In Vivo Indexes of Platelet and Vascular Function during Fish-Oil Administration in Patients with Atherosclerosis

Abstract

Populations that consume a diet rich in marine lipids may have a lower risk of atherosclerotic disease. Fish oil contains the N-3 polyunsaturated fatty acid eicosapentaenoate, and the biosynthesis of thromboxanes and prostacyclins from eicosapentaenoate (thromboxane A3 and prostaglandin I3), rather than from the usual precursor arachidonate (thromboxane A2 and prostaglandin I2), may help to reduce the risk. To examine this hypothesis, we studied the effect of eicosapentaenoate supplementation (10 g per day) for one month on the synthesis of thromboxanes and prostacyclins, as assessed by urinary metabolite excretion, in six patients with peripheral vascular disease and seven normal controls. Supplementation markedly increased the eicosapentaenoate content of phospholipids from red cells and platelets. Synthesis of the platelet agonist thromboxane A2, which was elevated in the patients at base line, declined by 58 percent during supplementation but did not reach normal values. The decline in thromboxane A2, which is synthesized from arachidonate, coincided with the formation of the inactive thromboxane A3, which is synthesized from eicosapentaenoate. A lower dose of eicosapentaenoate (1 g per day) was not sufficient to maintain the changes in thromboxane A2 synthesis. Platelet function was only moderately inhibited during eicosapentaenoate supplementation, consistent with incomplete suppression of thromboxane A2 synthesis. These studies show that a high dose of eicosapentaenoate alters the pattern of synthesis of thromboxanes and prostacyclins. However, effects comparable to those of aspirin require long-term administration in high doses. Whether other properties of fish oil might render it a more attractive antithrombotic therapy remains to be determined.

The Relationship of Dietary Factors to Cardiovascular Diseases among Japanese in Okinawa and Japanese Immigrants, Originally from Okinawa, in Brazil.

“…This study also examined various diet-related factors among the study populations. Previously known factors such as body mass index (5) and cholesterol level (6-8) as well as newer factors such as urinary taurine (37, 39-43) excretion and n-3 series fatty acids (FA) (44)(45)(46)(47)(48)(49) in plasma phospholipids, which possibly contribute to differences in the prevalence of HT and ECG ST-T changes, were investigated. Experimental data, especially those obtained from animal models for CVD such as spontanously hypertensive rats (SHR) (IS) and stroke-prone SHR (SHRSP) (16), provided findings that excess salt aggravates the development of HT and increases the incidence of stroke, whereas a high dietary intake of potassium, calcium, magnesium, unsaturated FA and proteins, especially those from animals including fish (i.e., taurine), attenuate the development of hypertension (9-11).…”

“…JB showed higher total n-6 series FA level, including linoleic acid (LA, 18:2), arachidonic acid (AA, 20:4) eicosadienoic acid (20:2), eicosatrienoic acid (20:3), and docosatetraenoic acid (22:4), than JJ. Since Dyerberg (44)(45)(46) reported that Greenland Eskimos, whose IHD mortality is among the lowest in the world, have high n-3 FA levels, derived from a diet of marine animals and fish, and have at the same time reduced platelet aggregation and increased bleeding time, many investigations have been carried out to extend these findings (47)(48)(49). N-3 series FA, especially EPA, are considered to have an inhibitory effect on platelet aggregation, through raising activity of PGI3 in arterial wall and TXA3 in platelets and reducing synthesis of TXA2 which increases platelet aggregation, having in total a beneficial effect on the process of atherosclerosis (45)(46)(47)(48).…”

Vitamin e status during dietary fish oil supplementation in rheumatoid arthritis

“…33, No. 9 (September 1990) plement (placebo control group). The supplements were contained in identical eapsules.…”

n-3 Fatty acids and cardiovascular disease: Actions and molecular mechanisms

“…The biological effects of n-3 FA on atherosclerosis include preventing arrhythmias [8,12,[19][20][21][22][23][24], decreasing platelet aggregation [27][28][29], lowering plasma triglycerides [30][31][32][33][34][35], increasing HDL cholesterol and LDL particle size [36][37][38][39][40], decreasing blood pressure [42][43][44][45], reversing cholesterol accumulation from atheromatous plaques [46,47] and decreasing inflammation [48][49][50].…”

“…Knapp et al [28] reported that high doses of eicosapentaenoic acid supplementation (10 g/day) for one month altered the pattern of synthesis of thromboxanes and prostacyclins and DeCaterina et al [29] patients with angiographically proven coronary artery disease find that n-3 FA supplementation (3 g/day EPA and 1.3 g/day DHA) for 28 days decreased serum thromboxane A 2 in 36% of subjects and bleeding times increased 40% from baseline.…”