Thromb Haemost 1999; 82(01): 128-133
DOI: 10.1055/s-0037-1614641
Rapid Communication
Schattauer GmbH

Persistent Impairment of Platelet Aggregation following Cessation of a Short-course Dietary Supplementation of Moderate Amounts of N-3 Fatty Acid Ethyl Esters

Anna Maria Cerbone
1   From the Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Napoli “Federico II”, Italy
,
Ferdinando Cirillo
1   From the Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Napoli “Federico II”, Italy
,
Antonio Coppola
1   From the Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Napoli “Federico II”, Italy
,
Patrizia Risè
2   Istituto di Scienze Farmacologiche, Università degli Studi di Milano, Italy
,
Eduardo Stragliotto
3   Medical Dept, Pharmacia and Upjohn Italy
,
Claudio Galli
2   Istituto di Scienze Farmacologiche, Università degli Studi di Milano, Italy
,
Mauro Giordano
4   Cattedra di Gerontologia e Geriatria, Università degli Studi di Palermo, Italy
,
Elena Tremoli
2   Istituto di Scienze Farmacologiche, Università degli Studi di Milano, Italy
,
Giovanni Di Minno
4   Cattedra di Gerontologia e Geriatria, Università degli Studi di Palermo, Italy
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 02. Oktober 1997

Accepted after resubmission 22. Januar 1999

Publikationsdatum:
11. Dezember 2017 (online)

Summary

The duration of the effect of a short-course (1-mo twice-daily) supplementation of moderate amounts (2.28 g) of n-3 fatty acid ethyl esters (FA) on platelet lipid composition and aggregation was compared with that of olive oil (3 g/d) supplementation in 14 healthy volunteers. The FA preparation employed contained eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) in a ratio of 1:1.4. A marked rise (p <0.05) in the plasma and platelet content of EPA and DHA, and minimal changes in the content of arachidonic acid (AA) were documented at withdrawal of the n-3 FA supplementation. EPA/AA and DHA/AA ratios in platelet phospholipids showed that the FA accumulation persisted 8-12 wks after stopping the supplementation (p <0.05). The aggregation of platelets in response to collagen or ADP, and thromboxane B2 (TXB2) formation were impaired at withdrawal. The impaired aggregation lasted 8-12 weeks (p always <0.05), whereas TXB2 formation returned to basal values 4 weeks after stopping the n-3 supplementation. No correlation was found between impaired aggregation and TXB2 formation. In contrast, the impaired sensitivity to ADP (p = 0.036) and, to a lesser extent, to collagen (p = 0.068) were related to changes in the intracellular pH (pHi) of the Na+/H+ reverse transport. No changes in platelet composition or function were observed either during or following olive oil supplementation. These results document a long-lasting impairment of platelet sensitivity to ADP and collagen; changes in the pHi values of the Na+/H+ reverse transport, and a simultaneous persistent accumulation of EPA and DHA in platelet phospholipids, after stopping a short-course dietary supplementation of moderate amounts of n-3 fatty acid ethyl esters.

 
  • References

  • 1 Kromhout D, Bosscheiter EB, DeLezzenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985; 312: 1205-9.
  • 2 Burr ML, Fehiky AM, Gilbert JF. et al. Effects of changes in fat, fish and fibre intakes on death and myocardial infarction: diet and reinfarction trial (DART). Lancet 1989; II: 757-61.
  • 3 De Catarina R, Gianessi D, Mazzone A, Bernini W, Lazzerini G, Maffei S, Cerri M, Salvatore S, Weksler B. Vascular prostacyclin in increased in patients ingesting n-3 fatty acids before coronary artery by-pass graft surgery. Circulation; 1990; 82: 428-38.
  • 4 Kumagi Y. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity, and cell deformability in healthy human subjects. Atherosclerosis 1983; 46: 321-31.
  • 5 Kristensen DS, Schmidt EB, Dyerbrg J. Dietary supplementation with n-3 polyunsaturated fatty acids and human platelet function: A review with particular emphasis on implication for cardiovascular disease. J Intern Med 1989; 226 (Suppl. 01) 141-50.
  • 6 Nordoy A, Goodnight SH. Dietary lipids and thrombosis. Relationship to atherosclerosis. Arteriosclerosis 1990; 10: 149-63.
  • 7 Nordoy A, Barstd L, Connor WE, Hatcher L. Absorption of n-3 eicosapentaenoic acids as ethyl esters and triglycerides in human. Am J Clin Nutr 1991; 53: 1185-90.
  • 8 Tremoli E, Eligini S, Colli S, Maderna P, Risè P, Pazzucconi F, Marangoni F, Sirtori C, Galli C. n-3 fatty acid ethyl ester administration to healthy subjects and to hypertriglyceridemic patients reduces tissue factor activity in adherent monocytes. Arterioscler Thromb 1994; 14: 1600-8.
  • 9 von Schacky C, Fisher S, Weber PC. Long-term effects of dietary marine n-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans. J Clin Invest 1985; 76: 1626-31.
  • 10 von Schacky C, Weber PC. Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans. J Clin Invest 1985; 76: 2446-50.
  • 11 Hamazaki T, Urakaze M, Makuta M, Ozawa A, Soda Y, Tatsumi H, Yano S, Kumagai A. Intake of different eicosapentaenoic acid-containig lipids and fatty acid pattern of plasma lipids in the rat. Lipids 1987; 22: 994-8.
  • 12 Terano T, Hirai A, Hamazaki T, Kobajashi S, Fujita T, Tamura Y, Kumagi A. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis 1983; 46: 321-31.
  • 13 Wojenski CM, Silver MJ, Walker J. Eicosapentaenoic acid ethyl ester as an antithrombotic agent: comparison to an extract of fish oil. Biochim Biophys Acta 1991; 1081: 33-8.
  • 14 Thorngren M, Gustafson A. Effects of 11-week increase in dietary eicosapentaenoic acid on bleeding time, lipids and platelet aggregation. Lancet 1981; II: 1190-3.
  • 15 Tremoli E, Maderna P, Marangoni F, Colli S, Eligini S, Catalano I, Angeli MT, Pazzucconi F, Gianfranceschi G, Davi’ G, Stragliotto E, Sirtori CR, Galli C. Prolonged inhibition of platelet aggregation after n-3 fatty acid ingestion by healthy volunteers. Am J Clin Nutr 1995; 61: 607-13.
  • 16 Nurden AT. Platelet membrane glycoproteins. In: Haemostasis and Thrombosis Third Edition. Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. eds. Churchill Livingstone London: 1994: 115-65.
  • 17 Cattaneo M, Lecchi A, Randi AM, McGregor JL, Mannucci PM. Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate. Blood 1992; 80: 2787-96.
  • 18 Di Minno G, Cerbone AM, Mattioli PL, Turco S, Iovine C, Mancini M. Functionally thrombasthenic state in normal platelets following the administration of ticlopidine. J Clin Invest 1985; 75: 328-38.
  • 19 Di Minno G, Davi’ G, Margaglione M, Cirillo F, Grandone E, Ciabattoni G, Catalano I, Strisciuglio P, Andria G, Patrono C. and Mancini M. Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism. J Clin Invest 1993; 92: 1400-6.
  • 20 Stragliotto E, Camera M, Postiglione A, Sirtori M, Di Minno G, Tremoli E. Functionally abnormal monocytes in hypercholesterolemia. Arterioscl Thrombos 1993; 13: 944-50.
  • 21 Livine A, Grinstein S, Rothstein A. Characterization of the Na+/H+ exchange in platelets. Thromb Haemost 1987; 58: 971-7.
  • 22 Ghigo D, Bussolino F, Garbarino G, Heller R, Turrini F, Pescarmona G, Gragoe EG. Role of Na+/H+ exchange in thrombin-induced platelet activating factor production by human endothelial cells. J Biol Chem 1988; 263: 19437-46.
  • 23 Di Minno G, Silver MJ, Murphy S. Monitoring the entry of new platelets into the circulation after ingestion of aspirin. Blood 1983; 61: 1081-5.
  • 24 Schick PK, Wojenski C, Walker J. The effect of olive oil, hydrogenated palm oil, and omega-3 fatty acid-enriched diets on megakaryocytes and platelets. Arterioscler Thromb 1993; 13: 84-9.
  • 25 Brown AJ, Pang E, Roberts DCK. Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications. Am J Clin Nutr 1991; 54: 668-73.
  • 26 Neuringer M, Connor WE, van Petten C, Barstadt L. Dietary omega 3 fatty acid deficiency and visual loss in infant rhesus monkeys. J Clin Invest 1984; 73: 272-9.
  • 27 Crawford MA, Hassam AG, Williams G. Essential fatty acids and fetal brain growth. Lancet 1976; 1: 452-3.
  • 28 Rosenthal MD, Garcia MC, Sprecher H. Substrate specificity of the agonist-stimulated release of polyunsaturated fatty acids from vascular endothelial cells. Arch Biochim Biophys 1989; 274: 590-600.
  • 29 Djeberg J, Bang HO, Stoffersen E, Moncada S, Vane JR. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis. Lancet 1978; II: 117-9.
  • 30 Knapp HR, Reilly IAG, Alessandrini P, FitzGerald GA. In vivo indices of platelet and vascular function during fish oil administration in patients with atherosclerosis. N Engl J Med 1986; 314: 937-42.
  • 31 Li X, Steiner M. Fish Oil: a potent inhibitor of platelet adhesiveness. Blood 1990; 76: 938-45.
  • 32 Li X, Steiner M. Dose response of dietary fish oil supplementations on platelet adhesion: Arterioscler Thromb. 1991; 11: 39-46.
  • 33 Crawford N, Scrutton MC. Biochemistry of the blood platelet. In: Haemostasis and Thrombosis Third Edition. Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. eds Churchill Livingstone London: 1994: 89-114.
  • 34 Siffert W, Muckenhoff K, Scheid P. Evidence for a role for Na+/K+ exchange in platelets activated with the ionophore A 23187. Biochem Biophys Res Commun 1984; 3: 1123-8.
  • 35 Borin M, Siffert W. Stimulation by thrombin increases the cytosolic free Na+ concentration in human platelets. J Biol Chem 1990; 265: 19543-50.
  • 36 Gaidano G, Ghigo D, Schena M, Bergui L, Treves S, Turrini F, Cappio FC, Bosia A. Na+/H+ exchange activation mediates the lipopolysaccharide-induced proliferation of human lymphocytes and is impaired in malignant B-chronic lymphocytic leukemia lymphocytes. J Immunol 1989; 142: 913-8.
  • 37 Resnik LM, Gupta RK, Sosa RE, Corbett LM, Laragh JH. Intracellular pH in human and experimental hypertension. Proc Natl Acad Sci USA 1987; 84: 7663-7.
  • 38 Calderaro V, Parrillo C, Balestrieri ML, Giovane A, Filippelli A, Rossi F. Docosahexaenoic acid and signaling pathways in rabbit colon. Mol Pharmacol 1994; 45: 737-46.
  • 39 Dehemer GJ. Another piece of the fish oil puzzle. Circulation 1990; 82: 624-8.