Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation
Status: | Completed |
---|---|
Conditions: | Peripheral Vascular Disease |
Therapuetic Areas: | Cardiology / Vascular Diseases |
Healthy: | No |
Age Range: | 20 - 45 |
Updated: | 11/3/2017 |
Start Date: | October 2011 |
End Date: | April 2014 |
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.
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.
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.
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.
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