Effect of Beta-Glucan on Cholesterol Lowering

Effect of Beta-Glucan Molecular Weight and Viscosity on the Mechanism of Cholesterol Lowering in Humans

The primary aim of this study is to determine whether the cholesterol-lowering efficacy of barley b- glucan varied as function of molecular weight (MW) and the total daily amount consumed. Our second aim is to investigate the mechanism responsible for the action, specifically, whether β-glucan lowers circulating cholesterol concentration via inhibiting cholesterol absorption and synthesis. Thirdly, we aim to determine if any gene-diet interactions are associated with cholesterol lowering by barley β-glucan. In addition, we aim to investigate the alteration of the gut microbiota after β-glucan consumption and the correlation between the altered gut microbiota and cardiovascular disease risk factors.

This study consists of four dietary phases which are separated by >28 days wash-out period. During the treatment phase, participants will be provided with all meals for the 35 day period. Breakfast meals will be consumed under the supervision of the research staff and lunch, dinner and snacks will be provided to take home in take-out packaging. While subjects are on the wash-out period they will return to their normal diet. The meals are on a 7 day rotating schedule that reflect an average Canadian diet. Changes in blood lipids, body weight, and waist circumference will be measured during each treatment phase. Cholesterol absorption and synthesis will be examined by stable isotope method. Single nucleotide polymorphisms (SNPs), rs3808607 of gene CYP7A1and rs429358 and rs7412 will be determined byTaqMan® SNP Genotyping assay following the manufacturer's protocol. Fecal samples will be collected at the end of each intervention phase and will be subjected to Illumina sequencing of 16S rRNA genes.

Beta-Glucan, Barley, Molecular Weight, Viscosity, Cholesterol, Stable isotope, Gene-nutrient interaction, Gut microbiota

The rate of cholesterol absorption and synthesis will be measured in each intervention phase using single stable isotope labelling technique.

The Single Nucleotide Polymorphism (SNP) rs3808607 of CYP7A1 gene, rs429358 and rs7412 of APOE gene, and their associations with different blood lipid responses to beta-glucan interventions will be determined.

Body weight will be monitored every day when subject visits the Richardson Centre. Waist circumference will be measured at the beginning and end of each study phase.

Inclusion Criteria: BMI 20-40 kg/m2 Fasting cholesterol levels of 5.0-8.0 mmol/L Fasting serum LDL cholesterol levels of 2.7-5.0 mmol/L Exclusion Criteria: Pregnant or lactating Taking lipid lowering medication or nutritional supplements that affect blood lipids Dietary restrictions which would affect consuming the study diet for 5-wk for four study phases. Not deemed healthy by study physician

Wang Y, Harding SV, Eck P, Thandapilly SJ, Gamel TH, Abdel-Aal el-SM, Crow GH, Tosh SM, Jones PJ, Ames NP. High-Molecular-Weight beta-Glucan Decreases Serum Cholesterol Differentially Based on the CYP7A1 rs3808607 Polymorphism in Mildly Hypercholesterolemic Adults. J Nutr. 2016 Apr;146(4):720-7. doi: 10.3945/jn.115.223206. Epub 2016 Mar 2.