A Review of Omega-3 Ethyl Esters for Cardiovascular Prevention and Treatment of Increased Blood Triglyceride Levels

The two marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevalent in fish and fish oils, have been investigated as a strategy towards prophylaxis of atherosclerosis. While the results with fish and fish oils have been not as clear cut, the data generated with the purified ethyl ester forms of these two fatty acids are consistent. Although slight differences in biological activity exist between EPA and DHA, both exert a number of positive actions against atherosclerosis and its complications. EPA and DHA as ethyl esters inhibit platelet aggregability, and reduce serum triglycerides, while leaving other serum lipids essentially unaltered. Glucose metabolism has been studied extensively, and no adverse effects were seen. Pro-atherogenic cytokines are reduced, as are markers of endothelial activation. Endothelial function is improved, vascular occlusion is reduced, and the course of coronary atherosclerosis is mitigated. Heart rate is reduced, and heart rate variability is increased by EPA and DHA. An antiarrhythmic effect can be demonstrated on the supraventricular and the ventricular level. More importantly, two large studies showed reductions in clinical endpoints like sudden cardiac death or major adverse cardiac events. As a consequence, relevant cardiac societies recommend using 1 g/day of EPA and DHA for cardiovascular prevention, after a myocardial infarction and for prevention of sudden cardiac death

Omega-3 Index and Cardiovascular Health

Recent large trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the cardiovascular field did not demonstrate a beneficial effect in terms of reductions of clinical endpoints like total mortality, sudden cardiac arrest or other major adverse cardiac events. Pertinent guidelines do not uniformly recommend EPA + DHA for cardiac patients. In contrast, in epidemiologic findings, higher blood levels of EPA + DHA were consistently associated with a lower risk for the endpoints mentioned. Because of low biological and analytical variability, a standardized analytical procedure, a large database and for other reasons, blood levels of EPA + DHA are frequently assessed in erythrocytes, using the HS-Omega-3 Index((R)) methodology. A low Omega-3 Index fulfills the current criteria for a novel cardiovascular risk factor. Neutral results of intervention trials can be explained by issues of bioavailability and trial design that surfaced after the trials were initiated. In the future, incorporating the Omega-3 Index into trial designs by recruiting participants with a low Omega-3 Index and treating them within a pre-specified target range (e.g., 8%-11%), will make more efficient trials possible and provide clearer answers to the questions asked than previously possible

Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations - a comparative bioavailability study of fish oil vs. krill oil

<p>Abstract</p> <p>Background</p> <p>Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared.</p> <p>Methods</p> <p>In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed.</p> <p>Results</p> <p>The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC_{0-72 h}: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC_{0-72 h}: 59.78 ± 36.75%*h) and EE (mean AUC_{0-72 h}: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (<it>p = </it>0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (<it>p </it>= 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA.</p> <p>Conclusion</p> <p>Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.</p

Food2Learn: Positive association between omega-3 index and cognition in healthy adolescents

Poster presentation at: 5th Mind-Body Interface International Symposium. Oct. 20-21, 2015, Taichung, Taiwa

Food2Learn: Effect of 1 year krill oil supplementation on mental well-being in typically developing Dutch adolescents

Poster presentation at: International Society for the Study of Fatty Acids and Lipids. Sep. 5-9, 2016, Cape Town, South Africa

De Novo Lipogenesis-Related Monounsaturated Fatty Acids in the Blood Are Associated with Cardiovascular Risk Factors in HFpEF Patients

De novo lipogenesis (DNL)-related monounsaturated fatty acids (MUFAs) in the blood are associated with incident heart failure (HF). This observation's biological plausibility may be due to the potential of these MUFAs to induce proinflammatory pathways, endoplasmic reticulum stress, and insulin resistance, which are pathophysiologically relevant in HF. The associations of circulating MUFAs with cardiometabolic phenotypes in patients with heart failure with a preserved ejection fraction (HFpEF) are unknown. In this secondary analysis of the Aldosterone in Diastolic Heart Failure trial, circulating MUFAs were analysed in 404 patients using the HS-Omega-3-Index$^{®}$ methodology. Patients were 67 ± 8 years old, 53% female, NYHA II/III (87/13%). The ejection fraction was ≥50%, E/e' 7.1 ± 1.5, and the median NT-proBNP 158 ng/L (IQR 82-298). Associations of MUFAs with metabolic, functional, and echocardiographic patient characteristics at baseline/12 months follow-up (12 mFU) were analysed using Spearman's correlation coefficients and linear regression analyses, using sex/age as covariates. Circulating levels of C16:1n7 and C18:1n9 were positively associated with BMI/truncal adiposity and associated traits (dysglycemia, atherogenic dyslipidemia, and biomarkers suggestive of non-alcoholic-fatty liver disease). They were furthermore inversely associated with functional capacity at baseline/12 mFU. In contrast, higher levels of C20:1n9 and C24:1n9 were associated with lower cardiometabolic risk and higher exercise capacity at baseline/12 mFU. In patients with HFpEF, circulating levels of individual MUFAs were differentially associated with cardiovascular risk factors. Our findings speak against categorizing FA based on physicochemical properties. Circulating MUFAs may warrant further investigation as prognostic markers in HFpEF

Omega-3 Index and Sudden Cardiac Death

Sudden cardiac death (SCD) is an unresolved health issue, and responsible for 15% of all deaths in Western countries. Epidemiologic evidence, as well as evidence from clinical trials, indicates that increasing intake and high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect from SCD and other major adverse cardiac events. Levels of EPA+DHA are best assessed by the Omega-3 Index, representing the red cell fatty acid content of EPA+DHA. Work is in progress that will further define the value of the Omega-3 Index as a risk factor for SCD, other cardiac events, and as target for treatment with EPA+DHA