Withania somnifera (Indian ginseng) in diabetes mellitus: A systematic review and meta‐analysis of scientific evidence from experimental research to clinical application

Withania somnifera Dunal, also known as Indian ginseng, has been in use since ancient times in the management of diabetes mellitus (DM). This systematic review and meta‐analysis evaluated the efficacy/effectiveness, safety and tolerability of W. somnifera in managing DM. Literature search (published/unpublished) was performed from inception to April 2019 in guidelines recommended databases. A total of 6 in‐vitro, 13 pre‐clinical and 5 clinical studies were included for systematic evaluation. W. somnifera treatment in DM significantly restored the altered levels of blood glucose (experimental data; mean difference, ?196.27; 95% confidence interval [?220.96, ?171.58]; p < .00001) glycosylated haemoglobin (HbA1c), insulin, lipid profile, serum and oxidative stress markers with no safety concerns. The results suggest the potential role of W. somnifera in managing DM. However, the available clinical data are not considerably enough to provide novel and sufficiently robust evidence for the use of W. somnifera in managing DM. To further strength the anti‐diabetic profile of W. somnifera, well‐designed randomized‐controlled trial(s) with a larger sample size and longer duration is warranted with evaluation of its effect primarily on blood glucose, HbA1c and insulin. Future research also needs to elucidate the molecular mechanism(s) of W. somnifera including its active principles in DM.     

Effect of Nigella sativa (black seed) supplementation on glycemic control: A systematic review and meta‐analysis of clinical trials

This study was aimed to quantify the antihyperglycemic effect of Nigella sativa (N. sativa). An in‐depth search to identify clinical trials investigating the impact of N. sativa on glycemic indices via MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, and Google scholar databases were performed up to November 2018. We used a random effects model to estimate pooled effect size of fasting plasma glucose (FPG), postprandial blood glucose (PPBG), and hemoglobin A1c (HbA1c). A total of 17 randomized controlled trials investigating the effects of N. sativa on FPG, PPBG, and HbA1c were included. Meta‐analysis suggested a significant association between N. sativa supplementation and reduction in FPG (weighted mean difference [WMD]: ?9.93 mg/dl, 95% CI [?13.44, ?6.41]), PPBG (WMD: ?14.79 mg/dl, 95% CI [?24.19, ?5.39]), and HbA1c (WMD: ?0.57%, 95% CI [?0.77, ?0.37]). Subgroup analysis revealed that N. sativa oil was more effective than N. sativa powder in reduction of FPG. To sum up, N. sativa consumption has a significant lowering effect on glycemic status. Further studies with prolonged durations and powerful design are needed to specify the exact mechanism, optimal dosage, and duration of N. sativa supplementation to obtain a beneficial effect on glycemic status.     

Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta‐analysis of randomized controlled trials

This systematic review and meta‐analysis of randomized controlled trials was performed to determine the effect of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until August 30, 2018. Nine studies with 10 effect sizes out of 357 selected reports were identified eligible to be included in current meta‐analysis. The pooled findings indicated that quercetin supplementation did not affect fasting plasma glucose (FPG), homeostasis model of assessment‐estimated insulin resistance, and hemoglobin A1c levels. In subgroup analysis, quercetin supplementation significantly reduced FPG in studies with a duration of ≥8 weeks (weighted mean difference [WMD]: ?0.94; 95% confidence interval [CI; ?1.81, ?0.07]) and used quercetin in dosages of ≥500 mg/day (WMD: ?1.08; 95% CI [?2.08, ?0.07]). In addition, subgroup analysis revealed a significant reduction in insulin concentrations following supplementation with quercetin in studies that enrolled individuals aged <45 years (WMD: ?1.36; 95% CI [?1.76, ?0.97]) and that used quercetin in dosages of ≥500 mg/day (WMD: ?1.57; 95% CI [?1.98, ?1.16]). In summary, subgroup analysis based on duration of ≥8 weeks and used quercetin in dosages of ≥500 mg/day significantly reduced FPG levels.     

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.     

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 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.     

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.     

Anti‐inflammatory and antioxidant activity of carvacrol in the respiratory system: A systematic review and meta‐analysis

Carvacrol is a monoterpene present in the essential oil of a number of plants and has been widely used in traditional medicine because it is considered to have a range of therapeutic effects including in relation to respiratory disease. To conduct a systematic review and meta‐analysis to assess the anti‐inflammatory and antioxidant activities of carvacrol when used in the treatment of respiratory disorders. A comprehensive literature search using Scopus, MEDLINE‐PubMed, Cochrane and Web of Science was undertaken. Papers related to the anti‐inflammatory or antioxidant properties of carvacrol in the treatment of an injury in the respiratory system in in vivo studies and published in the period up to and including August 2019. A total of 152 studies were initially identified, with only 17 meeting the inclusion criteria. Five of the studies were performed in humans, and 12 were performed in rodents. Among the 17 studies included in the systematic review, we performed the meta‐analysis with nine of the studies with animals. Carvacrol had a positive effect on the reduction of interleukin (IL)‐1β, IL‐4, IL‐8 and malondialdehyde (MDA); however, the analysis indicated that carvacrol had no effect on IL‐6 and tumor necrosis factor alpha (TNF‐α), probably due to the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti‐inflammatory effects of carvacrol, but its relationship with the reduction of some inflammatory mediators in animals with lung injury needs further elucidation.     

Fuzheng Huayu capsule as an adjuvant treatment for HBV‐related cirrhosis: A systematic review and meta‐analysis

Fuzheng Huayu (FZHY) capsule, a formulated traditional Chinese medicine product with 6 Chinese herbs, is widely used for HBV‐related cirrhosis as an adjuvant treatment. However, the efficacy of FZHY capsule for HBV‐induced cirrhosis did not be comprehensively proved by systematic analysis. Our current analysis was aimed to assess the efficacy and safety of FZHY capsule by an evidence‐based method. Databases, including China National Knowledge Infrastructure, Wangfang, VIP medicine information system, Pubmed, Embase, and Cochrane Library, were searched, and the randomized controlled trials of FZHY capsule were used for the treatment of HBV‐associated liver cirrhosis. Meta‐analysis was performed by Review Manager 5.3. The efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), Procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), Collagen C Type IV (IV‐C), Child‐Pugh score, portal vein diameter, spleen thickness, HBeAg negative conversion rate, and HBV‐DNA negative conversion rate were systematically assessed. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Nineteen studies with 1,769 patients were included in the meta‐analysis. Compared to conventional treatment, FZHY capsule was effective by increasing the efficacy. FZHY capsule was more efficient in improving ALT, AST, TBIL, PIIIP, HA, LN, IV‐C, Child‐Pugh grading score, portal vein diameter, spleen thickness, and HBV‐DNA negative conversion rate with no serious adverse reactions. Nevertheless, a variety of well‐designed randomized controlled trials are needed to confirm these findings since small samples were applied in the previous studies.     

Efficacy of natural,peroxide‐free tooth‐bleaching agents: A systematic review,meta‐analysis,and technological prospecting

The aim of this study is to analyze the efficacy of natural bleaching agents and the current technological development in this research field. Two reviewers performed a literature search up to July 2019 in 15 databases. Five laboratory studies and 25 patents were included. Data regarding natural bleaching agent used, application protocol, and the main findings of studies were analyzed. Laboratory studies that evaluated natural bleaching agents' peroxide‐free or associated to peroxides and patents related to natural bleaching agents were included. The studies evaluated papain, bromelain, chlorine dioxide, sodium chloride plus vinegar and sodium bicarbonate as peroxide‐free agents; and sweet potato extract, lactoperoxidase, and peroxidase associated to peroxide used were included. Twenty‐five patents were included; among the most cited are the papain and the chlorine. The addition of non‐peroxide agents into peroxide showed improvement in bleaching effect with the incorporation of these non‐peroxide agents (p < .05). On the other hand, peroxide‐free agents did not show an improvement in bleaching effect (p < .05). The evidence in literature suggested that natural bleaching agents incorporated to peroxide may improve the bleaching. Therefore, the current literature does not support the use of natural agents as dental bleaching.     

Effects of ginseng supplementation on selected markers of inflammation: A systematic review and meta‐analysis

The present meta‐analysis was performed to evaluate the efficacy of ginseng administration on serum level of inflammatory biomarkers. We performed a systematic search of all available randomized controlled trials (RCTs) conducted up to June 2018 in the following electronic databases: PubMed, Scopus, Cochrane, and Google Scholar. RCTs that investigated the effect ginseng supplementation on high‐sensitivity C‐reactive protein (hs‐CRP), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) were included for final analysis. A total of seven RCTs were included in the meta‐analysis. Results indicated significant reduction in IL‐6 (mean difference [MD]: ?0.265 pg/ml, 95% CI [?0.396, ?0.135], p < .001) and TNF‐α (MD: ?2.471 pg/ml, 95% CI [?2.904, ?2.039], p < .001) and no significant change in hs‐CRP (MD: ?0.125 mg/L, 95% CI [?0.597, 0.347], p = .604). Although there was publication bias across studies, trim and fill analysis showed that results from unpublished studies could not change the results for CRP. However, removing one study in sensitivity analysis did reveal a significant reduction in CRP. We conclude that ginseng supplementation significantly lowered IL‐6 and TNF‐α but did not significantly lower CRP. However, these findings were not robust, because they showed sensitivity for CRP and IL‐6, and future long‐term well‐designed dose‐escalating trials are required.     

The effects of curcumin supplementation on body mass index,body weight,and waist circumference in patients with nonalcoholic fatty liver disease: A systematic review and dose–response meta‐analysis of randomized controlled trials

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver‐related morbidity; its prevalence is elevating due to the rising epidemic of obesity. Several clinical trials have examined the effects of curcumin supplementation on anthropometric variables in NAFLD patients with inconclusive results. This dose–response meta‐analysis aimed to evaluate the impact of curcumin supplementation on body mass index (BMI), body weight, and waist circumference (WC) in patients with NAFLD. A systematic review of the literature was conducted using PubMed/Medline, ISI Web of Science, Scopus, Cochrane Library, EMBASE, Google Scholar, Sid.ir, and Magiran.com to identify eligible studies up to March 2019. A meta‐analysis of eligible studies was performed using the random‐effects model to estimate the pooled effect size. Eight randomized controlled trials with 520 participants (curcumin group = 265 and placebo group = 255) were included. Supplementation dose and duration ranged from 70 to 3,000 mg/day and 8 to 12 weeks, respectively. Curcumin supplementation significantly reduced BMI (weighted mean difference [WMD] = ?0.34 kg/m², 95% CI [?0.64, ?0.04], p < .05) and WC (WMD = ?2.12 cm, 95% CI [?3.26, ?0.98], p < .001). However, no significant effects of curcumin supplementation on body weight were found. These results suggest that curcumin supplementation might have a positive effect on visceral fat and abdominal obesity that have been associated with NAFLD.     

Effects of Tai Chi on health outcomes in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

ObjectiveTo explore the effects and dose–response relationship of Tai Chi for type 2 diabetes mellitus (T2DM) and to evaluate the methodological quality of the included trials and evidence quality of the outcomes.MethodsNine major English and Chinese databases were searched for randomized controlled trials of Tai Chi for T2DM from inception to December 2021. The effects and dose–response relationships were assessed with a meta-analysis and meta-regression using Stata.16. The methodological quality of the included studies was assessed using the risk of bias tool. The evidence quality of the outcomes was assessed using the GRADE tool.ResultsA total of 24 studies with 1314 patients were included. Compared with the usual care, Tai Chi improved HbA1c (MD = ?0.80%, 95% CI [?1.05, ?0.54], P < .001, I² = 18.29%, very low–quality evidence), FBG (SMD = ?0.58, 95% CI [?0.86, ?0.31], P < .001, I² = 53.2%, low-quality evidence), fasting insulin (FIN), diastolic blood pressure, BMI, and the outcomes of quality of life (QoL) in patients with T2DM. However, when Tai Chi was compared with other exercise, there was no between-group difference in the HbA1c, FBG, TC, TG, HDL, LDL, BMI, and waist circumference (WC). Furthermore, the findings showed that an increase at every 18 weeks in length or an 823-h increase in the total time of Tai Chi intervention resulted in approximately a one unit reduction in the SMD of FBG.ConclusionCompared with usual care, Tai Chi may improve HbA1c (with clinical significance), FBG, FIN, BMI, diastolic blood pressure, and outcomes of QoL in T2DM patients. The effects of Tai Chi were similar to those of other exercises on the HbA1c, FBG, TC, TG, HDL, LDL, BMI, and WC. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.     

The effect of green coffee extract supplementation on blood pressure: A systematic review and meta‐analysis of randomized controlled trials

Given the proliferation in studies investigating green coffee bean extract (GCBE) supplementation, the purpose of this study was to determine the efficacy and effectiveness of GCBE supplementation on indices of blood pressure. The literature search was performed in four databases, namely, PubMed/Medline, Scopus, the Cochrane Library, and Google Scholar, to identify clinical trials that examined the effects of green coffee supplements on systolic blood pressure (SBP) and diastolic blood pressure (DBP) up to February 2019. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the intervention group and the control group at follow‐up. Nine studies reported SBP and DBP as an outcome measure. Results revealed significant reduction in SBP (weighted mean difference: ?3.093 mmHg, 95% confidence interval [CI]: ?3.914, ?2.273; I² = 0.0%) and DBP (?2.170 mmHg, 95% CI: ?2.749, ?1.590; I²= 46.5%) after green coffee supplementation with low heterogeneity among the studies. In addition, in subgroup analysis, a significant reduction in SBP and DBP in studies with hypertensive patients, green coffee dosage <400 mg, and administered for 4 weeks was identified. The results of the current meta‐analysis study support the use of GCBE supplementation for the improvement of blood pressure indices, with subgroup analysis highlighting improvements in hypertensive patients.     

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.