Huschak et al. The recommended daily dose for parenteral lipids in adults is between 0. Fatty acids are oxidised in hepatocytes, myocardium, skeletal muscles, and other tissues. A lipid supply greater than the maximum rate of lipid oxidation, estimated between 1. Non-utilised lipid particles can be taken up by the mononuclear phagocyte system MPS , and the immune defence might deteriorate, as a result of inadequate chronic activation of the MPS [ 58 ], [ 59 ]. Hypertriglyceridemia induced by lipid infusion can usually be controlled by reducing the dose [ 60 ]; IIb. During the first days of infusion, plasma triglyceride levels should be monitored so that the dose can be modified, if necessary.
When lipid utilisation is impaired, e. Determination of serum opacity in the supernatant after centrifugation of whole blood is not considered useful. Lipid infusion with PN is not indicated in severe hyperlipidemia e. Organ failure, disturbances in microcirculation after blood transfusions, or disturbances in coagulation present no absolute contraindication for parenteral lipid administration. With a more critical metabolic situation, slower infusion rates such as continuous infusion over approximately 24 hours are recommended. Shorter infusion times may be chosen in stable patients, particularly those receiving long-term or home PN C.
In ARDS patients, a randomised study comparing intake of 1. Parenteral lipid emulsions based on soybean oil have been widely used for several decades. The administration of soybean oil emulsions resulted in high serum PUFA concentrations. Clinical, ex-vivo and animal studies suggested that the type of parenterally administered fatty acids may influence immune functions, and high PUFA containing lipid emulsions are associated with immunosuppressive effects [ 69 ], [ 70 ], [ 71 ], [ 72 ]; Ib. This lower essential fatty acid supply is adequate for meeting the needs of adults and infants [ 22 ], [ 76 ], [ 77 ], [ 78 ] Ib.
Although in vitro hydrolysis of medium-chain triglycerides by lipoprotein lipase is faster than that of long-chain triglycerides, clinical studies do not demonstrate uniform results. These emulsions contain triglyceride particles with re-esterification of medium-chain fatty acids made of coconut oil and long-chain fatty acids made of soybean oil in random distribution within the molecule.
The fatty acid composition is comparable to that of the physical mix of soybean oil and MCT. Lindgren et al. Randomly interesterified lipids 1. Although Chambrier et al. Rubin et al. In an in vitro test of peripheral white blood cells from healthy persons, olive oil showed less influence on the proliferation of lymphocyte subpopulations and their receptor expression than soybean oil emulsions [ 93 ], and similar effects were shown in monocytes and neutrophils [ 94 ], [ 95 ]. In randomised controlled studies in children and infants, the olive oil based emulsion showed comparable tolerance and safety to a soybean oil emulsion, but resulted in more favourable fatty acid levels in serum, reduced markers of lipid peroxidation, and higher serum vitamin E levels [ 56 ]; Ib; [ 53 ]; Ib.
In critically ill patients, the generation of pro-inflammatory lipid mediators can be reduced with the use of fish oil emulsions, which may prevent the escalation of SIRS to sepsis or even septic shock [ 97 ], [ 98 ]. Morlion et al. Schauder et al. Parenteral supplementation with fish oil emulsion in post-operative patients results in a rapid increase in the ratio of eicosapentaenoic acid n-3; EPA to arachidonic acid n-6; AA in thrombocyte phospholipids [ ], Ib.
A delay in collagen-induced, but not ADP-induced platelet aggregation did not result in altered bleeding times or bleeding complications following oesophagus resections. Lower mortality, shorter mechanical ventilation times, and shorter stays in intensive care units and hospitals were reported in post-operative patients, especially if the fish oil infusion had been administered prior to surgery [ ]; Ib. The stable HLA-DR expression patterns observed when receiving fish oil were associated with less severe infections [ ].
The use of fish oil emulsion in 56 patients with abdominal sepsis was associated with lower rates of re-operation and shorter length of stay in the intensive care units and total hospital stay [ ], abstract only. In an open case analysis of patients, increasing fish oil dosage was advantageous for survival in patients with sepsis and , 80 and 17 patients with either 1, 2 or 3 organ failures respectively [ ]; IIb. Parenteral fish-oil enriched lipid emulsion did not effect platelet function in critically ill patients [ ]; Ib.
The high unsaturated fatty acid content in fish oil tends undergo peroxidation, both during storage and in the patient after infusion. Apart from the direct effects of released oxygen radicals, lipid peroxidation products have a pro-inflammatory effect. Peroxidation of the high unsaturated fatty acids in the fish oil emulsions should be prevented by addition of vitamin E 15— In a very small group of 8 kidney donors and transplant recipients, infusion of this lipid emulsion induced no differences in coagulation, liver or renal functions or serum creatinine in transplant recipients [ ].
The currently available published clinical data on the use of this emulsion is still limited. A published study of postoperative patients showed that the rise in serum triglyceride levels, when receiving this mixed lipid emulsion, is the same as with a soybean oil emulsion [ ]. In an interim evaluation of a small number of surgical patients who received 5-days of postoperative PN, a reduction in hospital stay of 7 days was recorded in patients after a mixed emulsion Recent publication of the data of all patients in this study, however, did not show any significant difference in the biochemical and clinical parameters or in LOS length of stay , in either the intention-to-treat analysis or the per-protocol analysis [ ].
Furthermore, there was an increased ex vivo release of leukotriene B 5 and reduced leukotriene B 4 -release from leukocytes [ ].
Stability of commercial parenteral lipid emulsions repacking to polypropylene syringes
In a small group of intensive care patients a total of 20 patients , it was found that there was an increase in ALT in both groups after 5 days of PN in a comparison between mixed emulsions and soybean oil emulsions. There was, however, less tendency towards an increase in the mixed emulsion group n. Soybean oil-based emulsions meet energy and essential fatty acid requirements.
There are indications that mixture of soybean oil with other oils such as MCT or olive oil result in more favourable metabolic parameters and a more desirable, lower PUFA supply. Emulsions containing fish-oil may provide anti-inflammatory effects and offer the potential for a targeted approach in specific disease states.
Further research is needed on relevant clinical end points, and clear recommendations on clinical use of different emulsions cannot be given at this time. National Center for Biotechnology Information , U. Journal List Ger Med Sci v. Ger Med Sci. Published online Nov Adolph , 1 A. Heller , 2 T. Koch , 2 B. Koletzko , 3 K. Kreymann , 4 K. Krohn , 3 E. Pscheidl , 5 M. Senkal , 6 and Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine. Adolph 1 Dept.
Heller 2 Dept. Koch 2 Dept. Koletzko 3 Dept. Kreymann 4 Dept. Krohn 3 Dept. Pscheidl 5 Dept. Senkal 6 Dept. Surgery I, St. Author information Article notes Copyright and License information Disclaimer. Mary's Hospital Witten, Germany. Received Jan You are free to copy, distribute and transmit the work, provided the original author and source are credited.
This article has been cited by other articles in PMC. Abstract The infusion of lipid emulsions allows a high energy supply, facilitates the prevention of high glucose infusion rates and is indispensable for the supply with essential fatty acids. Keywords: lipid emulsions, alpha-tocopherol, hepatic steatosis, polyunsaturated fatty acids, critically ill. Background The infusion of lipid emulsions allows for high energy supply with iso-osmolar solutions.
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Lipoxins Lipoxins are derived from AA and are generated through different biosynthetic pathways. Open in a separate window. Figure 1. Eicosanoids synthesis pathways. Depending on the fatty acid content of cellular membranes lipid mediators with different pro-inflammatory potency or pro-resolving properties are generated from omega-3 or omega-6 polyunsaturated fatty acids via the cyclooxygenase or lipoxygenase pathway. Pro-inflammatory arachidonic acid AA -derived 5-series leukotrienes, 2-series prostanoids, and thromboxane A2 and eicosapentaenoic acid derived 3-series prostanoids and 5-series leukotrienes with largely reduced inflammatory properties.
Characteristics of lipid metabolism in critically ill patients Endogenous lipid stores are the main energy source for critically ill patients with an inadequate food intake. Fat-free parenteral nutrition can result in subnormal serum levels of essential fatty acids within one week IIb Administration of lipid emulsions is required within no more than one week after starting PN C.
Low-fat PN with a high glucose intake increases the risk of hyperglycaemia Ia In parenterally fed patients with a tendency to hyperglycaemia, an increase in the lipid-glucose ratio should be considered C. Commentary Tappy et al. Liver damage In adult patients with gastrointestinal disorders, administration of PN containing soybean oil, which provided either 2. Intravenous lipids should usually be provided with PN C. Commentary A lipid emulsion should usually be provided with PN to prevent depletion of essential fatty acids, lower the risk of hyperglycaemia, and prevent hepatic steatosis.
Commentary Fatty acids are oxidised in hepatocytes, myocardium, skeletal muscles, and other tissues. Commentary Organ failure, disturbances in microcirculation after blood transfusions, or disturbances in coagulation present no absolute contraindication for parenteral lipid administration. Available lipid emulsions Soybean oil emulsions Parenteral lipid emulsions based on soybean oil have been widely used for several decades.
Fish-oil based emulsions In critically ill patients, the generation of pro-inflammatory lipid mediators can be reduced with the use of fish oil emulsions, which may prevent the escalation of SIRS to sepsis or even septic shock [ 97 ], [ 98 ]. Conclusions Soybean oil-based emulsions meet energy and essential fatty acid requirements. References 1.
Frankfurt am Main: Umschau-Braus-Verl. Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol. Ariel A, Serhan CN. Resolvins and protectins in the termination program of acute inflammation. Trends Immunol. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol. Polarized light microscopy PLM is the most widely used technique for visualization of microstructural network of fats and has been applied so as to explain the differences in texture of fat mixtures, showing crystalline types and morphological alterations in crystal growth [ 53 ].
Control of crystallization to prevent crystal growth or to achieve the desired crystalline attributes is crucial for obtaining high-quality products with long useful life. Understanding the principles that underlie the crystallization phenomena is necessary to achieve this control [ 23 ]. Figure 2 presents a schematic of the crystallization process, storage of fats and associated mechanisms.
The behavior of crystallization, polymorphic transformation and microstructure of a fat is due to a combination of individual physical properties of each TAG and phase behavior of different TAG mixtures.
In general, the specific composition of a fat is one of the most important factors for final development of the crystal structure [ 54 ]. Process schematic of the process involving crystallization and storage of fats. Adapted from . Crystallization of fats is a critical factor associated with the structure and properties of most foods. The stability of many processed food products is influenced by changes in the physical state of the fats and changes in the crystallization processes, since the events of nucleation and crystal growth occur simultaneously at different rates as they are affected by conditions such as degree and rate of super-cooling, viscosity and agitation [ 13 ].
In the initial stages of food processing, the relative rates of nucleation and crystal growth determine the distribution, shape and size of the crystals, parameters that are directly related to the characteristics of consistency and texture. However, during the storage phase, several post-crystallization phenomena may occur, significantly affecting the properties and stability of foods. These include polymorphic transitions to thermodynamically more stable phases, formation of new crystals and crystal growth, and migration of oil or small crystals. It should be noted, however, that such events are not chronological; polymorphic transitions can occur even in the early stages of processing [ 31 ].
Additionally, in post-crystallization processes the phenomena known as sintering or bonding of adjacent surfaces can be verified, as well as spontaneous dissolution, also known as Ostwald ripening. The term sintering is described as the formation of solid bridges between fat crystals, with formation of a cohesive network associated with the undesirable increase in the hardness of the fat phase. Ostwald ripening, in turn, is associated with dissolution of previously existing small crystals in the fat phase and development of crystals with undesirable dimensions and weak crystal lattices, which causes loss of consistency of the products [ 56 ].
Furthermore, in some specific products the control of crystallization means, above all, avoiding this process, even if it is thermodynamically favored or due to storage or processing conditions [ 8 ]. Thus, control of crystallization and polymorphic transitions in fats is a factor of fundamental importance for the food industry. Interesterification is a technological alternative to the partial hydrogenation process, since it enables the production of oils and fats with specific functionalities. Due to the growing concern of the nutritional impact of trans fatty acids on health, interesterification has been indicated as the main method for obtaining plastic fats with low levels of trans isomers or absence of these compounds.
Lipid emulsions – Guidelines on Parenteral Nutrition, Chapter 6
In contrast to hydrogenation, this process does not promote the isomerization of double bonds of fatty acids and does not affect the their degree of saturation [ 57 ]. In the interesterification process the fatty acids are rearranged in the glycerol molecule. Interesterification is promoted by an alkaline catalyst chemical interesterification or by lipases enzymatic interesterification. The alkaline catalysts most frequently used are sodium methoxide and sodium ethylate [ 58 ].
In chemical interesterification the fatty acids are randomly distributed in the glycerol molecule along the three available positions within each molecule. When specific lipases are used to catalyze the interesterification reaction, rearrangement can occur in the sn1 and sn3 positions of the glycerol molecule, maintaining the sn2 position [ 59 ]. Chemical interesterification is currently the process most utilized by industry. The random distribution of fatty acids along the glycerol molecules leads to changes in the triacylglycerol composition, which alters the overall solids profile of the fat.
In interesterified fats, the random distribution of fatty acids results in great variability of TAGs, with intermediate melting points S 2 U and U 2 S. Other observations, such as decreased size of the crystals as well as distribution in the crystal lattice, were also observed in some studies [ 62 ].
Palm oil is obtained from the mesocarp of the fruit Elaesis guineensis. It is semi-solid at room temperature, consisting primarily of TAGs of palmitic and oleic acids. Palm oil is the vegetable oil most used worldwide in the food industry. In June , world production of palm oil reached 58 million tons, surpassing the production of soybean oil [ 63 ]. As a result of increased production, many studies are focused on palm oil, especially regarding its crystallization behavior and nutritional aspects.
Compared to other vegetable oils, palm oil presents a unique and differentiated fatty acid composition, containing similar percentages of saturated and unsaturated fatty acids. In addition to these features, palm oil contains small percentages of MAGs and DAGs as minor components, which are produced during maturation of palm fruits and oil processing. The removal of these compounds, however, is difficult even under optimal refining conditions [ 18 , 64 , 65 ].
The functional properties of palm oil and its fractions appear to be strongly related to its composition and the quantity and type of crystals formed at the temperature of application. Recent studies on the interactions between TAGs and DAGs in palm oil during crystallization show that the latter have a deleterious effect on the characteristics of crystallization, with intensity proportional to the concentration of these minority lipids in palm oil and its fractions [ 66 , 67 ].
According in [ 68 ], the negative effect of DAGs on the crystallization of palm oil may be related to the low nucleation rate of TAGs in the presence of these compounds. In addition to the slow crystallization of palm oil, another factor of great concern in industry is its post-processing stability. Palm oil is often associated with hardening problems during storage.
In some products based on this raw material, undesired crystal growth occurs which results in gritty texture and poor spreadability [ 69 ].
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In margarines, specifically, the formation of crystal agglomerates with mean diameter between 0. Classically, two methods are proposed for the production of soft PMF: the olein route most common in Asia and the stearin route, which is preferentially used in South America because of the need for olein with high iodine index in the first fractionation stage. Due to the closely related structural properties, TAGs can produce co-crystals by intersolubility, which frequently present solid solutions, monotectic interactions, eutectic systems and formation of molecular compounds [ 1 ].
As a result, the efficiency of fractionation depends not only on the separation efficiency, but is limited by the phase behavior of TAGs in the solid state. Most natural oils and fats have limited application in their unaltered forms, imposed by their particular composition of fatty acids and TAGs. Thus, oils and fats for various industrial applications are chemically modified by hydrogenation or interesterification, or physically by fractionation or mixture [ 75 ].
Although used for a long time, partial hydrogenation results in significant formation of trans fatty acids, associated with negative health effects [ 76 ]. In Brazil, controversial issues surrounding the role of trans fatty acids in the diet have led to progressive changes in legislation, aiming to include more information for consumers. Resolution RDC No. Companies had until July 31, to meet regulations, so that the trans fat content is declared in relation to the standard portion of a certain food, together with statements of total and saturated fats [ 77 ].
In response, Brazilian industries opted for the progressive substitution of trans fat in many products through the development of base fats with functionality and economic viability equivalent to partially hydrogenated fats, but without substantial increase in the content of saturated fatty acids in foods. In this sense, interesterification was found to be the main alternative for obtaining plastic fats with low levels of trans isomers or lack thereof. In particular, chemical interesterification of liquid oils with fully hydrogenated oils hardfats is currently the alternative of greatest versatility to produce zero trans fats, producing base fats favorable for the preparation of commonly used shortenings [ 61 ].
The use of blends, i. Although the interesterification, fractionation and mixing processes are very functional from a technological point of view, the substitution of partially hydrogenated fats in food products, especially in shortenings and confectionery products, is currently a challenge since appropriate crystallization and texture properties are difficult to obtain in the absence of trans fatty acids [ 78 ]. In particular, adequacy of crystallization kinetics of these base fats is of utmost importance so that their use may be adjusted to the limitations of industrial processes and to improve control of processing steps that involve recrystallization of the fat fraction, ensuring quality of the final product [ 79 ].
Contrarily, previously standardized processing times and equipment must be altered according to the characteristics of the fat used. This fact becomes particularly important as new fat fractions began to replace partially hydrogenated fats in most industrial applications, mainly in the production of biscuits and bakery products, where it is noted that fats with the same apparent solids profile present very different crystallization properties [ 80 ].
In the specific case of interesterified fats, the formation of partial acylglycerols, such as MAGs and DAGs as a result of chemical interesterification, can influence the crystallization kinetics via alterations to the crystal nucleation process [ 81 ]. According in [ 82 ], 0. Because the typical catalyst content used industrially ranges from 0. Although minority lipids present influence on the crystallization properties of these fats, their complete removal is still difficult and expensive, especially on a large scale [ 22 ].
Considering that in the Brazilian industry this substitution process is relatively recent, the problems of crystallization behavior due to the unsuitability of new fat fractions are numerous and aggravated, mainly due to regional differences in climate and conditions of transport and storage.
In this context, highlighted problems include unwanted polymorphic transitions, oil exudation, development of fat bloom, formation of crystalline agglomerates, and base fats with a maximum solid fat content or induction periods incompatible with certain industrial applications. Studies on modification, stabilization and control of crystallization of these base fats are therefore of crucial importance for development of the edible oils industry.
In a classic definition, an emulsifier is an expression applied to molecules which migrate to interfaces between two physical phases, and are therefore more concentrated in the interfacial region than in the solution phase [ 83 ]. The main molecular characteristic of an emulsifier is its amphiphilic nature, characterized by an ionic group polar region and a hydrocarbon chain nonpolar region.
According to their polar and nonpolar regions, emulsifiers are designated as hydrophilic or lipophilic, which affects their solubility in water or oil [ 84 ]. Thus, the term hydrophilic-lipophilic balance HLB was suggested, which measures the affinity of an emulsifier for oil or water.
Regarding emulsifiers in foods, lipophilic properties are generally the most important, but the hydrophilic-lipophilic balance HLB may vary considerably according to the chemical composition of the emulsifier. The dual affinity of emulsifiers results in the formation of a single phase between initially immiscible substances emulsion. Furthermore, these compounds perform functions that in some products are not related to emulsification, including modification of the crystal habit during crystallization of oils and fats [ 83 ].
The concept of HLB makes it possible to characterize the various emulsifiers or mixtures of emulsifiers. In general, the following guidelines are used for applying an emulsifier based on its HLB:. Nevertheless, the HLB value is limited because it provides a one-dimensional description of the emulsifier properties, and omits information such as the molecular weight and temperature dependence.
It is also difficult to calculate useful HLB values for various important emulsifiers in food applications eg: phospholipids. Additionally, HLB values do not include the important crystallization properties of emulsifiers [ 85 ]. Regarding the crystallization properties, in the crystal structure of emulsifiers, the predominant factor is the hydrophilic portion which is the relatively larger portion of the molecule.
The size of the hydrophilic group, along with the extension and spatial distribution of hydrogen bonding between adjacent groups, has a much larger influence on the molecular packing of the crystal than the nature of the fatty acid chain.
A simple emulsifier, such as a monoacylglycerol, generally crystallizes in the double chain length DCL , while those with larger hydrophilic groups more frequently crystallize in the SCL configuration Figure 3 [ 83 ]. Among crystallization properties, an important feature of emulsifiers is their ability to create mesophases.
On a micromolecular level, the emulsifier agent and water are separated phases, but at the macro level the mixture becomes uniform and is stable that is, the phases do not separate [ 86 ]. Liquid crystals are thermodynamic mesophases of the condensed material with a certain degree of ordering between the crystalline solid and liquid states [ 87 ]. There are two main families of liquid crystals: thermotropic and lyotropic. Thermotropic liquid crystals are composed of molecules, or mixture of molecules, which exhibit shape anisotropy also known as anisometry.
These molecules may have the shape of rods most common , disks and arcs, among others. The structural and ordering differences of these individual molecules occur as a function of temperature, and therefore are called thermotropic. On the other hand, lyotropic liquid crystals are mixtures of amphiphilic molecules and polar solvents, which under determined conditions of temperature, pressure and relative concentrations of different components, present the formation of aggregated molecular superstructures, which are organized in space, showing some degree of order [ 88 ].
The amphiphilic molecules such as emulsifiers may present both behaviors thermotropic and lyotropic in this case, called amphotropic liquid crystals [ 88 , 89 ]. A simplified schematic of the formation of some thermotropic and lyotropic mesophase structures is shown in Figure 4. Adapted from .
In addition to their known functions of emulsification and stabilization of emulsions, emulsifiers can modify the behavior of the continuous phase of a food product, giving it specific benefits. In fat-rich products, emulsifiers may be used to control or modify the crystallization properties of the fat phase. Study of the effects of emulsifiers in fat systems is of great interest to improve industrial products, particularly with respect to fat for use in chocolate, confectionery and baking.
However, the role of these compounds as modifiers of crystallization in natural and commercial fats is little exploited in technical literature [ 17 ]. To date, the vast majority of studies on the use of emulsifiers as modifiers of the crystallization process in fats were carried out with fully hydrogenated oils, model systems or pure TAGs, and therefore do not reflect the need to control crystallization in fats for industrial application [ 9 , 90 ]. In general, the effect of emulsifiers appears to be related to different crystalline organizations and the creation of imperfections.
Some of them can slow transformations via steric hindrance, while others promote these transformations by favoring molecular displacements [ 3 ]. Two different mechanisms have been reported in literature to interpret the effect of emulsifiers on crystallization of fats. Pichot R.
Analytical Techniques for Studying the Physical Properties of Lipid Emulsions
Tadros T. KGaA, Weinheim, p. Herrera M. Akhtar M. Whey protein—maltodextrin conjugates as emulsifying agents: an alternative to gum arabic. Food Hydrocolloids 21 4 Tavernier I. Food-grade particles for emulsion stabilization. Aserin A. Lam R. Food proteins: a review on their emulsifying properties using a structure—function approach. Food Chemistry 2 Dickinson E. Interfacial structure and stability of food emulsions as affected by protein—polysaccharide interactions.
Soft Matter 4 5 Evans M. Emulsion stabilisation using polysaccharide—protein complexes. Derkach S. Rheology of emulsions. Advances in Colloid and Interface Science Cakmak H. Food Studies 7 1 Wardhono E. Tontul, I. Mixture design approach in wall material selection and evaluation of ultrasonic emulsification in flaxseed oil microencapsulation.
Related Analytical Techniques for Studying the Physical Properties of Lipid Emulsions
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