Fat emulsions are one of the non-protein energy sources in the composition of TPN, and it is clearly of clinical importance to understand the metabolic characteristics of different fat emulsions in order to rationalize their application and reduce the metabolic complications associated with them.
Methods: Triglycerides are classified into long-chain, medium-chain and short-chain triglycerides according to their different carbon atomic numbers. Currently, fat emulsions with simple LCT and physical mixture of MCT/LCT are commonly used in clinical practice. Also in the research and clinical trial stage are preparations such as structural fat emulsions, fat agents containing ω-3 and fat emulsions containing olive oil.
RESULTS: Fat emulsions provide energy and essential fatty acids, maintain cell structure and adipose tissue constancy.
CONCLUSION: The different chain lengths and structures of triglycerides, constituting different metabolic characteristics of fat emulsions, determine their selection for clinical applications.
In the early 1960s, Wretlind et al. successfully developed a fat emulsion based on soybean oil, which put an end to the decades-long clinical application of intravenous nutrition mainly based on hypertonic glucose for non-protein energy, and opened a new era of parenteral nutrition (PN) in the true sense.
Since the introduction of the first generation of fat emulsions that can be safely applied clinically, research on their metabolic characteristics and application effects has been intensified; meanwhile, fat emulsion products with different characteristics have also been rapidly developed. Since fat emulsions constitute one of the non-protein energy sources in PN, it is obviously clinically relevant to understand the metabolic characteristics of different fat emulsions for rational application and to reduce the metabolic complications associated with them.
I. Composition and metabolic characteristics of fat emulsions
Fat emulsion is an oil-in-water emulsion, mainly composed of vegetable oil, emulsion and isotonic agent. The energy density of fat emulsion is high, providing high calories in a small volume. 1 gram of fat oxidized can provide 37.62 kilojoules (kJ). The significance of clinical application of fat emulsions is to provide essential fatty acids and energy, and to maintain the cellular structure and the constancy of human adipose tissue.
Currently, most of the fat emulsions commonly used in clinical practice are composed of soybean oil as raw material, but also of other vegetable oils. Due to the different raw materials that constitute fat emulsions, the number of carbon atoms in triglycerides varies. From 14 to 24 carbon atoms belong to the long-chain triglycerides (LCT), from 6 to 12 carbon atoms for medium-chain triglycerides (MCT), only from 2 to 4 carbon atoms for the short-chain triglycerides. According to the presence or absence of double bonds and the number of double bonds, fatty acids are classified into saturated fatty acids (without double bonds), monounsaturated fatty acids (with one double bond) and polyunsaturated fatty acids (with two or more double bonds); the latter are classified into ω-3, 6, 7 and 9 fatty acids according to the disposition of the first double bond.
Linoleic acid and octadecadiene-9,12-acid are the basic components of soybean oil, which are ω-6 polyunsaturated fatty acids; α-linolenic acid contains only a small amount in soybean oil, most often found in fish oil, which are ω-3 polyunsaturated fatty acids. The different metabolic characteristics of all these fatty acids determine their selective application in clinical diseases.
LCT fat emulsions provide essential fatty acids and energy, but LCT entry into mitochondrial metabolism is dependent on carnitine transport and oxidative metabolism is slow. Some studies found that it may accumulate in reticuloendothelial cells when applied for a longer period of time, and there may be fat pigmentation in the liver and spleen, and it also has a suppressive effect on the immune function of the body, and this immunosuppressive effect is not only related to the dose and infusion rate of fat emulsion, but also involves the fat source. Therefore, following LCT, MCT was fractionated from palm kernel and coconut oil with a view to improving the safety and efficacy of applied fat emulsions. From a theoretical point of view, MCT is more water soluble than LCT, can enter the mitochondria for rapid oxidation without relying on carnitine, has a faster clearance rate in the blood circulation than LCT, and is less likely to accumulate in the liver, which is undoubtedly beneficial for critically ill patients and neonates with carnitine deficiency.
However, MCT also has its shortcomings: it cannot provide essential fatty acids, and the application of pure MCT can cause metabolic acidosis and neurological side effects. Therefore, the fat emulsion formed by physically mixing MCT and LCT in a certain ratio can achieve the effect of improving the strengths and avoiding the weaknesses. Structural fat emulsions are new formulations characterized by chemical mixing after the physical mixing of MCT/LCT, i.e., combining fatty acids of different chain lengths on three carbon chains of one glycerol molecule. It is better tolerated, more rapidly oxidized, and less prone to ketosis or hyperlipidemia than pure MCT or MCT/LCT physically mixed fat emulsions, and can enhance nitrogen retention more significantly; its long-term effects have yet to be confirmed in clinical practice. Short-chain fatty acids have the characteristics of promoting intestinal blood flow, stimulating pancreatic enzyme secretion and promoting water and sodium absorption in the colon, which are suitable for patients with short bowel syndrome.
When TPN contains short-chain fatty acids, it can significantly reduce intestinal mucosal atrophy and intestinal bacterial translocation that may occur with standard TPN because of its stimulating effect on intestinal mucosa. Despite the above advantages of short-chain fatty acids, they are not suitable as the main energy supply. At present, short-chain fatty acids are only in the stage of animal experiments and clinical trials.
In addition to the above-mentioned fat emulsions, there are also newly developed fat emulsions containing olive oil, which are rich in monounsaturated fatty acids and contain more bioactive α-tocopherol than soybean oil fat emulsions. α-tocopherol can reduce fat peroxidation and is also beneficial for maintaining immune function. Fat emulsions containing fish oil are rich in omega-3 polyunsaturated fatty acids, which help to reduce the risk of cardiovascular disease, reduce platelet activation, prevent tumor growth, and improve immune function. Some of these new agents are still in the experimental stage, and their theoretical significance has yet to be clinically verified.
Second, the clinical application of fat emulsion
(a) Stress: Large surgeries, traumas and infections can induce the body to produce stress, which is a systemic metabolic reaction to maintain the body’s life. Generally speaking, under stressful conditions such as surgical trauma, with neuroendocrine changes, fat mobilization is accelerated, plasma free fatty acid and triglyceride levels are increased, and the renewal rate is accelerated; fat becomes the main energy supplying substance in the body. At this time, no matter what kind of fat emulsion is provided, when it accounts for 30% to 50% of the total energy, it is less likely to cause hyperlipidemia; if it is combined with carbohydrates to form non-protein calories, it has a better nitrogen-saving effect.
In acute severe pancreatitis (SAP), for example, the disease has a long duration, consumes a lot, sometimes requires multiple surgeries, and without active nutritional support, patients can suffer from severe malnutrition and complicate multiple organ dysfunction, affecting the prognosis. The use of parenteral nutrition (PN) support as one of the comprehensive treatment measures for SAP has become a consensus among clinicians, and PN contains fat emulsion, which can reduce the amount of exogenous glucose and make the hyperglycemia of SAP patients easier to control. Fat emulsions generally account for 40% to 60% of the non-protein calories. However, in some patients with acute severe pancreatitis, hyperlipidemia is often the cause of its development, and some patients have hyperlipidemia due to the pathological changes of pancreatitis itself; for these patients, it is controversial whether fat emulsions are suitable.
It is generally believed that hyperlipidemia in these patients is mostly due to abnormal or disturbed lipid metabolism in the body, and it is not clear whether the metabolism of exogenous fat emulsion is also affected, so for patients with acute pancreatitis who already have hyperlipidemia, fat emulsion is not advocated as the main energy supply substance. However, if hyperglycemia is also present, fat emulsion should be used as appropriate because the application of glucose is restricted, and MCT/LCT fat emulsion with faster oxidative metabolism should be chosen.
For safety reasons, it is advisable to actively monitor lipid metabolism and fat profile to facilitate timely revision of the nutritional support program. In a few patients with acute severe pancreatitis, coagulation disorders may occur. The hospital has observed several indicators of bleeding and coagulation in such patients before and after the application of fat emulsion, and found that patients with only mild abnormalities of bleeding and clotting time, the short-term, moderate application of fat emulsion of simple LCT or MCT/LCT physical mixture does not aggravate the abnormalities of the coagulation and fibrinolytic system, and is safe and effective.
(ii) Liver dysfunction: The prognosis of patients with severe liver dysfunction often depends on the regenerative capacity of hepatocytes. Cell regeneration requires energy, and the most basic way for the liver to obtain ATP is through fatty acid oxidation. When fatty acid oxidation is inhibited, the hepatocyte regeneration process is hindered. A comparison of the regenerative capacity of hepatocytes in rats after partial hepatectomy receiving isocaloric fat emulsion or glucose solution and saline showed that hepatocytes in rats receiving fat emulsion were the most active in mitosis. Another group of animals under the same conditions showed similar results: the protein content, protein/triglyceride ratio, and protein synthesis rate in mitochondria were better in the residual liver of rats in the fat emulsion group than in the non-fat emulsion group; moreover, liver function was significantly abnormal in the latter group, and fat infiltration in the liver lobules was more pronounced.
These findings suggest that fat is extremely important for the regenerative repair of damaged liver. This positive effect of fat may be related to its ability to enhance energy utilization by the liver and to promote the synthesis of phospholipids and cholesterol. Clinically, many patients with liver disease or liver dysfunction have a reduced ability to digest and absorb fats, and patients exhibit an aversion to fatty foods, which are often difficult to tolerate when supplied via the gastrointestinal route. Such patients may tolerate fat better if it is provided through intravenous route.
Comparing the metabolic characteristics of the commonly used fat emulsions, a fat emulsion with a physical mixture of MCT/LCT or a structured fat emulsion is the ideal choice in cases of liver dysfunction. When applied, it is preferable to combine it with glucose to form a non-protein energy and infuse it as a total nutrient mixture. The proportion of fat to non-protein energy should depend on the degree of hepatic impairment and the patient’s ability to metabolize and purify fat. In most cases, the ratio is comparable to that used in malnourished patients without liver dysfunction. Reduce the amount appropriately only in cases of severe liver damage.
(iii) The special role of fat emulsions: In the last decade, there has been increasing interest in fat-based drug carrier systems. Many clinical drugs have poor water solubility and must rely on solvents to function. Organic solvents not only have their own toxicity, but also may interfere with the drug effect. Fat emulsions with soybean oil as the main component have the advantage of both solvent properties and almost no toxicity.
Certain drugs, after using fat emulsions as solvents, reduce the occurrence of drug-related complications and effectively control the release of drugs. Drugs for which the application of fat emulsion as a carrier solvent is mostly seen clinically include dexamethasone, valium and short-acting anesthetics (Propofol). It has been found that when amphotericin B is added to fat emulsion, the toxic side effects of amphotericin B on the body are lighter than when it is added to 5% glucose solution, and the clearance rate in the body is also accelerated. It is believed that fat emulsions will be increasingly used in drug carrier systems in the near future.