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 resistance training combined with a ketogenic diet on body composition: a systematic review and meta-analysis.

We evaluated the effects of ketogenic diets (KDs) on body mass (BM), fat mass (FM), fat-free mass (FFM), body mass index (BMI), and body fat percentage (BFP) compared to non-KDs in individuals performing resistance training (RT). Online electronic databases including PubMed, the Cochrane Library, Web of Science, Embase, SCOPUS, and Ovid were searched to identify initial studies until February 2021. Data were pooled using both fixed and random-effects methods and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). Out of 1372 studies, 13 randomized controlled trials (RCTs) that enrolled 244 volunteers were included. The pooled results demonstrated that KDs significantly decreased BM [(WMD = -3.67 kg; 95% CI: -4.44, -2.90, p < 0.001)], FM [(WMD = -2.21 kg; 95% CI: -3.09, -1.34, p < 0.001)], FFM [(WMD = -1.26 kg; 95% CI: -1.82, -0.70, p < 0.001)], BMI [(WMD = -1.37 kg.m-2; 95% CI: -2.14, -0.59, p = 0.022)], and BFP [(WMD = -2.27%; 95% CI: -3.63, -0.90, p = 0.001)] compared to non-KDs. We observed beneficial effects of KDs compared to non-KDs on BM and body fat (both FM and BFP) in individuals performing RT. However, adherence to KDs may have a negative effect on FFM, which is not ameliorated by the addition of RT.

"Association between dietary inflammatory index (DII) and risk of irritable bowel syndrome: a case-control study".

BACKGROUND: Pathophysiology of IBS is not well recognized; however, several studies have shown the possible relationship between diet and risk of IBS. We assessed the ability of the dietary inflammatory index (DII) to predict the risk of IBS. METHODS: The subjects were 155 IBS cases and 310 age- and sex-matched healthy controls (aged ≥18 years). The participants were recruited from June, 2019 to March, 2020. IBS was recognized using the Rome IV criteria. DII score was computed based on dietary intake using a 168-item FFQ. The DII score was calculated based on energy-adjusted amounts of nutrients using residual method. Logistic regression models were used to estimate multivariable odds ratios (ORs). RESULTS: The mean DII score was significantly higher among IBS patients in comparison to healthy controls (0.78 ± 2.22 vs. - 0.39 ± 2.27). In crude model, increase in DII as continuous variable was associated with a significant increase in the risk of IBS (OR (95% CI): 1.26 (1.1-15.38)). Furthermore, the association remained significant even after adjusting for age and sex (OR (95% CI): 1.28 (1.1-17.41)) and after multivariate adjustment (OR (95% CI): 1.38 (1.2-1.56)). In crude, age and sex adjusted and multivariate-adjusted models subjects in fourth quartile of DII had higher OR in comparison to subjects in first quartile. CONCLUSIONS: This study showed a possible positive association between a pro-inflammatory diet and the risk of IBS. Thus, encouraging intake of more anti-inflammatory dietary factors and reducing intake of pro-inflammatory factors may be a strategy for reducing risk of IBS.

Serum Levels of Chemerin, Apelin, and Adiponectin in Relation to Clinical Symptoms, Quality of Life, and Psychological Factors in Irritable Bowel Syndrome.

BACKGROUND: Adipokines have endocrine roles in metabolism and immunity. Dysregulation of adipokine levels is associated with several diseases with chronic inflammation. We aimed to assess the serum concentrations of chemerin, apelin, and adiponectin in irritable bowel syndrome (IBS). Furthermore, we evaluated the possible association of these adipokines with clinical symptoms, quality of life (QoL), and psychological factors. MATERIALS AND METHODS: In this case-control study, 114 male and female IBS patients were recruited from outpatient clinics. Along with the IBS patients, 114 sex and age-matched healthy volunteers were recruited. Patients filled in the questionnaires of the IBS severity scoring system (IBSSS), gastrointestinal (GI) and somatic symptoms, IBS specific QoL (IBS-QoL), and psychological disorders, and went to the lab for blood sampling. RESULTS: Serum levels of both adiponectin and apelin were significantly (P=0.04, 0.03, respectively) lower, whereas chemerin was significantly (P=0.01) higher in IBS patients. Chemerin was higher in IBS-D compared with both IBS-C and IBS-A, while apelin and adiponectin were not different between subtypes. After adjustments for confounders only, chemerin had a positive association with IB severity scoring system and GI symptoms. Furthermore, chemerin had positive associations, whereas apelin and adiponectin had inverse associations with somatic symptoms and psychological factors. There were no significant associations between adipokines including chemerin, apelin, and adiponectin, and IBS-QoL. CONCLUSIONS: Chemerin had significant associations with both the severity of clinical symptoms and psychological factors in IBS; thus, it could be considered as a potential therapeutic target in these patients; however, further studies are needed.

Effects of gradual weight loss v. rapid weight loss on body composition and RMR: a systematic review and meta-analysis.

This systematic review and meta-analysis compared the effects of different rates of weight loss (WL), but equivalent total WL, on body composition and RMR. Studies examining gradual v. rapid WL on body composition and RMR in participants with overweight/obesity published up to October 2019 were identified through PubMed, the Cochrane Library, Web of Science, Embase, Scopus and Ovid databases. Meta-analysis was carried out using a fixed or random effects model as appropriate. Although the magnitude of WL was similar (mean difference 0·03 kg, 95 % CI ­0·65, 0·71), gradual WL promoted greater reductions in fat mass (FM) (­1 kg, 95 % CI ­1·70, ­0·29) and body fat percentage (BFP) (­0·83 %, 95 % CI ­1·49, ­0·17). Gradual WL significantly preserved RMR compared with rapid WL (407·48 kJ, 95 % CI 76·76, 118·01). However, there was no significant difference in waist and hip circumferences, waist:hip ratio and fat-free mass (FFM) between gradual and rapid WL. The present systematic review and meta-analysis indicates beneficial effects of gradual WL, as compared with rapid WL, on FM, BFP and RMR in individuals with overweight/obesity. However, FFM changes and anthropometric indices did not significantly differ following different rates of WL.

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.

Association of Serum Vitamin D Concentration With Clinical Symptoms and Quality of Life in Patients With Irritable Bowel Syndrome.

OBJECTIVE: A high prevalence of vitamin D deficiency (VDD) in gastrointestinal (GI) disorders and the role of vitamin D in the function of the gut have been shown previously. Therefore, we aimed to evaluated the VDD and the possible association of the GI symptoms severity and quality of life (QoL) score with the serum levels of vitamin D in irritable bowel syndrome (IBS). METHODS: A total of 90 patients with IBS based on Rome III criteria enrolled in the study from the tertiary referral university hospital. In addition, 90 sex- and age-matched healthy controls (HCs) were recruited. To measure the serum levels of 25(OH)D3, blood samples were taken from all the participants. Severity of clinical symptoms, IBS quality of life (IBS-QoL), and IBS symptom severity score (IBSSS) were assessed. RESULTS: In 66.7% of IBS patients, serum 25(OH)D3 concentrations were <20 ng/mL. The mean serum 25(OH)D3 of IBS patients was statistically (p < 0.05) lower vs. HCs. When different subtypes were analyzed, the serum 25(OH)D3 concentrations in diarrhea-predominant IBS were statistically (p < 0.05) lower as compared to HCs. Furthermore, the lower serum concentrations of 25(OH)D3 were associated (p < 0.05) with higher severity of abdominal pain and distention, flatulence, overall GI symptoms, and IBSSS. However, a direct significant association was seen between IBS-QoL and serum 25(OH)D3. CONCLUSION: Results of this study showed a high prevalence of VDD in patients with IBS. In addition, VDD was associated with a higher severity of clinical symptoms and lower QoL in IBS.

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.

Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: Association with digestive symptoms and quality of life.

A growing body of evidence suggests a possible role for low-grade inflammation in the pathogenesis of irritable bowel syndrome (IBS). The objectives of this study were to measure serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-17, interleukin (IL)-10, malondialdehyde (MDA) and total antioxidant capacity (TAC) in IBS patients and healthy controls (HCs), and to evaluate possible correlations of such markers with gastrointestinal (GI) symptoms and quality of life (QoL). Ninety Rome III positive IBS patients and 90 sex and age matched HCs were recruited. GI symptoms, IBS-QoL, IBS severity score system (IBSSS), and the serum levels of inflammatory cytokines and oxidative stress biomarkers were evaluated. In IBS patients, TNFα, IL-17 and MDA cytokines were significantly (P<0.05) higher, and IL-10 cytokine and TAC were significantly (P<0.05) lower vs. HCs. When comparing IBS subtypes, TNFα and IL-17 were significantly (P<0.05) higher, and IL-10 was significantly (P<0.05) lower in diarrhea predominant IBS (IBS-D) compared to HCs, whereas the inflammatory cytokine profile of other subtypes more closely resembled that of HCs. The serum levels of MDA and TAC were significantly different (P<0.05) in all the subtypes vs. HCs. All the inflammatory cytokines had significant (P<0.05) correlations with GI symptoms, IBSSS and IBS-QoL, whereas no significant association was found between oxidative stress biomarkers and these symptoms. IBS-D patients display increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines. Present study demonstrated a correlation between inflammatory cytokines and both IBS symptoms and QoL.

Sex-Related Differences in Clinical Symptoms, Quality of Life, and Biochemical Factors in Irritable Bowel Syndrome.

BACKGROUND: Due to the sex differences in physiological and psychological factors, it can be speculated that clinical presentation of symptoms in male and female patients with irritable bowel syndrome (IBS) might be different. AIM: To evaluate sex-related differences in clinical symptoms, quality of life, and biochemical factors in IBS. METHODS: Ninety IBS patients (29 men, 61 women (45 premenopausal, 16 postmenopausal)) were recruited from the outpatient clinic of the University Hospital. All the patients met the Rome III Diagnostic Criteria. The IBS severity score system (IBS-SSS), gastrointestinal (GI) symptoms, IBS specific quality of life (IBS-QoL), and biochemical factors (IL-17, IL-10, TNFα, malondialdehyde (MDA), total antioxidant capacity (TAC)) were assessed. RESULTS: Diarrhea predominant IBS (IBS-D) was more common in men (44.8%), whereas constipation-predominant IBS (IBS-C) and alternating bowel habits IBS (IBS-A) were more common in women (39.3, 42.6%, respectively). The women had a greater severity of abdominal distention, rumbling, flatulence, and dissatisfaction with bowel habits as compared with men. The scores of IBS-QoL in women were significantly (P < 0.05) lower than those in men. Moreover, pro-inflammatory cytokines (IL-17, TNFα) increased, and anti-inflammatory cytokine (IL-10) decreased in women versus men. In addition, there was no significant difference (P > 0.05) between pre- and postmenopausal women in the severity of symptoms. All of the GI symptoms and IBS-SSS have a significant negative correlation with IBS-QoL in both men and women. CONCLUSIONS: Female with IBS reports a greater severity of IBS symptoms, increased inflammatory cytokines, and has an impaired quality of life compared with male.

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.

The protective effects of alpha-pinene on high glucose-induced oxidative stress and inflammation in HepG2 cells.

Objectives: Hyperglycemia, a prevalent metabolic condition observed in diabetes, leads to oxidative damage, inflammatory responses, and other consequences. Natural compounds alleviate the adverse impacts of diabetes. We aimed to explore the effects of alpha-pinene (AP) as a monoterpene on oxidative damage and inflammation caused by high glucose (HG) in the human hepatocellular liver carcinoma (HepG2) cell line. Materials and Methods: The HepG2 cells were subjected to non or HG concentration (50 mM) and treated with or without AP (8, 16, and 32 µg/ml) for 48 hr. The effect of treatments on cellular viability, malondialdehyde (MDA), glutathione (GSH), and activity of anti-oxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), was determined. The gene expression levels of nuclear factor-κß (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and dipeptidyl peptidase-4 (DPP-4) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: HG exposure significantly increased cell death, MDA formation, and depletion of GSH content and GPx, CAT, and SOD activity (P<0.05). We have also seen a significant induction in NF-κB, TNF-α, IL-6, and DPP-4 gene expression in hepatocytes under HG conditions (P<0.05). Interestingly, co-treatment with AP in a dose-dependent manner improved cell death and altered levels of MDA and GSH, and activity of GPx and CAT (P<0.05). AP could also modulate the gene expression of NF-κB and inflammatory biomarkers dose-dependently (P<0.05). Conclusion: Our findings suggested the protective effect of AP on hepatocytes under HG conditions through attenuating oxidative stress markers and suppression of inflammatory pathways.

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.

Association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population: A case control study.

AIM: We aimed to assess the association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population. METHODS: In this retrospective case-control study that was conducted between 2012 and 2015, 278 first incident colorectal cancer cases (colon cancer = 103; rectal cancer = 175), and 278 sex and age matched healthy controls (HCs) were recruited. Serum 25(OH)D, dietary vitamin D, and calcium intake were assessed. Logistic regression was used to estimate the odds ratio (OR) between studied factors and colorectal cancer. Estimates of OR were calculated according to both bivariate analyses based on the matching factors and multivariate analyses, with additional adjustment for potential confounders. RESULTS: A strong inverse linear dose-response association was seen between serum 25(OH)D and colorectal cancer (P for trend = .002). In comparison to serum 25(OH)D more than 40 nmol/L, lower serum concentrations were significantly associated with an increased OR of colorectal cancer. When analyzing anatomical subsites separately, lower circulating 25(OH)D was associated with higher OR for both colon and rectum cancers. Dietary vitamin D and calcium intake were not associated with colorectal cancer. Interaction analysis between serum 25(OH)D and the amount of calcium intake demonstrated that the lowest level of both factors was associated with an increased OR of colorectal cancer. The highest OR of colorectal cancer that was associated with lowest circulating 25(OH)D was stronger at the highest retinol intakes. CONCLUSION: This study demonstrated an inverse strong association between 25(OH)D concentration and colorectal cancer in an Iranian population.

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 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.

Effects of the Mediterranean diet on cardiovascular risk factors in non-alcoholic fatty liver disease patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: We aimed to investigate the effect of the Mediterranean diet (MedDiet) on cardiovascular risk factors in patients with non-alcoholic fatty liver disease (NAFLD). METHOD: A systematic search was performed in Scopus, Web of Science, Cochrane library and PubMed databases to find randomized controlled trials (RCTs) related to the effect of the MedDiet in patients with NAFLD, up to July, 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: Primary search yielded 467 publications. Five RCTs were eligible. Our meta-analysis indicated that the MedDiet resulted in a significant decrease in serum levels of triglyceride and total cholesterol, and a decrease in body weight and HOMA-IR in comparison to a control diet, in NAFLD patients. Whereas, there were no significant improvement in the MedDiet group compared with the control group regarding other variables such as liver enzymes and blood pressure. CONCLUSIONS: This meta-analysis indicated the advantageous effects of the MedDiet on some cardiovascular risks factors, as compared with a control diet. It seems that the MedDiet can be considered as an appropriate strategy to reduce cardiovascular risk factors in NAFLD 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.

The Effects of Probiotic/Synbiotic on Serum Level of Zonulin as a Biomarker of Intestinal Permeability: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis was conducted to obtain a conclusive result on the influence of probiotics/synbiotic on serum levels of zonulin. Data related to serum levels of zonulin were extracted to determine the effects of probiotic/synbiotic on intestinal permeability. METHODS: The literature search was conducted across the Cochrane Central Register of Controlled Trials, Pub-Med, Scopus and ISI Web of Science, Search up to Nov 2018. Clinical trials evaluating the effect of probiotic/synbiotic on serum zonulin levels of all human subjects were included. RESULTS: Nine studies (including 496 intervention and 443 control subjects) met the inclusion criteria for the meta-analysis. According to the meta-analysis, probiotic/synbiotic has a significant effect on serum zonulin reduction (WMD=-10.55 [95% CI: -17.76, -3.34]; P=0.004). However, the high level of heterogeneity was observed among the studies (I2=97.8, P<0.001). The subgroup analysis suggested study quality, blinding, study duration, Participants age, subject's health status and supplement type as sources of heterogeneity. CONCLUSION: Probiotic/synbiotic have favorable effects on serum levels of zonulin as a measure of intestinal permeability. However, the results should be interpreted with caution due to the high heterogeneity and further evidence is required before definitive recommendations can be made.