Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

BACKGROUND: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. RESULTS: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). CONCLUSIONS: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

The effect of probiotics supplementation on cancer-treatment complications: a critical umbrella review of interventional meta-analyses.

Cancer-related complications pose significant challenges in the management and treatment of patients with malignancies. Several meta-analyses have indicated improving effects of probiotics on cancer complications, while some studies have reported contentious findings. The purpose of the present study was to evaluate the efficacy of probiotics in addressing cancer complications, including diarrhea, mucositis, and infections, following chemotherapy, radiotherapy, and surgery. Relevant studies were searched in the PubMed, Scopus, Embase and Web of Science databases and Google Scholar up to September 2023. All meta-analyses addressing the effects of probiotics on all cancer treatments-induced complications including infection, diarrhea and oral mucositis were included. The pooled results were calculated using a random-effects model. Analyses of subgroups, sensitivity and publication bias were also conducted. The results revealed that the probiotics supplementation was effective on reduction of total cancer complications (OR:0.53; 95% CI: 0.44, 0.62, p < 0.001; I2=79.0%, p < 0.001), total infection rate (OR:0.47; 95%CI: 0.41, 0.52, p < 0.001; I2= 48.8%, p < 0.001); diarrhea (OR:0.50; 95%CI: 0.44, 0.57, p < 0.001; I2=44.4%, p = 0.023) and severe diarrhea (OR: 0.4; 95%CI: 0.27, 0.56, p < 0.001; I2=31.3%, p = 0.178), oral mucositis (OR: 0.76; 95%CI: 0.58, 0.94, p < 0.001; I2=95.5%, p < 0.001) and severe oral mucositis (OR:0.65, 95%CI: 0.58, 0.72 p < 0.001; I2=22.1%, p = 0.274). Multi strain probiotic (OR:0.49; 95%CI: 0.32, 0.65, p < 0.001; I2=90.7%, p < 0.001) were more efficacious than single strain (OR:0.73; 95%CI: 0.66, 0.81, p < 0.001; I2=0.00%, p = 0.786). The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.

The effect of green coffee extract supplementation on obesity indices: critical umbrella review of interventional meta-analyses.

Despite a multitude of investigations assessing the impact of green coffee extract supplementation on obesity indices, there is still a great deal of heated debate regarding the benefits of this intervention in obesity management. Therefore, in order to clarify the effect of green coffee extract on waist circumference (WC), body mass index (BMI) and body weight (BW), we conducted an umbrella review of interventional meta-analyses. The Web of Science, Scopus, PubMed/Medline, and Embase databases were searched using specific keywords and word combinations. The umbrella meta-analysis was performed using the Stata software version 17 (Stata Corp. College Station, Texas, USA). We pooled effect sizes (ES) and confidence intervals (CI) for the outcomes using the random effects model (the DerSimonian and Laird method). In total, 5 eligible meta-analyses were included in the final quantitative assessment. Data pooled from 5 eligible papers revealed that green coffee extract can reduce BW (WMD: -1.22 kg, 95% CI: -1.53 to -0.92, p < 0.001), BMI (WMD: -0.48 kg/m2, 95% CI: -0.67 to -0.29, p < 0.001) and WC (WMD: -0.55 cm, 95% CI: -0.80 to -0.31, p < 0.001). Subgroup analyses highlighted that green coffee extract supplementation in dosages ≤600 mg/day and interventions lasting >7 wk are more likely to decrease BW. The present umbrella meta-analysis confirms the beneficial effects of green coffee extract in reducing WC, BMI, and BW. Thus, we may infer that green coffee extract can be used as a complementary therapy in the management of obesity.

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.

The influence of omega-3 supplementation on vitamin D levels in humans: a systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Inconsistencies exist with regard to the influence of omega-3 supplementation on 25-hydroxyvitamin D (25(OH)D) levels, which could be attributed to many factors, such as the duration and dose of omega-3 supplementation, and individuals' baseline 25(OH)D levels. Therefore, to address the inconsistencies, we conducted a systematic review and dose-response meta-analysis to accurately determine the effect of omega-3 supplementation on 25(OH)D levels in humans. METHODS: We performed a comprehensive literature search in Web of Science, PubMed/Medline, Scopus, and Embase databases from inception up to January 2020. We included only randomized controlled trials (RCTs). We used weighted mean difference (WMD) with 95% confidence interval (CI) to assess the influence of omega-3 supplementation on serum 25(OH)D levels using the random-effects model. RESULTS: Our pooled results of 10 RCTs demonstrated an overall significant increase in 25(OH)D levels following omega-3 intake (WMD = 3.77 ng/ml, 95% CI: 1.29, 6.25). In addition, 25(OH)D levels were significantly increased when the intervention duration lasted >8 weeks and when the baseline serum 25(OH)D level was ˂20 ng/ml. Moreover, omega-3 intake ≤1000 mg/day resulted in higher 25(OH)D levels compared to omega-3 intake >1000 mg/day. CONCLUSION: In conclusion, omega-3 supplementation increased 25(OH)D concentrations, particularly with dosages ≤1000 mg/day and intervention durations >8 weeks.

Wheat germ improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial.

Globally, Non-alcoholic fatty liver disease (NAFLD) has a rising prevalence with no definitive pharmacological treatments. The aim of this study was to assess the clinical effects of wheat germ in patients with NAFLD. Fifty participants with NAFLD were randomly allocated to take 40 g wheat germ (n = 25) or placebo (n = 25) in a randomized double-blind clinical trial over 12 weeks. Transient elastography (FibroScan) determined a diagnosis of NAFLD. After 12 weeks of intervention, reduction in serum alanine aminotransferase (p = 0.006) and γ-glutamyltransferase (p = 0.004), total cholesterol (p = 0.018), triglyceride (p = 0.046), and hepatic steatosis (p = 0.043) levels in the wheat germ group was significantly higher compared to the placebo group. Serum TAC levels in wheat germ group patients increased significantly higher than placebo group (p = 0.001). Reduction in serum hs-CRP level in the wheat germ group was significantly higher than in the placebo group (p = 0.031). In conclusion, our study shows that wheat germ consumption may improve total antioxidant capacity, hepatic steatosis, serum total cholesterol and triglyceride levels, alanine aminotransferase (ALT), and Gamma-glutamyl Transferase (GGT) in NAFLD patients. Longitudinal studies with larger sample sizes are needed to confirm biological effects of wheat germ on NAFLD patients.

Higher intakes of dietary caffeine are associated with 25-hydroxyvitamin D deficiency.

Low serum 25-hydroxyvitamin D [25(OH)D] levels remain a challenge worldwide. While some in vitro studies show a caffeine-induced decrease in vitamin D receptor expression, there is a paucity of research to define the extent of caffeine intake and effects on 25(OH)D levels. Therefore, we aimed to associate dietary caffeine intake with 25(OH)D deficiency through a recognized dataset. Using data collected from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), 25(OH)D levels and dietary caffeine intake were extracted from 13134 individuals (30-47 years, interquartile range). We used one-way ANOVA and chi-square tests for quantitative and qualitative variables, respectively, and performed multivariate logistic regression for four models to assess the odds ratio (OR) of 25(OH)D deficiency (<20 ng/ml or <50 nmol/L) based on quartiles of dietary caffeine intake. Both crude and multivariable models detected higher OR for 25(OH)D deficiency according to the highest intakes of caffeine (15.8±9.5, 51.9±11.9, and 177±156 mg/d) when compared to the reference category (2.19±1.04 mg/d), in which the OR in the highest category of caffeine intake was 1.24 (95% CI: 1.12 to 1.37) and 1.48 (95% CI: 1.16 to 1.78) for the crude model and the most complete multivariable analysis (adjustment for age, sex, race, body mass index, smoking, physical activity, occupation, energy intake, protein intake, and fat intake), respectively. In conclusion, higher dietary intakes of caffeine were associated with 25(OH)D deficiency in a representative sample of the American population, but further investigation is warranted to determine causation.

Serum Vitamin D Levels and Risk of Liver Cancer: A Systematic Review and Dose-Response Meta-Analysis of Cohort Studies.

Data regarding the relationship between serum vitamin D levels and the risk of liver cancer are conflicting. Therefore, we performed a systematic review and dose-response meta-analysis of all available data of cohort studies on the association of 25-OH-vitamin-D levels with the risk of hepatocellular carcinoma. We conducted a systematic search in PubMed-MEDLINE, Scopus, Cochrane and Web of Science databases for prospective observational studies conducted on the general population from inception to May 2019. Six studies provided data from 6357 participants. According to the pooled HR, the subjects with the highest serum concentrations of vitamin D had a 47% lower risk of liver cancer vs. the subjects with the lowest serum concentrations of vitamin D (pooled HR: 0.53, 95% CI: 0.41-0.68; P < 0.001). There was no significant heterogeneity among the studies (P = 0.431, I2 = 0.0). The pooled HR from the random-effects dose-response model indicated an indirect significant linear association between vitamin D and the risk of liver cancer (coef = -0.017, P < 0.001). However, there was no significant nonlinear dose-response association between serum vitamin D and the risk of liver cancer (coef = -0.0001, P = 0.342). The evidence from this meta-analysis suggests that there may be an inverse relationship between serum vitamin D levels and the risk of liver cancer.

The effect of fasting and energy restricting diets on markers of glucose and insulin controls: a systematic review and meta-analysis of randomized controlled trials.

Inconsistencies exist with regard to influence of fasting and energy-restricting diets on markers of glucose and insulin controls. To address these controversial, this study was conducted to determine the impact of fasting diets on fasting blood sugars (FBSs), insulin, homeostatic model assessment insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) levels. A comprehensive systematic search was carried out in electronic databases, i.e., Scopus, PubMed, and Web of Science through June 2019 for RCTs that investigated the impact of fasting and energy-restricting diets on circulating FBS, insulin, HOMA-IR and HbA1c levels from. Weighted mean difference (WMD) with the 95% CI were used for estimating combined effect size. The subgroup analysis was applied to specify the source of heterogeneity among articles. Pooled results from 30 eligible articles with 35 arms demonstrated a significant decrease in FBS (WMD): -3.376 mg/dl, 95% CI: -5.159, -1.594, p < 0.001), insulin (WMD: -1.288 µU/ml, 95% CI: -2.385, -0.191, p = 0.021), HOMA-IR (WMD: -0.41 mg/dl, 95% CI: -0.71, -0.10, p = 0.01) levels following fasting or energy-restricting diets. Nevertheless, no significant changes were observed in serum HbA1c levels. The subgroup analyses showed that overweight or obese people with energy restricting diets and treatment duration >8 weeks had a greater reduction in FBS, insulin and HOMA-IR level compared with other subgroups. The evidence from available studies suggests that the fasting or energy-restricting diets leads to significant reductions in FBS, insulin and HOMA-IR level and has modest, but, non-significant effects on HbA1c levels.

Effects of dehydroepiandrosterone (DHEA) supplementation on cortisol, leptin, adiponectin, and liver enzyme levels: A systematic review and meta-analysis of randomised clinical trials.

BACKGROUND AND AIMS: Dehydroepiandrosterone (DHEA) supplementation has been investigated in patients with altered cortisol levels and is proposed to ameliorate the metabolic profile related to adipose tissue. However, further research is warranted and evidence is no compelling for liver safety. Hence, we aimed to meta-analyse the effects of DHEA supplementation on circulating levels of cortisol, liver enzymes, and adipokines. METHODS: We searched literature published in PubMed, Web of Science, Embase and Scopus, until December 2020. We obtained overall results using the generic inverse of variance method with a random-effects model. RESULTS: Through 10 arms, serum cortisol levels decreased significantly after DHEA supplementation [weighted mean difference (WMD): -53.581 nmol/L, 95% confidence interval (CI): -88.2, -18.9, P = .002], without significant heterogeneity (I2  = 36%, P = .117). In contrast, any significance was noted for adiponectin (WMD: -0.045 µg/mL, 95% CI: -0.56, 0.47; P = .865), leptin (WMD: -2.55 µg/mL, 95% CI: -6.2, 1.06; P = .166), aspartate transaminase (AST) (WMD: -3.7 U/L, 95% CI: -10.35, 2.95; P = .276), and alanine aminotransferase (ALT) (WMD: -1.7 U/L, 95% CI: -3.45, 0.06; P = .058). CONCLUSION: DHEA supplementation decreased circulating cortisol but did not alter adiponectin, leptin, AST, and ALT levels. Hence, DHEA supplementation could be considered as an adjunct in the management of hypercortisolaemia and is safe for the liver.

Association between body mass index and urinary tract infection: a systematic review and meta-analysis of observational cohort studies.

BACKGROUND AND OBJECTIVE: Very few studies have investigated the relationship between body mass index (BMI) and risk of urinary tract infection (UTI), and conclusions from these available studies have been inconsistent. To resolve this inconsistency, we performed a systematic review and meta-analysis to precisely examine the association between BMI and UTI. METHODS: This meta-analysis was performed based on the PRISMA recommendations. PubMed, Web of Science, Scopus, Embase, and Google Scholar databases were searched for all published observational studies that reported the risk of UTI based on BMI categories up to March 2020. RESULTS: Fourteen (n = 14) articles comprising 19 studies in different populations met our inclusion criteria. The overall analysis showed a significant increased risk of UTI in subjects affected by obesity vs. individuals without obesity (RR = 1.45; 95% CI: 1.28 - 1.63; I2 = 94%), and a non-significant increased risk of UTI in subjects who were overweight (RR = 1.03; 95% CI: 0.98 - 1.10; I2 = 49.6%) and underweight (RR = 0.99; 95% CI: 0.81 - 21; I2 = 0.0%) when compared to subjects who had normal weight. In the stratified analysis, we showed that obesity increased the risk of UTI in females (RR = 1.63; 95% CI: 1.38 - 1.93) and in subjects below 60 years old (RR = 1.53; 95% CI: 1.33 - 1.75). CONCLUSION: This systematic review and meta-analysis recognized a significant relationship between BMI and incidence of UTI in obese vs. non-obese subjects, as well as in females and in individuals below 60 years old.

The effects of astaxanthin supplementation on obesity, blood pressure, CRP, glycemic biomarkers, and lipid profile: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Previous studies lack consistent conclusions as to whether astaxanthin is actually linked to various health benefits as claimed. Here, we attempt to unravel the association of astaxanthin consumption with selected health benefits by performing a systematic review and meta-analysis. METHODS: Online literature search databases including Scopus, Web of Science, PubMed/Medline, Embase and Google Scholar were searched to discover relevant articles available up to 17 March 2020. We used mean changes and SD of the outcomes to assess treatment response from baseline and mean difference, and 95 % CI were calculated to combined data and assessment effect sizes in astaxanthin and control groups. RESULTS: 14 eligible articles were included in the final quantitative analysis. Current study revealed that astaxanthin consumption was not associated with FBS, HbA1c, TC, LDL-C, TG, BMI, BW, DBP, and SBP. We did observe an overall increase in HDL-C (WMD: 1.473 mg/dl, 95 % CI: 0.319-2.627, p = 0.012). As for the levels of CRP, only when astaxanthin was administered (i) for relatively long periods (≥ 12 weeks) (WMD: -0.528 mg/l, 95 % CI: -0.990 to -0.066), and (ii) at high dose (> 12 mg/day) (WMD: -0.389 mg/dl, 95 % CI: -0.596 to -0.183), the levels of CRP would decrease. CONCLUSION: In summary, our systematic review and meta-analysis revealed that astaxanthin consumption was associated with increase in HDL-C and decrease in CRP. Significant associations were not observed for other outcomes.

The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis.

BACKGROUND: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials. METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels. RESULTS: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration. CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

Phytosterol Supplementation Could Improve Atherogenic and Anti-Atherogenic Apolipoproteins: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Phytosterol and phytostanol (PS) supplementation is reported to improve atherogenic and anti-atherogenic apolipoproteins (Apo). The purpose of the present study is to critically investigate the effectiveness of PS supplementation on Apo in adults.A comprehensive search was conducted of all randomized controlled trials (RCTs) conducted up to September 2018 in the following databases: PubMed, Web of Science, Cochrane Library, and Scopus. Mean difference with 95% confidence intervals (CIs) were pooled using a random-effects model (DerSimonian-Laird method).Fifty-one arms from 37 RCTs were included in the present meta-analysis. Findings showed that PS supplementation and fortification increased Apo-AI (weighted mean difference [WMD]: 0.014 mg/dl, 95% CI: 0.001, 0.028, p = 0.042) and Apo-CII (WMD: 0.303 mg/dl, 95% CI: 0.084, 0.523, p = 0.007) and lowered Apo-B (WMD: -0.063 mg/dl, 95% CI: -0.075, -0.051, p < 0.001), Apo-B/Apo-A-I ratio (WMD: -0.044 mg/dl, 95% CI: -0.062, -0.025, p < 0.001), and Apo-E (WMD: -0.255 mg/dl, 95% CI: -0.474, -0.036, p = 0.023). However, PS supplementation did not have significant effects on Apo-AII and Apo-CIII. PS supplementation or fortification significantly changes Apo-E (r = -0.137, p nonlinearity = 0.006) and Apo-CIII (r = 1.26, p nonlinearity = 0.028) based on PS dosage (mg/d) and Apo-CIII (r = 3.34, p nonlinearity = 0.013) and Apo-CII (r = 1.09, p nonlinearity = 0.017) based on trial duration (weeks) in a nonlinear fashion.Based on our findings, supplements or fortified foods containing PS might have a considerable favorite effect in achieving Apo profile target; however, due to high heterogeneity among included studies, results must be interpreted with caution.KEY TEACHING POINTSCardiovascular diseases (CVDs) recognized as main public health concern worldwide with considerable mortality of all global deaths.Apo-lipoproteins are amphipathic molecules involved in the lipoprotein metabolism which introduced as biomarkers in the evaluation of CVD risk.Phytosterols bioactive components of plants have important biological functions in cholesterol metabolism in humans.Here we showed that phytosterols and phytostanols improve apo-lipoproteins profile of humans; finding from meta-analysis of randomized controlled trials.Phytosterols supplementation lowered atherogenic apo-lipoproteins (Apo-B and Apo-E) and increased anti-atherogenic apo-lipoproteins (Apo-AI, Apo-CII).

Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Inflammatory processes are involved in chronic diseases. It has been suggested that melatonin reduces inflammation by its radical scavenging properties; however, the results of the previous studies are inconclusive. The objective of the present meta-analysis is to determine the direction and magnitude of melatonin supplementation effect on inflammatory biomarkers. METHODS: Databases including PubMed, Scopus, Cochran Library, Embase, and Google Scholar were searched up to April 2019. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis, and meta-regression were also carried out. RESULTS: Thirteen eligible studies with 22 datasets with total sample size of 749 participants were included in the meta-analysis. Melatonin supplementation significantly decreased TNF-α and IL-6 levels [(WMD = - 2.24 pg/ml; 95% CI - 3.45, - 1.03; P < 0.001; I2 = 96.7%, Pheterogeneity < 0.001) and (WMD = - 30.25 pg/ml; 95% CI - 41.45, - 19.06; P < 0.001, I2 = 99.0%; Pheterogeneity < 0.001)], respectively. The effect of melatonin on CRP levels was marginal (WMD = - 0.45 mg/L; 95% CI - 0.94, 0.03; P = 0.06; I2 = 96.6%, Pheterogeneity < 0.001). CONCLUSION: The results of the present meta-analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators.

The impact of probiotic yogurt consumption on lipid profiles in subjects with mild to moderate hypercholesterolemia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Potential beneficial effect of probiotic yogurt on the lipid profile has raised much interest. However, the results are inconsistent in this regard. The aim of the study is to determine the effects of probiotic yogurt on serum lipid profile in individuals with mild to moderate hypercholesterolemia. METHODS AND RESULTS: Online databases including PubMed, Scopus, ISI Web of Science, Cochrane Central Register of Controlled Trials, Science Direct, Google Scholar and Igaku Chuo Zasshi were searched until March 19th 2019. The effect sizes were expressed as the weighted mean difference (WMD) with 95% confidence interval (CI). Seven eligible trials with 274 participants were included in this systematic review. Pooling of 9 effect sizes from these seven articles revealed a significant reduction in total cholesterol and low density lipoprotein cholesterol levels following probiotic yogurt consumption (mean difference: -8.73 mg/dl, 95% CI: -15.98, -1.48, p-value = 0.018 and mean difference: -10.611 mg/dl, 95% CI: -16.529, -4.693, p-value = 0.000, respectively) without significant heterogeneity among the studies (I2 = 40.6%, p-value = 0.1 and I2 = 24.2%, p-value = 0.229, respectively). The results showed no significant changes in high density lipoprotein cholesterol and triglyceride levels. Also, none of the variables showed a significant change for sensitivity analysis. CONCLUSION: Available evidence suggests that probiotic yogurt can significantly reduce total cholesterol and LDL-c in subjects with mild to moderate hypercholesterolemia without a significant effect on HDL-c and triglyceride levels.

The effects of green coffee bean extract supplementation on lipid profile in humans: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: This systematic review and meta-analysis aimed to assess the effects of green coffee bean extract (GCBE) supplementation on lipid profile in adults. METHODS AND RESULTS: The PubMed/Medline, Scopus, Web of sciences, and Google Scholar were systematically searched for randomized controlled trials available in English and published before February 2019. The meta-analysis was conducted using fixed effects models, and between-study heterogeneity was assessed by Cochran's Q test and I2. A total of 17 effect sizes were included in the meta-analysis. Combined effect sizes on serum total cholesterol concentrations revealed significant effects of GCBE supplementation on serum total cholesterol [weighted mean difference (WMD): -4.51 mg/dL, 95% confidence interval (CI): -6.89, -2.12, p < 0.001], low density lipoprotein-cholesterol (LDL-C) (WMD: -4.38 mg/dL, 95% CI: -6.44, -2.31, p < 0.001), and high density lipoprotein-cholesterol (HDL-C) (WMD: 2.63 mg/dL, 95% CI: 2.20, 3.07, p < 0.001) compared to controls. Nevertheless, no significant changes were observed in serum triglycerides levels (WMD: -4.34 mg/dL, 95% CI: -9.00, 0.32, p = 0.068). CONCLUSION: The evidence from available studies suggests that the GCBE supplementation leads to significant reductions in total cholesterol, HDL-C, and LDL-C levels, and has modest, but, non-significant effects on triglycerides levels.

Effect of evening primrose oil supplementation on lipid profile: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Studies have shown that evening primrose oil (EPO) supplementation might be effective in improving lipid profile, however, the results are inconsistent. This study was performed to determine the direction and magnitude of the EPO effect on the lipid profile. METHODS: PubMed, Scopus, Cochrane Library, Embase and Web of Science databases and Google Scholar were searched up to September-2019. Meta-analysis was performed using the random-effects model. Lipid profile including high-density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was considered as the primary outcome. RESULTS: A total of 926 articles were identified through database searching, of which, six RCTs were included in the meta-analysis. There were six studies on HDL, TC, and TG and four studies on LDL. EPO supplementation had no significant effect on TC, TG, LDL, and HDL. However, in subgroup analysis, a significant reduction in TG at a dose of ≤4 g/day (weighted mean difference [WMD] = -37.28 mg/dl; 95% CI: -73.53 to -1.03, p = .044) and a significant increase in HDL in hyperlipidemic subjects (WMD = 5.468 mg/dl; 95% CI: 1.323 to 9.614, p = .010) was found. CONCLUSION: Oral intake of EPO at a dose of ≤4 g/day significantly reduces serum TG levels and significantly increases HDL levels in hyperlipidemic subjects.

The Effect of Zinc Supplementation on Serum Leptin Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Recently, obesity has become a common worldwide concern. Leptin, as an adipocytokine, plays a major role in the etiology of obesity. Prior studies have demonstrated that zinc potentially affects serum leptin levels. However, clinical trials carried out in this regard are not consistent. Therefore, current meta-analysis was conducted to ascertain the actual effect of zinc supplementation on serum leptin levels in adults. Databases of PubMed, SCOPUS, and Google Scholar were methodically searched to identify relevant articles up to April 2018. Clinical trials that examined the effect of zinc supplementation on serum leptin concentrations as outcome variables in human adults were included. The mean difference (SD) of leptin changes in the intervention and placebo groups were used to calculate the overall effect size. Totally, 663 articles were identified, of which 6 studies were eligible randomized controlled trials (RCTs) with 7 treatment arms. The analysis suggested that zinc supplementation exerts no significant effect on overall serum leptin (WMD: 0.74 ng/ml; 95% CI: -1.39 to 2.87, p=0.49). Nevertheless, sex and duration of intervention seemed to impact the extent of zinc's influence. In trials with female subjects, zinc consumption led to a significant decrease in serum leptin level (WMD: -1.93 ng/ml; 95% CI: -3.72 to -0.14, p=0.03) as well as trials that lasted for more than 6 weeks (WMD: -1.71 ng/ml; 95% CI: -3.07 to -0.35, p=0.01), in comparison to the control group. Zinc supplementation did not significantly improve leptin concentrations, but it may result in a decreased circulating leptin level in studies with a duration of more than 6 weeks especially among females.

Does cocoa/dark chocolate supplementation have favorable effect on body weight, body mass index and waist circumference? A systematic review, meta-analysis and dose-response of randomized clinical trials.

Background: Cocoa and dark chocolate (DC) have been reported to be effective for health promotion; however the exact effect of cocoa/DC on anthropometric measures have not been yet defined. Methods: A comprehensive search to identify randomized clinical trials investigating the impact of cocoa/DC on body weight, body mass index (BMI) and waist circumference (WC) was performed up to December 2017. A meta-analysis of eligible studies was performed using random effects model to estimate pooled effect size. Fractional polynominal modeling was used to explore dose-response relationships. Results: A total of 35 RCTs investigated the effects of cocoa/DC on weight, BMI and WC were included. Meta-analysis did not suggest any significant effect of cocoa/DC supplementation on body weight (-0.108 kg, 95% CI -0.262, 0.046 P = 0.168), BMI (-0.014 kg/m2 95% CI -0.105, 0.077, P: 0.759,) and WC (0.025 cm 95% CI -0.083, 0.129, P = 0.640). Subgroup analysis revealed that that weight and BMI were reduced with cocoa/DC supplementation ≥ 30 g chocolate per day in trials between 4-8 weeks. Cocoa/DC consumption resulted in WC reduction in non-linear fashion (r = 0.042, P-nonlinearity = 0.008).Conclusion: Cocoa/DC supplementation does not reduce anthropometric measures significantly. However subgroup analysis regarding dose (≥ 30 g/day) and duration (between 4 to 8 weeks) revealed significant reduction of body weight and BMI.