Health-Related Quality of Life in Patients Living with Wilson Disease in Spain: A Cross-Sectional Observational Study.

Wilson disease (WD) is a rare copper metabolism disorder caused by mutations in the ATP7B gene. It usually affects young individuals and can produce hepatic and/or neurological involvement, potentially affecting health-related quality of life (HRQoL). We assessed HRQoL in a cohort of Spanish patients with WD and evaluated disease impact on several domains of patients' lives, treatment adherence, drug preference and satisfaction, and healthcare resource utilisation in a cross-sectional, retrospective, multicentric, observational study. A total of 102 patients were included: 81.4% presented isolated liver involvement (group H) and 18.6% presented neurological or mixed involvement (group EH). Up to 30% of patients reported a deteriorated emotional status with anxiety and depression, which was greater in the EH subgroup; the use of neuropsychiatric drugs was high. Over 70% of the patients were satisfied with their current treatment but complained about taking too many pills, stating they would consider switching to another more patient-friendly treatment if available. The Simplified Medication Adherence Questionnaire revealed only 22.5% of patients were fully adherent to therapy, suggesting that alternative therapies are needed. This real-world study, even though is highly enriched with hepatic patients and mild disease, shows that WD impacts patients' HRQoL, especially in the emotional domain.

Stool-fermented Plantago ovata husk induces apoptosis in colorectal cancer cells independently of molecular phenotype.

Several studies have suggested that the partially fermentable fibre Plantago ovata husk (PO) may have a protective effect on colorectal cancer (CRC). We studied the potentially pro-apoptotic effect of PO and the implicated mechanisms in CRC cells with different molecular phenotypes (Caco-2, HCT116, LoVo, HT-29, SW480) after PO anaerobic fermentation with colonic bacteria as it occurs in the human colon. The fermentation products of PO induced apoptosis in all primary tumour and metastatic cell lines, independent of p53, adenomatous polyposis coli, ß-catenin or cyclo-oxygenase-2 status. Apoptosis was caspase-dependent and both intrinsic and extrinsic pathways were implicated. The intrinsic pathway was activated through a shift in the balance towards a pro-apoptotic environment with an up-regulation of B-cell lymphoma protein 2 homologous antagonist killer (BAK) and a down-regulation of B-cell lymphoma-extra large (Bcl-xL) seen in HCT116 and LoVo cells. This resulted in mitochondrial membrane depolarisation, increased expression of caspase activators second mitochondria-derived activator of caspases (Smac)/Diablo, death effector apoptosis-inducing factor, apoptosome member apoptotic protease activating factor 1 and down-regulation of inhibitors of apoptosis Survivin and X-linked inhibitor of apoptosis in most cells. The extrinsic pathway was activated presumably through the up-regulation of death receptor (DR5). Some important differences were seen between primary tumour and metastatic CRC cells. Thus, metastatic PO-treated LoVo cells had a remarkable up-regulation of TNF-α ligand along with death-inducing signalling complex components receptor interacting protein and TNF-α receptor 1-associated death domain protein. The extrinsic pathway modulator FCICE-inhibitory protein (FLIP), an inhibitor of both spontaneous death ligand-independent and death receptor-mediated apoptosis, was significantly down-regulated after PO treatment in all primary tumour cells, but not in metastatic LoVo. These findings suggest that PO could potentially be a useful chemotherapy adjuvant.

Gene expression analysis of a human enterocyte cell line reveals downregulation of cholesterol biosynthesis in response to short-chain fatty acids.

It has been suggested that the short-chain fatty acids (SCFAs) produced by anaerobic bacterial intestinal fermentation of soluble fiber may regulate lipid metabolism in intestine, thus reducing plasma cholesterol levels. However, the exact mechanism of action of SCFAs in lowering cholesterol levels is not fully understood. The aims of this study were to test the effects of SCFAs on gene expression in a human enterocyte cell line Caco-2/TC-7 and to validate microarray data by real-time PCR. Human Caco-2/TC-7 enterocytes were cultured on transwell filter inserts and incubated with the SCFAs acetate (Ac), propionate (Pr), and butyrate (Bu). Total RNA was then isolated for microarrays and quantitative real-time PCR analysis. Treatment of human enterocytes with Pr and Bu affects a wide variety of genes. These genes were classified according to the PANTHER classification system, and the results showed that different biological processes and metabolic pathways were modified by Pr and Bu treatment, including the intestinal cholesterol biosynthesis pathway. Differential array expression analysis showed that nine genes were downregulated in this pathway, and these results were validated by real-time PCR. This in vitro study allowed us to identify a wide variety of biological processes and metabolic pathways affected by the SCFAs tested. Importantly, our results show that the global effect of Pr and Bu is to downregulate the expression of nine key genes involved in intestinal cholesterol biosynthesis, thus possibly inhibiting this pathway.

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.

Effects of soluble fiber (Plantago ovata husk) on plasma lipids, lipoproteins, and apolipoproteins in men with ischemic heart disease.

BACKGROUND: New dietary strategies to reduce cardiovascular disease (CVD) risk include the addition of fiber to the diet. The effect of soluble-fiber consumption derived from Plantago ovata husk on lipid risk factors in patients with CVD is unknown. OBJECTIVE: We compared the effects of soluble fiber (P. ovata husk) with those of insoluble fiber (P. ovata seeds) on plasma lipid, lipoprotein, and apolipoprotein (apo) concentrations within a CVD secondary prevention program. DESIGN: In a randomized, crossover, controlled, single-blind design, 28 men with CVD (myocardial infarction or stable angina) and an LDL-cholesterol concentration

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.

A new look at an old drug for the treatment of cancer cachexia: megestrol acetate.

Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation, being often associated with anorexia. The aim of the present review is to examine the impact of megestrol acetate in the treatment of cancer cachexia, both at the biochemical and physiological level taking into account new experimental data related to protein muscle metabolism. Based on experimental evidence, it is concluded that megestrol acetate is a good candidate for muscle wasting treatment and future studies addressed at the interaction between the drug and protein turnover in human skeletal muscle should be performed.

Polymorphisms in LEP and NPY genes modify the response to soluble fibre Plantago ovata husk intake on cardiovascular risk biomarkers.

The satiating effect of fibre consumption has been related to gut hormones, such as peptide YY and leptin. These peptides may also influence cardiovascular (CVD) risk biomarkers. Nevertheless, there is wide interindividual variation in metabolic responses to fibre consumption. The objective was to investigate differences in the effects of soluble fibre, in the form of Plantago ovata husk (Po-husk) treatment, on CVD risk biomarkers according to selected polymorphisms in genes related to satiety. The study was a multi-centred, double-blind, placebo-controlled, parallel and randomised trial in mild-moderate hypercholesterolaemic patients (age range: 43-67 years). Eight polymorphisms in three genes related to satiety (LEP, NPY and PYY) were identified in 178 participants; 88 patients in the placebo (microcrystalline cellulose 14 g/day) group and 90 in the Po-husk (14 g/day) group, which had added to a low-saturated-fat diet for 8 weeks. The CVD biomarkers measured included the following: lipid profile, blood pressure (BP), glucose, insulin, hs-CRP, oxidised LDL and IL-6. Relative to the placebo, Po-husk consumption lowered the plasma total cholesterol concentration by 3.3 % according to rs7799039 polymorphism in the LEP gene (p < 0.05). Furthermore, the Po-husk reduced systolic BP (mean [95 % CI]) by -8 mmHg (-14.16; -1.90) and hs-CRP by 24.9 % in subjects with the AA genotype of the rs16147 polymorphism in the NPY gene (32 % of our total population; p < 0.05), which remained significant after Bonferroni correction. In conclusion, polymorphisms in the LEP and NPY genes potentiate the response to Po-husk, particularly the effects on systolic BP and the hs-CRP plasma concentration.

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.

Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides, insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial.

UNLABELLED: The objective was to evaluate whether the soluble fibre Plantago ovata (Po)-husk improves cardiovascular disease (CVD) risk biomarkers including low-density lipoprotein cholesterol (LDL-C). METHODS: In a multi-centred, double-blind, placebo-controlled, parallel, randomised trial conducted in primary care-clinics in Spain, France and Holland, mild-moderate hypercholesterolaemic patients (age range: 43-67 years) received 14 g/d of Po-husk (n=126) or placebo (microcrystalline-cellulose 14 g/d; n=128) in a low saturated fat diet for 8 weeks. Subsequently, if LDL-C remained > or = 3.35 mmol/L [130 mg/dL], participants proceeded with the fibre plus simvastatin (20mg/d) for further 8 weeks. Lipid profile, blood pressure (BP), insulin, oxidised LDL and some gene polymorphisms involved in CVD risk were measured. RESULTS: Relative to placebo, Po-husk reduced plasma LDL-C by -6% (P<0.0002), total cholesterol (TC) by -6%, triglycerides (TG) by -21.6%, apolipoprotein (Apo) B-100 by -6.7%, oxidised LDL by a mean of -6.82 U/L (95%CI: 3.15-10.48), insulin by -4.68 pmol/L (95%CI: 0.68-8.67) and systolic BP by -4.0mm Hg (95%CI; 1.2-6.7) (P<0.05). The TG-lowering effect in the Po-husk group was magnified by variants in plasminogen-activator-inhibitor (PAI-1; rs1799768) and fatty acid-binding protein (FABP-2; rs1799883) genes. At 16 weeks, the intra-group action of simvastatin (20mg/d) added to Po-husk or placebo was a similar LDL-C reduction. CONCLUSIONS: Po-husk, apart from lowering LDL-C, also reduced TG, TG related to certain gene variants, TC, Apo B-100, oxLDL, insulin-resistance and systolic BP in mild-moderate hypercholesterolaemic individuals. Thus, the target patients to receive Po-husk would be those who present a cluster of various CVD risk factors, such as metabolic syndrome.

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

A controlled, randomized, double-blind trial to evaluate the effect of a supplement of cocoa husk that is rich in dietary fiber on colonic transit in constipated pediatric patients.

OBJECTIVE: Although a diet that is rich in fiber is widely recommended for preventing and treating constipation, the efficacy of fiber supplements have not been tested sufficiently in children. Our aim with this pilot study was to evaluate if fiber supplementation is beneficial for the treatment of children with idiopathic chronic constipation. METHODS: Using a parallel, randomized, double-blind, controlled trial, we conducted an interventional study to evaluate the efficacy of a supplement of cocoa husk rich in dietary fiber on intestinal transit time and other indices of constipation in children with constipation. After screening, the patients were randomly allocated to receive, for a period of 4 weeks, either a cocoa husk supplement or placebo plus standardized toilet training procedures. Before and after 4 weeks of treatment, we (1) performed anthropometry, a physical examination, and routine laboratory measurements, (2) determined total and segmental colonic transit time, (3) evaluated bowel movement habits and stool consistency using a diary, and (4) received a subjective evaluation from the parents regarding the efficacy of the treatment. The main variable for verifying the efficacy of the treatment was the total colonic transit time. RESULTS: Fifty-six chronically constipated children were randomly assigned into the study, but only 48 children completed it. These children, who were aged between 3 and 10 years, had a diagnosis of chronic idiopathic constipation. With respect to total, partial colon, and rectum transit time, there seemed to be a trend, although statistically nonsignificant, toward faster transit times in the cocoa husk group than in the placebo group. When we analyzed the evolution of the intestinal transit time throughout the study of children whose total basal intestinal transit time was > 50th percentile, significant differences were observed between the groups. The total transit time decreased by 45.4 +/- 38.4 hours in the cocoa husk group and by 8.7 +/- 28.9 hours in the placebo group (-38.1 hours). In the case of the right colon, changes in transit time also were significant between groups. Mean changes tended toward faster transit times in the left colon and the rectum, although the differences were not statistically significant. The children who received cocoa husk supplements tended to increase the number of bowel movements by more than that of the children of the placebo group. We also observed a reduction in the percentage of patients who reported hard stools (hard scybalous or pebble-like stools), although this reduction was significantly greater in the cocoa husk group. At the end of the intervention, 41.7% and 75.0% of the patients who received cocoa husk supplementation or placebo, respectively, reported having hard stools. Moreover, a significantly higher number of children (or their parents) reported a subjective improvement in stool consistency. No significant adverse effects were reported during the study. CONCLUSIONS: This study confirms the beneficial effect of a supplement of cocoa husk that is rich in dietary fiber on chronic idiopathic constipation in children. These benefits seem to be more evident in pediatric constipated patients with slow colonic transit time.

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.