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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.
Hosseini, R, Ferns, GA, Sahebkar, A, Mirshekar, MA, Jalali, M
Cytokine. 2021;:155396
Abstract
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, I2 = 90.2%), tumor necrosis factor-alpha (TNF-α) (ES = -0.49 pg/mL, 95% CI = [-084, -0.14], P = 0.006, I2 = 34.6%) and malondialdehyde (MDA) (ES = -0.42, 95% CI = [-083, -0.01], P = 0.04, I2 = 76.1%) were significantly reduced in the groups receiving Zn. Serum interleukin 6 (ES = -1.02 pg/mL, 95% CI = [-2.06, 0.02], P = 0.05, I2 = 92.3%) was marginally reduced following Zn supplementation. Moreover, treatment duration was found as the source of inter-study heterogeneity. CONCLUSION This meta-analysis suggests that Zn supplements reduce serum concentrations of markers of inflammation and oxidation: CRP, TNF-α and MDA.
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Zinc status in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis of observational studies.
Ghoreishy, SM, Ebrahimi Mousavi, S, Asoudeh, F, Mohammadi, H
Scientific reports. 2021;(1):14612
Abstract
Previous studies regarding the zinc status in attention-deficit/hyperactivity disorder (ADHD) yielded inconsistent results. Thus, the present meta-analysis was aimed to estimate the association between hair and serum/plasma zinc levels and ADHD. Online databases of Medline, EMBASE, and Scopus were searched up to October 2020 with no limitation in time and language. Weighted mean differences (WMDs) of hair and serum/plasma zinc levels were calculated using a random-effects model. Overall, 22 articles with 1280 subjects with ADHD and 1200 controls were included. The pooled effect size indicated that serum/plasma zinc levels in subjects with ADHD were not statistically different than their controls (WMD = - 1.26 µmol/L; 95% CI - 3.72, 1.20). Interestingly, the exclusion of one study from the analysis showed that people with ADHD significantly have lower circulating levels of zinc compared to their controls (WMD: - 2.49 µmol/L; 95% CI - 4.29, - 0.69). Also, the pooled effect size indicated that hair zinc levels in cases with ADHD were not statistically different than their controls (WMD = - 24.19 μg/g; 95% CI - 61.80, 13.42). Present meta-analysis raises the possibility that subjects with ADHD are prone to have declined levels of zinc levels. Based on current findings, screening the zinc levels in subjects with ADHD could be reasonable. Further well-designed studies are needed to clarify the role of zinc in the etiology of ADHD.
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Ovarian cancer risk according to circulating zinc and copper concentrations: A meta-analysis and Mendelian randomization study.
Lin, S, Yang, H
Clinical nutrition (Edinburgh, Scotland). 2021;(4):2464-2468
Abstract
BACKGROUND & AIMS Ovarian cancer is a lethal disease with few modifiable risk factors. Circulating zinc and copper are potential biomarkers for ovarian cancer; however, evidence of their causal effects are scarce. This study aimed to examine the impact of circulating zinc and copper concentrations on ovarian cancer risk, using meta-analysis and Mendelian randomization (MR) approaches. METHODS Twenty case-control studies, including 699 patients with ovarian cancer, 567 patients with benign ovarian lesions, and 1194 healthy controls, were selected for meta-analysis. With a Two-sample MR approach, genetic instruments of 21 single nucleotide polymorphisms (SNPs) associated with circulating zinc and 25 SNPs associated with circulating copper were created. Their genetic associations with ovarian cancer were extracted from a genome-wide association study of 25,509 ovarian cancer cases and 40,941 controls. RESULTS Ovarian cancer patients had significantly lower concentrations of circulating zinc than healthy controls (Standardized mean differences [SMD] = -1.01, 95% CI: -1.38 to -0.64). In contrast, circulating copper concentrations were significantly higher in ovarian cancer patients (SMD = 1.46, 95% CI: 0.82 to 2.09). In MR analysis, we only found increased circulating zinc concentration causally associated with a lower risk of ovarian cancer (odds ratio = 0.968, 95% CI: 0.941 to 0.995, per SD of ranked-inverse normalized concentration), especially in the high-grade serous subtype. CONCLUSIONS Although increased circulating copper and decreased zinc concentrations were found in ovarian cancer patients, a suggestive causal association was only detected with zinc concentration, suggesting further studies on zinc interventions for ovarian cancer might have clinical impact.
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Profiling inflammatory cytokines following zinc supplementation: a systematic review and meta-analysis of controlled trials.
Faghfouri, AH, Baradaran, B, Khabbazi, A, Khaje Bishak, Y, Zarezadeh, M, Tavakoli-Rouzbehani, OM, Faghfuri, E, Payahoo, L, Alipour, M, Alipour, B
The British journal of nutrition. 2021;(10):1441-1450
Abstract
Chronic inflammation has been considered as the main cause of chronic diseases. Zn has anti-inflammatory effects by decreasing the expression of inflammatory markers. The present systematic review and meta-analysis study aims to evaluate the impact of Zn supplementation on inflammation. PubMed (Medline), Scopus, Web of Science, and Embase databases were searched up to 10 December 2020. Controlled trials which have investigated the effects of Zn supplementation on serum/plasma levels of inflammatory cytokines in subjects aged >15 years were included. A pooled meta-analysis was performed using a random effect model. Sensitivity analysis was performed to determine the robustness of the observed effect sizes. A total of twelve studies was included in meta-analysis. Zn could decrease IL-6 levels (standardised mean difference (SMD) = -0·76 pg/ml; 95 % CI -1·28, -0·24; P = 0·004). There was no significant change in TNF-α (SMD = 0·42 pg/ml; 95 % CI -0·31, 1·16; P = 0·257) and IL-2 levels (SMD = 1·64 pg/ml; 95 % CI -1·31, 4·59; P = 0·277) following Zn supplementation. However, Zn could increase IL-2 significantly after the deletion of one arm in sensitivity analysis (SMD = 2·96 pg/ml; 95 % CI 2·03, 3·88; P < 0·05). Conclusively, Zn supplementation can decrease the IL-6 level. Zn increased IL-2 level after the sensitivity analysis. Zn supplementation has not ameliorative effects on TNF-α.
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Blood and hair zinc levels in children with attention deficit hyperactivity disorder: A meta-analysis.
Luo, J, Mo, Y, Liu, M
Asian journal of psychiatry. 2020;:101805
Abstract
We summarized the observational studies on the correlation between zinc and attention deficit hyperactivity disorder (ADHD) since 1986, extracted relevant data for meta-analysis to determine the relationship between zinc and ADHD. We searched PubMed, Scopus, Cochrane Library, EMBASE (included EMBASE and Medline), Web of Science and Clinical Trials.gov databases from inception to April 8, 2019. We assessed the blood zinc, hair zinc and ADHD by combined the standardized mean difference (SMD) and 95% confidence interval (CI). Statistical analysis was performed using Stata 14.0. We included 11 studies for meta-analysis. Of these, 8 studies comprising 1311 participants reported blood zinc and 3 studies comprising 206 participants reported hair zinc. The zinc levels in blood (SMD: -0.91, 95% CI: -1.88-0.07, P(SMD) < 0.068), and hair (SMD: 1.42, 95% CI: -4.49-7.33, P(SMD) = 0.638) not significantly compare ADHD with controls. Nevertheless, high heterogeneity (I2 > 97.3%) emerged among the included studies. The subgroup analysis showed that the heterogeneity of samples >100 group was significantly reduced. The sensitivity analysis found that the results changed significantly after excluding the only cross-sectional study. In conclusion, our meta-analysis showed that there was no statistically significant difference in blood zinc and hair zinc levels between ADHD children and adolescents compared with healthy children and adolescents.
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Lower circulating zinc and selenium levels are associated with an increased risk of asthma: evidence from a meta-analysis.
Chen, M, Sun, Y, Wu, Y
Public health nutrition. 2020;(9):1555-1562
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Abstract
OBJECTIVE Previous studies evaluating the associations of circulating Zn and Se levels with asthma have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize and quantitatively synthesize the evidence from observational research. DESIGN Meta-analysis. SETTING We searched PubMed, Web of Science and Scopus databases up to May 2019 for relevant available articles. Random-effects model was adopted to estimate the pooled standardized mean difference (SMD) with 95 % CI. Meta-regression analysis and 'leave-one-out' sensitivity analysis were used to assess heterogeneity. PARTICIPANTS The meta-analysis focused on general populations. RESULTS A total of twenty-six studies for Zn and forty studies for Se were included in the meta-analysis. The overall analyses identified that asthma patients had lower Zn (SMD = -0·40; 95 % CI -0·77, -0·03; I2 = 94·1 %) and Se (SMD = -0·32; 95 % CI -0·48, -0·17; I2 = 90·9 %) levels in serum or plasma compared with healthy controls. After removing the studies that contributed to the heterogeneity, the pooled SMD were -0·26 (95 % CI -0·40, -0·13; I2 = 37·42 %) for Zn and -0·06 (95 % CI -0·13, 0·02; I2 = 43·54 %) for Se. CONCLUSIONS Lower circulating Zn and Se levels might be associated with an increased risk of asthma.
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Cord blood zinc status effects on pregnancy outcomes and its relation with maternal serum zinc levels: a systematic review and meta-analysis.
Akdas, S, Yazihan, N
World journal of pediatrics : WJP. 2020;(4):366-376
Abstract
BACKGROUND The association between maternal and cord blood zinc level and pregnancy outcomes remains uncertain. The present study aims to assess whether maternal blood zinc level represents cord blood zinc level correctly. METHODS In this meta-analysis, systematic search was performed in PubMed, Web of Science, and Scopus databases for relevant available English articles which included mean and standard deviation values of cord blood zinc level up to April 2019. For the assessment of the relation between cord blood zinc level and pregnancy outcomes, the pooled standard mean difference with 95% confidence interval (CI) was used and 23 studies were analyzed. RESULTS Cumulative analysis showed that cord blood zinc level was found significantly decreased in pregnancies with complications compared with healthy pregnancy controls [REM: P = 0.0007, mean difference - 7.9 (- 12.48, - 3.31)]. For further analysis, maternal serum zinc level status was determined from same studies to compare with cord blood levels and subgroups were detected as "Preterm", "Preeclampsia", "Small for gestational age/Intrauterine growth restriction and Low birth weight". It was observed that cord blood zinc levels in subgroup analysis were also decreased and/or tend to be decreased compared to healthy pregnancies, except for preeclampsia subgroup. Also, a correlation was seen between cord blood and maternal blood zinc level status (R = 0.4365, 95% CI - 0.530, 0.756; P = 0.0351). CONCLUSION It was thought that cord blood zinc level might tend to decrease more than maternal serum zinc level in the pathological conditions during pregnancies.
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Serum copper and zinc levels in breast cancer: A meta-analysis.
Feng, Y, Zeng, JW, Ma, Q, Zhang, S, Tang, J, Feng, JF
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2020;:126629
Abstract
BACKGROUND More and more studies have investigated the relationship between serum copper (Cu) and/or zinc (Zn) levels and breast cancer (BC). However, the results are inconsistent. It is unclear whether the serum Cu to Zn ratio (Cu/Zn) is associated with BC risk. Therefore, we evaluated serum Cu and Zn concentrations, and Cu/Zn in BC through meta-analysis. MATERIALS AND METHODS Studies reporting serum Cu and/or Zn concentrations in BC patients and controls from 1991 to 2020 were identified from PubMed, CNKI, and Wanfang databases online. Based on a random effects model, summary standard mean differences (SMDs) and the corresponding 95 % confidence intervals (95 % CIs) were applied to compare the serum levels of Cu, Zn and Cu/Zn between BC patients and controls. RESULTS Thirty-six eligible studies involving 5747 female subjects were included. The present study illustrated that the BC patients had significantly higher serum Cu levels than healthy controls (HC) (SMD (95 % CI): 1.99(1.48, 2.49)) and patients with benign breast diseases (BD) (SMD (95 % CI): 0.99(0.38, 1.61)). However, Zn concentrations were statistically decreased in BC patients than HC (SMD (95 % CI): -1.20(-1.74, -0.66)) and BD (SMD (95 % CI): -1.13 (-1.73, -0.54)). Cu/Zn concentrations were remarkably increased in BC patients than HC (SMD (95 % CI): 2.75(1.79, 3.60)) and BD (SMD (95 % CI): 2.98(1.91, 4.05)) in some studies. CONCLUSION The results show that elevated serum levels of Cu and Cu/Zn, as well as decreased Zn might be associated with increased risk of breast cancer. These three parameters have the potential to distinguish breast cancer from benign breast diseases.
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Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data.
Furihata, K, Tsuchikawa, M, Miwa, T, Naito, Y, Oba, K, Sakagami, M
Nutrients. 2020;(4)
Abstract
Zinc intake is recommended for zinc deficiency. In clinical practice, polaprezinc has been used as a zinc replacement therapy for zinc deficiency. However, the efficacy of polaprezinc has not been established. To confirm the efficacy on zinc deficiency of polaprezinc and provide additional information on an appropriate regimen, we conducted a systematic review using individual patient data (IPD). We searched PubMed, the Japanese database Ichushi, and the database owned by the marketing authorization holder of polaprezinc. Randomized placebo-controlled trials that reported the serum zinc concentration were eligible. The mean difference of the change from baseline in serum zinc concentration was estimated using a fixed-effects model. The linear dose-response relationship and the subgroup effects were also assessed. Out of 54 unique randomized clinical trials (RCTs), four studies met the eligibility criteria, and we could access IPD for all of them. All three doses of polaprezinc (75 mg, 150 mg, and 300 mg) and the placebo group were examined. The dose-combined overall polaprezinc increased the change from baseline by a mean of 9.08 µg/dL (95% confidence interval: 5.46, 12.70; heterogeneity: I2 = 0.61%) compared to the placebo. A significant dose-response relationship was confirmed (p < 0.001). Baseline serum zinc concentration was considered an effect modifier in polaprezinc 300 mg. All doses of polaprezinc were tolerable, but a dose-response relationship with adverse events (AEs) was observed in gastrointestinal disorders. The dose of 300 mg may be useful among patients with baseline serum zinc concentration of less than 70 µg/dL, and 150 mg for 70 µg/dL or more.
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Role of zinc supplementation in the management of chronic liver diseases: A systematic review and meta-analysis.
Diglio, DC, Fernandes, SA, Stein, J, Azeredo-da-Silva, A, de Mattos, AA, Tovo, CV
Annals of hepatology. 2020;(2):190-196
Abstract
INTRODUCTION AND OBJECTIVES Zinc deficiency has been associated with poor prognosis in chronic liver disease. This systematic review and meta-analysis aimed to evaluate the role of zinc supplementation in the management of chronic liver diseases. MATERIALS AND METHODS We searched MEDLINE, LILACS, EMBASE, and Cochrane CENTRAL databases from inception to August 2018. We included randomized controlled trials evaluating adult patients with chronic liver disease of any etiology receiving zinc supplementation. Studies with other designs or evaluating chronic conditions other than liver disease were excluded. Two reviewers independently screened and extracted data from eligible studies. Study quality was assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomized studies. RESULTS Of 1315 studies screened, 13 were included. Six assessed chronic hepatitis C treatment, with a relative risk of 0.83 indicating no protective effect of zinc supplementation on the improvement of sustained virological response. Three evaluated response to hepatic encephalopathy treatment, with a relative risk of 0.66 indicating a favorable effect of zinc supplementation on clinical improvement of this condition. Of four studies evaluating the management of cirrhosis, two analyzed the effect of zinc supplementation on serum albumin levels, with no statistical difference between zinc and placebo groups. CONCLUSIONS Clinical trials assessing zinc supplementation in liver diseases do not show benefits in terms of clinical improvement or disease halting. There are possible benefits of zinc supplementation on hepatic encephalopathy, however, this is based on limited evidence. This research question is still open for evaluation in larger, well-designed, clinical trials.