Effect of Dietary Supplementation with Eufortyn® Colesterolo Plus on Serum Lipids, Endothelial Reactivity, Indexes of Non-Alcoholic Fatty Liver Disease and Systemic Inflammation in Healthy Subjects with Polygenic Hypercholesterolemia: The ANEMONE Study.

We aimed to evaluate if dietary supplementation with a nutraceutical compound (Eufortyn® Colesterolo Plus) containing standardized bergamot polyphenolic fraction phytosome (Vazguard®), artichoke extract (Pycrinil®), artichoke dry extract. (Cynara scolymus L.), Q10 phytosome(Ubiqosome®) and zinc, could positively affect serum lipids concentration, systemic inflammation and indexes of non-alcoholic fatty liver disease (NAFLD) in 60 healthy subjects with polygenic hypercholesterolemia. Participants were adhering to a low-fat, low-sodium Mediterranean diet for a month before being randomly allocated to 8-week treatment with 1 pill each day of either Eufortyn® Colesterolo Plus or placebo. Dietary supplementation with Eufortyn® Colesterolo Plus was associated with significant improvement in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP) and endothelial reactivity (ER) in comparison with baseline, and with significant reductions in waist circumference, TC, LDL-C, LDL-C/HDL-C, lipid accumulation product and fatty liver index compared to placebo. The study shows that dietary supplementation with standardized bergamot polyphenolic fraction phytosome, artichoke extracts, Q10 phytosome and zinc safely exerts significant improvements in serum lipids, systemic inflammation, indexes of NAFLD and endothelial reactivity in healthy subjects with moderate hypercholesterolemia.

Effect of Synaid on cognitive functions and mood in elderly subjects with self-perceived loss of memory after COVID-19 infection.

INTRODUCTION: There is growing attention towards the possible long-term effect of COVID-19 on neuropsychiatric disorders. METHODS: We tested the effect of a combined nutraceutical (Synaid) with known nootropic effects in 40 elderly patients with self-perceived cognitive decline after SARS-CoV-2 infection, treated at home or in hospital. RESULTS: After 3 months of treatment, Synaid significantly improved functional status, MMSE and the main psychological disorders associated with mild cognitive impairment, both in patients previously cared for at home and in hospital because of SARS-CoV-2 infection. CONCLUSIONS: Synaid was well tolerated and effective in improving cognitive function and psychosocial parameters after SARS-CoV-2 infection.

Effect of combined lipid-lowering and antioxidant nutraceutical on plasma lipids, endothelial function, and estimated cardiovascular disease risk in moderately hypercholesterolemic patients: a double-blind, placebo-controlled randomized clinical trial.

INTRODUCTION: Nutraceuticals are a good means to lower cardiovascular risk. Having established a reasonable pharmacological background, a new nutraceutical combination should be tested in clinical trials. MATERIAL AND METHODS: This double-blind, placebo-controlled randomized clinical trial aims to evaluate the modulating effect, in a setting of controlled nutritional habits, of a combined food supplement with DIF1STAT (based on red yeast rice with a very low content of monacolins, linear aliphatic alcohols and niacin) and Olea europaea on plasma lipids and endothelial function, in a group of 40 healthy, moderately hypercholesterolemic patients in primary cardiovascular prevention. RESULTS: After 8 weeks of treatment, when compared to the placebo group, the active treated patients experienced significant improvements of different metabolic parameters and endothelial reactivity compared to placebo. The treated patients showed a statistically significant percentage change in total cholesterol (-12.25 delta% vs. -1.8%, p < 0.01), low-density lipoprotein (LDL) cholesterol (-28.7 delta% vs. -1.1%, p < 0.01), high-density lipoprotein (HDL) cholesterol (+4.99% vs. +0.9%, p < 0.05), non-HDL cholesterol (-16.02 delta% vs. -1.5%, p < 0.01), SUA (-12.96 delta%, p < 0.05) and endothelial reactivity (+6.73% vs. -1.4%, p < 0.01). In both groups, there was no case of intolerance and the safety parameters were unchanged. CONCLUSIONS: The tested nutraceutical association is able to significantly improve different lipid parameters compared to placebo, and endothelial reactivity compared to baseline. Even if the study power appears to be adequate for the primary endpoints, the effect on endothelial function needs confirmation in a longer clinical trial.

Efficacy and Safety of Armolipid Plus®: An Updated PRISMA Compliant Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

Armolipid Plus® is a multi-constituent nutraceutical that claims to improve lipid profiles. The aim of this PRISMA compliant systematic review and meta-analysis was to globally evaluate the efficacy and safety of Armolipid Plus® on the basis of the available randomized, blinded, controlled clinical trials (RCTs). A systematic literature search in several databases was conducted in order to identify RCTs assessing the efficacy and safety of dietary supplementation with Armolipid Plus®. Two review authors independently identified 12 eligible studies (1050 included subjects overall) and extracted data on study characteristics, methods, and outcomes. Meta-analysis of the data suggested that dietary supplementation with Armolipid Plus® exerted a significant effect on body mass index (mean difference (MD) = -0.25 kg/m2, p = 0.008) and serum levels of total cholesterol (MD = -25.07 mg/dL, p < 0.001), triglycerides (MD = -11.47 mg/dL, p < 0.001), high-density lipoprotein cholesterol (MD = 1.84 mg/dL, p < 0.001), low-density lipoprotein cholesterol (MD = -26.67 mg/dL, p < 0.001), high sensitivity C reactive protein (hs-CRP, MD = -0.61 mg/L, p = 0.022), and fasting glucose (MD = -3.52 mg/dL, p < 0.001). Armolipid Plus® was well tolerated. This meta-analysis demonstrates that dietary supplementation with Armolipid Plus® is associated with clinically meaningful improvements in serum lipids, glucose, and hs-CRP. These changes are consistent with improved cardiometabolic health.

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.

Prevalent Seasoning and Cooking Fats, Arterial Stiffness and Blood Lipid Pattern in a Rural Population Sample: Data from the Brisighella Heart Study.

Background: Dietary fats have been variably associated with the risk of cardiovascular disease. The aim of our study was to evaluate the association between everyday mainly used dietary fats in cooking and as seasoning and hemodynamic and lipid parameters. Methods: For this study, we selected from the Brisighella Heart Study cohort subjects who were not treated with antihypertensive drugs and report with certainty their daily mean intake of dietary fats in cooking and as seasoning. Depending on the main source of dietary fat, the involved subjects were classified as prevalent extra-virgin olive oil (EVO) users, prevalent corn oil users, prevalent users of different vegetable oils and prevalent animal fat users, and we compared their characteristics. Results: Everyday consumption of EVO as a main seasoning and cooking fat source was significantly associated to lower body mass index, visceral adiposity index, blood pressure, arterial stiffness, and cholesterolemia, when compared with predominantly animal fat users. Corn oil users also had lower blood pressure, arterial stiffness, and cholesterolemia, when compared with predominantly animal fat users, as well. In particular, in an age and systolic blood pressure adjusted model, the predictors of carotid-femoral pulse wave velocity were the prevalent use of EVO (RR = 0.84, 95%CI 0.67-0.94 vs. other prevalent fat sources), LDL-Cholesterol (RR= 1.12, 95% CI 1.02-1.42), serum uric acid (RR = 1.21, 95%CI 1.09-1.54) and estimated GFR (RR= 0.77, 95%CI 0.59-0.99). Conclusions: According to our findings, the choice of everyday seasoning and cooking fat is associated with a different metabolic and haemodynamic pattern.

Successful treatment of a patient with mitochondrial myopathy with alirocumab.

A 48-year-old man presented to our lipid clinic with statin intolerance and elevated serum creatine kinase levels, being affected by mitochondrial myopathy because of heteroplasmic mitochondrial DNA missense mutation in MTCO1 gene (m.7671T>A). He had just been treated with a coronary artery bypass 4 years before because of acute coronary syndrome, and he had consistently high levels of both low-density lipoprotein cholesterol and triglycerides. Dyslipidemia was successfully treated using 75 mg of alirocumab subcutaneously every 2 weeks, 10 mg of ezetimibe daily, 2 g of marine omega-3 fatty acids daily, and 145 mg of micronized fenofibrate every 2 days. Although muscle weakness persisted, myalgia did not reoccur and serum creatine kinase levels remained almost stable over the time.

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.

Effect of quantitative and qualitative diet prescription on children behavior after diagnosis of heterozygous familial hypercholesterolemia.

BACKGROUND: Diet and healthy modifications in lifestyle represent the first therapeutic approach for early intervention in hypercholesterolemia. We aimed to evaluate the impact of a qualitative dietetic program rather than a quantitative one on metabolic parameters and anxiety level of children affected by heterozygous familial hypercholesterolemia [heFH] and their mothers. METHODS: In a sample of 42 heFH normal weight children (11.4 ±â€¯2.9 years old), we investigated the factors which were associated with children perceived quality of life and with their mothers' anxiety levels after qualitative dietary changes rather than after quantitative ones. RESULTS: The administered diets had similar metabolic effects. However, higher Child Behavior Checklist (Behavior Problems subscale) [CBCL] scores were significantly associated with the permanence in quantitative diet, as well as children's higher age, higher Children's Depression Inventory 2 [CDI2] and State-Trait Anxiety Inventory for Children [STAI-CH] score, and with mothers' anxiety at the baseline. CONCLUSION: In heFH children, an intervention in the diet to improve food choice seems to be associated with a more healthy children behavior rather than a quantitative diet.

Three-arm, placebo-controlled, randomized clinical trial evaluating the metabolic effect of a combined nutraceutical containing a bergamot standardized flavonoid extract in dyslipidemic overweight subjects.

Our double-blind, placebo-controlled, parallel-group, dose-escalation, clinical trial aimed to test the effect of a combined nutraceutical containing bergamot extract (120-mg flavonoids), phytosterols, vitamin C, and chlorogenic acid from dry artichoke extract on 90 overweight dyslipidemic subjects. Participants were randomly allocated to treatment with two pills of either active treatment or placebo, or a combination of both (a pill per treatment). After 8 weeks, all active-treated groups experienced a significant improvement in triglycerides (TG) versus placebo and in low-density lipoprotein cholesterol (LDL-C) versus baseline and placebo treatments. In the high-dose-treated group, also total cholesterol (TC), nonhigh-density lipoprotein cholesterol (non-HDL-C), γ-glutamil transpeptidasi, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) significantly decreased. At 24-week follow-up, TG levels maintained lower than baseline in all groups. All patients allocated to either low-dose or high-dose active treatment experienced a significant decrease in TG, LDL-C, and homeostatin model assessment of insulin resistance. In subjects taking high-dose active treatment, adiponectin significantly increased, whereas TC, non-HDL-C, insulin (fasting plasma insulin), leptin, leptin/adiponectin ratio, hs-CRP, and TNF-α were significantly reduced. The tested nutraceutical showed to improve lipid and glucose metabolism, adipokines pattern, and systemic inflammation in dyslipidemic overweight subjects.

Emerging drugs for the treatment of hypercholesterolemia.

INTRODUCTION: Despite the consolidated role of statins and ezetimibe to treat hypercholesterolemia, often the desirable low-density lipoprotein cholesterol (LDL-C) values are not achieved, with a consequent increase of the residual cardiovascular (CV) risk. Areas covered: In this review, we summarize the main pharmacological characteristics of new lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, cholesteryl ester transfer protein inhibitors, microsomal triglyceride transfer protein inhibitors, ATP citrate lyase inhibitors, antisense oligonucleotides, small interfering RNA, and peroxisome proliferator-activated receptors type α agonists. The available clinical evidence of efficacy and safety as well as the prospects of application, based on the different mechanisms and targets of action, is critically discussed. Expert opinion: Some of these emerging agents represent an excellent therapeutic strategy to treat patients with LDL largely out of target, resistant or intolerant to statins, trying to minimize the residual CV risk, modulating different classes of lipoproteins, not just LDL. The main challenge for the large use of emerging drugs is their cost. Thus, the correct identification of the adequate target population for treatment is a priority. This is particularly true for safe, powerful, and fully developed drugs such as the PCSK9 inhibitors, for which a relatively large use is potentially expected.

Short-Term Effects of Dry Extracts of Artichokeand Berberis in Hypercholesterolemic Patients Without Cardiovascular Disease.

Hypercholesterolemia represents one of the main reversible cardiovascular risk factors. In this pilot clinical trial, we have tested the short-term efficacy and safety of a new combined cholesterol-lowering nutraceutical containing artichoke dry extract and berberine at enhanced bioavailability in subjects with moderate polygenic hypercholesterolemia in primary prevention for cardiovascular disease. After 2 months of treatment, the tested nutraceutical induced a significant reduction in plasma total cholesterol (-19%), low-density lipoprotein cholesterol (-16%), non-high-density lipoprotein cholesterol (-19%) and triglyceride levels (-15%), in association with a standardized control diet. No side effect has been observed during the trial. In conclusion, on the short-term, the tested nutraceutical has been shown to be well tolerated and effective, even if not containing any statin-like compound.

Is it Possible to Significantly Modify Blood Pressure with a Combined Nutraceutical on Top of a Healthy Diet? The Results of a Pilot Clinical Trial.

INTRODUCTION: Beyond the well-known effects on blood pressure (BP) of the dietary approaches to stop hypertension (DASH) and the Mediterranean diets associated to a correct lifestyle, often a lifestyle change is not simple and can show only long-time results: in this sense, a possible support might be derived from the use of some anti-hypertensive supplements or nutraceuticals, which may provide a significant reduction in blood pressure. AIM: We conducted a randomized, double-blind, placebo-controlled clinical trial in a group of 36 pre-hypertensive and first-degree hypertensive patients. METHODS: The treatment period with a mix of bioactive substances (BPLN®, containing a donor of nitric oxide, magnesium, and vitamins) or placebo was 16-week long and was preceded by 4 weeks of diet stabilization. RESULTS: At the end of the intervention, patients treated with the nutraceutical product showed a significant reduction of all morning pressure parameters and of evening systolic blood pressure, both versus the baseline and versus the group treated with placebo. These effects were maintained even after the first 16 weeks of treatment, confirming that the preliminary results were not due to simple changes in volume and do not lead to adaptation/tachyphylaxis. No patient complained of any side effects while taking the active treatment and placebo. CONCLUSIONS: The tested nutraceutical composite reduces systolic and diastolic blood pressure in the medium term, leading to a significant reduction in the estimated cardiovascular risk in a sample of patients with pre-hypertension or first-degree hypertension.

Optimizing Lipid Pattern by Adding a Combined Nutraceutical or Pravastatin to Fenofibrate Treatment in Hypertriglyceridemic Subjects: Single Site, Randomized, Open-Label, Post-Market Clinical Investigation.

INTRODUCTION: Fenofibrate is an effective and safe treatment for hypertriglyceridemia. However, after TG reduction a residual dyslipidemia could appear and require further treatment. AIM: To comparatively evaluate the short-term tolerability and efficacy of a combined lipid-lowering nutraceutical and pravastatin 40 mg in fenofibrate treated patients. METHOD: We prospectively enrolled 40 patients well-tolerating treatment with micronized fenofibrate 145 mg/day and with residual dyslipidemia (LDL-C > 115 mg/dL and TG > 150 mg/dL). Exclusion criteria have been type 2 diabetes, Familial Hypercholesterolemia, previous cardiovascular diseases and severe chronic kidney disease. Then, we have randomly assigned the patients to treatment with pravastatin 40 mg or a combined lipid-lowering nutraceutical (Armolipid Plus®, containing monacolin 3 mg and berberine 500 mg). RESULTS: After 8 weeks of treatment, 80% of pravastatin treated patients (N. 16/20) and 75% of those treated with Armolipid Plus® (N. 15/20) reached the desired LDL-C target, while 50% of pravastatin treated patients (N. 10/20) and 80% of the Armolipid Plus® treated ones reached the desired TG target (N. 16/20). No one adverse event has been registered during Armolipid Plus®, while 1 patient claimed myalgia and 1 reported significant increase of CPK (> 3 ULN) during pravastatin treatment. Both patients were then treated with Armolipid Plus® with resolution of symptoms and CPK increase, respectively. CONCLUSION: In hypertriglyceridemic patients treated with fenofibrate, the association with a combined lipid lowering nutraceutical seem to be more effective in optimizing residual hypertriglyceridemia than pravastatin 40 mg, while being more tolerable and having similar effect on LDL-C plasma level.

LDL-oxidation, serum uric acid, kidney function and pulse-wave velocity: Data from the Brisighella Heart Study cohort.

BACKGROUND: Serum uric acid (SUA) and oxidized LDL (oxLDL) may be associated with arterial aging. The aim of our study was to evaluate the relationship between SUA, oxLDL and arterial stiffness in subjects with normal renal function and in patients with mild or moderate renal impairment. METHODS: From the database of the 2012 Brisighella Heart Study, we compared age-matched adult, non-smoker subjects without cardiovascular disease and with normal renal function (n = 205), subjects with stage II chronic kidney disease (CKD) (n = 118) and subjects with stage III CKD (n = 94). All subjects underwent a determination of the LDL oxidative susceptibility, oxLDL levels, SUA and Pulse Wave Velocity (PWV). RESULTS: By univariate analysis, PWV correlated with a large number of clinical, haemodynamic and metabolic parameters, including estimated glomerular filtration rate (eGFR) in subjects with normal renal function and in those with stage II or III CKD. Stepwise multiple regression analyses showed that in the presence of normal renal function or stage II CKD, the main predictors of PWV were age, systolic blood pressure (SBP), ox-LDL, apolipoprotein B and SUA (p < 0.05), while in the presence of stage III CKD only age, SBP and apolipoprotein B remained significant (p < 0.05). CONCLUSION: Both ox-LDL and SUA independently predicts PWV only in subjects with normal or mildly reduced renal function, but not in the subjects with more compromised eGFR. This study confirms the complex relationship of SUA with cardiovascular and metabolic disease in the patient with established renal disease.

Pharmacokinetics, pharmacodynamics and clinical efficacy of non-statin treatments for hypercholesterolemia.

INTRODUCTION: Hypercholesterolemia is the main modifiable risk factor for atherosclerosis progression and cardiovascular disease (CVD) development. Its pharmacological management is usually based on the prescription of statins, that in some cases are not however fully effective to reach the desired Low-Density-Lipoproteins cholesterol (LDL-C) target, or are not tolerated by patients due to side effects. Areas covered: This manuscript summarizes the basic properties of the emerging new classes of lipid-lowering drugs such as ezetimibe, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, and Microsomal Triglyceride Transfer Protein (MTP) inhibitors, also citing new drugs in development. Our aim is to describe the main pharmacodynamic and pharmacokinetic characteristics, the available efficacy, tolerability and safety data obtained in randomized clinical trials where these drugs were tested. Expert opinion: Non-statin lipid-lowering drugs can be considered an excellent strategy to reduce the residual CV risk, also represented by non-target LDL-C values and high lipoprotein(a) serum levels. In particular, the approved PCSK9 inhibitors (Evolocumab and Alirocumab) have been very effective in optimizing plasma LDL-C values and reducing CV event risk.

The Effect of Xanthine Oxidase Inhibitors on Blood Pressure and Renal Function.

Several epidemiological studies have demonstrated the existence of a correlation between high serum uric acid (SUA) levels, hypertension, and chronic kidney disease (CKD). Xantine oxidase inhibitors (XOI) are the most powerful uric acid lowering drugs, with presumed beneficial effects on cardiovascular and renal system. The multifactorial mechanism linking hyperuricemia with cardiovascular and renal diseases involves both the SUA level and the xanthine oxidase (XO) activity. In this context, the clinical research has been recently focused at assessing the efficacy of urate-lowering drugs active on XO in patients with abnormal blood pressure values and renal dysfunction. The mechanism of action responsible for the beneficial effect of XOI has not completely elucidated, and long-term studies involving large population samples are needed. In particular, XOI could play an important role in the management of hypertension and CKD, especially in patients not entirely controlled by conventional therapies. In the present review, we summarize the results of recent clinical trials that largely support a positive effect of allopurinol and febuxostat on blood pressure, glomerular filtration rate (GFR), and serum creatinine in different populations of patients. Will these drugs be considered a reliable choice or alternative to currently used drugs for the hypertension and kidney failure treatment? The debate is open, but much evidence is accumulating and supporting this role.

Pharmacokinetic drug evaluation of ezetimibe + simvastatin for the treatment of hypercholesterolemia.

INTRODUCTION: Cholesterol lowering treatment is mainly based on statins eventually associated to adjunctive drugs of different class such as ezetimibe. In the present review, we analysed the pharmacokinetics, efficacy and safety of ezetimibe + simvastatin drug association. Areas covered: The bio-equivalence of ezetimibe and simvastatin when co-administrated in separate tablets or combined in a single pill is well documented. Ezetimibe is absorbed in small intestine, reaching peak plasma concentrations in 4-12 h, with a plasma half-life of 22 h. Simvastatin, ingested as a prodrug, is hydrolyzed in liver to its active beta-hydroxyacid metabolite, reaching peak plasma concentrations in 2-4 h, with a plasma half-life of approximately 5 h. The available evidence support the clinical efficacy of this drug combination, both in term of LDL-cholesterol reduction and cardiovascular risk decrease. Expert opinion: The synergistic action of these two drugs and the efficacy and safety extensively demonstrated of their association (in particular in the large IMProved Reduction of Outcomes: Vytorin Efficacy International Trial -IMPROVE-IT-) promote its clinical use, especially in subjects with high cardiovascular risk who need to optimize their LDL-Cholesterolemia, but also in patients who cannot tolerate high-dose of more powerful statins.

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 (10 mg), phytosterols (800 mg), and L-tyrosol (5 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 (-16.3% vs 9.9%, P < 0.001 always), LDL-C (-23.4% vs -13.2%, P < 0.001 always), and hepatic steatosis index (-2.8%, P < 0.01 vs -1.8%, P < 0.05). Moreover, ALT (-27.7%, P < 0.001), AST (-13.8%, P = 0.004), and serum uric acid (-12.3%, P = 0.005) were reduced by the tested nutraceutical compound both compared to randomization and to placebo, which did not affect these parameters (P < 0.01 for all). Regarding the hemodynamic parameters, there was a decrease of systolic blood pressure (-5.6%) with the active treatment not observed with placebo (P < 0.05 vs baseline and placebo) and endothelial reactivity improved, too (-13.2%, P < 0.001 vs baseline). Consequently, the estimated 10-year cardiovascular risk score improved by 1.19% (SE 0.4%) (P = 0.01) in the nutraceutical-treated patients. CONCLUSION: The tested nutraceutical association is able to improve the positive effects of a Mediterranean diet on a large number of CV risk factors and consequently of the estimated CV risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02492464. FUNDING: IBSA Farmaceutici.

Nutraceutical Effects on Glucose and Lipid Metabolism in Patients with Impaired Fasting Glucose: A Pilot, Double-Blind, Placebo-Controlled, Randomized Clinical Trial on a Combined Product.

INTRODUCTION: A number of natural compounds have individually demonstrated to improve glucose and lipid levels in humans. AIM: To  evaluate the short-term glucose and lipid-lowering activity in subjects with impaired fasting glucose. METHODS: To assess the effects of a combination of nutraceuticals based on Lagerstroemia speciosa, Berberis aristata, Curcuma longa, Alpha-lipoic acid, Chrome picolinate and Folic acid, we performed a double-blind, parallel group, placebo-controlled, randomized clinical trial in 40 adults affected by impaired fasting glucose (FPG = 100-125 mg/dL) in primary prevention of cardiovascular disease. After a period of 2 weeks of dietary habits correction only, patients continued the diet and began a period of 8 weeks of treatment with nutraceutical or placebo. Data related to lipid pattern, insulin resistance, liver function and hsCRP were obtained at the baseline and at the end of the study. RESULTS: No side effects were detected in both groups of subjects. After the nutraceutical treatment, and compared to the placebo-treated group, the enrolled patients experienced a significant improvement in TG (-34.7%), HDL-C (+13.7), FPI (-13.4%), and HOMA-Index (-25%) versus the baseline values. No significant changes were observed in the other investigated parameters in both groups (Body Mass Index, LDL-C, hsCRP). CONCLUSIONS: The tested combination of nutraceuticals showed clinical efficacy in the improvement of TG, HDL-C, FPI and HOMA-Index, with an optimal tolerability profile. Further confirmation is needed to verify these observations on the middle and long term with a larger number of subjects.