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.     

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.     

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.     

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.     

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.     

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.     

Anti-tumor necrosis factor-α monoclonal antibody alleviates parenteral nutrition-associated liver disease in mice

Background: The authors aimed to investigate the role of anti–tumor necrosis factor (TNF)–α monoclonal antibody treatment in a mouse model of parenteral nutrition–associated liver disease (PNALD). Methods: C57BL/6J male mice (aged 6–8 weeks) were randomly assigned to 3 groups: parenteral nutrition (PN), PN with anti–TNF‐α monoclonal antibody treatment (PN + mAb), and controls. A central venous catheter was inserted for intravenous infusion of a PN solution (PN and PN + mAb groups) or saline (controls) for 7 days. Liver pathology, hepatic biochemical indicators, and serum TNF‐α concentrations were analyzed. Levels of hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA were also evaluated in each group. Results: The PN group showed significant increases in serum transaminase, direct bilirubin, and bile acids relative to the control group (P < .05). Histopathological changes in this group were consistent with early stage cholestasis. The pathological score and serum alanine aminotransferase, total bilirubin, and direct bilirubin levels were improved in the PN + mAb group relative to the PN group (P < .05). The PN group showed significantly lower hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA expression than the controls (P < .05), but these were significantly increased compared to the PN group (P < .05). Conclusions: Infliximab administered at a single dose of 5 mg/kg body weight ameliorated the progression of PNALD and improved the expression of hepatic ABC transporter genes. Therefore, anti–TNF‐α monoclonal antibody may be a beneficial therapy for patients with PNALD.     

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.     

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.     

Supplemental Parenteral Vitamin E Into Conventional Soybean Lipid Emulsion Does Not Prevent Parenteral Nutrition–Associated Liver Disease in Full‐Term Neonatal Piglets

Background: Parenteral nutrition–associated liver disease (PNALD) continues to cause morbidity and mortality for neonates with intestinal failure. Lipid peroxidation is one potential etiological factor. This study was designed to test if supplementing vitamin E into conventional soy‐based lipid would reduce the risk of PNALD. Methods: Sixteen piglets, aged 2–5 days and weighing 1.8–2.5 kg, were randomized to parenteral nutrition (PN) with soy lipid (SO, n = 8) or the same lipid plus α‐tocopherol, the most bioactive form of vitamin E (SO+E, n = 8). After 17 days, bile flow, liver chemistry, gene expression associated with bile acid metabolism, and bile acid composition were assessed. C‐reactive protein (CRP) and oxidative stress markers, including plasma 8‐isoprostane, were measured. All results were compared with a sow‐reared control group (CON). Results: Comparing PN‐treated groups, SO vs SO+E mean bile flow (5.91 vs 5.54 µL/g liver; P = .83), serum bile acid concentration (39.2 vs 26.6 µmol/L; P = .12), and total bilirubin (35.2 vs 26.9 µmol/L; P = .56) were not different. Gene expression related to bile acid metabolism and bile composition was not different between PN groups. There was no difference in CRP (41.8 vs 36.8 µg/mL; P = .22) or in plasma 8‐isoprostane (27.9 vs 26.1 pg/mL; P = .77). Conclusions: In term neonatal piglets, supplemental vitamin E did not prevent cholestasis. Additional vitamin E was not associated with reduced inflammation or oxidative stress. The benefit of supplementing vitamin E into conventional lipid, vs adding fish oil, to prevent early onset of PNALD requires further clarification.     

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.     

Effects of ω‐3 Fish Oil Lipid Emulsion Combined With Parenteral Nutrition on Patients Undergoing Liver Transplantation

Background: The effect of parenteral nutrition (PN) support supplemented with ω‐3 fatty acids was investigated in a randomized, controlled clinical trial at the Affiliated Drum Tower Hospital, Medical School of Nanjing University. Materials and Methods: Ninety‐eight patients with the diagnosis of end‐stage liver disease or hepatic cellular carcinoma were admitted for orthotopic liver transplantation at the Affiliated Drum Tower Hospital. The patients were randomly divided into 3 groups: diet group (n = 32), PN group (n = 33), and polyunsaturated fatty acid (PUFA) group (n = 33). Patients in the PN and PUFA groups received isocaloric and isonitrogenous PN for 7 days after surgery. Venous heparin blood samples were obtained for assay on days 2 and 9 after surgery. A pathological test was performed after reperfusion of the donor liver and on day 9. Results: Alanine aminotransferase levels were improved significantly by PUFA treatment compared with traditional PN support (P < .05). Compared with the results on day 9 in the PN group, a significant difference was seen in the extent of increase of the prognostic nutrition index and prealbumin in the PUFA group. The pathological results also showed that ω‐3 fatty acid supplementation reduced hepatic cell injury. PUFA therapy also decreased the incidence of infectious morbidities and shortened the posttransplant hospital stay significantly. Conclusion: Posttransplant PN support can greatly improve metabolism of protein and nutrition states of patients. ω‐3 fatty acid–supplemented PN significantly reduces injury of the transplanted liver, decreases the incidence of infectious morbidities, and shortens posttransplant hospital stay.     

Choline Protects Against Intestinal Failure–Associated Liver Disease in Parenteral Nutrition–Fed Immature Rats

Background: Deficiency of choline, a required nutrient, is related to intestinal failure–associated liver disease (IFALD). Therefore, we aimed to investigate the effects of choline supplementation on IFALD and the underlying mechanisms. Methods: Male Sprague‐Dawley rats (4 weeks old) were fed AIN‐93G chow and administered intravenous 0.9% saline (control), parenteral nutrition (PN), or PN plus intravenous choline (600 mg/kg) for 7 days. We evaluated body weight, hepatic histology, biochemical indicators, triglycerides, oxidative status, methylation levels of peroxisomal proliferator‐activated receptor alpha (PPARα) gene promoter, expression of PPARα and carnitine palmitoyltransferase 1 (CPT1), and levels of choline metabolites. Results: The PN + choline group exhibited improved body weight compared with the PN group. PN impaired hepatic function, increased hepatic triglycerides, induced dyslipidemia, enhanced reactive oxygen species and malondialdehyde, and reduced total antioxidant capacity. The PN group had higher pathologic scores than the control group. These results were prevented by choline administration. Compared with the control group, PN increased PPARα promoter methylation and hepatic betaine concentration, reduced hepatic choline and phosphatidylcholine (PC) levels, decreased plasma choline and betaine concentrations, and downregulated PPARα and CPT1 mRNA and protein expression. Choline supplementation elevated hepatic choline and PC levels and enhanced plasma choline, betaine, and PC concentrations but reduced hepatic betaine level, reversed PPARα promoter hypermethylation, and upregulated PPARα and CPT1 mRNA and protein expression in PN‐fed rats, compared with rats receiving PN alone. Conclusion: Choline addition to PN may prevent IFALD by reducing oxidative stress, enhancing hepatic fat export, and promoting fatty acid catabolism in immature rats receiving PN.     

Vitamin E in New‐Generation Lipid Emulsions Protects Against Parenteral Nutrition–Associated Liver Disease in Parenteral Nutrition–Fed Preterm Pigs

Introduction: Parenteral nutrition (PN) in preterm infants leads to PN‐associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions. Hypothesis: Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs. Methods: We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d‐α‐tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, β‐sitosterol, campesterol, and stigmasterol). Results: Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low‐density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7‐hydroxylase and organic solute transporter–α expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo ¹³C‐CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance‐associated protein 2, were higher in ILE, OV, and PS vs IL. Conclusions: α‐tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD.     

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.     

Glucagon‐Like Peptide 2 Improves Cholestasis in Parenteral Nutrition–Associated Liver Disease

Background: Parenteral nutrition‐associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with intestinal failure. Although glucagon‐like peptide‐2 (GLP‐2) is being advanced as therapy, the effect of GLP‐2 treatment on PNALD is unknown. We aim to investigate the effect of exogenous GLP‐2 administration on hepatic function in a neonatal piglet model of PNALD. Methods: Neonatal piglets (aged 2–6 days) underwent jugular venous catheterization to receive isonitrogenous, isocaloric parenteral nutrition (PN). Piglets were allocated to 2 groups: group 1 (n = 8) received saline while group 2 (n = 7) received GLP‐2 (at 11 nmol/kg/d). After 17 days, piglets underwent terminal laparotomy, and bile flow was measured. Liver specimens were analyzed histologically and with immunoperoxidase staining. Age‐matched sow‐reared control piglets (group 3, n = 8) were used for comparison. Results: Both groups 1 and 2 receiving PN developed cholestasis relative to sow‐reared controls, as evidenced by a decrease in bile flow and increase in serum total bilirubin. However, group 2 had improved bile flow (1.35 vs 0.73 µL/g; P = .02) and diminished bilirubin (38.0 vs 78.5 µmol/L; P = .008) compared with group 1. Group 2 also had lower serum alanine aminotransferase levels, a marker of liver injury. Histologically, the liver specimens in group 1 had marked hepatocyte pigmentation, which was decreased in group 2 specimens. Conclusions: The exogenous administration of GLP‐2 is associated with the improvement of cholestasis and liver injury. This study introduces a novel role for GLP‐2 in improving PNALD in the setting of prolonged PN duration.     

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.     

Effects on Varying Intravenous Lipid Emulsions on the Small Bowel Epithelium in a Mouse Model of Parenteral Nutrition

Background: Injectable fat emulsions (FEs) are a clinically dependable source of essential fatty acids (FA). ω‐6 FA is associated with an inflammatory response. Medium‐chain triglycerides (MCT, ω‐3 FA), fish oil, and olive oil are reported to decrease the inflammatory response. However, the effect of these lipids on the gastrointestinal tract has not been well studied. To address this, we used a mouse model of parenteral nutrition (PN) and hypothesized that a decrease in intestinal inflammation would be seen when either fish oil and MCT or olive oil were added. Methods: Three FEs were studied in adult C57BL/6 mice via intravenous cannulation: standard soybean‐based FE (SBFE), 80% olive oil ‐supplemented FE (OOFE), or a combination of a soybean oil, MCT, olive oil, and fish oil emulsion (SMOF). PN was given for 7 days, small bowel mucosa‐derived cytokines, animal survival rate, epithelial cell (EC) proliferation and apoptosis rates, intestinal barrier function and mucosal FA composition were analyzed. Results: Compared to the SBFE and SMOF groups, the best survival, highest EC proliferation and lowest EC apoptosis rates were observed in the OOFE group; and associated with the lowest levels of tumor necrosis factor‐α, interleukin‐6, and interleukin‐1β expression. Jejunal FA content showed higher levels of eicosapentaenoic and docosapentaenoic acid in the SMOF group and the highest arachidonic acid in the OOFE group. Conclusion: The study showed that PN containing OOFE had beneficial effects to small bowel health and animal survival. Further investigation may help to enhance bowel integrity in patients restricted to PN.