Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial.

BACKGROUND: Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. METHODS: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. DISCUSSION: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. TRIAL REGISTRATION: ( Clinicaltrials.gov ): NCT05604846.

The effects of Anethum graveolens (dill) supplementation on lipid profile and glycemic control: a systematic review and meta-analysis of randomized controlled trials.

There is an increased interest in the potential health benefits of nutraceutical therapies, such as Anethum graveolens (dill). Therefore, this systematic review and meta-analysis aimed to evaluate the effects of Anethum graveolens supplementation on lipid profiles and glycemic indices in adults. A systematic search was performed for literature published through November 2020 via PubMed/Medline, Scopus, ISI Web of Science, and Embase to find randomized controlled trials (RCTs) evaluating the effects of oral supplementation with A. graveolens on lipid profile and measures of glycemic control in adults. The random-effects model was applied to establish the weighted mean difference (WMD) and associated 95% confidence intervals (CI). Seven RCTs with a total number of 330 subjects were included in the final analysis. Pooled results indicated that A. graveolens supplementation significantly decreased low-density lipoprotein cholesterol (LDL) concentration (WMD: -15.64 mg/dL; 95% CI: -24.55 to -6.73; P = 0.001), serum insulin (WMD: -2.28 µU/ml; 95% CI: -3.62 to -0.93; P = 0.001), and HOMA-IR (WMD: -1.06; 95% CI: -1.91 to -0.20; P = 0.01). However, there was no significant effect on serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and fasting blood glucose (FBS). Subgroup analysis suggested that using A. graveolens in higher doses and long-term duration had beneficial effects on lipid profiles. Dose-response analysis also showed a significant reduction in FBS at doses of 1500 mg/d. The present meta-analysis indicated that Anethum graveolens could exert favorable effects on insulin resistance and serum LDL. Further research is necessary to confirm our findings.

Does saffron supplementation have favorable effects on liver function indicators? A systematic review and meta-analysis of randomized controlled trials.

Several pharmaceutical and non-pharmaceutical approaches have been suggested to improve liver health. There is a large discrepancy in the effects of saffron supplementation on liver function in adults. To fill this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) assess the effects of saffron supplementation on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A systematic search current to August 2020 was performed in PubMed/Medline, Scopus, Web of Science, and Google Scholar using relevant keywords to detect eligible articles. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine eligible trials were included in the final analysis. The pooled analysis revealed that serum ALT concentrations were significantly reduced using saffron compared to placebo (WMD: -2.39 U/L; 95% CI: -4.57 to -0.22; P = 0.03, I2= 87.9%, P < 0.001). However, saffron supplementation did not affect levels of serum AST (WMD: 1.12 U/L; 95% CI: -1.42 to 3.65; P = 0.39) or ALP (WMD: 4.32 U/L; 95% CI: -6.91 to 15.54; P = 0.78). In the dose-response analysis, we did not find a significant dose-response relationship between dosage and duration of saffron supplementation on serum levels of ALT, AST, and ALP. We found that saffron supplementation can reduce ALT serum concentrations without significant effects on other liver function indicators, including AST and ALP. Nevertheless, future large RCTs on diverse populations are needed to understand better the effects of saffron and its constituents on these enzymes.

The effect of chromium intake on oxidative stress parameters: A systematic review and meta-analysis.

BACKGROUND: Trivalent chromium is a trace element thought to have a beneficial effect on oxidative stress (OS) parameters and inflammation. This review aimed to investigate the dose-response of chromium and summarize the effects of chromium supplementation on OS parameters in the literature. METHODS: MEDLINE, Scopus, Web of Science and Cochrane CENTRAL databases were searched for RCTs published from inception to January 2021 evaluating the effect of chromium supplementation on OS parameters, namely MDA, TBARS, SOD, TAS, CAT, GPx, and GSH. A random-effects model was used to pool data and calculated standard mean difference and 95 % confidence intervals. Quantified heterogeneity among studies was assessed through Cochrane's I2 values. RESULTS: Nine studies enrolling 550 participants met the inclusion criteria. The obtained results indicate that chromium supplementation significantly increases TAC (SMD: 0.46; 95 % CI: 0.08, 0.84; I2 = 00.0 % n = 2) and significantly decreases MDA levels (SMD: -0.46; 95 % CI: -0.86, -0.07; I2 = 52.4 % n = 5). Supplementation did not significantly change CAT, GPx, GSH, SOD, TAS, and TBARS. CONCLUSION: Chromium supplementation may improve OS parameters, however, due to high heterogeneity observed in the included studies, these findings should be interpreted with caution. Large RCTs on various patient groups evaluating the impact of chromium supplementation are needed to allow an adequate generalization of the benefits of chromium on human health.

The Effects of Folic Acid Supplementation on Pro-inflammatory Mediators: a Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Despite extensive research, findings regarding the effects of folic acid supplementation on inflammatory mediators have been controversial and inconclusive. This study therefore aimed to summarize the findings of all available clinical trials regarding the effects of folic acid supplementation on inflammatory biomarkers in adults. METHODS: A systematic search was conducted of PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Google Scholar until April 2020. All randomized controlled trials that examined the influence of folic acid supplementation on C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were included. Pooled effect sizes were calculated based on the random effects model, and dose-response analysis was modeled by using a fractional polynomial model. FINDINGS: In total, 18 randomized controlled trials involving 2286 participants were analyzed. Folic acid supplementation significantly reduced serum levels of C-reactive protein (mean difference [MD], -0.21 mg/L; 95% CI, -0.41 to -0.01; n = 16), TNF-α (MD, -14.88 pg/mL; 95% CI, -23.68 to -6.09; n = 10), and IL-6 (MD, -0.93 pg/mL; 95% CI, -1.72 to -0.14; n = 11). Subgroup analyses suggested a significant reduction at doses ≤5 mg/d and studies longer than 12 weeks in duration. A significant nonlinear association was also found between folic acid dosage (Pnonlinearity <0.001) and duration of administration (Pnonlinearity <0.001) with serum TNF-α levels. IMPLICATIONS: This meta-analysis indicates the beneficial effects of folic acid supplementation on pro-inflammatory cytokines. Further studies with a longer duration of administration, higher doses, and larger sample sizes should be performed exclusively on patients with chronic inflammatory disorders to elucidate the favorable role of folate intake on inflammatory biomarkers. International Prospective Register of Systematic Reviews identifier: CRD42021249947.

Sumac fruit supplementation improve glycemic parameters in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis.

BACKGROUND: Metabolic syndrome (MetS) is the one of the main causes of mortality worldwide. Several randomized controlled trials (RCTs) have revealed the beneficial effects of sumac (Rhus coriaria) on cardiometabolic risk factors. However, the entirety of the evidence has yet to be summarized in a systematic review. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the effects of sumac on several cardiometabolic risk factors in patients with MetS and related disorders. METHODS: We reviewed Medline, Scopus, Web of Science and Cochrane CENTRAL for RCTs published from inception to December 2020 evaluating the impact of sumac in adults with MetS or related disorders. Outcome measures included anthropometric measures, glycemic indices, blood lipids, blood pressure and liver enzymes. Pooled effect sizes were reported as standard mean differences (SMDs) and 95% confidence intervals (CIs). Trials were pooled using a random effects model. RESULTS: Nine studies enrolling 526 participants met the inclusion criteria for this meta-analysis. Our results indicate that sumac intake significantly decrease fasting blood sugar (FBS) (SMD: -0.28; 95% CI: -0.54, -0.02; I2 = 00.0%), insulin (SMD: -0.67; 95% CI: -0.99, -0.36; I2 = 03.7%), and insulin resistance (measured through the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)) (SMD: -0.79; 95% CI: -1.24, -0.34; I2 = 50.1%). Sumac intake did not have a significant impact on weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHR), HbA1c, total cholesterol (TC), triglycerides (TG), high density lipoproteins (HDL), low density lipoprotein (LDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST) and alanine transaminase (ALT). CONCLUSION: Sumac, as an adjuvant therapy, may decrease serum levels of FBS, insulin and HOMA-IR. However, due to high heterogeneity in the included studies, these findings must be interpreted with great caution. Larger, well-designed placebo-controlled clinical trials are still needed to further evaluate the capacity of sumac as a complementary treatment to control MetS risk factors.

What is the influence of cinnamon supplementation on liver enzymes? A systematic review and meta-analysis of randomized controlled trials.

Existing evidence has uncovered the potential health benefits of cinnamon intake; however, its effect on liver function is unclear. Thus, the aim of this systematic review and meta-analysis was to examine the effect of cinnamon supplementation on liver enzymes. Relevant articles were identified through a systematic search in PubMed/Medline, Scopus, Web of Science, Cochrane Library, and Embase up to September 2020. All trials assessing the effect of oral cinnamon supplementation on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in adults were included. The pooled effect sizes were obtained using the random-effects model and expressed as mean difference (MD) and 95% confidence intervals (CI). A total of seven original trials (nine treatment arms) involving a total of 256 subjects were included in the final analysis. The pooled analysis indicated that cinnamon supplementation had no significant effect on serum levels of ALT, AST, and ALP. However, there was a significant reduction in ALT levels in patients with type 2 diabetes (MD: -4.01 U/L; 95% CI: -6.86, -1.15) and in trials with low-dose supplementation (<1,500 mg/d), follow-up duration longer than 12 weeks, and in the elderly patients (aged>50 years). The beneficial effects of cinnamon intake were also shown in AST levels in patients with type 2 diabetes and trials with long-term follow-up (>12 weeks). Longer-term, oral cinnamon supplementation may improve serum levels of liver enzymes in patients with type 2 diabetes. Further high-quality studies are needed, especially in populations with abnormal liver enzyme levels, to firmly establish the clinical efficacy of cinnamon on liver function.

Effect of ginger (Zingiber officinale) supplementation on oxidative stress parameters: A systematic review and meta-analysis.

A wide variety of antioxidant properties are attributed to ginger (Zingiber officinale) and several randomized controlled trials (RCTs) have investigated the effect of ginger intake on major oxidative stress (OS) parameters. We conducted a systematic review and meta-analysis to evaluate the effects of using ginger to improve OS levels. Medline, Scopus, ISI Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched up until March 2020 to gather RCTs that evaluated the impact of ginger intake on the levels and activity of OS parameters in adult subjects. Means and standard deviations for relevant OS variables were extracted and evaluated to assess the quality of the trials based on the Cochrane risk-of-bias tool for randomized trials. The gathered data were pooled and expressed as standardized mean difference (SMD) with 95% Confidence Intervals (95% CI). Twelve trials were included in this review. Ginger intake was shown to significantly increase glutathione peroxidase (GPx) activity (SMD: 1.64; 95% CI: 0.43, 2.85; I2  = 86.8%) and total antioxidant capacity (TAC) (SMD: 0.40; 95% CI: 0.06, 0.73; I2  = 42.8%) and significantly decrease malondialdehyde (MDA) levels (SMD: -0.69; 95% CI: -1.26, -0.12; I2  = 85.8%) compared to control groups. Ginger supplementation also non-significantly associated with an increase in CAT activity (SMD: 1.09; 95% CI: -0.07, 2.25; I2  = 87.6%). This systematic review and meta-analysis presents convincing evidence supporting the efficacy of ginger supplementation on improving OS levels. PRACTICAL IMPLICATIONS: In health sciences, OS, due to its pivotal role in the pathophysiology of several chronic diseases, is a subject with a long history. Recent research strives for a safe, ideal, and effective antioxidant. Ginger is herbal medicine, which has been widely used in traditional and complementary medicine. Proving the antioxidant effect and potential benefit of ginger has positive clinical implications for the application of this practical herb.

Effect of melatonin supplementation on oxidative stress parameters: A systematic review and meta-analysis.

BACKGROUND: Oxidative stress, defined as an imbalance between pro-oxidants and neutralizing antioxidants within the body, is a growing public health concern. Oxidative stress is involved in the progression of nearly all chronic diseases. Melatonin has been suggested to reduce oxidative stress by its potential radical scavenging properties. OBJECTIVE: To determine the efficacy and safety of melatonin as a therapy for the improvement of oxidative stress parameters in randomized controlled trials. METHODS: A systematic database search using Scopus, PubMed/Medline, EMBASE, Web of Science, the Cochrane Controlled Register of Trials and clinicaltrials.gov (https://clinicaltrials.gov) for studies published up to July 2020 was conducted. We included studies which investigated the effect of supplemental melatonin compared to placebo on oxidative stress parameters in unhealthy patients. Quantitative data synthesis was conducted using a random-effects model with standard mean difference (SMD) and 95 % confidence intervals (CI). Cochrane's Q and I2 values were used to evaluate heterogeneity. RESULTS: A total of 12 randomized controlled trials (RCTs) were eligible. The meta-analysis indicated an association between melatonin intake and a significant increase in total antioxidant capacity (TAC) (SMD: 0.76; 95 % CI: 0.30, 1.21; I2 = 80.1 %), glutathione (GSH) levels (SMD: 0.57; 95 % CI: 0.32, 0.83; I2 = 15.1 %), superoxide dismutase (SOD) (SMD: 1.38; 95 % CI: 0.13, 2.62; I2 = 86.9 %), glutathione peroxidase (GPx) (SMD: 1.36; 95 % CI: 0.46, 2.30; I2 = 89.3 %), glutathione reductase (GR) (SMD: 1.21; 95 % CI: 0.65, 1.77; I2 = 00.0 %) activities, and a significant reduction in malondialdehyde (MDA) levels (SMD: -0.79; 95 % CI: -1.19, -0.39; I2 = 73.1 %). Melatonin intake was not shown to significantly affect nitric oxide (NO) levels (SMD: -0.24; 95 % CI: -0.61, 0.14; I2 = 00.0 %) or catalase (CAT) activity (SMD: -1.38; 95 % CI: -1.42, 4.18; I2 = 96.6 %). CONCLUSION: Melatonin intake was shown to have a significant impact on improving Oxidative stress parameters. However, future research through large, well-designed randomized controlled trials are required to determine the effect of melatonin on oxidative stress parameters in different age groups and different disease types.

The effects of omega-3 fatty acid supplementation on inflammatory factors in HIV-infected patients: A systematic review and meta-analysis of randomized clinical trials.

High concentrations of C-reactive protein (CRP) and inflammatory markers are common in human immunodeficiency virus (HIV)-infected patients and are associated with non-HIV related comorbidity and mortality. Data on the benefits of omega-3 fatty acid (omega-3 FA) supplementation for improving inflammation status in HIV-infected patients are controversial. Thus, we conducted a systematic review and meta-analysis on the beneficial effects of omega-3 FAs on controlling inflammation in HIV-infected patients. We conducted a comprehensive search of the major biomedical databases, including PubMed, EMBASE, Scopus, Web of Science and Cochrane library, for all potentially relevant studies published without restriction from the beginning of time to June 2020. Overall, nine RCTs were included comprising a total of 427 participants. A random-effects model was used to calculate 95% confidence intervals (CI) and the effect was measured as standardized mean difference (SMD). Supplementation of omega-3 FAs showed a significant reduction of CRP (SMD: -0.27, 95% CI: -0.48 to -0.07, P = 0.007). There was no significant difference in levels of TNF-α (SMD: 0.03, 95% CI: -0.79 to 0.85, P = 0.94, I2 = 87%) and IL-6 (SMD: -0.13, 95% CI: -0.59 to 0.32, P = 0.57, I2 = 73%, Fig. 3). The results indicate that the supplementation of omega-3 FAs in HIV-infected patients significantly decreases serum CRP levels when compared to the control group, however has no significant effect on IL-6 and TNF-α levels.