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 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.

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.

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.

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.

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.

Effects of a Combined Nutraceutical on Lipid Pattern, Glucose Metabolism and Inflammatory Parameters in Moderately Hypercholesterolemic Subjects: A Double-blind, Cross-over, Randomized Clinical Trial.

BACKGROUND: There is an increasing interest for combined nutraceuticals that can act on several points of lipid and glucose metabolism with preventive purposes. However, the simple assemblage of nutraceuticals with potentially additive mechanism of action need to be clinically tested. METHODS: To assess the effects of a combination of nutraceuticals based on artichoke, red yeast rice, banaba, and coenzyme Q10, we performed a double bind, cross-over designed trial versus placebo in 30 adults with LDL cholesterol suboptimal in primary prevention of cardiovascular disease. After a period of 3 weeks of dietary habits correction, patients began a period of 6 weeks of treatment with nutraceutical or placebo, followed by 2 weeks of washout and finally 6 weeks in cross-over. Data related to lipid pattern, insulin resistance, renal function, liver and CPK have been obtained at each visit. RESULTS: In particular, the after the nutraceutical treatment the enrolled patients experienced a significant improvement in total cholesterol (-13.6 %), LDL-C (-18.2 %), non-HDL-C (-15 %), glutamic oxaloacetic transaminase (-10 %), glutamate-pyruvate transaminase (-30.9 %), and hs-CRP (-18.2 %) versus placebo. No changes have been observed in the other investigated parameters in both groups. CONCLUSIONS: The tested combination of nutraceuticals has shown clinical efficacy in the reduction of total cholesterol, non-HDL, LDL and triglycerides, while improving the level of liver transaminases and high sensitivity C-reactive protein. Further confirmation are needed to verify these observations on the middle and long term with a larger number of subjects.

Additional therapy for cholesterol lowering in ezetimibe-treated, statin-intolerant patients in clinical practice: results from an internal audit of a university lipid clinic.

OBJECTIVE: The aim of our study was to evaluate the tolerability and efficacy of alternative approaches to improve cholesterolemia control in patients with statin-related myalgia treated with ezetimibe. RESEARCH DESIGN AND METHODS: We retrospectively evaluated 3534 Clinical Report Forms (CRFs) filled in the period June 2012-June 2015 for first visits to the lipid clinic of the University of Bologna. For this study, we selected 252 CRFs based on the following criteria: statin-related myalgia, previous failed treatment with at least two low-dosed statins, well tolerated treatment with ezetimibe. Then, the following lipid-lowering treatments were added in order to improve the ezetimibe low density lipoprotein cholesterol (LDL-C) lowering efficacy, based on clinical judgment: fenofibrate 145 mg, rosuvastatin 5 mg 1 tablet/week, rosuvastatin 5 mg 2 tablets/week, red yeast rice (standardized in monacolin K 3 mg) + berberine 500 mg, berberine 500 mg b.i.d., phytosterols 900 mg + psyllium fiber 3.5 g b.i.d. Patients continuing to claim a tolerable myalgia were then treated with coenzyme Q10 nanoemulsions 200 mg/day. RESULTS: The treatment with standard lipid-lowering diet plus ezetimibe alone was associated with a mean LDL-C reduction of 17 ± 2%. The additive LDL-lowering effect with the various tested treatment was: -16 ± 2% with fenofibrate 145 mg/day, -13 ± 1% with rosuvastatin 5 mg 1 tablet/week, -17 ± 3% with rosuvastatin 5 mg 2 tablets/week, -19 ± 4% with red yeast rice + berberine, -17 ± 4% with berberine b.i.d. and -10 ± 3% with phytosterols + psyllium b.i.d.; 11% of the patients treated with fenofibrate required treatment modification because of myalgia recurrence, while the percentage was negligible for the other tested treatments. In patients with residual tolerable myalgia, treatment with coenzyme Q10 for 8 weeks was associated with a mean improvement of the graduated myalgia score from 4.8 ± 1.9 to 2.9 ± 1.3 (p = 0.013). CONCLUSIONS: Some alternative treatments seems to be effective and well tolerated, thus improving the ezetimibe effect on cholesterolemia.

Omega 3 polyunsaturated fatty acids supplementation and blood pressure levels in hypertriglyceridemic patients with untreated normal-high blood pressure and with or without metabolic syndrome: a retrospective study.

Recent evidence suggests that at least a part of the polyunsaturated fatty acids (PUFAs) heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. We retrospectively evaluated the long-term effect of a PUFA supplementation on the blood pressure level of 111 hypertriglyceridemic subjects with untreated normal-high blood pressure that were prescribed a 2 grams PUFA supplementation in order to improve their plasma lipid pattern. After 12 months of treatment, systolic blood pressure (SBP) meanly decreased by 2.7 +/- 2.5 mmHg (p = 0.001) and diastolic blood pressure (DBP) by 1.3 +/- 3.3 mmHg (p < 0.001), while basal heart rate decreased by 4.0 +/- 4.4 bpm (p < 0.001). Both SBP and DBP reduction were significantly related to the baseline SBP (p < 0.001) and DBP (p < 0.001), respectively. Diastolic blood pressure change was also inversely related to the patient's age (p = 0.004). No significant difference was perceived in the metabolic syndrome subgroup. In our retrospective study, highly purified omega-3 PUFA long-term supplementation is associated with a significant reduction in SBP, DBP, Pulse pressure (PP), and basal heart rate in hypertriglyceridemic patients with normal-high blood pressure. No significant difference was perceived in the metabolic syndrome subgroup. The main determinants of the PUFA anti-hypertensive effect appear to be the basal blood pressure level and age.

Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial.

In the setting of a six-month, open-label clinical trial, 141 consecutively enrolled, hypertensive, overweight patients were randomized to the oral ingestion of psyllium powder or guar gum 3.5 gr t.i.d., to be taken 20 min before the main two meals, or to standard diet. Both fibers improved significantly BMI, FPG, FPI, HOMA Index, HbA1c, LDL-C, and ApoB. Psyllium supplementation only exerted a significant improvement in plasma TG concentration, in SBP and DBP. In our study, six-month supplementation with psyllium fiber, but not with guar fiber nor standard diet, appears to significantly reduce both SBP and DBP in hypertensive overweight subjects.