Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects

Terano, Takashi; Hirai, Aizan; Hamazaki, Tomohito; Kobayashi, Satoru; Fujita, Takao; Tamura, Yasushi; Kumagai, Akira

doi:10.1016/0021-9150(83)90181-8

Cited by 372 publications

(110 citation statements)

References 25 publications

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“…Terano, et al studied the antiplatelet effect of EPA on healthy subjects. 11) In their study, following supplementation with EPA-E 3.6 g/day for 4 weeks, platelet aggregation and platelet retention were significantly suppressed. The same authors showed that the EPA content in platelet phospholipids increased markedly, whereas the AA content did not change.…”

Section: Discussionmentioning

confidence: 93%

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

et al. 2014

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SummaryEicosapentaenoic acid (EPA) has been widely accepted to have antiatherosclerotic effects. The aim of this study was to investigate the antiplatelet effect of EPA combined with acetylsalicylic acid (ASA) following stent implantation. Eighteen patients who had undergone coronary stent implantation at least 8 months previously were included. All patients were given EPA ethyl ester (EPA-E) 1.8 g/day in addition to ASA 100 mg/day for 12 weeks. After the treatment, the plasma EPA/arachidonic acid (AA) ratio increased signifi cantly from 0.40 ± 0.2 to 1.08 ± 0.39 (P < 0.001). There were no changes in the maximum platelet aggregation (MPA) induced by adenosine diphosphate (5 and 20 µmol/L), AA (0.3 and 0.5 mg/mL), or collagen (2 and 4 µg/mL). Furthermore, no signifi cant differences were observed in the expression of PAC-1 and CD62P on the platelet surface membranes or in the soluble P-selectin concentration. With further analysis, a signifi cant negative correlation was found between collagen (2 µg/mL)-induced MPA and plasma EPA/AA ratio (r = -0.507, P = 0.032). The patients were then divided into 2 groups according to the median EPA/AA ratio value of 0.92. In the high EPA/AA ratio group (n = 10), collagen-induced MPA was signifi cantly suppressed after EPA-E administration (45.3 ± 15.9 versus 39.0 ± 16.3, P = 0.033). In contrast, there were no signifi cant changes in platelet aggregation (56.0 ± 9.8 versus 57.1 ± 11.4, P = 0.745) in the low EPA/AA ratio group (n = 8). EPA treatment had a potential to suppress collagen-induced platelet aggregation in patients with a high plasma EPA/AA ratio. (Int Heart J 2014; 55: 228-233) Key words: Omega-3 polyunsaturated fatty acids, Coronary artery disease C oronary revascularization with drug-eluting stents (DES) has become a widespread technique for treating coronary artery disease (CAD). The guidelines recommend that patients with DES should receive dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and thienopyridine for at least 1 year in order to prevent stent thrombosis.1,2) When the risk of stent thrombosis decreases in the chronic phase following DES implantation, secondary prevention becomes a primary target of patient care. In fact, in the chronic phase, the risks of CAD or cerebrovascular disease are much higher than that of stent thrombosis.3,4) Therefore, lifelong treatment with ASA is also recommended for the secondary prevention of atherothrombotic events following DAPT termination. 1,2)Eicosapentaenoic acid (EPA) has been widely accepted to have antiatherosclerotic effects. 5,6) In relation to secondary prevention, the use of eicosapentaenoic acid ethyl ester (EPA-E) in combination with statins successfully reduced the recurrence of cardiovascular events in the Japan EPA lipid intervention study (JELIS). 7) In particular, in patients who underwent coronary artery intervention, the JELIS sub-study showed that the incidence of major coronary events was significantly reduced by 41% in the EPA treatment group. 8) EPA is known to improve vascula...

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Section: Discussionmentioning

confidence: 93%

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

et al. 2014

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“…We speculate that anti-inflammatory effects of EPA might be principally responsible for reducing atherosclerotic lesions and prevent cardiovascular events 15,[19][20][21][22][23][24][25] . Concerning the prevention of CAD by EPA as well as its anti-inflammatory effect, it should be noted that EPA exhibits an antiarrhythmic effect 26) , inhibits platelet aggregation 27,28) , exhibits vasodilatory activity 29) , increases the circulating adiponectin level 30) , has a triglyceride-lowering effect 31) , and induces plaque stabilization 24,32) . These effects may function synergistically to prevent CAD.…”

Section: Discussionmentioning

confidence: 99%

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

Itakura¹,

Yokoyama

Matsuzaki

et al. 2011

JAT

202

146

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Aim:The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. Methods: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/ stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. Results: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio 0.83, p 0.049, in all participants and hazard ratio 0.71, p 0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 g/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 g/mL) group. Conclusion: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events. J Atheroscler Thromb, 2011; 18:99-107.

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“…We suggest that DHA, through modulation of complex blood flow potentially via changes in viscosity,72 transduces and inhibits apical inflammatory signals that orchestrate inflammation in atherosclerosis. Human studies suggest that supplementing the diet of young males with DHA in fish oil significantly reduces IL‐1β production in LPS (lipopolysaccharide)‐stimulated monocytes 73.…”

Section: Discussionmentioning

confidence: 94%

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

Alfaidi

Chamberlain

Rothman

et al. 2018

JAHA

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BackgroundHypertension is a complex condition and a common cardiovascular risk factor. Dietary docosahexaenoic acid (DHA) modulates atherosclerosis and hypertension, possibly via an inflammatory mechanism. IL‐1 (interleukin 1) has an established role in atherosclerosis and inflammation, although whether IL‐1 inhibition modulates blood pressure is unclear.Methods and ResultsMale apoE−/− (apolipoprotein E–null) mice were fed either a high fat diet or a high fat diet plus DHA (300 mg/kg per day) for 12 weeks. Blood pressure and cardiac function were assessed, and effects of DHA on wall shear stress and atherosclerosis were determined. DHA supplementation improved left ventricular function, reduced wall shear stress and oscillatory shear at ostia in the descending aorta, and significantly lowered blood pressure compared with controls (119.5±7 versus 159.7±3 mm Hg, P<0.001, n=4 per group). Analysis of atheroma following DHA feeding in mice demonstrated a 4‐fold reduction in lesion burden in distal aortas and in brachiocephalic arteries (P<0.001, n=12 per group). In addition, DHA treatment selectively decreased plaque endothelial IL‐1β (P<0.01).ConclusionsOur findings revealed that raised blood pressure can be reduced by inhibiting IL‐1 indirectly by administration of DHA in the diet through a mechanism that involves a reduction in wall shear stress and local expression of the proinflammatory cytokine IL‐1β.

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Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects

Cited by 372 publications

References 25 publications

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

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