocyte hormones such as lepin and adiponectin were measured by enzyme immunoassay. Inflammatory markers and leptin were significantly higher, but adiponectin was significantly lower in obese women than non-obese women. Zinc supplementation increased serum zinc by 15% and urinary zinc by 56% (P < 0.05). The levels of hs-CRP (P = 0.03) and IL-6 (P = 0."},{"id":"source_32","type":"source","study":"Efficacy of zinc supplementation on serum calprotectin, inflammatory cytokines and outcome in neonatal sepsis - a randomized controlled trial.","year":2017,"doi":"10.1080/14767058.2016.1220524","url":"https://doi.org/10.1080/14767058.2016.1220524","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Banupriya 2017","excerpt":"OBJECTIVE: To find out the efficacy of zinc supplementation in decreasing the levels of serum calprotectin and inflammatory cytokines with improvement in outcome in neonatal sepsis. METHODS: Neonates with clinical signs suggestive of sepsis and at least two screening tests positive were randomized into two groups - zinc group and control group. The zinc group received 3 mg/kg of zinc sulfate monohydrate twice a day orally for 10 days along with antibiotics. The control group received antibiotics and supportive care. Serum zinc, calprotectin, TNF-α and IL-6 were estimated in serum at recruitment and 10 days later after completion of antibiotics. The babies were monitored daily till discharge and mortality rate was compared between the groups. RESULTS: Baseline characteristics were similar between the groups. Serum zinc levels were considerably increased in the zinc group after supplementation. There was significant decline in concentrations of serum calprotectin, TNF-α and IL-6 (p < 0.05) in the zinc group. In the control group also, serum calprotectin and IL-6 levels were found to be decreased significantly after antibiotic treatment (p < 0."}],"edges":[{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_1","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_2","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_3","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_4","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_5","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_6","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_7","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_8","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_9","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_10","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_11","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_12","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_13","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_14","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_15","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_16","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_17","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_18","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_19","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_20","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_21","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_22","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_23","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_24","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_25","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_26","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_27","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_28","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_29","type":"contains_claim"},{"from":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","to":"claim_30","type":"contains_claim"}],"screening":{"identified":32,"screened":32,"excluded":0,"included":32,"included_or_retained":32,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"32 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}