Introduction

The sales of fish oil supplements have risen dramatically over recent years. Sales in Australia increased by 65% between 2008 and 2011, when approximately 70 different brands sold seven million items. However, are there benefits to taking fish oil? Fish oil is primarily advertised to both improve cardiovascular health and ease joint inflammation. As cardiovascular disease continues to be the leading cause of death in Australia, this article will focus on the evidence for fish oil in cardiovascular disease.

Fish oil is rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids cannot be made by the body so therefore must be obtained from diet or supplements. EPA and DHA can be found in oily fish such as salmon, mackerel or trout, or through supplementation with commercial fish oil products.

Recommendations

Both the Australian Heart Foundation (AHF) and the American Heart Association (AHA) endorse adequate intake of EPA and DHA to reduce cardiovascular disease. The AHF Position Statement, updated in 2008, advocates 500mg of EPA and DHA daily for everyone, and higher doses of 1g daily for those with existing cardiovascular disease. Doses of up to 4g daily are suggested for patients with elevated triglycerides. This can be achieved through eating oily fish at least twice a week or through supplementing the diet with fish oil products. The AHA also recommends adequate EPA and DHA intake for patients as follows:

  • Without documented coronary heart disease:
    • A variety of fish at least twice a week, including foods rich in gamma-linolenic acid (flaxseed, canola, walnuts)
  • With documented coronary heart disease:
    • A minimum of 1g of EPA and DHA per day
  • Requiring triglyceride lowering:
    • 2-4g of EPA and DHA per day

Mechanism of Action

The exact mechanism of fish oil is not known, however its effect on cardiovascular disease is likely to be due to its reduction in triglyceride levels, as well as its anti-inflammatory and anti-thrombotic properties.

EPA competes with arachidonic acid in the cyclooxygenase and lipoxygenase pathways. This decreases the production of pro-inflammatory and pro-thrombotic eicosanoids and increases production of anti-inflammatory and anti-thrombotic eicosanoids.

DHA and EPA also seem to have an effect on triglyceride levels, most likely through altering the metabolism of very-low-density-lipoprotein (VLDL), which is the primary endogenous source of triglycerides.

Diagram 1. EPA in the production of anti-inflammatory eicosanoids.

Evidence

The evidence of fish oil reducing triglyceride levels is well established. Doses of 4g of fish oil can reduce triglyceride levels by 25-30% in a dose-dependent manner, over at least two weeks. This reduction is similar to that of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase inhibitors (“statins”), which reduce triglyceride levels by 22-45%. There is a greater response to higher base-line triglyceride levels. However, care needs to be taken as fish oil can increase LDL levels by 10-15% and therefore healthcare professionals should be consulted before starting fish oil supplementation for lipid management.

Evidence for the cardiovascular protective effects of fish oil is less definitive. Several epidemiological studies, involving Eskimos, confirmed an inverse relationship between dietary intake of omega-3 fatty acid and cardiovascular mortality. This led to multiple intervention studies investigating the effect that omega-3 fatty acids (dietary or supplementary) have on cardiovascular morbidity and mortality. Several hundred studies concluded that a daily dose of at least 1g DHA and EPA can reduce total mortality as well as cardiovascular morbidity and mortality. These findings led to the 2008 recommendations from the AHA regarding EPA and DHA intake.

More recent studies, however, have found evidence to be less conclusive. A 2012 meta-analysis of 20 studies totalling over sixty thousand patients found no significant difference in all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke. Additionally, a Cochrane Review concluded that fish oil has no clear effect on overall mortality, cardiovascular events, or cancers in any of the study groups, including: the general population, those at high risk of cardiovascular disease, or patients with existing cardiovascular disease.

Safety

There are minimal drug interactions with fish oil. Doses of up to 3g of omega-3 fatty acids are generally regarded as safe by the FDA (Food and Drugs Administration). The main concern is the anti-thrombotic effect exhibited by fish oil. There is an increased risk of bleeding at doses above 3g per day, especially when combined with conventional antiplatelet or anticoagulant agents. Research has indicated that fish oil has no effect on INR, however it should be noted this study had very limited numbers (11 participants) and was conducted over a short four week period. Until further research is conducted, it seems prudent to combine fish oil with antiplatelet and anticoagulant medicines cautiously; avoiding the combination if possible. However, the previously mentioned Cochrane Review also concluded there is no evidence to support advising patients to cease fish oil supplements for safety reasons.

Conclusion

Omega-3 fatty acids have a proven positive impact on triglyceride levels, however their effect on overall cardiovascular mortality is less well defined. They have minimal safety concerns and are widely available. Omega-3 fatty acids may have a role in helping to reduce the burden of cardiovascular disease, however they should not replace conventional therapies.

References:

  1. Heart Foundation. Position Statement: Fish, fish oils, n-3 polyunsaturated fatty acids and cardiovascular health. 2nd ed. National Heart Foundation of Australia; 2008.
  2. 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 Jul; 5(3): 257-261.
  3. Royal Pharmaceutical Society. Dietary Supplements: Fish oil.  Medicines Complete 2014; May.
  4. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997 May; 65(5 Suppl): 1645S-54S.
  5. Hooper L, Harrison RA, Summerbell CD, Moore H, Worthington HV, Ness A, et al. Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev. 2004 Oct 18; (4): CD003177.
  6. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19; 106(21): 2747-57.
  7. Natural Medicines Comprehensive Database. Fish Oil. Stockton, CA: Therapeutic Research Faculty; 2014.
  8. Stein EA, Lane M, Laskarzewski P. Comparison of statins in hypertriglyceridemia. Am J Cardiol. 1998 Feb 26; 81(4A): 66B-69B. Review.
  9. Vital Kids Medicine. Why essential fats are essential. Seattle, WA: Vital Kids Medicine, PLLC; 2014.
  10. Von Schacky C. The role of omega-3 fatty acids in cardiovascular disease. Curr Atheroscler Rep. 2003 Mar; 5(2): 139-45.
  11. Weitz D, Weintraub H, Fisher E, Schwartzbard AZ. Fish oil for the treatment of cardiovascular disease. Cardiol Rev. 2010 Sep-Oct; 18(5): 258-63.

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