Clinical trial NCT00981981: Effect of the Molecular Weight of Oat β-glucan on Its Ability to Lower Serum Cholesterol
Official title: Effect of Varying Dose and Molecular Weight on the Serum LDL-cholesterol-lowering Properties of Oat β-glucan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: humans
randomized clinical trial
dietary fiber
nutrition
beta-glucan
oats
LDL cholesterol
coronary heart disease
Lead sponsor: Glycemic Index Laboratories, Inc
Sponsor class: INDUSTRY
Collaborators: name: CreaNutrition, AG
name: University of Guelph
name: University of Sydney
name: Laval University
name: Reading Scientific Services Ltd.
name: University of Toronto
name: Agriculture and Agri-Food Canada
First posted: 2009-09-22
Enrollment: 367
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purposes of this study were:

1. To determine if a breakfast cereal containing 3g of high molecular weight oat beta-glucan fiber would lower low-density lipoprotein (LDL) - cholesterol (the "bad" cholesterol) compared to a control cereal containing wheat fiber.
2. To determine if the LDL-cholesterol-lowering effect of oat beta-glucan fiber was reduced when the molecular weight of the fiber was reduced.

Detailed description: The FDA allows a health claim that oat products may reduce the risk of heart disease, based on meta-analyses showing a cholesterol-lowering effect of oat beta-glucan, if the product delivers at least a 3g daily dose of oat beta-glucan. However, not all studies have demonstrated a lowering of oat products. This may be due to variable bioactivity of the beta-glucan in the oat products. The bioactivity of oat beta-glucan is believed to depend upon its viscosity in the gut. Factors influencing viscosity include the molecular weight (MW) of the beta-glucan molecule and the amount of soluble beta-glucan in the product, which, in turn determines its concentration (C) in solution. In finished food products both MW and C can be modified by beta-glucanase enzymes present in other ingredients in the food (eg. wheat flour), processing (eg. extrusion) and storage (eg. freezing of moist products such as muffins). The effect of altering the MW and solubility of beta-glucan in foods on glycemic responses has been shown, but a role for MW and C in cholesterol lowering has not been established.

To address this issue, this study was designed with 2 primary objectives:

1. An extruded oat cereal containing 3g high-molecular weight oat β-glucan daily will reduce LDL cholesterol compared to a control wheat bran cereal.
2. A significant correlation exists between LDL cholesterol and log(C×MW), where C is the amount of soluble β-glucan in the daily dose of cereal and MW is the molecular weight of the β-glucan in the cereal.

Eligibility criteria: Inclusion Criteria:

* body mass index 18.5 to 40.0 kg/m\^2
* no intention to lose or gain weight
* fasting total cholesterol 5.0 to 8.0 mmol/L
* fasting LDL cholesterol 3.0 to 5.0 mmol/L
* consuming diet containing \<15% energy from saturated fat

Exclusion Criteria:

* use of any cholesterol-lowering drug, herbal or nutritional supplement
* regular consumption of oatmeal, oat bran or psyllium - containing cereals
* fasting serum triglycerides \>4.0mmol/L
* serum aspartate transaminase \>1.5 times upper limit of normal
* serum urea or creatinine \>1.8 times upper limit of normal
* presence of diabetes or fasting glucose \>6.9mmol/L
* presence or recent major surgical or medical event
* allergy to wheat or oats
* presence of condition or drug which alters digestion or absorption of foods

Primary outcomes:
measure: Serum LDL-cholesterol lowering effect of 3g high MW beta-glucan
timeFrame: 4 weeks
measure: Correlation between serum LDL-cholesterol lowering and log(MW*C)
timeFrame: 4 weeks
Secondary outcomes:
measure: Total cholesterol
timeFrame: 4 weeks
measure: Serum triglycerides
timeFrame: 4 weeks
measure: Serum HDL cholesterol
timeFrame: 4 weeks
measure: Fasting serum glucose
timeFrame: 4 weeks
measure: Serum aspartate transaminase
timeFrame: 4 weeks
measure: serum c-reactive protein
timeFrame: 4 weeks
measure: Serum urea
timeFrame: 4 weeks
measure: Serum creatinine
timeFrame: 4 weeks
measure: Time course of changes in blood lipids
timeFrame: 4 weeks
measure: Blood pressure
timeFrame: 4 weeks
measure: Macronutrient composition of diet
timeFrame: 4 weeks
measure: Symptoms questionnaire
timeFrame: 4 weeks
measure: apolipoprotein B
timeFrame: 4 weeks
measure: Serum markers of cholesterol absorption and synthesis
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: SUGiRS Human Nutrition Unit, School of Molecular & Microbial Biosciences, Unviersity of Sydney
state: New South Wales
city: Guelph
country: Canada
facility: Human Nutraceutical Research Unit, Department of Human Health and Nutritional Sciences, University of Guelph
state: Ontario
city: Toronto
country: Canada
facility: Glycemic Index Laboratories, Inc.
state: Ontario
city: Laval
country: Canada
facility: Nutraceuticals and Functional Foods Institute, Faculte des science de l'agriculture et de l'alimentation, Universite Laval
state: Quebec
city: Reading
country: United Kingdom
facility: Reading Scientific Services, Ltd (RSSL)
state: Berkshire
Study officials:
affiliation: Glycemic Index Laboratories, Inc
name: Thomas MS Wolever, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Agriculture and Agri-Food Canada
name: Peter J Wood, PhD
role: STUDY_DIRECTOR
affiliation: Agriculture and Agri-Food Canada
name: Susan M Tosh, PhD
role: STUDY_DIRECTOR
affiliation: Department of Statistics, University of Toronto
name: Alison L Gibbs, PhD
role: STUDY_DIRECTOR
References:
citation: Wolever TM, Tosh SM, Gibbs AL, Brand-Miller J, Duncan AM, Hart V, Lamarche B, Thomson BA, Duss R, Wood PJ. Physicochemical properties of oat beta-glucan influence its ability to reduce serum LDL cholesterol in humans: a randomized clinical trial. Am J Clin Nutr. 2010 Oct;92(4):723-32. doi: 10.3945/ajcn.2010.29174. Epub 2010 Jul 21.
citation: Tosh SM, Brummer Y, Miller SS, Regand A, Defelice C, Duss R, Wolever TM, Wood PJ. Processing affects the physicochemical properties of beta-glucan in oat bran cereal. J Agric Food Chem. 2010 Jul 14;58(13):7723-30. doi: 10.1021/jf904553u.
citation: Wolever TM, Gibbs AL, Brand-Miller J, Duncan AM, Hart V, Lamarche B, Tosh SM, Duss R. Bioactive oat beta-glucan reduces LDL cholesterol in Caucasians and non-Caucasians. Nutr J. 2011 Nov 25;10:130. doi: 10.1186/1475-2891-10-130.