Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio

Abstract

The clinical efficacy of fish oil and high-purity eicosapentaenoic acid ethyl ester (hp-EPA-E) for treating cardiovascular disease (CVD) has been reported. Fish oil contains saturated and monounsaturated fatty acids that have pharmacological effects opposite to those of ω3 fatty acids (ω3). Moreover, ω3, such as EPA and docosahexaenoic acid (DHA), do not necessarily have the same metabolic and biological actions. This has obscured the clinical efficacy of ω3. Recently, the Japan EPA Lipid Intervention Study (JELIS) of hp-EPA-E established the clinical efficacy of EPA for CVD, and higher levels of blood EPA, not DHA, were found to be associated with a lower incidence of major coronary events. A significant reduction in the risk of coronary events was observed when the ratio of EPA to arachidonic acid (AA) (EPA/AA) was ＞0.75. Furthermore, the ratio of prostaglandin (

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases

“…Baseline and post-treatment RBC PUFA levels in EMT study participants were similar to those reported previously in studies of omega-3 PUFA supplementation in healthy volunteers [13,19], women with breast hyperplasia [20][21] and in patients with lung cancer [22]. In particular, post-treatment % RBC EPA values were similar to those observed in an eight-week study of exactly the same EPA-FFA formulation and dose in healthy volunteers and inflammatory bowel disease patients [23].…”

“…Longer-term follow-up would have been required in order to confirm the return of the PUFA profile in RBCs to that observed pre-intervention. 'Washout' kinetics were not dependent on the prior degree of RBC incorporation or duration of EPA treatment and are similar (in these CRC patients) to the decay in RBC EPA content observed in at least three healthy volunteer studies, in which peak RBC EPA content was similar to that seen in the EMT study [13,19,27], as well as two more recent studies of pre-and post-menopausal women [20][21].…”

“…There was a concurrent, statistically significant decrease in omega-6 PUFA AA content (mean absolute 1.31±0.57% reduction) in those individuals receiving EPA (P<0.05; Figure 1D and Figure 2G). The EPA/AA ratio is widely quoted as a predictive biomarker of omega-3 PUFA activity, particularly in cardiology studies [13]. There Individual RBC PUFA content profiles varied significantly between individuals in both EPA and placebo groups (Figure 2A-H).…”

Association of Fish Consumption-Derived Ratio of Serum n-3 to n-6 Polyunsaturated Fatty Acids and Cardiovascular Risk With the Prevalence of Coronary Artery Disease

“…7) It seems therefore likely that in vivo, EPA and DHA exhibit different physiological activities. [8][9][10][11] A strong positive correlation is known to exist between serum EPA and DHA levels, and this was also shown in our study cited above. [4][5][6] Because serum EPA and serum DHA levels serve as confounding factors for each other, there are limits to discussing their effects on the incidence of coronary artery disease.…”

“…12) This result suggests that interventions targeting the serum EPA level or serum EPA/arachidonic acid (AA) ratio could be useful for the prevention of CAD. 11,13) Thus, the n-3/n-6 PUFA ratio may play an important role in reducing the risk of a CV event.…”