Structured Triglycerides Research Articles

Construction and in vitro digestibility evaluation of a novel human milk fat substitute rich in structured triglycerides

The infants who cannot be breastfeed need to obtain energy and nutrition from other sources, such as formula. In this study, a human milk fat substitute (HMFS) rich in structured triglycerides (STG) and with a variety of fatty acids was prepared by one-step transesterification reaction. The optimum conditions for the lipase-catalyzed transesterification between basa catfish oil solid fraction, Cinnamomum camphora seed kernel oil, linseed oil, microbial oil and algae oil were studied and the in vitro digestibility of the constructed HMFS was investigated. Under the optimal conditions, the obtained HMFS contained 58.86% STG and 39.73% sn-2 palmitic acid (PA). Fatty acid composition analysis showed that HMFS was composed of capric acid (Ca), lauric acid (La), oleic acid (O), linoleic acid (L), linolenic acid (Ln), arachidonic acid (ARA) and docosahexaenoic acid (DHA). LC-MS/MS analysis found that 142 new triglycerides were generated, such as Ca-P-ARA, Ca-P-Ln, La-P-ARA, La-P-L and P-O-ARA. Moreover, compared with physical mixture (PM), HMFS had better melting and crystallization temperature and the fatty acid release rate of HMFS was significantly improved. These results suggested that HMFS may have a great application in infant food as a nutritional ingredient.

Structured triglyceride attenuates lung injury and inflammation in lipopolysaccharide‑induced acute lung injury by enhancing GPR120 expression.

Acute lung injury(ALI) is a serious clinical problem. The present study was performed to investigate the effect of structured triglyceride(STG) on the development of lipopolysaccharide(LPS)‑induced ALI and its underlying mechanism of action. To establish an LPS‑induced ALI mouse model, mice were intranasally administered 50µl LPS. The pathological changes in the lung were observed via haematoxylin‑eosin staining. The lung injury score, lung wet/dry weight(W/D) ratio, and myeloperoxidase(MPO) activity were used to evaluate the degree of lung injury. The expression levels of interleukin(IL)‑1β, IL‑6 and tumour necrosis factor‑α in lung tissues were measured through reverse transcription‑quantitative polymerase chain reaction. The enzyme‑linked immunosorbent assay was used to measure the levels of pro‑inflammatory cytokines in bronchoalveolar lavage fluid. Furthermore, western blotting was performed to detect the activity of the transforming growth factor‑α‑activated kinase1(TAK1)/NF‑κB pathway. LPS‑induced ALI mice were treated with AH7614 [a G‑protein coupled receptor 120 (GPR120) inhibitor] to confirm the effect of STG on GPR120. STG treatment decreased the lung pathological changes, lung injury score, lung W/D ratio, and proinflammatory cytokine expression levels and inhibited TAK1/NF‑κB pathway activity in the LPS‑induced ALI mouse model. Additionally, AH7614 reversed the inhibitory effects of STG on lung injury, inflammation, and TAK1/NF‑κB pathway activity in ALI. Moreover, AH7614 weakened the inhibitory effects of STG on inflammation and TAK1/NF‑κB pathway activity in LPS‑induced RAW264.7 cells. Collectively, STG may suppress the TAK1/NF‑κB pathway activity by enhancing GPR120 expression to alleviate the lung injury and inflammation in ALI. These results suggest the therapeutic potential of STG in the treatment of ALI.

PRM16 - Cost-Effectiveness of Parenteral Nutrition in Hospitalized Adult Patients

Management of severely malnourished adults often requires parenteral nutrition (PN) as a life-sustaining feeding mode in patients with intestinal failure. Different types of PN are commercially available. The choice of an optimal treatment should be made considering their benefits, harms and costs. This study aimed to establish cost-effectiveness of different types of PN based on a systematic review. A comprehensive literature search was performed in PubMed/Medline and Tufts registry for economic evaluations published since 2000 through 2017. Full economic evaluations that compared different parenteral fluids in malnourished adults published in English were included. Quality of the studies was assessed using 24-item Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Forty-seven potentially relevant articles were found, with 6 satisfying predefined inclusion criteria. The studies evaluated different PN formulations enriched with either omega-3 fatty-acid lipid emulsions (n=4), glutamine (n=2) or structured triglyceride (STG)-based emulsions (n=1) compared to standard PN. The studies captured patient (n=3), hospital (n=2) and healthcare provider perspective (n=1), analyzing context of European countries (n=3) or China (n=3) and most of them were cost-effectiveness analyses (n=5). Five studies were model-based economic evaluations with four of them applying discrete event simulation. None of the studies reported cost per quality-adjusted life year. Special PN formulations appeared to be cost-effective when compared to standard PN. The CHEERS assessment resulted in total score of 16.3 (SD=4.42), with none of the studies reporting discount rates or measurement and valuation of preference based outcomes and with only one study characterizing heterogeneity. Addition of omega-3 lipids, glutamines or structured triglyceride-based emulsions into parenteral fluids appear to be generally cost-effective from the study perspectives. The lack of a well-designed pharmacoeconomic analysis highlights the need for further economic evaluations, which will provide a rationale for the informed healthcare decision-making.

Meta-analysis of the efficacy and safety of structured triglyceride lipid emulsions in parenteral nutrition therapy in China

We performed a meta-analysis of data from recent studies to evaluate the safety and efficacy of parenteral nutrition (PN) with structured triglyceride (STG) lipid emulsions compared to medium-chain triglyceride (MCT)/long-chain triglyceride (LCT) lipid emulsions in Chinese patients. PubMed, Embase, Cochrane Library, China National Knowledge Internet, Wanfang, and VIP were searched for randomized controlled trials comparing STGs with MCTs/LCTs published in English or Chinese between January 1987 and October 2017. Two independent investigators screened and selected studies according to prespecified selection criteria. Data were pooled and analysed using RevMan® version 5.3. Thirty-two studies comprising 1944 patients were included in the meta-analysis. Compared with MCT/LCT emulsions, STGs resulted in a shorter hospital length of stay (LOS) (weighted mean difference [WMD],-1.65 days; 95% confidence interval [CI]:-2.63,-0.67; P=0.001) and lower adverse event rates (relative risk, 0.64; 95% CI: 0.48, 0.85; P=0.002). STGs were associated with a significantly better cumulative nitrogen balance (WMD, 4.04g/24h; 95% CI: 3.10, 4.97; P<0.0001) as well as higher concentrations of pre-albumin (WMD 35.20mg/L; 95% CI: 26.59, 43.81; P<0.0001) and albumin (WMD, 1.64g/L; 95% CI: 1.17, 2.10; P<0.0001) compared with MCTs/LCTs. In contrast, significantly lower concentrations of plasma triglycerides (WMD,-0.21mmol/L; 95% CI:-0.30,-0.12; P<0.0001), total cholesterol (WMD,-0.45mmol/L; 95% CI:-0.60,-0.29; P<0.0001), alanine aminotransferase (WMD,-7.68IU/L; 95% CI:-9.68,-5.68; P<0.0001) and aspartate aminotransferase (WMD,-10.27IU/L; 95% CI:-16.05,-4.49; P=0.0005) were observed in patients receiving STGs compared with MCT/LCTs. STGs were also associated with reduced inflammation and improved immunological function, as reflected by significantly lower C-reactive protein concentrations (WMD,-2.67mg/L; 95% CI:-4.55,-0.79; P=0.005) and increased concentrations of IgG (WMD, 2.11g/L; 95% CI: 0.23, 3.99; P=0.03), IgA (WMD, 0.21g/L; 95% CI: 0.14, 0.28; P<0.0001), CD3+ (WMD, 5.81%; 95% CI: 0.92, 10.70; P=0.02), and CD4+/CD8+ (WMD, 0.12; 95% CI: 0.00, 0.24; P=0.04) compared with MCT/LCTs. Administration of STGs was shown to improve hepatic function, nutrition status, and immunological function and reduce inflammation, LOS, and adverse events compared with MCT/LCTs in Chinese patients receiving PN.

Pharmacoeconomics of parenteral nutrition in surgical and critically ill patients receiving structured triglycerides in China.

A prior meta-analysis showed favorable metabolic effects of structured triglyceride (STG) lipid emulsions in surgical and critically ill patients compared with mixed medium-chain/long-chain triglycerides (MCT/LCT) emulsions. Limited data on clinical outcomes precluded pharmacoeconomic analysis. We performed an updated meta-analysis and developed a cost model to compare overall costs for STGs vs MCT/LCTs in Chinese hospitals. We searched Medline, Embase, Wanfang Data, the China Hospital Knowledge Database, and Google Scholar for clinical trials comparing STGs to mixed MCT/LCTs in surgical or critically ill adults published between October 10, 2013 and September 19, 2015. Newly identified studies were pooled with the prior studies and an updated meta-analysis was performed. A deterministic simulation model was used to compare the effects of STGs and mixed MCT/LCT's on Chinese hospital costs. The literature search identified six new trials, resulting in a total of 27 studies in the updated meta-analysis. Statistically significant differences favoring STGs were observed for cumulative nitrogen balance, pre- albumin and albumin concentrations, plasma triglycerides, and liver enzymes. STGs were also associated with a significant reduction in the length of hospital stay (mean difference, -1.45 days; 95% confidence interval, -2.48 to -0.43; p=0.005) versus mixed MCT/LCTs. Cost analysis demonstrated a net cost benefit of ¥675 compared with mixed MCT/LCTs. STGs are associated with improvements in metabolic function and reduced length of hospitalization in surgical and critically ill patients compared with mixed MCT/LCT emulsions. Cost analysis using data from Chinese hospitals showed a corresponding cost benefit.

Effects of different types of triglycerides on hepatic and renal function and lipometabolism of patients with acute necrotizing pancreatitis: a prospective study

Objective To investigate the effects of structured triglyceride (STG) and physical mixed medium chain/ long chain triglycerides (MCT/ LCT) on hepatic and renal function and lipometabolism of patients with acute necrotizing pancreatitis (ANP) . Methods The clinical data of 30 patients with ANP who were admitted to the PLA General Hospital between January 2012 and June 2014 were prospectively analyzed. A double-blind, randomized, controlled study was performed in 30 patients who were allocated into the experimental group (15 patients received STG) and the control group (15 patients received physical mixed MCT/ LCT) . All the patients received isometrical nitrogen and isocaloric parenteral nutrition more than 5 days. The levels of alanine transaminase (ALT) , aspartate transaminase (AST) , glutamyl-transpeptidase (GGT) , alkaline phosphatase (ALP) , creatinine (Cr) , blood urea nitrogen (BUN) , triglyceride (TG) and total cholesterol (TC) were assayed before nutritional support treatment and at day 1 , 3 and 5 after nutritional support therapy. The measurement data with normal distribution was presented as ±s. The skew distribution data were described as M (range) . The comparison between groups were evaluated with an independent sample t test or one-way ANOVA. The count data were analyzed using the chi-square test. Results A total of 30 patients were screened for eligibility. The levels of ALT, AST, GGT, ALP, Cr, BUN, TG and TC were changed within a certain range at day 1, 3 and 5 after nutritional support treatment. The levels of ALT, AST, GGT, ALP, Cr, BUN and TC before treatment and at day 5 after treatment were changed from 29. 0 U/ L, 25. 4 U/ L, 83.2 U/ L, (193 ± 115) U/ L, (124 ± 97) μmol/ L, (8 ±6) mmol/ L and (2.4 ± 1.1) mmol/ L to 29.4 U/ L, 33.0 U/ L, 77.7 U/ L, (172 ± 74) U/ L, (117 ± 103) μmol/ L, (8 ± 5) mmol/ L and (2.3 ± 1.0) mmol/ L in the experimental group, and from 23.8 U/ L, 22. 9 U/ L, 96. 2 U/ L, (148 ± 108) U/ L, (82 ± 57) μmol/ L, (9 ± 7) mmol/ L and (2.5 ± 0.7) mmol/ L to 21. 3 U/ L, 24. 5 U/ L, 127.4 U/ L, (179 ± 126) U/ L, (80 ± 54) μmol/ L, (10 ± 6) mmol/ L and (2.4 ± 0. 8 ) mmol/ L in the control group, respectively. There were no significant differences in the changing trends of the levels of ALT, AST, GGT, ALP, Cr, BUN and TC between the 2 groups (F =0.647, 1.186, 0.282, 0.553, 0.862, 0.182, 0.369, P >0.05) . The level of TG in the experimental group from pre-treatment to day 5 after treatment was changed from (1. 5 ± 0.6) mmol/ L to (1. 5 ± 0.7) mmol/ L, with increasing trend from pre-treatment to day 1 after treatment and reaching the normal level at day 3 and 5 after treatment. The level of TG in the control group from pre-treatment to day 5 after treatment was changed from (1.5 ± 0.6) mmol/ L to (2.4 ± 0. 6) mmol/ L, with increasing trend from pre-treatment to day 1 , 3 and 5 after treatments. There were significant differences in the changing trends of TG before and after nutritional support therapy between the 2 groups (F = 7.940, P <0.05) . Conclusion STG and physical mixed MCT/ LCT don't influence the hepatic and renal function of patients with ANP undergoing parenteral nutritional support therapy, while STG has a better effect of lipometabolism compared with physical mixed MCT/ LCT. Registry This study was registered with the UMIN Clinical Trial Registry with the registry number of UMI16958 Key words: Acute necrotizing pancreatitis; Nutritional support therapy; Structured triglyceride; Lipometabolism

Influence of structured triglyceride on the surgical patients with liver disease

Objective To study the influence of structured triglyceride on liver function,nitrogen balance and protein metabolism in surgical patients with liver disease.Methods A prospective,random,and double-blind clinical trial was performed,and 86 surgical patients with liver disease were randomly divided into two groups according to the treatment of structured triglyceride (STG) or physical mixture of medium-chain/long-chain triglycerides (MCT/LCT) emulsion.Both groups received isonitrogenous and isocaloric parenteral nutrition (PN) in the six days after operation.The liver function,nitrogen balance and protein metabolism were compared between the two groups.Results There were no harmful to liver function in both groups.There is less influence on the biliburbin metabolism in STG group as compared with MCT/LCT group.The nitrogen balance in the STG group was significantly higher than those in the MCT/LCT group.The serum level of proteins in STG group back to the normal value on POD +4,while in MCT/LCT group was on POD +7.Conclusion STG can improve the nutrition of surgical patients with liver disease more rapidly than MCT/LCT. Key words: Structured triglyceride; Nitrogen balance; Protein metabolism; Liver operation

Incorporation of medium chain fatty acids into fish oil triglycerides by chemical and enzymatic interesterification

Structured triglycerides (STs) containing both medium-chain fatty acids (MCFA) and polyunsaturated fatty acids (PUFA) in the same molecule offer nutritional and therapeutic benefits. The aim of this work was to establish the incorporation of MCFA into fish oil triglycerides (TAGs), while maintaining substantial levels of docosahexaenoic and eicosapentaenoic acids. The effects of different acyl donors (capric acid methyl ester/MeC10 or medium chain triglyceride/TCM) and of the catalyst (chemical or enzymatic) on the fatty acid composition of the reaction product were studied. The fatty acid composition of the fish oil TAG was modified after interesterification to contain MCFA, and it depended on the catalyst and on the substrates. Thermograms obtained by Differential Scanning Calorimetry (DSC) showed that interesterification promoted noteworthy changes in the melting profile of the samples. STs of clinical nutrition interest containing both EPA and DHA obtained from fish oil along with MCFA were successfully produced.

The hypertriglyceridemic clamp technique. Studies using long-chain and structured triglyceride emulsions in healthy subjects

In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (±SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 ± 0.1 vs 3.9 ± 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 ± 0.04 vs 0.21 ± 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 ± 0.13 vs 0.96 ± 0.09 mmol/L; P < .05), free glycerol (1.30 ± 0.07 vs 0.76 ± 0.08 mmol/L; P < .001), and β-OH butyrate (1.61 ± 0.44 vs 1.17 ± 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 ± 0.62 vs 3.15 ± 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of infused TG during the steady-state period ( r = 0.58; P < .05). In conclusion, the hypertriglyceridemic clamp method was found to give reproducible results and could be considered for comparison of metabolic clearance properties of different types of fat emulsions. The capacity of healthy subjects to eliminate STGs from blood was greater than for LCTs. An increased LPL activity induced by the higher TG infusion rate may have contributed to the increased metabolic clearance of STGs.

Metabolism of defined structured triglyceride particles compared to mixtures of medium and long chain triglycerides intravenously infused in dogs

The present study aimed to determine whether including medium-chain fatty acids (MCFA) in specifically designed structured triglycerides (STG) with a MCFA in sn-1 and sn-3 positions and a long-chain (LC) FA in sn-2 position (MLM) would lead to different effects on plasma lipids and FA distribution into plasma and tissue lipids by comparison to a mixture of separate MCT and LCT molecules (MMM/LLL). The fatty acid (FA) composition was comparable in both lipid emulsions. Lipids were infused over 9 h daily, in 2 groups of dogs ( n=6 each), for 28 days as a major component (55% of the non-protein energy intake) of total parenteral nutrition (TPN). Blood samples were obtained on specific days, before starting and just before stopping TPN. The concentration of plasma lipids was measured before starting and before stopping TPN on days 1, 2, 3, 4, 5, 8, 10, 12, 16 and 28. Biopsies were obtained from liver, muscle and adipose tissue 15 days before starting, and again on the day following cessation of TPN. In addition, the spleen was removed after the TPN period. FA composition in plasma and tissue lipids was analysed by gas liquid chromatography in different lipid components of plasma and tissues. No differences in either safety or tolerance parameters were detected between both lipid preparations. A lower rise of plasma TG ( P<0.05) was observed during MLM infusion, indicating a faster elimination rate of MLM vs MMM/LLL emulsion. In spite of the differences of TG molecules which would be assumed to affect the site of FA delivery and metabolic fate, FA distribution in phospholipids (PL) of hepatic and extrahepatic tissues did not substantially differ between both emulsions.

Production of structured triglycerides rich in n-3 polyunsaturated fatty acids by the acidolysis of cod liver oil and caprylic acid in a packed-bed reactor: equilibrium and kinetics

Structured triglycerides (ST) enriched in n-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA) in position 2 of the triglyceride backbone were synthesised by acidolysis of cod liver oil (CLO) and caprylic acid (CA) catalysed by the 1,3-specific immobilised lipase Lipozyme IM. The reaction was carried out in three ways: (1) in a batch reactor (where the influence of temperature on the incorporation of CA into the CLO triglyceride was studied); (2) in an immobilised lipase packed-bed reactor (PBR) by recirculating the reaction mixture from the exit of the bed to the substrate reservoir (product recirculation) to determine the equilibrium composition; and (3) in a PBR without recirculation. A “lag” period of duration inversely proportional to the initial water amount of the lipase, was observed when new lipase was used. Apparently, during this “lag” period the hydro-enzymatic layer that surrounds the lipase surface reaches its water equilibrium content. A reaction scheme, where only the fatty acid in the positions 1 and 3 of the glycerol backbone were exchanged by CA, was proposed. The exchange equilibrium constants between CA and the native fatty acids of CLO were determined. The n-3 PUFAs (EPA and DHA) were the most resistant native fatty acids to exchange with exchange equilibrium constants of 1.32 and 0.28, respectively. Also, average reaction rates and kinetic constants of exchange of CA and native fatty acid of CLO were calculated. Low kinetic constants were observed for EPA, DHA and palmitic acid. For acidolysis reaction in the continuous mode PBR, the lipase amount/(flow rate × substrate concentration) ratio ( m L / q[TG] 0) could be considered as the intensive variable of the process for use in scale up of the PBR. A simple equation was proposed for the prediction of the fatty acid composition of the ST at the exit of the PBR as a function of the intensive variable m L / q[TG] 0. At equilibrium, the ST produced had the following composition: CA 57%, EPA 5.1%, DHA 10.0% and palmitic acid 6.3% (only considering the major fatty acids). In addition, the proportion of EPA and DHA that esterified the position 2 of the ST was 13.5%, which represented 44% of the total fatty acids in the position 2 of the resultant ST.

Randomized Structured Triglycerides Increase Lymphatic Absorption of Tocopherol and Retinol Compared with the Equivalent Physical Mixture in a Rat Model of Fat Malabsorption

Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

Nitrogen sparing effect of structured triglycerides containing both medium-and long-chain fatty acids in critically ill patients; a double blind randomized controlled trial

Background and Aims: Patients with sepsis and trauma are characterised by hypermetabolism, insulin resistance and protein catabolism. Fat emulsions containing medium chain triglycerides have been suggested to be beneficial for these patients since medium chain fatty acids are a more readily available source of energy when compared to long chain fatty acids. The aim of this study was to compare a medium and long chain triglyceride emulsion consisting of structured triglycerides (ST) with a long chain triglyceride (LCT) emulsion in terms of effects on nitrogen balance, energy metabolism and safety.Methods: 30 ICU patients with sepsis or multiple injury received a fat emulsion with ST or 20% LCT (1.5 g triglycerides/kg body weight/day) as a component of total parenteral nutrition (TPN), for 5 days in a double blind randomised parallel group design. The main analysis was made on the 3 day per protocol population due to lack of patients at day 5.Results: There were no differences in baseline characteristics of the two groups receiving either the LCT or the ST emulsion. The efficacy analysis was performed on the per protocol population (n=9 ST, n=11 LCT). There was a significant difference between the two treatments regarding daily nitrogen balances when the first 3 days were analysedP =0.0038). This resulted in an amelioration of the nitrogen balance on day 3 in the group on ST as compared to those on LCT (0.1±2.4 g vs −9.9±2.1 g P=0.01). The 3 day cumulative nitrogen balance was significantly better in the group receiving ST compared to those on LCT (−0.7±6.0 vs −16.7±3.9P =0.03). This better cumulative nitrogen balance on day 3 was also preserved as a tendency (P=0.061) in the analysis of the intention to treat population, but on day 5 there was no significant difference (P=0.08). The ST emulsion was well tolerated and no difference was found compared to the LCT emulsion regarding respiratory quotient, energy expenditure, glucose or triglyceride levels during infusion.Conclusion: Administration of a structured triglyceride emulsion resulted in an amelioration of nitrogen balance despite no effect on energy expenditure in short term administration over 3 days to ICU patients when compared to a long chain triglyceride emulsion. No side effects linked to medium chain triglycerides were noted.

Effects of structurally different lipid emulsions on human neutrophil migration

Aim: To test the hypothesis that structurally different lipid emulsions have distinct immunomodulatory properties, we analysed neutrophil migration in the presence of various lipid emulsions. Method: Neutrophils of 8 volunteers were pre-incubated in medium or physiological 2.5 mM emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, α -tocopherol-enriched LCT/MCT (LCT/MCT-E) or structured triglycerides (SL). Thereafter, the cells were put on top of 3 μm-pore-sized cell culture filters and incubated for one hour in the presence or absence of a chemo-attractant. Neutrophil migration was measured as the percentage of cells that had passed the filter in the presence (chemotaxis) or absence (random migration) of a chemotactic factor. Results: Compared to lipid-free incubation (19±1%) random neutrophil migration significantly decreased with LCT/MCT (11±2%), LCT/MCT-E (12±2) and MCT (5±2%), while LCT (18±3%) and SL (20±1%) had no effect. N-formyl-methionyl-leucyl-phenylalanine- (fMLP, 10−8M) or zymosan-activated-serum-induced (ZAS, 10%) filter passage under lipid-free conditions amounted to 61±14% and 70±13%, respectively. These values decreased with LCT/MCT to 11±9% and 15±7%; with LCT/MCT-E to 18±10% and 28±12%; with SL to 39±18% and 57±14%, and with MCT to 5±2% and 10±6%, (all P<0.01), while LCT had no effect. Compared to LCT/MCT, the α -tocopherol-enriched formulation significantly increased ZAS- and fMLP-induced chemotaxis. fMLP-induced chemotaxis decreased in direct proportion to LCT/MCT triglyceride concentration. Conclusions: Human neutrophil migration is distinctively inhibited by structurally different lipid emulsions, depending on triglyceride chain-length and concentration as well asα -tocopherol content.

Effects of structurally different lipid emulsions on human neutrophil migration

Aim: To test the hypothesis that structurally different lipid emulsions have distinct immunomodulatory properties, we analysed neutrophil migration in the presence of various lipid emulsions. Method: Neutrophils of 8 volunteers were pre-incubated in medium or physiological 2.5 mM emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, α -tocopherol-enriched LCT/MCT (LCT/MCT-E) or structured triglycerides (SL). Thereafter, the cells were put on top of 3 μm-pore-sized cell culture filters and incubated for one hour in the presence or absence of a chemo-attractant. Neutrophil migration was measured as the percentage of cells that had passed the filter in the presence (chemotaxis) or absence (random migration) of a chemotactic factor. Results: Compared to lipid-free incubation (19±1%) random neutrophil migration significantly decreased with LCT/MCT (11±2%), LCT/MCT-E (12±2) and MCT (5±2%), while LCT (18±3%) and SL (20±1%) had no effect. N-formyl-methionyl-leucyl-phenylalanine- (fMLP, 10−8M) or zymosan-activated-serum-induced (ZAS, 10%) filter passage under lipid-free conditions amounted to 61±14% and 70±13%, respectively. These values decreased with LCT/MCT to 11±9% and 15±7%; with LCT/MCT-E to 18±10% and 28±12%; with SL to 39±18% and 57±14%, and with MCT to 5±2% and 10±6%, (all P<0.01), while LCT had no effect. Compared to LCT/MCT, the α -tocopherol-enriched formulation significantly increased ZAS- and fMLP-induced chemotaxis. fMLP-induced chemotaxis decreased in direct proportion to LCT/MCT triglyceride concentration. Conclusions: Human neutrophil migration is distinctively inhibited by structurally different lipid emulsions, depending on triglyceride chain-length and concentration as well asα -tocopherol content.

Lymphatic absorption of structured triglycerides vs. physical mix in a rat model of fat malabsorption.

Comparison was made between the intestinal absorption and lymphatic transport of a randomly interesterified fish oil and medium-chain triglyceride (MCT) structured triglycerides (STG) vs. the physical mix in rat small intestine following ischemia and reperfusion (I/R) injury. Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both treatment groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 ml of the fish oil-MCT STG or physical mix (7 rats/group) through the gastric tube followed by an infusion of PBS at 3 ml/h for 8 h. Lymph was collected hourly for 8 h. Lymph triglyceride, cholesterol, and decanoic and eicosapentaenoic acids increased rapidly and maintained a significantly higher output (P < 0.01) with STG compared with physical mix in control rats over 8 h. After I/R, lymphatic triglyceride output decreased 50% compared with control. Gastric infusion of STG significantly improved lipid transport by having a twofold higher triglyceride, cholesterol, and decanoic and eicosapentaenoic acids output to lymph compared with its physical mix (P < 0.01). We conclude that STG is absorbed into lymph significantly better than physical mix by both the normal intestine and the intestine injured by I/R.

Influence of structurally different lipid emulsions on human neutrophil oxygen radical production.

The aim of this study was to evaluate immunomodulatory properties of lipid emulsions applied in parenteral nutrition by measuring neutrophil oxygen radical production (the 'respiratory burst') after lipid incubation. Neutrophils, isolated from the blood of 10 healthy individuals, were incubated in medium or in lipid emulsions in a physiological concentration (2.5 mmol L-1) containing long-chain [Intralipid (LCT)], mixed medium and long-chain [Lipofundin (LCT/MCT)] or structured triglycerides (SL). After washing and stimulation with phorbol 12-myristate 13-acetate (PMA) or serum-treated zymosan (STZ) particles, the respiratory burst was evaluated by measuring maximum oxygen uptake, superoxide and hydrogen peroxide production rates and chemiluminescence. Unlike LCT and SL, LCT/MCT increased PMA- and STZ-induced oxygen uptake rate by 45% and 31% respectively (both P = 0.006 compared with medium) as well as superoxide (+56%, P = 0.006) and hydrogen peroxide (+14%, P = 0.04) production, within 5 min after stimulation. Increased LCT/MCT-mediated early respiratory burst was confirmed by decreased PMA- (-65%) and STZ-stimulated (-54%) chemiluminescence peak time (time after stimulation to peak) in combination with unchanged peak height (maximum rate of radical production). Late respiratory burst (within 2 h) of LCT/MCT, indicated by overall luminescence (overall radical production), remained unchanged (PMA) or decreased (STZ, P = 0.02). The addition of 2.5 mmol L-1 LCT/MCT or MCT emulsion to unstimulated neutrophils, in contrast to LCT and SL, resulted in significant luminescence. Early neutrophil respiratory burst is accelerated by the LCT/MCT emulsion Lipofundin, whereas LCT (Intralipid) and structured lipid emulsions exert no effect. MCT-containing emulsions, contrary to LCT and structured lipid emulsions, can induce oxygen radical production in unstimulated neutrophils.

Uptake and metabolism of structured triglyceride by Caco-2 cells: reversal of essential fatty acid deficiency.

Structured lipids have been proposed as efficient vehicles for the supplementation of essential fatty acids (EFA) to patients with malabsorption. We investigated how a novel structured triglyceride (STG), containing purely octanoic acid in the sn-1/sn-3 and [14C]linoleic acid in the sn-2 positions, was incorporated into different lipid classes in Caco-2 cells. We also evaluated the contribution of gastric lipase in the uptake and metabolism of [14C]linoleic acid from the STG. We furthermore determined the potential of the STG to correct EFA deficiency induced in Caco-2 cells. The absorption of STG by Caco-2 cells was significantly greater compared with that of triolein. The addition of human gastric lipase significantly enhanced cellular uptake of the labeled substrate, reflecting the stereoselectivity of gastric lipase to hydrolyze medium chain FA. Analysis of the intracellular lipids synthesized revealed a predominance of phospholipids-monoglycerides. Most of the radioactivity in the lipoproteins isolated from Caco-2 cells was recovered in TG-rich lipoproteins (45%) and to a lesser extent in the high-density lipoprotein (36%) and low-density lipoprotein (17%) fractions. The administration of STG to Caco-2 cells rendered EFA deficient produced a marked increase of the cellular level of linoleic and arachidonic acids. This resulted in a lower ratio of 20:3(n-9) to 20:4(n-6), reflecting the correction of EFA deficiency in Caco-2 cells. Our data demonstrate that STG, in the presence of gastric lipase, have beneficial effects on lipid incorporation, lipoprotein production, and EFA status, utilizing Caco-2 cells as a model of EFA deficiency.