Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial).

Abstract

BACKGROUND:

Patients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD.

METHODS AND RESULTS:

Eighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: -34±46 mg/dL, P<0.001; placebo -10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group.

CONCLUSIONS:

High-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids-derived products and mediators in patients with PAD.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270.

• Authors: S Marlene Grenon, Christopher D Owens, Emily V Nosova, Millie Hughes-Fulford, Hugh F Alley, Karen Chong, Sandra Perez, Priscilla K Yen, John Boscardin, Jason Hellmann, Matthew Spite, Michael S Conte
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 4 Issue 8 Pg. e002034 (Aug 21 2015) ISSN: 2047-9980 [Electronic] England
• PMID: 26296857 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Chemical References

• Biomarkers
• Fatty Acids, Omega-3
• Fish Oils
• Inflammation Mediators
• Triglycerides

Topics

• Administration, Oral
• Aged
• Biomarkers (blood)
• Brachial Artery (drug effects, physiopathology)
• Dietary Supplements
• Double-Blind Method
• Exercise Tolerance (drug effects)
• Fatty Acids, Omega-3 (administration & dosage, blood)
• Female
• Fish Oils (administration & dosage, blood)
• Humans
• Inflammation Mediators (blood)
• Male
• Middle Aged
• Peripheral Arterial Disease (blood, diagnosis, drug therapy, physiopathology)
• San Francisco
• Surveys and Questionnaires
• Time Factors
• Treatment Outcome
• Triglycerides (blood)
• Vasodilation (drug effects)