Antidiabetic, hypolipidemic, and antioxidant activities of Pistacia atlantica: A systematic review and meta-analysis of preclinical studies.

To determine the pharmaceutical applications, we assessed the evidence from preclinical studies about the hypoglycemic, hypolipidemic, and antioxidant potential of Pistacia atlantica (PA) as a natural source for prevention and treatment of diabetes. A comprehensive literature search of the articles published until March 12, 2022 was conducted on PubMed, Embase, Web of Sciences, and Scopus databases, using relevant keywords. This meta-analysis included 12 articles that examined the blood glucose (BG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA) and superoxide dismutase (SOD). A random-effects model was used to estimate the pooled effect size. Findings indicated that PA supplementation significantly decreased BG, HOMA-IR, TC, TG, and MDA, and increased insulin and SOD in diabetic animals compared with control group (p < .05). However, PA supplementation had no significant effects on HDL-C (p > .05). The subgroup analysis also confirmed the beneficial effect of PA supplementation with longer duration (>4 weeks) and higher doses (≥100 mg/kg/day) as well as in the extract type. The studies have heterogeneity associated with methodological diversity and there were some concerns about the risk of bias, especially about randomization and blind outcome assessment. This meta-analysis provided convincing evidence for antidiabetic, hypolipidemic, and antioxidant activity of PA in animals. Further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

Effects of green tea supplementation on serum concentrations of adiponectin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

CONTEXT: A decrease in adiponectin concentration is associated with obesity-related diseases such as insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). OBJECTIVE: We aimed to evaluate the effects of green tea supplementation on serum concentrations of adiponectin in patients with T2DM. METHODS: A systematic search was performed on the ISI Web of Science, PubMed, Embase and Scopus to find articles related to the effects of the green tea supplementation on adiponectin concentrations in T2DM patients, up to June 2019. Meta-analyses were performed using both the random and fixed effects model where appropriate. RESULTS: The initial search yielded 1010 publications. Data were pooled from five trials including 333 patients with T2DM. A meta-analysis of five RCTs demonstrated that green tea supplementation significantly increased adiponectin concentrations compared to control groups. CONCLUSION: Our meta-analysis revealed that green tea supplementation increased adiponectin concentrations in patients with T2DM.

Effect of green tea on glycemic control in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Several studies have investigated the potential beneficial effects of green tea in patients with type 2 diabetes mellitus (T2DM). Therefore, we aimed to perform a systematic review and meta-analysis of the randomized controlled trials (RCTs) that assessed the effect of supplementary intake of green tea on fasting plasma glucose (FPG), fasting insulin, hemoglobin A1c (HbA1c) and HOMA-IR in patients with T2DM. METHODS: A systematic search was performed in Web of Science, PubMed and Scopus without any language and time restriction up to June 2019, to retrieve the related RCTs. Meta-analysis was carried out using both the random and fixed effects model where appropriate. I2 index was used to evaluate the heterogeneity. RESULTS: Initial search yielded 780 publications. Fourteen articles were eligible. Our meta-analysis indicated that the supplementary intake of green tea had no significant effect on FPG, fasting insulin, HbA1c and HOMA-IR in patients with T2DM. CONCLUSION: Results of the present systematic review and meta-analysis indicated that the supplementary intake of green tea had no significant effect on FPG, fasting insulin, HbA1c and HOMA-IR in patients with T2DM.

Effect of Green Tea on Anthropometric Indices and Body Composition in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

AIM: Previous studies that investigated the effect of green tea/green tea extract on anthropometric indices among type 2 diabetes mellitus (T2DM) patients found inconsistent results. Thus, in order to clarify the efficacy of green tea supplementation on anthropometric indices and body composition, we conducted a systematic review and meta-analysis to sum up the evidence of randomized controlled trials. METHODS: A systematic search was conducted in the Scopus, ISI Web of Science and PubMed to find the related articles, up to June 2019. Meta-analysis was performed using the random effects model, and the I2 index was used to evaluate the heterogeneity. RESULTS: Eleven articles were eligible. Our meta-analysis indicated that green tea consumption significantly decreased body weight, body mass index (BMI), and body fat (BF). The beneficial effect of green tea intake was observed in long-term intervention (>8 weeks), at lower doses of green tea (dosage ≤800 mg/day), and in overweight patients. CONCLUSION: This study revealed the beneficial effects of green tea consumption in reducing body weight, BMI, and BF in T2DM patients. It should be noted that green tea was effective in long-term intervention, at lower doses of green tea, and in overweight patients.

Effect of L-Carnitine Supplementation on Lipid Profiles of Patients with Liver Disease: A Systematic Review and Meta-Analysis.

Results of previous studies regarding the effect of L-carnitine on lipid profiles in the patients with liver diseases are contradictory. This meta-analysis was performed to assess the effect of L-carnitine on serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC) in overweight patients with liver diseases. A systematic search was carried out using the Web of Science, PubMed, Scopus, and Cochrane library databases to identify articles published before April 2019 investigating the effects of L-carnitine supplementation on patients with liver disease. There was no language or time limitation for the studies. A meta-analysis was carried out using both the random and fixed effects model where appropriate, and I2 index were used to evaluate heterogeneity. These results indicated that L-carnitine supplementation significantly reduces blood levels of TC and TG in patients with liver disease, whereas carnitine had no effect on the levels of HDL and LDL. The reducing effect of L-carnitine on both TC and TG was found following long-term carnitine supplementation (≥24 weeks), supplementation with doses less than or equal to 2,000 mg/d, and in patients with chronic hepatitis C. This meta-analysis indicates the beneficial effect of L-carnitine on TC and TG in overweight patients with liver disease, particularly patients with chronic hepatitis C, in both long-term and low doses.

Effect of Vitamins C and E Co-Supplementation on Serum C-Reactive Protein Level: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Studies assessing the effect of vitamin C and E co-supplementation on levels of circulating C-reactive protein (CRP) show contradictory results. We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of vitamin C and E co-supplementation on CRP. A systematic search was carried out using PubMed, Scopus, Ovid, Cochrane, Embase, and the Web of Science without any language or time restriction (until 31 March 2019) to retrieve RCTs that examined the effect of vitamin C and E co-supplementation on CRP. A meta-analysis was carried out using a random effects model, and I2 indexes were used to evaluate the heterogeneity. The search yielded 5,134 publications, including 8 eligible RCTs. The results indicate that vitamin C and E co-supplementation does not significantly impact levels of serum CRP [weighted mean difference and 95% confidence interval with random effects model analysis: -0.22 mg/L (-0.85, 0.41), P=0.5]. Subgroup analysis demonstrated that vitamin C and E co-supplementation significantly reduced serum CRP in participants ≥30 years of age, but significantly increased serum CRP in participants <30 years of age. The results of this meta-analysis indicate beneficial effects of vitamins C and E co-supplementation on CRP in participants ≥30 years of age, and not in younger participants. To confirm these results, further well-designed RCTs are needed.

Effect of green tea extract on lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Previous studies have indicated controversial results regarding the efficacy of green tea extract (GTE) in improving the lipid profile of type 2 diabetes mellitus (T2DM) patients. We aimed to conduct a systematic review and meta-analysis to pool data from randomized controlled trials (RCTs). METHODS: A systematic search was performed in Web of Science, PubMed, and Scopus databases, without any language and time restriction until August 2019, to retrieve the RCTs which examined the effects of GTE on serum concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG) or total cholesterol (TC) in T2DM patients. Meta-analyses were carried out using a random effects model. I2 index was used to evaluate the heterogeneity. RESULTS: Initial search yielded 780 publications. Of these, seven studies were eligible. The supplementary intake of GTE improved lipid profile by reducing serum TG concentrations in patients with T2DM. Meanwhile, subgroup analyses based on duration of interventions (≤8 and > 8 weeks) and intervention dosage (≤800 and > 800 mg/day) showed that the GTE supplementation longer than 8 weeks and in doses >800 mg/day resulted in a significant decrease in serum TG concentrations. Furthermore, intervention longer than 8 weeks with doses lower than 800 mg/day resulted in a significant reduction in serum TC concentrations. CONCLUSION: In conclusion, present systematic review and meta-analysis revealed that the supplementary intake of GTE may improve lipid profile by reducing serum concentrations of TG in patients with T2DM. Furthermore, the results of our stratified analyses suggested that long-term GTE intervention may reduce serum concentrations of TG and TC.

Effect of l-arginine supplementation on C-reactive protein and other inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of L-arginine on inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6) and TNFα. METHODS: A systematic search was carried out in PubMed, Embase, Scopus, Cochrane library databases and ISI web of sciences to retrieve the RCTs which examined the effect of L-arginine supplementation on inflammatory biomarkers up to October 2019, with no language and time restriction. Meta-analysis was performed using a random effects model, and I2 index was used to evaluate the heterogeneity. RESULTS: Search yielded 2452 publications. Eleven RCTs were eligible. Results indicated that L-arginine supplementation had no significant effect on inflammatory biomarkers including CRP, IL-6 and TNFα. However, when subgroup analysis was performed, we found that L-arginine supplementation increased CRP levels in subjects with ages >60 years old, participants with baseline circulating CRP levels >3 mg/dl, patients with cancer and when used in enteral formula. CONCLUSION: Results of the present meta-analysis indicated that L-arginine supplementation increased the circulating concentrations of CRP in subjects with ages >60 years old, subjects with higher levels of CRP, patients with cancer and when used in enteral formula. Therefore, L-arginine should be used with caution in these subjects. However, further well designed, large-scale studies are needed.

The effect of green tea on C-reactive protein and biomarkers of oxidative stress in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: The beneficial effects of green tea on regulating insulin sensitivity and preventing the development of type 2 diabetes mellitus (T2DM) have been identified. OBJECTIVES: We aimed to investigate the effect of green tea on serum levels of C-reactive protein (CRP) and biomarkers of oxidative stress in patients with T2DM. METHODS: A systematic search was performed in the ISI Web of science, PubMed and Scopus to find articles related to the effect of the green tea on CRP, malondealdehyde (MDA) and total antioxidant capacity (TAC) in T2DM patients, up to June 2019. There was no language and time limitation. Meta-analyses were performed using both the random and fixed effects model where appropriate, and I2 index was used to evaluate the heterogeneity. RESULTS: Initial search yielded 780 publications. Eight articles with 614 T2DM patients were eligible. Following green tea consumption, CRP levels significantly decreased (weighted mean difference (WMD): -5.51 mg/dl, 95% CI: -9.18 to -1.83, p = 0.003) compared with the controlled group. Green tea consumption had no significant effect on plasma levels of TAC and MDA (0.02 mg/dl, CI: -0.06 to 0.10; -0.14 mg/dl, CI: -0.40 to 0.12; respectively). CONCLUSION: This systematic review and meta-analysis indicated that green tea significantly reduced the circulating levels of CRP, whereas, it had no significant effect on MDA and TAC. Overall, green tea can be considered as a healthy drink to reduce CRP levels in T2DM patients.

Effect of Omega-3 and vitamin E co-supplementation on serum lipids concentrations in overweight patients with metabolic disorders: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Results of the studies assessed the effect of omega-3 and vitamin E co-supplementation on lipid profile in patients with metabolic syndrome (MS) are contradictory. Therefore, we carried out a systematic review and meta-analysis of randomized controlled trials (RCTs), to assess the effect of omega-3 and vitamin E co-supplementation on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in patients with MS. METHODS: A systematic search was performed to find the related articles, up to April, 2019. There was no language and time limitation. Meta-analyses were carried out using both the random and fixed effects model where appropriate, and I2 index was used to evaluate the heterogeneity. RESULTS: Search yielded 1236 publications. Five RCTs with 254 patients were eligible. Results of the meta-analysis indicated that omega-3 and vitamin E co-supplementation significantly reduced the serum concentrations of TG and LDL, whereas, it had no significant effect on the serum levels of TC and HDL in overweight patients with MS. CONCLUSION: Present systematic review and meta-analysis revealed that omega-3 and vitamin E co-supplementation have beneficial effects on lipid profile of overweight patients with MS. It significantly reduced the serum levels of TG and LDL in such patients.

Effect of L-carnitine on liver enzymes and biochemical factors in hepatic encephalopathy: A systematic review and meta-analysis.

BACKGROUND AND AIMS: We aimed to investigate the effect of L-carnitine on biochemical factors including ammonia, bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) in patients with hepatic encephalopathy (HE). METHODS: A systematic search was carried out in Web of Science, PubMed, Scopus, and Cochrane Library databases to find articles related to the effect of L-carnitine supplementation in patients with HE, up to 7 February 2019. There was no language and time limitation. Meta-analyses were carried out using both the random and fixed effects models where appropriate, and I2 index was used to evaluate the heterogeneity. RESULTS: Search yielded 3462 publications. Nine randomized clinical trials with 779 patients were eligible. L-carnitine supplementation significantly reduced blood levels of ammonia. Furthermore, our results indicated that L-carnitine supplementation significantly reduced blood levels of bilirubin, AST, BUN, and Cr in patients with HE. Subgroup analysis demonstrated that L-carnitine significantly reduced ammonia in patients with all the ages, long and short duration of the supplementation, doses less or higher than 4000 mg/day, any route of treatment (intravenous or oral), and in patients with any grade of the symptoms of HE. Moreover, we found that L-carnitine significantly increased circulating levels of albumin in HE patients. CONCLUSIONS: Present systematic review and meta-analysis revealed that L-carnitine supplementation significantly reduced blood levels of ammonia, bilirubin, AST, BUN, and Cr in HE patients. Moreover, we found that L-carnitine significantly increased circulating levels of albumin. However, further large-scale randomized clinical trials are needed.

Effect of Calcium­Vitamin D Co­Supplementation on Insulin, Insulin Sensitivity, and Glycemia: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of calcium-vitamin D co­supplementation on insulin, insulin sensitivity, and glycemia. A systematic search was carried out in Web of Science, PubMed, EMBASE, Scopus, and Cochrane library without any language and time restriction up to 12 August 2018, to retrieve the RCTs, which examined the effect of calcium and vitamin D co-supplementation on fasting blood glucose (FBG), insulin, HOMA-B, HOMA-IR, and QUICKI. Meta-analyses were carried out using a random effects model, and I2 indexes were used to evaluate the heterogeneity. Search yielded 2225 publications. Twelve RCTs with 4395 patients were eligible. Results demonstrated that calcium and vitamin D co­supplementation had significantly reducing effects on FBG, HOMA-IR and circulating levels of insulin. As the subgroup analysis demonstrated, short-term (≤12 weeks) calcium and vitamin D co­supplementation had a significant reducing effect on FBG. However, beneficial effects of calcium and vitamin D co­supplementation on circulating level of insulin and HOMA-IR were seen in both short-term and long-term (>12 weeks) supplementations. Furthermore, we found that high doses of vitamin D and calcium co-supplementation (vitamin D≥2000 mg/day and calcium≥1000 mg/day) had significantly reducing effects on FBG, HOMA-IR and insulin. Present meta-analysis indicated the beneficial effects of high-dose and short-term combined vitamin D and calcium supplementation on insulin, insulin resistance and glycemia; however, further large-scale RCTs with adequate and multiple dosing schedules are needed.

Vitamin D3 Induced Decrease in IL-17 and Malondialdehyde, and Increase in IL-10 and Total Antioxidant Capacity Levels in Patients with Irritable Bowel Syndrome.

BACKGROUND: Given the variations in clinical presentation and physiopathological mechanisms in irritable bowel syndrome (IBS) subtypes, it is an acknowledged fact that the response to treatments can be disparate. OBJECTIVE: To assess the effect of vitamin D on inflammatory cytokines (IL-17, IL-10, TNF-α), and biomarkers of oxidative stress (total antioxidant capacity (TAC), and malondialdehyde (MDA)) among IBS patients. METHODS: A double-blind, randomized, placebo-controlled 6-month intervention study was carried out on 90 IBS patients (85 were analyzed), as defined by the Rome III criteria. Study participants were randomly assigned to receive either 50,000 IU vitamin D3 or a placebo fortnightly. RESULTS: Vitamin D supplementation significantly reduced the IL-17 and MDA serum levels (P<0.05) and observably increased the TAC and IL-10 serum levels (P<0.05), compared with the placebo group. Comparing different bowel habit subtypes, we observed that it was only in diarrhea predominant IBS (IBS-D) that vitamin D supplementation was able to significantly reduce the serum levels of TNF-α and IL-17 (P<0.05). However, in all subtypes, IL-10 and TAC increased, while MDA decreased (P<0.05) in vitamin D group, compared to the placebo group. CONCLUSION: Vitamin D3 supplementation reduces the serum IL-17 and MDA levels, and augments the serum IL-10 and TAC levels in IBS patients, particularly in IBS-D subtype. Thus, the present study demonstrates the beneficial effects of vitamin D on patients with IBS-D.

Effect of Vitamin E Supplementation on Plasma and Urine Levels of Isoprostane F2α in Randomized Controlled Clinical Trials: A Systematic Review and Meta-Analysis.

Vitamin E can reduce the level of lipid peroxidation and the related markers such as urine and plasma levels of isoprostanes. However, effects of vitamin E supplementation on plasma and urine level of isoprostane F2α as markers of lipid peroxidation were conflicting in various clinical trials. The current meta-analysis was carried out to determine the effects of vitamin E supplementation on plasma and urine levels of isoprostanes F2α in randomized clinical trials. A systematic search of RCTs was carried out in PubMed, Scopus, Science Direct and Cochrane Library databases. OF 889 relevantly founded articles, only four articles with five arms met the criteria for meta-analysis of plasma level of isoprostanes F2α. For the urine level of isoprostane F2α, three studies with 14 arms were included in the meta-analysis. After pooled analyzing, a significant reduction of 6.98 ng / l was seen in plasma level of isoprostane F2α in vitamin E receiving group (95% CI = -11.2, -2.76; P < 0.001) while no significant heterogeneity was seen between the studies included in this meta-analysis (P = 0.81 and I2 = 0.0%). However, the pooled effect of vitamin E supplementation on urine level of isoprostane F2α was not statistically significant (-11.31 pg / mg creatinine (95% CI = -26.4, 3.78; P = 0.88). Results of this meta-analysis have shown that vitamin E supplementation can only reduce plasma level of isoprostane F2α and has no significant effect on reducing urine level of this biomarker.