Impact of EPA and DHA Supplementation on Plasma Biomarkers of Inflammation (n3) (n3)

February 21, 2018 updated by: Benoit Lamarche, Laval University

Impact of EPA and DHA Supplementation on Plasma Biomarkers of Inflammation in Men and Women With Metabolic Syndrome

Subclinical inflammation is now indisputably recognized as a key etiological factor in the development of atherosclerosis and subsequent cardiovascular disease. Obesity and related dysmetabolic states including metabolic syndrome (MetS) are highly prevalent causes of subclinical inflammation. Obesity and MetS are both diet and lifestyle-related and there is a growing body of literature suggesting that specific nutrients, such as long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), may attenuate the pro-inflammatory state associated with these conditions. However, careful review of existing literature on this topic reveals important gaps in knowledge, the purported anti-inflammatory effects of LCn-3PUFA even being questioned by many. Significant confounding attributable to study design, sample size and biomarker selection may be responsible in part for inconsistencies in the literature on LCn-3PUFA and inflammation. We also found that evidence available to date (for and against) is based primarily on secondary analyses, as most of the studies published were not primarily designed to investigate inflammation as a primary outcome. It remains unclear whether the different LCn-3PUFA, primarily docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3), have similar effects on pro-inflammatory processes as almost all studies were undertaken using a mix of LCn-3PUFA. Whether efficacy of EPA and DHA is influenced by sex/gender is also unknown. Finally, a better understanding of the systemic and tissue-specific mechanisms underlying the anticipated anti-inflammatory effects of different LCn-3PUFA in MetS would also be of great value. Addressing these gaps has important public health implications, considering that LCn-3PUFA supplements are broadly and indiscriminately recommended for the prevention of cardiovascular disease.

The overarching objective of the proposed research is to compare the anti-inflammatory effects of EPA and DHA in men and women with MetS.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The proposed study will be undertaken according to a double-blind randomized placebo controlled cross-over design with 3 treatment phases: 1- high DHA, 2- High EPA, 3- Control. Each treatment phase will last 10 weeks and will be separated by 8-week washouts. Participants will be randomized to one of 6 treatment sequences while stratifying for sex. Treatments will provide 3 identical 1g capsules per day. During the 3 treatment periods, subjects will receive in random order 0g/d EPA+DHA (3g corn oil placebo), 3g/d EPA (>90% EPA), and 3g/d DHA (>90% DHA). Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) will be provided in their re-esterified triacylglycerol form as studies have shown that bioavailability was greater when EPA and DHA were consumed as TG rather than as ethyl esters. The therapeutic dose that maximizes the anti-inflammatory effects of LCn-3PUFA in patients with inflammation has not been established, although data suggest that they may be dose-dependent. However, studies in healthy human volunteers suggest that an intake > 2 g EPA + DHA/day is required to affect inflammatory processes. Many of the available studies have used a dose of EPA+DHA that was lower than 2g/d, with no apparent anti-inflammatory effects. A study has shown that a dose of 1.8g/d of EPA+DHA induced significant changes in peripheral blood cell (PBC) inflammation gene expression, with no change in plasma CRP concentrations. In the present study, we propose to use a dose of 3 g/d for each individual LCn-3PUFA tested, which is at the higher end of the recommended intake for patients with high plasma TG, but which will maximize our chance to observe changes in inflammatory markers and to differentiate the effects of EPA and DHA, if they exist. Participants will be instructed to maintain a constant body weight during the course of the study. They will also be counselled on how to exclude fatty fish meals (including salmon, tuna, mackerel, and herring), fish-oil supplements, flax products, walnuts, and omega-3-enriched eggs during the study. Vitamin supplements and natural health products will be strictly forbidden during the entire experimental period, with the exception of calcium and vitamin D, which will be allowed at a stable dose. Although alcohol consumption will be permitted during the study with intakes not exceeding one serving (12-15 g alcohol) per day, it will be forbidden for the 4 days that precede the various tests at the end of each treatment phase. Subjects will also be instructed to maintain their usual physical activity except for the 4 days that precede blood sampling at the various stages of the study, during which they will be asked to remain sedentary.

Study Type

Interventional

Enrollment (Anticipated)

170

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G1V 0A6
        • Institute of Nutrition and Functional Foods (INAF), Laval University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Men and women aged between 18 and 70 years with abdominal obesity as defined by the International Diabetes Federation criteria and a measure of plasma CRP >1 mg/L
  • Stable body weight for at least 3 months prior to randomization.
  • Pre-menopausal women with regular menstrual cycle (25-35 days)

Exclusion Criteria:

  • Plasma CRP > 10 mg/L at screening
  • Extreme dyslipidemias such as familial hypercholesterolemia
  • Previous history of cardiovascular disease (coronary heart disease, cerebrovascular disease or peripheral arterial disease)
  • Subjects taking medications known to affect inflammation (e.g. steroids, binging alcohol)
  • Subjects taking LCn-3PUFA supplements within 2 months of study onset.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High DHA
High DHA supplementation (3g/day)
Dietary supplement: High DHA
10 week supplementation period
Experimental: High EPA
EPA supplementation (3g/day)
Dietary supplement: High EPA
10 week supplementation period
Placebo Comparator: Placebo
Placebo (3g corn oil/day)
Dietary supplement: Placebo
10 week supplementation period

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in plasma biomarkers of inflammation (CRP, Interleukin (IL)-6, IL-18 and Tumor necrosis factor-α)
Time Frame: At the beginning and the end of each 10-week period
Change between treatments based on post-treatment values, adjusting for treatment-specific baseline values
At the beginning and the end of each 10-week period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in lipid concentrations (LDL-C, HDL-C, TG)
Time Frame: At the beginning and the end of each 10-week period
Change between treatments based on post-treatment values, adjusting for treatment-specific baseline values
At the beginning and the end of each 10-week period
Change in blood pressure
Time Frame: At the beginning and the end of each 10-week period
Change between treatments based on post-treatment values, adjusting for treatment-specific baseline values
At the beginning and the end of each 10-week period
Change in endogenous production and clearance rate of CRP (in a subsample of the entire study population)
Time Frame: At the end of the three 10-week periods
Change between treatments based on post-treatment values
At the end of the three 10-week periods
Change in expression of inflammation genes in peripheral blood cells (in a subsample of the entire study population)
Time Frame: At the end of the three 10-week periods
Change between treatments based on post-treatment values
At the end of the three 10-week periods
Change in anthropometric measures (waist and hip circumference)
Time Frame: At the beginning and the end of each 10-week period
Change between treatments based on post-treatment values, adjusting for treatment-specific baseline values
At the beginning and the end of each 10-week period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Laval University

Collaborators

Canadian Institutes of Health Research (CIHR)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2013

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

March 4, 2013

First Submitted That Met QC Criteria

March 11, 2013

First Posted (Estimate)

March 13, 2013

Study Record Updates

Last Update Posted (Actual)

February 22, 2018

Last Update Submitted That Met QC Criteria

February 21, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INAF-2012-143

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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