The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses.

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases. Several meta-analyses have shown that curcumin could improve the function of the knee and alleviate pain in OA, while some meta-analyses demonstrate controversial results. Hence, we assessed curcumin's effects on knee OA in an umbrella meta-analysis. PubMed, Scopus, Embase, and Web of Science databases were employed to find English-language meta-analyses of randomized controlled trials investigating the effect of curcumin supplementation on OA outcomes up to September 2023. The visual analog scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, function, and stiffness scales were analyzed. Effect sizes and 95% confidence intervals were utilized to obtain the overall effect size. A random-effects model was applied to perform the meta-analysis. Heterogeneity was determined by I2 statistics and the Cochrane Q-test. The pooled effect of the 11 included meta-analyses showed that curcumin could significantly decrease the VAS score (weighted mean difference [WMD] and standardized mean difference [SMD]), WOMAC-total (SMD and WMD), WOMAC-Function (SMD and WMD), WOMAC-Pain (SMD), and WOMAC-Stiffness scores (SMD) (p ≤ 0.001, ≤0.001, ≤0.001, 0.007, ≤0.001, 0.002, ≤0.001, ≤0.001, respectively). The results strongly support curcuminoid supplementation in relieving pain, improving joint mobility and stiffness, and shortening medication usage of OA patients.

The Effect of Vitamin D Supplementation on Lipid Profiles: an Umbrella Review of Meta-Analyses.

According to published meta-analyses, vitamin D exerts different beneficial effects in preventing and controlling risk factors associated with noncommunicable chronic diseases; however, the results are still conflicting. The purpose of this umbrella meta-analysis was to investigate the effect of vitamin D supplementation on low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), and triglyceride (TG) as components of the lipid profile. PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews were systematically searched for meta-analyses of randomized controlled trials. The umbrella meta-analysis followed the PRISMA guidelines. The random-effects model was employed to estimate the overall effect size (ES). Overall, 25 meta-analyses were included. In the standardized mean difference analysis, vitamin D significantly decreased TG (ES: -0.15; 95% CI: -0.23, -0.08; P ≤ 0.001) and TC levels (ES: -0.17; 95% CI: -0.23, -0.11; P ≤ 0.001) and increased HDL levels (ES: 0.08; 95% CI: 0.01, 0.15; P = 0.025). In the weighted mean difference analysis, vitamin D significantly decreased only TG levels (ES: -4.63 mg/dL; 95% CI: -7.70, -1.57; P = 0.003). The present study supports that vitamin D supplementation could be considered a beneficial adjuvant therapy in managing lipid profile levels, especially in individuals with vitamin D deficiency. This systematic review was registered in PROSPERO as CRD42022306334.

The effectiveness of treatment with probiotics in Helicobacter pylori eradication: results from an umbrella meta-analysis on meta-analyses of randomized controlled trials.

Background and aims: The purpose of this umbrella meta-analysis was to quantitatively summarize meta-analyses of randomized controlled trial (RCT) studies regarding the effects of probiotic supplementation on Helicobacter pylori (H. pylori) eradication. Methods: A thorough search of the electronic databases including PubMed, Web of Science, Embase, Scopus, and Google Scholar was carried out from the inception up to May 2022. For the evaluation of overall effect sizes, the pooled relative risk (RR) or odds ratio (OR) and their corresponding 95% confidence intervals (CI) were calculated. The random-effects model was used for the meta-analysis. Results: Overall, 18 eligible studies (47 278 participants in total) were included in the study. The findings revealed that probiotics have a beneficial impact on H. pylori eradication (pooled ESRR: 1.13; 95% CI: 1.11, 1.14, p < 0.01, and ESOR = 1.86, 95% CI: 1.70, 2.03, p < 0.01). Greater effects on H. pylori eradication were observed when higher doses (>10 × 1010 CFU) and mixed strains were supplemented. Conclusion: The present umbrella meta-analysis suggests that supplementation with probiotics may be considered as an efficient approach to ameliorate H. pylori complications, particularly probiotics with higher CFUs and mixed strains.

The effect of propolis supplementation in improving antioxidant status: A systematic review and meta-analysis of controlled clinical trials.

The present study aimed to assess the effect of propolis supplementation on oxidative status, a key contributor to the etiology of many chronic diseases. A systematic search of multiple databases, including Web of Science, SCOPUS, Embase, PubMed, and Google Scholar, was conducted from inception to October 2022 to identify articles examining the effect of propolis on glutathione (GSH), glutathione peroxidase (GPX), total antioxidant capacity (TAC), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. The quality of the included studies was evaluated using the Cochrane Collaboration tool. A total of nine studies were included in the final analysis, and a random-effects model was used to pool the estimated effects. Results showed that propolis supplementation significantly increased the levels of GSH (SMD = 3.16; 95% CI: 1.15, 5.18; I2 = 97.2%), GPX (SMD = 0.56; 95% CI: 0.07, 1.05; p = 0.025; I2 = 62.3%), and TAC (SMD = 3.26; 95% CI: 0.89, 5.62; I2 = 97.8%, p < 0.001). However, the effect of propolis on SOD was not significant (SMD = 0.05; 95% CI: -0.25, 0.34; I2 = 0.0%). Although the MDA concentration was not significantly decreased overall (SMD = -0.85, 95% CI: -1.70, 0.09; I2 = 93.3%), a significant decrease in MDA levels was observed at doses ≥1000 mg/day (SMD = -1.90; 95% CI: -2.97, -0.82; I2 = 86.4) and supplementation durations of less than 11 weeks (SMD = -1.56; 95% CI: -2.60, -0.51; I2 = 90.4). These results suggest that propolis is a safe supplement with a beneficial effect on GSH, GPX, and TAC levels and may be an effective adjunctive therapy for diseases where oxidative stress is a key factor in the etiology. However, further high-quality studies are necessary to make more precise and comprehensive recommendations given the limited number of studies, clinical diversity, and other limitations.

N-acetylecysteine, a powerful agent in the reinforcement of anti-oxidant profile: A systematic review and dose-response meta-analysis of controlled clinical trials.

BACKGROUND AND AIM: Several studies have been conducted to evaluate the effect of N-acetylecysteine (NAC) supplementation on antioxidant status, while no dose-response meta-analysis summarized the efficacy of NAC supplementation. METHODS: The systematic search of literatures was conducted on Scopus, PubMed, Embase, Web of Science electronic databases. Controlled clinical trials investigating the effects of NAC on antioxidant biomarkers were included in the current meta-analysis. Random-effect model was used to perform meta-analysis. Heterogeneity was examined using I2 index. Subgroup analysis was carried out to find the possible sources of heterogeneity. Dose-response analysis was performed to find the non-linear relationships between effect size and independent variables. RESULTS: Overall, 26 eligible studies were included in the review. NAC supplementation significantly increased TAC (SMD = 0.77 µmol/L; 95% CI: 0.38, 1.16; p < 0.001), GSH (SMD = 0.80 nmol/ml; 95% CI:0.25, 1.34; p = 0.004) and CAT (SMD = -0.57 IU/L; 95% CI:-1.13, -0.02; p = 0.042) levels. However, no significant improving effect was observed in terms of GR (SMD = 0.25 IU/g; 95% CI:-0.14, 0.63; p = 0.210), SOD (SMD = 0.14 U/ml; 95% CI:-0.20, 0.49; p = 0.414) and GPx (SMD = 0.19 IU/g; 95% CI:-0.48, 0.86; p = 0.576) levels. Furthermore, dose-response analysis show that NAC supplementation in participants with mean age up to 30 years had more robust effect on increasing GSH levels. CONCLUSION: We found a significant effect of NAC supplementation on TAC, GSH, CAT in adults. Overall, NAC could be considered as a potent agent in enhancing antioxidant capacity.

Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials.

PURPOSE: Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS: Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS: A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION: Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.

Effects of probiotics supplementation on blood pressure: An umbrella meta-analysis of randomized controlled trials.

AIMS: Several meta-analyses have revealed that probiotics could lower blood pressure (BP), but the findings were inconsistent. In this regard, an umbrella meta-analysis was carried out to provide a more accurate estimate of the overall impacts of probiotics supplementation on BP. DATA SYNTHESIS: We searched the following international databases till November 2021: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar. A random-effects model was applied to evaluate the effects of probiotics on BP. Sensitivity analysis was performed by using the leave-one-out method. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. Pooled effect size of 14 meta-analyses with 15,494 participants indicated significant decreases in both systolic (Weighted mean difference (WMD) = -1.96 mmHg; 95% confidence interval (CI): -2.78, -1.14, p < 0.001, and standardized mean difference (SMD) = -2.62; 95% CI: -4.96, -0.28, p < 0.001) and diastolic BP (WMD = -1.28 mmHg; 95% CI: -1.76, -0.79, p < 0.001, and SMD = -0.60 mmHg; 95% CI: -1.08, -0.12, p = 0.014) following probiotics supplementation. Greater effects on SBP were revealed in trials with a mean age of >50 years and the duration of intervention ≤10 weeks. DBP was also more reduced in studies with a dosage of ≥1010 colony forming unit (CFU), and SBP was decreased in patients with hypertension or diabetes analyzing WMD. CONCLUSION: The present umbrella meta-analysis suggests probiotics supplementation to improve BP and claims that probiotics could be used as a complementary therapy for controlling high BP. PROSPERO ID: CRD42022306560.

Probiotics as an effective therapeutic approach in alleviating depression symptoms: an umbrella meta-analysis.

Growing evidence has suggested that the consumption of probiotics can decrease depressive symptoms. However, even the results of meta-analyses are conflicting. In this regard, we performed an umbrella meta-analysis and proposed the decisive impacts of probiotics on depressive symptoms. The following international databases were searched up to July 2021: PubMed/Medline, Web of Science, Scopus, EMBASE, and Google Scholar. Meta-analyses investigating the impact of supplementation of probiotics on depression symptoms in adults were included. According to the studies, random-effects model was used to perform the analysis. Subgroup analysis was performed by dosage of probiotics, duration of supplementation and total sample size. Publication bias was assessed using Egger's, Begg's and visual inspection of funnel plot. Ten meta-analyses (n = 8886 participants) were included in study. The pooled data indicated that probiotic supplementation significantly reduced depression symptoms (ES= -1.41; 95% CI: -2.53, -0.30, p = 0.016; I2 = 99.4, p = <0.001). Subgroup analysis of studies with intervention duration >8 weeks and dosage >10 × 109 CFU demonstrated a more robust effect of probiotics on decreasing depression symptoms. There was also significant between-study heterogeneity in which dosage was identified as source of it. The results of present umbrella meta-analysis suggest administration of probiotics for relieving depression symptoms for >8 weeks with dosage of >10 × 109 CFU.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2051164.

The effects of phytosterol and phytostanol supplementation on the lipid profile in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

Various studies have proven that phytosterols and phytostanols (PS) are lipid-lowering agents. These compounds play a role in regulating high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) metabolism. Although various drugs are available and are currently used to treat dyslipidemia, the management of lipid abnormalities during the postmenopausal period remains a challenge. Thus, scientists are trying to develop new strategies to reduce serum lipids concentrations using natural products. However, the impact of PS administration on serum lipids in postmenopausal women remains unclear. Hence, the purpose of this study was to assess the effect of PS supplementation on the lipid profile in postmenopausal women based on a systematic review of the literature and a meta-analysis of randomized controlled trials. PubMed/Medline, Scopus, Embase, and Web of Science were searched to identify suitable papers published until January 18, 2022. We combined the effect sizes with the DerSimonian and Laird method using a random effects model. PS supplementation resulted in a significant decrease in TC (weighted mean difference [WMD]: -16.73 mg/dl) and LDL-C (WMD: -10.06 mg/dl) levels. No effect of PS supplementation on TG (WMD: -1.14 mg/dl) or HDL-C (WMD: -0.29 mg/dl) concentrations was detected. In the stratified analysis, there was a notable reduction in TC and LDL-C levels when the PS dose was ≥2 g/day (TC: -22.22 mg/dl and LDL-C: -10.14 mg/dl) and when PS were administered to participants with a body mass index ≥25 kg/m2 (TC: -20.22 mg/dl and LDL-C: -14.85 mg/dl). PS administration can decrease TC and LDL-C, particularly if the dose of administration is ≥2 g/day and if the participants are overweight or obese. Further high-quality studies are needed to firmly establish the clinical efficacy of PS usage in postmenopausal females.

Probiotic therapy, a novel and efficient adjuvant approach to improve glycemic status: An umbrella meta-analysis.

BACKGROUND: Probiotics exert several promoting effects on the glycemic status, however, the results of meta-analyses are inconsistent. we conducted an umbrella meta-analysis, across existing systematic reviews and meta-analyses of clinical trials to determine the definite effects of supplementation with probiotics on glycemic indices. METHODS: A comprehensive systematic search of PubMed/Medline, Scopus, EMBASE, and Web of Science was carried out till August 2021. The random-effects model was employed to conduct meta-analysis. Meta-analysis studies of randomized clinical trials examining the impacts of probiotics supplementation on glycemic indices were qualified in the current umbrella meta-analysis. RESULTS: 48 articles out of 693 in the literature search qualified for inclusion in the umbrella meta-analysis. Pooled effects of probiotics on fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and insulin levels were reported in articles 45, 21, 35, and 33, respectively. The analysis indicated a significant decrease of FPG (ES= -0.51 mg/dL; 95% CI: -0.63, -0.38, p < 0.001), HbA1c (ES = -0.32 mg/dL; 95% CI: -0.44, -0.20, p < 0.001), HOMA-IR (ES= -0.56; 95% CI: -0.66, -0.47, p < 0.001), and insulin levels (ES= -1.09 IU/mL; 95% CI: -1.37, -0.81, p = 0.006) by probiotics supplementation. CONCLUSION: Probiotics have amending effects on FPG, HbA1c, HOMA-IR, and insulin levels. A < 8-week period of probiotic supplementation in the moderate dosages (108 or 109 CFU) is an efficacious approach in improving glycemic parameters. Overall, probiotics could be recommended as an adjuvant anti-hyperglycemic agent.

Anti-obesity properties of probiotics; a considerable medical nutrition intervention: Findings from an umbrella meta-analysis.

Although several studies have indicated that consumption of probiotics is effective in the treatment of obesity, the results in this regard have yielded controversial findings. The current umbrella meta-analysis was performed to evaluate the effects of probiotics supplementation on obesity indices in adults. Scopus, PubMed, Web of Science, Embase and Google Scholar were searched for relevant studies published till November 2021. Meta-analysis was conducted using the random-effects model. Sensitivity and subgroup analyses were performed. In total, 29 meta-analyses with 14,366 participants, including 112, 78, and 38 unique trials for body mass index (BMI), body weight (BW), and waist circumference (WC), were included in the study, respectively. The findings demonstrated that the probiotics supplementation was significantly effective on decreasing of BMI (ES = -0.21; 95% CI: -0.30, -0.13, p < 0.001; I2 = 83.0%, p < 0.001), BW (ES = -0.38, 95% CI: -0.60, -0.16; p < 0.001; I2 = 81.8%, p < 0.001), and WC (ES = -0.60; 95% CI: -0.89, -0.31; p < 0.001; I2 = 89.1%, p < 0.001). Greater effects on BW were observed when intervention duration was >8 weeks and on obese individuals. BMI was also greatly modified in participants with metabolic syndrome and when intervention duration lasted for ≥12 weeks. The methodological quality (AMSTAR2) was moderate in 83%, low in 10%, and critically low in 7% of included studies. The current umbrella meta-analysis indicated that supplementation of probiotics in adults led to a meaningful reduction in BW, BMI, and WC. Therefore, our findings strongly recommend supplementation with probiotics as a potent intervention in the management of obesity.

The effect of 17ß-estradiol plus norethisterone acetate treatment on the lipid profile in women: a dose-response meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The impact of 17ß-estradiol plus norethisterone acetate administration on serum lipids in women is controversial as previously published studies have produced conflicting results. Thus, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of 17ß-estradiol plus norethisterone acetate therapy on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in females. METHODS: We searched the PubMed/MEDLINE, Scopus, Embase, and Web of Science databases for relevant trials published in English until 15 July 2021. The weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using a random-effects model (the DerSimonian and Laird methods). RESULTS: A total of 32 RCTs were included in the final analysis. Treatment with 17ß-estradiol plus norethisterone acetate significantly decreased LDL-C (WMD: -13.49 mg/dL, 95% CI: -16.46 to -10.52; P < 0.001), HDL-C (WMD: -3.57 mg/dL, 95% CI: -5.56 to -1.58; P < 0.001), TC (WMD: -19.33 mg/dL, 95% CI: -24.14 to -14.52; P < 0.001), and TG (WMD: -10.86 mg/dL, 95% CI: -16.06 to -5.13; P < 0.001) levels in females. The non-linear dose-response meta-analysis revealed a negative correlation between HDL-C levels and increased treatment periods (P ˂ 0.001). CONCLUSION: Evidence to date suggests that the administration of 17ß-estradiol plus norethisterone acetate in females reduces LDL-C, HDL-C, TC, and TG concentrations. Future investigations should clarify whether the reduction in HDL-C following the administration of 17ß-estradiol plus norethisterone acetate is clinically significant and poses any risks to the subjects who receive this treatment.

Cinnamon, an effective anti-obesity agent: Evidence from an umbrella meta-analysis.

The evidence provided by meta-analyses on the beneficial impacts of cinnamon supplementation on anthropometric indices are still conflicting. Present study's aim was to evaluate the effects of cinnamon on obesity indices by an umbrella meta-analysis. The electronic databases including Web of Science, PubMed, EMBASE, Scopus were systematically searched up to March 2021. Data for the effects of cinnamon on anthropometric indices were collected from the meta-analyses. An umbrella meta-analysis was carried out using a random-effects model. The pooled effects of 7 meta-analyses showed that cinnamon supplementation significantly reduced body weight (ES: -0.67 kg; 95% CI: -0.99, -0.35, p Ë‚ .001), body mass index (ES: -0.45 kg/m2 ; 95% CI: -0.57, -0.33, p Ë‚ .001) in comparison to control group. However, the effects of cinnamon on waist circumference (ES: -1.05 cm; 95% CI: -2.26, 0.15, p = .087) were not considerable. According to results, cinnamon could be suggested as a complementary weight loss agent. Favorable results were obtained at a dose of ≥3 g/day. In this study, a comprehensive study was performed on meta-analyses performed on the effect of cinnamon on anthropometric indices. This study could be considered as a final conclusion about the effect of cinnamon on anthropometric indices. The results of this study showed that supplementation with cinnamon significantly reduces BMI and body weight. The impacts were greater in doses of ≥3 g/day and in PCOS patients. PRACTICAL APPLICATIONS: In this study, a comprehensive study was performed on meta-analyses performed on the effect of cinnamon on anthropometric indices. This study could be considered as a final conclusion about the effect of cinnamon on anthropometric indices. The results of this study showed that supplementation with cinnamon significantly reduces BMI and body weight. The impacts were greater in doses of ≥3 g/day and in PCOS patients.

Melatonin effectiveness in amelioration of oxidative stress and strengthening of antioxidant defense system: Findings from a systematic review and dose-response meta-analysis of controlled clinical trials.

BACKGROUND AND AIM: Oxidative stress is involved in the development of chronic diseases. It has been suggested that melatonin has a protective role against oxidative stress by activation of antioxidant enzymes and scavenging free-radicals. Present study aimed to investigate the effect of melatonin supplementation on oxidative stress and antioxidant biomarkers such as malondialdehyde (MDA), increased total antioxidant capacity (TAC), superoxide dismutase (SOD), and Glutathione peroxidase (GPx). METHODS: Systematic search was performed to identify relevant studies in PubMed/Medline, SCOPUS, Web of Science and Embase databases and Google Scholar up to September 2020. Meta-analysis was conducted using random-effect model. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. The quality of studies was assessed using Cochrane Collaboration's tool. Publication bias was assessed by visual inspection of funnel plot. RESULTS: A total number of 16 eligible articles were included in the meta-analysis. The dosages of melatonin varied between 3 and 400 mg/day, with a duration range between 1.42 and 12 weeks. Melatonin supplementation significantly increased serum levels of TAC [SMD: 1.59; 95% CI: 0.89, 2.29; P < 0.001; (I2 = 93.53%, P < 0.001 No significant effects were observed on MDA [SMD: -3.09; 95% CI: -7.07, 0.89; P = 0.12; (I2 = 99.57%, P < 0.001)], GPx [SMD: 0.86; 95% CI: -3.46, 5.19; P = 0.61; (I2 = 98.17%, P < 0.001)] and SOD levels [SMD: 1.92; 95% CI: -3.57, 7.41; P = 0.35; (I2 = 98.27%, P < 0.001)]. CONCLUSION: Results of the current meta-analysis showed that melatonin supplementation had a significant impact on attenuating of oxidative stress and enhancing antioxidant performance. Melatonin supplementation could be suggested as a safe complementary approach in amelioration of the chronic diseases.