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DOI: 10.1055/s-2001-11913
© Georg Thieme Verlag Stuttgart · New York
Fettemulsionen - Strukturierte Lipide und Omega-3-Fettsäuren
Publikationsverlauf
Publikationsdatum:
31. Dezember 2001 (online)

Zusammenfassung
Die unerwünschten Wirkungen von Omega-6-fettsäurereichen Fettemulsionen sind in den letzten Jahren in den Mittelpunkt des wissenschaftlichen Interesses gerückt. Zur Vermeidung dieser Nebenwirkungen wurden verschiedene Wege eingeschlagen. Zum einen wurde versucht, mit einer Reduzierung des Omega-6-Fettsäurenanteils durch den teilweisen Ersatz mit mittelkettigen Fettsäuren oder Omega-9-Fettsäuren in den Emulsionen, die unerwünschten Effekte zu minimieren. Bei anderen Studien mit Omega-3-Fettsäuren wurde nicht nur der Präkursorenpool aus den Omega-6-Fettsäuren vermindert, sondern zusätzlich die Synthese von Mediatoren mit zum Teil sehr unterschiedlichen Wirkungen ermöglicht. Weitere Forschungsansätze beinhalteten die Zufuhr von chemisch synthetisierten Triglyzeridmolekülen mit einem in der Natur nicht vorkommenden Molekülaufbau. Auch Kombinationen dieser neuen Triglyzeridstrukturen mit verschiedenen Fettsäureklassen scheinen durchaus positive Effekte zu haben. Alle diese neuen Fettemulsionen wurden in unterschiedlichen Tiermodellen sowie bei verschiedenen Erkrankungen und unterschiedlichen Krankheitsstadien getestet. Die publizierten Ergebnisse waren jedoch zum Teil widersprüchlich. Zum einen waren deutlich positive Effekte gefunden worden, während andere Autoren keine oder sogar negative Auswirkungen fanden. Da die neuen Fettemulsionen in der Herstellung zum Teil mit erheblichen Mehrkosten belastet sind, müssen bis zur routinemäßigen Anwendung kontrollierte Studien klinische Vorteile dieser neuen Lipide beweisen, aber auch Indikationen für den Einsatz der unterschiedlichen Emulsionen aufzeigen. Neben den rein nutritiven Eigenschaften der Fette können durch Veränderungen der Fettsäuremuster zum Teil positive Effekte auf den Metabolismus, die Mikrozirkulation und auf Entzündungsreaktionen bewirkt werden. Durch die Modulation des Präkursorenpools für die Eicosanoidbildung wird jedoch auch in Signalwege eingegriffen, die bis heute noch nicht vollständig aufgeklärt sind. Dies muss bei der Übertragung der Befunde aus Tiermodellen auf klinische Studien sorgfältig beachtet werden, um nicht einen vermeintlichen Nutzen durch wesentlich schädlichere Nebenwirkungen zu erkaufen. Diesbezügliche Untersuchungen werden auch von einem Konsensuspapier des National Institutes of Health und der beiden großen amerikanischen Ernährungsgesellschaften gefordert [73]. Zusammenfassend kann man sicherlich feststellen, dass es im 21. Jahrhundert keine Lipidemulsion geben wird, die für alle Erkrankungen die optimale Zusammensetzung hat. Die Studien der letzten Jahre haben deutlich gezeigt, dass die einzelnen Fettsäureklassen mit ihren unterschiedlichen Auswirkungen auf den Metabolismus, den Immunstatus und die Mikrozirkulation differenziert eingesetzt werden müssen. Lipide werden in Zukunft nicht nur aufgrund ihrer kalorischen Wertigkeit, sondern auch aufgrund pharmakologischer Wirkungen Verwendung finden.
Fatty Emulsions - Structural Lipids and Omega-3-Fatty-Acids
Side effects of poly-unsaturated fatty acids (PUFA) used for clinical nutrition have been extensively investigated in recent years. To avoid the negative effects of omega-6-fatty-acids, it is recommended to use preparations with a reduced content of these PUFA. For this, medium-chain fatty acids or omega-9-fatty-acids can be used instead of omega-6-fatty-acids. The use of omega-3-fatty-acids not only reduces the amount of omega-6-fatty-acids, but also leads additionally to synthesis of prostaglandins and leukotrienes with a function different to those derived from the omega-6-fatty-acids. A genuinely new substrate in the evolution of lipid emulsions are the structured triglycerides. In these emulsions the individual molecules are composed of fatty acids of different fatty acid classes. All these recent lipid emulsions have been used in different animal models and clinical settings to define their effects on metabolism, immunology, pulmonary function and microcirculation. The results of these studies were sometimes controversial and confusing. However, it seems that the exchange of a part of the omega-6-fatty-acids in the lipid emulsions is beneficial in some diseases. In conclusion, the properties of the different fatty acids lead to a pharmacological use of lipid emulsions in addition to their caloric value. With this in mind, there will be not only one emulsion for all critical ill patients in future, but for different diseases different lipid emulsion will be required.
Literatur
-
1 Blackburn G L, Wan J, Teo T C. et al .
Metabolic support in organ failure. In: Bihan D, Cerra F (eds) New Horizons III: Multiple organ failure. Fullerton CA; Society of Critical Care Medicine 1989: 337-370 - 2 Adolph M. Lipid emulsions in parenteral nutrition. Ann Nutrition and Metabolism. 1999; 43 1-13
- 3 Baldermann H, Wickelmayr M, Rett K. et al . Changes of hepatic morphology during parenteral nutrition with lipid emulsions containing LCT or MCT/LCT quantified by ultrasound. JPEN. 1991; 15 601-603
- 4 Roth B, Ekelmund M, Hägerstrand I. et al . Biochemical and ultra-structural reactions to parenteral nutrition with two different fat emulsions in rats. Int Care Med. 1998; 24 716-724
- 5 Sobrado J, Moldawer L L, Pomposelli J J. et al . Lipid emulsions and reticuloendothelial system function in healthy and burned guinea pigs. Am J Clin Nutr. 1985; 42 855-863
- 6 Seidner D L, Mascioli E A, Istfan N W. et al . Effects of long-chain-triglyceride emulsions on reticuloendothelial system function. JPEN. 1989; 13 614-619
- 7 Sedman P C. Effects of different lipid emulsions on lymphocyte function during total parenteral nutrition. Br J Surg. 1991; 78 1396-1399
- 8 Gogos C A, Kalfarentzos F. Total parenteral nutrition and immune system activity: a review. Nutrition. 1995; 11 339-344
- 9 Gelas P, Gotte L, Poitevin-Later F. et al . Effect of parenteral medium- and long-chain triglycerides on lymphocytes subpopulations and functions in patients with AIDS: a prospective study. JPEN. 1998; 22 67-71
- 10 Skeie B, Askanazi J, Rothkopf M M. et al . Intravenous fat emulsion and lung function: A review. Crit Care Med. 1988; 16 183-194
- 11 Venus B, Smith R A, Patel C B. et al . Hemodynamic and gas exchange alterations during intralipid infusion in patients with adult respiratory distress syndrome. Chest. 1989; 95 1278-1281
- 12 Hageman J R, Hunt C E. Fat emulsions and lung function. Clin Chest Med. 1986; 7 69-77
- 13 Babayan V K. Medium-chain triglycerides and structured lipids. Lipids. 1987; 22 417-420
- 14 Stein J. Chemically defined structured lipids; current status and future in gastrointestinal diseases. Nutrition. 1999; 14 79-85
- 15 Ball M J. Parenteral nutrition in the critically ill: use of medium-chain triglyceride emulsion. Intensive Care Med. 1993; 19 89-95
- 16 Carpentier Y A, Richelle M, Haumont D. et al . New developments in fat emulsions. Proc Nutr Soc. 1990; 49 375-380
- 17 Radermacher P, Santak B, Strobach H. et al . Fat emulsions containing medium-chain triglycerides in patient with sepsis syndrome: effects on pulmonary hemodynamies and gas exchange. Int Care Med. 1992; 18 231-234
- 18 Smirniotis V, Kostopanagiotou G, Vassiliou J. et al . Long-chain versus medium-chain lipids in patients with ARDS: effects on pulmonary haemodynamics and gas exchange. Int Care Med. 1998; 24 1029-1033
- 19 Pscheidl E, Reisch S, Rügheimer E. Chemically defined structured lipids with omega-3 fatty acids maintain splanchnic blood flow in a low-dose endotoxin rat model. Infusionsther Transfusionsmed. 1994; 21 380-387
- 20 Nordenstorm J, Thorne A, Olivecrona T. Metabolic effects of infusion of a structured triglyceride emulsion in healthy subjects. Nutrition. 1995; 11 269-274
- 21 Sandström R, Hyltander A, Körner U. et al . Structured triglycerides to postoperative patients: a safety and tolerance study. JPEN. 1993; 17 153-157
- 22 Magnusson Borg I K, Sandberg L G, Wennberg A K. et al . Effects of a fat emulsion containing medium-chain fatty acids and long-chain fatty acids on protein and energy metabolism in partially hepatectomized rats. Clin Nutr. 1995; 14 23-28
- 23 Sandström R, Hyltander A, Körner U. et al . Structured triglycerides were well tolerated and induced increased whole body fat oxidation compared with long-chain triglycerides in postoperative patients. JPEN. 1995; 19 381-386
- 24 Kruimel J W, Naber A HJ, van der Vlieth J A. et al . Parenteral administration of structured triglycerides improves nitrogen balance in postoperative patients. JPEN. 1997; 21 S6
- 25 Kruimel J W, Naber A HJ. Educational Program, 19th ESPEN Congress 1997. 1997: 102-104
- 26 Chambrier C, Guiraud M, Gibault J P. et al . Medium- and long-chain triacylglycerols in postoperative patients: structured lipids versus a physical mixture. Nutrition. 1999; 15 274-277
- 27 Drews D, Schluter M D, Stein P T. Glyzerol kinetics with parenteral lipid emulsions (long-chain triglycerides, medium-chain triglycerides, and structured lipids) in rats. Metabolism. 1993; 42 743-748
- 28 Flaaten H, Aanderung L, Carneheim C. et al . A randomized, single blind, cross over study comparing a new structured triglyceride fat emulsion with Vasolipid®. Clin Nutr. 1995; 14 S58
- 29 Lutz O, Lave T, Frey A. et al . Activities of lipoprotein lipase and hepatic lipase on long- and medium-chain triglyceride emulsions used in parenteral nutrition. Metabolism. 1989; 38 507-513
- 30 Hultin M, Müllertz A, Zundel M A. et al . Metabolism of emulsions containing medium and long-chain triglycerides or interesterified triglycerides. J Lipid Res. 1994; 35 1850-1860
- 31 Pscheidl E, Hedwig-Geissing M, Rügheimer E. Chemisch definierte strukturierte Lipide in der parenteralen Ernährung bei Sepsis. Anästhesist. 1994; 46, Suppl 136
- 32 Pscheidl E, Reisch S, Rugheimer E. Chemically defined structured lipids with omega-3 fatty acids maintain splanchnic blood flow in a low-dose continuous endotoxin model. Infusionsther Transfusionsmed. 1994; 21 380-387
- 33 Linseisen J, Wolfram G. Efficancy of different triglycerides in total parenteral nutrition for preventing atrophy of the gut in traumatized rats. JPEN. 1997; 21 21-26
- 34 Dyerberg J, Bang H O, Stoffersen E. et al . Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis?. Lancet. 1978, July; 15 117-119
- 35 Shimokawa H, Vanhoutte P M. Dietary ω3 fatty acids and endothelium-dependent relaxations in porcine coronary arteries. Am J Physiol. 1989; 256 968-973
- 36 Black S C, Katz S, McNell J H. Influence of omega-3 fatty acids treatment on cardiac phospholipid composition and coronary flow of streptozocin-diabetic rats. Metabolism. 1993; 42 320-326
- 37 McLennan P L. Relative effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on cardiac arrhythmias in rats. Am J Clin Nutr. 1993; 57 207-212
- 38 Lorenz R, Spengler U, Fischer S. et al . Platelet function, thromboxane formation and blood pressure control during supplementation of the western diet with cod liver oil. Circulation. 1983; 67 504-511
- 39 Yang B, Saldeen T GP, Nicjols W W. et al . Dietary fish oil supplementation attenuates myocardial dysfunction and injury caused by global ischemia and reperfusion in isolated rat hearts. J Nutr. 1993; 125 2067-2074
- 40 Gapinski J P, van Ruiswyk J V, Heudebert G R. et al . Prevention restenosis with fish oil following coronary angioplasty. A meta analysis. Arch Intern Med. 1993; 153 1595-1601
- 41 GISSI-Prevenzione-Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-prevenzione trial. Lancet. 1999; 354 447-455
- 42 Pscheidl E, Böke Pröls T. Omega-3 fatty acids enriched fat emulsions modulate splanchnic blood flow and micronial translocation in a low dose endotoxin rat model. Nutrition. 1997; 16, Suppl 16
- 43 Pscheidl E, Schywalsky M, Tschaikowsky K, Böke-Pröls Th. Fish oil supplemented parenteral diets normalize splanchnic blood flow and improve killing of translocated bacteria in a low dose endotoxin rat model. Crit Care Med. 2000; 28 1489-1496
- 44 Pscheidl E M, Wan J M, Blackburn G L. et al . Influence of omega-3 fatty acids on splanchnic blood flow and lactate metabolism in an endotoxemic rat model. Metabolism. 1992; 41 698-705
- 45 Mascioli E A, Leader L, Flores E A. et al . Enhanced survival to endotoxin in guinea pigs fed i. v. fish oil emulsion. Lipids. 1988; 23 623-625
- 46 Breil I, Koch T, Heller A. et al . Alteration of n-3 fatty acid composition in lung tissue after short-term infusion of fish oil emulsion attenuates inflammatory vascular reaction. Crit Care Med. 1996; 24 1893-1902
- 47 Mancuso P, Whelan J, DeMichele J J. et al . Dietary fish oil and fish and broage oil suppress intrapulmonary proinflammatory eicosanoid biosynthesis and attenuate pulmonary neutrophil accumulation in endotoxemic rats. Crit Care Med. 1997; 264 828-834
- 48 Archer S L, Johnson G J, Gebhard R E. et al . Effect of dietary fish oil on lung lipid profile and hypoxic pulmonary hypertension. J Appl Physiol. 1989; 66 1662-1673
- 49 Palombo J D, Bistrian B R, Fechner K D. et al . Rapid incorporation of fish or olive oil fatty acids into rat hepatic sinusoidal cell phospholipids after continuous enteral feeding during endotoxemia. Am J Clin Nutr. 1993; 57 643-649
-
50 Neuhof H.
Eicosanoides in trauma and traumatic shock. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis, and organ failure. Berlin; Springer 1993: 79-91 - 51 Lefer A M. Eicosanoids as mediators of ischemia and shock. Federation Proc. 1985; 44 275-280
- 52 Tempel G E, Cook J A, Wise W C. et al . Improvement in organ blood flow by inhibition of thromboxane synthetase during experimental endotoxic shock in the rat. J Cardiovasc Pharmacol. 1986; 8 514-519
- 53 Schützer K M, Haglund U, Falk A. The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to iv infusion of live E. coli. Acta Physiol Scand. 1987; 130 359-366
-
54 Mainous M R, Deitch E A.
Bacterial Translocation. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis and organ failure. Berlin; Springer 1993: 265-278 - 55 Radermacher P, Buhl R, Santak B. et al . The effects of prostacyclin on gastric intramucosal ph in patients with septic shock. Intensive Care Med. 1995; 21 414-421
- 56 Kramer H J, Stevens J, Grimminger F. et al . Fish oil acids and human platelets: dose dependent decrease in dienoic and increase in trienoic thromboxane generation. Biochem Pharmacol. 1996; 52 1211-1217
- 57 Koch T, Dunker H P, Klein A. et al . Modulation of pulmonary vascular resistance and edema formation by short term infusion of a 10 % fish oil emulsion. Infusionsther Transfusionsmed. 1993; 20 291-300
- 58 Carpentier Y A, Simoens C, Sidcrova V. et al . Recent developments in lipid emulsions: relevance to intensive care. Nutrition. 1997; 13 73-78
- 59 Endres S, Ghorbani R, Kelley V E. et al . The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989; 320 265-271
- 60 Miura S, Imaeda H, Shiozaki H. et al . Attenuation of endotoxin-induced intestinal microcirculatory damage by eicosapentanoic acid. Am J Physiol. 1993; G828-G834
- 61 Leaf A. Cardiovascular effects of fish oil: Beyond the platelet. Circulation. 1990; 82 624-628
- 62 Endres S, Lorenz R, Loeschke K. Lipid Treatment of inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 1999; 2 117-120
- 63 Suchner U, Senftleben U. Effekte von mehrfach ungesättigten Fettsäuren auf den Immunstatus: Bedeutung als Struktur- und Mediatorbausteine. Infusionsther Transfusionsmed. 1994; 21 59-70
- 64 Grimm H, Tibell A, Norrlind B. et al . Immunoregulation by parenteral lipids: Impact of the n-3 to n-6 fatty acid ratio. JPEN. 1994; 18 417-421
- 65 Palombo J D, DeMichelle S J, Lydon E. et al . Cyclic vs continuous enteral feeding with omega-3 and gamma-linolenic fatty acids: Effects on modulation of phospholipid fatty acids in rat lung and liver immune cells. JPEN. 1997; 21 123-132
- 66 Ling P R, Istfan N W, Lopes S M. et al . Structured lipid made from fish oil and medium-chain triglycerides alters tumour and host metabolism in Yoshida-sarcoma-bearing rats. Am J Clin Nutr. 1991; 53 1177-1184
- 67 Davies G R, Rampton D S. Eicosanoids: role in gastrointestinal inflammation and cancer. Eur J Gastroenterol Hepatol. 1997; 9 56-61
- 68 Bougnoux P. N-3 polyunsaturated fatty acids and cancer. Curr Opin Clin Nutr Metab Care. 1999; 2 121-126
- 69 Ohira T, Nishio K, Ohe Y. Improvement by eicosanoids in cancer cachexia induced by LLC-116 transplantation. J Cancer Res Clin Oncol. 1996; 122 711-715
- 70 Oliveira F LC, Rumsey S C, Schlotzer E. et al . Triglyceride hydrolysis of soy oil vs fish oil emulsions. JPEN. 1997; 21 224-229
- 71 Carpentier Y A, Siderova V S, Richelle M. et al . Does the presence of fish oil in emulsion particels affect the elimination of MCT/LCT emulsion. Clin Nutr. 1996; 15 2
- 72 Treskova E, Carpentier Y A, Ramakrishnan R. et al . Blood clearance and tissue uptake of intravenous lipid emulsions containing long-chain and medium-chain triglycerides and fish oil in a mouse model. JPEN. 1999; 23 253-259
- 73 Klein S, Kinney J, Jeejeebhoy K. Nutrition support in clinical practice: review of published data and recommendations for future research directions. JPEN. 1997; 21 133-156
Dr. med. E. Pscheidl
Klinik für Anästhesiologie, Universität Erlangen-Nürnberg
Krankenhausstraße 12
91054 Erlangen