0000000000202129
AUTHOR
Arrigo F G Cicero
Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials.
International audience; 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 oth…
Short-Term Effects of a Combined Nutraceutical on Lipid Level, Fatty Liver Biomarkers, Hemodynamic Parameters, and Estimated Cardiovascular Disease Risk: A Double-Blind, Placebo-Controlled Randomized Clinical Trial
Introduction: There is a growing interest in nutraceuticals improving cardiovascular risk factor levels and related organ damage. Methods: This double-blind, placebo-controlled randomized clinical trial aims to compare the effect of a combined nutraceutical containing red yeast rice (10Â mg), phytosterols (800Â mg), and l-tyrosol (5Â mg) on lipid profile, blood pressure, endothelial function, and arterial stiffness in a group of 60 patients with polygenic hypercholesterolemia resistant to Mediterranean diet. Results: After 8 weeks of treatment, when compared to the placebo group, the active treated patients experienced a more favorable percentage change in total cholesterol (â16.3% vs 9.9…
Nutraceuticals and functional foods for the control of plasma cholesterol levels. An intersociety position paper
Current evidence shows that cholesterol management either reduces the likelihood of cardiovascular disease (CVD) or slows down its progression. Hence, it is important that all health professionals make appropriate use of all the available intervention strategies to control risk factors: from dietary improvement and positive lifestyle changes to the use of functional foods, food supplements, and drugs. This review examines the effect of the most frequently occurring cholesterol-lowering substances in functional foods or in supplements across Europe, namely plant sterols and stanols, monacolin K found in red yeast rice, berberine and beta-glucans. We conclude that currently available suppleme…
Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features
Abstract Background and aims Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma levels of low density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease (ASCVD). HoFH is caused by pathogenic variants in several genes, such as LDLR, APOB and PCSK9, responsible for autosomal dominant hypercholesterolemia (ADH), and LDLRAP1 responsible for autosomal recessive hypercholesterolemia (ARH). Aim of this study was the review of the clinical and molecular features of patients with HoFH identified in Italy from 1989 to 2019. Methods Data were collected from lipid clinics and laboratories, …
Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia
Introduction: Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated. Areas covered: This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program. Expert opinion: Data from the clinical trials in the ORION program demonstrated efficacy and safety o…
Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study
The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognos…
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 combina…
Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies
Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA an…
Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years
Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart…
Randomised comparison of zofenopril and ramipril plus acetylsalicylic acid in postmyocardial infarction patients with left ventricular systolic dysfunction: a post hoc analysis of the SMILE-4 Study in patients according to levels of left ventricular ejection fraction at entry
Objective Conflicting evidence exists on the benefits of treating patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF) with an ACE inhibitor. This retrospective analysis of the SMILE-4 Study sought to compare the efficacy of zofenopril 60 mg plus acetylsalicylic acid (ASA) versus ramipril 10 mg plus ASA 100 mg in patients with acute myocardial infarction (AMI) and heart failure, according to an impaired or preserved LVEF. Methods The primary study end point was 1-year combined occurrence of death or hospitalisation for cardiovascular causes. A preserved LVEF was defined by a baseline LVEF >40% and an impaired one by an LVEF ≤40%. Results 448 patients…
Renin-Angiotensin System Inhibition in Cardiovascular Patients at the Time of COVID19: Much Ado for Nothing? A Statement of Activity from the Directors of the Board and the Scientific Directors of the Italian Society of Hypertension
Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin-Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease. The available literature, indeed, presents contrasting results, all concentrated in experimental models. Evidence in humans is lacking that those mechanisms are actually occurring in the present…
Natural approaches in metabolic syndrome management
Metabolic syndrome (MetS) is characterized as a group of cardiometabolic risk factors that raise the risk for heart disease and other health problems, such as diabetes mellitus and stroke. Treatment strategies include pharmacologic interventions and supplementary (or "alternative") treatments. Nutraceuticals are derived from food sources (isolated nutrients, dietary supplements and herbal products) that are purported to provide health benefits, in addition to providing basic nutritional value. Nutraceuticals are claimed to prevent chronic diseases, improve health, delay the aging process, increase life expectancy, and support the structure and function of the body. The study of the benefici…
Testing the Short-Term Efficacy of a Lipid-Lowering Nutraceutical in the Setting of Clinical Practice: A Multicenter Study
Abstract The main guidelines for cardiovascular disease prevention suggest that nutraceuticals could be an efficacious tool to improve lipid pattern. Our aim was to carry out a clinical trial comparing the metabolic effects of a combined nutraceutical containing both red yeast rice and polyunsaturated fatty acids (PUFAs) and a phytosterol-based approach in a setting of clinical practice. This was a multicenter open study with parallel control. We consecutively enrolled 107 pharmacologically untreated subjects affected by primary polygenic hypercholesterolemia and metabolic syndrome, assigned to 8-week treatment with a combined treatment with red yeast rice (Dif1Stat®, including 5 mg monacol…
Future Perspectives in Nutraceutical Research
Nutraceuticals are largely used by general population. During the last decades, academicians and industries are intensifying the research of new bioactive compounds in order to improve the quality of life and to prevent disease in humans. The quality of the published research is however not always based on the rules of the Good Clinical Practice nor finalized to create a new Evidence-Based nutraceutical sciences. This chapter will resume some basic rules that we will expect to be applied to nutraceutical research in the next years.
Altilix® Supplement Containing Chlorogenic Acid and Luteolin Improved Hepatic and Cardiometabolic Parameters in Subjects with Metabolic Syndrome: A 6 Month Randomized, Double-Blind, Placebo-Controlled Study
The objective was to evaluate the effects of 6 months of supplementation with Altilix®
Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.
1.1. Cardiovascular disease and dyslipidemia: prevalence and global economic impact Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, reaching 31% of deaths in 2012 [1]. In particular, atherosclerosis and ischemic heart disease (IHD) are the main causes of premature death in Europe and are responsible for 42% of deaths in women and 38% in men under 75 years old [2]. The global economic impact of CVD is estimated to have been US $906 billion in 2015 and is expected to rise by 22% by 2030 [3]. Cardiovascular diseases also represent the major cause of disability in developed countries. It has been estimated that their growing burden could lead to a global increase in…
May Measurement Month 2018: an analysis of blood pressure screening results from Italy
Abstract Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness and blood pressure (BP) control are still unsatisfactory. In 2017, 30.6% of a >10 000 individual sample who took part in the May Measurement Month (MMM) campaign in Italy was found to have high BP. To raise awareness on the hypertension issue and to report BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2018. Blood pressure measurement, the def…
High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid.
Abstract Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discriminat…
Drug Induced Liver Injury (DILI) due to variability in monacolin K content in Red Yeast Rice (RYR): An expert opinion
Abstract Introduction Red yeast rice (RYR) is an effective cholesterol-lowering nutraceutical reversibly inhibiting 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. As liver damage is a possible (albeit rare) side effect of HMG-CoA inhibitors, it make sense to focus on the tolerability of the liver to RYR extracts. The aim of this paper is to offer an expert opinion on the risk of liver damage by the use of RYR extract. Methods A review of the available literature has been carried out and critically reviewed by the authors. Results According to a large meta-analysis of 53 randomized clinical trials comprising 112 treatment arms, which included 8535 subjects with 4437 in the RYR arm and …
Postmarketing nutrivigilance safety profile: a line of dietary food supplements containing red yeast rice for dyslipidemia
IntroductionIn the absence of a European standardized postmarketing food supplement surveillance system (nutrivigilance), some member states and companies have developed their own approaches to monitoring potential adverse reactions to secure a high level of product safety. This paper describes the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected adverse reactions associated with food supplements containing red yeast rice (RYR).Material and methodsWe report the data from a widely used product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manu…
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-…
Polyphenols: Potential Use in the Prevention and Treatment of Cardiovascular Diseases
Background: Polyphenols are bioactive compounds that can be found mostly in foods like fruits, cereals, vegetables, dry legumes, chocolate and beverages such as coffee, tea and wine. They are extensively used in the prevention and treatment of cardiovascular disease (CVD) providing protection against many chronic illnesses. Their effects on human health depend on the amount consumed and on their bioavailability. Many studies have demonstrated that polyphenols have also good effects on the vascular system by lowering blood pressure, improving endothelial function, increasing antioxidant defences, inhibiting platelet aggregation and low-density lipoprotein oxidation, and reducing inflammator…
Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study
Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-c…
Pasta Supplemented with Opuntia ficus-indica Extract Improves Metabolic Parameters and Reduces Atherogenic Small Dense Low-Density Lipoproteins in Patients with Risk Factors for the Metabolic Syndrome: A Four-Week Intervention Study
Food supplementation with Opuntia ficus-indica (OFI) has been associated with a significant reduction in total cholesterol, body fat, hyperglycemia and blood pressure. Since OFI may also have antioxidant and anti-atherogenic properties, we hypothesized that its supplementation might reduce atherogenic lipoproteins, including small, dense low-density lipoproteins (sdLDL). Forty-nine patients (13 men and 36 women, mean age: 56 ±
Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel
In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is…
Daily Use of Extra Virgin Olive Oil with High Oleocanthal Concentration Reduced Body Weight, Waist Circumference, Alanine Transaminase, Inflammatory Cytokines and Hepatic Steatosis in Subjects with the Metabolic Syndrome: A 2-Month Intervention Study
Extra virgin olive oil (EVOO) intake is associated with reduced cardiovascular risk, and its phenolic compound oleocanthal (OC) has anti-oxidant and anti-inflammatory properties. The cardiometabolic effects of EVOO with a high OC concentration have not been fully elucidated. We administered EVOO with a high OC concentration daily to 23 subjects with the metabolic syndrome (MetS) and hepatic steatosis (15 men and 8 women, age: 60 ±
The Role of Nutraceuticals in Statin Intolerant Patients.
Abstract Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activ…