Effects of a nutraceutical combination containing berberine (BRB), policosanol, and red yeast rice (RYR), on lipid profile in hypercholesterolemic patients: A meta-analysis of randomised controlled trials / Efectos de la combinación de productos nutricéuticos con berberina, policosanol y arroz de levadura roja en el lipidograma de pacientes con hipercolesterolemia: un metaanálisis de ensayos clínicos aleatorizados

Background and aim: A nutraceutical combination containing berberine, policosanol, and red yeast rice, largely marketed in Europe (Armolipid Plus®) (AP), has been reported to induce significant improvements in plasma lipids, insulin resistance and other components of the metabolic syndrome. However, literature study designs and results were heterogeneous and it was thus necessary to systematically review and meta-analyse all relevant randomised clinical trials (RCTs) to explore and quantify the effects of the dietary supplement AP on lipid profile. The aim of our meta-analysis was the evaluation of the effect of AP on lipid profile. Methods and results: We conducted a structures search on PubMed and Google Scholar to identify eligible articles published prior to 2015. Eleven RCTs were subjected to meta-analysis by means of random effects models using the Standardised Mean Differences approach (Hedges’ method) and the Mean Differences approach as a sensitivity analysis. Data from 11 randomised clinical trials, corresponding to 1970 nutraceutical combination and 1954 control patients (3924 total patients), were included after the peer evaluation and data extraction of two independent evaluators. Heterogeneity was significant in all models. A significant effect was found for all lipid parameters. The effect size (relative change from baseline (%)) was -1.3 (9.9%) for total cholesterol, -1.17 (-13.7%) for LDL-c, +0.17 (+3.7%) for HDL-c and -0.24 (-7.0%) for Triglycerides. Conclusion: This meta-analysis confirms that the nutraceutical combination containing berberine, policosanol, and red yeast rice has shown to be an effective product for the improvement of the lipid profile

Antecedentes y objetivos: Se ha observado que una combinación de productos nutricéuticos con berberina, policosanol y arroz de levadura roja, altamente comercializada en Europa (Armolipid Plus®) (AP), induce mejoras significativas del lipidograma, resistencia a la insulina y otros componentes del síndrome metabólico. Sin embargo, los diseños y resultados del estudio de la literatura fueron heterogéneos y por tanto es necesario realizar una revisión y metaanálisis sistemático de todos los ensayos clínicos aleatorizados (ECA) relevantes para explorar y cuantificar los efectos del suplemento dietético AP en el lipidograma. El objetivo de nuestro metaanálisis fue la evaluación del efecto de AP en el lipidograma. Métodos y resultados: Se llevó a cabo una búsqueda estructurada en PubMed y Google Scholar para identificar los artículos aptos para publicación antes del 2015. Se sometieron once ECA a metaanálisis por medio de modelos de efectos aleatorios utilizando el enfoque de diferencias medias estandarizadas (método Hedges) y el enfoque de diferencias medias estandarizadas como análisis de la sensibilidad. Los datos de los once ensayos clínicos aleatorizados, correspondientes a 1970 pacientes con combinación de productos nutricéuticos y 1954 pacientes de control (3924 pacientes en total), se incluyeron después de la evaluación científica externa y la extracción de datos de dos evaluadores independientes. La heterogeneidad fue significativa en todos los modelos. Se encontró un efecto significativo para todos los parámetros lipídicos. El tamaño del efecto (cambio relativo conforme a los valores de referencia, %) fue de -1,3 (9,9%) para el colesterol total, -1,17 (-13,7%) para el colesterol LDL, +0,17 (+3,7%) para el colesterol HDL y de -0,24 (-7%) para los triglicéridos. Conclusión: Este metaanálisis confirma que la combinación de productos nitrucéuticos con berberina, policosanol y arroz de levadura roja es un producto eficaz para la mejora del lipidograma

Effects of a nutraceutical combination containing berberine (BRB), policosanol, and red yeast rice (RYR), on lipid profile in hypercholesterolemic patients: A meta-analysis of randomised controlled trials.

BACKGROUND AND AIM: A nutraceutical combination containing berberine, policosanol, and red yeast rice, largely marketed in Europe (Armolipid Plus(®)) (AP), has been reported to induce significant improvements in plasma lipids, insulin resistance and other components of the metabolic syndrome. However, literature study designs and results were heterogeneous and it was thus necessary to systematically review and meta-analyse all relevant randomised clinical trials (RCTs) to explore and quantify the effects of the dietary supplement AP on lipid profile. The aim of our meta-analysis was the evaluation of the effect of AP on lipid profile. METHODS AND RESULTS: We conducted a structures search on PubMed and Google Scholar to identify eligible articles published prior to 2015. Eleven RCTs were subjected to meta-analysis by means of random effects models using the Standardised Mean Differences approach (Hedges' method) and the Mean Differences approach as a sensitivity analysis. Data from 11 randomised clinical trials, corresponding to 1970 nutraceutical combination and 1954 control patients (3924 total patients), were included after the peer evaluation and data extraction of two independent evaluators. Heterogeneity was significant in all models. A significant effect was found for all lipid parameters. The effect size (relative change from baseline (%)) was -1.3 (9.9%) for total cholesterol, -1.17 (-13.7%) for LDL-c, +0.17 (+3.7%) for HDL-c and -0.24 (-7.0%) for Triglycerides. CONCLUSION: This meta-analysis confirms that the nutraceutical combination containing berberine, policosanol, and red yeast rice has shown to be an effective product for the improvement of the lipid profile.

Effects of poly-bioactive compounds on lipid profile and body weight in a moderately hypercholesterolemic population with low cardiovascular disease risk: a multicenter randomized trial.

UNLABELLED: A dietary supplement (AP, Armolipid Plus) that combines red yeast rice extract, policosanol, berberine, folic acid, coenzyme Q10 and asthaxantine can have beneficial effects on cardiovascular disease (CVD) biomarkers. The aim of this study was to assess whether the intake of AP, in combination with dietary recommendations, reduces serum low density lipoprotein cholesterol (LDL-c) concentrations and other CVD biomarkers in patients with hypercholesterolemia. Eligible patients were recruited from the outpatient clinics of six Spanish hospitals Hospital Virgen del Rocío (Sevilla); Hospital San Jorge (Huesca); Hospital San Pedro (Logroño); Hospital Gregorio Marañón (Madrid), Hospital la Fe (Valencia) and Hospital Universitari Sant Joan (Reus) as recruiting and coordinating center. 102 participants (mean age ± SD; 50.91 ± 11.61; 32 men) with low CVD, with mild-to-moderately elevated LDL-c (between 3.35 mmol/L and 4.88 mmol/L) without hypolipemic therapy were randomized in a double-blind, parallel, controlled, multicenter trial commencing January 2012 and ending December 2012. Among the exclusion criteria were any concomitant chronic disease, triglycerides (TG) >3.97 mmol/L, pregnant or lactating, and history of CVD. At 12 weeks, compared to placebo, AP reduced LDL-c by -6.9%, apolipoprotein (Apo) B-100 by -6.6% and total cholesterol/HDL-c ratio by -5.5%, the ApoB/ApoA1 ratio by -8.6%, while increasing ApoA1 by +2.5% (p<0.05). AP consumption was associated with modest mean weight loss of -0.93 kg (95%CI: -1.74 to -0.12; P = 0.02) compared with control group while dietary composition remained unchanged in the AP group. The AP product was well tolerated. In conclusion, AP, combined with dietary recommendations, reduced LDL-c levels as well as total cholesterol/HDL-c and ApoB/ApoA1 ratios, while increasing Apo A1, all of which are improvements in CVD risk indicators. AP is a product which could benefit patients having moderate hyperlipidemia and excess body weight. TRIAL REGISTRATION: ClinicalTrials.gov NCT01562080.

Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.

UNLABELLED: DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process. TRIAL REGISTRATION: Clinicaltrials.govNCT00511420 and NCT00502047.

[Low doses of megestrol acetate increase weight and improve nutrition status in patients with severe chronic obstructive pulmonary disease and weight loss]. / Dosis bajas de acetato de megestrol aumentan el peso y mejoran la nutrición de los pacientes con enfermedad pulmonar obstructiva crónica grave y pérdida de peso.

BACKGROUND AND OBJECTIVE: Weight loss in patients with severe chronic obstructive pulmonary disease (COPD) is a prognostic bad factor. The objective of this study is to analyze the effectively of megestrol acetate (MA) to increase appetite of these patients. PATIENTS AND METHODS: Randomized double blind placebo controlled trial to study the effect of 160 mg/bid of MA, for 8 weeks, on nutritional, functional, analytical and quality of life parameters, in 38 patients with severe COPD and body mass index (BMI) < 21 kg/m(2), or between 21-25 with involuntary weight loss of 5% in the last 3 months. RESULTS: At 8 weeks, in the MA group the body weight increased (2.3 kg) with respect to the control group (0.1 kg) (p<0.04). MA improved significantly the triceps skin-fold thickness (p < 0.04), prealbumin (p<0.004), lymphocytes (p<0.0006), C3 (p<0.04), PCO(2) (p<0.007) and bicarbonate levels (p<0.008). MA did not increase the MRC and SGRQ scales, the distance of 6 MWT nor BODE index. The IL-6 and TNF alpha levels were not modified in the MA group, but leptin did increase (p<0.043). MA improved the sense of wellbeing (p<0.02) and the appetite (p<0.008), compared to the control group. Adverse effects were similar in both groups. CONCLUSIONS: MA safely increases the body weight and the appetite in severe COPD patients with weight loss. MA improves blood gases and nutritional parameters and the sense of wellbeing, but it does not improve the respiratory muscular function or exercise tolerance.

Plantago ovata husks-supplemented diet ameliorates metabolic alterations in obese Zucker rats through activation of AMP-activated protein kinase. Comparative study with other dietary fibers.

BACKGROUND & AIMS: Our aim was to compare the effects of intake of diets supplemented with different dietary fibers, namely cellulose, methylcellulose or Plantago ovata husks, (insoluble, soluble non-fermentable, and soluble fermentable fiber, respectively), on the abnormalities clustered in the metabolic syndrome. METHODS: Adult obese Zucker rats were distributed in four groups which were fed respectively a standard, a cellulose-supplemented, a methylcellulose-supplemented or a P. ovata husks-supplemented diet, for ten weeks. RESULTS: Increased body weight, hyperlipidemia, hyperinsulinemia and hyperleptinemia, increased TNF-alpha and reduced adiponectin secretion by adipose tissue found in obese Zucker rats were significantly improved in obese rats fed the P. ovata husks-supplemented diet, together with a lower hepatic lipid content which parallels activation of the signaling pathway of AMP-protein kinase in the liver. The methylcellulose-supplemented diet reduced body weight, hyperlipidemia, circulating free fatty acids concentration and ameliorated adipose tissue secretion of adiponectin and TNF-alpha. Feeding with the cellulose-supplemented diet only reduced free fatty acids circulating levels. CONCLUSIONS: The soluble dietary fibers essayed are more beneficial than insoluble fiber in the treatment of metabolic syndrome, being the soluble and fermentable the more efficient to improve metabolic alterations. Fermentation products of P. ovata husks must play an important role in such effects.

Effect of two doses of a mixture of soluble fibres on body weight and metabolic variables in overweight or obese patients: a randomised trial.

The aim of the study was to compare the effect of the administration of a mixture of fibres on body weight-loss, satiety, lipid profile and glucose metabolism. We included 200 overweight or obese patients in a parallel, double-blind, placebo-controlled clinical trial, who were randomised to receive, in the context of an energy-restricted diet for a period of 16 weeks, a mixed fibre dose (3 g Plantago ovata husk and 1 g glucomannan) twice (b.i.d. group) or three times daily (t.i.d. group) or placebo. Weight change was the primary efficacy endpoint. Satiety, dietary compliance, lipid profile, glucose tolerance, insulin resistance and high-sensitivity C-reactive protein were secondary endpoints. Weight loss tended to be higher after both doses of fibre (-4.52 (SD 0.56) and -4.60 (SD 0.55) kg) than placebo (-0.79 (SD 0.58) kg); the differences in changes between groups were not statistically significant. Postprandial satiety increased in both fibre groups compared to the placebo. The differences between groups in LDL-cholesterol levels were significant (P = 0.03), with greater reductions in the two fibre-supplemented groups (-0.38 (SD 0.10) and -0.24 (SD 0.09) mmol/l in the b.i.d. and t.i.d. groups v. -0.06 (SD 0.09) mmol/l in placebo group). A similar pattern was observed for changes in total cholesterol:HDL-cholesterol and HDL-cholesterol:LDL-cholesterol ratios. Interventions were well tolerated and had no effects on HDL-cholesterol, glucose and insulin concentrations, glucose tolerance or high-sensitivity C-reactive protein. In conclusion, a 16-week dietary supplement of soluble fibre in overweight or obese patients was well tolerated, induced satiety and had beneficial effects on some CVD risk factors, the most important of which was a significant decrease in plasma LDL-cholesterol concentrations.

A diet supplemented with husks of Plantago ovata reduces the development of endothelial dysfunction, hypertension, and obesity by affecting adiponectin and TNF-alpha in obese Zucker rats.

The aim of the present study was to analyze whether consumption of a fiber-supplemented diet containing 3.5% Plantago ovata husks prevented many of the abnormalities clustered in the metabolic syndrome, including obesity, dyslipidemia, hypertension and endothelial dysfunction. For this purpose, obese Zucker rats, a model of type 2 diabetes, and their lean littermates were studied. Rats consumed a standard control diet or that diet supplemented with 3.5% P. ovata husks for 25 wk. Body weights were measured weekly. Systolic blood pressure (SBP) was measured monthly. At the end of the treatment, plasma concentrations of triglycerides, total cholesterol, FFAs, glucose, insulin, adiponectin, and tumor necrosis factor alpha (TNF-alpha) were determined, and studies on vascular function were performed using aortic rings. Rats fed the P. ovata husk-supplemented diet had a significantly reduced body weight gain compared with those fed the standard diet. Decreased endothelium-dependent relaxation in response to acetylcholine (ACh) by aortic rings from obese Zucker rats was improved in those fed the fiber-supplemented diet. The greater SBP, higher plasma concentrations of triglycerides, total cholesterol, FFA, glucose, insulin, and TNF-alpha, and the hypoadinectinemia that occurred in obese Zucker rats that consumed the control diet were significantly improved in those fed the fiber-supplemented diet. We conclude that intake of a P. ovata husk-supplemented diet prevents endothelial dysfunction, hypertension, and obesity development, and ameliorates dyslipidemia and abnormal plasma concentrations of adiponectin and TNF-alpha in obese Zucker rats.