Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation

Phase 3

Completed

Conditions: Inflammation
Cardiovascular Disease

Interventions: Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)

Registration Number: NCT01078909

Lead Sponsor: Penn State University

Brief Summary: The purpose of this study is to determine the lowest effective dose of EPA + DHA (300, 600, 900 and 1,800 mg/day delivered as fish oil supplements) that significantly attenuates the inflammatory response to in vivo and ex vivo endotoxin challenge as measured by the production over time of several inflammatory markers.

Detailed Description: Inflammation is an important biological process initiated by the immune system in response to injury, irritation or infection. Prolonged or chronic inflammation is involved in the etiology of several diseases such as cardiovascular disease (CVD), diabetes, rheumatoid arthritis, cancer, and neurodegenerative diseases such as Alzheimer disease. The evidence base clearly demonstrates benefits of diet in ameliorating inflammation and reducing the burden of chronic disease. With respect to marine-derived omega-3 fatty acids and various markers of inflammation related to cardiovascular disease (CVD), both population studies and randomized controlled supplementation trials have yielded mixed results.

Some studies have demonstrated a dose-response relationship between dietary eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and increased membrane (phospholipid) EPA and DHA. Red blood cell (RBC) EPA + DHA content has been proposed as a potential, modifiable marker for coronary heart disease (CHD) risk. It is well established that these fatty acids are precursors of series-3 prostanoids, thromboxanes, 5-series leukotrienes, and novel lipid mediators such as resolvins and protectins that have anti-inflammatory effects. We hypothesize that nutritionally-relevant intakes of omega-3 fatty acids are able to blunt the usual response to an inflammatory stimulus. We propose to test this hypothesis using both in vivo (i.v. endotoxin challenge) and ex vivo (endotoxin-stimulated monocytes) models in a 6-month, dose-response study with marine-derived omega-3 fatty acid supplements in healthy volunteers.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 125

Inclusion Criteria

Healthy men and non-pregnant/lactating women between the ages of 20 and 45
BMI >19.9 and <30.0
Able to give written informed consent and willing to comply with all study- related procedures.

Exclusion Criteria

Previous history of heart disease or diabetes
Renal Insufficiency
Chronic anti-inflammatory use
Systolic blood pressure < 90
Individuals currently using tobacco products or have done so in the previous 30 days
Individuals taking Omega-3 fatty acid supplements or their usual intake of fish is greater than 3-4 servings per month.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
300mg Fish Oil (EPA + DHA) Supplement	Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)	-
600mg Fish Oil (EPA+DHA) Supplement	Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)	-
900mg Fish Oil (EPA + DHA) Supplement	Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)	-
Placebo	Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)	-
1800mg Fish Oil (EPA + DHA) Supplement	Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)	-

Primary Outcome Measures

Name	Time	Method
Mean Concentrations of CRP Following 5 Months of Treatment	5 months
Mean Concentrations of Inflammatory Markers (TNF-alpha and IL-6) Following 5 Months of Treatment	5 months

Secondary Outcome Measures

Name	Time	Method
Change in Lipid Mediators	1, 2, 3 and 5 days post LPS administration	0 Participants Analyzed; Lipid mediators were unable to be detected therefore there are no data to report.