High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants.

BACKGROUND: In-hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering. For preterm infants who cannot be fed maternal or donor breast milk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs) or long chain triglycerides (LCTs) may be chosen to support nutrient utilization and to improve growth. MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervous system development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant's short-term growth remain unclear. This is an update of a review originally published in 2002, then in 2007. OBJECTIVES: To determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula.  SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included all randomized and quasi-randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short-term growth of preterm (< 37 weeks' gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition. DATA COLLECTION AND ANALYSIS: The review authors assessed each study's quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We identified 10 eligible trials (253 infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, or blinding. We found no evidence of differences in short-term growth parameters when high and low MCT formulas were compared. As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of -0.21 g/kg/d (95% confidence interval (CI) -1.24 to 0.83; 6 studies, 118 infants; low-certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d (95% CI -5.93 to 5.93; 1 study, 18 infants; very low-certainty evidence), finding an average weight gain of 20 ± 5.9 versus 20 ± 6.9 g/d for high and low MCT groups, respectively. We found that length gain showed no difference between low and high MCT formulas, with a typical MD of 0.10 cm/week (95% CI -0.09 to 0.29; 3 studies, 61 infants; very low-certainty evidence). Head circumference gain also showed little to no difference during the intervention period, with an MD of -0.04 cm/week (95% CI -0.17 to 0.09; 3 studies, 61 infants; low-certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference (2 studies, 32 infants; very low-certainty evidence). There are conflicting data (5 studies) as to formula tolerance, with 4 studies reporting narrative results of no observed clinical difference and 1 study reporting higher incidence of signs of gastrointestinal intolerance in high MCT formula groups. There is no evidence of effect on the incidence of necrotizing enterocolitis (NEC), based on small numbers in two trials. Review authors found no studies addressing long-term growth parameters or neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: We found evidence of very low to low certainty suggesting no differences among short-term growth data for infants fed low versus high MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short-term growth outcomes or have fewer adverse effects. Further studies are necessary because the results from included studies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence.

Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil.

Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer's disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups. PARTICIPANTS: Healthy subjects without cognitive deficits <65years, similarly healthy subjects >=65years, and those with Alzheimer's Disease were assessed. INTERVENTION: Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period. MEASUREMENTS: BHB measured by finger prick sampling hourly for 5 hours after ingestion. Each subject attended four different days for each ascending dose. Data was also collected on body composition, BMI, waist/hip ratio, grip strength, gait speed, nutrient content of pre-study breakfast and side effects. RESULTS: Twenty-five participants: eight healthy; average age of 44yr (25-61), nine healthy; 79yr (65-90) and eight with AD; 78.6yr (57-86) respectively. Compiled data showed the expected linear dose response relationship. No group differences, with baseline corrected area under the blood vs. time curve (r2=0.98) and maximum concentrations (r2=0.97). However, there was notable individual variability in maximum BHB response (42g dose: 0.4 -2.1mM), and time to reach maximum BHB response both, within and between individuals. Variability was unrelated to age, sex, sarcopenic or AD status. Visceral fat, BMI, waist/hip ratio and pretest meal CHO and protein content all affected the BHB response (p<0.001). CONCLUSION: There was a large inter-individual variability, with phenotype effects identified. This highlights challenges in interpreting clinical responses to MCT intake.

Does the use of fish oil-based lipid emulsion in the clinical setting of total parenteral nutrition and lipid rescue therapy interfere with common laboratory analytes on Roche Cobas 6000?

BACKGROUND: Lipaemic interference on automated analysers has been widely studied using soy-based emulsion such as Intralipid. Due to the greater adoption of fish oil-based lipid emulsion for total parenteral nutrition in view of improved clinical outcomes, we seek to characterize the optical properties of SMOFlipid 20% (Fresenius Kabi, Bad Homburg, Germany), a fish oil-based emulsion, on the Roche Cobas 6000 chemistry analyser (Roche Diagnostic, Basel, Switzerland). METHOD: Various amounts of SMOFlipid were spiked into pooled serums. We plotted Roche Cobas Serum Index Gen.2 Lipaemia Index (L-index) against the amount of SMOFlipid added. We then studied the interference thresholds for aspartate aminotransferase, alanine aminotransferase, albumin and renal panel analytes using SMOFlipid. We subjected five levels of spiked lipaemia to high-speed centrifugation and analysed the specimens pre- and post-centrifugation. To postulate whether fish oil-based lipid emulsion interferes with laboratory results in the clinical setting, we calculated concentrations of SMOFlipid post-lipid rescue therapy and steady-state concentration of a typical total parenteral nutrition regime using pharmacokinetic principles. RESULTS: SMOFlipid optical behaviour is similar to Intralipid using the Serum Index Gen.2 L-index, with 1 mg/dL of SMOFlipid representing 1 unit of L-index. Manufacturer-stated interference thresholds are accurate for alanine aminotransferase, aspartate aminotransferase, albumin, urea and creatinine. High-speed centrifugation at 60 min 21,100g facilitates the removal of fish oil-based SMOFlipid. CONCLUSION: Based on the interference thresholds we verified and pharmacokinetics parameters provided by SMOFlipid manufacturer, total parenteral nutrition may not interfere with chemistry analytes given sufficient clearance, but lipid rescue therapy will interfere. Further studies assessing lipaemic interference on immunoassays are needed.

[Effectiveness and safety of two lipid emulsions for parenteral nutrition in postsurgical critically ill patients: Clinoleic® versus SMOFlipid®]. / Eficacia y seguridad de dos emulsiones lipídicas de nutrición parenteral en pacientes críticos posquirúrgicos: Clinoleic® frente a SMOFlipid®.

INTRODUCTION: Introduction: a lipid emulsion (LE) may result in different immunomodulatory effects depending on its fatty acid composition. LEs enriched with fish oil and those based on olive oil (OOBE) have shown advantages over those derived from soybean oil, although very few studies have compared these with each other, and none was performed in critically ill surgical patients. Objectives: to demonstrate non-inferiority for the therapeutic efficacy of SMOFlipid® (enriched with fish oil) versus Clinoleic® (OOBE) in relation to the occurrence of nosocomial infection and other evolutionary parameters. To demonstrate non-inferiority in the safety profile of SMOFlipid® versus Clinoleic® in terms of mortality and adverse events. Material and method: a phase-III, non-inferiority clinical trial performed in critically ill postsurgical patients. The subjects were randomized to receive SMOFlipid® or Clinoleic®. For comparison of qualitative variables case frequencies and percentages were obtained using the Chi-squared test or Fisher's exact test. Means were compared between groups using Student's t-test. A p-value lower than 0.05 was considered statistically significant. The Farrington-Manning, Miettinen-Nurminen, and Gart-Nam tests were applied in the main non-inferiority analysis of the primary endpoint. Results: during de inclusion period 73 patients were selected, 37 of whom received Clinoleic® and 36 SMOFlipid®. Regarding the variable "decrease in nosocomial infections", SMOFlipid® proved to be non-inferior to Clinoleic®. Regarding the main variable "mortality", SMOFlipid® proved to be non-inferior to Clinoleic®. There were no statistically significant differences in the occurrence of adverse effects either. Conclusions: in our study, SMOFlipid® proved to be non-inferior to Clinoleic® in terms of efficacy and safety.

INTRODUCCIÓN: Introducción: las emulsiones lipídicas (EL) pueden asociar distintos efectos inmunomoduladores dependiendo de su composición de ácidos grasos. Las EL enriquecidas con aceite de pescado y las basadas en aceite de oliva (EBAO) han mostrado ventajas frente a las derivados del aceite de soja, aunque son muy escasos los estudios que las comparan entre sí y no existe ninguno en pacientes críticos quirúrgicos. Objetivos: Demostrar la no inferioridad de la eficacia terapéutica de SMOFlipid® (enriquecida con aceite de pescado) frente a Clinoleic® (EBAO) en relación con la aparición de infecciones nosocomiales y otros parámetros evolutivos. Demostrar la no inferioridad de la seguridad de SMOFlipid® frente a Clinoleic® expresada como aparición de mortalidad y acontecimientos adversos. Material y método: ensayo clínico de fase III, de no inferioridad, realizado en pacientes críticos posquirúrgicos. Los sujetos se aleatorizaron para recibir SMOFlipid® o Clinoleic®. Para comparar variables cualitativas se obtuvieron la frecuencia y el porcentaje de casos, realizando la prueba del chi cuadrado o el test de Fisher. Las medias entre dos grupos se compararon empleando el test de la "t" de Student. Se consideró estadísticamente significativo un valor de p menor de 0,05. Para el análisis principal de no inferioridad de la variable principal se aplicaron los test de Farrington-Manning, Miettinen-Nurminen y Gart-Nam. Resultados: se incluyeron 73 pacientes, de los cuales 37 recibieron Clinoleic® y 36 SMOFlipid®. En la variable "disminución de infecciones nosocomiales", SMOFlipid® demostró no ser inferior a Clinoleic®. En la variable principal "mortalidad", SMOFlipid® demostró no ser inferior a Clinoleic®. Tampoco existieron diferencias estadísticamente significativas en cuanto a la aparición de efectos adversos. Conclusiones: en nuestro estudio, SMOFlipid® demostró no ser inferior a Clinoleic® en términos de eficacia y seguridad.

Triheptanoin: First Approval.

Triheptanoin (Dojolvi™), a synthetic medium-chain triglyceride, is being developed by Ultragenyx Pharmaceutical as a pharmaceutical-grade anaplerotic compound for use in the treatment of inherited metabolic disorders. In June 2020, triheptanoin received its first regulatory approval, in the USA, for use as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD). Triheptanoin has also been investigated for use as a treatment in a range of other metabolic disorders or other diseases where energy deficiency is implicated. This article summarizes the milestones in the development of triheptanoin leading to this first regulatory approval for use in the treatment of pediatric and adult patients with LC-FAOD.

The effects of GSK2981710, a medium-chain triglyceride, on cognitive function in healthy older participants: A randomised, placebo-controlled study.

OBJECTIVE: This double-blind, randomised, placebo-controlled, two-part study assessed the impact of GSK2981710, a medium-chain triglyceride (MCT) that liberates ketone bodies, on cognitive function, safety, and tolerability in healthy older adults. METHODS: Part 1 was a four-period dose-selection study (n = 8 complete). Part 2 was a two-period crossover study (n = 80 complete) assessing the acute (Day 1) and prolonged (Day 15) effects of GSK2981710 on cognition and memory-related neuronal activity. Safety and tolerability of MCT supplementation were monitored in both parts of the study. RESULTS: The most common adverse event was diarrhoea (100% and 75% of participants in Parts 1 and 2, respectively). Most adverse events were mild to moderate, and 11% participants were withdrawn due to one or more adverse events. Although GSK2981710 (30 g/day) resulted in increased peak plasma ß-hydroxybutyrate (BHB) concentrations, no significant improvements in cognitive function or memory-related neuronal activity were observed. CONCLUSION: Over a duration of 14 days, increasing plasma BHB levels with daily administration of GSK2981710 had no effects on neuronal activity or cognitive function. This result indicates that modulating plasma ketone levels with GSK2981710 may be ineffective in improving cognitive function in healthy older adults, or the lack of observed effect could be related to several factors including study population, plasma BHB concentrations, MCT composition, or treatment duration.

New Insights into Mechanisms of Action for Omega-3 Fatty Acids in Atherothrombotic Cardiovascular Disease.

PURPOSE OF REVIEW: Treatment of hypercholesterolemia with statins results in significant reductions in cardiovascular risk; however, individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels, but persistent high triglycerides (TG), remain at increased risk. Genetic and epidemiologic studies have shown that elevated fasting TG levels are associated with incident cardiovascular events. At effective doses, omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower TG levels but may have additional atheroprotective properties compared to other TG-lowering therapies such as niacin and fibrates. The purpose of this review is to evaluate mechanisms related to the potential benefits of omega-3 fatty acids in atherothrombotic disease. RECENT FINDINGS: Large randomized clinical trials are currently under way to test the cardiovascular benefits of omega-3 fatty acids at a pharmacologic dosage (4 g/day). A large randomized trial with a prescription EPA-only formulation was shown to reduce a composite of cardiovascular events by 25% in statin-treated patients with established cardiovascular disease or diabetes and other CV risk factors. EPA and DHA have distinct tissue distributions as well as disparate effects on membrane structure and lipid dynamics, rates of lipid oxidation, and signal transduction pathways. Compared to other TG-lowering therapies, EPA has been found to inhibit cholesterol crystal formation, inflammation, and oxidative modification of atherogenic lipoprotein particles. The anti-inflammatory and endothelial benefits of EPA are enhanced in combination with a statin. Omega-3 fatty acids like EPA only at a pharmacologic dose reduce fasting TG and interfere with mechanisms of atherosclerosis that results in reduced cardiovascular events. Additional mechanistic trials will provide further insights into their role in reducing cardiovascular risk in subjects with well-managed LDL-C but elevated TG levels.

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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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, 4.04 g/24 h; 95% CI: 3.10, 4.97; P < 0.0001) as well as higher concentrations of pre-albumin (WMD 35.20 mg/L; 95% CI: 26.59, 43.81; P < 0.0001) and albumin (WMD, 1.64 g/L; 95% CI: 1.17, 2.10; P < 0.0001) compared with MCTs/LCTs. In contrast, significantly lower concentrations of plasma triglycerides (WMD, -0.21 mmol/L; 95% CI: -0.30, -0.12; P < 0.0001), total cholesterol (WMD, -0.45 mmol/L; 95% CI: -0.60, -0.29; P < 0.0001), alanine aminotransferase (WMD, -7.68 IU/L; 95% CI: -9.68, -5.68; P < 0.0001) and aspartate aminotransferase (WMD, -10.27 IU/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, -2.67 mg/L; 95% CI: -4.55, -0.79; P = 0.005) and increased concentrations of IgG (WMD, 2.11 g/L; 95% CI: 0.23, 3.99; P = 0.03), IgA (WMD, 0.21 g/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. CONCLUSIONS: 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.

Lipemia retinalis in an infant treated for retinopathy of prematurity.

Lipemia retinalis is an unusual ocular finding associated with hypertriglyceridemia. We report the case of an infant treated for retinopathy of prematurity who later developed lipemia retinalis, with triglyceride levels of 4736 mg/dl. There was a paradoxical worsening of hypertriglyceridemia with the use of medium chain triglyceride supplement. On discontinuing the supplement, the triglycerides level drastically dropped, and retinal vasculature returned to a normal hue.

Ghrelin activation and neuropeptide Y elevation in response to medium chain triglyceride administration in anorexia nervosa patients.

BACKGROUND & AIMS: Ghrelin, a peptide found in the stomach, increases appetite and fat-free mass while suppressing energy expenditure. Ghrelin requires modification by medium-chain triglycerides (MCTs) to exert its physiological effects. In this study, we investigated ghrelin activation and the resulting physiological changes following MCT administration. METHODS: Thirty participants were selected from among inpatients diagnosed with anorexia nervosa (AN). The patients were randomly divided into three groups by the MCT content of their nutritional supplement: (1) 'MCT high' (>6 g/day), (2) 'MCT moderate' (1-6 g/day), and (3) 'MCT low' (<1 g/day). Physical factors such as body weight and composition, as well as levels of nutrition-related serum factors such as acylated (active form) and desacyl (inactive form) ghrelin, leptin, growth hormone, insulin-like growth factor, and neuropeptide Y (NPY) were measured at weeks 0, 2, 4, and 6 of the treatment protocol. RESULTS: Significantly higher ghrelin activation was found in the 'MCT high' than in the 'MCT low' group (P < 0.05). The amount of consumed MCT had a curvilinear relationship with the active ghrelin level (P = 0.00). NPY levels in the 'MCT high' group were significantly more elevated than in the 'MCT low' group (P < 0.05). MCT administration did not significantly affect the remaining factors. CONCLUSIONS: This study clearly demonstrated that MCT activates ghrelin and increases NPY, suggesting that nutritional supplementation with MCT may be effective for the treatment of AN patients in an emaciated state.

Palm oil and human health. Meeting report of NFI: Nutrition Foundation of Italy symposium.

The use of palm oil by the food industry is increasingly criticized, especially in Italy, for its purported negative effects on human health and environment. This paper summarizes the conclusions of a Symposium on this topic, gathered by the Nutrition Foundation of Italy, among experts representing a number of Italian Medical and Nutritional Scientific Societies. Toxicological and environmental issues were not considered. Participants agreed that: no evidence does exist on the specific health effects of palm oil consumption as compared to other saturated fatty acids-rich fats; the stereospecific distribution of saturated fatty acids in the triacylglycerol molecule of palm oil limits their absorption rate and metabolic effects; in agreement with International guidelines, saturated fatty acids intake should be kept <10% of total energy, within a balanced diet; within these limits, no effect of palm oil consumption on human health (and specifically on CVD or cancer risk) can be foreseen.

Fat-Modified Breast Milk Resolves Chylous Pleural Effusion in Infants With Postsurgical Chylothorax but Is Associated With Slow Growth.

BACKGROUND: Chylothorax occurs in ~3%-5% of infants undergoing cardiac surgery. Standard treatment requires discontinuation of breast milk feeding, due to the abundance of long-chain triglycerides and transition to a medium-chain triglyceride (MCT)-based formula. OBJECTIVE: To determine the effectiveness of fat-modified breast milk (MBM) for the treatment of chylothorax compared with MCT formula. MATERIALS AND METHODS: Infants diagnosed with chylothorax following surgery for congenital heart disease between January 2008 and December 2009 at The Hospital for Sick Children were eligible for this nonrandomized open-label study. Treatment infants (n = 8) received mother's own milk that had been modified by removing the fat layer via centrifugation and adding MCT, nutrients, and essential fatty acids to provide an estimated 74 kcal/100 mL and 1.4 g/100 mL protein (MBM group). Control infants (n = 8) received an MCT formula (MCT group). The feeding intervention was a minimum of 6 weeks after chest tube removal per The Hospital for Sick Children standard chylothorax treatment protocol. RESULTS: Daily volume and duration of chest tube drainage were not different between the MBM and MCT groups. While there was no statistically significant difference in rates of weight gain (g/d) between feeding groups, infants in the MBM group, who tended to be younger, experienced a decline in mean weight (P = .04) and length (P = .01) for age z scores. CONCLUSION: Fat-modified breast milk resolved chylothorax; however, strategies to address poor growth need to be developed and evaluated in larger trials prior to widespread clinical adoption of this novel treatment.

Role of adenosine 5'-monophosphate-activated protein kinase in α-linolenic acid-induced intestinal lipid metabolism.

n-3 Long-chain PUFA up-regulate intestinal lipid metabolism. However, whether these metabolic effects of PUFA on intestine are mediated by AMP-activated protein kinase (AMPK) remains to be elucidated. To determine the effects of α-linolenic acid (ALA) on intestinal fatty acid (FA) metabolism and whether these effects were affected by AMPK deletion, mice deficient in the catalytic subunit of AMPKα1 or AMPKα2 and wild-type (WT) mice were fed either a high-fat diet (HF) or HF supplemented with ALA (HF-A). The results showed that ALA supplementation decreased serum TAG content in WT mice. ALA also increased mRNA expression of genes (carnitine palmitoyltransferase 1a, acyl-CoA oxidase 1, medium-chain acyl-CoA dehydrogenase, cytochrome P450 4A10 and pyruvate dehydrogenase kinase isoenzyme 4a) involved in intestinal lipid oxidation and mRNA expression of TAG synthesis-related genes (monoacylglycerol O-acyltransferase 2, diacylglycerol O-acyltransferases 1 and 2) in WT mice. Consistent with these, expression levels of phosphorylated AMPKα1 and AMPKα2 were also increased in WT mice after ALA addition. However, in the absence of either AMPKα1 or AMPKα2, ALA supplementation failed to increase intestinal lipid oxidation. In addition, no significant effects of either diet (HF and HF-A) or genotype (WT, AMPKα1(-/-) and AMPKα2(-/-)) on FA uptake in the intestine and faecal TAG output were observed. Our results suggest that AMPK is indispensable for the effects of ALA on intestinal lipid oxidation.

Possible adverse effects of frying with vegetable oils.

The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.

The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice.

OBJECTIVE: Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. MATERIALS/METHODS: Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. RESULTS: All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. CONCLUSION: These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation.

Medium-chain triglyceride supplementation exacerbates peritonitis-induced septic shock in rats: role on cell membrane remodeling.

BACKGROUND AND AIMS: Lipid emulsions for parenteral nutrition interfere with immunity and may alter the cell plasma membrane and microparticle release, thus modulating their biological effects. Our aim was to evaluate the effect of two lipid emulsions for parenteral nutrition containing either a mixture of long- and medium-chain triglycerides (LCTs and MCTs) or LCTs only, to assess their role on microparticle release and acute inflammation during septic shock in rats. METHODS AND RESULTS: Septic rats (cecal ligation and puncture) and sham rats were infused with 5% dextrose or a lipid emulsion during 22 h. After 18 h, rats were resuscitated during 4 h and hemodynamic parameters monitored. Circulating microparticles and their phenotype were measured by prothrombinase assay; heart and aorta were collected for Western blotting and electron paramagnetic resonance measurements. No significant effect of lipid emulsions was observed in sham rats. In septic rats, norepinephrine requirements were increased in MCT/LCT-infused rats compared with 5% dextrose- or LCT-infused rats (2.7 ± 0.2 vs. 1.9 ± 0.8 and 1.2 ± 0.3 µg/kg per minute, respectively; P < 0.05) with increased procoagulant microparticle generation (38.6 ± 5.8 vs. 18.8 ± 3.1 and 19.2 ± 3.0 nM equivalent phosphatidylserine [Eq PhtdSer]; P < 0.05), leukocyte- (17.4 ± 3.5 vs. 7.7 ± 1.8 and 6.0 ± 1.1 nM Eq PhtdSer; P < 0.05), platelet- (13.9 ± 2.5 vs. 4.4 ± 0.7 and 5.4 ± 1.3 nM Eq PhtdSer; P < 0.05), and endothelial-derived microparticles (16.9 ± 3.6 vs. 6.4 ± 1.4 and 5.6 ± 0.8 nM Eq PhtdSer; P < 0.05). The mixture of MCTs/LCTs significantly increased cardiac and vascular nitric oxide and superoxide anion production, phosphorylated IκB, and cyclooxygenase 2 expression compared with the lipid emulsion containing only LCTs. CONCLUSIONS: Compared with 5% dextrose, MCT/LCT supplementation during septic shock in rats induced deleterious effects with increased inflammation and cell activation, associated to vascular hyporeactivity. During septic shock, LCT supplementation seemed to be neutral compared with 5% dextrose infusion.

Palmitic acid in the sn-2 position of dietary triacylglycerols does not affect insulin secretion or glucose homeostasis in healthy men and women.

BACKGROUND/OBJECTIVES: Dietary triacylglycerols containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose. SUBJECTS/METHODS: We used a cross-over designed feeding trial in 53 healthy Asian men and women (20-50 years) to test this hypothesis by exchanging 20% energy of palm olein (PO; control) with randomly interesterified PO (IPO) or high oleic acid sunflower oil (HOS). After a 2-week run-in period on PO, participants were fed PO, IPO and HOS for 6 week consecutively in randomly allocated sequences. Fasting (midpoint and endpoint) and postprandial blood at the endpoint following a test meal (3.54 MJ, 14 g protein, 85 g carbohydrate and 50 g fat as PO) were collected for the measurement of C-peptide, insulin, glucose, plasma glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, lipids and apolipoproteins; pre-specified primary and secondary outcomes were postprandial changes in C-peptide and plasma glucose. RESULTS: Low density lipoprotein cholesterol was 0.3 mmol/l (95% confidence interval (95% CI)) 0.1, 0.5; P<0.001) lower on HOS than on PO or IPO as predicted, indicating good compliance to the dietary intervention. There were no significant differences (P=0.58) between diets among the 10 male and 31 female completers in the incremental area under the curve (0-2 h) for C-peptide in nmol.120 min/l: GM (95% CI) were PO 220 (196, 245), IPO 212 (190, 235) and HOS 224 (204, 244). Plasma glucose was 8% lower at 2 h on IPO vs PO and HOS (both P<0.05). CONCLUSION: Palmitic acid in the sn-2 position does not adversely impair insulin secretion and glucose homeostasis.