Effect of the Molecular Weight of Oat β-glucan on Its Ability to Lower Serum Cholesterol (Bluebird)

• ClinicalTrials.gov Identifier: NCT00981981
• Recruitment Status: Completed
• First Posted: September 22, 2009
• Last Update Posted: June 21, 2011
• Sponsor: Glycemic Index Laboratories, Inc
• Collaborators: CreaNutrition, AG; University of Guelph; University of Sydney; Laval University; Reading Scientific Services Ltd.; University of Toronto; Agriculture and Agri-Food Canada
• Information provided by: Glycemic Index Laboratories, Inc

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Dietary Supplement: Wheat bran; Dietary Supplement: 3g high MW; Dietary Supplement: 4g medium MW; Dietary Supplement: 3g medium MW; Dietary Supplement: 4g low MW	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 367 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Varying Dose and Molecular Weight on the Serum LDL-cholesterol-lowering Properties of Oat β-glucan
• Study Start Date: November 2008
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: August 2009

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control; Wheat bran cereal	Dietary Supplement: Wheat bran; 21g per day of ready to eat breakfast cereal containing wheat bran with 8g of total dietary fiber and 0.5g beta-glucan.
Active Comparator: 3g high MW; Cereal containing 3g high molecular weight oat beta glucan	Dietary Supplement: 3g high MW; 20.2 grams per day of ready to eat cereal containing 6g total dietary fiber and 3g oat beta glucan with high molecular weight
Active Comparator: 4g medium MW; Cereal containing 4g oat beta glucan with medium molecular weight	Dietary Supplement: 4g medium MW; 28.5g ready to eat cereal containing 8g total dietary fiber and 4g oat beta glucan with medium molecular weight
Active Comparator: 3g medium MW; Cereal containing 3g oat beta glucan with medium molecular weight	Dietary Supplement: 3g medium MW; 21.1g of ready to eat cereal containing 6g total fiber and 3g oat beta glucan with a medium molecular weight
Active Comparator: 4g low MW; Cereal containing 4g oat beta glucan with low molecular weight	Dietary Supplement: 4g low MW; 28.7g ready to eat cereal containing 8g total dietary fiber and 4g oat beta glucan with low molecular weight

Outcome Measures

Primary Outcome Measures :

1. Serum LDL-cholesterol lowering effect of 3g high MW beta-glucan [ Time Frame: 4 weeks ]
2. Correlation between serum LDL-cholesterol lowering and log(MW*C) [ Time Frame: 4 weeks ]

Secondary Outcome Measures :

1. Total cholesterol [ Time Frame: 4 weeks ]
2. Serum triglycerides [ Time Frame: 4 weeks ]
3. Serum HDL cholesterol [ Time Frame: 4 weeks ]
4. Fasting serum glucose [ Time Frame: 4 weeks ]
5. Serum aspartate transaminase [ Time Frame: 4 weeks ]
6. serum c-reactive protein [ Time Frame: 4 weeks ]
7. Serum urea [ Time Frame: 4 weeks ]
8. Serum creatinine [ Time Frame: 4 weeks ]
9. Time course of changes in blood lipids [ Time Frame: 4 weeks ]
10. Blood pressure [ Time Frame: 4 weeks ]
11. Macronutrient composition of diet [ Time Frame: 4 weeks ]
12. Symptoms questionnaire [ Time Frame: 4 weeks ]
13. apolipoprotein B [ Time Frame: 4 weeks ]
14. Serum markers of cholesterol absorption and synthesis [ Time Frame: 4 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Australia, New South Wales

SUGiRS Human Nutrition Unit, School of Molecular & Microbial Biosciences, Unviersity of Sydney

Sydney, New South Wales, Australia, 2006

Canada, Ontario

Human Nutraceutical Research Unit, Department of Human Health and Nutritional Sciences, University of Guelph

Guelph, Ontario, Canada, N1G 2W1

Glycemic Index Laboratories, Inc.

Toronto, Ontario, Canada, M5C 2X3

Canada, Quebec

Nutraceuticals and Functional Foods Institute, Faculte des science de l'agriculture et de l'alimentation, Universite Laval

Laval, Quebec, Canada

United Kingdom

Reading Scientific Services, Ltd (RSSL)

Reading, Berkshire, United Kingdom, RG6 6LA

Sponsors and Collaborators

Glycemic Index Laboratories, Inc

CreaNutrition, AG

University of Guelph

University of Sydney

Laval University

Reading Scientific Services Ltd.

University of Toronto

Agriculture and Agri-Food Canada

Investigators

• Principal Investigator: Thomas MS Wolever, MD, PhD; Glycemic Index Laboratories, Inc
• Study Director: Peter J Wood, PhD; Agriculture and Agri-Food Canada
• Study Director: Susan M Tosh, PhD; Agriculture and Agri-Food Canada
• Study Director: Alison L Gibbs, PhD; Department of Statistics, University of Toronto

More Information

Publications of Results:

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.

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.

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

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.

• Responsible Party: Thomas MS Wolever, President, Glycemic Index Laboratories, Inc.
• ClinicalTrials.gov Identifier: NCT00981981
• Other Study ID Numbers: GIL8034
• First Posted: September 22, 2009
• Last Update Posted: June 21, 2011
• Last Verified: June 2011

Keywords provided by Glycemic Index Laboratories, Inc:

humans; randomized clinical trial; dietary fiber; nutrition; beta-glucan; oats; LDL cholesterol; coronary heart disease

Additional relevant MeSH terms:

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