Effects of Polyunsaturated Fatty Acids on Intestinal Lipid Metabolism in Insulin-resistant Men

NCT ID: NCT01934543

Last Updated: 2016-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2016-05-31

Brief Summary

The overaccumulation of apolipoprotein (apo)B-48-containing lipoproteins of intestinal origin observed in patients with insulin-resistance is now thought to be attributable to both elevated intestinal production and reduced clearance of these lipoproteins. Substantial evidence exists indicating that elevated plasma levels of these lipoproteins are associated with increased cardiovascular disease (CVD) risk. Therefore, reduction of atherogenic plasma TRL levels of intestinal origin appears to be crucial to improve CVD risk associated with insulin-resistance. In this regard, there is some evidence that the clinical recommendation to replace dietary saturated fatty acids (SFAs) by n-6 polyunsaturated fatty acids (PUFAs) reduces CVD risk in the general population. Although the beneficial impact of n-6 PUFAs on CVD risk has been related primarily to favorable changes in plasma LDL-cholesterol levels, recent data suggest that chronic n-6 PUFA consumption may also exert beneficial effects on CVD risk by reducing postprandial lipemia. The impact of substituting SFAs by n-6 PUFAs on postprandial lipid response may be of even greater significance in dyslipidemic patients with insulin-resistance among whom intestinal triglyceride-rich lipoproteins (TRLs) represent a large proportion of the atherogenic lipoproteins. The general objective of the proposed research is to investigate how dietary n-6 PUFAs in place of SFAs modify intestinal lipoprotein metabolism in men with dyslipidemia associated with insulin-resistance. The investigators hypothesize that the intestinal secretion of apoB-48-containing lipoproteins will be lower following a diet rich in n-6 PUFAs than after consuming a diet rich in SFAs. The investigators also hypothesize that substitution of SFAs by n-6 PUFAs will be associated with significant alterations in expression of key genes and proteins involved in intestinal lipoprotein metabolism.

Conditions

Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Polyunsaturated fatty acids diet

During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).

Group Type: EXPERIMENTAL

Polyunsaturated fatty acids diet

Intervention Type: OTHER

During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).

Saturated fatty acids diet

During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).

Group Type: EXPERIMENTAL

Saturated fatty acids diet

Intervention Type: OTHER

During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).

Interventions

Polyunsaturated fatty acids diet

During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).

Intervention Type: OTHER

Saturated fatty acids diet

During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Men aged between 18-60 years
• Waist circumference > 102 cm
• HDL-cholesterol < 1.1 mmol/L
• Triglycerides > 1.7 mmol/L
• Fasting blood glucose > 6.1 mmol/L
• Normal blood pressure (<130/85)

Exclusion Criteria

• Women
• Men < 18 or > 60 years
• Smokers (> 1 cigarette/day)
• Body weight variation > 10% during the last 6 months prior to the study baseline
• Subjects with a previous history of cardiovascular disease
• Subjects with type 2 diabetes
• Subjects with a monogenic dyslipidemia
• Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa
• Subjects with endocrine or gastrointestinal disorders
• History of alcohol or drug abuse within the past 2 years
• Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Laval University

OTHER

Sponsor Role: lead

Responsible Party

Patrick Couture

MD, FRCP, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Couture, MD,FRCP,PhD

Role: PRINCIPAL_INVESTIGATOR

Laval University

Locations

Institute of Nutrition and Functional Foods (INAF)

Québec, Quebec, Canada

Countries

Canada

References

Drouin-Chartier JP, Tremblay AJ, Lepine MC, Lemelin V, Lamarche B, Couture P. Substitution of dietary omega-6 polyunsaturated fatty acids for saturated fatty acids decreases LDL apolipoprotein B-100 production rate in men with dyslipidemia associated with insulin resistance: a randomized controlled trial. Am J Clin Nutr. 2018 Jan 1;107(1):26-34. doi: 10.1093/ajcn/nqx013.

Reference Type: DERIVED

PMID: 29381796 (View on PubMed)

Other Identifiers

INAF-PUFA

Identifier Type: -

Identifier Source: org_study_id