title: 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.
  
  
  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.
  
  
  BACKGROUND
  URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270.
authors: Department of Surgery, University of California, San Francisco, San Francisco, CA (M.G., C.D.O., E.V.N., M.H.F., H.F.A., K.C., M.S.C.) Department of Surgery, Veterans Affairs Medical Center, San Francisco, CA (M.G., C.D.O., M.H.F., S.P.) Vascular Integrated Physiology and Experimental Therapeutics (VIPERx) Lab, San Francisco, CA (M.G., C.D.O., H.F.A., K.C., S.P.).
authors: S Marlene
authors: SM
authors: Grenon
authors: Department of Surgery, University of California, San Francisco, San Francisco, CA (M.G., C.D.O., E.V.N., M.H.F., H.F.A., K.C., M.S.C.) Department of Surgery, Veterans Affairs Medical Center, San Francisco, CA (M.G., C.D.O., M.H.F., S.P.) Vascular Integrated Physiology and Experimental Therapeutics (VIPERx) Lab, San Francisco, CA (M.G., C.D.O., H.F.A., K.C., S.P.).
authors: Christopher D
authors: CD
authors: Owens
authors: Department of Surgery, University of California, San Francisco, San Francisco, CA (M.G., C.D.O., E.V.N., M.H.F., H.F.A., K.C., M.S.C.).
authors: Emily V
authors: EV
authors: Nosova
authors: Department of Surgery, University of California, San Francisco, San Francisco, CA (M.G., C.D.O., E.V.N., M.H.F., H.F.A., K.C., M.S.C.) Department of Surgery, Veterans Affairs Medical Center, San Francisco, CA (M.G., C.D.O., M.H.F., S.P.).
authors: Millie
authors: M
authors: Hughes-Fulford
authors: Department of Surgery, University of California, San Francisco, San Francisco, CA (M.G., C.D.O., E.V.N., M.H.F., H.F.A., K.C., M.S.C.) Vascular Integrated Physiology and Experimental Therapeutics (VIPERx) Lab, San Francisco, CA (M.G., C.D.O., H.F.A., K.C., S.P.).
authors: Hugh F
authors: HF
authors: Alley
authors: Department of Surgery, University of California, San Francisco, San Francisco, CA (M.G., C.D.O., E.V.N., M.H.F., H.F.A., K.C., M.S.C.) Vascular Integrated Physiology and Experimental Therapeutics (VIPERx) Lab, San Francisco, CA (M.G., C.D.O., H.F.A., K.C., S.P.).
authors: Karen
authors: K
authors: Chong
authors: Department of Surgery, Veterans Affairs Medical Center, San Francisco, CA (M.G., C.D.O., M.H.F., S.P.) Vascular Integrated Physiology and Experimental Therapeutics (VIPERx) Lab, San Francisco, CA (M.G., C.D.O., H.F.A., K.C., S.P.).
authors: Sandra
authors: S
authors: Perez
authors: Department of Biostatistics, University of California Los Angeles, Los Angeles, CA (P.K.Y.).
authors: Priscilla K
authors: PK
authors: Yen
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA (J.B.).
authors: John
authors: J
authors: Boscardin
authors: Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (J.H., M.S.).
authors: Jason
authors: J
authors: Hellmann
authors: Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (J.H., M.S.).
authors: Matthew
authors: M
authors: Spite
authors: Department of Surgery, University of California, San Francisco, San Francisco, CA (M.G., C.D.O., E.V.N., M.H.F., H.F.A., K.C., M.S.C.).
authors: Michael S
authors: MS
authors: Conte
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D019587:Dietary Supplements; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012495:San Francisco; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D018836:Inflammation Mediators; D014280:Triglycerides
keywords: fish oil; n‐3 polyunsaturated fatty acids; peripheral artery disease; specialized pro‐resolving mediators; vascular function