ARTICLE IN PRESS Clinical Nutrition Supplements (2005) 1, 5–7
Evolution of parenteral lipid emulsions Dan L. Waitzberg Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de Sa˜o Paulo, FMUSP, Av. Dr. Arnaldo 455-31 andar, CEP:01246-903, Sa˜o Paulo, Brazil
Lipid emulsions can be used as a parenteral source of essential fatty acids (FA), fat-soluble vitamins and energy.1 The evolution of parenteral lipid emulsions may be divided into three generations of products and concepts. The first generation is represented by conventional lipid emulsions based on soybean and/or safflower oil, very rich in o-6 polyunsaturated fatty acids (PUFA).1 These pioneering lipid emulsions were developed by a group of scientists under the guidance of Dr. Arvid Wretlind who managed to demonstrate a good correlation between the outcomes in both experimental studies and clinical trials.2 The second generation of parenteral lipid emulsions was developed in response to indications of the potential disadvantageous effects of the high levels of PUFA present in the previous generation of lipid emulsions. Critical evaluation indicated that an excessive intake of o-6 PUFA in parenteral nutrition was associated with an unbalanced FA pattern in cell membranes, which may lead to a modification of the production of lipid mediators (prostaglandins and leukotrienes) and a promotion of immunosuppression and systemic inflammatory reactions (trauma, surgery and sepsis).1,3–6 At the experimental level we could show a decreased phagocytosis by liver and lung resident macrophages of rats treated with total parenteral nutrition containing o-6-PUFA-rich lipid emulsions.7 We also found a decreased bacterial killing function E-mail address: [email protected]
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of neutrophils in malnourished patients with gastric cancer; however, this function remained within the normal range values in 80% of the patients.8 This second generation of lipid emulsions is represented by the physical and chemical (structured lipid emulsions) mixtures of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT), as well as the olive oil containing lipid emulsions. The MCT/LCT lipid emulsions claim faster clearance from the blood-stream, a higher degree of immediate oxidation and positive influence on the immune system due to the reduced amount of o-6 FA.9,10 Some experimental evidence indicates that such lipid emulsions decrease chemotaxis, phagocytosis and the bacterial killing functions of polymorphonuclear cells.11,12 The olive oil containing lipid emulsion, available since 1998, is a mixture of 80% olive oil and 20% soybean oil. It is asserted that they are immunologically neutral, providing a more physiological FA pattern with less peroxidation and demonstrating good stability in all-in-one mixtures.13,14 In our laboratory tests, the culture of human monocytes/macrophages with an olive-oil-based lipid emulsion did change neither the expression of surface molecules with antigen presenting function (HLA-DR) nor surface receptors to the Fc fraction of immunoglobulins that participate in phagocytosis opsonization (CD16 and CD32).15 The third generation of parenteral lipid emulsions is characterized by the inclusion of fish oil and design according to a specific FA pattern. They are
ARTICLE IN PRESS 6 represented by a pure fish oil lipid emulsion, introduced in 1998 by Fresenius Kabi, which is used in combination with a conventional lipid emulsion, a ready-mixed MCT/LCT/fish oil lipid emulsion and a new type of emulsion made of a physical mixture of soybean-LCT, MCT, olive oil and fish oil supplemented with vitamin E (SMOFlipids). This innovative lipid emulsion was designed to decrease the amount of o-6 FA and to increase the amount of o-3 FA, thereby reducing the ratio o-6:o-3 FA to approximately 2.5:1, which is in accordance with current recommended levels.16–19 There is evidence that o-3-FA-enriched lipid emulsions, in comparison with conventional lipid emulsions, exert anti-inflammatory and immunomodulatory effects. This was also experimentally observed in our laboratory tests on rats with experimental colitis, where a parenteral infusion of an o-3-rich lipid emulsion with an o-6:o-3 FA ratio of 3:1 reduced diarrhea, preserved oral intake–weight ratio, attenuated morphological consequences and decreased colonic concentrations of inflammatory mediators.20 Quoting Professor Peter Fu ¨rst from his visionary article in Clinical Nutrition published in 2000: ‘Indeed, the time is ripe to collect the knowledge from all available studies and put it into the clinical context. Nutritional therapy with fish oil can improve the chances of survival and healing in conditions where o3 FA and cytokines have been elicited’.16 The newly available lipid emulsion SMOFlipids contains 30% soybean oil (mainly essential FA), 30% MCT, 25% olive oil (high in monounsaturated FA), and an substantial amount of fish oil (15%)—mainly very long-chain PUFA—and thus combines the advantages of the four types of oils currently used in parenteral nutrition. For the first time a lipid emulsion with a well-balanced FA pattern resulting in an optimal o-6/o-3 ratio is easily available facilitating the ease, of intravenous application of o-3 FA. The scientific rationale for the new lipid emulsion, the evidence of the beneficial effects of the addition of o-3 FA and recent clinical experience with the new product are the subject matters of this supplement. Professor Robert Grimble explains the immune response to inflammatory stress and correlates it with a demand for adapted types of lipid emulsions. He concludes that ‘y there is the need to develop lipid emulsions which are ‘‘neutral’’ in terms of their ‘‘immunosuppressive’’ properties. y The inclusion of o-3 FA and fats rich in monounsaturated FA allows these goals to be achieved.’ Professor Thea Koch focuses on the documented effects of o-3 FA on postoperative immune and inflammatory responses as well as on outcome
D.L. Waitzberg parameters. She presents data showing that o-3 FA lower the magnitude of inflammatory response and improve host defence. Furthermore, significantly reduced lengths of ICU and hospital in-patient care were observed in several studies. There is increasing evidence that perioperative application of o-3 FA is more effective with regard to cytokine biology and patient recovery than postoperative treatment solely. A summary of all available data on SMOFlipids is provided by Professor Helmut Grimm. Clinical experiences show that this new emulsion is safe and well tolerated. Triglycerides are eliminated efficiently. Furthermore, several findings indicate a better liver tolerance. o-3 FA contained in SMOFlipids beneficially influence the lipid mediator profile, most probably contributing to the favourable effect of this emulsion on the length of hospital stay in a subgroup of patients participating in a multi-centre study. We hope that this supplement on the symposium ‘New Emulsions in Parenteral Nutrition’, held at the ESPEN Congress 2004 in Lisbon, will provide new information for practitioners, clinical and basic scientists to better understand the role of this new generation of parenteral lipid emulsions in clinical practice.
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