In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis
A 1-month study employing a simulated Eskimo diet of fish oil containing the N-3 polyunsaturated fatty acid, eicosapentaenoate (EP), assessed its beneficial effects in 6 peripheral vascular disease patients vs. 7 normal control subjects. Fish oil supplementation using a dose that simulates an Eskimo...
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| Published in | The New England journal of medicine Vol. 314; no. 15; pp. 937 - 942 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Massachusetts Medical Society
10.04.1986
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0028-4793 1533-4406 |
| DOI | 10.1056/NEJM198604103141501 |
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| Abstract | A 1-month study employing a simulated Eskimo diet of fish oil containing the N-3 polyunsaturated fatty acid, eicosapentaenoate (EP), assessed its beneficial effects in 6 peripheral vascular disease patients vs. 7 normal control subjects. Fish oil supplementation using a dose that simulates an Eskimo diet lowered the elevated excretion of 2,3-dinor-thromboxane B2 in patients with severe atherosclerosis (AS). The results provide evidence that biologically inert thromboxane A3 is formed from EP in vivo. Despite a 1-month high fish oil supplementation, however, the formation of the potent vasoconstrictor and platelet agonist, thromboxane A2, was not completely inhibited. The possible implications of these results for treating AS patients are discussed.(wz) |
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| AbstractList | A 1-month study employing a simulated Eskimo diet of fish oil containing the N-3 polyunsaturated fatty acid, eicosapentaenoate (EP), assessed its beneficial effects in 6 peripheral vascular disease patients vs. 7 normal control subjects. Fish oil supplementation using a dose that simulates an Eskimo diet lowered the elevated excretion of 2,3-dinor-thromboxane B2 in patients with severe atherosclerosis (AS). The results provide evidence that biologically inert thromboxane A3 is formed from EP in vivo. Despite a 1-month high fish oil supplementation, however, the formation of the potent vasoconstrictor and platelet agonist, thromboxane A2, was not completely inhibited. The possible implications of these results for treating AS patients are discussed.(wz) 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 l3), rather than from the usual precursor arachidonate (thromboxane A2 and prostaglandin l2), 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. (N Engl J Med 1986; 314:937-42.) 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. 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.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. 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 A 3 and prostaglandin l 3 ), rather than from the usual precursor arachidonate (thromboxane A 2 and prostaglandin l 2 ), 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 A 2 , 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 A 2 , which is synthesized from arachidonate, coincided with the formation of the inactive thromboxane A 3 , which is synthesized from eicosapentaenoate. A lower dose of eicosapentaenoate (1 g per day) was not sufficient to maintain the changes in thromboxane A 2 synthesis. Platelet function was only moderately inhibited during eicosapentaenoate supplementation, consistent with incomplete suppression of thromboxane A 2 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. (N Engl J Med 1986; 314:937–42.) EPIDEMIOLOGIC comparisons of Greenland Eskimos and mainland Danes have suggested that a diet rich in marine lipids may be associated with a reduction in the incidence of occlusive vascular disease. 1 More recently, studies based on dietary history have suggested that even a small intake of fish may have reduced the incidence of coronary vascular disease in both European and North American study populations. 2 , 3 A hypothetical mechanism that has been advanced to explain these observations has been the competition between eicosapentaenoic acid (eicosapentaenoate) and arachidonic acid (arachidonate) as potential substrates for the enzyme cyclooxygenase. Whereas the predominant product of arachidonate formed . . . |
| Author | Knapp, H.R Alessandrini, P Reilly, I.A.G FitzGerald, G.A |
| Author_xml | – sequence: 1 fullname: Knapp, H.R – sequence: 2 fullname: Reilly, I.A.G – sequence: 3 fullname: Alessandrini, P – sequence: 4 fullname: FitzGerald, G.A |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/3007982$$D View this record in MEDLINE/PubMed |
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| References | Mortensen (r014) 1983; 50 Knapp (r023) 1985; 13 Bang (r034) 1985; 313 r020 r042 r043 Goodnight (r013) 1981; 58 r022 r044 Lord (r029) 1947; 34 r040 r041 r039 r019 Bieri (r018) 1979; 32 r035 Galloway (r015) 1985; 68 r016 r038 Moore (r027) 1975; 250 Fitzgerald (r045) 1985; 33 Bang (r001) 1980; 27 Sanders (r012) 1981; 61 Spector (r050) 1985; 26 FitzGerald (r021) 1985; 15 r031 r032 r011 r033 r051 r006 r028 r007 r008 r009 Di Minno (r037) 1983; 61 r002 r024 r003 r047 r004 Mielke (r036) 1973; 59 r048 r005 r049 Brox (r010) 1981; 46 Skipski (r026) 1964; 90 Folch (r025) 1957; 226 |
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| Snippet | A 1-month study employing a simulated Eskimo diet of fish oil containing the N-3 polyunsaturated fatty acid, eicosapentaenoate (EP), assessed its beneficial... 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... 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... |
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| SubjectTerms | 6-Ketoprostaglandin F1 alpha 6-Ketoprostaglandin F1 alpha - analogs & derivatives 6-Ketoprostaglandin F1 alpha - urine ACEITES DE PESCADO Acids administration & dosage Adult Aged analogs & derivatives analysis ARTERIOSCLEROSE ARTERIOSCLEROSIS Arteriosclerosis - blood Arteriosclerosis - urine Atherosclerosis beta-Thromboglobulin beta-Thromboglobulin - analysis Biosynthesis Bleeding Time blood Blood Platelets Blood Platelets - analysis Blood Platelets - drug effects Chromatography Diet diet therapy DIETA TERAPEUTICA Dietary Fats Dietary Fats - administration & dosage Dietary Fats - pharmacology drug effects eicosapentaenoic acid Eicosapentaenoic Acid - blood Eicosapentaenoic Acid - metabolism Eicosapentaenoic Acid - pharmacology Epoprostenol Epoprostenol - biosynthesis Erythrocytes Erythrocytes - analysis Fatty Acids Fatty Acids - blood Fish oils Fish Oils - administration & dosage Fish Oils - pharmacology HUILE DE POISSON Humans Lipids Male metabolism Metabolites Middle Aged Neutrophils pharmacology Phospholipids Phospholipids - blood Platelet Count Platelet Factor 4 Platelet Factor 4 - analysis Polyunsaturated fatty acids PREVENCION PREVENTION REGIME THERAPEUTIQUE Thromboxane A2 Thromboxane A2 - biosynthesis Thromboxane B2 Thromboxane B2 - analogs & derivatives Thromboxane B2 - urine Thromboxanes Thromboxanes - biosynthesis Urine |
| Title | In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis |
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