Clinical trial NCT01233778: Canola Oil Multicentre Intervention Trial (COMIT)
Official title: Canola and Flax Oils in Modulation of Vascular Function and Biomarkers of Cardiovascular Disease Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Keywords: Cardiovascular disease
Omega-3 fatty acids
Inflammation
Endothelial function
Canola oil
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: University of Manitoba
First posted: 2010-11-03
Enrollment: 43
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The objectives of this study are to examine how the consumption of treatment oils (including canola oil, DHA enriched canola-oil, high oleic acid canola oil, flax oil, and safflower oil) influence endothelial function, inflammation, oxidation, body composition, and plasma lipoprotein characterization.

Detailed description: The consequence of total fat consumption on circulating plasma lipids and the incidence of cardiovascular disease has long been a central theme in nutrition research. Less well known is the influence of specific fatty acids on vascular endothelial function and the oxidative and inflammatory responses characteristic of atherogenesis. Omega 3 ( ω-3) fatty acids, including plant derived alpha-linolenic acid (18:3n-3, ALA) and marine derived eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) have been shown to effectively modulate multiple cardiovascular risk factors in epidemiological, animal model and human clinical investigations. ALA is most commonly consumed as a major component of dietary canola and flaxseed oils and has a recommended intake of 1.1 and 1.6 g/d for women and men, respectively. EPA and DHA are consumed as fatty fish or fish oil and algae supplements with current recommended intakes of 500 mg/d (combined EPA and DHA).

ALA is thought to improve cardiovascular health by modulating circulating lipid concentrations, altering membrane structure and function by enhancing the total ω-3 fatty acid content of cell membrane phospholipids, and reducing inflammatory reactions by blocking the formation of arachidonic acid derived eicosanoids. However, there are extensive knowledge gaps in our understanding of the molecular mechanisms and clinical efficacy of ω-3 fatty acids in human health and disease prevention. Therefore, the purpose of this study is to further examine these relationships.

Feeding protocol and study treatments:

The study will proceed as a double blind, randomized cross-over controlled feeding study. Each treatment phase will be 30 days in duration, separated by 4-week washout periods. Subjects will consume a fixed composition of a precisely controlled basal, weight-maintaining diet (35% energy from fat, 50% carbohydrate, and 15% protein) supplemented with 60g/d of the following treatment oils: 1) canola oil; 2) DHA enriched canola-oil; 3) high oleic acid canola oil; 4) flax/corn oil (40:60); or 5) safflower/corn oil (75:25). Study diets will be prepared in a metabolic kitchen facility at each clinical site. Three isocaloric meals will be prepared each day for every subject. A 7-day rotating menu cycle will be used. Subjects will consume at least 1 of 3 daily meals under supervision. The other meals will be prepared and packed for every subject to be taken out. The study control and intervention oils will be delivered in milkshakes provided twice daily. Subjects will be instructed to consume only the prepared meals and limit their intake of alcohol to 2 drinks/week and caffeinated calorie free beverages to 40oz (5 drinks) per day. Diets will be planned for every subject according to his/her energy requirements and will be nutritionally adequate.

Eligibility criteria: Inclusion Criteria:

* Aged 20-65 years
* BMI = 22-32 kg/m2

In addition, eligibility will be based on metabolic syndrome criteria where we define eligibility on the basis of subjects having elevated waist circumference + 1 or more of the remaining 5 criteria:

* Elevated waist circumference - \> 102 cm for men and \>88 cm for women
* Elevated triglycerides - ≥ 1.7 mmol/L ( ≥150mg/dl) ( no upper limit)
* Reduced HDL - \< 1 mmol/L (\<40 mg/dl) for men and \< 1.3 mmol/L (\<50 mg/dl)for women
* Fasting glucose - ≥ 100 mg/dl (no upper limit)
* Elevated blood pressure - systolic ≥130 and/or diastolic ≥85 mm HG

  * Unmedicated participants - upper limit of Stage 1 Hypertension: systolic ≤ 159 and/or diastolic ≤ 99 mm HG and participants must be free of end stage/target organ disease symptoms
  * BP medicated participants: acceptable as long as individuals meet the specified blood pressure range of \<140/90 mmHg, and have been stable for at least 6 months.

Exclusion Criteria:

* Smokers\*\*
* History of thyroid disease, diabetes, kidney or liver disease, heart disease, or other chronic diseases
* Heavy alcohol consumption (\>14 drinks/week)
* Chronic anti-inflammatory medication use
* Lactation, pregnancy, or desire to become pregnant during the study
* Taking lipid lowering medications (cholestyramine, colestipol, niacin, clofibrate, gemfibrozil probucol, HMG CoA reductase inhibitors) within the last three months
* Not willing to refrain from blood/plasma donation during the study period
* Gall bladder removal

  * For purposes of the this study non-smoking is defined as \>6 months smoke-free; there is some evidence to show that smoking cessation increases HDL levels and 6 months is adequate time for this to stabilize, however this time span was chosen based on the decreased rate of relapse after 6 months.

Primary outcomes:
measure: Endothelial Health
timeFrame: End of diet period 1 (week 4)
measure: Endothelial Health
timeFrame: End of diet period 2 (week 12)
measure: Endothelial Health
timeFrame: End of diet period 3 (week 20)
measure: Endothelial Health
timeFrame: End of diet period 4 (week 28)
measure: Endothelial Health
timeFrame: End of diet period 5 (week 36)
Secondary outcomes:
measure: Body Composition
timeFrame: Week 4, 12, 20, 28 and 36 - End of each diet period
measure: Production of long chain fatty acids
timeFrame: Week 4, 12, 20, 28 and 36 - End of each diet period
measure: Plasma Lipids
timeFrame: Week 4, 12, 20, 28 and 36 - End of each diet period
measure: Plasma Cytokines
timeFrame: Week 4, 12, 20, 28 and 36 - End of each diet period
Other outcomes:
Locations:
city: University Park
country: United States
facility: Penn State University
state: Pennsylvania
Study officials:
affiliation: Penn State University
name: Penny M Kris-Etherton, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References: