ω‐3 Fatty Acids Prevent Hepatic Steatosis,Independent of PPAR‐α Activity,in a Murine Model of Parenteral Nutrition–Associated Liver Disease

Objectives: ω‐3 Fatty acids (FAs), natural ligands for the peroxisome proliferator‐activated receptor–α (PPAR‐α), attenuate parenteral nutrition–associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω‐3 FAs are still unknown. The aim of this study was to determine the effects of ω‐3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR‐α and microsomal triglyceride transfer protein (MTP) in this experimental setting. Methods: 129S1/SvImJ wild‐type or 129S4/SvJaePparatm/Gonz/J PPAR‐α knockout mice were fed chow and water (controls); oral, fat‐free PN solution only (PN‐O); PN‐O plus intraperitoneal (IP) ω‐6 FA‐predominant supplements (PN–ω‐6); or PN‐O plus IP ω‐3 FA (PN–ω‐3). Control and PN‐O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR‐α messenger RNA were assessed after 19 days. Results: In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN‐O and PN–ω‐6 groups accumulated significantly greater amounts of TG when compared with PN–ω‐3 mice. Studies in PPAR‐α null animals showed that PN feeding increases hepatic TG as in wild‐type mice. PPAR‐α null mice in the PN‐O and PN–ω‐6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω‐3 FAs. Conclusions: PN induces TG accumulation (steatosis) in wild‐type and PPAR‐α null mice. In PN‐fed wild‐type and PPAR‐α null mice given IP ω‐3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω‐3 FAs results from PPAR‐α–independent pathways.     

Effects of ω‐3 Polyunsaturated Fatty Acids on the Homeostasis of CD4+ T Cells and Lung Injury in Mice With Polymicrobial Sepsis

Background: Sepsis is a common cause of death in critically ill patients. An overwhelming inflammatory response and imbalance of helper T (Th) cells and regulatory T (Treg) cells are thought to be involved in the progression of sepsis. ω‐3 Polyunsaturated fatty acids (PUFAs) were found to have anti‐inflammatory and immunomodulatory properties. This study investigated the effects of ω‐3 PUFAs on the balance of Th subsets, Treg cells, and the inflammatory response in septic mice. Methods: Mice were randomly assigned to soybean oil (SO) and fish oil (FO) groups. The 2 groups received an identical nutrient distribution except for the sources of the fat. The SO group was fed soybean oil, while part of the soybean oil was replaced by fish oil in the FO group. The FO group had an ω‐6/ω‐3 PUFA ratio of 2:1. After feeding the diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed on days 0, 1, and 3. Results: Compared with the SO group, the FO group had lower inflammatory mediator levels in the plasma and peritoneal lavage fluid after CLP. Also, the FO group had lower Th1, Th2, and Th17 percentages and a higher Th1/Th2 ratio in blood. In lung tissues, neutrophil infiltration was reduced, whereas peroxisome proliferator–activated receptor γ expression was upregulated. Conclusions: A fish oil diet with an ω‐6/ω‐3 PUFA ratio of 2:1 may elicit more balanced Th polarization, alleviate inflammatory responses, and attenuate lung injury in CLP‐induced sepsis.     

Effects of the ω‐6:ω‐3 Fatty Acid Ratio of Fat Emulsions on the Fatty Acid Composition in Cell Membranes and the Anti‐Inflammatory Action

Background: This study investigated the effects of parenterally administered fish oil (FO) on the fatty acid composition in rats to determine the optimal ω‐6:ω‐3 polyunsaturated fatty acid (PUFA) ratio of fat emulsions to achieve an anti‐inflammatory effect. Methods: Male Sprague‐Dawley rats were infused a parenteral nutrition (PN) solution containing fat emulsions with different ω‐6:ω‐3 PUFA ratios. The fatty acid content of phospholipids in the membranes of splenocytes was analyzed by gas chromatography (experiment 1). In addition, the amounts of leukotriene (LT) B₄ and LTB₅ released from peritoneal polymorphonuclear leukocytes (PMNs) were measured by high‐performance liquid chromatography (experiment 2). Results: In experiment 1, after infusion of the fat emulsion containing FO, the ω‐3 PUFA content in cell membranes rose to 70% of the peak value on day 1 and nearly reached a plateau on day 3. The highest ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) was achieved by administrating a PN solution with the smallest ω‐6:ω‐3 PUFA ratio. In experiment 2, a larger amount of LTB₅ was released from Ca‐ionophore‐stimulated PMNs taken from rats given a larger quantity of FO. The ratio of LTB₅:LTB₄ released from PMNs correlated positively with the EPA:AA ratio in the membranous phospholipid and in serum. Conclusions: The ω‐3 PUFAs were readily incorporated into the cell membrane within 3 days of infusion with the fat emulsion. The EPA:AA ratio in membranous phospholipid in PMNs was positively correlated with the LTB₅:LTB₄ production ratio and was a good indicator of anti‐inflammatory effects.     

Reversal of Parenteral Nutrition–Associated Liver Disease With a Fish Oil–Based Lipid Emulsion (Omegaven) in an Adult Dependent on Home Parenteral Nutrition

Patients with intestinal failure and short bowel syndrome usually require chronic parenteral nutrition (PN). PN is associated with risks, including infections, vascular thrombosis, and liver disease. PN‐associated liver disease (PNALD) can progress from steatosis to chronic hepatitis and ultimately to cirrhosis. The etiology of PNALD is not completely understood. Therapies for PNALD include carbohydrate or lipid calorie reduction, antibiotics, or the use of ursodeoxycholic acid. When these efforts fail, therapeutic options are limited and liver transplantation may be required. The transition from a soybean‐ to a fish oil–based lipid formulation, such as the ω‐3 parenteral lipid formulation (Omegaven), has shown a dramatic reversal of PNALD within the pediatric population. This is the first report of a PN‐dependent adult in the United States complicated by PNALD and hepatic failure who had improvement of liver disease with an ω‐3 fish oil–based parenteral formulation.     

Rapid Enrichment of Cell Phospholipids in Long‐Chain Polyunsaturated ω‐3 Fatty Acids After a Bolus Intravenous Injection of a Medium‐Chain Triacylglycerol

The present review aims at highlighting the use of a recently developed medium‐chain triacylglycerol:fish oil (MCT:FO) emulsion for the rapid and sustained enrichment of long‐chain polyunsaturated ω‐3 fatty acids in cell phospholipids. Preclinical in vitro, in vivo, and ex vivo experiments are briefly considered with emphasis on the changes in the fatty acid pattern of cell phospholipids in several organs, the partial correction of liver steatosis, and the cardiovascular modification of cationic and functional variables observed in ω‐3‐depleted rats examined 60–120 minutes after a bolus intravenous (IV) injection (1.0 mL) of the MCT:FO emulsion. The clinical findings collected in healthy male volunteers before or after the bolus IV injection (50.0 mL) of either the MCT:FO emulsion or a control medium‐chain triacylglycerol:long‐chain triacylglycerol emulsion are also reviewed, with emphasis on the rapid (within 60 minutes) and sustained (up to 2–3 days) enrichment of platelet and white blood cell phospholipids in long‐chain polyunsaturated ω‐3 fatty acids and hemostatic safety of the present procedure proposed as a tool for the rapid prevention or correction of metabolic and functional disturbances in humans with a relative deficiency in such ω‐3 fatty acids.     

Soybean and Fish Oil Mixture With Different ω‐6/ω‐3 Polyunsaturated Fatty Acid Ratios Modulates Dextran Sulfate Sodium–Induced Changes in Small Intestinal Intraepithelial γδT‐Lymphocyte Expression in Mice

Background: This study investigated the effect of different ω‐6/ω‐3 polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)–induced changes to small intestinal intraepithelial lymphocyte (IEL) γδT‐cell expression. Methods: Mice were assigned to 3 control and 3 DSS‐treated groups and were maintained on a low‐fat semipurified diet. One of the control (S) groups and a DSS (DS) group were provided with soybean oil; the other 2 control (Hω‐3 and Lω‐3) groups and 2 other DSS (DHω‐3 and DLω‐3) groups were fed either a soybean and fish oil mixture with a ω‐6/ω‐3 ratio of 2:1 or 4:1. After feeding the respective diets for 2 weeks, the DSS groups were given distilled water containing 2% DSS, and the control groups were given distilled water for 5 days. All groups were further provided distilled water 5 days for recovery, and the small intestinal IEL γδT‐cell subset was isolated for analysis. Results: DSS treatment resulted in a lower small intestinal IEL γδT‐cell percentage and higher messenger RNA (mRNA) expressions of Reg IIIγ, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by IEL γδT cells. Fish oil administration enhanced the proportion of small intestinal IEL γδT cells. Compared with the DLω‐3 group, the DHω‐3 group had lower Reg IIIγ, KGF, and C5aR mRNA expressions and higher expression of peroxisome proliferator‐activated receptor (PPAR)–γ gene by small intestinal IEL γδT cells. Conclusions: Fish oil diets with a ω‐6/ω‐3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in improving DSS‐induced small intestinal injury, and activation of PPAR‐γ in IEL γδT cells may be associated with resolution of small intestinal inflammation.     

Rapid Incorporation of ω‐3 Fatty Acids Into Colonic Tissue After Oral Supplementation in Patients With Colorectal Cancer

Background: The purpose of the study was to examine whether a preoperative supplement with ω‐3 fatty acids (FAs) leads to their incorporation into colonic tissue in patients scheduled for colorectal cancer surgery. This would be of interest because ω‐3 FAs have potential beneficial (local) immunological effects that might benefit these patients. Methods: In a randomized, double‐blind, prospective, placebo‐controlled, single‐center intervention trial, patients referred for elective colorectal cancer surgery received either an ω‐3 FA–enriched oral nutrition supplement (ONS) (200 mL twice daily) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for 7 days before surgery. Tissue samples from healthy colonic tissue (mucosa and muscular layer) were obtained during surgery, and tissue fatty acid composition was analyzed by gas chromatography. Results: EPA was significantly higher in colonic mucosa (P = .001) and in the colonic muscular layer (P = .004) in the ω‐3 FA group compared with controls. Patients in the ω‐3 FA group also tended to have higher docosapentaenoic acid and DHA levels in colonic tissue. Conclusions: EPA is incorporated rapidly into colonic mucosa and colonic muscular layer in patients given 3 g of ω‐3 FA daily for 7 days before surgery for colorectal cancer. This may lead to potential beneficially effects on (local) immune function, which might benefit these patients.     

Partial replacement of ω-6 fatty acids with medium-chain triglycerides, but not olive oil, improves colon cytokine response and damage in experimental colitis

Background: Soybean oil is rich in ω‐6 fatty acids, which are associated with higher incidence and more severe cases of inflammatory bowel diseases. The authors evaluated whether partial replacement of soybean oil by medium‐chain triglycerides (MCTs) or olive oil influenced the incidence and severity of experimental ulcerative colitis by using different parenteral lipid emulsions (LEs). Methods: Wistar rats (n = 40) were randomized to receive parenteral infusion of the following LE: 100% soybean oil (SO), 50% MCT mixed with 50% soybean oil (MCT/SO), 80% olive oil mixed with 20% soybean oil (OO/SO), or saline (CC). After 72 hours of infusion, acetic acid experimental colitis was induced. After 24 hours, colon histology and cytokine expression were analyzed. Results: SO was not significantly associated with overall tissue damage. MCT/SO was not associated with necrosis (P < .005), whereas OO/SO had higher frequencies of ulcer and necrosis (P < .005). SO was associated with increased expression of interferon‐γ (P = .005) and OO/SO with increased interleukin (IL)–6 and decreased tumor necrosis factor–α expression (P < .05). MCT/SO appeared to decrease IL‐1 (P < .05) and increase IL‐4 (P < .001) expression. Conclusions: Parenteral SO with high concentration of ω‐6 fatty acids was not associated with greater tissue damage in experimental colitis. SO partial replacement with MCT/SO decreased the frequency of histological necrosis and favorably modulated cytokine expression in the colon; however, replacement with OO/SO had unfavorable effects.     

Dietary ω‐6/ω‐3 Polyunsaturated Fatty Acid Ratios Affect the Homeostasis of Th/Treg Cells in Mice With Dextran Sulfate Sodium–Induced Colitis

Background: This study evaluated the effect of different dietary ω‐6/ω‐3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)–induced colitis. Methods: There were 3 control and 3 colitis groups. Mice were fed for 24 days with diets with soybean oil (S), a mixture of soybean oil and low fish oil content (LF), or high fish oil content (HF). The ratio of ω‐6/ω‐3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups were provided 2% DSS in drinking water during days 15–19. All mice drank distilled water from days 20–24 for recovery and were sacrificed on day 25. Results: Colitis resulted in higher blood Th1, Th2, and Th17 and lower Treg percentages. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Furthermore, the percentages of blood Th1, Th2, and Th17 cells were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with an ω‐6/ω‐3 PUFA ratio of 2:1 had more pronounced effects than the group with a ratio of 4:1. Conclusions: Diets with an ω‐6/ω‐3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared with the ω‐6/ω‐3 PUFA ratio of 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS‐induced colitis.     

A New Intravenous Fat Emulsion Containing Soybean Oil,Medium‐Chain Triglycerides,Olive Oil,and Fish Oil

Background: SMOFlipid 20% is an intravenous lipid emulsion (ILE) containing soybean oil, medium‐chain triglycerides, olive oil, and fish oil developed to provide energy, essential fatty acids (FAs), and long‐chain ω‐3 FAs as a mixed emulsion containing α‐tocopherol. The aim was to assess the efficacy and safety of this new ILE in pediatric patients receiving home parenteral nutrition (HPN) compared with soybean oil emulsion (SOE). Methods: This single‐center, randomized, double‐blind study included 28 children on HPN allocated to receive either SMOFlipid 20% (n = 15) or a standard SOE (Intralipid 20%, n = 13). ILE was administered 4 to 5 times per week (goal dose, 2.0 g/kg/d) within a parenteral nutrition regimen. Assessments, including safety and efficacy parameters, were performed on day 0 and after the last study infusion (day 29). Lipid peroxidation was determined by measurement of thiobarbituric acid reactive substances (TBARS). Results: There were no significant differences in laboratory safety parameters, including liver enzymes, between the groups on day 29. The mean ± standard deviation changes in the total bilirubin concentration between the initial and final values (day 29 to day 0) were significantly different between groups: SMOFlipid group ?1.5 ± 2.4 µmol/L vs SOE group 2.3 ± 3.5 µmol/L, P < .01; 95% confidence interval [CI], ?6.2 to ?1.4). In plasma and red blood cell (RBC) phospholipids, the ω‐3 FAs C20:5ω‐3 (eicosapentaenoic acid) and + C22:6ω‐3 (docosahexaenoic acid) increased significantly in the SMOFlipid group on day 29. The ω‐3:ω‐6 FA ratio was significantly elevated with SMOFlipid 20% compared with SOE group (plasma, day 29: 0.15 ± 0.06 vs 0.07 ± 0.02, P < .01, 95% CI, 0.04–0.11; and RBC, day 29: 0.23 ± 0.07 vs 0.14 ± 0.04, P < .01, 95% CI, 0.04–0.13). Plasma α‐tocopherol concentration increased significantly more with SMOFlipid 20% (15.7 ± 15.9 vs 5.4 ± 15.2 µmol/L, P < .05; 95% CI, ?2.1 to 22.6). The low‐density lipoprotein–TBARS concentrations were not significantly different between both groups, indicating that lipid peroxidation did not differ between groups. Conclusions: SMOFlipid 20%, which contains 15% fish oil, was safe and well tolerated, decreased plasma bilirubin, and increased ω‐3 FA and α‐tocopherol status without changing lipid peroxidation.     

Impact of Providing a Combination Lipid Emulsion Compared With a Standard Soybean Oil Lipid Emulsion in Children Receiving Parenteral Nutrition

Background: Soybean oil lipid emulsion may compromise immune function and promote hepatic damage due to its composition of long‐chain fatty acids, phytosterols, high proportion of ω‐6 fatty acids, and low α‐tocopherol levels. Combination lipid emulsions have been developed using medium‐chain triglyceride oil, fish oil, and/or olive oil, which provide adequate essential fatty acids, a smaller concentration of ω‐6 fatty acids, and lower levels of phytosterols. The purpose of this systematic review is to determine if combination lipid emulsions have a more favorable impact on bilirubin levels, triglyceride levels, and incidence of infection compared with soybean oil lipid emulsions in children receiving parenteral nutrition. Methods: This study comprises a systematic review of published studies. Data were sufficient and homogeneous to conduct a meta‐analysis for total bilirubin and infection. Results: Nine studies met the inclusion criteria. Meta‐analysis showed that combination lipid emulsion decreased total bilirubin by a mean difference of 2.09 mg/dL (95% confidence interval, –4.42 to 0.24) compared with soybean oil lipid emulsion, although the result was not statistically significant (P = .08). Meta‐analysis revealed no statistically significant difference in incidence of infection between the combination lipid emulsion and the soybean oil lipid emulsion groups (P = .846). None of the 4 studies that included triglyceride as an outcome detected a significant difference in triglyceride levels between the combination lipid emulsion and soybean oil lipid emulsion groups. Conclusion: There is inadequate evidence that combination lipid emulsions offer any benefit regarding bilirubin levels, triglyceride levels, or incidence of infection compared with soybean oil lipid emulsions.     

ω-3 Fatty acids have no impact on serum lactate levels after major gastric cancer surgery

Background: Preoperative and intraoperative nutrition support in patients undergoing major surgery results in decreased incidence of morbidity and mortality. Studies investigating the role of ω‐3 fatty acids in these patients are increasing. Some are focused on perfusion at the cellular level. This study was undertaken to address the effect of postoperative administration of ω‐3 fatty acids on cellular hypoperfusion associated with major gastric surgery. Methods: Twenty‐six patients undergoing gastric cancer surgery were randomly assigned to receive parenteral nutrition (PN) supplemented with a combination of ω‐6 and ω‐3 fatty acids (Omegaven, 0.2 g/kg/d; Lipovenoes 10%, 0.6 g/kg/d) or with ω‐6 fatty acid (Lipovenoes 10%, 0.8 g/kg/d) for 5 days. Blood samples were taken preoperatively, postoperative day 1, and on the last day of PN therapy (day 5). Results: Patients receiving ω‐3 and ω‐6 fatty acids showed neither lower serum lactate levels nor lower rates of complications compared with patients receiving ω‐6 only. There were no statistically significant differences between the groups in other biochemical parameters, complications, or length of hospital stay or mortality. Conclusion: PN with ω‐3 fatty acid supplementation does not have a significant impact on cellular hypoperfusion and lactate clearance after major gastric surgery.     

A Comparison of 2 Intravenous Lipid Emulsions

Objective. To assess the safety and efficacy of a fish oil–based intravenous fat emulsion (FIFE) in reducing the incidence of cholestasis in neonates compared with the traditional soybean oil–based intravenous fat emulsion (SIFE). Methods. A double‐blind randomized controlled trial was conducted. Nineteen neonates were enrolled (10 SIFE; 9 FIFE). Nutrition assessments and laboratory studies were serially obtained for the duration of PN support or until 6 months’ corrected gestational age. Neurodevelopmental outcomes were assessed at 6 and 24 months’ corrected age. Results. There were no differences between groups in demographic characteristics, with an overall median age of 2 days, gestational age of 36 weeks, and birth weight of 2410 g. There were no differences between groups in baseline laboratory values other than alkaline phosphatase (lower in the FIFE group) or in the duration of parenteral nutrition (PN), amount of enteral intake, or the number of operative procedures. The incidence of cholestasis among enrolled patients was significantly lower than expected, resulting in early study termination and an inability to assess for differences in the incidence of cholestasis. The FIFE was associated with no increased risk of growth impairment, coagulopathy, infectious complications, hypertriglyceridemia, or adverse neurodevelopmental outcomes. No patient developed essential fatty acid deficiency. Conclusion. The FIFE at 1 g/kg/d was well tolerated in the neonates recruited for this study. Given the necessary early termination of this study, a follow‐up trial with revised eligibility criteria is necessary to determine whether the provision of FIFE decreases the incidence of PN‐cholestasis compared with the traditional SIFE.     

Intravenous ω‐3 Fatty Acids Plus Gemcitabine

Background: Marine‐derived ω‐3 fatty acids (ω‐3FAs) have proven antitumor activity in vivo and in vitro and improve quality of life (QOL) in clinical cancer studies. These changes may be mediated by reduction in circulating proangiogenic and proinflammatory factors. In this first study of intravenous ω‐3FAs as a therapy in cancer patients, we aimed to assess if it could augment the antitumor activity of gemcitabine in patients with advanced pancreatic cancer and improve QOL. Materials and Methods: Patients were administered gemcitabine 1000 mg/m³ weekly followed by up to 100 g (200 mg/mL) of ω‐3 rich lipid emulsion for 3 weeks followed by a rest week. This was continued for up to 6 cycles, progression, unacceptable toxicity, patient request, or death. The primary outcome measure was objective response rate, with secondary outcome measures of overall and progression free survival, QOL scores, and adverse events. Results: Fifty patients were recruited. Response rate was 14.3% and disease control rate was 85.7%. Overall and progression free survival were 5.9 and 4.8 months, respectively. Increase in global health of > 10% over baseline was seen in 47.2% of patients. More than 50% of patients had > 10% increase in QOL scores in generic symptom scores and both disease‐specific domains. Grade 3/4 adverse events were thrombocytopenia (8%), neutropenia (12%), nausea or vomiting (4%), and chills (6%). Conclusion: Intravenous ω‐3FAs in combination with gemcitabine shows evidence of improved activity and benefit to QOL in patients with advanced pancreas cancer and is worthy of investigation in a randomized phase III trial.     

Phytonadione Content in Branded Intravenous Fat Emulsions

Background: Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by‐product of vegetable and animal oil during the refining processes. Likewise, other lipid‐soluble vitamins may be present in IVFE. No data, however, exist about phytonadione (vitamin K1) concentration in IVFE information leaflets. Therefore, our aim was to evaluate the phytonadione content in different IVFE. Materials and Methods: Analyses were carried out in triplicate on 6 branded IVFE as follows: 30% soybean oil (100%), 20% olive‐soybean oil (80%–20%), 20% soybean–medium‐chain triglycerides (MCT) coconut oil (50%–50%), 20% soybean‐olive‐MCT‐fish oil (30%‐25%‐30%‐15%), 20% soybean‐MCT‐fish oil (40%‐50%‐10%), and 10% pure fish oil (100%). Phytonadione was analyzed and quantified by a quali‐quantitative liquid chromatography–mass spectrometry (LC‐MS) method after its extraction from the IVFE by an isopropyl alcohol–hexane mixture, reverse phase–liquid chromatography, and specific multiple‐reaction monitoring for phytonadione and vitamin d3 (as internal standard). This method was validated through specificity, linearity, and accuracy. Results: Average vitamin K1 content was 500, 100, 90, 100, 95, and 70 µg/L in soybean oil, olive‐soybean oil, soybean‐MCT coconut oil, soybean‐olive‐MCT‐fish oil, soybean‐MCT‐fish oil, and pure fish oil intravenous lipid emulsions (ILEs), respectively. The analytical LC‐MS method was extremely effective in terms of specificity, linearity (r = 0.99), and accuracy (coefficient of variation <5%). Conclusions: Phytonadione is present in IVFE, and its intake varies according to IVFE type and the volume administered. It can contribute to daily requirements and become clinically relevant when simultaneously infused with multivitamins during long‐term parenteral nutrition. LC‐MS seems adequate in assessing vitamin K1 intake in IVFE.     

Liver Disease,Systemic Inflammation,and Growth Using a Mixed Parenteral Lipid Emulsion,Containing Soybean Oil,Fish Oil,and Medium Chain Triglycerides,Compared With Soybean Oil in Parenteral Nutrition–Fed Neonatal Piglets

Background: The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure–associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω‐6 and ω‐3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil–based emulsion (ω‐6:ω‐3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium‐chain triglycerides, 25% olive oil, and 15% fish oil (ω‐6:ω‐3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Method: Neonatal piglets, 3–6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C‐reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Results: Compared with the IL group, ML‐treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω‐6 long‐chain PUFA content was lower in plasma and brain for the ML group. The key ω‐3 long‐chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. Conclusion: The mixed lipid, having less ω‐6 PUFA and more ω‐3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN‐fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes.     

Parenteral ω‐3 Fatty Acid Lipid Emulsions for Children With Intestinal Failure and Other Conditions

Background: There is growing interest in the use of ω‐3 fatty acid (n‐3FA) lipid emulsions to prevent complications associated with parenteral nutrition. The authors systematically reviewed the evidence on the benefits and safety of n‐3FA compared with standard lipid emulsions in children with intestinal disease, critical illness, trauma, or postoperative complications. Materials and Methods: The authors searched 4 bibliographic databases from their inception to March 2011, conference proceedings, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodological quality, and rated the strength of the evidence. One reviewer extracted and a second reviewer verified data. The authors summarized findings qualitatively and conducted meta‐analysis when appropriate. Results: Five randomized controlled trials with unclear risk of bias and 3 high‐quality prospective cohort studies were included. The studies examined premature, low birth weight infants (n = 6) and children with heart disease (n = 1) or intestinal failure (n = 1). The strength of evidence was consistently low or very low across all lipid emulsion comparisons and outcomes. In young children, n‐3FA emulsions resulted in improvement in some biochemical outcomes of intestinal failure–associated liver disease but no difference in mortality. Few studies examined patient‐important outcomes, such as length of hospital and intensive care stay; need for transplantation, growth, and cognitive development; or the long‐term effects and potential harms associated with these therapies. Conclusions: Currently, there is a lack of sufficient high‐quality data to support the use of parenteral n‐3FA lipid emulsions in children. Future trials examining long‐term clinical outcomes and harms are needed.     

脂肪乳在肠外营养中的应用进展

脂肪乳作为肠外营养支持中主要的能量来源,数十年来,已发展出多种不同配方的制剂.LCT脂肪乳由于代谢方面的缺陷,目前在临床上已被MCT/LCT脂肪乳逐步取代.较新的配方是由结构三酰甘油或橄榄油构成,此种新型脂肪乳更为安全,耐受性更好.含鱼油 ( n-3脂肪酸)的脂肪乳,可改善不同病人危重情况下的组织灌注.最新的脂肪乳SMOF,由添加维生素E的大豆长链脂肪酸、中链脂肪酸、橄榄油和鱼油混合配制而成,已在一项双盲试验中获得良好的应用,其效能尚有待进一步的临床验证.     

ω‐3 Fatty Acids Reduce Chemotherapy‐Induced Hematological Toxicity by Bone Marrow Stimulation in Mice

Background: ω‐3 Fatty acids exert several benefits during chemotherapy, such as preventing intestinal mucosal damage and improving response to chemotherapy. However, little is known about the effect of ω‐3 fatty acids on chemotherapy‐induced hematological toxicities. Methods: Mice that had consumed either an ω‐3–rich or an ω–3‐poor diet for 2 weeks were intraperitoneally administered cisplatin. The resultant changes in blood cell count, bone marrow cell count, and cytokine levels in bone marrow supernatant were analyzed. The effect of ω‐3 fatty acids on human peripheral blood mononuclear cells (PBMCs) exposed to cisplatin was also examined. Results: Although peripheral blood cell counts decreased after cisplatin treatment in both groups of mice, the decrease in white blood cell count was significantly lower in mice that consumed the ω‐3–rich diet. The decrease in bone marrow cells after cisplatin treatment was also reduced in mice that consumed the ω‐3–rich diet. Levels of stem cell factor (SCF) and fibroblast growth factor 1 (FGF‐1) were significantly higher in bone marrow supernatants from mice that consumed the ω‐3–rich diet. The rate of apoptosis in PBMCs (after exposure to cisplatin) cultured in medium containing ω‐3 fatty acids was significantly lower than in PBMCs cultured in control medium. Conclusion: ω‐3–Rich diets reduced chemotherapy‐induced leukopenia in mice. This may be the result of increased numbers of bone marrow cells due to higher levels of SCF and FGF‐1 in the bone marrow.     

Evolution of Lipid Profile,Liver Function,and Pattern of Plasma Fatty Acids According to the Type of Lipid Emulsion Administered in Parenteral Nutrition in the Early Postoperative Period After Digestive Surgery

Background: The metabolic effects of intravenous lipid emulsions (ILEs) used in parenteral nutrition (PN) depend on their fatty acid composition. Methods: Subjects in this prospective and randomized double‐blind study were 28 adult patients post digestive surgery. PN was started after surgery and lasts for 5 days. Randomly, patients receive 1 of 4 different ILEs: medium‐chain triglycerides/long‐chain triglycerides (soybean oil; MCT/LCT), olive/soybean oil (oleic), long‐chain triglycerides (soybean oil; LCT), and structured lipid. On days 0 and 6, serum liver function tests were analyzed for cholesterol, triglycerides, lipoproteins, and serum fatty acids. Results: No differences were found in the 4 groups according to their gender, age, body mass index, diagnosis, baseline white blood cell, C‐reactive protein, glucose levels, and other study parameters. Differential significant changes were not observed in any of the hepatic function parameters or plasmatic lipid levels between the groups. A significant decrease was observed in cis monounsaturated fatty acids (MUFAs) and a significant increase in ω‐6 polyunsaturated fatty acids (PUFAs) andω ‐3 PUFA values in LCT and structured groups compared with MCT/LCT and oleic groups, and a tendency for a decrease in trans fatty acids in the oleic and structured groups was found. Conclusions: All ILEs administered were safe and well tolerated. The changes in serum fatty acids reflected the pattern of fatty acids administered with different ILEs. The group receiving the olive oil emulsion achieved a fatty acid composition of serum lipids that could offer major therapeutic or biological advantages.