Clinical trial NCT01078909: Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation
Official title: Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Disease
Inflammation
Keywords: Cardiovascular disease
Inflammation
Fish Oil
Omega-3 Fatty Acids
LPS
Endotoxin
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: United States Department of Agriculture (USDA)
First posted: 2010-03-02
Enrollment: 125
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Concentrations of Inflammatory Markers (TNF-alpha and IL-6) Following 5 Months of Treatment
timeFrame: 5 months
measure: Mean Concentrations of CRP Following 5 Months of Treatment
timeFrame: 5 months
Secondary outcomes:
measure: Change in Lipid Mediators
timeFrame: 1, 2, 3 and 5 days post LPS administration
Other outcomes:
Locations:
city: University Park
country: United States
facility: Penn State University
state: Pennsylvania
Study officials:
affiliation: Penn State University
name: Gordon L Jensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Flock MR, Skulas-Ray AC, Harris WS, Etherton TD, Fleming JA, Kris-Etherton PM. Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. J Am Heart Assoc. 2013 Nov 19;2(6):e000513. doi: 10.1161/JAHA.113.000513.