Effect of Citrus bergamia extract on lipid profile: A combined in vitro and human study.

With the aim of characterising the hypo-lipidemic function of the Brumex™ ingredient obtained from the whole fruit of Citrus bergamia, a combined pre-clinical and clinical study was conducted. In the HepG2 experimental model, we first demonstrated that Brumex™ does not trigger any significant alteration in cell viability over the tested concentration range of 1-2000 µg/mL (4 and 24 h). By stimulating the phosphorylation of AMP-activated protein kinase (AMPK) at threonine 172, Brumex™ significantly reduces both cholesterol and triglyceride (TG) intracellular content of HepG2 cells and impairs the expression levels of lipid synthesis-related genes (namely, SREBF1c, SREBF2, ACACA, SCD1, HMGCR and FASN). In vitro data have been validated in a dedicated double-blind, placebo-controlled, randomised clinical trial performed in 50 healthy moderately hyper-cholesterolemic subjects, undergoing supplementation with either Brumex™ (400 mg) or placebo for 12 weeks. Clinical and blood laboratory data were evaluated at the baseline and at the end of the trial. Brumex™ positively impacted on both plasma lipid pattern and liver enzymes compared with the placebo, mainly in terms of significant reduction of total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein B100 (ApoB), fasting plasma glucose (FPG), glutamic-oxaloacetic transaminase (GOT), glutamate pyruvate transaminase (GPT) and gamma-glutamyl-transferase (gGT).

Effect of dietary supplementation with Diuripres® on blood pressure, vascular health, and metabolic parameters in individuals with high-normal blood pressure or stage I hypertension: The CONDOR randomized clinical study.

Our aim was to evaluate if a nutritional intervention with a dietary supplement (Diuripres®) containing magnesium, standardized extract of orthosiphon, hawthorn, and hibiscus could positively affect blood pressure (BP), vascular health, and metabolic parameters in 60 individuals with high-normal BP or stage I hypertension. Participants followed a low-fat low-sodium Mediterranean diet for 4 weeks before being randomly allocated to 8-week treatment with two pills each day of either Diuripres® or placebo. Diuripres® significantly decreased systolic BP compared to placebo after 4 weeks (3.1 ± 0.8 mmHg; p < 0.05) and more consistently after 8 weeks (3.4 ± 0.9 mmHg; p < 0.05). At 8-week follow-up, after correction for multiple testing, dietary supplementation with Diuripres® was associated with significant improvements in diastolic BP (-3.1 ± 0.6 mmHg; p < 0.05), aortic BP (-4.3 ± 0.4 mmHg; p < 0.05), and high-sensitivity C-reactive protein (hs-CRP; 0.04 ± 0.01 mg/dL; p < 0.05) in comparison with baseline. The reductions in diastolic BP (--3.8 ± 0.7 mmHg; p < 0.05), aortic BP (-5.2 ± 1.0 mmHg; p < 0.05), and hs-CRP (-0.03 ± 0.01 mg/dL; p < 0.05) were also significant compared to placebo. Therefore, our study shows that dietary supplementation with Diuripres® may be useful in individuals with high-normal BP or stage I hypertension.

Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods.

Apolipoprotein(a) (apo(a)) is the protein component that defines lipoprotein(a) (Lp(a)) particles and is encoded by the LPA gene. The apo(a) is extremely heterogeneous in size due to the copy number variations in the kringle-IV type 2 (KIV2) domains. In this review, we aim to discuss the role of genetics in establishing Lp(a) as a risk factor for coronary heart disease (CHD) by examining a series of molecular biology techniques aimed at identifying the best strategy for a possible application in clinical research and practice, according to the current gold standard.

Purine Metabolism Dysfunctions: Experimental Methods of Detection and Diagnostic Potential.

Purines, such as adenine and guanine, perform several important functions in the cell. They are found in nucleic acids; are structural components of some coenzymes, including NADH and coenzyme A; and have a crucial role in the modulation of energy metabolism and signal transduction. Moreover, purines have been shown to play an important role in the physiology of platelets, muscles, and neurotransmission. All cells require a balanced number of purines for growth, proliferation, and survival. Under physiological conditions, enzymes involved in purines metabolism maintain a balanced ratio between their synthesis and degradation in the cell. In humans, the final product of purine catabolism is uric acid, while most other mammals possess the enzyme uricase that converts uric acid to allantoin, which can be easily eliminated with urine. During the last decades, hyperuricemia has been associated with a number of human extra-articular diseases (in particular, the cardiovascular ones) and their clinical severity. In this review, we go through the methods of investigation of purine metabolism dysfunctions, looking at the functionality of xanthine oxidoreductase and the formation of catabolites in urine and saliva. Finally, we discuss how these molecules can be used as markers of oxidative stress.

Nutraceuticals in the Management of Dyslipidemia: Which, When, and for Whom? Could Nutraceuticals Help Low-Risk Individuals with Non-optimal Lipid Levels?

PURPOSE OF REVIEW: The aim of this review is to summarize the available clinical efficacy and safety data related to the most studied and used lipid-lowering nutraceuticals. RECENT FINDINGS: A growing number of meta-analyses of randomized clinical trials supports the effectiveness and tolerability of some lipid-lowering nutraceuticals such as red yeast rice, plant sterols and stanols, soluble fibers, berberine, artichoke extracts, bergamot polyphenol fraction, garlic, green tea, and spiruline. No significant safety concern has been raised for the use of such products. Association of more lipid-lowering nutraceuticals and of some nutraceuticals with lipid-lowering drugs has been tested as well. Current evidence suggests that some clinically tested lipid-lowering nutraceuticals could be safely used to improve plasma lipid levels in subjects affected by mild-to-moderate dyslipidaemia with low cardiovascular risk.

Impact of a short-term synbiotic supplementation on metabolic syndrome and systemic inflammation in elderly patients: a randomized placebo-controlled clinical trial.

PURPOSE: The connection between gut microbiota imbalance, inflammation and its role in the pathogenesis of metabolic syndrome (MetS) clustering factors has been increasingly recognized. However, data on the efficacy of probiotics supplementation on MetS components are few and almost lacking in the elderly. To address this issue, we conducted a randomized, double-blind, placebo-controlled, parallel-group, clinical study on a large sample of MetS elderly patients. METHODS: After 14 days of diet and physical activity standardization, 60 elderly patients were randomized to treatment with a synbiotic formula of Lactobacillus plantarum PBS067, Lactobacillus acidophilus PBS066 and Lactobacillus reuteri PBS072 with active prebiotics or placebo. Patients were evaluated anamnestically and by the execution of a physical examination and laboratory and haemodynamic analyses at the baseline and after 60 days of treatment. At enrollment and at the end of the trial, all enrolled patients complete the EuroQol-5 Dimension (EQ-5D) questionnaire. RESULTS: Through the 2-month period of treatment, patients who received active treatment experienced a statistically significant improvement in waist circumference and in fasting plasma insulin, total cholesterol, high-density lipoprotein cholesterol, non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and tumor necrosis factor alpha serum levels, compared both to the baseline and the control group. Visceral adiposity index improvement in the synbiotic treatment group was significantly greater than in placebo group. Compared to baseline, treatment with synbiotics also significantly reduced mean arterial pressure and fasting plasma glucose. All treatment groups demonstrated a significant decrease in TG. TG reduction in the synbiotic group was significantly greater than in the control group. The EQ-5D VAS questionnaire significantly improved only in probiotics-treated subjects. CONCLUSION: Treatment with a synbiotic formula of L. plantarum PBS067, L. acidophilus PBS066 and L. reuteri PBS072 with active prebiotics decreased MetS syndrome prevalence, several cardiovascular risk factors and markers of insulin resistance in elderly patients.

Inequalities in enrollment of women and racial minorities in trials testing uric acid lowering drugs.

AIMS: We investigated sex and racial inequalities in clinical trials testing serum uric acid (SUA) lowering drugs and analyzed the temporal trends of participation among the pre-specified demographic groups. Data were collected from publications of clinical trials testing SUA-lowering drugs. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled in clinical studies. DATA SYNTHESIS: The mean percentage enrollment of women in clinical trials significantly decreased over the time (r = -0.43, P-value = 0.02). Moreover, there was a statistically significant difference in mean percentage enrollment of women among trials testing different SUA-lowering drugs, with the highest representation in rasburicase (71.1%) and the lowest representation of women in dotinurad (0.8%). Over the time, also the mean percentage enrollment of racial minorities decreased, passing from 8.7% to 2.2% in a 10-year period. Women were proportionally underrepresented compared with their share of the population with asymptomatic hyperuricemia, overall (participation-to-prevalence ratio (PPR) = 0.34), in trials testing xanthine oxiase inhibitors (PPR = 0.38) and uricosurics (PPR = 0.29), and in trials with febuxostat, allopurinol, pegloticase, halofenate/arhalofenate, verinurad, lesinurad and dotinurad. Women were proportionally underreppresented also compared with their share of the population with gout, overall (PPR = 0.69) and in trials testing XOIs (PPR = 0.69), uricosurics (PPR = 0.68), and all SUA-lowering drugs excepted for rasburicase, pegloticase and topiroxostat. CONCLUSIONS: Our analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.

Application of the Sampson equation to estimate LDL-C in children: Comparison with LDL direct measurement and Friedewald equation in the BLIP study.

BACKGROUND AND AIMS: In epidemiological trials and in clinical practices, it is relevant to have affordable and reliable methods to measure the main lipid cardiovascular risk factors, and in particular low-density lipoprotein cholesterol (LDL-C) plasma level. In this context, we aimed to compare the reliability of the Friedewald's (LDL-Cf) and Sampson's (LDL-Cs) equations with the LDL-value dosed by a validated dosage method (LDL-Cd) in a large cohort of children. METHODS AND RESULTS: We considered the lipid values of 145 infants, 278 preschoolers, 810 scholar children, and 1372 adolescents (Total N. 2605, 1291 males, 1314 females), with mean total cholesterol (TC) = 169.8 ± 39.7 mg/dL, HDL-Cholesterol = 50.8 ± 12.7 mg/dL, non HDL-Cholesterol = 118.9 ± 35.9 mg/dL, Triglycerides (TG) = 90.3 ± 77.9 mg/dL, LDL-Cd = 106.2 ± 29.9 mg/dL, LDL-Cf = 100.9 ± 33.8 mg/dL, and LDL-Cs = 102.2 ± 33.4 mg/dL. Comparing the distance to the LDL-Cd, Friedewald's equation mildly but significantly underestimated in infants (3.4 ± 5.3 mg/dL), preschoolers (1.5 ± 7.1 mg/dL). Children (1.2 ± 2.2 mg/dL) and adolescents (1.1 ± 5.9 mg/dL) compared to Sampson's equation (all comparisons, p < 0.001). CONCLUSIONS: Our analysis, being carried out on a large population sample, shows that Sampson's equation is more reliable than Friedewald's one at each considered age class and even for extreme TG values.

Clinical Effects of Xanthine Oxidase Inhibitors in Hyperuricemic Patients.

This review aims to critically present the available clinical evidence supporting the treatment of chronic hyperuricemia with xanthine oxidase inhibitors. For this reason, the studies published on uric acid (UA)-lowering drugs in the English language from 2000 to August 2019 have been carefully reviewed. The terms "serum uric acid," "xanthine oxidase," "allopurinol," "febuxostat," and "topiroxostat" were incorporated into an electronic search strategy, alone and in combinations, in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). Even if new urate-lowering drugs seem of particular efficacy for acute treatment of refractory hyperuricemia, their use is supported by relatively small clinical evidence. On the contrary, large long-term clinical trials have demonstrated that xanthine oxidase inhibitors (XOIs, namely, allopurinol and febuxostat) are effective, safe, and relatively well-tolerated in most of the patients. They have mainly been tested in the elderly, in patients affected by chronic diseases such as heart failure and cancer, and in patients taking a large number of drugs, confirming their safety profile. Recent data also show that they could exert some positive effects on vascular health, renal function, and glucose metabolism. Their cost is also low. In conclusion, XOIs remain the first choice of UA-lowering drug for chronic treatment.

Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update.

This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that further well-designed clinical research is needed to deepen their efficacy and safety profile.

Sudden Fall in the Lipid-Lowering Effect of Evolocumab: The Butler Is Not Always Guilty.

A 78-year-old man came to our attention after undergoing coronary computed tomography angiography documenting multivessel coronary artery disease. He was started on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab 140 mg subcutaneously every 2 weeks. Treatment-emergent changes in lipids and lipoproteins were long-lasting, and the medication was well tolerated by the patient in the long-term. Unexpectedly, after 2 years of continuous treatment with evolocumab, serum lipids increased, apparently without any reasonable explanation. During the follow-up visit, the patient was found to have habitually injected evolocumab into his right thumb instead of into the appropriate injection sites (i.e., abdomen, thighs or upper arms) after turning the injector upside down.

Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis.

BACKGROUND: Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. METHODS AND FINDINGS: We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD -14.94%; 95% CI -17.31%, -12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD -18.17%; 95% CI -21.14%, -15.19%; p < 0.001), low-density lipoprotein cholesterol (MD -22.94%; 95% CI -26.63%, -19.25%; p < 0.001), low-density lipoprotein particle number (MD -20.67%; 95% CI -23.84%, -17.48%; p < 0.001), apolipoprotein B (MD -15.18%; 95% CI -17.41%, -12.95%; p < 0.001), high-density lipoprotein cholesterol (MD -5.83%; 95% CI -6.14%, -5.52%; p < 0.001), high-density lipoprotein particle number (MD -3.21%; 95% CI -6.40%, -0.02%; p = 0.049), and hsCRP (MD -27.03%; 95% CI -31.42%, -22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD -1.51%; 95% CI -3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI -9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD -1.83%; 95% CI -5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. CONCLUSIONS: Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.

Efficacy and Safety of Volanesorsen (ISIS 304801): the Evidence from Phase 2 and 3 Clinical Trials.

PURPOSE OF REVIEW: To revise the clinical evidence supporting the use of volanesorsen as new lipid-lowering drug and to assess the efficacy and safety of volanesorsen (ISIS 304801) through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies. RECENT FINDINGS: The meta-analysis of three clinical studies comprising 11 arms (N = l 156 subjects, with 95 in the active-treated arm and 61 in the control one) shows that volanesorsen significantly affects plasma levels of triglycerides (TG) [MD = - 67.90%, 95%CI = - 85.32, - 50.48, P < 0.001], high-density lipoprotein cholesterol (HDL-C) [MD = 40.06%, 95%CI: 32.79, 47.34, P < 0.001], very-low-density lipoprotein cholesterol (VLDL-C) [MD = - 72.90%, 95%CI = - 82.73, - 63.07, P < 0.001], apolipoprotein B (Apo B) [MD = 8%, 95%CI = 2.17, 13.84, P = 0.007], Apo B-48 [MD = - 64.63, 95%CI = - 105.37, - 23.88, P = 0.002], ApoCIII [MD = - 74.83%, 95%CI = - 85.93, - 63.73, P < 0.001], and VLDL ApoCIII [MD = - 83.69%, 95%CI = - 94.08, - 73.29, P < 0.001], without significant impact on LDL-C [MD = 47.01%, 95%CI = - 1.31, 95.33, P = 0.057] levels. Treatment with volanesorsen was associated with an higher risk of injection site reaction (OR = 32.89, 95%CI = 7.97,135,74, P < 0.001) and with an increased risk of upper respiratory tract infections (OR = 10.58, 95%CI = 1.23, 90.93, P < 0.05) when compared to placebo. Volanesorsen has a relevant impact on plasma TG and related parameters without affecting LDL cholesterolemia and is associated with an acceptable safety profile.

Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and non-alcoholic fatty liver disease indices: a double-blind, placebo-controlled clinical trial.

PURPOSE: Curcumin has shown to exert a positive impact on human glucose metabolism, even if its bioavailability is usually very low. The present study aimed to explore the effect of phosphatidylserine- and piperine-containing curcumin phytosomes on a large number of metabolic parameters related to insulin resistance, in the context of a randomized double-blind placebo-controlled trial involving 80 overweight subjects with suboptimal fasting plasma glucose. METHODS: Subjects were randomized to be treated with indistinguishable tablets (2 per day, to be taken after dinner) containing 800 mg phytosomal curcumin (Curserin®: 200 mg curcumin, 120 mg phosphatidylserine, 480 mg phosphatidylcholine and 8 mg piperine from Piper nigrum L. dry extract) for 8 weeks. RESULTS: After 56-day treatment, the curcumin-treated group experienced a significant improvement in fasting plasma insulin (FPI), HOMA index, waist circumference, blood pressure, triglycerides (TG), HDL-C, liver transaminases, gamma-GT, index of liver steatosis and serum cortisol compared to the baseline. FPI, TG, liver transaminases, fatty liver index and serum cortisol level also significantly improved compared with the placebo-treated group. Compared to the baseline, at the end of the study placebo group experienced an improvement only in FPG and TG. CONCLUSION: In conclusion, the present trial shows that supplementation with a phytosomal preparation of curcumin containing phosphatidylserine and piperine could improve glycemic factors, hepatic function and serum cortisol levels in subjects with overweight and impaired fasting glucose.

Awareness of major cardiovascular risk factors and its relationship with markers of vascular aging: Data from the Brisighella Heart Study.

BACKGROUND AND AIM: General population awareness about cardiovascular risk factors is usually low. The aim of the present study was to evaluate the vascular aging of subjects aware and not aware to be hypertensive, hypercholesterolemic, hypertriglyceridemic or diabetics in a general population sample. METHODS AND RESULTS: We interviewed 1652 subjects without atherosclerotic cardiovascular diseases (M: 46.6%, F: 53.4%) about their awareness of hypertension, hypercholesterolemia, hypertriglyceridemia or type 2 diabetes. Then we compared the augmentation index and pulse wave velocity of subjects aware and not aware of the investigated cardiovascular risk factors. 1049 participants declared not to be hypertensive, while 32 were not sure. Among them, respectively, 23.5% and 50% were hypertensive. Subjects not aware of their hypertension had significantly higher aortic blood pressure than aware ones (p < 0.001). 841 participants declared not to be hypercholesterolemic, while 60 were not sure. Among them, respectively, 18.1% and 40% were hypercholesterolemic. Subjects not aware of their hypercholesterolemia had significantly higher augmentation index than the aware ones (p < 0.05). 1226 participants declared not to be hypertriglyceridemic, while 200 were not sure. Among them, respectively, 19.2% and 44% were hypertriglyceridemic. Subjects not aware of their hypertriglyceridemia had significantly higher TG levels aware ones (p < 0.05), although this seemed to not related to increased arterial stiffness. 1472 participants declared not to be diabetic, while 20 were not sure. Among them, respectively, 2.0% and 25.0% were diabetics. Subjects not aware of their diabetes had significantly higher augmentation index than the aware ones (p < 0.05). CONCLUSIONS: In conclusion, the lack of awareness of hypertension and hypercholesterolemia is relatively frequent in the general population and is associated to significantly higher arterial stiffness.

Effect of Omega-3 Polyunsaturated Fatty Acids Treatment on Lipid Pattern of HIV Patients: A Meta-Analysis of Randomized Clinical Trials.

Even though omega-3 polyunsaturated fatty acids (PUFAs) seem to be effective in the treatment of human immunodeficiency virus (HIV)-associated dyslipidemia, their impact is still debated. For this reason, our aim was to perform a meta-analysis of the clinical evidence available to date. A systematic literature search was conducted in order to identify published clinical trials assessing the effect of PUFAs treatment on serum lipoproteins, and its safety profile. The effect sizes for lipid changes were expressed as mean difference (MD) and 95% confidence interval (CI). For safety analysis, odd ratios and the 95% CI were calculated with the Mantel-Haenszel method. Data were pooled from nine clinical studies comprising overall 578 HIV-affected subjects. Meta-analysis of the data suggested that omega-3 PUFAs significantly reduced triglycerides (TG) (MD = -1.04, 95% CI: -1.5, -0.58 mmol/L, p < 0.001), while increasing high-density lipoprotein cholesterol (MD = 0.36, 95% CI: 0.12, 0.61 mmol/L, p = 0.004), without affecting serum levels of total cholesterol, very-low- and low-density lipoprotein cholesterol, and apolipoprotein B and A1. Change in TG was significantly associated with eicosapentaenoic acid administered via daily dose. PUFA treatment did not lead to an increased risk of adverse events. In conclusion, PUFAs are safe and exert a significant plasma lipid improving effect in HIV-positive patients.

Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials.

Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1-5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects.

Effect of pistachio on brachial artery diameter and flow-mediated dilatation: A systematic review and meta-analysis of randomized, controlled-feeding clinical studies.

BACKGROUND: Results of previous clinical trials evaluating the effect of pistachio supplementation on endothelial reactivity (ER) are controversial. AIMS: We aimed to assess the impact of pistachio on ER through systematic review of literature and meta-analysis of available randomized, controlled-feeding clinical studies (RCTs). METHODS: The literature search included SCOPUS, PubMed-Medline, ISI Web of Science and Google Scholar databases up to 1st August 2017 to identify RCTs investigating the impact of pistachio on ER. Two independent reviewers extracted data on study characteristics, methods and outcomes. Overall, the impact of pistachio on ER was reported in 4 trials. RESULTS: The meta-analysis did not suggest a significant change in brachial artery flow-mediated dilatation (FMD) (WMD: +0.28%; 95%CI: -0.58, 1.13; p = 0.525) while brachial artery diameter (BAD) improved (WMD: +0.04%; 95%CI: 0.03, 0.06; p<0.001) following pistachios consumption. CONCLUSION: The present meta-analysis suggests a significant effect of pistachios on ER, affecting BAD but not FMD.

Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials.

Introduction: Results of previous clinical trials evaluating the effect of resveratrol supplementation on blood pressure (BP) are controversial. Purpose: We aimed to assess the impact of resveratrol on BP through systematic review of literature and meta-analysis of available randomized, controlled clinical trials (RCTs). Methods: Literature search included SCOPUS, PubMed-Medline, ISI Web of Science and Google Scholar databases up to 17th October 2017 to identify RCTs investigating the impact of resveratrol on BP. Two review authors independently extracted data on study characteristics, methods and outcomes. Overall, the impact of resveratrol on BP was reported in 17 trials. Results: Administration of resveratrol did not significantly affect neither systolic BP [weighted mean difference (WMD): -2.5 95% CI:(-5.5, 0.6) mmHg; p=0.116; I2=62.1%], nor diastolic BP [WMD: -0.5 95% CI:(-2.2, 1.3) mmHg; p=0.613; I2=50.8], nor mean BP [MAP; WMD: -1.3 95% CI:(-2.8, 0.1) mmHg; p=0.070; I2=39.5%] nor pulse pressure [PP; WMD: -0.9 95% CI:(-3.1, 1.4) mmHg; p=0.449; I2=19.2%]. However, significant WMDs were detected in subsets of studies categorized according to high resveratrol daily dosage (≥300 mg/day) and presence of diabetes. Meta-regression analysis revealed a positive association between systolic BP-lowering resveratrol activity (slope: 1.99; 95% CI: 0.05, 3.93; two-tailed p= 0.04) and Body Mass Index (BMI) at baseline, while no association was detected neither between baseline BMI and MAP-lowering resveratrol activity (slope: 1.35; 95% CI: -0.22, 2.91; two-tailed p= 0.09) nor between baseline BMI and PP-lowering resveratrol activity (slope: 1.03; 95% CI: -1.33, 3.39; two-tailed p= 0.39). Resveratrol was fairly well-tolerated and no serious adverse events occurred among most of the eligible trials. Conclusion: The favourable effect of resveratrol emerging from the current meta-analysis suggests the possible use of this nutraceutical as active compound in order to promote cardiovascular health, mostly when used in high daily dose (≥300 mg/day) and in diabetic patients.

Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

The aim of this study is to assess the impact of a combination of berberine and silymarin on serum lipids and fasting plasma glucose (FPG) through a systematic review of literature and meta-analysis of the available randomized, double-blind, placebo-controlled clinical trials (RCTs). A systematic literature search in SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases was conducted up to October 2, 2018, in order to identify RCTs assessing changes in plasma concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and FPG during treatment with berberine and silymarin in combination. Two review authors independently extracted data on study characteristics, methods, and outcomes. Quantitative data synthesis was performed using a random-effects model. We identified five eligible RCTs, with 497 subjects overall included. Berberine and silymarin combination treatment exerted a positive effect on TC (mean difference [MD]: -25.3, 95% CI [-39.2, -11.4] mg/dl; p < 0.001), TG (MD: -28, 95% CI [-35.3, -20.6] mg/dl; p < 0.001), HDL-C [MD: 6, 95% CI [3.2, 8.8] mg/dl; p < 0.001), LDL-C (MD: -29.1, 95% CI [-39.7, -18.6] mg/dl; p < 0.001), and FPG (MD: -7.5, 95% CI [-13, -1.9] mg/dl; p = 0.008). The present findings suggest that the coadministration of berberine and silymarin is associated with an advantageous improvement in lipid and glucose profile, suggesting the possible use of this nutraceutical combination in order to promote the cardiometabolic health.