Effect of Beta-Glucan on Cholesterol Lowering

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Dietary Supplement: Control
* Dietary Supplement: 3g LMW beta-glucan
* Dietary Supplement: 5g LMW beta-glucan
* Dietary Supplement: 3g HMW beta-glucan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5g LMW beta glucan<br>5 gram low molecular weight barley beta-glucan diet for 35 days | Dietary Supplement: Control<br>* Minimal beta-glucan<br>|
| Experimental: 3g HMW beta glucan<br>3 gram high molecular weight barley beta-glucan diet for 35 days | Dietary Supplement: 3g LMW beta-glucan<br>* 3grams beta-glucan<br>|
| Experimental: 3g LMW beta glucan<br>3 grams of low molecular weight beta-glucan diet for 35 days | Dietary Supplement: 5g LMW beta-glucan<br>* 5 grams beta-glucan<br>|
| Placebo Comparator: Control<br>control diet containing negligible amount of beta glucan | Dietary Supplement: 3g HMW beta-glucan<br>* 3 grams of high molecular weight beta-glucan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changs in Total Cholesterol | Fasted total cholesterol concentration will be measured using the automated enzymatic methods. | Beginning and end of each phase | 
| Changes in LDL Cholesterol | Serum LDL cholesterol will be estimated using the Friedewald equation. | Beginning and end of each phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cholesterol Absorption/Synthesis | The rate of cholesterol absorption and synthesis will be measured in each intervention phase using single stable isotope labelling technique. | End of each phase | 
| Potential Gene-nutrient Interactions: CYP7A1 and APOE | 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. | Once for each participant | 
| Changes in Body Weight and Waist Circumference(WC) | 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. | Every day for body weight; beginning and end of each phase for WC | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta-Glucan, Barley, Molecular Weight, Viscosity, Cholesterol, Stable isotope, Gene-nutrient interaction, Gut microbiota