Hypercholesterolemia
Conditions
Keywords
Beta-Glucan, Barley, Molecular Weight, Viscosity, Cholesterol, Stable isotope, Gene-nutrient interaction, Gut microbiota
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.
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.
Interventions
DIETARY_SUPPLEMENTControl
Minimal beta-glucan
DIETARY_SUPPLEMENT3g LMW beta-glucan
3grams beta-glucan
DIETARY_SUPPLEMENT5g LMW beta-glucan
5 grams beta-glucan
DIETARY_SUPPLEMENT3g HMW beta-glucan
3 grams of high molecular weight beta-glucan
Sponsors
Agriculture and Agri-Food Canada
University of Manitoba
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changs in Total Cholesterol | Beginning and end of each phase | Fasted total cholesterol concentration will be measured using the automated enzymatic methods. |
| Changes in LDL Cholesterol | Beginning and end of each phase | Serum LDL cholesterol will be estimated using the Friedewald equation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cholesterol Absorption/Synthesis | End of each phase | The rate of cholesterol absorption and synthesis will be measured in each intervention phase using single stable isotope labelling technique. |
| Potential Gene-nutrient Interactions: CYP7A1 and APOE | 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. |
| Changes in Body Weight and Waist Circumference(WC) | 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. |
Countries
Canada
Participant flow
Recruitment details
Participants were recruited at the Richardson Centre for Functionals Foods and Nutraceuticals, University of Manitoba, Winnipeg during July 2010 to May 2011
Pre-assignment details
Over 200 subjects were screened; 45 subjects were enrolled in the study and randomly assigned to the experimental diets (treatment groups).
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 3g LMW followed by control, followed by 3g HMW, followed by 5g LMW | 2 |
| Sequence 2 Control, followed by 3g HMW, followed by 5g LMW, followed by 3g LMW | 3 |
| Sequence 3 3g LMW, followed by 3g HMW, followed by 5g LMW, followed by control | 1 |
| Sequence 4 5g LMW, followed by 3g LMW, followed by 3g HMW, followed by control | 2 |
| Sequence 5 3g HMW, followed by 3g LMW, followed by control, followed by 5g LMW | 3 |
| Sequence 6 control, followed by 5g LMW, followed by 3g HMW, followed by 3g LMW | 3 |
| Sequence 7 5g LMW, followed by 3g LMW, followed control, followed by 3g HMW | 2 |
| Sequence 8 3g LMW, followed by 3g HMW, followed by control, followed by 5g HMW | 2 |
| Sequence 9 Control, followed by 5g HMW, followed by 3g LMW, followed by 3g HMW | 1 |
| Sequence 10 Control, followed by 3g LMW, followed by 5g LMW, followed by 3g HMW | 1 |
| Sequence 11 3g HMW, followed by control, followed by 5g LMW, followed by 3g LMW | 2 |
| Sequence 12 5g LMW, followed by control, followed by 3g LMW, followed by 3g HMW | 2 |
| Sequence 13 3g HMW, followed by control, followed by 3g LMW, followed by 5g LMW | 1 |
| Sequence 14 3g LMW, followed by 5g LMW, followed by 3g HMW, followed by control | 3 |
| Sequence 15 3g LMW, followed by 5g LMW, followed by control, followed by 3g HMW | 1 |
| Sequence 16 3g HMW, followed by 5g LMW, followed 3g LMW, followed by control | 1 |
| Sequence 17 3g HMW, followed by 3g LMW, followed 5g LMW, followed by control | 2 |
| Sequence 18 5g LMW, followed by 3g HMW, followed by control, followed by 3g LMW | 1 |
| Sequence 19 Control, followed by 3g HMW, followed by 3g LMW, followed by 5g LMW | 1 |
| Sequence 20 3g HMW, followed by 5g LMW, followed by control, followed by 3g LMW | 1 |
| Total | 35 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 | Sequence 5 | Sequence 6 | Sequence 7 | Sequence 8 | Sequence 9 | Sequence 10 | Sequence 11 | Sequence 12 | Sequence 13 | Sequence 14 | Sequence 15 | Sequence 16 | Sequence 17 | Sequence 18 | Sequence 19 | Sequence 20 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 15.6 | 52.7 years STANDARD_DEVIATION 3.5 | 40 years STANDARD_DEVIATION 0 | 63 years STANDARD_DEVIATION 1.4 | 70 years STANDARD_DEVIATION 10.6 | 55 years STANDARD_DEVIATION 14 | 55.5 years STANDARD_DEVIATION 2.12 | 67 years STANDARD_DEVIATION 1.4 | 57 years STANDARD_DEVIATION 0 | 27 years STANDARD_DEVIATION 0 | 62.5 years STANDARD_DEVIATION 0.7 | 59.5 years STANDARD_DEVIATION 4.9 | 62 years STANDARD_DEVIATION 0 | 59.3 years STANDARD_DEVIATION 3.8 | 76 years STANDARD_DEVIATION 0 | 58 years STANDARD_DEVIATION 0 | 53 years STANDARD_DEVIATION 8.5 | 59 years STANDARD_DEVIATION 0 | 65 years STANDARD_DEVIATION 0 | 59 years STANDARD_DEVIATION 0 | 57.9 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
Outcome results
Primary
Changes in LDL Cholesterol
Serum LDL cholesterol will be estimated using the Friedewald equation.
Time frame: Beginning and end of each phase
Primary
Changs in Total Cholesterol
Fasted total cholesterol concentration will be measured using the automated enzymatic methods.
Time frame: Beginning and end of each phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5g LMW Beta Glucan | Changs in Total Cholesterol | -0.42 mmol/L | Standard Error 0.09 |
| 3g HMW Beta Glucan | Changs in Total Cholesterol | -0.60 mmol/L | Standard Error 0.09 |
| 3g LMW Beta Glucan | Changs in Total Cholesterol | -0.46 mmol/L | Standard Error 0.09 |
| Control | Changs in Total Cholesterol | -0.30 mmol/L | Standard Error 0.09 |
Secondary
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.
Time frame: Every day for body weight; beginning and end of each phase for WC
Secondary
Cholesterol Absorption/Synthesis
The rate of cholesterol absorption and synthesis will be measured in each intervention phase using single stable isotope labelling technique.
Time frame: End of each phase
Secondary
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.
Time frame: Once for each participant