Zinc Supplementation in Individuals with Prediabetes and type 2 Diabetes: a GRADE-Assessed Systematic Review and Dose-Response Meta-analysis.

Zinc supplementation has therapeutic effects on cardiovascular disease (CVD) risk factors, including dyslipidemia, hyperglycemia, and inflammation as the main contributors to CVD pathogenesis. Since CVD is a major cause of mortality among people with type 2 diabetes mellitus (T2DM), this study aimed to overview the potential effects of zinc supplementation on CVD risk factors in T2DM patients. To determine appropriate randomized clinical trials (RCTs) investigating the effects of zinc supplementation on CVD risk factors, electronic sources including PubMed, Web of Science, and Scopus were systematically searched until January 2023. The heterogeneity of trials was checked using the I2 statistic. According to the heterogeneity tests, random-effects models were estimated, and pooled data were defined as the weighted mean difference (WMD) with a 95% confidence interval (CI). Of the 4004 initial records, 23 studies that met inclusion criteria were analyzed in this meta-analysis. The pooled findings indicated the significant lowering effects of zinc supplementation on triglycerides (TG), total cholesterol (TC), fasting blood glucose (FBG), hemoglobin A1C (HbA1C), and C-reactive protein (CRP), while high-density cholesterol (HDL) concentrations showed an elevation after zinc supplementation. In addition to statistical significance, the effect of zinc supplementation on most of the variables was clinically significant; however, the quality of evidence in the included studies is regarded as low or very low for most variables. Our study demonstrated that zinc supplementation has beneficial effects on glycemic control markers, lipid profile, and CRP levels as a classic marker of inflammation in T2DM. Due to the high degree of heterogeneity between studies and the low rate of quality in them, further well-designed studies are necessitated to strengthen our findings.

Zinc supplementation and cardiovascular disease risk factors: A GRADE-assessed systematic review and dose-response meta-analysis.

BACKGROUND AND OBJECTIVE: A deficit in zinc has been related to a higher probability of developing cardiovascular diseases (CVDs). The anti-inflammatory and anti-oxidative capabilities of zinc may have a wide range of therapeutic impacts on CVDs. We conducted a comprehensive systematic review and meta-analysis of the possible impacts that zinc supplementation may have on the risk factors associated with CVDs. METHODS: To identify eligible randomized clinical trials (RCTs) evaluating the effects of zinc supplementation on CVDs risk factors, electronic databases including PubMed, Web of Science, and Scopus were systematically searched up to January 2023. The heterogeneity of trials was checked using the I2 statistic. According to the heterogeneity tests, random effects models were estimated and pooled data were defined as the weighted mean difference (WMD) with a 95% confidence interval (CI). RESULTS: Of 23165 initial records, 75 studies that met inclusion criteria were analyzed in this meta-analysis. The pooled findings indicated the significant lowering effects of zinc supplementation on triglycerides (TG), total cholesterol (TC), fasting blood glucose (FBG), Hemoglobin A1C (HbA1C), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione (GSH), with no noticeable effects on low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST), and Alanine aminotransferase (ALT). CONCLUSION: Overall, zinc supplementation may boost recognized coronary risk factors that contribute to the development of CVDs. Future research should be conducted to bolster our results.

The effects of beetroot and nitrate supplementation on body composition: a GRADE-assessed systematic review and meta-analysis.

This systematic review and meta-analysis aimed to investigate the effects of beetroot (BR) or nitrate supplements on body composition indices. A systematic search was conducted for randomised controlled trials (RCT) published up to August 2022 among online databases including Scopus, PubMed/Medline, Web of Science and Embase. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCT. A total of twelve RCT met the inclusion criteria for this meta-analysis. The pooled effect size of included studies indicated that BR or nitrate supplementation did not change body weight (weighted mean differences (WMD): -0·14 kg, 95 % CI -1·22, 1·51; P = 0·836; I2 = 0 %), BMI (WMD: -0·07 kg/m2, 95 % CI -0·19,0·03; P = 0·174, I2 = 0 %), fat mass (WMD: -0·26 kg, 95 % CI -1·51, 0·98; P = 0·677, I2 = 0 %), waist circumference (WMD: -0·28 cm, 95 % CI -2·30, 1·74; P = 0·786, I2 = 0 %), body fat percentage (WMD: 0·18 %, 95 % CI -0·62, 0·99; P = 0·651, I2 = 0 %), fat-free mass (WMD: 0·31 kg, 95 % CI -0·31, 1·94; P = 0·703, I2 = 0 %) and waist-to-hip ratio (WMD: 0, 95 % CI -0·01, 0·02; P = 0·676, I2 = 0 %). Subgroup analyses based on trial duration, BR or nitrate dose, study design, baseline BMI and athletic status (athlete v. non-athlete) demonstrated similar results. Certainty of evidence across outcomes ranged from low to moderate. This meta-analysis study suggests that BR or nitrate supplements cannot efficiently ameliorate body composition indices regardless of supplement dosage, trial duration and athletic status.

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.

Effects of beta-alanine supplementation on body composition: a GRADE-assessed systematic review and meta-analysis.

Purpose: Previous studies have suggested that beta-alanine supplementation may benefit exercise performance, but current evidence regarding its effects on body composition remains unclear. This systematic review and meta-analysis aimed to investigate the effects of beta-alanine supplementation on body composition indices. Methods: Online databases, including PubMed/Medline, Scopus, Web of Science, and Embase, were searched up to April 2021 to retrieve randomized controlled trials (RCTs), which examined the effect of beta-alanine supplementation on body composition indices. 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 1413 studies that were identified from electronic databases search, 20 studies involving 492 participants were eligible. Pooled effect size from 20 studies indicated that beta-alanine supplementation has no effect on body mass (WMD: -0.15 kg; 95% CI: -0.78 to 0.47; p = 0.631, I2 = 0.0%, p = 0.998), fat mass (FM) (WMD: -0.24 kg; 95% CI: -1.16 to 0.68; p = 0.612, I2 = 0.0%, p = 0.969), body fat percentage (BFP) (WMD: -0.06%; 95% CI: -0.53 to 0.40; p = 0.782, I2 = 0.0%, p = 0.936), and fat-free mass (FFM) (WMD: 0.05 kg; 95% CI: -0.71 to 0.82; p = 0.889, I2 = 0.0%, p = 0.912). Subgroup analyses based on exercise type (resistance training [RT], endurance training [ET], and combined training [CT]), study duration (<8 and ≥8 weeks), and beta-alanine dosage (<6 and ≥6 g/d) demonstrated similar results. Certainty of evidence across outcomes ranged from low to moderate. Conclusions: This meta-analysis study suggests that beta-alanine supplementation is unlikely to improve body composition indices regardless of supplementation dosage and its combination with exercise training. No studies have examined the effect of beta-alanine combined with both diet and exercise on body composition changes as the primary variable. Therefore, future studies examining the effect of the combination of beta-alanine supplementation with a hypocaloric diet and exercise programs are warranted.

Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis.

Controversy regarding the effects of betaine supplementation on cardiovascular markers has persisted for decades. This systematic review and meta-analysis compared the effects of betaine supplementation on cardiovascular disease (CVD) markers. Studies examining betaine supplementation on CVD markers published up to February 2021 were identified through PubMed, the Cochrane Library, Web of Science, Embase, and SCOPUS. Betaine supplementation had a significant effect on concentrations of betaine (MD: 82.14 µmol/L, 95% CI: 67.09 to 97.20), total cholesterol (TC) (MD: 14.12 mg/dl, 95% CI%: 9.23 to 19.02), low-density lipoprotein (LDL) (MD: 10.26 mg/dl, 95% CI: 6.14 to 14.38)], homocysteine (WMD: -1.30 micromol/L, 95% CI: -1.61 to -0.98), dimethylglycine (DMG) (MD: 21.33 micromol/L, 95% CI: 13.87 to 28.80), and methionine (MD: 2.06 micromol/L, 95% CI: 0.23 to 3.88). Moreover, our analysis indicated that betaine supplementation did not affect serum concentrations of triglyceride (TG), high-density lipoprotein (HDL), fasting blood glucose (FBG), C-reactive protein (CRP), liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)], and blood pressure. Our subgroup analysis suggested that a maximum dose of 4 g/d might have homocysteine-lowering effects without any adverse effect on lipid profiles reported with doses of ≥4 g/d. In conclusion, the present systematic review and meta-analysis supports the advantage of a lower dose of betaine supplementation (<4 g/d) on homocysteine concentrations without the lipid-augmenting effect observed with a higher dosage.

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.

The effect of barberry (Berberis vulgaris) consumption on flow-mediated dilation and inflammatory biomarkers in patients with hypertension: A randomized controlled trial.

Hypertension is considered as an important cardiovascular risk factor and evidence suggests that hypertension and endothelial dysfunction reinforce each other. Polyphenol-rich foods, such as barberry can reduce the risk of cardiovascular disease. Our aim was to investigate the effects of barberry consumption on vascular function and inflammatory markers in hypertensive subject. In this randomized controlled parallel trial, 84 hypertensive subjects of both genders (aged 54.06 ± 10.19 years; body mass index 28.02 ± 2.18 kg/m2 ) were randomly allocated to consume barberry (10 g/day dried barberry) or placebo for 8 weeks. Before and after the intervention, changes in brachial flow-mediated dilation (FMD) and plasma macrophage/monocyte chemo-attractant protein-1 (MCP-1), vascular cellular adhesion molecule-1, and intracellular adhesion molecule-1 (ICAM-1) were measured. An intention-to-treat analysis was performed. Compared to placebo (n = 42), barberry consumption (n = 42) improved FMD (B [95% CI] was 6.54% [4.39, 8.70]; p < .001) and decreased plasma ICAM-1 (B [95% CI] was -1.61 ng/ml [-2.74, -0.48]; p = .006). MCP-1 was significantly lower in the barberry group compared with the placebo group (B [95% CI] was -37.62 pg/ml [-72.07, -3.17]; p = .033). Our results indicate that barberry consumption improves FMD and has a beneficial effect on plasma ICAM-1 and MCP-1 in hypertensive patients. This trial was registered at the Iranian Registry of Clinical Trial (IRCT) with number IRCT20160702028742N8.

Pistachios and cardiometabolic risk factors: A systematic review and meta-analysis of randomized controlled clinical trials.

BACKGROUND: Previous experimental studies have reported that pistachios can elicit positive effects on lipid profile, blood pressure, and inflammation; however, a meta-analysis of the available evidence has yet to be performed. OBJECTIVE: the aim of this study was to conduct systematic review and meta-analysis of the effect of pistachio enriched diets on cardiometabolic risk factors, such as weight, BMI, blood pressure, serum lipids, blood glucose, and inflammatory biomarkers. DESIGN: A literature search was carried out for RCTs in medical databases, including PubMed/MEDLINE, Scopus, and Cochrane databases, with no time limitation up to August 2019, and conducted in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analysis guidelines. RESULTS: 11 RCTs, with 506 participants, that reported the effect of pistachios consumption on cardiometabolic risk factors were included in this systematic review and meta-analysis. Our findings indicated that pistachios consumption significantly reduced FBS (WMD: -3.73, 95 % CI: -6.99, -0.46, I2 = 99 %), TC/HDL (WMD: -0.46, 95 % CI: -0.76, -0.15, I2 = 95 %), LDL/HDL (WMD: -0.24, 95 % CI: -0.38, -0.11, I2 = 96 %), HbA1C (WMD: -0.14, 95 % CI: -0.26, -0.02, I2 = 60 %), Insulin (WMD: -2.43, 95 % CI: -4.85, -0.001, I2 = 58 %), SBP (WMD: -3.10, 95 % CI: -5.35, -0.85, I2 = 63 %), and MDA (WMD: -0.36, 95 % CI: -0.49, -0.23, I2 = 0%). Importantly, we did not observe adverse effects of pistachios consumption on BMI or blood pressure. CONCLUSION: This systematic review and meta-analysis demonstrates that pistachios consumption can elicit a beneficial effect on some cardiometabolic risk factors. All previous clinical studies are well designed but some points have still remained unclear including the effects of different pistachios dosages on cardio metabolic risk factors and efficacy of pistachios consumption in preventing endothelial dysfunction. Further examination is required to determine the effect of pistachios consumption on further endothelial function risk factors.