The effects of green tea extract supplementation on body composition, obesity-related hormones and oxidative stress markers: a grade-assessed systematic review and dose-response meta-analysis of randomised controlled trials.

Research indicates that green tea extract (GTE) supplementation is beneficial for a range of conditions, including several forms of cancer, CVD and liver diseases; nevertheless, the existing evidence addressing its effects on body composition, oxidative stress and obesity-related hormones is inconclusive. This systematic review and meta-analysis aimed to investigate the effects of GTE supplementation on body composition (body mass (BM), body fat percentage (BFP), fat mass (FM), BMI, waist circumference (WC)), obesity-related hormones (leptin, adiponectin and ghrelin) and oxidative stress (malondialdehyde (MDA) and total antioxidant capacity (TAC)) markers. We searched proper databases, including PubMed/Medline, Scopus and Web of Science, up to July 2022 to recognise published randomised controlled trials (RCT) that investigated the effects of GTE supplementation on the markers mentioned above. A random effects model was used to carry out a meta-analysis. The heterogeneity among the studies was assessed using the I2 index. Among the initial 11 286 studies identified from an electronic database search, fifty-nine studies involving 3802 participants were eligible to be included in this meta-analysis. Pooled effect sizes indicated that BM, BFP, BMI and MDA significantly reduced following GTE supplementation. In addition, GTE supplementation increased adiponectin and TAC, with no effects on FM, leptin and ghrelin. Certainty of evidence across outcomes ranged from low to high. Our results suggest that GTE supplementation can attenuate oxidative stress, BM, BMI and BFP, which are thought to negatively affect human health. Moreover, GTE as a nutraceutical dietary supplement can increase TAC and adiponectin.

Folic acid supplementation and blood pressure: a GRADE-assessed systematic review and dose-response meta-analysis of 41,633 participants.

Hypertension is a predisposing factor for cardiovascular disease (CVD). The extant literature regarding the effects of folic acid supplementation on blood pressure (BP) is inconsistent. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to summarize the effects of folic acid supplementation on BP. A systematic search was carried out in PubMed, Scopus, ISI Web of Science, and Cochrane library, from database inception to August 2021. Data were pooled using the random-effects method and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). The pooled results of 22 studies, including 41,633 participants, showed that folic acid supplementation significantly decreased systolic BP (SBP) (WMD: -1.10 mmHg; 95% CI: -1.93 to -0.28; p = 0.008). Subgroup analysis showed that the results remained significant when baseline SBP was ≥120 mmHg, intervention duration was ≤6 weeks, intervention dose was ≥5 mg/d, in patients with CVD, males and females, and overweight participants, respectively. Furthermore, the changes observed in diastolic BP (DBP) (WMD: -0.24 mmHg; 95% CI: -0.37 to -0.10; p < 0.001) were also statistically significant. However, subgroup analysis showed that the results remained significant in subject with elevated DBP, long term duration of intervention (>6 weeks), low dose of folic acid (<5 mg/day), CVD patients, both sexes and male, and participants with normal BMI. Dose-response analysis showed that folic acid supplementation changed SBP and DBP significantly based on dose and duration. However, meta-regression analysis did not reveal any significant association between dose and duration of intervention with changes in SBP. The present study demonstrates the beneficial effects of folic acid supplementation on BP by decreasing both SBP and DBP.

The effects of guar gum supplementation on lipid profile in adults: a GRADE-assessed systematic review, meta-regression and dose-response meta-analysis of randomised placebo-controlled trials.

Recent meta-analytic work indicated that guar gum supplementation might improve lipid profile markers in different populations. However, critical methodological limitations such as the use of some unreliable data and the lack of inclusion of several relevant studies, and the scarcity in assessments of regression and dose-specific effects make it difficult to draw meaningful conclusions from the meta-analysis. Therefore, current evidence regarding the effects of guar gum supplementation on lipid profile remains unclear. The present systematic review, meta-regression and dose-response meta-analysis aimed to examine the effects of guar gum supplementation on lipid profile (total cholesterol (TC), LDL, TAG and HDL) in adults. Relevant studies were obtained by searching the PubMed, SCOPUS, Embase and Web of Science databases (from inception to September 2021). Weighted mean differences (WMD) and 95 % CI were estimated via a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. Pooled analysis of nineteen randomised controlled trials (RCT) revealed that guar gum supplementation led to significant reductions in TC (WMD: -19·34 mg/dl, 95 % CI -26·18, -12·49, P < 0·001) and LDL (WMD: -16·19 mg/dl, 95 % CI -25·54, -6·83, P = 0·001). However, there was no effect on TAG and HDL among adults in comparison with control group. Our outcomes suggest that guar gum supplementation lowers TC and LDL in adults. Future large RCT on various populations are needed to show further beneficial effects of guar gum supplementation on lipid profile and establish guidelines for clinical practice.

The effects of conjugated linoleic acid supplementation on lipid profile in adults: A systematic review and dose-response meta-analysis.

Background: The findings of trials investigating the effect of conjugated linoleic acid (CLA) administration on lipid profile are controversial. This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of CLA supplementation on lipid profile. Methods: Two authors independently searched electronic databases including PubMed, Web of Science, and Scopus until March 2022, in order to find relevant RCTs. The random effects model was used to evaluate the mean and standard deviation. Results: In total, 56 RCTs with 73 effect sizes met the inclusion criteria and were eligible for the meta-analysis. CLA supplementation significantly alter triglycerides (TG) (WMD: 1.76; 95% CI: -1.65, 5.19), total cholesterols (TC) (WMD: 0.86; 95% CI: -0.42, 2.26), low-density lipoprotein cholesterols (LDL-C) (WMD: 0.49; 95% CI: -0.75, 2.74), apolipoprotein A (WMD: -3.15; 95% CI: -16.12, 9.81), and apolipoprotein B (WMD: -0.73; 95% CI: -9.87, 8.41) concentrations. However, CLA supplementation significantly increased the density lipoprotein cholesterol (HDL-C) (WMD: -0.40; 95% CI: -0.72, -0.07) concentrations. Conclusion: CLA supplementation significantly improved HDL-C concentrations, however, increased concentrations of TG, TC, LDL-C, apolipoprotein A, and apolipoprotein B. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022331100.

The effect of grape products on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.

The favorable influence of grape consumption on metabolic diseases has previously been shown in studies. We sought to assess the effects of grape intake on liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), in adults. We performed literature search in online databases, to find eligible randomized controlled trials (RCTs). we considered RCTs that met the following criteria: RCTs consisted of use of grape products on ALT, AST, and ALP in adults (≥18 years) with at least 2 weeks intervention duration. Pooling data from 11 trials showed that grape products intake significantly reduced ALP (p = .010), without any significant changes in ALT (p = .234) and AST (p = .300). In subgroup analysis, we found a significant reduction in ALP, ALT, and AST when the duration of intervention was ≥12 weeks, and when grape seed extract (GSE) was administered. The variable duration and dosage of intervention was one of the sources of bias in our meta-analysis. Additionally, participants involved in included studies had different physiological status and various age groups. Grape products administration may significantly improve ALT, AST, and ALP in adults in long-term interventions and/or when GSE is administered. It should be noted that the favorable effects of grape consumption were small and may not reach clinical importance.

Food groups and nutrients consumption and risk of endometriosis: a systematic review and meta-analysis of observational studies.

Dietary factors may play a role in the etiology of endometriosis and dietary intake of some food groups and nutrients could be associated with endometriosis risk. This systematic review and meta-analysis of observational studies was conducted to summarize the findings on the association between dietary intakes of selected food groups and nutrients (dairy, fats, fruits, vegetables, legumes, and animal-derived protein sources), and the risk of endometriosis among adult women. PubMed, Scopus, and ISI Web of Science were systematically searched up to September 2022. The inverse variance-weighted fixed-effect method was used to estimate the effect size and corresponding 95% CI. A total of 8 publications (4 studies) including 5 cohorts and 3 case-control with a sample size ranging from 156 to 116,607 were included in this study. A higher intake of total dairy [all low-fat and high-fat dairy foods] was associated with decreased risk of endometriosis (RR 0.90; 95% CI, 0.85 to 0.95; P < 0.001; I2 = 37.0%), but these associations were not observed with intakes of low or high-fat dairy, cheese or milk. Increased risk of endometriosis was associated with higher consumption of red meat (RR 1.17; 95% CI, 1.08 to 1.26; P < 0.001; I2 = 82.4%), trans fatty acids (TFA) (RR 1.12; 95% CI, 1.02 to 1.23; P = 0.019; I2 = 73.0%), and saturated fatty acids (SFA) (RR 1.06; 95% CI, 1.04 to 1.09; P < 0.001; I2 = 57.3%). The results of this meta-analysis suggest that there may be differing associations between dietary intake of dairy foods, red meat, SFAs, and TFAs and the risk of endometriosis. It may be useful to extend the analysis to other types of food groups and dietary patterns to obtain a complete picture. Additionally, further investigations are needed to clarify the role of diet in the incidence and progression of endometriosis.Trial registration: PROSPERO, CRD42020203939.

The effects of selenium supplementation on blood lipids and blood pressure in adults: A systematic review and dose-response meta-analysis of randomized control trials.

BACKGROUND: Previous studies evaluating the effects of selenium supplementation on lipid profile and blood pressure (BP) offer contradictory findings. This systematic review and meta-analysis assessed the effects of selenium supplementation on these lipid profile and BP. METHODS: In order to identify interrelated clinical trials, we performed a comprehensive literature search in the online databases, including PubMed, Scopus, Embase, and ISI web of science, up to December 2021. RESULTS: The analysis of the data established that selenium supplementation did not significantly affect TG level (WMD: -0.84 mg/dL; 95 % CI: -4.74, 3.05, p = 0.671), LDL-C (WMD: 0.86 mg/dL; 95 % CI: -1.21, 2.95, p = 0.416), and HDL-C (WMD: 0.3 mg/dL; 95 % CI: -0.66, 1.27, p = 0.535). however, there was a significant reduction in TC levels following selenium supplementation (WMD: -2.11 mg/dL; 95 % CI: -4.09, -0.13, p = 0.037). After subgroup analysis, when the baseline levels of LDL-C were < 130 mg/dL, selenium supplementation elicited a significant increase in LDL-C levels (WMD: 2.89 mg/dL; 95 % CI: 0.26, 5.51, p = 0.031). For BP, selenium supplementation significantly increased SBP (WMD: 2.02 mmHg; 95 % CI: 0.50, 3.55, p = 0.009), while it had no significant effect on DBP (WMD: 0.39 mmHg; 95 % CI: (-0.89, 1.68, p = 0.551)). CONCLUSION: Although our findings suggest selenium may have possible therapeutic effects in improving TC and VLDL, because of its negative effects on LDL and BP, selenium supplementation for cardiovascular protection should be recommended with caution.

The effects of conjugated linoleic acid supplementation on blood pressure and endothelial function in adults: A systematic review and dose-response meta-analysis.

BACKGROUND: Findings of studies investigating the effect of conjugated linoleic acid (CLA) supplementation on blood pressure (BP) and endothelial function are controversial. METHOD: This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of CLA supplementation on BP and endothelial function. Two authors independently searched electronic databases using PubMed, Web of Science, and Scopus until March 2022, in order to find relevant RCTs. RESULTS: Eighteen RCTs with 20 effect sizes met the inclusion criteria and were eligible for meta-analysis. CLA supplementation did not significantly alter systolic blood pressure (SBP) (WMD: -0.48; 95% CI: -3.23, 2.27), diastolic blood pressure (DBP) (WMD: -0.71; 95% CI: -3.54, 2.12), and vascular cell adhesion molecule (VCAM) (WMD: -34.02; 95% CI: -88.08, 20.03) levels. However, CLA supplementation significantly reduced intercellular adhesion molecule (ICAM) (WMD: -8.02; 95% CI: -13.95, -2.09) level. CONCLUSION: This systematic review and meta-analysis showed CLA association with reduction of ICAM. The PROSPERO registration number: CRD42022331108.

Effects of almond on cardiometabolic outcomes in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

An enhanced risk for cardiovascular disease (CVD) still exists even when T2DM patients have tight control on blood sugar. Thus, identification of treatment approaches that address CVD risk factors may be useful for patients beyond the blood sugar management. Although emerging evidence suggests that nuts consumption have beneficial effects on cardiometabolic health, the effects of almond intake in patients with type 2 diabetes are still controversial. Therefore, our objective was to investigate the effect of almond on cardiometabolic outcomes in patients with T2DM through a systematic review and meta-analysis of available randomized controlled trials (RCTs). A systematic search was conducted in PubMed, Web of Science, Scopus, Embase, and Google Scholar to identify relevant RCTs up to March 2021. There was no language and time limitation. Weighted mean difference (WMD) was pooled using a random effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods. Nine RCTs were included in the final analysis. Almond intake resulted in significant reduction in low-density lipoprotein cholesterol (LDL-C) (WMD: -5.28 mg/dL; 95% CI, -9.92, -0.64; p = .026) compared with the control group. This lowering effect of LDL-C was robust in subgroups with almond consumption >50 g/day, and baseline LDL-C level <130 mg/dL. However, the effect of almond on total cholesterol, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, insulin, hemoglobin A1c, body mass index, weight, body fat, systolic and diastolic blood pressure, and CRP was not significant compared with the control group. In summary, the current meta-analysis indicated that almond consumption decreased LDL-C, and had no favorable effect on other cardiometabolic outcomes in patients with T2DM. However, further high-quality studies are needed to firmly establish the clinical efficacy of the almond.

The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines.

The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (- 6.45 ± 0.82 mg/dl vs - 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (- 2.02 ± 0.30 ng/ml vs - 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.

Beneficial effects of folic acid supplementation on lipid markers in adults: A GRADE-assessed systematic review and dose-response meta-analysis of data from 21,787 participants in 34 randomized controlled trials.

Folic acid supplementation has received considerable attention in the literature, yet there is a large discrepancy in its effects on lipid markers in adults. Therefore, this systematic review and meta-analysis of 34 randomized controlled trials (RCTs) evaluated the effects of folic acid supplementation on triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations in a cohort of 21,787 participants. A systematic search current as of March 2021 was performed in PubMed/Medline, Scopus, Web of Science, and Embase using relevant keywords to identify eligible studies. A fix or random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence intervals (CIs). Thirty-four RCTs were included in this meta-analysis. The pooled analysis revealed that serum TG (WMD: -9.78 mg/dL; 95% CI: -15.5 to -4.00; p = 0.001, I2=0.0%, p = 0.965) and TC (WMD: -3.96 mg/dL; 95% CI: -6.71 to -1.21; p = 0.005, I2=46.9%, p = 0.001) concentrations were significantly reduced following folic acid supplementation compared to placebo. However, folic acid supplementation did not affect serum concentrations of LDL (WMD: -0.97 mg/dL; 95% CI: -6.82 to 4.89; p = 0.746, I2=60.6%, p < 0.001) or HDL cholesterol (WMD: 0.44 mg/dL; 95% CI: -0.53 to 1.41; p = 0.378, I2= 0.0%, p = 0.831). A significant dose-response relationship was observed between the dose of folic acid supplementation and serum concentrations of HDL cholesterols (r = 2.22, p = 0.047). Folic acid supplementation reduced serum concentrations of TG and TC without affecting LDL or HDL cholesterols. Future large RCTs on various populations are needed to show further beneficial effects of folic acid supplementation on lipid profile.

The Effects of Soy Products on Cardiovascular Risk Factors in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis of Clinical Trials.

Previous studies have suggested that soy products may be beneficial for cardiometabolic health, but current evidence regarding their effects in type 2 diabetes (T2D) remains unclear. The aim of this systematic review and meta-analysis was to determine the impact of soy product consumption on cardiovascular risk factors in patients with T2D. PubMed, Scopus, Embase, and the Cochrane library were systematically searched from inception to March 2021 using relevant keywords. All randomized controlled trials (RCTs) investigating the effects of soy product consumption on cardiovascular risk factors in patients with T2D were included. Meta-analysis was performed using random-effects models and subgroup analysis was performed to explore variations by dose and baseline risk profile. A total of 22 trials with 867 participants were included in this meta-analysis. Soy product consumption led to a significant reduction in serum concentrations of triglycerides (TGs) [weighted mean difference (WMD): -24.73 mg/dL; 95% CI: -37.49, -11.97], total cholesterol (WMD: -9.84 mg/dL; 95% CI: -15.07, -4.61), LDL cholesterol (WMD: -6.94 mg/dL; 95% CI: -11.71, -2.17), and C-reactive protein (WMD: -1.27 mg/L; 95% CI: -2.39, -0.16). In contrast, soy products had no effect on HDL cholesterol, fasting blood sugar (FBS), fasting insulin, glycated hemoglobin, HOMA-IR, systolic blood pressure (SBP) and diastolic blood pressure, or BMI (all P ≥ 0.05). In subgroup analyses, there was a significant reduction in FBS after soy consumption in patients with elevated baseline FBS (>126 mg/dL) and in those who received higher doses of soy intake (>30 g/d). Moreover, soy products decreased SBP in patients with baseline hypertension (>135 mm Hg). Our meta-analysis suggests that soy product consumption may improve cardiovascular parameters in patients with T2D, particularly in individuals with poor baseline risk profiles. However, larger studies with longer durations and improved methodological quality are needed before firm conclusions can be reached.

Effect of zinc supplementation on mortality in under 5-year children: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Several clinical trials evaluated the effect of zinc supplementation on mortality in children, but the results were inconsistent. We aimed to conduct a systematic review and meta-analysis on the impact of zinc supplementation on mortality in under 5-year children. METHODS: A comprehensive search was conducted using the electronic (PubMed, Scopus, Web of Science) databases, and Google Scholar, up to June 2020. Randomized clinical trials (RCTs) that reported the effect of zinc supplementation on death incidence in under 5-year children were included in the analysis. Screening was performed based on title/abstract and full-text. A random effects model was applied to calculate the summary relative risk (SRR). Risk of Bias 2.0 tool was used to rate the quality of trials. The body of evidence was assessed by the GRADE approach. RESULTS: Combining 30 RRs from 28 RCTs including 237,068 participants revealed that zinc supplementation has significantly reduced the risk of all-causes mortality by 16% in children (SRR: 0.84, 95% CI: 0.74, 0.96). A follow-up duration of less than 1 year after supplementation resulted in 54% reduced risk of mortality (0.46; 0.33, 0.63) with no heterogeneity between investigations. Subgroup analysis by zinc dosage showed that assigning ≥ 10 mg/d zinc to under five children and duration of less than 11 months of intervention decreased the risk of all-cause mortality by 44% (0.56; 0.42, 0.75) and 48% (0.52; 0.38, 0.72), respectively. In low birth weight (LBW) infants, zinc supplementation was reduced all-cause mortality by 52% (0.48; 0.23, 1.00). Zinc supplementation significantly reduced the risk of death from pneumonia (0.70: 0.64, 0.98) and infection (0.54; 0.39, 0.76), also changed the risk of mortality from diarrhea by 15% (0.85; 0.70, 1.03) and sepsis by 57% (0.43; 0.18, 1.02). CONCLUSION: This meta-analysis on RCTs revealed that zinc supplementation in under 5-year children has significantly reduced the risk of all-cause mortality. Notable decreases were found in trials with a dose of 10 mg/d or more zinc supplementation, a maximum of 11 months of supplementation, a follow-up less than one year and especially in LBW infants.

The effects of green tea supplementation on cardiovascular risk factors: A systematic review and meta-analysis.

Purpose: A bulk of observational studies have revealed the protective role of green tea supplementation in cardiovascular diseases. The current systematic review and meta-analysis study aimed to establish the effects of green tea supplementation on cardiovascular risk factors including lipid profile, blood pressure, glycemic control markers and CRP. Methods: A systematic literature search of randomized clinical trials (RCTs) that investigated the effects of green tea supplementation and cardiovascular risk factors was undertaken in online databases including PubMed/Medline, Scopus, Web of Science, and Embase using a combination of green tea and cardiovascular risk factors search terms. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCTs. Results: Among the initial 11,286 studies that were identified from electronic databases search, 55 eligible RCTs with 63 effect sizes were eligible. Results from the random effects meta-analysis showed that GTE supplementation significantly reduced TC (WMD = -7.62; 95% CI: -10.51, -4.73; P = < 0.001), LDL-C (WMD = -5.80; 95% CI: -8.30, -3.30; P = < 0.001), FBS (WMD = -1.67; 95% CI: -2.58, -0.75; P = < 0.001), HbA1c (WMD = -0.15; 95% CI: -0.26, -0.04; P = 0.008), DBP (WMD = -0.87; 95% CI: -1.45, -0.29; P = 0.003), while increasing HDL-C (WMD = 1.85; 95% CI: 0.87, 2.84; P = 0.010). Subgroup analyses based on the duration of supplementation (≥ 12 vs. < 12 weeks), dose of green tea extract (GTE) (≥1,000 vs. < 1,000 mg/d), sex (male, female, and both), baseline serum levels of lipid profile, and glycemic control factors demonstrated different results for some risk factors. Conclusion: The current study suggests improvements in the lipid and glycemic profiles following green tea supplementation. These findings support previous evidence showing the health benefits of green tea supplementation on cardiometabolic risk factors.

The Effect of Saffron Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The favorable influences of saffron supplementation on metabolic diseases have previously been shown. We aimed to assess the effects of saffron supplementation on blood pressure in adults. METHODS: A systematic search was performed in Scopus, Embase, and the Cochrane library databases to find randomized controlled trials (RCTs) related to the effect of saffron supplementation on blood pressure in adults up to March 2021. The primary search yielded 182 publications, of which eight RCTs were eligible. RESULTS: Our results showed that saffron supplementation resulted in a significant decrease in systolic blood pressure (weighted mean difference (WMD): -0.65 mmHg; 95% CI: -1.12 to -0.18, p = 0.006) and diastolic blood pressure (DBP) (WMD: -1.23 mmHg; 95% CI: -1.64 to -0.81, p < 0.001). Moreover, saffron supplementation reduced DBP in a non-linear fashion, based on duration (r = -2.45, p-nonlinearity = 0.008). CONCLUSIONS: Saffron supplementation may significantly improve both systolic and diastolic blood pressure in adults. It should be noted that the hypotensive effects of saffron supplementation were small and may not reach clinical importance.

Effects of Folic Acid Supplementation on Inflammatory Markers: A Grade-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

It has been theorized that folic acid supplementation improves inflammation. However, its proven effects on inflammatory markers are unclear as clinical studies on this topic have produced inconsistent results. To bridge this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of folic acid supplementation on serum concentrations of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Methods: To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, Web of Science, EMBASE, Cochrane databases, and Google Scholar using relevant keywords. A fix or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Twelve RCTs were included in the present meta-analysis. The pooled analysis revealed that serum concentrations of CRP (WMD: -0.59 mg/L, 95% CI -0.85 to -0.33, p < 0.001) were significantly reduced following folic acid supplementation compared to placebo, but did not affect serum concentrations of IL-6 (WMD: -0.12, 95% CI -0.95 to 0.72 pg/mL, p = 0.780) or TNF-α (WMD: -0.18, 95% CI -0.86 to 0.49 pg/mL, p = 0.594). The dose-response analysis demonstrated a significant relationship between an elevated dosage of folic acid supplementation and lower CRP concentrations (p = 0.002). Conclusions: We found that folic acid supplementation may improve inflammation by attenuating serum concentrations of CRP but without significant effects on IL-6 and TNF-α. Future RCTs including a larger number of participants and more diverse populations are needed to confirm and expand our findings.

Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is a growing interest in the considerable benefits of dietary supplementations, such as folic acid, on the glycemic profile. We aimed to investigate the effects of folic acid supplementation on glycemic control markers in adults. METHODS: Randomized controlled trials examining the effects of folic acid supplementation on glycemic control markers published up to March 2021 were detected by searching online databases, including Scopus, PubMed, Embase, and ISI web of science, using a combination of related keywords. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the intervention and control groups at follow-up. Meta-regression and non-linear dose-response analysis were conducted to evaluate the association between pooled effect size and folic acid dosage (mg/day) and duration of the intervention (week). From 1814 detected studies, twenty-four studies reported fasting blood glucose (FBG), fasting insulin, hemoglobin A1C (HbA1C), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as an outcome measure. RESULTS: Results revealed significant reductions in FBG (weighted mean difference (WMD): -2.17 mg/dL, 95% CI: -3.69, -0.65, p = 0.005), fasting insulin (WMD: -1.63 pmol/L, 95% CI: -2.53, -0.73, p < 0.001), and HOMA-IR (WMD: -0.40, 95% CI: -0.70, -0.09, p = 0.011) following folic acid supplementation. No significant effect was detected for HbA1C (WMD: -0.27%, 95% CI: -0.73, 0.18, p = 0.246). The dose-response analysis showed that folic acid supplementation significantly changed HOMA-IR (r = -1.30, p-nonlinearity = 0.045) in non-linear fashion. However, meta-regression analysis did not indicate a linear relationship between dose, duration, and absolute changes in FBG, HOMA-IR, and fasting insulin concentrations. CONCLUSIONS: Folic acid supplementation significantly reduces some markers of glycemic control in adults. These reductions were small, which may limit clinical applications for adults with type II diabetes. Further research is necessary to confirm our findings.

Effects of chromium supplementation on blood pressure, body mass index, liver function enzymes and malondialdehyde in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Several studies reported beneficial effects of chromium supplementation for management of type 2 diabetes mellitus (T2DM). The present study aimed to provide a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effects of chromium supplementation on blood pressure, body mass index (BMI), liver function enzymes and malondialdehyde (MDA) in patients with T2DM. METHODS: PubMed, Scopus, and Embase were searched up to 15 November 2020 with no language and time restriction. RCTs that reported the effects of chromium supplementation on blood pressure, BMI, liver function enzymes and MDA in patients with T2DM were included. A random-effects model was used to compute weighted mean differences (WMDs) with 95 % confidence intervals (CIs). Between-study heterogeneity was assessed by Cochran's Q test and quantified by I2 statistic. RESULTS: Of 3586 publications, 15 RCTs were included for the meta-analysis. Pooled effect sizes indicated that chromium significantly reduced diastolic blood pressure (DBP) (WMD): -2.36 mmHg, 95 % CI: -4.14, -0.60; P = 0.008), and MDA (WMD: -0.55 umol/l, 95 % CI: -0.96, -0.14; P = 0.008). However, chromium supplementation did not significantly affect BMI, systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST). Meta-regression analysis did not show significant linear relationship between dose of chromium and change in BMI (p = 0.412), SBP (p = 0. 319), DBP (p = 0.102), ALT (p = 0.923), AST (p = 0.986) and MDA (p = 0.055). CONCLUSION: The present systematic review and meta-analysis shows that supplementation with chromium at dose of 200-1000 µg/day may reduce DBP and MDA in T2DM patients.

The Effects of Nano-Curcumin Supplementation on Risk Factors for Cardiovascular Disease: A GRADE-Assessed Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Previous studies have indicated that curcumin supplementation may be beneficial for cardiometabolic health; however, current evidence regarding the effects of its nanorange formulations, popularly known as "nano-curcumin", remains unclear. This systematic review and meta-analysis aimed to determine the impact of nano-curcumin supplementation on risk factors for cardiovascular disease. METHODS: PubMed, Scopus, Embase, and ISI web of science were systematically searched up to May 2021 using relevant keywords. All randomized controlled trials (RCTs) investigating the effects of nano-curcumin supplementation on cardiovascular disease risk factors were included. Meta-analysis was performed using random-effects models, and subgroup analysis was performed to explore variations by dose and baseline risk profiles. RESULTS: According to the results of this study, nano-curcumin supplementation was associated with improvements in the glycemic profile by decreasing fasting blood glucose (FBG) (WMD: -18.14 mg/dL; 95% CI: -29.31 to -6.97; p = 0.001), insulin (WMD: -1.21 mg/dL; 95% CI: -1.43 to -1.00; p < 0.001), and HOMA-IR (WMD: -0.28 mg/dL; 95% CI: -0.33 to -0.23; p < 0.001). Interestingly, nano-curcumin supplementation resulted in increases in high-density lipoprotein (HDL) (WMD: 5.77 mg/dL; 95% CI: 2.90 to 8.64; p < 0.001). In terms of other lipid profile markers (triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL)), subgroup analyses showed that nano-curcumin supplementation had more favorable effects on lipid profiles in individuals with dyslipidemia at baseline. Nano-curcumin supplementation also showed favorable anti-inflammatory effects by decreasing C-reactive protein (CRP) (WMD: -1.29 mg/L; 95% CI: -2.15 to -0.44; p = 0.003) and interleukin-6 (IL-6) (WMD: -2.78 mg/dL; 95% CI: -3.76 to -1.79; p< 0.001). Moreover, our results showed the hypotensive effect of nano-curcumin, evidenced by a decrease in systolic blood pressure (SBP). CONCLUSIONS: In conclusion, our meta-analysis suggests that nano-curcumin supplementation may decline cardiovascular disease risk by improving glycemic and lipid profiles, inflammation, and SBP. Future large-scale investigations with longer durations are needed to expand on our findings.

Effects of Folic Acid Supplementation on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

(1) Background: This systematic review and meta-analysis aimed to assess the effects of folic acid supplementation on oxidative stress markers. (2) Methods: Online database including PubMed, Scopus, Web of Science, and Cochrane were searched up to January 2021, to retrieve randomized controlled trials (RCTs) which examined the effect of folic acid supplementation on markers of oxidative stress. Meta-analyses were carried out using a random-effects model. I2 index was used to evaluate the heterogeneity of RCTs. (3) Results: Among the initial 2322 studies that were identified from electronic databases search, 13 studies involving 1013 participants were eligible. Pooled effect size from 13 studies indicated that folic acid supplementation elicits a significant rise in serum concentrations of glutathione (GSH) (WMD: 219.01 umol/L, 95% CI 59.30 to 378.71, p = 0.007) and total antioxidant capacity (TAC) (WMD: 91.70 umol/L, 95% CI 40.52 to 142.88, p < 0.001) but has no effect on serum concentrations of nitric oxide (NO) (WMD: 2.61 umol/L, 95% CI -3.48 to 8.72, p = 0.400). In addition, folic acid supplementation significantly reduced serum concentrations of malondialdehyde (MDA) (WMD: -0.13 umol/L, 95% CI -0.24 to -0.02, p = 0.020). (4) Conclusions: This meta-analysis study suggests that folic acid supplementation may significantly improve markers within the antioxidative defense system by increasing serum concentrations of GSH and TAC and decreasing serum concentrations of MDA.