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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cardiovascular Disease, Inflammation

Intervention / Treatment
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* Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 300mg Fish Oil (EPA + DHA) Supplement<br> | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)<br>* Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period<br>* Other names: Fish Oil;|
| Experimental: 600mg Fish Oil (EPA+DHA) Supplement<br> | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)<br>* Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period<br>* Other names: Fish Oil;|
| Experimental: 900mg Fish Oil (EPA + DHA) Supplement<br> | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)<br>* Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period<br>* Other names: Fish Oil;|
| Experimental: 1800mg Fish Oil (EPA + DHA) Supplement<br> | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)<br>* Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period<br>* Other names: Fish Oil;|
| Placebo Comparator: Placebo<br> | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)<br>* Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period<br>* Other names: Fish Oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Concentrations of Inflammatory Markers (TNF-alpha and IL-6) Following 5 Months of Treatment |  | 5 months | 
| Mean Concentrations of CRP Following 5 Months of Treatment |  | 5 months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular disease, Inflammation, Fish Oil, Omega-3 Fatty Acids, LPS, Endotoxin