The Impact of Vitamin D Supplementation on Improving Blood Pressure: Evidence Obtained From an Umbrella Meta-analysis.

PURPOSE: The results of meta-analyses regarding the effect of vitamin D on blood pressure are conflicting. The present umbrella meta-analysis was conducted to provide definite and conclusive results. METHODS: Systematically, Scopus, EMBASE, PubMed, and Web of Science databases and Google Scholar were searched for relevant literature published up to July 2022. All meta-analyses of clinical trials addressing the effect of vitamin D on blood pressure were included. Random effects analysis was performed to obtain the overall effect size based on the standardized mean differences (SMDs) and weighted mean differences (WMDs) separately. The quality of included meta-analyses was assessed by using the Measurement Tool for Assessing Multiple Systematic Reviews 2 questionnaire. FINDINGS: Overall, 21 meta-analyses were enrolled in the umbrella review. The results indicated that systolic blood pressure was significantly reduced after the intervention based on WMD effect size analysis (ESWMD = -0.69 mm Hg; 95% CI, -1.35 to -0.04 [P < 0.038]; I2 = 46.7%, P = 0.021); however, no considerable impact was observed based on analysis of SMD effect sizes (ESSMD = -0.05 mm Hg; 95% CI, -0.24 to 0.14; P = 0.615). Also, vitamin D supplementation indicated a significant improvement in diastolic blood pressure based on WMD effect sizes (ESWMD = -0.66 mm Hg; 95% CI, -1.05 to -0.27 [P < 0.001]; I2 = 56.4%, P = 0.004) but not SMD analysis (ESSMD = -0.04 mm Hg; 95% CI, -0.13 to 0.04 [P = 0.328]; I2 = 53.4%, P = 0.057). IMPLICATIONS: Based on obtained evidence, vitamin D could be considered an efficient adjuvant for improving blood pressure.

The influence of arginine supplementation on IGF-1: A systematic review and meta-analysis.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) secretion is thought to be induced by a semi-essential amino acid called arginine (Arg). Existing research on the effect of Arg on IGF-1 levels has provided conflicting results. This systematic review and meta-analysis investigated the efficacy of acute and chronic Arg supplementation on IGF-1 levels. METHODS: PubMed, Web of Science, and Scopus were systematically searched until November 2022. The meta-analysis was performed using random- and fixed-effects models. Sensitivity and subgroup analyses were also carried out. Publication bias was assessed using Begg's test. RESULTS: Nine studies were included in this meta-analysis. Chronic Arg supplementation did not significantly change IGF-1 levels (SMD = 0.13 ng/ml; %95 CI: -0.21, 0.46; p = 0.457). Furthermore, the IGF-1 level was not significantly affected by acute Arg supplementation (SMD = 0.10 ng/mL; CI: -0.42, 0.62; p = 0.713). The meta-analysis results did not change following subgroup analyses based on the duration, dosage, age, placebo, and study population. CONCLUSION: In conclusion, there was no significant effect of Arg supplementation on IGF-1 concentration. The meta-analyses revealed no acute or chronic Arg supplementation impact on IGF-1 levels.

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.

Can omega-3 fatty acids and vitamin E co-supplementation affect obesity indices?

Background: Studies have shown that vitamin E as an antioxidant protects omega-3 fatty acids (FAs) from oxidation. Several studies have evaluated the effect of omega-3 FAs and vitamin E co-supplementation on obesity indices; however, the results are inconsistent. The present systematic review and meta-analysis was conducted to address the role of omega-3 FAs plus vitamin E on obesity indices. Methods: Cochrane Library, PubMed, Scopus, Embase, and Web of Science databases were searched up to February 2022. Among all of the qualified studies, 10 articles were selected. The effect size was presented as weighted mean difference (WMD) and 95% confidence interval (CI). Fixed-effects model was employed to perform meta-analysis. Subgroup analysis and publication bias assessment were carried out. Results: Ten eligible randomized controlled trials comprising 558 participants were included. The average dose of omega-3 FAs and vitamin E co-supplementation in studies was 1000-4000 mg/day and 400 IU, respectively. Intervention duration varied from 6 to 16 weeks. There was no significant effect of omega-3 and vitamin E co-supplementation on body weight (BW) (WMD=0.14 kg; 95% CI: -0.13 to 0.42; p=0.297), and body mass index (BMI) (WMD=0.08, 95% CI: -0.01 to 0.16, p=0.073). However, subgroup analysis showed that it might increase BMI in women over 50 years and if the intervention lasted more than 8 weeks. Conclusion: There was no significant impact of combined omega-3 FAs and vitamin E supplementation on BW and BMI; however, it should be noted that the intervention has an increasing impact when supplementation duration was >8 weeks and in individuals with type 2 diabetes mellitus, >50 years old, and BMI>25 kg/m2.

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.

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.

The effects of N-acetylcysteine on recovery biomarkers: A systematic review and meta-analysis of controlled trials.

N-acetylcysteine (NAC) is one of the antioxidant supplements which is thought to improve recovery. Existing studies regarding NAC and recovery presented conflicting results. This systematic review and meta-analysis evaluated the existing trials and determined the efficacy of acute and chronic NAC administration on recovery biomarkers. PubMed, Web of Science, and Scopus were searched up to July 2021. The random effects or fixed effects model was applied in the meta-analysis. Sensitivity and subgroup analyses were performed. In case of the presence of publication bias, standard methods were applied. The meta-analysis comprised 37 papers (1,388 participants). All included studies were in English language. Acute NAC administration indicated no significant effects on lactate, pH, VO2 , and CPK-MB ([SMD = -0.06 mmol/L; 95% CI: -0.40, 0.28; p = .714], [SMD = 0.17; 95% CI: -0.28, 0.62; p = .454], [SMD = -0.11 L/min; 95% CI: -0.63, 0.41; p = .686], and [SMD = -0.19 units/L; 95% CI: -0.62, 0.24; p = .395]). Additionally, no evidence of significant influence of chronic NAC administration on lactate, pH, VO2 , and CK was revealed ([SMD = 0.01 mmol/L; 95% CI: -0.25, 0.27; p = .950], [SMD = -0.51; 95% CI: -1.73, 0.70; p = .424], [SMD = -0.18 L/min; 95% CI: -0.56, 0.20; p = .361], and [SMD = -0.04 units/L; 95% CI: -0.36, 0.29; p = .821]). No considerable effect of NAC on recovery was found. PRACTICAL APPLICATIONS: Previous studies on the influence of NAC administration on recovery biomarkers have presented conflicting results. This systematic review and meta-analysis offers a broad range of detailed information on the influence of chronic and acute NAC supplementation outcomes regarding recovery biomarkers. Overall, the results support that NAC supplementation may not be effective in improving recovery biomarkers. However, subgroup analyses based on NAC dosage indicated the meaningful effect of NAC on CK-MB at the dosage of ≥100 mg/kg.

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.

The effect of vitamin D on the lipid profile as a risk factor for coronary heart disease in postmenopausal women: a meta-analysis and systematic review of randomized controlled trials.

BACKGROUND AND AIM: The exact effect of vitamin D administration on the lipid profile in postmenopausal women is unknown. However, as dyslipidemia is a recognized risk factor for coronary heart disease (CHD) in this population, the lipid-lowering effects of vitamin D need to be explored Thus, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated the impact of vitamin D use on triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) as a risk factor for coronary heart disease (CHD) in postmenopausal women. METHODS: We developed a search strategy for multiple databases (PubMed/Medline, Scopus, Embase, and Web of Science) to identify relevant RCTs whose results were published until June 1st, 2021. We combined the results using a random effects model (the DerSimonian and Laird random effects model). Lipid profile outcomes were expressed as weighted mean difference (WMD) and 95% confidence intervals (CIs) between intervention and comparator groups. RESULTS: Supplementation with vitamin D decreased TG (WMD: -3.55 mg/dL, 95% CI: -5.34 to -1.76, P < 0.001) in postmenopausal females versus controls. In the subgroup analyses, vitamin D increased TC when the treatment duration was ˂26 weeks (WMD: 6.56 mg/dL, 95% CI: 0.78 to 12.35, P = 0.02) as compared to ≥26 weeks (WMD: -2.06 mg/dL, 95% CI: -5.49, 1.36, P = 0.23) and in the participants with a BMI ≥30 kg/m2 (WMD: 3.65 mg/dL, 95% CI: 0.09, 7.22, P = 0.044). Moreover, vitamin D increased HDL-C when the treatment duration was ˂26 weeks (WMD: 2.67 mg/dL, 95% CI: 0.66 to 4.68, P = 0.009). In addition, vitamin D decreased LDL-C when the vitamin D dose was ˃400 IU/day (WMD: -1.89 mg/dL, 95% CI: -2.47 to -1.31, P < 0.001) as compared to ≤400 IU/day (WMD: 2.50 mg/dL, 95% CI: -2.50, 7.52, P = 0.327). CONCLUSIONS: Vitamin D administration on the lipid profile as a risk factor for CHD in postmenopausal women reduces TG. Its effects to lower LDL-C and increase HDL-C and TC levels are clinically negligible but should be investigated in future research. In addition, supplementation with vitamin D results in a clinically significant reduction in TG, particularly in postmenopausal females with hypertriglyceridemia at baseline.