The role of vitamin D in outcomes of critical care in COVID-19 patients: evidence from an umbrella meta-analysis of interventional and observational studies.

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; I2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I2 = 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.

The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses.

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases. Several meta-analyses have shown that curcumin could improve the function of the knee and alleviate pain in OA, while some meta-analyses demonstrate controversial results. Hence, we assessed curcumin's effects on knee OA in an umbrella meta-analysis. PubMed, Scopus, Embase, and Web of Science databases were employed to find English-language meta-analyses of randomized controlled trials investigating the effect of curcumin supplementation on OA outcomes up to September 2023. The visual analog scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, function, and stiffness scales were analyzed. Effect sizes and 95% confidence intervals were utilized to obtain the overall effect size. A random-effects model was applied to perform the meta-analysis. Heterogeneity was determined by I2 statistics and the Cochrane Q-test. The pooled effect of the 11 included meta-analyses showed that curcumin could significantly decrease the VAS score (weighted mean difference [WMD] and standardized mean difference [SMD]), WOMAC-total (SMD and WMD), WOMAC-Function (SMD and WMD), WOMAC-Pain (SMD), and WOMAC-Stiffness scores (SMD) (p ≤ 0.001, ≤0.001, ≤0.001, 0.007, ≤0.001, 0.002, ≤0.001, ≤0.001, respectively). The results strongly support curcuminoid supplementation in relieving pain, improving joint mobility and stiffness, and shortening medication usage of OA patients.

Effects of fenugreek supplementation on the components of metabolic syndrome: A systematic review and dose-response meta-analysis of randomized clinical trials.

Metabolic syndrome (MetS) is a cluster of metabolic disorders with a heavy disease burden. Fenugreek was reported to be effective in some components of MetS. Therefore, a comprehensive review and meta-analysis of randomized controlled trials was conducted to study the effects of fenugreek on MetS indices. From the beginning until August 2022, PubMed, Embase, Scopus, and Web of science were searched. Data were analyzed using the random-effect model, and presented as weighted mean difference (WMD) and associated 95 % confidence interval (CI). This meta-analysis comprised from a total of 29 eligible RCTs with 31 arms measuring fasting plasma glucose (FPG), Triglyceride (TG), high-density lipoprotein (HDL), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The results indicated significant improving effects of fenugreek on FPG (WMD: -16.75 mg/dL; 95 % CI: -23.36, -10.15; P < 0.001), TG (-20.12 mg/dL; 95 % CI: -34.238, -5.994; P < 0.001), HDL (WMD: 3.55 mg/dL; 95 % CI: 1.98, 5.12; P < 0.001), WC (WMD: -2.51; 95 % CI: -3.78, -1.24; P < 0.001) and SBP (WMD: -3.45 mmHg; 95 % CI: -6.38, -0.52; P = 0.021); However the effect on DBP (WMD: 3.17; 95 % CI: -5.40, 11.73; P = 0.469) and BMI (WMD: -0.40 kg/m2; 95 % CI: -1.114, 0.324; P = 0.281) was not significant. Administration of fenugreek can meaningfully reduce FPG, TG, WC, and SBP and increase HDL. The overall results support possible protective and therapeutic effects of fenugreek on MetS parameters.

Vitamin D protects against depression: Evidence from an umbrella meta-analysis on interventional and observational meta-analyses.

Meta-analyses of interventional and observational studies investigating the efficacy and the relationship between vitamin D and depression provided inconsistent results. The current umbrella meta-analysis was conducted to assess the available evidence and provide a conclusive outcome in this regard. The following international databases were systematically searched till March 2022: PubMed, Scopus, Embase, Web of Science, and Google Scholar. Random-effects model was carried out to calculate the pooled point estimates and their respective 95 % confidence intervals (CI). Ten meta-analyses of randomised controlled trials (RCTs) revealed significant reduction in depression symptoms comparing participants on vitmain D supplements to those on placebo (Pooled standardised mean difference: - 0.40; 95 % CI: - 0.60, - 0.21, p < 0.01: I2 = 89.1 %, p < 0.01). Four meta-analyses of cohort studies (with one having two subgroups) revealed that participants with lower levels of serum vitamin D were at increased odds of depression than those with higher levels of serum vitamin D (Pooled odds ratio: 1.60; 95 % CI: 1.08, 2.36, p < 0.01; I2 = 91.3 %, p < 0.01). The present umbrella meta-analysis confirms the potential benefits of vitamin D supplementation and higher serum vitamin D levels in reducing the development and symptoms of depression.

Probiotics act as a potent intervention in improving lipid profile: An umbrella systematic review and meta-analysis.

Several meta-analysis studies have revealed improving effects of probiotics on lipid profile, while some studies have reported controversial findings. The purpose of present study was to evaluate the efficacy of probiotics on blood lipids. Relevant studies were searched in the international databases, including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central Library up to August 2021. The pooled results were calculated with the use of a random-effects model to assess the effects of probiotics on blood lipids. Overall, 38 meta-analyses were inclueded in the study. The results indicated that the probiotics supplementation was effective on reduction of total cholesterol (TC) (ES= -0.46 mg/dL; 95% CI: -0.61, -0.30, p < 0.001; I2= 83.8%, p < 0.001), triglycerides (TG) (ES= -0.13 mg/dl; 95% CI: -0.23, -0.04, p = 0.006; I2= 74.7%, p < 0.001), and low-density lipoprotein cholesterol (LDL-C)levels (ES= -0.29 mg/dL; 95% CI: -0.40, -0.19, p < 0.001; I2= 77.8%, p < 0.001). There was no significant effect of probiotics on high-density lipoprotein cholesterol (HDL-C) levels (ES= 0.02 mg/dl; 95% CI: -0.04, 0.08, p = 0.519; I2= 72.5%, p= <0.001). The results of present umbrella meta-analysis strongly support supplementation with probiotics as an influential intervention for improving lipid profile.

Probiotics as an effective therapeutic approach in alleviating depression symptoms: an umbrella meta-analysis.

Growing evidence has suggested that the consumption of probiotics can decrease depressive symptoms. However, even the results of meta-analyses are conflicting. In this regard, we performed an umbrella meta-analysis and proposed the decisive impacts of probiotics on depressive symptoms. The following international databases were searched up to July 2021: PubMed/Medline, Web of Science, Scopus, EMBASE, and Google Scholar. Meta-analyses investigating the impact of supplementation of probiotics on depression symptoms in adults were included. According to the studies, random-effects model was used to perform the analysis. Subgroup analysis was performed by dosage of probiotics, duration of supplementation and total sample size. Publication bias was assessed using Egger's, Begg's and visual inspection of funnel plot. Ten meta-analyses (n = 8886 participants) were included in study. The pooled data indicated that probiotic supplementation significantly reduced depression symptoms (ES= -1.41; 95% CI: -2.53, -0.30, p = 0.016; I2 = 99.4, p = <0.001). Subgroup analysis of studies with intervention duration >8 weeks and dosage >10 × 109 CFU demonstrated a more robust effect of probiotics on decreasing depression symptoms. There was also significant between-study heterogeneity in which dosage was identified as source of it. The results of present umbrella meta-analysis suggest administration of probiotics for relieving depression symptoms for >8 weeks with dosage of >10 × 109 CFU.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2051164.

Effects of probiotics supplementation on blood pressure: An umbrella meta-analysis of randomized controlled trials.

AIMS: Several meta-analyses have revealed that probiotics could lower blood pressure (BP), but the findings were inconsistent. In this regard, an umbrella meta-analysis was carried out to provide a more accurate estimate of the overall impacts of probiotics supplementation on BP. DATA SYNTHESIS: We searched the following international databases till November 2021: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar. A random-effects model was applied to evaluate the effects of probiotics on BP. Sensitivity analysis was performed by using the leave-one-out method. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. Pooled effect size of 14 meta-analyses with 15,494 participants indicated significant decreases in both systolic (Weighted mean difference (WMD) = -1.96 mmHg; 95% confidence interval (CI): -2.78, -1.14, p < 0.001, and standardized mean difference (SMD) = -2.62; 95% CI: -4.96, -0.28, p < 0.001) and diastolic BP (WMD = -1.28 mmHg; 95% CI: -1.76, -0.79, p < 0.001, and SMD = -0.60 mmHg; 95% CI: -1.08, -0.12, p = 0.014) following probiotics supplementation. Greater effects on SBP were revealed in trials with a mean age of >50 years and the duration of intervention ≤10 weeks. DBP was also more reduced in studies with a dosage of ≥1010 colony forming unit (CFU), and SBP was decreased in patients with hypertension or diabetes analyzing WMD. CONCLUSION: The present umbrella meta-analysis suggests probiotics supplementation to improve BP and claims that probiotics could be used as a complementary therapy for controlling high BP. PROSPERO ID: CRD42022306560.

Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials.

PURPOSE: Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS: Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS: A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION: Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.

The effect of propolis supplementation in improving antioxidant status: A systematic review and meta-analysis of controlled clinical trials.

The present study aimed to assess the effect of propolis supplementation on oxidative status, a key contributor to the etiology of many chronic diseases. A systematic search of multiple databases, including Web of Science, SCOPUS, Embase, PubMed, and Google Scholar, was conducted from inception to October 2022 to identify articles examining the effect of propolis on glutathione (GSH), glutathione peroxidase (GPX), total antioxidant capacity (TAC), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. The quality of the included studies was evaluated using the Cochrane Collaboration tool. A total of nine studies were included in the final analysis, and a random-effects model was used to pool the estimated effects. Results showed that propolis supplementation significantly increased the levels of GSH (SMD = 3.16; 95% CI: 1.15, 5.18; I2 = 97.2%), GPX (SMD = 0.56; 95% CI: 0.07, 1.05; p = 0.025; I2 = 62.3%), and TAC (SMD = 3.26; 95% CI: 0.89, 5.62; I2 = 97.8%, p < 0.001). However, the effect of propolis on SOD was not significant (SMD = 0.05; 95% CI: -0.25, 0.34; I2 = 0.0%). Although the MDA concentration was not significantly decreased overall (SMD = -0.85, 95% CI: -1.70, 0.09; I2 = 93.3%), a significant decrease in MDA levels was observed at doses ≥1000 mg/day (SMD = -1.90; 95% CI: -2.97, -0.82; I2 = 86.4) and supplementation durations of less than 11 weeks (SMD = -1.56; 95% CI: -2.60, -0.51; I2 = 90.4). These results suggest that propolis is a safe supplement with a beneficial effect on GSH, GPX, and TAC levels and may be an effective adjunctive therapy for diseases where oxidative stress is a key factor in the etiology. However, further high-quality studies are necessary to make more precise and comprehensive recommendations given the limited number of studies, clinical diversity, and other limitations.

Can omega-3 fatty acids and vitamin E co-supplementation affect obesity indices?

Background: Studies have shown that vitamin E as an antioxidant protects omega-3 fatty acids (FAs) from oxidation. Several studies have evaluated the effect of omega-3 FAs and vitamin E co-supplementation on obesity indices; however, the results are inconsistent. The present systematic review and meta-analysis was conducted to address the role of omega-3 FAs plus vitamin E on obesity indices. Methods: Cochrane Library, PubMed, Scopus, Embase, and Web of Science databases were searched up to February 2022. Among all of the qualified studies, 10 articles were selected. The effect size was presented as weighted mean difference (WMD) and 95% confidence interval (CI). Fixed-effects model was employed to perform meta-analysis. Subgroup analysis and publication bias assessment were carried out. Results: Ten eligible randomized controlled trials comprising 558 participants were included. The average dose of omega-3 FAs and vitamin E co-supplementation in studies was 1000-4000 mg/day and 400 IU, respectively. Intervention duration varied from 6 to 16 weeks. There was no significant effect of omega-3 and vitamin E co-supplementation on body weight (BW) (WMD=0.14 kg; 95% CI: -0.13 to 0.42; p=0.297), and body mass index (BMI) (WMD=0.08, 95% CI: -0.01 to 0.16, p=0.073). However, subgroup analysis showed that it might increase BMI in women over 50 years and if the intervention lasted more than 8 weeks. Conclusion: There was no significant impact of combined omega-3 FAs and vitamin E supplementation on BW and BMI; however, it should be noted that the intervention has an increasing impact when supplementation duration was >8 weeks and in individuals with type 2 diabetes mellitus, >50 years old, and BMI>25 kg/m2.

Saffron, as an adjunct therapy, contributes to relieve depression symptoms: An umbrella meta-analysis.

BACKGROUND: Saffron is a traditional herbal medicine that has been used to treat various ailments such as depressive mood. However, the findings of several meta-analyses regarding anti-depressive properties of saffron (Crocus sativus L.) are controversial. The current umbrella meta-analysis was carried out to determine the magnitude and direction of saffron administration on depression. METHODS: Relevant studies were searched in international databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central Library up to June 2021. Meta-analysis studies investigating the effects of saffron on depression were considered to include in the study. Random-effects model was used to perform the meta-analysis. Additional analyses including subgroup and sensitivity analyses were carried out. RESULTS: Overall, 7 meta-analyses were included in the study. The results demonstrated that the consumption of saffron resulted in a significant reduction in BDI scores (ES: -3.87; 95% CI: -5.27, -2.46). However, saffron did not change the HAMD scores (ES: -2.10; 95% CI: -5.05, 0.86, p = 0.164) and mixed scores (HAM-D/BDI/DASS) (ES: 0.02; 95% CI: -0.39, 0.43,p = 0.941). CONCLUSION: Present umbrella meta-analysis demonstrated that saffron intake might contribute to alleviation of depression disorder, however, it cannot be considered as a single therapeutic approach to treat depression.

Probiotic therapy, a novel and efficient adjuvant approach to improve glycemic status: An umbrella meta-analysis.

BACKGROUND: Probiotics exert several promoting effects on the glycemic status, however, the results of meta-analyses are inconsistent. we conducted an umbrella meta-analysis, across existing systematic reviews and meta-analyses of clinical trials to determine the definite effects of supplementation with probiotics on glycemic indices. METHODS: A comprehensive systematic search of PubMed/Medline, Scopus, EMBASE, and Web of Science was carried out till August 2021. The random-effects model was employed to conduct meta-analysis. Meta-analysis studies of randomized clinical trials examining the impacts of probiotics supplementation on glycemic indices were qualified in the current umbrella meta-analysis. RESULTS: 48 articles out of 693 in the literature search qualified for inclusion in the umbrella meta-analysis. Pooled effects of probiotics on fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and insulin levels were reported in articles 45, 21, 35, and 33, respectively. The analysis indicated a significant decrease of FPG (ES= -0.51 mg/dL; 95% CI: -0.63, -0.38, p < 0.001), HbA1c (ES = -0.32 mg/dL; 95% CI: -0.44, -0.20, p < 0.001), HOMA-IR (ES= -0.56; 95% CI: -0.66, -0.47, p < 0.001), and insulin levels (ES= -1.09 IU/mL; 95% CI: -1.37, -0.81, p = 0.006) by probiotics supplementation. CONCLUSION: Probiotics have amending effects on FPG, HbA1c, HOMA-IR, and insulin levels. A < 8-week period of probiotic supplementation in the moderate dosages (108 or 109 CFU) is an efficacious approach in improving glycemic parameters. Overall, probiotics could be recommended as an adjuvant anti-hyperglycemic agent.

Profiling inflammatory cytokines following zinc supplementation: a systematic review and meta-analysis of controlled trials.

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.

The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies.

BACKGROUND: Cytochrome P450s (CYPs) are a class of hemoproteins involved in drug metabolism. It has been reported that body composition, proportion of dietary macronutrients, fasting and nutritional status can interfere with the activity of drug-metabolizing CYPs. OBJECTIVES: The present systematic review was conducted to summarize the effect of obesity, weight reduction, macronutrients, fasting and malnutrition on the CYP-mediated drug metabolism. METHODS: PubMed (Medline), Scopus, Embase and Cochrane Library databases and Google Scholar were searched up to June 2020 to obtain relevant studies. The PRISMA guidelines were employed during all steps. Two reviewers independently extracted the information from the included studies. Studies investigating CYPs activity directly or indirectly through pharmacokinetics of probe drugs, were included. Increase in clearance (CL) or decrease in elimination half-life (t½) and area under the curve (AUC) of probe drugs were considered as increase in CYPs activity. RESULTS: A total of 6545 articles were obtained through searching databases among which 69 studies with 126 datasets fully met the inclusion criteria. The results indicated that obesity might decrease the activity of CYP3A4/5, CYP1A2 and CYP2C9 and increase the activity of CYP2E1. The effect of obesity on CYP2D6 is controversial. Also, weight loss increased CYP3A4 activity. Moreover, CYP1A2 activity was decreased by high carbohydrate diet, increased by high protein diet and fasting and unchanged by malnutrition. The activity of CYP2C19 was less susceptible to alterations compared to other CYPs. CONCLUSION: The activity of drug-metabolizing CYPs are altered by body composition, dietary intake and nutritional status. This relationship might contribute to drug toxicity or reduce treatment efficacy and influence cost-effectiveness of medical care.

Effect of L-carnitine supplementation on lipid profile and apolipoproteins in children on hemodialysis: a randomized placebo-controlled clinical trial.

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).

Spirulina supplementation and oxidative stress and pro-inflammatory biomarkers: A systematic review and meta-analysis of controlled clinical trials.

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/m2 . 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.

Spirulina supplementation as an adjuvant therapy in enhancement of antioxidant capacity: A systematic review and meta-analysis of controlled clinical trials.

BACKGROUND: Spirulina, a type of blue-green algae, is used as an adjuvant treatment of metabolic and inflammatory diseases. Evidence about the effects of spirulina on antioxidant system are conflicting. Thus, this quantitative review aimed to summarise the effects of spirulina administration on antioxidant status biomarkers. METHODS: Systematic searches were conducted using the PubMed/Medline, Scopus, Web of Science and EMBASE, up to May 2021. 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. Trim and fill analysis were also carried out in case of the presence of publication bias. RESULTS: A total of nine articles that enrolled 415 subjects were included in the present meta-analysis. Obtained findings exhibited that spirulina supplementation had marginal significant effect on total antioxidant capacity (TAC) (SMD = 0.49; 95% CI: -0.001, 0.98; P = .05) and superoxide dismutase (SOD) activity (SMD = 0.72; 95% CI: -0.03, 1.46; P = .06), while did not affect glutathione peroxidase (GPx) activity (SMD=0.27; 95% CI: -0.23, 0.77; P = .29). CONCLUSIONS: Spirulina consumption may exert beneficial effects on enhancement of antioxidant system. A marginal significant increasing effect on TAC and SOD activity were found by spirulina administration. However, it did not affect GPx activity.

Investigation of the clinical efficacy of Zn supplementation in improvement of oxidative stress parameters: A systematic review and dose-response meta-analysis of controlled clinical trials.

BACKGROUND/OBJECTIVES: Clinical efficacy of zinc (Zn) supplementation in the improvement of oxidative stress biomarkers has been investigated in some clinical trial studies. The purpose of the current dose-response meta-analysis is to systematically aggregate and evaluate all related studies to highlight the possible effect of Zn supplementation on oxidative stress. METHODS: Systematic search was performed on Scopus, PubMed/Medline, Web of Science and Embase up to 31 December 2020. The random effect method was used to perform pooled analysis. Possible sources of heterogeneity were found using subgroup analysis and meta-regression. In the presence of publication bias, trim and fill analysis was performed to adjust the results. Non-linear relationship between effect size and variables was investigated by performing dose-response analysis. The quality of included studies was assessed using Cochrane Collaboration's tool. RESULTS: Pooled-analysis of 18 studies showed that Zn supplementation improved MDA and Hcys levels (SMD = -1.53 µmol/L; 95% CI: -2.22, -0.85; P < .001 and SMD = -0.62 µmol/L; 95% CI: -1.08, -0.15; P < .001, respectively). There was no significant effect of Zn supplementation on TBARS (SMD = -0.59 µmol/l; 95% CI: -1.31, 0.13; P = .108). Zn had maximum reducing effect on MDA in <40 mg/day dosage. CONCLUSION: Zn supplementation reduces MDA and Hcys levels, but not TBARS level. Supplementation with Zn <40 mg/day has an optimum effect on MDA level. Zn supplementation could be considered clinically as a beneficial approach in amending oxidative stress.

Spirulina supplementation and anthropometric indices: A systematic review and meta-analysis of controlled clinical trials.

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; I2 = 82.4%, p < .001), and waist circumference (WMD = -1.09 cm; 95% CI: -2.16, -0.01; p = .046; I2 = 0.0%, p = .757) while no significant effect was shown on body mass index, even after sensitivity analysis (SMD = -0.53 Kg/m2 ; 95% CI: -1.25, 0.19; p = .149; I2 = 92.9%, p < .001); however, spirulina was effective in studies lasted for at least 12 weeks (SMD = -1.25 Kg/m2 ; 95% CI: -2.21, -0.28; p = .011; I2 = 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.

The effect of L-arginine supplementation on obesity-related indices: A systematic review and meta-analysis of randomized clinical trials.

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 I2 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/m2; 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.