by Lewis Chang, PhD
Fish oil is rich in omega-3 fatty acids EPA and DHA. Increased intake of EPA and DHA is beneficial for cardiovascular health, cognitive function, mental health, maternal and child health, immunity and inflammation. EPA and DHA supplements are becoming more and more popular across a wide diversity of people; from healthy individuals to vulnerable populations with impaired health.
Higher omega-3 concentrations may compete with fatty acids such as arachidonic acid for metabolizing enzymes. The interaction results in a decreased production of compounds that induce platelet aggregation and an increased production of compounds with anti-platelet properties, hence the anticoagulation benefits of omega-3. However, for patients who are under antithrombotic therapy (either with platelet aggregation inhibitors such as aspirin or anticoagulant drugs such as warfarin), the potential risk of bleeding due to the concurrent use of omega-3 fatty acids has been a concern by many clinicians, particularly surgeons.1,2
Multiple clinical studies have been conducted to investigate whether omega-3 fatty acids pose a clinically significant bleeding risk. So far, the findings have been consistent:
- A 2004 Cochrane review of 48 randomized controlled trials and 41 epidemiological analyses concludes that 0.4-7 g/day omega-3 fatty acids do not result in any change in clinical bleeding manifestations3
- A 2007 review of 19 clinical studies involving nearly 4400 surgical patients concludes that the risk for clinically significant bleeding was virtually nonexistent with the use of 1.4-21 g/day of omega-3 fatty acid supplements, even with the concurrent use of antiplatelet or antithrombotic medications4
- A 2013 systematic review of 10 randomized trials involving nearly 1000 adults 60 years or older concludes that there is no difference in total adverse event rates between daily use of placebo or 0.03-1.86 g EPA and/or DHA for 6-52 weeks5
- A 2014 review of 7 randomized controlled trials and 3 epidemiological studies concludes that omega-3 fatty acid treatment has no effect on the risk of clinically significant bleeding in either monotherapy or combination therapy settings and there is no support for discontinuing the use of omega-3 fatty acid treatment before invasive procedures6
- A 2017 systematic review based on 32 publications on healthy subjects and 20 publications on patients undergoing surgery finds that fish oil supplements reduce platelet aggregation in healthy subjects and do not increase intra- or post-operative bleedings in patients, and concludes that discontinuation of fish oils supplements prior to surgery is not recommended7
Despite the accumulating evidence demonstrating the safety of fish oil, the worry seems to persist, especially when at risk patients are involved.
In 2018, researchers from Danone Food Safety Centre (Palaiseau, France) and Nutricia Research (Utrecht, the Netherlands) evaluated the safety data from 8 clinical intervention studies involving over 600 patients, including oncology patients, HIV patients, ICU patients, and patients with Alzheimer’s disease.8 The levels of omega-3 fatty acids received by these patients (either via oral consumption or tube feeding) ranged from 1.5-10.2 g/day with a duration of 8 days to 52 weeks. The outcomes included bleeding-related adverse events, prothrombin time, and partial thromboplastin time. In the end, the researchers found no evidence of increased risk of bleeding with the use of omega-3 fatty acid products in these patients, with or without concomitant use of antithrombotic medications.
In summary, the legitimate concern of increased bleeding as a result of omega-3 fatty acid intake has not been supported by numerous randomized controlled trials and epidemiological studies involving a wide range or participants, from healthy young folks to surgical patients to very vulnerable older patients.
Why is this Clinically Relevant?
- Fish oil or EPA/DHA products are associated with a variety of benefits, from cardiovascular health to cognitive function to anti-inflammation
- The concern of increased risks of bleeding associated with these ingredients has not been validated by a large number of clinical studies and systemic reviews
- Clinicians should inform patients of the safety of omega-3 fatty acids for the vast majority of the population, and there is no scientific evidence supporting the discontinuation of omega-3 products prior to surgery
- Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C.
- Braga M, Ljungqvist O, Soeters P, et al. ESPEN Guidelines on Parenteral Nutrition: surgery. Clin Nutr. 2009;28(4):378-386.
- Hooper L, Thompson RL, Harrison RA, et al. Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev. 2004(4):CD003177.
- Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol. 2007;99(6A):44C-46C.
- Villani AM, Crotty M, Cleland LG, et al. Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature. BMC Geriatr. 2013;13:41.
- 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.
- Begtrup KM, Krag AE, Hvas AM. No impact of fish oil supplements on bleeding risk: a systematic review. Dan Med J. 2017;64(5).
- Jeansen S, Witkamp RF, Garthoff JA, van Helvoort A, Calder PC. Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: Analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition. Clin Nutr. 2018;37(3):948-957.