Effect of inulin supplementation on clinical symptoms, inflammatory and oxidative stress markers in women with migraine: study protocol for a randomized clinical trial.

BACKGROUND: Migraine is a complex, chronic, and debilitating multifactorial disorder characterized by recurrent episodes of headache and related symptoms. It typically begins in early ages and is more prevalent in women than in men. Recently, the gut-brain axis has emerged as a new candidate that may be linked to neurological diseases. We hypothesize that selective modulation of the intestinal microbiota, oxidative stress, and inflammation through inulin supplementation may improve clinical outcomes in these patients. Therefore, this study aims to examine the effects of high-performance inulin supplementation on clinical symptoms, mental health, quality of life (QOL), intestinal permeability, and inflammatory and oxidative stress factors in women with migraine. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial involving 80 women with migraine who meet the inclusion criteria (aged between 20 and 50 years with a diagnosis of migraine by a neurologist based on the ICDH-3). Participants will be assigned to receive a daily dose of 10 g of inulin for 12 weeks (intervention group, n = 40) or 10 g of maltodextrin as a placebo for the same duration (control group, n = 40). The primary outcome will measure the variations in the frequency of headache experienced by the patients. Secondary outcomes will encompass serum levels of zonulin, high-sensitive C-reactive protein, total antioxidant capacity, total oxidant status, nitric oxide, mental status, QOL, duration, and severity of migraine attacks. DISCUSSION: This clinical trial aims to evaluate the effect of inulin supplementation on inflammatory status, oxidative stress, intestinal permeability, clinical symptoms, mental health, and QOL in women with migraine. The findings of this trial could contribute to the identification of mechanistic action and evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in the management of clinical outcomes in migraine patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20121216011763N58). Registration date: 23 April 2023. TRIAL STATUS: The protocol is version 3.0, September 17, 2023. Recruitment began August 21, 2023, and is anticipated to be completed by March 22, 2024.

Effect of soluble fiber on blood pressure in adults: a systematic review and dose-response meta-analysis of randomized controlled trials.

OBJECTIVES: Pervious epidemiologic evidence indicates that soluble fiber is protective against hypertention: however, randomized controlled trials (RCTs) have presented varying results. In the present study, we aimed to conduct a systematic review and dose-response meta-analysis to summarize published RCTs which assess the effect of soluble fiber supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: Scopus, PubMed, and ISI Web of Sciences were searched to identify relevant studies up to Aug 2022. We estimated the change in blood pressure for each 5 g/d increment in soluble fiber supplementation in each trial and then calculated the weighted mean difference (WMD) and 95%CI using a random-effects model. We estimated dose-dependent effects using a dose-response meta-analysis of differences in means. The risk of bias for study was assessed using the Cochrane tool. Publication bias was evaluated via funnel plot and Begg's test and Egger's test. RESULTS: Eighty-three eligible studies with total sample size of 5,985 participants were included in the meta-analysis. Soluble fiber supplementation significantly decreased SBP (WMD: -1.36 mmHg, 95% CI: -2.13 to -0.60, P < 0.001; I2 = 47.1%, P < 0.001) and DBP (WMD: -0.72 mmHg, 95% CI: -1.26 to -0.18, P = 0.009; I2 = 45.4%, P < 0.001). Each 5 g/d increment in soluble fiber supplementation had a significant reduction in SBP (WMD: -0.54 mmHg; 95%CI: -0.86, -0.22, P = 0.001; I2 = 52.2, Phet < 0.001) and DBP (WMD: -0.28 mmHg; 95%CI: -0.49, -0.80, P = 0.007; I2 = 43.1%, Phet < 0.001). The levels of SBP decreased proportionally with the increase in soluble fiber supplementation up to 20 g/d (MD20g/d: -1.79 mmHg, 95%CI: -2.86, -0.71). CONCLUSION: Current evidence indicated the beneficial effect of soluble fiber supplementation on blood pressure. Our findings suggest that soluble fiber supplementation could contribute to the management of hypertension and the reduction of cardiovascular disease risk.

Soluble Fiber Supplementation and Serum Lipid Profile: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

To present a comprehensive synthesis of the effect of soluble fiber supplementation on blood lipid parameters in adults, a systematic search was undertaken in PubMed, Scopus, and ISI Web of Science of relevant articles published before November 2021. Randomized controlled trials (RCTs) evaluating the effects of soluble fibers on blood lipids in adults were included. We estimated the change in blood lipids for each 5 g/d increment in soluble fiber supplementation in each trial and then calculated the mean difference (MD) and 95% CI using a random-effects model. We estimated dose-dependent effects using a dose-response meta-analysis of differences in means. The risk of bias and certainty of the evidence was evaluated using the Cochrane risk of bias tool and the Grading Recommendations Assessment, Development, and Evaluation methodology, respectively. A total of 181 RCTs with 220 treatment arms (14,505 participants: 7348 cases and 7157 controls) were included. There was a significant reduction in LDL cholesterol (MD: -8.28 mg/dL, 95% CI: -11.38, -5.18), total cholesterol (TC) (MD: -10.82 mg/dL, 95% CI: -12.98, -8.67), TGs (MD: -5.55 mg/dL, 95% CI: -10.31, -0.79), and apolipoprotein B (Apo-B) (MD: -44.99 mg/L, 95% CI: -62.87, -27.12) after soluble fiber supplementation in the overall analysis. Each 5 g/d increase in soluble fiber supplementation had a significant reduction in TC (MD: -6.11 mg/dL, 95% CI: -7.61, -4.61) and LDL cholesterol (MD: -5.57 mg/dl, 95% CI: -7.44, -3.69). In a large meta-analysis of RCTs, results suggest that soluble fiber supplementation could contribute to the management of dyslipidemia and the reduction of cardiovascular disease risk.

Effects of L-arginine supplementation on biomarkers of glycemic control: a systematic review and meta-analysis of randomised clinical trials.

The present meta-analysis aimed to determine the effectiveness of L-arginine supplementation in improving biomarkers of glycemic control in adults. Electronic databases including PubMed, ISI Web of Science, Scopus, and the Cochrane Collaboration Library were searched up to January 2020. The meta-analysis of twelve randomised clinical trials indicated that L-arginine had no significant effect on serum fasting blood sugar (FBS) (weighted mean difference [WMD]: -3.38 mg/dl, 95% CI: -6.79 to 0.04, p = .53), serum insulin (WMD: -0.12 Hedges' g 95% CI: -0.33 to 0.09, p = .27), glycated haemoglobin A1c (HbA1c; WMD: -0.04%, 95% CI: -0.25 to 0.17, p = .71), and homeostasis model assessment for insulin resistance (WMD: -0.48, 95% CI: -1.15 to 0.19, p = .15). Although several animal studies have proposed that L-arginine supplementation might improve blood glucose control, the present study could not confirm this benefit in humans.

Effect of soy isoflavones supplementation on migraine characteristics, mental status and calcitonin gene-related peptide (CGRP) levels in women with migraine: results of randomised controlled trial.

BACKGROUND: Literature suggests a relationship between estrogen levels and migraine headache pathogenesis. However, the effect of soy isoflavones on migraine characteristic remains unclear. This study aimed to investigate the effect of soy isoflavones on migraine characteristics and calcitonin gene-related peptide (CGRP) levels in women with migraine. METHODS: Eighty-three participants completed a randomized double-blind controlled trial, receiving 50 mg per day soy isoflavones or placebo supplementation for 8 weeks. Migraine severity, migraine days per month, frequency and duration of attacks, mental status, quality of life and serum CGRP levels were measured at baseline and the end of the intervention. Bivariate comparison and intention-to-treat (ITT) were used for analysis. RESULTS: Soy isoflavones intake resulted in a significant decrease in mean frequency (-2.36 vs -0.43, P < 0.001), duration (-2.50 vs -0.02, P < 0.001) of migraine attacks and CGRP level (-12.18 ng/l vs -8.62, P = 0.002) in compared to placebo group. Also, a significant improvement was found in quality of life (16.76 vs 2.52, P < 0.001). Although, reduction in the migraine severity and mental status did not reach a statistically significant level (P > 0.05). CONCLUSION: soy isoflavones supplementation may be considered as a complementary treatment for women with migraine to improve migraine characteristics and reduce the burden of disease.

Effect of cherry consumption on blood pressure: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The present systematic review and meta-analysis aimed to summarize the findings of randomized controlled trials (RCTs) evaluating the effect of tart and sweet cherries on systolic and diastolic blood pressure (SBP and DBP). METHODS: PubMed, Scopus, Embase, and Web of Science were searched to acquire the RCTs up to December 2020. RESULTS: Seven RCTs comprising 201 participants were included. The meta-analysis showed that cherry supplementation does not lead to a significant decrease in SBP or DBP. CONCLUSIONS: Incorporating cherries into the diet has no significant effect on blood pressure.

Biological and pharmacological effects and nutritional impact of phytosterols: A comprehensive review.

Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low-density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health-promoting effects of PSs include anti-obesity, anti-diabetic, anti-microbial, anti-inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol-rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.

The effect of zinc supplementation in children with attention deficit hyperactivity disorder: A systematic review and dose-response meta­analysis of randomized clinical trials.

OBJECTIVE: The present systematic review and dose-response meta-analysis was conducted to quantify the efficacy of zinc supplementation on clinical symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. METHODS: Electronic databases including PubMed, Scopus, ISI web of science, and Google Scholar were searched until January 2021. Results were reported as standardized mean difference (SMD) with a 95% confidence interval (CI) using Hedges's adjusted g method. RESULTS: six randomized clinical trials with 489 school-aged children were identified for the meta-analysis. Our findings showed a significant effect of zinc supplementation on ADHD total scores (SMD: -0.62 Hedges' g; 95% CI: -1.24 to -0.002, p = 0.04) but not in hyperactivity scores (SMD: -0.93 Hedges' g; 95% CI: -3.31 to 1.45, p = 0.44) and inattention scores (SMD: 0.21 Hedges' g; 95% CI: -0.09 to 0.51, p = 0.17) compared to the control group. Besides, the dose-response analysis did not find any significant non-linear association between zinc supplementation dosage or duration on ADHD total scores. The certainty of the evidence was rated moderate to very low for all outcomes. CONCLUSION: Zinc supplementation may have beneficial effects in improving ADHD symptoms in children with ADHD. Future well-designed, large-scale randomized controlled trials are needed to establish the benefit of zinc supplementation for ADHD.

Effects of zinc supplementation on inflammatory biomarkers and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & OBJECTIVE: Current evidence is debatable regarding the feasible effects of zinc supplementation on the inflammation and oxidative stress status of adults. This systematic review and meta-analysis aimed to clarify this inconclusiveness. MATERIALS AND METHODS: Literature search was conducted via online databases such as PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar until June 2020. The overall effect was presented as the weighted mean difference (WMD) at 95 % confidence interval (CI) in a random-effects meta-analysis model. Publication bias was also assessed using Egger's and Begg's statistics. RESULTS: In total, 25 clinical trials (n = 1428) were reviewed, which indicated that zinc supplementation significantly affects the concentration of C- reactive protein (WMD: -0.03 mg/l; 95 % CI: -0.06, 0.0; P = 0.029), interlukin-6 (WMD: -3.81 pg/mL; 95 % CI: -6.87, -0.76; P = 0.014), malondialdehyde (WMD: -0.78 µmol/l; 95 % CI: -1.14, -0.42; P < 0.001), and total antioxidant capacity (WMD: 95.96 mmol/l; 95 % CI: 22.47, 169.44; P = 0.010). In addition, a significant between-study heterogeneity and a non-significant increment was reported in nitric oxide (WMD: 1.47 µmol/l; 95 % CI: -2.45, 5.40; P = 0.461) and glutathione (WMD: 34.84 µmol/l; 95 % CI: -5.12, 74.80; P = 0.087). CONCLUSION: According to the results, zinc supplementation may have beneficial anti-inflammatory and anti-oxidative effects in adults.

Effect of synbiotics and probiotics supplementation on autoimmune diseases: A systematic review and meta-analysis of clinical trials.

BACKGROUND & AIMS: Today synbiotics are considered as immunomodulatory agents. The current systematic review and meta-analysis investigated the effect of synbiotics and probiotics on inflammatory and oxidative stress markers in autoimmune disease. MATERIALS & METHODS: The English literature search was performed using PubMed, Scopus, Web of Science, and the Central Cochrane Library through March 2020. Random effects models and generic inverse variance methods were used to synthesize quantitative data by STATA14. RESULTS: From a total of 623 entries identified via searches, ten RCTs (n = 440; 216 as intervention, 224 as controls) were included. An additional eleven studies with same intervention and different markers were also explained systematically. The pooled effect size showed that Interleukin (IL)-6 (WMD = -7.79 pg/ml; 95% CI = -13.81, -1.77, P = 0.011), Tumor Necrosis Factor (TNF)-α (WMD = -1.05 pg/ml; 95% CI = -2.01, -0.10, P = 0.030), high sensitivity C-Reactive Protein (hs-CRP) (SMD = -0.58; 95% CI = -0.79, -0.37, P < 0.001), Malondialdehyde (MDA) (SMD = -0.36; 95% CI = -0.68, -0.04; P = 0.026), Homeostasis Model of Assessment-estimated Insulin Resistance (HOMA-IR) (WMD = -0.71; 95% CI = -1.05, -0.37, P < 0.001), and beta cell function (HOMA-ß) (WMD = -15.18; 95% CI = -22.08, -8.28, P < 0.001) changed following probiotics (or synbiotics) supplementation. Also supplementation with doses more than 2 billion CFU could reduce IL-10 concentrations (WMD = -1.84; 95% CI = -2.23, 1.87; P < 0.001). Glutathione (GSH) and Total Antioxidant Capacity (TAC) levels did not influence by synbiotics and probiotics; insignificancy was remained after subgrouping for participants' age, study duration, and disease duration. CONCLUSION: Our findings revealed that synbiotics and probiotics supplementation has significant effect on some inflammatory and oxidative stress markers; although, the number of trials was too small to powerful conclusion and further investigations may be needed.

Effects of resveratrol supplementation on liver enzymes: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The available evidence regarding the possible effects of resveratrol on liver function is inconsistent. Therefore, the present meta-analysis was performed to investigate the overall effects of resveratrol supplementation on liver enzymes in adults. METHODS: A systematic and comprehensive search of the online medical databases including PubMed, Scupos, Web of Science and Cochran Library was performed up to February 2020. All RCTs using resveratrol supplements in adults were included in this systematic review and meta-analysis. The overall effect was presented as weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis model. RESULTS: Finally, 15 randomised trials including 714 participants were selected for the present meta-analysis. Pooled analysis did not show any significant changes in alanine aminotransferase (ALT) (WMD: 0 IU/L, 95% CI: -3.17 to 3.17, P = .99; I2 = 74.2%), aspartate aminotransferase (AST) (WMD: -2.40 IU/L, 95% CI: -5.45 to 0.65, P = .11; I2 = 82.9%), gamma-glutamyl transferase (GGT) (WMD: -1.26 IU/L, 95% CI: -4.64 to 2.13, P = .64; I2 = 23.7%), alkaline phosphatase (ALP) (WMD: 3.80 IU/L, 95% CI: -4.65 to 12.25, P = .37; I2 = 29.9%) and bilirubin (WMD: 0.13 IU/L, 95% CI: -0.43 to 0.17, P = .39; I2 = 8.9%) after supplementation with resveratrol. CONCLUSION: Overall, in our study, resveratrol does not affect liver enzyme levels significantly, but subgroup analysis indicates that these results may be influenced by resveratrol dose, duration of the study and population status, so future high-quality studies are necessary to get definitive results.

The effect of magnesium supplementation on anthropometric indices: a systematic review and dose-response meta-analysis of clinical trials.

The aim of this study was to determine the effects of Mg supplementation on anthropometric indices consisting of body weight, waist circumference (WC), BMI and body fat percentage. In this systematic review and dose­response meta-analysis, we searched PubMed, Cochrane Library, Scopus, Web of Science and Google Scholar from databases inception up to February 2020 for relevant randomised controlled trials. Quality of evidence was evaluated using the Cochrane Collaboration Tool. All the outcomes of this meta-analysis were pooled using the random effect model. Analysis of dose­response for Mg dosage was carried out using a fractional polynomial model. The systematic review and meta-analysis include twenty-eight randomised clinical trials, comprising 2013 participants. There were no significant changes in anthropometric indices after Mg supplementation in the overall analysis. However, subgroup analysis revealed that Mg supplementation decreases WC in subjects with BMI > 30 kg/m2 (obese) (twelve trials, n 997 participants; weighted mean difference = ­2·09 cm, 95 % CI ­4·12, ­0·07, P = 0·040; I2 = 0 %). Dose­response analysis revealed a non-significant non-linear effect of supplementation dosage on anthropometric indices. The results suggest that Mg supplementation is associated with lower WC only in obese subjects. However, more high-quality studies are needed to clarify the nature of this association.

What is the Impact of Cinnamon Supplementation on Blood Pressure? A Systematic Review and Meta-Analysis.

AIM: This study was designed to make a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of cinnamon on blood pressure (BP). METHODS: A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar databases was conducted up to August 2019. All RCTs using cinnamon supplements in adults were included in this systematic review and meta-analysis. RESULTS: Out of 927 records, 8 trials that enrolled 582 participants were included. The pooled effect size showed that SBP did not change following cinnamon supplementation. (WMD: -0.61mmHg; 95% CI: -1.36, 0.14, P= 0.111). Also cinnamon supplementation in long-duration (≥ 8weeks) had a significant effect on SBP (WMD: -1.25 mmHg; 95% CI: -2.22, -0.28, P= 0.012). Pooled analysis showed that cinnamon had a significant effect on DBP (WMD: -0.93mmHg, 95% CI: -1.55 to -0.32, P= 0.003). In addition, results from both duration subsets and high dose (>1500 mg/day) of cinnamon supplementation were significant. CONCLUSION: Our findings revealed that cinnamon supplementation has favorable effects on DBP although results of SBP were not the same. Nonetheless, further studies are required.

The effects of quinoa seed supplementation on cardiovascular risk factors: A systematic review and meta-analysis of controlled clinical trials.

This meta-analysis was designed to determine the effect of quinoa seed on cardiovascular disease (CVD) risk factors in adults. PubMed, Scopus, ISI Web of Science, and Cochrane library were searched electronically from their inception to February 2020 to identify eligible RCTs. We calculated the pooled estimates of weighted mean differences (WMDs) and their 95% confidence intervals (CIs) by using random-effects models. Five eligible RCTs representing 206 subjects were enrolled. The pooled result showed that quinoa seed supplementation significantly lowered the body weight (WMD: -1.26 kg, 95% CI: -2.35, -0.18, p = .02), waist circumference (WC) (WMD: -1.15 cm, 95% CI: -2.08, -0.21, p = .01), fat mass (FM) (WMD: -0.59%, 95% CI: -1.14, -0.03, p = .03), insulin serum level (WMD: -0.86 pmol/L, 95% CI: -13.38, -1.59, p = .01), triglyceride (TG) (WMD: -7.20 mg/dl, 95% CI: -9.52, -4.87, p < .001), total cholesterol (TC) (WMD: -6.86 mg/dl, 95% CI: -10.64, -3.08, p < .001), and low density lipoprotein (LDL) (WMD: -3.08 mg/dl, 95% CI: -5.13, -1.03, p = .003) levels. However, no significant changes were seen in other markers (p > .05). The current evidence suggests that quinoa seed might be utilized as a possible new effective and safe supplementary option to better prevent and control CVD in humans.

The effect of barberry (Berberis vulgaris L.) supplementation on blood pressure: A systematic review and meta-analysis of the randomized controlled trials.

OBJECTIVE: We identified and quantified the results of randomized clinical trials by examining the effect of barberry supplementation on blood pressure. METHODS: We conducted a comprehensive search in the medical bibliographic database up to May 2020 on randomized clinical trials investigating the effect of barberry supplementation on adult blood pressure. Intensive literature searches and data extraction according to a prefixed scheme was performed independently by two investigators. RESULTS: Through 5 randomized clinical trial studies, 350 subjects with 175 cases for the intervention group and 175 cases for control group were included in our study. The intervention period ranged from 4 to 12 weeks. In general, barberry supplementation did not have a significant effect on systolic blood pressure (WMD: -4.15 mmHg; 95 % CI: -10.3, 1.99, P = 0.185) and diastolic blood pressure (WMD: -1.22 mmHg; 95 % CI: -6.26, 3.82, P = 0.635). Our study was heterogeneous and subgroup analysis did not eliminate heterogeneity. CONCLUSION: Totally, based on this study, we cannot conclude that barberry supplementation has beneficial effects on blood pressure. Also, all included studies had limitations such as different in geographical situations, Dietary of participants, health conditions, and pharmacological forms of berberis. Therefore, further study in this area is recommended.

Efficacy of resveratrol supplementation in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and refers to the accumulation of triglycerides in hepatocytes. Recent studies have showed that resveratrol (antioxidant of grape) can be effective in the treatment of NAFLD through its inhibitory effect on lipid accumulation. METHOD: We systematically searched databases including: ISI web of science, Scopus, PubMed and Embase by using related keywords. Then, by considering inclusion and exclusion criteria, appropriate articles were selected. All the analyses were conducted in Review Manager (RevMan) Version 5.3. RESULTS: Finally, 6 RCTs were included in meta-analysis and systematic review. Our results showed that resveratrol supplementation significantly reduced levels of TNF-alpha (SMD = -0.46; 95% CI (-0.78, 0.14); P = 0.005) and hs-CRP (SMD = -0.53; 95% CI (-1.01, -0.05); P = 0.030), but for other markers (BW, BMI, WC, HC, WHR, SBP, DBP, ALT, AST, GGT, ALP, bilirubin, TC, TG, HDL, LDL, LDL to HDL ratio, apo-A1, apo-B, insulin, HOMA-IR, glucose, creatinine and IL-6), no significant change was observed. CONCLUSION: Overall, the results of the present study show that resveratrol supplementation does not affect the management of NAFLD although it can improve some inflammatory markers.

The effect of pomegranate (Punica granatum) supplementation on metabolic status in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: Several randomized controlled clinical trials (RCTs) have investigated the effect of pomegranate (Punica granatum) supplementation in patients with type 2 diabetes mellitus (T2DM), with conflicting results. Therefore, the present study assessed the effect of pomegranate on metabolic status and oxidative stress in patients with T2DM. METHODS: A comprehensive search was conducted in Pubmed, EMBASE, ISI web of science, Cochrane library and Scopus databases until April 2020, to identify RCTs investigating the effect of pomegranate supplementation on glycemic markers (fasting blood glucose (FBG), homeostasis model assessment-estimated insulin resistance index (HOMA-IR), glycosylated hemoglobin percentage (HbA1c) and insulin levels), anthropometric indices (body mass index (BMI) and body weight (BW)), blood lipids (triglycerides (TG), total cholesterol (TC), high lipoprotein cholesterol (HDL-C) and low lipoprotein cholesterol (LDL-C)), inflammatory markers (high sensitive c-reactive protein (Hs-CRP)) and markers of oxidative stress (total antioxidant capacity (TAC)) in adults with T2DM. Mean difference was pooled using a random-effects model. RESULTS: Seven trials, comprising 350 participants, were included in the present systematic review and meta-analysis. The results of the meta-analysis revealed that pomegranate supplementation did not have any significant effects on metabolic status and oxidative stress biomarkers of subjects with T2DM. There were no evidence of publication bias regarding to selected outcomes. CONCLUSION: There were no significant favorable effects of pomegranate supplementation on metabolic parameters in patients with T2DM. Future well-designed, large scale RCTs, with longer duration are needed in this field.

The effect of barberry (Berberis vulgaris L.) on glycemic indices: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: We performed a meta-analysis to evaluate the efficacy of barberry (Berberis vulgaris L.) supplementation on glycemic indices in adults. METHODS: A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and ISI Web of Science from inception up to January 2020, to identify randomized controlled trials (RCTs) investigating the effect of barberry supplementation on glycemic markers including fasting blood sugar (FBS) concentrations, insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and glycosylated hemoglobin (HbA1c) percentage. The results of this meta-analysis were reported, based on the random effects model. RESULTS: In total, 7 studies, comprising 452 participants, were included in the systematic review. The meta-analysis revealed that barberry significantly reduces insulin levels (Hedges's: -0.67; 95% CI: -1.31 to -0.03, P = 0.04, I2 = 73.3%). However, no considerable changes was observed for FBS levels (WMD: -8.06 mg/dL; 95% CI: -20.46 to 4.33, P = 0.23, I2 = 96.1%), HbA1c percentage (WMD: -0.83 %; 95% CI: -2.33 to 0.67, P = 0.27, I2 = 88.3%), and HOMA-IR index (WMD: -0.55; 95% CI: -1.60 to 0.50, P = 0.30, I2 = 99.4%). CONCLUSION: The present study suggests that although barberry supplementation significantly improves insulin levels; however, other glycemic indices might not be affected. However, more high-quality RCTs with longer duration are needed to further clarify the effects of barberry on blood glucose control, especially among patients with diabetes.

Benefits and harms of ginseng supplementation on liver function? A systematic review and meta-analysis.

OBJECTIVE: Existing evidence on the possible effects of ginseng on liver function has not been fully established. Therefore, the present review was undertaken to evaluate the overall effects of ginseng supplementation on liver enzymes in adults. METHODS: A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google scholar databases was conducted up to May 2019. All RCTs using ginseng supplements in adults were included in this systematic review and meta-analysis. RESULTS: Overall, 14 randomized trials (with 20 arms) including 992 subjects were identified. Pooled analysis did not illustrate any significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin (ALB) levels, however, it showed a minor significant increase in bilirubin (BIL) levels. Subgroup analysis by dosage and study population revealed significant increase of bilirubin after ginseng supplementation ≥3 g/day or in unhealthy individuals. CONCLUSION: Ginseng appears to have neither hepatoprotective nor hepatotoxic effects in conventional doses and duration. It is noteworthy that this seems applicable only for individuals with healthy liver function. Further largescale studies are warranted to confirm present findings.