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Comment & Response
September 2016

Fish Oils and Bleeding—Where Is the Evidence?

Author Affiliations
  • 1Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls
JAMA Intern Med. 2016;176(9):1405-1406. doi:10.1001/jamainternmed.2016.3968

To the Editor In an article in a recent issue of JAMA Internal Medicine1 on the growing use of dietary supplements and the potential adverse interactions with ethical drugs, Qato et al indicated in Table 4 that the potential adverse drug event for warfarin sodium–ω-3 (omega-3) fish oil was increased risk of bleeding. The idea that fish oils increase risk for bleeding is a legend that persists despite substantial evidence to the contrary. In 2014, we reviewed the literature regarding the risk for clinically significant bleeding associated with fish oil use and concluded, “We found no evidence to contravene the statement in the US Food and Drug Administration-approved package inserts for the currently marketed ω-3 pharmaceutical products stating that these agents ‘do not produce clinically significant bleeding episodes.’”2

Our review2 included a study with 511 patients who underwent coronary artery bypass graft surgery, all on aspirin or warfarin, given fish oil or not for 9 months. The authors concluded, “no excess of bleeding episodes could be ascribed to the use of fish oil, even when given in addition to either aspirin or warfarin.” Another study3 with 1523 patients who had an acute myocardial infarction found no relationship between either the use of fish oil supplements or the ω-3 index (erythrocyte eicosapentaenoic acid + docosahexaenoic acid levels) and adverse bleeding episodes during hospitalization. In a multicenter trial4 testing the effects of high dose fish oil in 1516 patients undergoing open heart surgery, over half of whom were on antiplatelet drugs and 16% on anticoagulants, there was less bleeding compared with placebo.4 When testing the effects of 4 g/d of an ω-3 pharmaceutical product (eicosapent ethyl; Amarin Corp) on warfarin pharmacokinetics and anticoagulation parameters, the authors concluded that the combination was safe and well tolerated.5 In 11 patients on stable warfarin therapy, fish oil did not alter international normalized ratios or increase risk for bleeding.6 The assertions that fish oils cause bleeding and adversely interact with blood thinners are not evidence based.

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Article Information

Corresponding Author: William S. Harris, PhD, Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, 5009 W 12th St, Ste 8, Sioux Falls, SD 57105 (bill.harris@usd.edu).

Conflict of Interest Disclosures: The author is also the president of OmegaQuant Analytics, LLC, a laboratory that specializes in the analysis of fatty acids and markets to consumers a blood test to measure ω-3 fatty acid levels.

Qato  DM, Wilder  J, Schumm  LP, Gillet  V, Alexander  GC.  Changes in prescription and over-the-counter medication and dietary supplement use among older adults in the United States, 2005 vs 2011.  JAMA Intern Med. 2016;176(4):473-482.PubMedGoogle ScholarCrossref
Wachira  JK, Larson  MK, Harris  WS.  n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights.  Br J Nutr. 2014;111(9):1652-1662.PubMedGoogle ScholarCrossref
Salisbury  AC, Harris  WS, Amin  AP, Reid  KJ, O’Keefe  JH  Jr, Spertus  JA.  Relation between red blood cell omega-3 fatty acid index and bleeding during acute myocardial infarction.  Am J Cardiol. 2012;109(1):13-18.PubMedGoogle ScholarCrossref
Mozaffarian  D, Marchioli  R, Macchia  A,  et al; OPERA Investigators.  Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.  JAMA. 2012;308(19):2001-2011.PubMedGoogle ScholarCrossref
Braeckman  RA, Stirtan  WG, Soni  PN.  Phase 1 study of the effect of icosapent ethyl on warfarin pharmacokinetic and anticoagulation parameters.  Clin Drug Investig. 2014;34(7):449-456.PubMedGoogle ScholarCrossref
Bender  NK, Kraynak  MA, Chiquette  E, Linn  WD, Clark  GM, Bussey  HI.  Effects of marine fish oils on the anticoagulation status of patients receiving chronic warfarin therapy.  J Thromb Thrombolysis. 1998;5(3):257-261.PubMedGoogle ScholarCrossref