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

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.

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.