Effects of n-3 Polyunsaturated Fatty Acids and Antioxidants on Postprandial Hyperlipidemia and Vascular Function in Men

Study Overview
=================
Brief Summary
-----------------
Diet has long been used as a way to provide enough nutrients to an individual in order to meet metabolic requirements. However, recent scientific advancements have suggested that beyond meeting nutrition needs, diet may also be health promoting through the modulation of various body functions. In a way, the role of nutrition has evolved from hunger satisfaction and maintenance of body integrity to the promotion of a state of well-being and prevention of important chronic diseases such as cancer, diabetes and cardiovascular disease (CVD). In recent years, n-3 polyunsaturated fatty acids (PUFA) have attracted much attention as consumption of a n-3 PUFA rich diet has been reported to reduce CVD risk. However, n-3 PUFA are also highly susceptible to free radical damage and therefore could be unable to fully exert their health benefits under an oxidative stress condition. The general objective of the present application is to investigate the mechanisms by which n-3 PUFA improve cardiovascular health in abdominal obesity and explore the potential of dietary antioxidants to modulate these effects in individuals at high risk of oxidative stress. For that purpose, we plan to study the changes in fasting and postprandial plasma lipoprotein-lipid levels, markers of lipid and lipoprotein oxidation, inflammation and endothelial dysfunction following 12 weeks of n-3 PUFA supplementation with or without low-calorie cranberry juice cocktail (as a source of antioxidants) in a group of 160 men. We feel that the present study will broaden our understanding of the physiological mechanisms underlying the beneficial effects of consuming unsaturated fatty acids and give further insights on the role of antioxidants in preserving and potentiating these cardiovascular health benefits.

Official Title
-----------------
Physiological Mechanisms Underlying the Effects of PUFA and Antioxidants on Postprandial Lipemia, Oxidative Stress, Endothelial Dysfunction and Inflammation in Men

Conditions
-----------------
Cardiovascular Diseases, Vasodilation

Intervention / Treatment
-----------------
* Behavioral: Nutrition


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Waist circumference > 90 cm Fasting triglycerides > 1.7 mmol/L No use (ever) of medications for the treatment for dyslipidemia or hypertension Exclusion Criteria: Alcohol consumption > 1 drink per day i.e  15 g of alcohol/day or the equivalent of 1 beer (12 oz or 341 mL), 1 glass of wine (4 oz or 125 mL) or 1 ounce (30 mL) of liquor. Chronic use of supplements (vitamins, minerals or flavonoids) Body mass index > 35 kg/m2 Chronic diseases: CHD, diabetes, etc. Smokers (1 or more cigarette/day) Dyslipidemia secondary to renal insufficiency, hypothyroidism or others Any prior or current use of medications known to affect lipoprotein-lipid metabolism (e.g. statins, fibrates), endothelial function (hypotensive drugs). Use (ever) of anticoagulant drugs (e.g. warfarin) because of possible detrimental interaction with the consumption of cranberry juice. Current or recent (<2 weeks) use of anti-inflammatory drugs Note: If for any reason, a subject would have to go an any of these drugs during the protocol, they would be automatically dropped from the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo capsules + 500 mL/day of placebo juice | Behavioral: Nutrition<br> <br> |
| Experimental: Cranberry Juice<br>Placebo capsules + 500 mL/day of cranberry juice | Behavioral: Nutrition<br> <br> |
| Experimental: Fish Oil<br>2 g/day of fish oil + 500 mL/day of placebo juice | Behavioral: Nutrition<br> <br> |
| Experimental: Cranberry Juice + Fish Oil<br>2 g/day of fish oil + 500 mL/day of cranberry juice | Behavioral: Nutrition<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in postprandial lipemia, oxidative stress, endothelial activation and inflammation: TG (plasma, chylomicron and VLDL), OxLDL, 8-iso-PGF2alpha, ICAM-1, VCAM-1, E-selectin and CRP concentrations |  | June 2008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in arterial flow-mediated vasodilatory response |  | June 2008 |