Effect of Beta-Glucan on Cholesterol Lowering

• ClinicalTrials.gov Identifier: NCT01408719
• Recruitment Status: Completed
• First Posted: August 3, 2011
• Results First Posted: March 11, 2014
• Last Update Posted: November 5, 2015
• Sponsor: University of Manitoba
• Collaborator: Agriculture and Agri-Food Canada
• Information provided by (Responsible Party): Dr. Nancy Ames, University of Manitoba

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Dietary Supplement: Control; Dietary Supplement: 3g LMW beta-glucan; Dietary Supplement: 5g LMW beta-glucan; Dietary Supplement: 3g HMW beta-glucan	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Effect of Beta-Glucan Molecular Weight and Viscosity on the Mechanism of Cholesterol Lowering in Humans
• Study Start Date: November 2010
• Actual Primary Completion Date: February 2012
• Actual Study Completion Date: February 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: 5g LMW beta glucan; 5 gram low molecular weight barley beta-glucan diet for 35 days	Dietary Supplement: Control; Minimal beta-glucan
Experimental: 3g HMW beta glucan; 3 gram high molecular weight barley beta-glucan diet for 35 days	Dietary Supplement: 3g LMW beta-glucan; 3grams beta-glucan
Experimental: 3g LMW beta glucan; 3 grams of low molecular weight beta-glucan diet for 35 days	Dietary Supplement: 5g LMW beta-glucan; 5 grams beta-glucan
Placebo Comparator: Control; control diet containing negligible amount of beta glucan	Dietary Supplement: 3g HMW beta-glucan; 3 grams of high molecular weight beta-glucan

Outcome Measures

Primary Outcome Measures :

1. Changs in Total Cholesterol [ Time Frame: Beginning and end of each phase ]
   Fasted total cholesterol concentration will be measured using the automated enzymatic methods.
2. Changes in LDL Cholesterol [ Time Frame: Beginning and end of each phase ]
   Serum LDL cholesterol will be estimated using the Friedewald equation.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 78 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Canada, Manitoba

Richardson Centre for Functional Foods and Neutraceuticals

Winnipeg, Manitoba, Canada, R3T 2N2

Sponsors and Collaborators

University of Manitoba

Agriculture and Agri-Food Canada

Investigators

• Principal Investigator: Nancy Ames, PhD; AAFC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 β-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.

• Responsible Party: Dr. Nancy Ames, Research Scientist & Adjunct Professor, University of Manitoba
• ClinicalTrials.gov Identifier: NCT01408719
• Other Study ID Numbers: B2010:216
• First Posted: August 3, 2011
• Results First Posted: March 11, 2014
• Last Update Posted: November 5, 2015
• Last Verified: October 2015

Keywords provided by Dr. Nancy Ames, University of Manitoba:

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

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases