Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines. Methods: The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-ß), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method. Findings: Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-ß in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05). Conclusion: Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22.

The effects of Ellagic acid supplementation on neurotrophic, inflammation, and oxidative stress factors, and indoleamine 2, 3-dioxygenase gene expression in multiple sclerosis patients with mild to moderate depressive symptoms: A randomized, triple-blind, placebo-controlled trial.

BACKGROUND: Depression is one of the most common psychological disorders among multiple sclerosis (MS) patients that characterized as the first symptoms. Ellagic acid is a natural polyphenol that may have neuroprotective properties through antioxidant, anti-inflammatory, and immunomodulatory effects. PURPOSE: The aim of the present study was to investigate the effects of Ellagic acid on circulating levels of brain derived neurotrophic factor (BDNF), interferon-γ (IFN-Æ´), nitric oxide (NO), nuclear factor erythroid-2-related factor 2 (Nrf2), cortisol, serotonergic system, and indoleamine 2, 3-dioxygenase (IDO) gene expression in MS patients with mild to moderate depressive symptoms. STUDY DESIGN: A randomized triple-blind clinical trial. METHODS: The eligible patients according to the inclusion criteria were randomly divided into two groups: either 180 mg Ellagic acid (Axenic company) (n = 25) or 180 mg maltodextrin (n = 25) group for 12 weeks. The Ellagic acid supplement were identical to placebo in shape, color and odor. Serum BDNF, NO, Nrf2, cortisol, serotonin, and IFN-Æ´ were measured by ELISA kit in the baseline and end of the study. Also, demographic characteristics, anthropometric measurements, physical activity, food intake, Beck Depression Inventory-II (BDI-II) and expanding disability status scale (EDSS) questionnaires, as well as IDO gene expression were assessed. SPSS software version 24 was used for statistical analysis. RESULTS: Fifty patients were evaluated, and a significant decrease in BDI-II (p = 0.001), IFN-Æ´ (p = 0.001), NO (p = 0.004), cortisol (p = 0.015), IDO gene expression (p = 0.001) and as well as increased the level of BDNF (p = 0.006) and serotonin (p = 0.019) was observed among those who received 90 mg Ellagic acid twice a day for 12 weeks versus control group. However, there were no significant differences between groups for Nrf2 levels (p>0.05) at the end of study. CONCLUSION: The current study indicates that Ellagic acid intervention has a favorable effect on depression in MS patients. This is achieved by reducing BDI-II scores, as well as levels of NO, cortisol, IFN-Æ´, and IDO gene expression. Furthermore, we found a significant elevation in circulating levels of BDNF and serotonin.

Effects of berberine and barberry on selected inflammatory biomarkers in adults: A systematic review and dose-response meta-analysis of randomized clinical trials.

The previous meta-analysis showed an advantageous effect of berberine supplementation on interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and serum C-reactive protein (CRP) concentrations; however, it is unknown the dosage that this component influences inflammatory biomarkers. A comprehensive search was done in Scopus, PubMed, and Web of Science until September 2022 to find randomized controlled trials (RCT) that assessed the effects of berberine/barberry on IL-6, TNF-α, and CRP in adults but not trials without a control group. Studies bias was assessed using RoB 2. A random-effects model was performed to calculate the weighted mean difference (WMD). A dose-dependent effect was calculated. Eighteen clinical trials with 1600 participants were included in the current meta-analysis. These interventions significantly mitigate IL-6 levels (-1.18 pg/mL), TNF-α levels (-3.72 pg/mL), and CRP levels (-1.33 mg/L). In addition, the non-linear analysis showed a significant lowering effect of berberine/barberry on IL-6 and TNF-α levels in doses <1000 mg/day and less than 5 weeks of intervention. There are limitations to our findings, including low-quality studies and significant heterogeneity. These interventions might be considered adjunct therapy to managing inflammation status. However, more investigation and high-quality evidence must be conducted to obtain more comprehensive and generalizable results.

Is there any hepatic impact associated with rice bran arabinoxylan compound supplementation? A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Rice Bran Arabinoxylan Compound (RBAC) results from an enzymatic modification of rice bran, which is reported to have immunomodulatory, anti-oxidant, and anti-inflammatory effects by regulating the production of pro-inflammatory cytokines. The current systematic review and meta-analysis aimed to determine the hepatic adverse effects of RBAC by assessing the effect through liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). METHODS: In the present study, the Medline (PubMed), Web of Sciences, and Scopus databases were searched for relevant publications from the beginning to October 2022. The meta-analysis was based on the Mixed effect model to generate the mean effect sizes in weighted mean differences (WMD) and the 95% confidence intervals (95%CI). The heterogeneity was assessed using the Cochrane Chi-squared test, and the analysis of Galbraith plots was applied. RESULTS: Subgroup meta-analysis on five eligible randomized controlled trials (n = 239) showed a significant decrease in serum AST regarding RBAC supplementation in powder form (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170), three months and more supplementation duration (WMD (95%CI) = -3.71 (-5.95, -1.48) U/L; P-value = 0.001, I2 (%) = 29.9; P heterogeneity = 0.240) and studies with a good quality (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170). CONCLUSIONS: In conclusion, RBAC supplementation seems to not have any hepatic adverse effects and its supplementation as powder or for three months and more may decrease serum AST levels. However, we need further studies to confirm the results. REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYZES: CRD42022361002, registration time: 29/09/2022.

Theobromine supplementation in combination with a low-calorie diet improves cardiovascular risk factors in overweight and obese subjects with metabolic syndrome: a randomized controlled trial.

Background & aims: The beneficial effects of theobromine (TB) on obesity and features of metabolic syndrome (MetS) have been reported in several studies. However, the findings are equivocal. The present study aimed to investigate the effects of 12 week pure TB supplementation (450 mg day-1) combined with a low-calorie diet on the anthropometric and metabolic syndrome indices in overweight and obese adults with MetS. Methods: In a randomized double-blind parallel controlled trial, 80 participants aged 40-55 years were randomly assigned to take 450 mg day-1 TB or placebo along with a low-calorie diet for 12 weeks. Dietary intake, anthropometric indices, blood pressure, lipid profile and glycemic indices were assessed at the start and end of the intervention. Results: Seventy-two participants completed the study. After 12 weeks, TB supplementation significantly decreased the waist circumference (WC) (-0.86 cm; P = 0.045), LDL-c/HDL-c (-0.26; P = 0.008), TG/HDL-c (-0.41; P = 0.001), TC/HDL-c (-0.38; P = 0.006) and increased HDL-c (1.72 mg dl-1; P = 0.036) compared to the placebo group. There were no significant differences regarding body weight, BMI, hip circumference (HC), hip-to-waist circumference ratio (WHR), systolic and diastolic blood pressure, fasting levels of total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-c), fasting blood glucose, insulin, homoeostatic model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) between the two groups (p > 0.05). Conclusion: The results of the current study revealed that TB supplementation along with a low-calorie diet had favorable effects on WC, LDL-c/HDL-c, TG/HDL-c, TC/HDL-c, and serum level of HDL-c in overweight and obese subjects with MetS. Trial registration number: IRCT20091114002709N59. Registration date: 5 March 2022.

The effect of pomegranate consumption on cardiovascular risk factors in hemodialysis patients: A systematic review of clinical trials.

Patients undergoing maintenance dialysis have a significantly higher incidence of cardiovascular disease (CVD) compared with the general population. CVD is the most common cause of morbidity and mortality among hemodialysis patients, and has been attributed, among other causes, to increased oxidative stress, inflammation, hypertension and dyslipidemia. Pomegranate, a popular fruit worldwide, has demonstrated health benefits such as antioxidative, antidiabetic, antihypertensive, antihyperlipidemic and anti-inflammatory effects. In this systematic review of clinical trials, we aim to summarize the effect of different parts of pomegranate and the effects of its use on CVD risk factors in hemodialysis patients. PubMed/MEDLINE, EMBASE, Scopus, and Web of Science were searched to identify eligible clinical trials up to December 2021. Ultimately, seven clinical trials were included in this study. Different parts of pomegranate used in these trials were pomegranate juice, pomegranate extract and pomegranate peel extract. The duration of the studies varied from one dialysis session to 1 year. Our results showed that different parts of pomegranate may have anti-hypertensive, antioxidant, anti-inflammatory effects and improve lipid profile by decreasing TG (triglycerides) and increasing HDL-C (high-density lipoprotein cholesterol) in hemodialysis patients. However, due to limited number of studies, more clinical trials need to be performed.

The effect of selenium supplementation on disease activity and immune-inflammatory biomarkers in patients with mild-to-moderate ulcerative colitis: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: Selenium (Se) supplementation may help reduce inflammation and disease activity in ulcerative colitis (UC) patients. We investigated the therapeutic effects of Se administration in cases with mild-to-moderate active UC. METHODS: A multicenter, double-blind, randomized clinical trial (RCT) was conducted on 100 cases with active mild-to-moderate UC. The patients were randomly allocated to be given an oral selenomethionine capsule (200 mcg/day, n = 50) or a placebo capsule (n = 50) for 10 weeks. The primary outcome was defined as disease activity via the Simple Clinical Colitis Activity Index (SCCAI), and secondary outcomes were measured at the end of the study. RESULTS: After 10 weeks, the SCCAI score's mean was reduced in the Se group (P < 0.001). At the end of the intervention, clinical improvement (decline of 3 ≥ score from baseline score) was observed in 19 patients (38%) of the Se group and 3 patients (6%) of the placebo group. The patients with clinical remission (defined as SCCAI ≤ 2) were assigned in the Se group (P = 0.014). The Se group's quality of life and Se serum levels were enhanced at the end of the study (P < 0/001). In the Se group, the mean concentration of interleukin-17 decreased (P < 0/001). However, the levels of interleukin-10 showed no considerable change between the two groups in the 10th week (P = 0.23). CONCLUSION: Se supplementation as add-on therapy with medical management induced remission and improved the quality of life in patients with active mild-to-moderate UC. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: IRCT20091114002709N51; 2020-04-13.

A comprehensive insight into the molecular effect of theobromine on cardiovascular-related risk factors: A systematic review of in vitro and in vivo studies.

Theobromine may have beneficial effects on cardiovascular risk factors. This study aimed to find molecular effects of theobromine on lipid profile, glycemic status, inflammatory factors, and vascular function through a comprehensive assessment of all in vitro and in vivo studies. The search process was started at 18 July 2022. Databases including PubMed, Scopus, and Web of Science were searched to find all articles published up to 18 July 2022. Nineteen studies were included in this study. In vitro studies showed the improving effects of theobromine on inflammatory markers. Of four animal studies assessing the effect of theobromine on inflammatory markers, two reported favorable effects. Among five animal studies assessing the effects of theobromine on lipid profile, three reported improving effects on either triglyceride, total cholesterol, low- or high-density lipoprotein cholesterol. Of the three human studies, two revealed that theobromine had improving effects on lipid profile. A favorable effect of theobromine on augmentation index was also reported in two RCTs. The results for other outcomes were inconclusive. Theobromine may have favorable effects on inflammatory factors, lipid profile, and vascular function markers. However, studies with a longer duration and lower, dietary-relevant doses are required for future confirmation.

The effects of aqueous and ethanolic extracts of Rheum ribes on insulin-resistance and apolipoproteins in patients with type 2 diabetes mellitus: a randomized controlled trial.

BACKGROUND AND AIM: Previous studies have shown that Rheum ribes (R. ribes) could be effective in controlling the blood glucose levels. This study was conducted to determine the effects of R. ribes supplementation on glycemic indices and apolipoproteins in patients with type 2 diabetes mellitus (T2DM). METHODS: In the present randomized double-blind controlled trial, 60 type 2 diabetic patients aged 30-60 years with a body mass index (BMI) of 20-30 kg/m2 and hemoglobin A1c (HbA1c) of 6-8% were enrolled. Patients were randomly assigned to receive 450 mg of aqueous R. ribes extract (AG), 450 mg of ethanolic R. ribes extract (EG), or placebo (PG) three times daily for 6 weeks. At the baseline and at the end of the study, blood glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) and the homeostatic model assessment of ß-cell dysfunction (HOMA-B), as well as apolipoprotein A-I (ApoA1) and apolipoprotein B (ApoB) were measured. RESULTS: There was a significant decrease in the serum levels of insulin in AG and EG groups (P = 0.003 and P = 0.001, respectively), HOMA-IR (P = 0.01 and P = 0.001, respectively), HOMA-B (P = 0.002 and P = 0.001, respectively), ApoB (P = 0.006 and P = 0.03, respectively), ApoB/ApoA1 ratio (P = 0.016 and P = 0.04, respectively). However, a significant increase in ApoA1 (P = 0.08 and P = 0.05, respectively) with no significant changes in blood glucose, at the end of study compared to beginning values, were observed. None of the variables showed a significant change in PG. At the end of the study; while there were significant differences in insulin (P = 0.04), HOMA-IR (P = 0.03), HOMA-B (P = 0.01), ApoB (P = 0.02), and ApoB/ApoA1 ratio (P = 0.03) among the groups but ApoA1 had no significant change. CONCLUSION: Consumption of R. ribes intake could have beneficial effects on insulin resistance and apolipoproteins in type 2 diabetic patients. (Registered at en.irct.ir, identification number: IRCT201410142709N31).

Comparing the effects of docosahexaenoic and eicosapentaenoic acids on cardiovascular risk factors: Pairwise and network meta-analyses of randomized controlled trials.

BACKGROUND: Evidence from clinical trial studies suggests that docosahexaenoic acids (DHA) may have greater potential effects on improving cardiovascular risk factors than eicosapentaenoic acid (EPA). However, this evidence has not yet been meta-analyzed and quantified. The aim of this study was to evaluate and compare the effect of DHA and EPA monotherapy on cardiovascular risk factors based on paired and network meta-analysis. METHODS: Relevant articles published up to January 2022 were systematically retrieved from relevant databases. We included all Randomized Controlled Trials (RCTs) on adults that directly compared the effects of DHA with EPA and RCTs of indirect comparisons (DHA and EPA monotherapy compared to control groups). Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. The study protocol was registered with PROSPERO (Registration ID: CRD42022328630). RESULTS: Network meta-analysis of comparisons of DHA and EPA suggested significant comparable effects only on LDL-C (MD EPA versus DHA = -8.51 mg/L; 95% CI: -16.67; -0.35). However, the Network meta-analysis not show a significant effect for other risk factors. Furthermore, pairwise meta-analysis of direct comparisons of DHA and EPA showed significant difference in their effects on plasma glucose (MD EPA versus DHA = -0.31 mg/L; 95% CI: -0.60, -0.02), Insulin (MD EPA versus DHA = -2.14 mg/L; 95% CI: -3.26, -1.02), but the results were not significant for risk factors. CONCLUSION: Our findings suggest that both EPA and DHA act similarly on the markers under study, with slight changes in plasma glucose, insulin, and LDL-C.

Probiotics supplementation and brain-derived neurotrophic factor (BDNF): a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: An emerging body of evidence has demonstrated the beneficial effects of probiotics on various mental health conditions. In this systematic review and meta-analysis, we sought to examine the effects of probiotics supplementation on brain-derived neurotrophic factor (BDNF) in adults. METHODS: PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to April 2021, for eligible randomized controlled trials (RCTs). We pooled mean differences and standard deviations from RCTs using random-effect models. RESULTS: Overall, meta-analysis of 11 trials (n = 648 participants) showed no significant changes in serum level of BDNF following probiotics. However, subgroup analysis revealed that probiotics increased BDNF levels in individuals suffering from neurological disorders (n = 214 participants; WMD = 3.08 ng/mL, 95% CI: 1.83, 4.34; P = 0.001; I2 = 7.5%; P-heterogeneity 0.34), or depression (n = 268 participants; WMD = 0.77 ng/mL, 95% CI: 0.07, 1.47; P = 0.032; I2 = 88.4%; P-heterogeneity < 0.001). Furthermore, a significant increase in BDNF levels was found in studies that administered the mixture of Lactobacillus and Bifidobacterium genera, and were conducted in Asia . CONCLUSION: Our main findings suggest that probiotics may be effective in elevating BDNF levels in patients with depression and neurological disorders, and a mixed of Lactobacillus and Bifidobacterium appear to show greater efficacy than the single genus supplement. The low quality of evidence reduces clinical advocacy, and indicates that more large-scale, high-quality, RCTs are needed to facilitate reliable conclusions.

L-Arginine is a feasible supplement to heal chronic anal fissure via reducing internal anal sphincter pressure: a randomized clinical trial study.

The hypertonicity of internal anal sphincter resting pressure is one of the main causes of chronic anal fissure. Therefore, the aim of this study was to assess the effect of oral administration of L-arginine on the improvement of the anal fissures by relaxing the internal anal sphincter. Seventy-six chronic anal fissure patients (aged 18-65 years) who were referred to Rasoul-e-Akram Hospital, Tehran, Iran from February 2019 to October 2020 participated in this randomized, double-blind, placebo-controlled trial. Participants were allocated into treatment (L-arginine) and placebo groups. They took a 1000 mg capsule three times a day for 1 month, and then we followed them at the end of the first and third months after the intervention. Clinical symptoms, anal sphincter resting pressure, and quality of life (QoL) were completed at baseline and the end of the study. The analysis of data showed a significant decrease in bleeding, fissure size, and pain for each group; however, in the L-arginine group was more than the control group at the end of the study (P values < 0.001). Following that, a significant increase in QoL was seen just in patients treated with L-arginine (P value = 0.006). In addition, the comparison of anal pressures at baseline and, between groups at the end of the study showed a significant reduction in sphincter pressure in patients treated with L-arginine (P value < 0.001, = 0.049; respectively). The oral administration of 3000 mg L-arginine can heal chronic anal fissures by reducing internal anal sphincter pressure with more negligible side effects. However, we recommend long-term study with more extended follow-up.Clinical trial registry: IRCT20190712044182N1 at Iranian clinical trials, date: 2019-08-27.

The effects of chitosan supplementation on anthropometric indicators of obesity, lipid and glycemic profiles, and appetite-regulated hormones in adolescents with overweight or obesity: a randomized, double-blind clinical trial.

BACKGROUND: Chitosan is one of dietary fiber that has received great attention in improving obesity-related markers, but little is known on its effects on adolescents. OBJECTIVES: To analyze the effects of chitosan supplementation on obesity-related cardiometabolic markers and appetite-related hormones in adolescents with overweight or obesity. METHODS AND ANALYSIS: A randomized clinical trial was performed on 64 adolescents with overweight and obesity, who were randomly allocated to receive chitosan supplementation (n = 32) or placebo as control (n = 32) for 12 weeks. Anthropometric measures, lipid and glycemic profiles, and appetite-related hormones were examined. RESULTS: Sixty-one participants completed study (chitosan = 31, placebo = 30). Chitosan supplementation significantly improved anthropometric indicators of obesity (body weight: - 3.58 ± 2.17 kg, waist circumference: - 5.00 ± 3.11 cm, and body mass index: - 1.61 ± 0.99 kg/m2 and - 0.28 ± 0.19 Z-score), lipid (triglycerides: - 5.67 ± 9.24, total cholesterol: - 14.12 ± 13.34, LDL-C: - 7.18 ± 10.16, and HDL-C: 1.83 ± 4.64 mg/dL) and glycemic markers (insulin: - 5.51 ± 7.52 µIU/mL, fasting blood glucose: - 5.77 ± 6.93 mg/dL, and homeostasis model assessment of insulin resistance: - 0.24 ± 0.44), and appetite-related hormones (adiponectin: 1.69 ± 2.13 ng/dL, leptin - 19.40 ± 16.89, and neuropeptide Y: - 41.96 ± 79.34 ng/dL). When compared with the placebo group, chitosan supplementation had greater improvement in body weight, body mass index (kg/m2 and Z-score), waist circumference, as well as insulin, adiponectin, and leptin levels. Differences were significant according to P-value < 0.05. CONCLUSION: Chitosan supplementation can improve cardiometabolic parameters (anthropometric indicators of obesity and lipid and glycemic markers) and appetite-related hormones (adiponectin, leptin, and NPY) in adolescents with overweight or obesity.

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.

Consumption of sesame seeds and sesame products has favorable effects on blood glucose levels but not on insulin resistance: A systematic review and meta-analysis of controlled clinical trials.

Sesame, with an oily seed containing oil, lignans, and proteins, is a popular plant that has demonstrated health benefits such as antioxidative, antiobesity, and antiinflammatory effects. In this systematic review and meta-analysis, we aimed to summarize the effect of sesame seeds and their consumption compared to a control group on blood glucose and insulin resistance in human adults. PubMed/MEDLINE, SCOPUS, Web of Science, Google Scholar, and EMBASE were searched to identify eligible controlled clinical trials up to February 2021. Finally, eight clinical trials were included in this study. Sesame products used in these trials were sesame oil, sesamin, and tahini, and the duration of the intervention varied from 45 days to 9 weeks. Our results showed the significant positive effects of sesame and its products on fasting blood glucose FBG (weighted mean difference, WMD: -21.31 mg/dl, 95% CI: -41.23, -1.39, p = .036) and HbA1c (WMD: -0.75, 95% CI: -1.16, -0.34, p < .001) levels but results about fasting serum insulin (WMD: 5.51 µU/ml, 95% CI: -2.31, 13.33, p = .167) and HOMA-IR (WMD: -0.07, 95% CI: -0.33, 0.20, p = .617) were not meaningful. Sesame may be considered a beneficial agent for human glucose metabolism and can be a part of glucose-lowering diets.

The effect of lycopene supplement from different sources on prostate specific antigen (PSA): A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prostate cancer is a major malignancy, affecting men, worldwide. The protective effect of dietary or supplemental lycopene on prostate cancer has been reported in several studies; however, the findings are equivocal. OBJECTIVE: The aim of this study was to evaluate the effects of supplemental lycopene on PSA level, by conducting a systematic review and meta-analysis of randomized controlled trials. METHODS: We searched online databases, including PubMed, Scopus, and Web of Science, up to 9 Jun 2020, to obtain relevant publications. The publication search was not limited by language or date. RESULTS: A total of 1036 records were identified in the systematic search; from these, 9 were included in the systematic review and 6 in meta-analysis. The pooled analysis of the 6 studies showed no significant differences in PSA levels in subjects treated with lycopene or tomato extract containing lycopene (WMD= -0.12 ng/ml; 95% CI: -0.62, 0.38 ng/ml; P = 0.64) compared to the control. CONCLUSION: Overall, tomato extracts or lycopene treatment yielded no significant effect on PSA level compared to the control. However, more consistent clinical trials, with larger sample sizes, are required to better discern the actual effect of tomato extract or lycopene on PSA level.

Effect of whey protein consumption on IL-6 and TNF-α: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Due to inconsistent data about WP supplementation on inflammatory markers, present systematic review and meta-analysis was done to summarize its effect on TNF-α and IL-6. METHODS: Our search was done in Pubmed, Scopus, Embase, and Cochrane up to June 2021. Weighted mean difference (WMD) and 95% confidence intervals (CI) was used to indicate the effect sizes. Conceivable sources of heterogeneity were detected by subgroup analysis. RESULTS: Overall, 11 eligible RCTs were included. The pooled results showed that WP supplementation had no significant effect on TNF-α and IL-6 status compare to those receiving carbohydrate and other types of proteins as placebo. Results from subgroup analysis based on health status, study duration, WP dosage and sex, expressed no favorable effect of WP on TNF-α and IL-6 levels. CONCLUSION: It can be concluded that whey supplementation had no favorable effects on inflammatory biomarkers including TNF- α and IL-6.

The effects of probiotic/synbiotic supplementation compared to placebo on biomarkers of oxidative stress in adults: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: During the last decades, there has been a burst of scientific literature hypothesizing the antioxidant effect of probiotics. However, the results of these studies are inconsistent and a final conclusion has yet to be reached. Thus, the aim of this study was to assess the effects of probiotic/synbiotic supplementation on serum total antioxidant capacity (TAC), glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) levels in adults. METHODS AND RESULTS: The following online databases were searched until August 26th 2020: PubMed/Medline, Scopus, Clarivate Analytics Web of Science, Cochrane Central Register of Controlled Trials, Science Direct, Google Scholar and Igaku Chuo Zasshi. The effect sizes were expressed as the weighted mean difference (WMD) with 95% confidence intervals (CI). A total of 31 eligible trials with 1681 participants (839 cases and 842 controls) were included in this meta-analysis. The results revealed that the supplementation with probiotics/synbiotics, significantly increased serum TAC (WMD: 54.14 mmol/L, 95% CI: 27.87, 80.40, P < 0.001), GSH (WMD: 40.38 µmol/L, 95% CI: 20.72, 60.03, P < 0.001) and NO (WMD: 3.54 µmol/L, 95% CI: 1.73, 5.34, P < 0.001) levels. In addition, MDA levels were significantly reduced (WMD: -0.45 µmol/L, 95% CI: -0.58,-0.32, P < 0.001) following probiotic/synbiotic supplementation. None of the variables showed a significant change in the sensitivity analysis. CONCLUSION: Available evidence suggests that probiotic/synbiotic supplementation can significantly increase serum TAC, GSH and NO, as well as reduce MDA levels in adults. Therefore, probiotic/synbiotic supplementation may play a role in improving antioxidant indices and reducing oxidative stress in the body.

Impact of orange juice consumption on cardiovascular disease risk factors: a systematic review and meta-analysis of randomized-controlled trials.

Cardiovascular disease (CVD) is the greatest cause of premature death and disability globally. Numerous therapeutic strategies have been developed to improve and prevent the adverse cardiovascular events, including nutritional approaches. This systematic review and meta-analysis summarized the evidence on orange juice consumption on CVD risk factors. Four databases were searched up to September 2020. Ten randomized controlled trials were included in the final analysis. Pooled results demonstrated a significant effect of orange juice on glucose (WMD: -2.92 mg/dl, 95% CI: -5.327, -0.530, p = 0.017), insulin (WMD: -1.229 µU/ml, 95% CI: -2.083, -0.374, p = 0.005), HOMA-IR (WMD: -0.464, 95% CI: -0.747, -0.181, p = 0.001), total cholesterol (WMD: -9.84 mg/dl, 95% CI: -15.43, -4.24, p = 0.001), LDL-C (WMD: -9.14 mg/dl, 95% CI: -15.79, -2.49, p = 0.007), and CRP (WMD: -0.467 mg/l, 95% CI: -0.815, -0.120, p = 0.008) compared to control group. However, the effect of orange juice on body composition factors and other CVD risk factors was not significant compared to control group. These lowering effects of glucose, HOMA-IR, total cholesterol, and LDL-C were robust in subgroups with orange juice consumption ≥500 ml/day. This meta-analysis suggests that orange juice may be beneficial in improving several CVD risk factors.

The effect of cranberry supplementation on Helicobacter pylori eradication in H. pylori positive subjects: a systematic review and meta-analysis of randomised controlled trials.

Helicobacter pylori infection is one of the most common chronic bacterial infections. Cranberry has been suggested for H. pylori eradication. We aimed to conduct the first meta-analysis to summarise current evidence on effects of cranberry supplementation on H. pylori eradication in H. pylori positive subjects. We searched the online databases up to December 2020. Four randomised clinical trials (RCT) were included with human subjects, investigating the effect of cranberry on H. pylori eradication. The pooled results were expressed as the OR with 95 % CI. Based on five effect sizes with a total sample size of 1935 individuals, we found that according to the OR, there was a positive effect of cranberry supplementation on H. pylori eradication, increasing the chance of H. pylori eradication by 1·27 times, but this relationship was not statistically significant (overall OR: 1·27; 95 % CI 0·63, 2·58). The results also indicated the moderate between-study heterogeneity (I2 = 63·40 %; P = 0·03) of the studies. However, there were no significant differences in some subgroup analyses in the duration of treatment, the duration of follow-up and the Jadad score. Our findings revealed that although cranberry had a positive effect on H. pylori eradication in adults, this effect was not statistically significant. Due to the small number of included studies and moderate heterogeneities, the potential of cranberry supplementation on H. pylori eradication should be validated in large, multicentre and well-designed RCT in the future.