The effects of curcumin supplementation on endothelial function: A systematic review and meta‐analysis of randomized controlled trials

Impaired endothelial function is an important risk factor for cardiovascular disease (CVD). Curcumin supplementation might be an appropriate approach to decrease the complications of CVD. Randomized controlled trials assessing the effects of curcumin supplementation on endothelial function were included. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science with no time restriction. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. Between‐study heterogeneities were estimated using the Cochran's Q test and I‐square (I²) statistic. Data were pooled using a random‐effects model, and weighted mean differences (WMDs) were considered as the overall effect sizes. Ten studies with 11 effect sizes were included. We found a significant increase in flow‐mediated dilation (FMD) following curcumin supplementation (WMD: 1.49; 95% CI [0.16, 2.82]). There was no effect of curcumin supplement on pulse wave velocity (PWV; WMD: ?41.59; 95% CI [?86.59, 3.42]), augmentation index (Aix; WMD: 0.71; 95% CI [?1.37, 2.79]), endothelin‐1 (ET‐1; WMD: ?0.30; 95% CI [?0.96, 0.37]), and soluble intercellular adhesion molecule‐1 (sICAM‐1; WMD: ?10.11; 95% CI [?33.67, 13.46]). This meta‐analysis demonstrated the beneficial effects of curcumin supplementation on improving FMD, though it did not influence PWV, Aix, Et‐1, and sICAM‐1.     

Effects of garlic supplementation on liver enzymes: A systematic review and meta‐analysis of randomized controlled trials

Current evidence on the beneficial effects of garlic on liver enzymes is contradictory. Therefore, the aim of this systematic review and meta‐analysis is to evaluate the effect of garlic supplementation on human liver enzymes, such as Alanine Transaminase (ALT/SGPT) and Aspartate Transaminase (AST/SGOT). To collect the required data, PubMed, Scopus, ISI Web of Science, and Google scholar databases were systematically searched from inception to June 2019. A meta‐analysis was conducted using the random‐effects model to evaluate the effects of garlic supplementation on ALT and AST levels. The Cochran's Q‐test and inconsistency index were also used to evaluate heterogeneity among the studies. Among a total of 15,514 identified articles, six studies (containing 301 participants) met the inclusion criteria. Results of the meta‐analysis showed that garlic supplementation significantly decreased AST level (Hedges' g = ?0.36, 95% confidence interval [CI]: ?0.72, ?0.004, p = .047); whereas, it had no significant effect on ALT level (Hedges' g = ?0.22, 95% CI: ?0.64, 0.20, p = .310). Results showed that garlic supplementation reduced AST levels significantly; however, had no significant effect on ALT levels. Further studies are still needed to confirm the results.     

Metabolic benefits of curcumin supplementation in patients with metabolic syndrome: A systematic review and meta‐analysis of randomized controlled trials

The finding of studies on the effect of curcumin extract on metabolic factor in patients with metabolic syndrome has had arguable results. This systematic review with meta‐analysis of randomized controlled trials (RCT) aimed to analyze the effect of curcumin/turmeric on metabolic factors in patients with metabolic syndrome. The PICO strategy was used to establish the guiding question of this review. Several databases for RCT were searched until September 2018. Of the 144 articles initially identified, seven trials met the eligibility criteria. A random‐effects model with a mean weight difference (WMD) and a 95% confidence interval was performed for quantitative data synthesis. Pooled estimates of WMD were calculated between intervention and control groups using random‐effects model in the presence of high level of heterogeneity between the studies. The results showed significant improvement of fasting blood glucose (p = 0.01), triglycerides (p < 0.001), high‐density lipoprotein cholesterol (p = 0.003), and diastolic blood pressure (p = 0.007) levels. Curcumin was not associated with a significant change in waist circumference measurement (p = 0.6) and systolic blood pressure level (p = 0.269). Curcumin supplementation improves some components of metabolic syndrome.     

Possible anti‐obesity effects of phytosterols and phytostanols supplementation in humans: A systematic review and dose–response meta‐analysis of randomized controlled trials

Present meta‐analysis investigates the effects of phytosterols and phytostanol (PS) supplementation on anthropometric indices, using data from randomized controlled trials. We performed a systematic search in the databases: PubMed, Scopus, Cochran, and Web of Science. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were presented. Overall, 79 randomized controlled trials investigated the effects of PS on anthropometric indices. Meta‐analysis results did not reveal any significant effect of PS supplementation on weight (66 trials‐WMD: ?0.083 kg; CI [?0.233, 0.066]; I² = 42.5%), percentage fat mass (6 trials‐WMD: ?0.090%; CI [?0.789, 0.610]; I² = 0.0%), and waist circumference (WC; 5 trials‐WMD: ?0.039 cm; CI [?0.452, 0.374]; I² = 0.0%). However, body mass index (BMI) significantly decreased after PS supplementation (39 trials‐WMD: ?0.063 kg/m2, p = 0.024, I² = 25.1%). Subgroup analyses showed that PS supplementation in subjects with baseline BMI ≥25 and hyperlipidemic significantly decreased body weight and BMI. The overall results showed that although PS supplementation did not affect anthropometric indices (except BMI), baseline status regarding BMI and hyperlipidemia and also dose and duration could be contributing factors for favorable effects.     

Impact of flaxseed supplementation on plasma lipoprotein(a) concentrations: A systematic review and meta‐analysis of randomized controlled trials

The aim of the study was to investigate the impact of supplementation with flaxseed on plasma lipoprotein(a) [Lp(a)] levels through a systematic review and meta‐analysis of eligible randomized placebo‐controlled trials. PubMed, Scopus, Cochrane Library, and ISI Web of Science were searched for randomized controlled trials (RCTs) which have been published up to November 2019. RCTs that investigated the effect of flaxseed supplementation on plasma Lp(a) levels in adults were included for final analysis. The random effects model was used for calculating the overall effects. Meta‐analysis of 7 selected RCTs with 629 individuals showed significant lowering effect of flaxseed supplementation on Lp(a) (MD ?2.06 mg/dl; 95% CI: ?3.846, ?0.274, p = .024), without considerable heterogeneity between studies (p = .986, I² = 0%). Subgroup analysis also revealed that longer duration only showed significant lowering effect of flaxseed supplementation on Lp(a). This meta‐analysis has shown that flaxseed supplementation might significantly decrease plasma Lp(a) levels. Future well‐designed and long‐term clinical trials are required to confirm these results.     

Effects of green tea or green tea catechin on liver enzymes in healthy individuals and people with nonalcoholic fatty liver disease: A systematic review and meta‐analysis of randomized clinical trials

The therapeutic potential of green tea as a rich source of antioxidants and anti‐inflammatory compounds has been investigated by several studies. The present study aimed to systematically review and analyze randomized clinical trials (RCTs) assessing the effects of green tea, catechin, and other forms of green tea supplementation on levels of liver enzymes. PubMed, SCOPUS, EMBASE, and Cochrane databases were searched until February 2019. All RCTs investigating the effect of green tea or its catechin on liver enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin were included. A total of 15 RCTs were included. The overall effect of green tea on liver enzymes was nonsignificant (ALT [Standardized mean difference (SMD)= ?0.17, CI ?0.42 to 0.08, p = .19], AST [SMD = ?0.07, CI ?0.43 to 0.29, p = .69], and ALP [SMD = ?0.17, CI ?0.45 to 0.1, p = .22]). However, subgroup analyses showed that green tea reduced the levels of liver enzymes in participants with nonalcoholic fatty liver disease (NAFLD) but in healthy subjects, a small significant increase in liver enzymes was observed. In conclusion, the results of this study suggest that the effect of green tea on liver enzymes is dependent on the health status of individuals. While a moderate reducing effect was observed in patients with NAFLD, in healthy subjects, a small increasing effect was found.     

The effects of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomized controlled trials

Besides other benefits, curcumin is getting more recognized for its antioxidant and anti‐inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta‐analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta‐analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL‐6) (SMD ?2.08; 95% CI [?3.90, ?0.25]; p = 0.02), high‐sensitivity C‐reactive protein (hs‐CRP) (SMD ?0.65; 95% CI [?1.20, ?0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD ?3.14; 95% CI [‐4.76, ?1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor‐alpha (SMD ?1.62; 95% CI [?3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [?1.06, 1.74], p = 0.63). Overall, this meta‐analysis suggests that taking curcumin‐containing supplements may exert anti‐inflammatory and antioxidant properties through a significant reduction in IL‐6, hs‐CRP, and MDA levels.     

The effects of black seed supplementation on cardiovascular risk factors in patients with nonalcoholic fatty liver disease: A randomized,double‐blind,placebo‐controlled clinical trial

Nonalcoholic fatty liver disease (NAFLD) is highly related to cardiovascular disorders risk factors. This study aimed to evaluate the effects of black seed (Nigella sativa) supplementation on cardiovascular disorders risk factors in patients with NAFLD. This randomized, double‐blind, placebo‐controlled clinical trial was conducted on 50 patients with NAFLD. Participants were assigned to receive a lifestyle modification plus 2 g/day of either N. sativa or placebo for 12 weeks. Compared with the placebo, N. sativa supplementation led to significant reductions in serum glucose (?7.95 vs. ?1.22; p = .041), serum insulin (?3.87 vs. ?1.07; p = .027), homeostatic model of assessment for insulin resistance (?1.02 vs. ?0.28; p = .021), and a significant increase in quantitative insulin sensitivity check index (0.03 vs. 0.006; p = .002). All of these changes were remained significant after adjusting for known confounding variables; however, there was no significant difference in lipid profile changes between the two groups (p = .05). N. sativa supplementation significantly decreased hepatic steatosis percentage compared with the placebo after adjustment for confounding variables (p = .005). In conclusion, our results indicate that daily intake of 2‐g N. sativa plus lifestyle modification is superior to lifestyle modification alone in amelioration of insulin resistance and hepatic steatosis in patients with NAFLD.     

Effects of silymarin supplementation on blood lipids: A systematic review and meta‐analysis of clinical trials

Dyslipidemia is a leading cause of endothelial dysfunction and cardiovascular disease. Several studies used silymarin as an herbal supplement in hyperlipidemic subjects. The aim of the present systematic review and meta‐analysis was to examine the effect of silymarin supplementation on blood lipids. PubMed, Scopus, Ovid (Cochrane library), ISI Web of Science, and Google Scholar were systematically searched until March 2018 to find intervention studies that examined the impact of silymarin supplementation on blood lipids in adults. Changes in blood lipids and potential sources of between‐study variation were extracted. We run a subgroup analysis to determine potential sources of inter‐study heterogeneity. Ten clinical trials fulfilled the eligibility criteria. Meta‐analysis indicated that silymarin supplementation in combination with other treatments (not silymarin alone) reduced total cholesterol (change: ?25.45 mg/dl; 95% confidence interval [CI] [?47.89, ?3.01 mg/dl]) and low‐density lipoprotein (change: ?28.25 mg/dl; 95% CI [?53.09, ?3.42 mg/dl]). Also, silymarin increased high‐density lipoprotein concentration (change: 4.82 mg/dl; 95% CI [2.01, 7.63 mg/dl]). Blood concentration of triglyceride was significantly after silymarin supplementation in comparison with controls (change: ?22.55 mg/dl; 95% CI [?44.32, ?0.78 mg/dl]). Present systematic review and meta‐analysis revealed that silymarin supplementation in combination with other treatments had a favorable effect on blood lipids.     

The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta‐analysis of clinical trials

The effects of pycnogenol on plasma lipids are controversial. A systematic review and meta‐analysis of clinical trials were conducted to obtain a conclusive result in humans. PubMed, Scopus, and Google Scholar were systematically searched until March 2018, to explore the clinical trials that examined the effect of pycnogenol supplementation on lipid parameters among adult human. Methodological quality of the eligible studies was evaluated using the Cochrane Collaboration's tool. To estimate the effect size, changes in blood lipids were implemented. Results were pooled using a random effects model. Potential sources of heterogeneity were explored by subgroup analysis. A systematic review and meta‐analysis of 14 clinical trials with 1,065 participants suggested a significant increase in plasma concentration of high density lipoprotein cholesterol (HDL‐C; 3.27 mg/dL; 95% CI [0.19, 6.36]; p = 0.038). In contrast, plasma levels of total cholesterol (TC; ?4.45 mg/dL, 95% CI [?11.24, 2.34]; p = 0.199), triacylglycerol (TAG; ?3.64 mg/dL; 95% CI [?17.89, 10.61]; p = 0.616), and low density lipoprotein cholesterol (LDL‐C; ?3.61 mg/dl; 95% CI [?8.76, 1.55]; p = 0.171) were not altered. Adjustment for confounding variables was poor in included studies. Also, these studies did not assess dietary lipid intake. The results indicate that pycnogenol supplementation improves levels of HDL‐C; however, the changes in TC, TAG, and LDL‐C were not clinically relevant. Since there are few phytochemicals that have a significant increasing effect on HDL‐C levels, pycnogenol may have important role in prevention of cardiovascular diseases.     

Effects of cardamom supplementation on lipid profile: A systematic review and meta‐analysis of randomized controlled clinical trials

Cardiovascular disease is a highly prevalent issue worldwide and one of its main manifestations, dyslipidemia, needs more attention. Recent studies have suggested that cardamom has favorable effects beyond lipid lowering, but the result are contradictory. Our objective was to conduct a systematic review and meta‐analysis on randomized controlled trials (RCTs) that assessed the effect of cardamom on lipids. The search included PubMed, Scopus, ISI Web of Science, Google Scholar, and the Cochrane library (up to March, 2019) to identify RCTs investigating the effects of cardamom supplementation on serum lipid parameters. Weighted mean differences (WMDs) were pooled using a random‐effect model. Meta‐analysis of data from five eligible RCTs showed that cardamom supplementation did not significantly change the concentrations of total cholesterol (WMD: ?6.11 mg/dl, 95% CI [?13.06, 0.83], I² = 0.0%), low‐density lipoprotein cholesterol (WMD: ?4.31 mg/dl, 95% CI [?9.75, 1.13], I² = 0.0%), or high‐density lipoprotein cholesterol (WMD: 1.75 mg/dl, 95% CI [?1.95 to 5.46], I² = 71.4%). However, a significant reduction was observed in serum triglyceride (TG; WMD: ?20.55 mg/dl, 95% CI [?32.48, ?8.63], I² = 0.0%) levels after cardamom supplementation. Cardamom might be able to change TG, but for confirming the results, more studies exclusively on dyslipidemia patients and considering the intake of lipid lowering agents as exclusion criteria are necessary.     

Effect of garlic supplementation on serum C‐reactive protein level: A systematic review and meta‐analysis of randomized controlled trials

The present study was designed to systematically review randomized controlled trials (RCTs) that report on the effects of garlic supplementation on serum C‐reactive protein (CRP) levels. We conducted a literature search of Scopus, PubMed, Cochrane Library, and Google Scholar up to January 2018. Weighted mean differences (WMD) were estimated for net change in serum CRP. Subgroup analyses were also performed by duration of study, dose of supplementation, baseline CRP level, and the quality of studies. From 438 articles found and screened in our initial search, nine RCTs with the sum of total sample size of 363 were included in the meta‐analysis. Compared with the controls, garlic intake significantly reduced the concentrations of serum CRP by 0.8 mg/L (95% CI [?1.5, ?0.1], p = 0.02) with the evidence of heterogeneity among studies. Subgroup analyses showed that garlic significantly lowered CRP by 0.82 mg/L (95% CI [?1.02, ?0.62], p < 0.001) among studies with a daily garlic dose ≥1,200 mg/day and by 2.44 mg/L (95% CI [?4.02, ?0.87], p = 0.002) among studies with baseline CRP ≥2 mg/L. Current data confirmed that garlic supplementation would reduce serum CRP levels. However, the changes were related to the supplemental doses and baseline levels of serum CRP.     

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

This study aimed to evaluate the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) characteristics. In this randomized, double‐blind, controlled clinical trial, 50 NAFLD patients were supplemented with either 1‐g hesperidin capsule or identical placebo capsule for 12 weeks. During the intervention, both groups were advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, hesperidin supplementation, compared with placebo, was associated with a significant reduction in alanine aminotransferase (p = .005), γ‐glutamyltransferase (p = .004), total cholesterol (p = .016), triglyceride (p = .049), hepatic steatosis (p = .041), high‐sensitivity C‐reactive protein (p = .029), tumor necrosis factor‐α, and nuclear factor‐κB (NF‐κB). In conclusion, our results indicate that hesperidin supplementation accompanied with lifestyle modification is superior to lifestyle modification alone in management of NAFLD at least partially through inhibiting NF‐κB activation and improving lipid profile. Further studies with higher dose of hesperidin are required to find the optimal dose.     

Hesperidin,a major flavonoid in orange juice,might not affect lipid profile and blood pressure: A systematic review and meta‐analysis of randomized controlled clinical trials

Previous studies have led to conflicting results regarding the effect of hesperidin supplementation on cardiometabolic markers. This study aimed to evaluate the efficacy of hesperidin supplementation on lipid profile and blood pressure through a systematic review and meta‐analysis of randomized controlled trials (RCTs). PubMed, Web of Science, Scopus, and Google Scholar, as well as the reference lists of the identified relevant RCTs, were searched up to May 2018. Effect sizes were pooled by using the random effects model. Ten RCTs (577 participants) were eligible to be included in the systematic review. The meta‐analysis revealed that hesperidin supplementation had no effect on serum total cholesterol (weighted mean difference [WMD] = ?1.04 mg/dl; 95% confidence interval [CI]: ?5.65, 3.57), low‐density lipoprotein cholesterol (WMD = ?1.96 mg/dl; 95% CI [?7.56, 3.64]), high‐density lipoprotein cholesterol (WMD = 0.16 mg/dl; 95% CI [?1.94, 2.28]), and triglyceride (WMD = 0.69 mg/dl; 95% CI [?5.91, 7.30]), with no significant between‐study heterogeneity. Hesperidin supplement also had no effect on systolic (WMD = ?0.85 mmHg; 95% CI [?3.07, 1.36]) and diastolic blood pressure (WMD = ?0.48 mmHg; 95% CI [?2.39, 1.42]). Hesperidin supplementation might not improve lipid profile and blood pressure. Future well‐designed trials are still needed to confirm these results.     

The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials

This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; −7.79 U/L) and glutamyl transferase (−6.0 U/L) in patients with liver disorders, and ALT (−2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.     

The effects of grape seed extract on glycemic control,serum lipoproteins,inflammation, and body weight: A systematic review and meta‐analysis of randomized controlled trials

The aim of this systematic review and meta‐analysis was to analyze the effects of grape seed extract (GSE) on glycemic control and serum lipoproteins, inflammation and body weight. Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until May 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I‐square (I²) statistic. Data were pooled using a random‐effects model and weighted mean difference (WMD) was considered as the overall effect size. Fifty trials were included in this meta‐analysis. Pooling effect sizes from studies demonstrated a significant decrease in fasting plasma glucose (FPG) (WMD): ?2.01; 95% confidence interval (CI): ?3.14, ?0.86), total cholesterol (TC; WMD: ?6.03; 95% CI: ?9.71, ?2.35), low‐density lipoprotein (LDL) cholesterol (WMD: ?4.97; 95% CI: ?8.37, ?1.57), triglycerides (WMD: ?6.55; 95% CI: ?9.28, ?3.83), and C‐reactive protein (CRP) concentrations (WMD: ?0.81; 95% CI: ?1.25, ?0.38) following GSE therapy. Grape seed did not influence HbA1c, HDL cholesterol levels, and anthropometric measurements. This meta‐analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.     

Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: A randomized controlled trial

Recent reports indicated that curcumin had beneficial effects in animal models of liver injury and cirrhosis. Current study aimed to investigate the effects of curcumin supplementation in patients with liver cirrhosis. In this randomized double‐blind placebo‐controlled trial, 70 patients with liver cirrhosis aged 20–70 years were randomly divided into two groups to receive 1,000 mg/day curcumin (n = 35) or placebo (n = 35) for 3 months. Model for end‐stage liver disease (MELD) (i), MELD, MELD‐Na, and Child–Pugh scores were used to assess the severity of cirrhosis. Sixty patients (29 in the curcumin group and 31 in the placebo group) completed the study. MELD(i) (15.55 ± 3.78 to 12.41 ± 3.07), MELD (15.31 ± 3.07 to 12.03 ± 2.79), MELD‐Na (15.97 ± 4.02 to 13.55 ± 3.51), and Child–Pugh (7.17 ± 1.54 to 6.72 ± 1.31) scores decreased significantly in the curcumin group after 3‐month intervention (p < .001, p < .001, p = .001, and p = .051, respectively), whereas they increased significantly in the placebo group (p < .001, p < .001, p < .001, p = .001, respectively). Significant differences were only observed between the two groups in MELD(i), MELD, MELD‐Na, and Child–Pugh scores after 3‐month intervention (p < .001 for all of them). In this pilot study, beneficial effects of curcumin supplementation were observed in decreasing disease activity scores and severity of cirrhosis in patients with cirrhosis.