Ethyl-EPA benefits in peripheral arterial disease

Peripheral arterial disease (PAD) is a disease in which plaque builds up in the arteries that carry blood to the head, organs, and limbs.  Having PAD increases the risk of developing coronary heart disease (CHD), which can increase the risk of suffering a heart attack or having a stroke. An increasing body of evidence indicates that dietary intake of fish-derived polyunsaturated fatty acids shows favourable outcomes in patients with PAD. A recent Japanese study focusing on specific fats suggests that manipulating the ratio of the long-chain fatty acids arachidonic acid (AA) and eicosapentaenoic acid (EPA) can help those suffering from PAD, given their findings that a high AA:EPA ratio may also be a key player in the development of PAD1.

The balance of omega-6 and omega-3 fatty acids within plasma and red blood cell membranes has, for many years, been accepted as a recognised marker of cardiovascular health.  More recently, specific information on individual fatty acids has led researchers to acknowledge that the omega-6:omega-3 ratio may not be as truly a representative biomarker as previously thought.    Both classes of fatty acids encompass many different types of fats but were previously grouped together under one ‘roof’ in regard to their health benefits. Recognising that not all omega-6 and omega-3 fatty acids within these families offer the same health benefits has led to the investigation of the specific long-chain fatty acids EPA and AA, which, unlike their short-chain precursors, give rise to a family of hormone-like substances that have mutually opposing effects on cardiovascular health.  As such, the plasma AA:EPA ratio is becoming recognised not only as a marker of inflammation but more specifically as an atherosclerotic biomarker reflecting the intrinsic omega-6:omega-3 ratio.

The specific ratio of the principal omega-3 and omega-6 fatty acids EPA and AA provides valuable information on the measure and balance of eicosanoids – hormone-like substances produced by the body that regulate a variety of immune, inflammatory and cardiovascular processes.   As a useful indicator of general health status, managing the AA/EPA ratio can offer significant long-term health benefits.  A lower AA/EPA ratio, of less than 3 but not less than 1.5, indicates a better balance of ’anti-inflammatory’ to ’inflammatory’ eicosanoids in the body. If the body reaches a ratio of 7 or over, this implies that the body is in a state of ‘silent-inflammation’ and may be at a higher risk of developing inflammatory-based conditions.  In contrast, anything exceeding a ratio of 15 means a high level of inflammation, common to many inflammatory conditions, including PAD.

Reducing the AA:EPA ratio by high dose supplementation with ethyl-EPA (E-EPA) can have significant positive benefits for many areas of cardiovascular health.     For example, the JELIS study is one of the largest cardiovascular studies and the first to have shown the benefits of high E-EPA dosing in individuals with elevated cholesterol levels. Subjects given 1.8g EPA daily saw a marked reduction in the AA:EPA ratio associated with 19% reduction in cardiovascular events during the next four and a half years2. Since then, outcomes from the JELIS study have continued to show the cardiovascular health benefits of E-EPA, which is now becoming hailed as the ‘gold standard’ in treatments for PAD3.  The benefits of supplementing with E-EPA, it seems, lies in the reduction of the AA:EPA ratio and subsequent reduced production of inflammatory products produced by AA.

Igennus Healthcare Nutrition have recently launched E-EPA 90, the purest ethyl-EPA concentrate available without prescription, suitable for counteracting omega-3 deficiencies and restoring a healthy omega-6 to omega-3 ratio.   Taking just two capsules daily provides the 1g E-EPA that is consistent with published findings for long-chain omega-3 and heart health benefits.


1. Fujihara M, Fukata M, Odashiro K, Maruyama T, Akashi K, Yokoi Y. Reduced Plasma Eicosapentaenoic Acid-Arachidonic Acid Ratio in Peripheral Artery Disease. Angiology. 2012 Feb 26. [Epub ahead of print]

2. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators.  Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.  Lancet. 2007 369:1090-8.

3. Yamanouchi D, Komori K. Eicosapentaenoic acid as the gold standard for patients with peripheral artery disease? – subanalysis of the JELIS trial -. Circ J. 2010 Jul;74(7):1298-9.

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