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

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Vasodilation
• Intervention / Treatment: Behavioral: Nutrition

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1K 7P4
    • Institute of Nutraceuticals and Functional Foods

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Laval University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Charles Couillard, Ph.D., Laval University

Publications and helpful links

General Publications

• Ruel G, Pomerleau S, Couture P, Lamarche B, Couillard C. Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption. Metabolism. 2005 Jul;54(7):856-61. doi: 10.1016/j.metabol.2005.01.031.
• Couillard C, Ruel G, Archer WR, Pomerleau S, Bergeron J, Couture P, Lamarche B, Bergeron N. Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity. J Clin Endocrinol Metab. 2005 Dec;90(12):6454-9. doi: 10.1210/jc.2004-2438. Epub 2005 Sep 27.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: February 9, 2006
• First Submitted That Met QC Criteria: February 24, 2006
• First Posted (Estimate): February 27, 2006

Study Record Updates

• Last Update Posted (Estimate): September 22, 2015
• Last Update Submitted That Met QC Criteria: September 21, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: MOP-64438