Canola Oil Multicentre Intervention Trial (COMIT)

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.

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.