Pomegranate (Punica granatum L.) peel extract ameliorates metabolic syndrome risk factors in patients with non-alcoholic fatty liver disease: a randomized double-blind clinical trial.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome (MS)-related liver disorder that has an increasing prevalence. Thus, the aim of our study is to evaluate the effects of pomegranate peel extract (PP) supplementation on hepatic status and metabolic syndrome risk factors. METHODS: In phase one, the hydro-alcoholic extraction of the peel of 750 kg of pomegranate (Punica granatum L.) was performed by the soaking method. Then, in phase two, NAFLD patients received 1500 mg of placebo (n = 37) or pomegranate peel capsules (n = 39) with a 500-kcal deficit diet for 8 weeks. Gastrointestinal intolerance, dietary intake, lipid and glycemic profiles, systolic and diastolic blood pressure, body composition, insulin resistance indexes, and elastography-evaluated NAFLD changes were followed. RESULTS: The mean age of participants was 43.1 ± 8.6 years (51.3% female). Following the intervention, the mean body weight (mean changes: -5.10 ± 2.30 kg), waist circumference (-7.57 ± 2.97 cm), body mass index (-1.82 ± 0.85 kg/m2), body fat index (-1.49 ± 0.86), and trunk fat (- 3.93 ± 3.07%), systolic (-0.63 ± 0.29 cmHg) and diastolic (-0.39 ± 0.19 cmHg) blood pressure, total cholesterol (-10.51 ± 0.77 mg/dl), triglyceride (-16.02 ± 1.7 mg/dl), low-density lipoprotein cholesterol (-9.33 ± 6.66 mg/dl; all P < 0.001), fat free mass (- 0.92 ± 0.90 kg; P < 0.003), and fasting blood sugar (-5.28 ± 1.36 mg/dl; P = 0.02) decreased significantly in PP in contrast to the placebo group in the raw model and when adjusted for confounders. Also, high-density lipoprotein cholesterol (5.10 ± 0.36 mg/dl), liver steatosis and stiffness (- 0.30 ± 0.17 and - 0.72 ± 0.35 kPa, respectively, all P < 0.001) improved in the PP group. However, fasting insulin (P = 0.81) and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.93) were not significantly different when comparing two groups during the study in the raw and even adjusted models. CONCLUSION: In conclusion, 1500 mg pomegranate peel extract along with a weight-loss diet improved metabolic syndrome risk factors and reduced hepatic steatosis in patients with NAFLD after 8 weeks.

The effect of combination therapy with statins and ezetimibe on proinflammatory cytokines: A systematic review and meta-analysis of randomized controlled trials.

It remains unknown whether statin therapy in combination with ezetimibe is a beneficial and equivalent alternative to statin monotherapy in reducing proinflammatory cytokines. In the present systematic review and meta-analysis, we aimed to assess the effect of combination therapy with statins and ezetimibe on some proinflammatory cytokines. Databases, including MEDLINE, SciVerse, Scopus, and Clarivate Analytics Web of Science databases, were searched up to February 2022, for terms related to combination therapy with statins and ezetimibe and proinflammatory cytokines. The quality of the included studies was evaluated with Cochrane risk of bias tool 1, and weighted mean difference [WMD] and SD of changes were used for meta-analysis. The results were expressed as differences in means and 95 % CIs with an inverse variance and a random-effects model. Finally, 12 studies [13 arms] were included in the qualitative and quantitative synthesis. The average patient's age ranged from 49.3 to 71 years, and the duration of intervention lasted seven days to 12 months. Overall, our result did not show any significant reduction in interleukin-1beta (IL-1ß) (3 randomized controlled trial studies (RCTs), 292 participants, WMD: -0.4 pg/ml; 95 % CI: -1.3, 0.4, P = 0.3, I2 = 93.1 %, P < 0.001), tumor necrosis factor-alpha (TNF-α) (4 RCTs, 199 participants, WMD: -0.3 pg/ml; 95 % CI: -0.8, 0.1, P = 0.1, I2 = 13.8 %, P = 0.3) and monocyte chemoattractant protein-1 (MCP-1) (4 RCTs, 216 participants, WMD: -7.8 pg/ml; 95 % CI: -18.5, 2.8, P = 0.1, I2 = 30.8 %, P = 0.2). However, there was a significant reduction in interleukin-6 (IL-6) (9 RCTs, 514 participants, WMD: -1.4 pg/ml; 95 % CI: -2.4, -0.3, P < 0.007, I2 = 97.1 %, P < 0.001) and interferon-gamma (IFN-γ) (2 RCTs, 78 participants, WMD: -0.2 pg/ml; 95 % CI: -0.4, -0.1, P < 0.001, I2 = 0 %, P = 0.7). Following subgroup analysis, there was a significant reduction in IL-6 in the age group ≥ 60 years and the Asian population. Statin therapy in combination with ezetimibe causes a significant decrease in IL-6 and IFN-γ, and the reduction in IL-6 is significant in ≥ 60 years and the Asian population.

Impact of walnut consumption on cardio metabolic and anthropometric parameters in metabolic syndrome patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials.

BACKGROUND: In recent years, the effect of walnut consumption on various components of metabolic syndrome (Mets) in different populations has been investigated. However, the findings on the alterations of cardiometabolic and anthropometric indices following walnut consumption in adults with Mets have not been fully conclusive. METHODS: The current study of eight randomized controlled trials (RCTs) examined the effects of walnut consumption on glucose homeostasis factors (fasting plasma glucose (FPG), insulin, hemoglobin A1C (HbA1c)), lipid profile (triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)), high sensitivity C-reactive protein (hs-CRP) concentrations and anthropometric indices (body weight (BW), body mass index (BMI), and waist circumference (WC)) in trials of 549 participants. A systematic search was conducted in online databases including MEDLINE, Scopus, and Clarivate Analytics Web of Science uses related keywords to detect eligible studies until December 2021. To calculate the weighted mean difference (WMD) and 95% confidence intervals (CIs), a random-effects model was used. RESULTS: Results from the pooled analysis showed that serum TG concentration was significantly reduced (WMD, - 0.1 mmol/L; 95%CI (- 0.3 to - 0.02); p = 0.02; I2 = 38.6%; p = 0.10), although other lipid profile components (TC, LDL-c, and HDL-c), glucose homeostasis markers (FPG, insulin, and HbA1c), hs-CRP levels, anthropometric indices (BW, BMI, and WC) and blood pressure (SBP and DBP) were not influenced by walnut consumption. A significant dose-response association was detected between the dose of walnut intake and serum concentrations of FPG (Pnon-linearity < 0.03, Pdose-response < 0.001) and HDL-c (Pnon-linearity = 0.01, Pdose-response = 0.006). CONCLUSIONS: Walnut consumption reduces serum TG levels in individuals with metabolic syndrome, but it cannot affect other cardiometabolic indices. Future well-designed and large RCTs are required to clarify further beneficial effects of walnut consumption on the cardiometabolic profile.