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Objectives: Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella meta-analysis aims to evaluate influence of vitamin D supplementation on clinical outcomes and the mortality rate of COVID-19 patients., Design: Present study was designed as an umbrella meta-analysis. The following international databases were systematically searched till March 2023: Web of Science, PubMed, Scopus, and Embase., Settings: Random-effects model was employed to perform meta-analysis. Using AMSTAR critical evaluation tools, the methodological quality of the included meta-analyses was evaluated., Participants: Adult patients suffering from COVID-19 were studied., Results: Overall, 13 meta-analyses summarising data from 4 randomised controlled trial and 9 observational studies were identified in this umbrella review. Our findings revealed that vitamin D supplementation and status significantly reduced mortality of COVID-19 [Interventional studies: (ES = 0·42; 95 % CI: 0·10, 0·75, P < 0·001; I 2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I 2 = 00·0 %, P = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients., Conclusion: Overall, vitamin D status is a critical factor influencing the mortality rate, disease severity, admission to intensive care unit and being detached from mechanical ventilation. It is vital to monitor the vitamin D status in all patients with critical conditions including COVID patients.

Background and Aim: Several studies have been conducted to evaluate the effect of N-acetylecysteine (NAC) supplementation on antioxidant status, while no dose-response meta-analysis summarized the efficacy of NAC supplementation., Methods: The systematic search of literatures was conducted on Scopus, PubMed, Embase, Web of Science electronic databases. Controlled clinical trials investigating the effects of NAC on antioxidant biomarkers were included in the current meta-analysis. Random-effect model was used to perform meta-analysis. Heterogeneity was examined using I 2 index. Subgroup analysis was carried out to find the possible sources of heterogeneity. Dose-response analysis was performed to find the non-linear relationships between effect size and independent variables., Results: Overall, 26 eligible studies were included in the review. NAC supplementation significantly increased TAC (SMD = 0.77 μmol/L; 95% CI: 0.38, 1.16; p < 0.001), GSH (SMD = 0.80 nmol/ml; 95% CI:0.25, 1.34; p = 0.004) and CAT (SMD = -0.57 IU/L; 95% CI:-1.13, -0.02; p = 0.042) levels. However, no significant improving effect was observed in terms of GR (SMD = 0.25 IU/g; 95% CI:-0.14, 0.63; p = 0.210), SOD (SMD = 0.14 U/ml; 95% CI:-0.20, 0.49; p = 0.414) and GPx (SMD = 0.19 IU/g; 95% CI:-0.48, 0.86; p = 0.576) levels. Furthermore, dose-response analysis show that NAC supplementation in participants with mean age up to 30 years had more robust effect on increasing GSH levels., Conclusion: We found a significant effect of NAC supplementation on TAC, GSH, CAT in adults. Overall, NAC could be considered as a potent agent in enhancing antioxidant capacity., Competing Interests: Declaration of competing interest None., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Although several studies have indicated that consumption of probiotics is effective in the treatment of obesity, the results in this regard have yielded controversial findings. The current umbrella meta-analysis was performed to evaluate the effects of probiotics supplementation on obesity indices in adults. Scopus, PubMed, Web of Science, Embase and Google Scholar were searched for relevant studies published till November 2021. Meta-analysis was conducted using the random-effects model. Sensitivity and subgroup analyses were performed. In total, 29 meta-analyses with 14,366 participants, including 112, 78, and 38 unique trials for body mass index (BMI), body weight (BW), and waist circumference (WC), were included in the study, respectively. The findings demonstrated that the probiotics supplementation was significantly effective on decreasing of BMI (ES = -0.21; 95% CI: -0.30, -0.13, p < 0.001; I 2  = 83.0%, p < 0.001), BW (ES = -0.38, 95% CI: -0.60, -0.16; p < 0.001; I 2  = 81.8%, p < 0.001), and WC (ES = -0.60; 95% CI: -0.89, -0.31; p < 0.001; I 2  = 89.1%, p < 0.001). Greater effects on BW were observed when intervention duration was >8 weeks and on obese individuals. BMI was also greatly modified in participants with metabolic syndrome and when intervention duration lasted for ≥12 weeks. The methodological quality (AMSTAR2) was moderate in 83%, low in 10%, and critically low in 7% of included studies. The current umbrella meta-analysis indicated that supplementation of probiotics in adults led to a meaningful reduction in BW, BMI, and WC. Therefore, our findings strongly recommend supplementation with probiotics as a potent intervention in the management of obesity., (Copyright © 2022. Published by Elsevier B.V.)

N-acetylcysteine (NAC) is one of the antioxidant supplements which is thought to improve recovery. Existing studies regarding NAC and recovery presented conflicting results. This systematic review and meta-analysis evaluated the existing trials and determined the efficacy of acute and chronic NAC administration on recovery biomarkers. PubMed, Web of Science, and Scopus were searched up to July 2021. The random effects or fixed effects model was applied in the meta-analysis. Sensitivity and subgroup analyses were performed. In case of the presence of publication bias, standard methods were applied. The meta-analysis comprised 37 papers (1,388 participants). All included studies were in English language. Acute NAC administration indicated no significant effects on lactate, pH, VO 2 , and CPK-MB ([SMD = -0.06 mmol/L; 95% CI: -0.40, 0.28; p = .714], [SMD = 0.17; 95% CI: -0.28, 0.62; p = .454], [SMD = -0.11 L/min; 95% CI: -0.63, 0.41; p = .686], and [SMD = -0.19 units/L; 95% CI: -0.62, 0.24; p = .395]). Additionally, no evidence of significant influence of chronic NAC administration on lactate, pH, VO 2 , and CK was revealed ([SMD = 0.01 mmol/L; 95% CI: -0.25, 0.27; p = .950], [SMD = -0.51; 95% CI: -1.73, 0.70; p = .424], [SMD = -0.18 L/min; 95% CI: -0.56, 0.20; p = .361], and [SMD = -0.04 units/L; 95% CI: -0.36, 0.29; p = .821]). No considerable effect of NAC on recovery was found. PRACTICAL APPLICATIONS: Previous studies on the influence of NAC administration on recovery biomarkers have presented conflicting results. This systematic review and meta-analysis offers a broad range of detailed information on the influence of chronic and acute NAC supplementation outcomes regarding recovery biomarkers. Overall, the results support that NAC supplementation may not be effective in improving recovery biomarkers. However, subgroup analyses based on NAC dosage indicated the meaningful effect of NAC on CK-MB at the dosage of ≥100 mg/kg., (© 2022 Wiley Periodicals LLC.)

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.

Background: Cardiovascular disease (CVD) is the leading cause of death in children with chronic kidney disease (CKD) and accounts for 40% of all deaths among pediatric patients with stage 5 chronic kidney disease (CKD 5). Dyslipidemia is common in children with CKD and is considered one of the major causes of CVD in these patients. As carnitine plays a key role in lipid metabolism and because plasma levels are reduced in hemodialysis patients, the aim of this study was to determine the effects of L-carnitine supplementation on serum lipid profiles, apolipoproteins, and free carnitine (FC) levels., Methods: A total of 30 children on hemodialysis (6-18 years) were enrolled and 24 completed the study. Twelve patients received 50 mg/kg/day L-carnitine, while the other 12 patients received placebo for 10 weeks. Serum FC, total cholesterol (TC), LDL-C, HDL-C, TG, Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1) were determined at the baseline and after the intervention. One-way repeated measures analysis was used to evaluate the effects of L-carnitine supplementation., Results: Oral L-carnitine supplementation led to decreased ApoB levels and ApoB/ApoA1 ratio, but these changes were not significant compared to placebo. Meanwhile, L-carnitine supplementation significantly reduced serum LDL-C and TC and increased serum FC compared to placebo. No significant changes were observed in serum TG and HDL-C levels., Conclusion: Given the significant reduction in LDL-C and TC levels, L-carnitine supplementation had positive effects on improving hyperlipidemia in children receiving hemodialysis. For more decisive results, studies with longer duration of L-carnitine therapy on children receiving hemodialysis with significant dyslipidemia are recommended., Trial Registration: We registered the present trial in the Iranian Registry of Clinical Trials website (available at: http://www.irct.ir , identifier: IRCT20170202032367N2)., (© 2021. IPNA.)

Oxidative stress is a contributing factor to many chronic diseases. It has been investigated that zinc (Zn) may enhance the antioxidant defense. The current dose-response and time-response meta-analysis aims to determine the efficacy of Zn supplementation in improving antioxidant defense. Scopus, PubMed/Medline, Web of Science, and Embase databases were searched systematically up to December 30, 2020. Meta-analysis was performed on human controlled clinical trials using random effects method. To find any source of heterogeneity, subgroup analysis and meta-regression were performed. Trim and fill analysis was used for adjusting the publication bias. To find any non-linear relationship between variables and effect size, dose-response and time-response analyses were performed. Cochrane Collaboration's tool was used for evaluating the quality assessment. A total of 23 controlled clinical trials were analyzed. The range of Zn supplementation duration in various studies was within 4-24 weeks. Zn supplementation did not have beneficial effects on glutathione peroxidase (GPx) activity (SMD = -0.34 U/g; 95% CI: -0.93, 0.25; P = 0.258). There were significant increasing effects of Zn supplementation on glutathione (GSH) (SMD = 1.28 μmol/l; 95% CI: 0.42, 2.14; P = 0.003) and total antioxidant capacity (TAC) levels (SMD = 1.39 mmol/l; 95% CI: 0.44, 2.35; P = 0.004). Zn had ameliorative effects on superoxide dismutase (SOD) activity after elimination of publication bias (SMD: 0.84 U/g; 95% CI: 0.12, 1.56, P < 0.05). Zn could also elevate GSH and TAC levels, plus SOD activity after modifying the publication bias. Finally, Zn had no significant effect on GPx activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Studies investigating the effects of spirulina on inflammation and oxidative stress status are controversial. Therefore, the current systematic review and meta-analysis aimed to evaluate the impacts of spirulina supplementation on oxidative stress indicators and inflammatory markers. PubMed-Medline, SCOPUS, Web of Science, Embase databases and Google Scholar were searched up to 1 October 2020. Random-effect analysis was applied to perform meta-analysis. Subgroup analyses and multivariate meta-regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration's tool. A total of 11 studies that enrolled 465 subjects were included in our meta-analysis. Pooled results demonstrated a significant increase in interleukin-2 (IL-2) concentrations [Standardized mean difference (SMD = 2.69 pg/mL; 95% CI: 0.26, 5.11; P = .03)]; however this result changed to insignificant (SMD = 0.54 pg/mL; 95% CI: -1.29, 2.27; P > .05) when sensitivity analysis performed. A marginal decreasing effect were also found on interleukin-6 (IL-6) (SMD = -0.72 mg/dL; 95% CI: -1.50, 0.07; P = .073) and thiobarbituric acid reactive substances (TBARS) levels (SMD = -0.65; 95% CI: -1.37, 0.08; P = .08). In addition, results of subgroup analysis revealed a significant reduction in IL-6 and TBARS concentrations when the baseline body mass index (BMI) of participants was lower than 25 kg/m 2 . Moreover, spirulina had no significant effect on tumour necrosis factor-α (TNF-α) (SMD = -0.07 mg/dL; 95% CI: -0.33, 0.18; P = .56) and malondialdehyde (MDA) concentrations (SMD = -0.42; 95% CI: -0.98, 0.14; P = .14). Spirulina consumption contributed to a significant increase in IL-2 concentrations changing to insignificant after sensitivity analysis and marginal decreasing effects on IL-6 and TBARS levels. No considerable impacts were observed on TNF-α and MDA concentrations., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: Several mechanisms have been proposed for the effect of vitamin E on weight loss. Yet various interventional studies with wide ranges of doses and durations have reported contradictory results., Methods: Cochrane Library, PubMed, Scopus, and Embase databases were searched up to December 2020. Meta-analysis was performed using random-effect method. Effect size was presented as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was evaluated using the I 2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta regression analyses was conducted., Results: A total of 24 studies with 33 data sets were included. There was no significant effect of vitamin E on weight (WMD: 0.15, 95% CI: -1.35 to 1.65, P = 0.847), body mass index (BMI) (WMD = 0.04, 95% CI: -0.29 to 0.37, P = 0.815), and waist circumference (WC) (WMD = -0.19 kg, 95% CI: -2.06 to 1.68, P = 0.842), respectively. However, subgroup analysis revealed that vitamin E supplementation in studies conducted on participants with normal BMI (18.5-24.9) had increasing impact on BMI (P = 0.047)., Conclusion: There was no significant effect of vitamin E supplementation on weight, BMI and WC. However, vitamin E supplementation might be associated with increasing BMI in people with normal BMI (18.5-24.9)., Competing Interests: Conflicts of interest All authors declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Obesity and overweight are associated with the burden of chronic diseases. The aim of the present meta-analysis is to determine the efficacy of spirulina in reducing of obesity indices. PubMed, Web of Science, Scopus, EMBASE and Cochrane library databases were searched up to November 2019. Randomized controlled trials comparing spirulina supplementation with a placebo or no treatment for anthropometric indices were included. Meta-analysis was performed using random-effects model. Subgroup analysis and meta-regression were carried out. Publication bias was evaluated using standard methods. Spirulina had ameliorative effects on weight (WMD = -1.85 Kg; 95% CI: -2.44, -1.26; p < .001; I 2 = 82.4%, p < .001), and waist circumference (WMD = -1.09 cm; 95% CI: -2.16, -0.01; p = .046; I 2 = 0.0%, p = .757) while no significant effect was shown on body mass index, even after sensitivity analysis (SMD = -0.53 Kg/m 2 ; 95% CI: -1.25, 0.19; p = .149; I 2 = 92.9%, p < .001); however, spirulina was effective in studies lasted for at least 12 weeks (SMD = -1.25 Kg/m 2 ; 95% CI: -2.21, -0.28; p = .011; I 2 = 90.8%, p < .001). Spirulina supplementation exerts beneficial effects on weight and waist circumference. The ameliorative effect of spirulina on body mass index was revealed in longer duration of supplementation., (© 2020 John Wiley & Sons Ltd.)

The clinical studies regarding the effect of L-arginine in human anthropometry have not been fully consistent, therefore, we carried out a systematic review and meta-analysis of randomized clinical trials in order to precisely evaluate and quantify the efficacy of L-arginine on weight, waist circumference, and BMI. We searched online databases including PubMed, SCOPUS, and Google Scholar for relevant articles up to September 2017. Eligible articles were reviewed by two independent investigators. Mean differences of the outcomes were used for calculation of weighted mean difference (WMD) derived from the random-effects model. Statistical heterogeneity between studies was examined using Cochran's Q-test and I index. Funnel plot and Egger's tests were performed to assess the publication bias. In our initial search, we found 1598 publications, of which 8 RCTs (9 treatment arms) were included. The results of the meta-analysis displayed a significant reduction in WC following L-arginine supplementation (WMD: -2.97 cm; 95% CI: -4.75 to -1.18, P = 0.001). However, L-arginine intervention had not elicited a significant effect on BMI (WMD: -0.51 kg/m 2 index. Funnel plot and Egger's tests were performed to assess the publication bias. In our initial search, we found 1598 publications, of which 8 RCTs (9 treatment arms) were included. The results of the meta-analysis displayed a significant reduction in WC following L-arginine supplementation (WMD: -2.97 cm; 95% CI: -4.75 to -1.18, P = 0.001). However, L-arginine intervention had not elicited a significant effect on BMI (WMD: -0.51 kg/m 2 ; 95% CI: -1.11 to .08, P = 0.09) and body weight (WMD: -0.57 kg; 95% CI: -1.77 to 0.61, P = 0.34). Subgroup analyses displayed that longer-term interventions (≥8 weeks) had a positive effect on body weight and using < 8 g/day L-arginine with longer duration (≥8 weeks) could significantly decrease BMI. In conclusion, this meta-analysis result suggested L-arginine supplementation could reduce waist circumference without any significant effect on body weight and body mass index.

Background: Inconsistencies exist with regard to influence of vitamin D supplementation on IGF-1 levels. The inconsistencies could be attributed to several factors, such as dosage and duration of intervention, among others. To address these inconsistencies, this study was conducted to determine the impact of vitamin D supplementation on IGF-1 levels through a systematic review and meta-analysis of randomized controlled trials (RCTs)., Methods: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase for RCTs that investigated the impact of vitamin D intake on circulating IGF-1 levels from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating combined effect size. Subgroup analysis was performed to specify the source of heterogeneity among studies., Results: Pooled results from eight studies demonstrated an overall non-significant increase in IGF-1 following vitamin D supplementation (WMD: 4 ng/ml, 95 % CI: -4 to 11). However, a significant degree of heterogeneity among studies was observed (I 2 = 66 %). The subgroup analyses showed that vitamin D dosage of ≤1000 IU/day (WMD: 10 ng/ml) significantly increased IGF-1 compared to the vitamin D dosage of <1000 IU/day (WMD: -1 ng/ml). Moreover, intervention duration ≤12 weeks (WMD: 11 ng/ml) significantly increased IGF-1 compared to intervention duration <12 weeks (WMD: -3 ng/ml). In the epidemiological cohort study, participants under 60 years of age with a higher dietary vitamin D intake had significantly higher IGF-1 levels when compared to those with lower dietary vitamin D intake in second categories., Conclusion: The main results indicate a non-significant increase in IGF-1 following vitamin D supplementation. Additionally, vitamin D dosages of <1000 IU/day and intervention durations of <12 weeks significantly raised IGF-1 levels., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recently, obesity has become a common worldwide concern. Leptin, as an adipocytokine, plays a major role in the etiology of obesity. Prior studies have demonstrated that zinc potentially affects serum leptin levels. However, clinical trials carried out in this regard are not consistent. Therefore, current meta-analysis was conducted to ascertain the actual effect of zinc supplementation on serum leptin levels in adults. Databases of PubMed, SCOPUS, and Google Scholar were methodically searched to identify relevant articles up to April 2018. Clinical trials that examined the effect of zinc supplementation on serum leptin concentrations as outcome variables in human adults were included. The mean difference (SD) of leptin changes in the intervention and placebo groups were used to calculate the overall effect size. Totally, 663 articles were identified, of which 6 studies were eligible randomized controlled trials (RCTs) with 7 treatment arms. The analysis suggested that zinc supplementation exerts no significant effect on overall serum leptin (WMD: 0.74 ng/ml; 95% CI: -1.39 to 2.87, p=0.49). Nevertheless, sex and duration of intervention seemed to impact the extent of zinc's influence. In trials with female subjects, zinc consumption led to a significant decrease in serum leptin level (WMD: -1.93 ng/ml; 95% CI: -3.72 to -0.14, p=0.03) as well as trials that lasted for more than 6 weeks (WMD: -1.71 ng/ml; 95% CI: -3.07 to -0.35, p=0.01), in comparison to the control group. Zinc supplementation did not significantly improve leptin concentrations, but it may result in a decreased circulating leptin level in studies with a duration of more than 6 weeks especially among females., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aims Patients with type 2 diabetes mellitus (T2DM) are prone to cardiovascular disease (CVD) due to inflammation process and oxidative stress. ADMA (Asymmetric dimethylarginine) and ICAM-1 (inter-cellular adhesion molecule-1) play an important role in CVD pathogenesis. Ginger as an anti-oxidant and anti-inflammation can effect on these biomarkers. The aim of present study was to characterize the effect of ginger supplementation on ADMA and ICAM-1 serum levels in patients with T2DM. Methods The present study is a randomized double-blind clinical trial which is conducted among 45 diabetic patients (nginger=23, nplacebo=22). The participants were randomly divided into two intervention and placebo groups which were received 2 g ginger powder and 2 g wheat flour for 10 weeks, respectively. ADMA and ICAM-1 concentration were measured by ELISA method. Results Ginger supplementation decreased ADMA serum levels significantly (P=0.002) and sICAM-1 serum levels marginally (P=0.097) in supplementation group after intervention. No significant difference was observed between placebo and supplementation groups. Conclusions Present study was conducted among patients with type 2 diabetes mellitus to investigate the effect of ginger supplementation on ADMA and sICAM-1 levels. There was a significant decrement in ADMA serum concentration and slight reduction in sICAM-1 levels in intervention group. The amount of reduction in both biomarkers was not statistically significant in between-groups comparison.