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Barley β-glucan reduces blood cholesterol levels via interrupting bile acid metabolism
Underlying mechanisms responsible for the cholesterol-lowering effect of β-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barley β-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7α hydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n 30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barley β-glucan or a control diet, each for 5 weeks. Cholesterol absorption was determined by assessing the enrichment of circulating 13C-cholesterol over 96 h following oral administration; fractional rate of synthesis for cholesterol was assessed by measuring the incorporation rate of 2H derived from deuterium oxide within the body water pool into the erythrocyte cholesterol pool over 24 h; bile acid synthesis was determined by measuring serum 7α-hydroxy-4-cholesten-3-one concentrations. Consumption of 3 g HMW β-glucan decreased total cholesterol (TC) levels (P=0·029), but did not affect cholesterol absorption (P=0·25) or cholesterol synthesis (P=0·14). Increased bile acid synthesis after consumption of 3 g HMW β-glucan was observed in all participants (P=0·049), and more pronounced in individuals carrying homozygous G of rs3808607 (P=0·033). In addition, a linear relationship between log (viscosity) of β-glucan and serum 7α-HC concentration was observed in homozygous G allele carriers. Results indicate that increased bile acid synthesis rather than inhibition of cholesterol absorption or synthesis may be responsible for the cholesterol-lowering effect of barley β-glucan. The pronounced TC reduction in G allele carriers of rs3808607 observed in the previous study may be due to enhanced bile acid synthesis in response to high-viscosity β-glucan consumption in those individuals.
Journal Article
Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial
Dyslipidaemia remains a significant risk factor for cardiovascular disease and additional lipid-modifying treatments are warranted to further decrease the cardiovascular disease burden. We assessed the safety, tolerability and efficacy of a novel cholesterol esterase transfer protein (CETP) inhibitor TA-8995 in patients with mild dyslipidaemia.
In this randomised, double-blind, placebo-controlled, parallel-group phase 2 trial, we recruited patients (aged 18–75 years) from 17 sites (hospitals and independent clinical research organisations) in the Netherlands and Denmark with fasting LDL cholesterol levels between 2·5 mmol/L and 4·5 mmol/L, HDL cholesterol levels between 0·8 and 1·8 mmol/L and triglyceride levels below 4·5 mmol/L after washout of lipid-lowering treatments. Patients were randomly allocated (1:1) by a computer-generated randomisation schedule to receive one of the following nine treatments: a once a day dose of 1 mg, 2·5 mg, 5 mg, or 10 mg TA-8995 or matching placebo; 10 mg TA-8995 plus 20 mg atorvastatin; 10 mg TA-8995 plus 10 mg rosuvastatin or 20 mg atorvastatin or 10 mg rosuvastatin alone. We overencapsulated statins to achieve masking. The primary outcome was percentage change in LDL cholesterol and HDL cholesterol from baseline at week 12, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01970215.
Between Aug 15, 2013, and Jan 10, 2014, 364 patients were enrolled. At week 12, LDL cholesterol levels were reduced by 27·4% in patients assigned to the 1 mg dose, 32·7% in patients given the 2·5 mg dose, 45·3% in those given the 5 mg dose, and 45·3% in those given the 10 mg dose (p<0·0001). LDL cholesterol levels were reduced by 68·2% in patients given 10 mg TA-8995 plus atorvastatin, and by 63·3% in patients given rosuvastatin plus 10 mg TA-8995 (p<0·0001). A daily dose of 1 mg TA-8995 increased HDL cholesterol levels by 75·8%, 2·5 mg by 124·3%, 5 mg by 157·1%, and 10 mg dose by 179·0% (p<0·0001). In patients receiving 10 mg TA-8995 and 20 mg atorvastatin HDL cholesterol levels increased by 152·1% and in patients receiving 10 mg TA-8995 and 10 mg rosuvastatin by 157·5%. We recorded no serious adverse events or signs of liver or muscle toxic effects.
TA-8995, a novel CETP inhibitor, is well tolerated and has beneficial effects on lipids and apolipoproteins in patients with mild dyslipidaemia. A cardiovascular disease outcome trial is needed to translate these effects into a reduction of cardiovascular disease events.
Dezima.
Journal Article
The relationship between circulating lipids and breast cancer risk: A Mendelian randomization study
A number of epidemiological and genetic studies have attempted to determine whether levels of circulating lipids are associated with risks of various cancers, including breast cancer (BC). However, it remains unclear whether a causal relationship exists between lipids and BC. If alteration of lipid levels also reduced risk of BC, this could present a target for disease prevention. This study aimed to assess a potential causal relationship between genetic variants associated with plasma lipid traits (high-density lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides, TGs) with risk for BC using Mendelian randomization (MR).
Data from genome-wide association studies in up to 215,551 participants from the Million Veteran Program (MVP) were used to construct genetic instruments for plasma lipid traits. The effect of these instruments on BC risk was evaluated using genetic data from the BCAC (Breast Cancer Association Consortium) based on 122,977 BC cases and 105,974 controls. Using MR, we observed that a 1-standard-deviation genetically determined increase in HDL levels is associated with an increased risk for all BCs (HDL: OR [odds ratio] = 1.08, 95% confidence interval [CI] = 1.04-1.13, P < 0.001). Multivariable MR analysis, which adjusted for the effects of LDL, TGs, body mass index (BMI), and age at menarche, corroborated this observation for HDL (OR = 1.06, 95% CI = 1.03-1.10, P = 4.9 × 10-4) and also found a relationship between LDL and BC risk (OR = 1.03, 95% CI = 1.01-1.07, P = 0.02). We did not observe a difference in these relationships when stratified by breast tumor estrogen receptor (ER) status. We repeated this analysis using genetic variants independent of the leading association at core HDL pathway genes and found that these variants were also associated with risk for BCs (OR = 1.11, 95% CI = 1.06-1.16, P = 1.5 × 10-6), including locus-specific associations at ABCA1 (ATP Binding Cassette Subfamily A Member 1), APOE-APOC1-APOC4-APOC2 (Apolipoproteins E, C1, C4, and C2), and CETP (Cholesteryl Ester Transfer Protein). In addition, we found evidence that genetic variation at the ABO locus is associated with both lipid levels and BC. Through multiple statistical approaches, we minimized and tested for the confounding effects of pleiotropy and population stratification on our analysis; however, the possible existence of residual pleiotropy and stratification remains a limitation of this study.
We observed that genetically elevated plasma HDL and LDL levels appear to be associated with increased BC risk. Future studies are required to understand the mechanism underlying this putative causal relationship, with the goal of developing potential therapeutic strategies aimed at altering the cholesterol-mediated effect on BC risk.
Journal Article
The new American Heart Association cookbook
\"If you want to improve your health or simply maintain it, The New American Heart Association cookbook, Centennial Edition, is for you. This comprehensive resource provides information on grocery shopping strategies, stocking a healthy kitchen, preparing delicious recipes, eating well, meal planning, and much more. This revised edition of the American Heart Association's flagship cookbook offers not only more than 800 recipes-100 of which are all new and 100 refreshed-to satisfy every palate but also provides the most current dietary and lifestyle recommendations. It is the one-stop guide that should be in everyone's kitchen. The new and revised recipes are based on today's flavor profiles; eating preferences, such as Mediterranean and vegetarian; family favorites; and diverse cultural cuisines, as well as popular appliances including the air fryer, slow cooker, and Instant Pot. This edition includes more than 13 categories of scrumptious recipes, including: Mexican Noodle Soup; Korean Cucumber Salad; Seared Jerk Fish with Broiled Asparagus; Sheet Pan Chicken, Sweet Potatoes, and Green Beans; Slow Cooker Pulled Pork Tostadas; Pressure Cooker Five-Spice Beef with Hoisin Sauce; Roasted Vegetable Macaroni and Cheese; Air Fryer Plantains with Lime Crema; Whole-Wheat Sourdough Bread; Mixed Berry Cobbler\"-- Provided by publisher.
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Effect of Torcetrapib on the Progression of Coronary Atherosclerosis
In this 24-month clinical trial, torcetrapib, a cholesteryl ester transfer protein inhibitor, failed to cause regression of coronary atherosclerosis, as seen on intravascular ultrasonography, even though levels of high-density lipoprotein cholesterol were markedly elevated. The drug was also associated with an elevation in blood pressure, and the entire torcetrapib research program has been suspended.
Torcetrapib, a cholesteryl ester transfer protein inhibitor, failed to cause regression of coronary atherosclerosis, even though levels of high-density lipoprotein cholesterol were markedly elevated.
Epidemiologic studies demonstrate an inverse relationship between levels of high-density lipoprotein (HDL) cholesterol and the incidence of cardiovascular disease.
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Limited clinical trials have suggested that an increase in HDL cholesterol levels may reduce the progression of coronary atherosclerosis and decrease cardiovascular morbidity.
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Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester from HDL cholesterol to low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol. Recently, the administration of the CETP inhibitor torcetrapib has been shown to increase HDL cholesterol levels by more than 50%.
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However, the effectiveness of CETP inhibition as a strategy for antiatherosclerotic therapy has . . .
Journal Article
Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk
In a randomized trial, patients with type 2 diabetes, hypertriglyceridemia, and low HDL cholesterol who received pemafibrate did not have fewer cardiovascular events, although some lipid levels decreased.
Journal Article