Nutraceutical approach to Non-alcoholic fatty liver disease (NAFLD): the available clinical evidence.

Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of Salvia milthiorriza, and probiotics. In conclusion, Silymarin, vitamin E and vitamin D, polyunsaturated fatty acids of the omega-3 series, coenzyme Q10, berberine and curcumin, if well dosed and administered for medium\u2013long periods, and associated to lifestyle changes, could exert positive effects on NAFLD and NAFLD-related parameters. View Full-Tex

Application of a new processing method to post-LDL-apheresis data.

Our aim was to elaborate a method to optimise treatment intervals for the individual low-density lipoprotein (LDL)-apheresis treated patients. After each treatment, plasma LDL concentrations show a time-related increase with a decreasing speed until a maximum level.We searched to interpret the post- LDL-apheresis experimental data trend as the physical process that produces the observed curve, so that the fitting presupposed theoretical function is a direct consequence of the physic process, because to establish the better time. Applying the proposed fitting method to a succession of 15 samples obtained from the mean of six plasmapheresis executed on five different subjects, small estimate standard error (5 mg/dl) and relative error (1.7%) with a dispersion evidently related to the experimental error were observed. Obviously, applying the same method to a single case, the dispersion is more marked (relative error ,5%), with a SE of 10–13 mg/dl, even though the aspect of a casual phenomenon is conserved. Our physical interpretation appears to be a practical model to predict the LDL-rebound kinetic of the single patient

A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice

Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively investigated the persistence on therapy and the extent of blood pressure (BP) control in 347 hypertensive patients (age 59.4 +/- 6 years) randomly allocated to a first-line treatment with: angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), beta-blockers, angiotensin-II receptor blockers (ARBs), or diuretics and followed-up for 24-months. Persistence on treatment was higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs CCBs (51.6%; p < 0.05), beta-blockers (44.8%, p < 0.05), and diuretics (34.4%, p < 0.01). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs (59.3% vs 46.6%, p < 0.05). Systolic and diastolic BP was decreased more successfully in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) compared with beta-blockers (-4.0/-2.3 mmHg p < 0.05) and diuretics (-2.3/-2.1 mmHg, p < 0.05). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class. A trend toward a better BP control was observed in response to lercanidipine vs other CCBs (p = 0.059). The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice

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

The Effect of Maintenance Treatment with Erdosteine on Exacerbation Treatment and Health Status in Patients with COPD: A Post-Hoc Analysis of the RESTORE Dataset.

Purpose: To explore the effect of erdosteine on COPD exacerbations, health-related quality of life (HRQoL), and subjectively assessed COPD severity. Patients and methods: This post-hoc analysis of the RESTORE study included participants with COPD and spirometrically moderate (GOLD 2; post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV1 30‒49% predicted; n = 191) who received erdosteine 300 mg twice daily or placebo added to usual maintenance therapy for 12 months. Antibiotic and oral corticosteroid use was determined together with patientreported HRQoL (St George’s Respiratory Questionnaire, SGRQ). Patient and physician subjective COPD severity scores (scale 0‒4) were rated at baseline, 6 and 12 months. Data were analyzed using descriptive statistics for exacerbation severity, COPD severity, and treatment group. Comparisons between treatment groups used Student’s t-tests or ANCOVA as appropriate. Results: Among GOLD 2 patients, 43 of 126 erdosteine-treated patients exacerbated (7 moderate-to-severe exacerbations), compared to 62 of 128 placebo-treated patients (14 moderate-to-severe exacerbations). Among those with moderate-to-severe exacerbations, erdosteine-treated patients had a shorter mean duration of corticosteroid treatment (11.4 days vs 13.3 days for placebo, P = 0.043), and fewer patients required antibiotic treatment with/without oral corticosteroids (71.4% vs 85.8% for placebo, P < 0.001). Erdosteine-treated GOLD 2 patients who exacerbated showed significant improvements from baseline in SGRQ total scores and subjective disease severity scores (patient- and physician-rated), compared with placebo-treated patients regardless of exacerbation severity. Among GOLD 3 patients, there were no significant differences between treatment groups on any of these measures. Conclusion: Adding erdosteine to the usual maintenance therapy of COPD patients with moderate airflow limitation reduced the number of exacerbations, the duration of treatment with corticosteroids and the episodes requiring treatment with antibiotics. Additionally, treatment with erdosteine improved HRQoL and patient-reported disease severity

Clinical evidence of efficacy of red yeast rice and berberine in a large controlled study versus diet

Efficacy of a new patented proprietary combination of natural nutraceuticals (PN) containing natural hypolipidemic as red yeast, policosanol and berberine was tested in a large study on dyslipidemic patients in clinical practice. A parallel, controlled, randomized, multicenter study was designed. After 2 weeks on a stable dietary regimen, the patients were randomized to PN 1 tablet/day associated with diet (PN + D) or diet alone (D) for 16 weeks. Entry criteria were: Tot-Chol >200 mg/dL or LDL-Chol >150 mg/dL without a clear indication for statins, or plasma triglycerides >150 mg/dL. Lipid pattern and CV parameters were evaluated at baseline and monthly. 1,751 patients were enrolled in 248 Italian units, 933 patients on PN + D and 818 on D. The baseline lipid values were: Tot-Chol 255.4 versus 243.1 mg/dL, LDL-Chol 170.1 versus 162.2 mg/dL, HDL-Chol 50.0 versus 48.8 mg/dL, and TG 190.5 versus 184.4 mg/dL. PN constantly and significantly improved lipid parameters versus D group: at 16 weeks −19.1 versus −9.4% for Tot-Chol (p < 0.001), −23.5 versus −10.8% for LDL-Chol (p < 0.001), +11.6 versus +4.0% for HDL-Chol (p < 0.001), −17.9 versus −11.3% for TG (p < 0.001). In conclusions, PN plus diet allows an effective improvement of blood lipids with a significant reduction of global CV risk, suggesting a role for PN in CHD prevention

Cost effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post- hoc analysis of the smile-4 study.

BACKGROUND: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. METHODS: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. RESULTS: Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%-49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). CONCLUSION: Zofenopril is a viable and cost-effective treatment for managing patients with left ventricular dysfunction after acute myocardial infarction

effects of one year treatment of sibutramine on insulin resistance parameters in type 2 diabetic patients

Purpose. Comparison of the effects of one year treatment with sibutramine compared to placebo on body weight, glycemic control, lipid profile, and insulin resistance parameters in type 2 diabetic patients. Methods. Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP). Results. We observed a faster improvement of HbA1c, FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups. Conclusions. Sibutramine gave a faster improvement of glycemic control, and of insulin resistance parameters compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight

PCSK9 induces a pro-inflammatory response in macrophages.

Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250\u2009\uf7\u20092.5\u2009\ub5g/ml) of human recombinant PCSK9 (hPCSK9). After 24\u2009h incubation with 2.5\u2009\ub5g/ml PCSK9, a significant induction of IL-1\u3b2, IL-6, TNF-\u3b1, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-\u3b1 (2.4\u2009\ub1\u20090.5 fold) and IL-1\u3b2 (8.6\u2009\ub1\u20091.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-\u3b1 mRNA in murine LDLR-/- bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3\u2009\ub1\u20091.6 fold vs 31.1\u2009\ub1\u20096.1 fold for LDLR-/- and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-\u3b1 plasma levels of healthy adult subjects (males 533, females 537) was observed (B\u2009=\u20098.73, 95%CI 7.54\u2009\uf7\u20099.93, p\u2009&lt;\u20090.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR