Mieke van Driel
This is the third article in a series providing evidence-based answers to common questions about complementary medicines from consumers and healthcare professionals.
What is fish oil?
Fish oil, derived from fatty fish, is an important source of omega-3 polyunsaturated fatty acids (n-3 PUFA) including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). In Australia, it is widely used and 25.2% of respondents in the 2010 health survey reported that they had taken fish oil in the previous 24 hours.1 Fish oil, in the form of cod liver oil, became popular in the 19th century as a source of vitamin D for sun-deprived children in Europe. Today it is used mostly by consumers hoping to prevent cardiovascular disease and stroke. The National Heart Foundation of Australia recommends an intake of 500 mg DHA and EPA daily for the general population, and double that for patients with confirmed heart disease2 whereas others question this advice.3
Fish oil has also been used for inflammatory conditions such as joint pains, ulcerative colitis and Crohn’s disease.4–6 There are few systematic reviews relating to indications for fish oils and controlled clinical trials continue to produce conflicting results, not only for effectiveness but also for the dose required for efficacy. Investigations across a variety of inflammatory diseases suggest efficacy is dose-dependent. Collectively, these studies indicate that the anti-inflammatory dose of fish oil requires 2.7 g or more of n-3 PUFA daily. However, this requires a daily dose of nine or more standard fish oil capsules, which typically contain 30% long chain n-3 PUFAs w/w, whereas people who self-medicate with fish oil generally take one or two capsules daily.3,7
Who asks about fish oil?
The medicine call centres received 1067 queries from consumers about fish oil (10.4% of all complementary medicine questions) and 323 from healthcare professionals (6.0%).8
The average age of consumers calling about fish oil was 59 years; 80% were women and most questions focused on interactions (33%), efficacy (20%) and adverse drug reactions (ADRs, 16%). Similarly, health professionals were predominantly concerned about interactions (43%) and ADRs (27%), but less about efficacy (9%).8
Common consumer and health professional question
Is it safe to combine fish oil with anticoagulants or antiplatelets?
If the dose of fish oil is <3 g daily, combinations of fish oil and warfarin or antiplatelet medication (eg aspirin or clopidogrel) are considered safe.4,9–11
However, no studies of fish oil used in combination with the new oral anticoagulants (dabigatran, rivaroxaban) or antiplatelets (abciximab, eptifibatide, prasugrel, ticagrelor) were retrieved.
The mechanism for the anticoagulant activity of fish oil relates to changes in the ratio of phospholipids in platelet membranes, as fish oil decreases the synthesis of thromboxane A2 from arachidonic acid in platelets.9 Consumption of fish-rich diets or fish oil supplements may reduce platelet aggregation.9 Therefore, combined use of fish oil with anticoagulant or antiplatelet agents may, theoretically, increase the risk of bleeding.
In commonly used doses (<3 g daily), fish oil does not seem to increase the risk of bleeding, as previously suggested.4,9–11 However, the safety of higher doses (>3 g/day) is less clear.9 Although not confirmed in trials, bruising and minor bleeding are frequently reported by people taking fish oils, so it is wise to monitor for these potential adverse effects and reduce the dose if they occur.
Common consumer question
How does fish oil compare with aspirin for prevention of cardiovascular disease?
Currently, neither aspirin nor fish oil is well supported by high-level evidence for primary prevention of cardiovascular disease. For aspirin, this is because the harms seem to outweigh the benefits.12 In secondary prevention fish oil does not seem to provide any further benefit beyond modern medical therapy, particularly statins,13,14 whereas aspirin is effective in preventing further myocardial infarctions (MI) after a first cardiovascular event.15–18
In large, well-designed secondary prevention studies, fish oil did not prevent cardiovascular death, Myocardial Infarction (MI) or stroke in patients with risk factors for heart disease or with previous MI.14,16,17 In contrast, there is ample evidence that aspirin is protective against these in patients at high risk of cardiovascular disease.14,18
Common health professional question
Is it safe to take fish oil in pregnancy?
Although fish oil supplements are unlikely to be harmful in pregnancy, they are not routinely recommended for pregnant women. There is no strong evidence for benefits to the mother or child unless the mother has a deficiency of or inadequate intake of omega-3-fatty acids.19–22
A joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Consultation on fats and oils in human nutrition recommended that pregnant women should consume at least 2.6 g of omega-3 fatty acids, incorporating 100–300 mg of DHA daily to cover fetal requirements.23 Postnatal deficiencies caused by low maternal intake have been associated with reduced visual acuity, poor neurodevelopment and ill-effects on behaviour.23,24
A number of studies have shown a positive effect on cognitive development and intelligence quotient of children whose mothers consumed greater amounts of essential fatty acids.21,25,26 However, the Evidence Report/Technology Assessment prepared for the Agency of Healthcare Research and Quality (AHRQ) of the US Department of Health and Human Services, and other reviews conclude that, based on the small number of current well-designed studies, there is no conclusive evidence of benefit.19–22,27
Sanne Kreijkamp-Kaspers MD, PhD, FRACGP, MSc, Senior Lecturer, Discipline of General Practice, School of Medicine, The University of Queensland, Brisbane, QLD. firstname.lastname@example.org
Treasure McGuire PhD, BPharm, BSc, GradDipClinHospPharm, GCHEd, Associate Professor; Faculty of Health & Medical Sciences, Bond University, Gold Coast; Senior Lecturer, School of Pharmacy, The University of Queensland, Brisbane; Assistant Director (Practice and Development), Mater Pharmacy Services, Mater Health Services, Brisbane, QLD
Suzanne Bedford PhD, BSc, Honorary Research Fellow at Mater Research Institute, The University of Queensland, Brisbane, QLD
Peter Loadsman BPharm, BSc, Mater Pharmacy Services, Mater Health Services, Brisbane, QLD
Marie Pirotta FRACGP, PhD, NHMRC Career Development Fellow, Department of General Practice, University of Melbourne, Carlton, VIC
Geraldine Moses BPharm, DClinPharm, Senior Clinical Pharmacist, Mater Pharmacy Services, Mater Health Services, Brisbane, QLD
Mieke van Driel MD, MSc, PhD, FRACGP, Professor and Head, Discipline of General Practice, School of Medicine, The University of Queensland, Brisbane, QLD
Competing interests: The authors received an Integrative Medicine grant from the RACGP.
Provenance and peer review: Commissioned, externally peer reviewed.
- Morgan TK, Williamson M, Pirotta M, Stewart K, Myers SP, Barnes J. A national census of medicines use: A 24-hour snapshot of australians aged 50 years and older. Med J Aust 2012;196:50–53.
- Heart Foundation. Position statement. Fish, ﬁsh oils, n-3 polyunsaturated fatty acids and cardiovascular health. Updated November 2008. Available at www.heartfoundation.org.au/SiteCollectionDocuments/Fish-FishOils-position-statement.pdf [Accessed 11 June 2014].
- Greene J, Ashburn SM, Razzouk L, Smith DA. Fish oils, coronary heart disease, and the environment. Am J Public Health 2013;103:1568–76.
- 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.
- Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 2007;129:210–23.
- Turner D, Shah PS, Steinhart AH, Zlotkin S, Griffiths AM. Maintenance of remission in inflammatory bowel disease using omega-3 fatty acids (fish oil): A systematic review and meta-analyses. Inflamm Bowel Dis 2011;17:336–45.
- Cleland LG, James MJ, Proudman SM. Fish oil: What the prescriber needs to know. Arthritis Res Ther 2006;8:202.
- Kreijkamp-Kaspers S, McGuire T, Bedford S, et al. Your questions about complementary medicines answered. Aust Fam Physician 2015;44:373–74.
- Harris WS. Expert opinion: Omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol 2007;99:44C–46C.
- Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother 2004;38:50–52.
- Wang C, Chung M, Lichtenstein A, et al. Effects of omega-3 fatty acids on cardiovascular disease. Evid Rep Technol Assess (Summ) 2004;1–8.
- Sutcliffe P, Connock M, Gurung T, et al. Aspirin in primary prevention of cardiovascular disease and cancer: A systematic review of the balance of evidence from reviews of randomized trials. PLoS One 2013;8:e81970.
- Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: A systematic review. Clin Cardiol 2009;32:365–72.
- Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: A systematic review and meta-analysis. JAMA 2012;308:1024–33.
- Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86.
- Kwak SM, Myung SK, Lee YJ, Seo HG, Korean Meta-analysis Study G. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: A meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med 2012;172:686–94.
- Roncaglioni MC, Tombesi M, Silletta MG. N-3 fatty acids in patients with cardiac risk factors. N Engl J Med 2013;369:781–82.
- Antithrombotic Trialists C. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86.
- Mozurkewich EL, Klemens C. Omega-3 fatty acids and pregnancy: Current implications for practice. Curr Opin Obstet Gynecol 2012;24:72-77.
- Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by preclampsia or intrauterine growth restriction. Cochrane Database Syst Rev 2006;CD003402.
- Moher D. Effects of omega-3 fatty acids on child and maternal health. US Department of Health and Human Services, 2005.
- Dennehy C. Omega-3 fatty acids and ginger in maternal health: Pharmacology, efficacy, and safety. J Midwifery Womens Health 2011;56:584–90.
- FDA. Section b: Overview of scientific information on the effect of fish consumption and omega-3 fatty acids on neurodevelopmental health benefits, January 2009. Available at www.fda.gov/Food/FoodborneIllnessContaminants/ChemicalContaminants/ucm153054.htm [Accessed 4 June 2014].
- Bambrick HJ, Kjellstrom TE. Good for your heart but bad for your baby? Revised guidelines for fish consumption in pregnancy. Med J Aust 2004;181:61–62.
- Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s iq at 4 years of age. Pediatrics 2003;111:e39–44.
- Helland IB, Saugstad OD, Saarem K, Van Houwelingen AC, Nylander G, Drevon CA. Supplementation of n-3 fatty acids during pregnancy and lactation reduces maternal plasma lipid levels and provides dha to the infants. J Matern Fetal Neonatal Med 2006;19:397–406.
- Makrides M, Gould JF, Gawlik NR, et al. Four-year follow-up of children born to women in a randomized trial of prenatal dha supplementation. JAMA 2014;311:1802–04.