Alternative lipid sources for enteral and parenteral nutrition: long- and medium-chain triglycerides, structured triglycerides, and fish oils

This article reviews current investigations of the use of alternative lipid sources to enhance the metabolic and immune functions of hospitalized patients. Conventional lipids have been implicated as the cause of a variety of iatrogenic side effects in critically ill hospitalized patients, and long-chain triglycerides of the omega-6 family have been shown to be potentially detrimental to immune function. Alternative lipids (fish oils, medium-chain triglycerides, and structured triglycerides) have been proposed as substitutes for conventional long-chain, polyunsaturated omega-6 fatty acids. Unlike long-chain triglycerides, medium-chain triglycerides are more rapidly cleared from the blood and are completely oxidized for energy. However, medium-chain triglycerides contain no essential fatty acids. On the other hand, structured triglycerides offer the advantages of long-chain triglycerides (essential fatty acids) and of medium-chain triglycerides (rapid clearance and oxidation). Fish oils, which contain long-chain polyunsaturated omega-3 fatty acids, appear to be anti-inflammatory and to affect immune function differently from the omega-6 long-chain triglycerides.     

Structured lipid made from fish oil and medium-chain triglycerides alters tumor and host metabolism in Yoshida-sarcoma-bearing rats

The effects of structured lipid composed of fish oil and medium-chain triglycerides (Fish/MCT) on tumor and the host metabolism was compared with conventional long-chain triglycerides (LCTs) in Yoshida-sarcoma-bearing rats receiving TPN for 3 d. The two parenterally fed groups were divided into two treatments, saline or tumor necrosis factor (TNF), given intravenously at 20 micrograms/kg body wt. Changes in tumor volume, body weight, urinary nitrogen, whole-body and tissue protein kinetics, and fatty acid composition were measured. The study revealed that Fish/MCT feeding inhibited tumor growth, which could be attributed to decreased tumor protein synthesis. Body weight and nitrogen were better maintained by Fish/MCT feeding. In addition, the effects of Fish/MCT on tumor growth were synergistic with TNF treatment. The results demonstrate that dietary fat composition can influence fatty acid compositions of tumor tissue as well as tumor protein kinetics after a short period of TPN feeding.     

Metabolic clearance of a fat emulsion containing medium-chain triglycerides in cirrhotic patients.

Medium-chain triglycerides (MCTs) may be advantageous in cirrhotic patients, but data on the clearing capacity are lacking. Intravenous fat tolerance test (IVFTT) was performed on 28 cirrhotic patients (Child's A, n = 9; Child's B, n = 13; Child's C, n = 6) to determine the clearance rate of Lipofundin MCT 20%, which contains a physical mixture of MCT and long-chain triglycerides (LCT). The mean fractional elimination rate (k2) of MCT/LCT physical blend in the cirrhotic patients (7.72%/min) was comparable with that of the healthy control subjects (n = 9, k2 = 5.43%/min). Significantly higher serum free fatty acid (FFA) levels were found in the cirrhotic patients during IVFTT. The difference could be accounted for by their higher basal levels. In all patients, serum FFA concentrations returned to basal value at the end of 1 hour. Prompt appearance of glycerol and beta-hydroxybutyrate was seen during IVFTT, indicating that hydrolysis of triglycerides and release of ketone bodies from the liver were rapid. It was concluded that the ability to eliminate MCT/LCT physical blend was not impaired in the cirrhotic patients.     

Effect of fat emulsions containing medium-chain triglycerides and glucose on ketone body production and excretion

The parenteral application of fat emulsions containing medium-chain triglycerides results in an increase of ketone bodies as expression of the rapid metabolism of medium-chain triglycerides. Although ketoacidosis could not be watched, it should be of advantage to reduce the ketonemia. This might be reached by application of carbohydrates. The simultaneous infusion of glucose--given to 10 healthy persons--together with a 10% fat emulsion containing 75% medium-chain triglycerides almost completely inhibited the increase of ketone bodies in serum and its urinary excretion. Other prosperous metabolic effects, eg, the rapid clearance of the triglycerides from the serum were not affected by this regimen.     

Effect of dietary olive oil, corn oil and medium-chain triglycerides on the lipid composition of rat red blood cell membranes

The effects of dietary olive oil, corn oil and medium-chain triglycerides (MCT) on factors that characterized erythrocyte membrane lipid fluidity were studied. Weanling rats were fed for 3 or 5 wk high fat diets (10%) containing olive oil, corn oil or a mixture of MCT with olive oil or corn oil. Total phospholipids and phosphatidylcholine of erythrocyte ghosts obtained from olive oil-fed animals, as compared to those fed corn oil, showed an increase in long-chain polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) series and a decrease in saturated fatty acids. The addition of MCT to the olive oil diet induced an increase in palmitic, palmitoleic and delta-5,8,11-eicosatrienoic acids and a decrease in long-chain PUFA of the (n-6) series in erythrocyte membrane phospholipids. Conversely, rats fed a mixture of MCT and corn oil, as compared to those fed exclusively corn oil, showed increase in long-chain PUFA of the (n-6) and (n-3) series, with no changes in saturated fatty acid levels. The cholesterol/phosphorus molar ratio showed only a slight increase with MCT supplementation. Olive oil feeding induced important changes in fatty acid composition of erythrocyte membrane phospholipids as compared to corn oil feeding without modifying the cholesterol/phosphorus ratio and MCT feeding slightly affected red blood cell membrane lipid composition.     

Parenteral infusion of long- and medium-chain triglycerides and reticuloendothelial system function in man

Previous study demonstrated that patients who received total parenteral nutrition (TPN) with standard intermittent infusion of long chain triglyceride (LCT) at 0.13 g kg-1hr-1 over 10 hr for each of three days showed a significant decline in 99Tc-sulfur colloid (TSC) clearance rate by the reticuloendothelial system (RES). The present studies evaluated eight patients who received the same total lipid dose of LCT infused continuously as in a three-in-one admixture, and another nine patients receiving the same amount of fat as a medium chain triglyceride (MCT)/LCT (75%/25%) emulsion intermittently over 10 hr at 0.13 g kg-1hr-1 for three consecutive days. Patients were given continuous total parenteral nutrition (TPN) comprised of protein, 1.5 g kg-1day-1, and dextrose, 4.5 g kg-1day-1. RES function was examined by measuring the clearance rates of intravenously injected TSC while receiving TPN containing only protein and dextrose, and again after three days of fat infusion. Mean (+/- SEM) clearance rate constants before and after continuous LCT infusion were 0.38 +/- 0.09 and 0.41 +/- 0.08 min-1, respectively, while those before and after intermittent MCT/LCT infusion were 0.50 +/- 0.18 and 0.73 +/- 0.24 min-1, respectively. In contrast to intermittent LCT infusion, the administration of continuous LCT or an intermittent MCT/LCT mixture does not impair TSC clearance by the RES. These findings suggest that condensing the daily period of LCT infusion at standard dosage may exceed the rate of metabolic utilization, resulting in increased fat removal and diminished TSC uptake by the RES.(ABSTRACT TRUNCATED AT 250 WORDS)     

长链脂肪乳剂及中/长链脂肪乳剂水解速率的比较研究

目的：比较长链脂肪乳剂、物理混合的中／长链脂肪乳剂及结构脂肪乳剂的水解速率。方法：应用1、^14C甘油棕榈酸标记的长链三酰甘油（LCT）和2，3－^3H甘油辛酸标记的中链三酰甘油（MCT），分别标记Intralipid,Lipofundin及Structolipid，在体外添加缓冲液、脂蛋白酯酶和肝酯酶后，置37℃温箱中水浴、卵育。采用气相色谱仪测定核素核记的各种脂肪酸及三酰甘油浓度，游离脂肪酸浓度用放射性核素扫描计数测定，通过计算培养液中^14C标记的长链脂肪酸及^3H标记的中链脂肪酸分别在^14C标记LCT及^3H标记MCT中的比例。来计算三种脂肪乳剂的水解率。结果：物理混合的中／长链脂肪乳剂及结构脂肪乳剂的水解程度明显高于长链脂肪乳剂，差异有统计学意义。物理混合的中／长链脂肪乳剂水解程度高于结构脂肪乳剂，但在水解程度及水解速度上却无统计学差异。结论：物理混合的中／长链脂肪乳剂及结构脂肪乳剂的水解率明显高于长链脂肪乳剂。     

In vivo and in vitro properties of an intravenous lipid emulsion containing only medium chain and fish oil triglycerides

BACKGROUND & AIMS: The triglyceride (TG) fatty acyl composition in lipid emulsions influences their metabolism. Little is known about the effects of long chain omega-3 polyunsaturated fatty acids (PUFA) on lipid emulsion metabolism. We investigated possible differences between omega-3 containing emulsions in their metabolism and tissue-targeting in vivo in a mouse model, and in vitro using lipolysis and cell culture experiments. METHODS: Soy oil (LCT), MCT/LCT/omega-3 (5:4:1, wt/wt/wt), and MCT/omega-3 (8:2, wt/wt) emulsions were radiolabeled with nondegradable 1alpha,2alpha (n)-[3H] cholesteryl oleoyl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection. Blood samples obtained over 25 min and extracted organs were used to measure the tissue distribution of lipid emulsion particles. Lipoprotein lipase (LpL)-mediated hydrolysis experiments and cell uptake studies in cultured J774 murine macrophages were also performed. RESULTS: Blood clearance of 8:2 was 13.4% and 29.8% faster compared to 5:4:1 and LCT, respectively. LCT had greatest liver uptake. LpL-mediated hydrolysis was greatest in 8:2 and lowest in LCT. Overall, cell TG accumulation in the presence of apolipoprotein E was least with 8:2. CONCLUSIONS: Our data shows that 8:2 had the most efficient blood clearance but less hepatic uptake in vivo. In vitro, 8:2 had both highest hydrolysis by LpL and intracellular TG utilization in the presence of apoE. Thus, an 8:2 lipid emulsion undergoes efficient blood clearance and may direct omega-3 PUFA more towards extrahepatic tissues.     

Inclusion of 10% fish oil in mixed medium-chain triacylglycerol-long-chain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids

BACKGROUND: Lipolysis of a fish oil (FO) emulsion is much slower than that of a soybean [long-chain triacylglycerol (LCT)] emulsion; in contrast, emulsions containing medium-chain triacylglycerol (MCT) are efficiently hydrolyzed by lipoprotein lipase. OBJECTIVES: We questioned whether incorporating 10% FO in a mixed MCT-LCT emulsion would affect plasma triacylglycerol clearance and provide efficient delivery of n-3 polyunsaturated fatty acids to cells and tissues. DESIGN: This prospective crossover study was conducted in 8 normolipidemic subjects with the use of the hypertriglyceridemic clamp model and compared plasma triacylglycerol clearance of a lipid emulsion (5:4:1) made of 50% MCT, 40% LCT, and 10% FO (wt:wt:wt) to a control (5:5) preparation with 50% MCT and 50% LCT. Subjects were daily infused for 5 h, over 4 consecutive days. Fatty acyl pattern was daily measured in plasma phospholipids as well as in leukocyte and platelet phospholipids. RESULTS: Inclusion of 10% FO in mixed emulsion particles enhanced plasma clearance of infused triacylglycerols (18%; P < 0.0001). The faster elimination of the 5:4:1 emulsion appears related to an enhanced uptake of remnant particles rather than to faster intravascular lipolysis. Each infusion of 5:4:1 raised the eicosapentaenoic acid (C20:5n-3) concentration in blood cell phospholipids to reach a 7-fold enrichment in platelets and a >2-fold enrichment in leukocytes after 4 infusions. In contrast, the docosahexaenoic acid (C22:6n-3) concentration remained unchanged in blood cell phospholipids. CONCLUSIONS: Infusion of a mixed emulsion with MCTs, soy LCTs, and FO is associated with efficient plasma triacylglycerol clearance and results in rapid incorporation of C20:5n-3 but not C22:6n-3 in leukocyte and platelet phospholipids.     

Food intake in dieters and nondieters after a liquid meal containing medium-chain triglycerides

Medium-chain triglycerides (MCT) may be of benefit in the control of body weight by reducing food intake but this has not been established in humans. The effect of three doses (100, 200, and 300 kcal) of preloads of two complete liquid diets containing either 30% long-chain triglycerides (LCT) or 24% MCT with 6% LCT on subsequent intake was tested in dieting and nondieting females. Thirty minutes after consuming these preloads, subjects were offered a varied self-selection lunch. The major finding was that in the nondieters MCT at all doses was followed by a significantly decreased caloric intake in the lunch. Dieters were unresponsive to the type of dietary fat and tended to eat the same number of calories regardless of the preload. Although MCT can reduce short-term food intake in some individuals, further experiments are required to establish the possible benefit of MCT in weight control.     

Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on reducing sepsis-induced liver fat deposition. Preinfusion with MCT before sepsis, however, had no effect on inflammatory-related cytokines or leukotriene in peritoneal lavage fluid. In addition, plasma arginine appears to be a more sensitive indicator than glutamine for septic insult.     

铬、鱼油对肥胖模型大鼠血脂、血糖的影响

肥胖在全球范围内流行 ,而且严重危害身体健康。铬、鱼油参与并调节糖、脂肪代谢 ,因此 ,我们选择了铬、鱼油作为影响因素 ,观察其对饮食诱导肥胖大鼠的影响。方法 :将肥胖模型大鼠按体重随机分为 4组 ,每组 8只。分别为肥胖组 ;鱼油组 ;鱼油 +铬组和铬组 ,另设基础对照组。喂养 6周后处死动物。取睾周及肾周脂肪称重记录。测定全血血糖和血清血脂。结果 :三个实验组的血糖值、胆固醇、甘油三酯低于肥胖组 ,高密度脂蛋白胆固醇高于肥胖组。结论 :铬、鱼油能降低高血脂、高血糖 ,调节糖、脂代谢 ,这提示我们铬、鱼油能降低肥胖引起的健康危害     

Effects of particle size on blood clearance and tissue uptake of lipid emulsions with different triglyceride compositions

BACKGROUND: Particle size of IV lipid emulsions affects the catabolism of long-chain triglyceride (LCT) emulsions, but little is known about its effect on the catabolism of medium-chain triglyceride (MCT)- and fish oil (FO)-containing emulsions. METHODS: Large (VLDL size), intermediate, and small (IDL size) emulsions with different triglyceride (TG) compositions were labeled with [3H]cholesteryl oleoyl ether: LCT (triolein 100%), MCT:LCT (trioctanoin:triolein 50%:50%), MCT:LCT:FO (trioctanoin:triolein:triDHA 50%:40%:10%), and FO (triDHA 100%). Emulsions (0.4 mg TG/mouse) were injected into C57BL/6J mice, and blood clearance and tissue uptake of emulsion particles were determined. RESULTS: Large emulsion particles had 2- to 3-fold faster fractional catabolic rates (FCR) compared with small particles with the same TG content. There was 1.5- to 2.0-fold higher FCR of large FO-containing emulsions (FO and MCT:LCT:FO) compared with large LCT and MCT:LCT emulsions, whereas effects of FO on FCR in small emulsions were not observed. Large FO-containing emulsions were taken up more by adipose tissue compared with small particles with concomitant decreases in hepatic uptake. Preinjection of heparin reduced heart and adipose uptakes of FO and MCT:LCT:FO emulsions with increased uptake by liver, suggesting a role of lipoprotein lipase in catabolism of FO-containing emulsions. CONCLUSIONS: In a mouse model, FO addition to large emulsions increased blood clearance and changed organ delivery. In contrast, there was no or little effect when particle size became smaller. We hypothesize that in humans, FO addition to lipid emulsions can help target emulsion delivery to certain extrahepatic tissues, a factor that may be of use for delivering specific fatty acids, or even drugs, to specific organs.     

Thermic effect of medium-chain and long-chain triglycerides in man

The thermic effects of 400 kcal meals of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) were compared in seven healthy men. Metabolic rate was measured before the meals and for 6 h after the meals by indirect calorimetry. Mean postprandial oxygen consumption was 12% higher than basal oxygen consumption after the MCT meal but was only 4% higher than the basal oxygen consumption after the LCT meal. There was a 25-fold increase in plasma beta-hydroxybutyrate concentration and a slight increase in serum insulin concentration after MCT ingestion but not after LCT ingestion. Plasma triglyceride concentrations increased 68% after the LCT meal and did not change after the MCT meal. These data raise the possibility that long-term substitution of MCT for LCT would produce weight loss if energy intake remained constant.     

中链甘油三酯的代谢特点及临床应用研究进展

中链甘油三酯（MCT）作为一种饱和脂肪酸,既有长链甘油三酯（LCT）的共性,又有自身的特点。本文从MCT代谢、对能量及物质代谢的影响、应用研究等方面综述了近十年来国外的研究进展。