share: Bleeding and Fish Oil
Expert Opinion: Omega-3 Fatty Acids and Bleeding — Cause for
William S. Harris, PhD
Omega-3 fatty acid ethyl esters have well-known triglyceride-lowering properties and
were shown >30 years ago to inhibit platelet function. With the recent US Food and
Drug Administration (FDA) approval of these agents for treating severe triglyceride
elevations, concerns about excess bleeding naturally arise. However, an objective
assessment of the evidence for clinically significant bleeding reveals that such concerns
are unfounded. As such, the benefits of triglyceride lowering with omega-3 fatty
acids more than outweigh any theoretical risks for increased bleeding.
© 2007 Elsevier Inc. All rights reserved.
(Am J Cardiol 2007;99[suppl]:44C–46C)
As the health benefits of omega-3 fatty acids become
clearer, interest in defining the potential adverse effects of
these nutrients naturally increases. In the review by Bays1 in
this supplement, the possibility of increased risk for bleeding
with omega-3 fatty acids is addressed. Bays clearly
describes the role of omega-3 fatty acids in eicosanoid
metabolism, which forms the biochemical basis for the
concern for increased bleeding with omega-3 fatty acids. He
concludes that although there is little evidence for increased
risk for clinically significant bleeding with omega-3 fatty
acid supplementation, clinicians should be mindful of this
as a theoretical possibility. This commentary provides a
more detailed discussion of the evidence supporting this
conclusion.
The relevant clinical question is the following: What is
the evidence that taking long-chain omega-3 fatty acids in
doses of 1–4 g/day causes clinically significant bleeding?
To answer that question, studies were examined in which
these doses (and typically even greater doses) were provided
to patients who underwent major vascular surgery
(coronary artery bypass grafting or endarterectomy) or femoral
artery puncture for either diagnostic cardiac catheterization
or percutaneous transluminal coronary angioplasty.
There have been 2 studies in which patients who underwent
coronary artery bypass grafting were given omega-3
fatty acids, 2 trials including carotid endarterectomy, and 15
trials in which omega-3 fatty acids were tested in patients
who underwent femoral artery catheterization. These studies
are summarized in Table 1,2–20 along with the concomitant
medications and findings with regard to bleeding complications.
In these studies, the risk for clinically significant
bleeding was virtually nonexistent.
Several years ago, Knapp21 reviewed the published research
regarding omega-3 fatty acids and human thrombosis
and hemostasis. In addition to noting the lack of significant
bleeding with omega-3 fatty acid supplementation in cardiovascular
studies to date, he also referred to studies in
pregnant women in which supplementation with omega-3
fatty acids 2.7 g/day did not lead to increased blood loss at
delivery,22 and he noted that supplemented dialysis patients
were not at increased risk for bleeding.23,24 There had been
1 report that fish oil (5 g) caused increased risk for nosebleeds
in children with hypercholesterolemia,25 but this
could not be replicated in a later trial in children on dialysis.
26
Thus, the experience has been virtually unanimous: omega-
3 fatty acid supplements do not increase the risk for clinically
significant bleeding, even in patients also being treated
with antiplatelet or antithrombotic medications. Anecdotal
reports of an increased bruising tendency have not been
tested in a controlled setting, nor has the possible adverse
interaction between omega-3 fatty acids and newer antiplatelet
drugs (eg, clopidogrel) been examined directly.
Given our present knowledge, I would agree with Bays1
that we are “confident” that omega-3 fatty acids do not
increase risk for adverse bleeding episodes. However, I
would consider the evidence to be at the “A” (well designed
randomized controlled clinical trials) — instead of “C” (reports
to regulatory agencies; multiple case studies; strong
trends; prospective cohort studies; metabolic or clinical surrogate
studies) — level, given the number of randomized,
controlled clinical trials in which these agents were found to
be safe, bearing in mind that more studies are still needed to
determine the combined effects of glycoprotein IIb/IIIa inhibitors
and omega-3 fatty acids. Nevertheless, in considering
the risks and benefits of omega-3 fatty acids for
cardiovascular risk reduction, the latter continue to outweigh
the former.
Sanford School of Medicine of the University of South Dakota, Sioux
Falls, South Dakota, USA.
Address for reprints: William S. Harris, PhD, Department of Medicine,
Sanford School of Medicine of the University of South Dakota, 1400 West
22nd Street, Sioux Falls, South Dakota 57105.
E-mail address: bill.harris@usd.edu.
0002-9149/07/$ – see front matter
© 2007 Elsevier Inc. All rights reserved.
www.AJConline.org
doi:10.1016/j.amjcard.2006.11.021
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Add a Comment1 Comments
Thank you for your post but I hope people reading your posting do not shy away from consuming omega-3 oils contained in many fish such as salmon and non-fish such as flax seeds. In a recent study the United Stated rated the lowest on consumption of this essential fatty acid. We also rated the highest on ADD, ADHD and depression. Omega-3 oil defficiency is linked to this dismal statistic.
I rather have a high dosage of omega-3 oils on my diet to prevent cardiovascular disease than take Cumadin (blood thinning drug) which has more harmful side effects besides bleeding.
The American Heart Association sponsored and endorsed research conducted on the benefits of taking fish oils for heart health. The results were published in 2002. More recent data leaves no doubt that this is the healthiest path to not only a healthy heart but to help with treatment of depression and many other inflammatory conditions. http://circ.ahajournals.org/cgi/content/full/106/21/2747
Many more clinical trials continue. Progressed of those studies can be viewed by visiting http://clinicaltrials.gov
April 8, 2009 - 9:32pmThis Comment