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

NCT01810003 | Completed

• 1 other identifier: INAF-2012-143
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiovascular Disease, Inflammation

Keywords

Cardiovascular disease; Inflammation; EPA/DHA supplementation

Outcome Measures

Primary Outcomes (1)

• Change in plasma biomarkers of inflammation (CRP, Interleukin (IL)-6, IL-18 and Tumor necrosis factor-α)

  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 Outcomes (5)

• Change in lipid concentrations (LDL-C, HDL-C, TG)

  At the beginning and the end of each 10-week period

• Change in blood pressure

  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)

  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)

  At the end of the three 10-week periods

• Change in anthropometric measures (waist and hip circumference)

  At the beginning and the end of each 10-week period

Study Arms (3)

High DHA

EXPERIMENTAL

High DHA supplementation (3g/day)

Dietary Supplement: High DHA

High EPA

EXPERIMENTAL

EPA supplementation (3g/day)

Dietary Supplement: High EPA

Placebo

PLACEBO COMPARATOR

Placebo (3g corn oil/day)

Dietary Supplement: Placebo

Interventions

High DHA DIETARY_SUPPLEMENT

10 week supplementation period

High DHA

High EPA DIETARY_SUPPLEMENT

10 week supplementation period

High EPA

Placebo DIETARY_SUPPLEMENT

10 week supplementation period

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laval University: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Institute of Nutrition and Functional Foods (INAF), Laval University

Québec, Quebec, G1V 0A6, Canada

Location

Related Publications (4)

• Vallee Marcotte B, Allaire J, Guenard F, de Toro-Martin J, Couture P, Lamarche B, Vohl MC. Genetic risk prediction of the plasma triglyceride response to independent supplementations with eicosapentaenoic and docosahexaenoic acids: the ComparED Study. Genes Nutr. 2020 Jun 15;15(1):10. doi: 10.1186/s12263-020-00669-x.

  PMID: 32539794 DERIVED

• Allaire J, Vors C, Tremblay AJ, Marin J, Charest A, Tchernof A, Couture P, Lamarche B. High-Dose DHA Has More Profound Effects on LDL-Related Features Than High-Dose EPA: The ComparED Study. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2909-2917. doi: 10.1210/jc.2017-02745.

  PMID: 29846653 DERIVED

• Vors C, Allaire J, Marin J, Lepine MC, Charest A, Tchernof A, Couture P, Lamarche B. Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the ComparED study. Atherosclerosis. 2017 Feb;257:116-122. doi: 10.1016/j.atherosclerosis.2017.01.025. Epub 2017 Jan 20.

  PMID: 28131045 DERIVED

• Allaire J, Couture P, Leclerc M, Charest A, Marin J, Lepine MC, Talbot D, Tchernof A, Lamarche B. A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study. Am J Clin Nutr. 2016 Aug;104(2):280-7. doi: 10.3945/ajcn.116.131896. Epub 2016 Jun 8.

  PMID: 27281302 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Benoît Lamarche, PhD

  Laval University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 13, 2013
• Study Start: March 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2017
• Last Updated: February 22, 2018

Record last verified: 2018-02

Locations

CA (1)