Understanding the importance of EPA in cardiovascular health, by Dr Nina Bailey


Many of the health benefits associated with fish and marine food consumption are now widely recognised to be due to

Inuit’s are known to have a high intake of fatty fish and low incidence of cardiovascular disease.  Pure EPA supplements derived from purified fish oil are a convenient alternative.

Inuits are known to have a high intake of fatty fish and low incidence of cardiovascular disease. Pure EPA supplements derived from purified fish oil are a convenient alternative.

their high content of the long-chain omega-3 fatty acids EPA and DHA.  For those individuals who are not lovers of oily fish (only around 27% of the UK population actually eat oily fish regularly) [1] the use of supplements offers a convenient alternative and, in addition to supporting general health, they can be used to obtain the therapeutic levels required to treat some health conditions.  Individuals using fish oil for cardiovascular support, such as cholesterol and/or triglyceride management, may be surprised to know, however, that some fish oil supplements, although high in omega-3, may not actually offer the heart health benefits that manufactures claim.  Indeed, unless the oil is rich in EPA, or ideally delivers pure EPA, the consumer may well be wasting their money.

The differential roles of EPA and DHA

Numerous clinical trials have reported the effects of omega-3 intervention using fish oil or purified omega-3 for the prevention or treatment of numerous conditions.  Effects of the individual fatty acids EPA and DHA are, however, rarely differentiated.   For example, DHA concentrations within nerve tissue are several hundred times higher than EPA, highlighting DHA’s important structural role within the brain and its role in normal functioning of the central nervous system.  In contrast, EPA has a unique role as the precursor to eicosanoids, hormone-like substances that, in addition to modulating several areas of cardiovascular health, regulate inflammatory and immune pathways.  These differences highlight potential and important differences in their physiological roles.  Yet despite our growing understanding of them as unique fatty acids with individual and widely different functions in the areas of brain function, immune and inflammatory support and as cardiovascular modulators, they are generally pooled together under the umbrella term of ‘omega-3’.  Unsurprisingly, the outcomes of some clinical trials have been obscured because the ratio of EPA to DHA and the consequential differences in outcomes is not taken into account.

Omega-3 and Heart Disease – cardiovascular health is related to high omega-3 intake

Blood levels of EPA (not DHA) are associated with a lower risk of cardiovascular disease.

Blood levels of EPA (not DHA) are associated with a lower risk of cardiovascular disease.

Early evidence for the role of EPA and DHA in cardiovascular disease risk factors originated from observational studies of populations such as the Greenland Inuit, known to have a high intake of omega-3 and low incidence of cardiovascular disease.  When the fatty acid compositions of plasma phospholipids from the Inuit were compared with Danes, the most notable difference between these two populations was the high content of EPA (but not DHA) observed in Inuit phospholipids, with these levels correlating with their high consumption of EPA-rich marine foods. [2, 3]

EPA, DHA, cholesterol and triglycerides

Erythrocyte levels of EPA and DHA (the omega-3 index) is now recognised as a valid biomarker of cardiovascular disease (CVD) risk. [4] The benefits of oils containing  omega-3 on the cardiovascular system have been widely documented and include anti-hypertensive, anti-arrhythmic, anti-thrombotic and anti-inflammatory effects.  Raising levels of EPA and DHA is also beneficial for  a high cholesterol level and triglycerides, levels of which are biomarkers for increased risk of coronary heart disease (CHD).  Total cholesterol levels are made up of ‘good’ cholesterol (HDL-C) and ‘bad’ cholesterol (LDL-C and VLDL-C). When serum triglycerides are elevated, the non-HDL level enhances CVD risk prediction, with non-HDL the secondary target of therapy when triglyceride levels are ≥ 200 mg/dL.

Cholesterol: the good and the bad
– HDL High-density lipoprotein
     – Makes up 20%–30% of total cholesterol
     – The “good” cholesterol moves cholesterol from arteries to the  liver
– LDL Low-density lipoprotein
     – Makes up 60%–70% of total cholesterol
     – Main form of “bad” cholesterol
     – Causes build-up of plaque inside arteries
– VLDL Very-low-density lipoprotein
     – Makes up 10%–15% of total cholesterol with LDL, the main form of “bad” cholesterol
     – A precursor of LDL

How to lower Cholesterol – only pure EPA lowers both triglyceride and cholesterol levels

Although both EPA and DHA lower triglyceride levels, they exert very different effects on cholesterol levels. A meta-analysis of 21 randomised, controlled trials showed that compared with placebo, EPA reduced LDL-C levels, whereas DHA raised LDL-C levels.  [27]. Thus, products that contain both DHA and EPA may actually increase LDL-C levels.  [5]  In addition,  a systemic review of 22 randomised controlled trials of EPA and/or DHA reported that increased LDL-C levels were observed in 71% of studies of DHA monotherapy but in none of the studies of EPA monotherapy.  Furthermore, these results were observed in direct head-to-head comparisons, with DHA increasing LDL-C levels by 2.6% on average, and EPA decreasing LDL-C levels by 0.7%. [6] In summary, products that contain both DHA and EPA reduce triglycerides but increase LDL-C levels, whereas EPA-only oils reduce both.

Ditch the DHA

If the presence of DHA with oil aimed at lipid management for cardiovascular health gives rise to opposing outcomes than those desired it would be logical therefore to remove DHA and treat with pure EPA.  Currently in the UK, the only prescription product available for triglyceride management (Omacor®) contains both EPA and DHA.   In contrast, ethyl-EPA (as the drug Epadel®) is considered the ‘gold standard’ treatment in Japan for preventing recurrent coronary events [7] and the recent launch of the FDA approved drug Vascepa®, clinically shown to reduce both triglyceride and cholesterol, [8] shows that both the USA and Japan recognise the importance of a DHA-free prescription product for optimal cardiovascular health.

The AA to EPA ratio

EPA and DHA do not have the same metabolic and biological actions [9].  EPA, unlike DHA, is the precursor to cardiovascular, inflammatory and immune regulating eicosanoids that have opposing effects to those derived from the omega-6 fatty acid arachidonic acid (AA).  The AA to EPA ratio influences cardiovascular health via effects on platelet aggregation, vasoconstriction, arrhythmia, blood pressure and inflammation.  Compared with DHA, EPA administration reduces the AA to EPA ratio and thus has favourable effects on the ratio of eicosanoid products to one that inhibits the onset and/or progression of CVD. [10]

Summary

Elevated triglyceride and cholesterol levels are risk factors for heart disease and managing lipid levels is essential for good cardiovascular health.  Blood levels of EPA (not DHA) are associated with a lower risk of cardiovascular disease events and of all-cause death. [11] Treating with pure EPA has cardiovascular health benefits that are clinically superior to DHA-containing oils or pure DHA oils.

References

1.            Ian Givens D, Gibbs RA: Current intakes of EPA and DHA in European populations and the potential of animal-derived foods to increase them. The Proceedings of the Nutrition Society 2008, 67:273-280.

2.            Dyerberg J, Bang HO, Hjorne N: Fatty acid composition of the plasma lipids in Greenland Eskimos. The American journal of clinical nutrition 1975, 28:958-966.

3.            Bang HO, Dyerberg J, Hjoorne N: The composition of food consumed by Greenland Eskimos. Acta medica Scandinavica 1976, 200:69-73.

4.            Harris WS, Von Schacky C: The Omega-3 Index: a new risk factor for death from coronary heart disease? Preventive medicine 2004, 39:212-220.

5.            Wei MY, Jacobson TA: Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Current atherosclerosis reports 2011, 13:474-483.

6.            Jacobson TA, Glickstein SB, Rowe JD, Soni PN: Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. Journal of clinical lipidology 2012, 6:5-18.

7.            Yamanouchi D, Komori K: Eicosapentaenoic acid as the gold standard for patients with peripheral artery disease? – subanalysis of the JELIS trial. Circulation journal : official journal of the Japanese Circulation Society 2010, 74:1298-1299.

8.            Ballantyne CM, Braeckman RA, Soni PN: Icosapent ethyl for the treatment of hypertriglyceridemia. Expert opinion on pharmacotherapy 2013, 14:1409-1416.

9.            Mozaffarian D, Wu JH: (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? The Journal of nutrition 2012, 142:614S-625S.

10.          Ohnishi H, Saito Y: Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio. Journal of atherosclerosis and thrombosis 2013.

11.          Chien KL, Lin HJ, Hsu HC, Chen PC, Su TC, Chen MF, Lee YT: Comparison of predictive performance of various fatty acids for the risk of cardiovascular disease events and all-cause deaths in a community-based cohort. Atherosclerosis 2013, 230:140-147.

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Dr Nina Bailey

About Dr Nina Bailey

Nina is a leading expert in marine fatty acids and their role in health and disease. Nina holds a master’s degree in Clinical Nutrition and received her doctorate from Cambridge University. Nina’s main area of interest is the role of essential fatty acids in inflammatory disorders. She is a published scientist and regularly features in national health publications and has featured as a nutrition expert on several leading and regional radio stations including SKY.FM, various BBC stations and London’s Biggest Conversation. Nina regularly holds training workshops and webinars both with the public and health practitioners.