Effect of intravenous omega-3 fatty acid infusion and hemodialysis on fatty acid composition of free fatty acids and phospholipids in patients with end-stage renal disease

Background: Patients treated with hemodialysis (HD) have been reported to have decreased levels of ω‐3 polyunsaturated fatty acids (PUFAs) in plasma and cells. The aim of this study was to investigate the effect of ω‐3 PUFAs administered intravenously during HD, as well as the effect of HD treatment, on the fatty acid composition of plasma free fatty acids (FFAs), plasma phospholipids, and platelet phospholipids. Methods: Forty‐four HD patients were randomized to groups receiving either a single dose of a lipid emulsion containing 4.1 g of ω‐3 PUFAs or placebo (saline) administered intravenously during HD. Blood was drawn immediately before (baseline) and after (4 hours) HD and before the next HD session (48 hours). Fatty acid composition was measured using gas chromatography. Results: The increase in ω‐3 FFAs was greater in the ω‐3 PUFA group compared with the placebo group, whereas the increase in total FFAs was similar between the 2 groups. In the ω‐3 PUFA group, ω‐3 PUFAs in plasma phospholipids were higher after 48 hours than at baseline, and in platelet phospholipids, ω‐3 PUFAs increased after 4 hours. In the placebo group, no changes were observed in ω‐3 PUFAs in plasma and platelet phospholipids. Conclusions: Intravenous ω‐3 PUFAs administered during HD caused a transient selective increase in ω‐3 FFA concentration. Furthermore, ω‐3 PUFAs were rapidly incorporated into platelets, and the content of ω‐3 PUFAs in plasma phospholipids increased after 48 hours.     

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.     

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.     

Impact of the omega-3 to omega-6 polyunsaturated fatty acid ratio on cytokine release in human alveolar cells

Background: ω‐3 polyunsaturated fatty acids (PUFAs) and ω‐6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)–induced cytokine release by human alveolar cells was affected by changes in the ω‐3/ω‐6 ratio of cell membranes induced by different supplies of PUFAs. Methods: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω‐3) and arachidonic acid (AA, ω‐6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured. Results: The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω‐6 over ω‐3 in the ω‐3/ω‐6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin‐6, and interleukin‐8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti‐inflammatory interleukin‐10 (P < .001). The balance between proinflammatory and anti‐inflammatory cytokines showed an anti‐inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001). Conclusions: This study showed that proinflammatory cytokine release was dependent on the proportion of ω‐3 in the ω‐3/ω‐6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω‐6 to ω‐3 in nutrition support of patients with acute lung injury.     

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.     

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 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.     

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.     

Lipid Emulsion Formulation of Parenteral Nutrition Affects Intestinal Microbiota and Host Responses in Neonatal Piglets

Background: Total parenteral nutrition (TPN) is a cause of intestinal microbial dysbiosis and impaired gut barrier function. This may contribute to life‐threatening parenteral nutrition–associated liver disease and sepsis in infants. We compared the effects of a lipid emulsion containing long‐chain ω‐3 polyunsaturated fatty acids (PUFAs; SMOFlipid) and a predominantly ω‐6 PUFA emulsion (Intralipid) on microbial composition and host response at the mucosal surface. Materials and Methods: Neonatal piglets were provided isocaloric, isonitrogenous TPN for 14 days versus sow‐fed (SF) controls. Equivalent lipid doses (10 g/kg/d) were given of either SMOFlipid (ML; n = 10) or Intralipid (SO; n = 9). Ileal segments and mucosal scrapings were used to characterize microbial composition by 16S rRNA gene sequencing and quantitative gene expression of tight junction proteins, mucins, antimicrobial peptides, and inflammatory cytokines. Results: The microbial composition of TPN piglets differed from SF, while ML and SO differed from each other (analysis of molecular variance; P < .05); ML piglets were more similar to SF, as indicated by UniFrac distance (P < .05). SO piglets showed a specific and dramatic increase in Parabacteroides (P < .05), while ML showed an increase in Enterobacteriaceae (P < .05). Gene expression of mucin, claudin 1, β‐defensin 2, and interleukin 8 were higher in TPN; overall increases were significantly less in ML versus SO (P < .05). Conclusion: The formulation of parenteral lipid is associated with differences in the gut microbiota and host response of TPN‐fed neonatal piglets. Inclusion of ω‐3 long‐chain PUFAs appears to improve host‐microbial interactions at the mucosal surface, although mechanisms are yet to be defined.     

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.     

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.     

Fish Oil–Based Lipid Emulsions Prevent and Reverse Parenteral Nutrition–Associated Liver Disease: The Boston Experience

Parenteral nutrition–associated liver disease (PNALD) is the most prevalent and most severe complication of long‐term parenteral nutrition. Its underlying pathophysiology, however, largely remains to be elucidated. The currently approved parenteral lipid emulsions in the United States contain safflower or soybean oils, both rich in ω‐6 polyunsaturated fatty acids (PUFAs). Mounting evidence indicates that the ω‐6 PUFAs originating from plant oils in these lipid emulsions may play a role in the onset of liver injury. Fish oil–based lipid emulsions, in contrast, are primarily composed of ω‐3 PUFAs, thus providing a promising alternative. The authors review the literature on the role of lipid emulsions in the onset of PNALD and discuss prevention and treatment strategies using a fish oil–based lipid emulsion. They conclude that a fish oil–based emulsion is hepatoprotective in a murine model of PNALD, and it appears to be safe and efficacious for the treatment of this type of liver disease in children. A prospective randomized trial that is currently under way at the authors' institution will objectively determine the place of fish oil monotherapy in the prevention of PNALD.     

Restoration of Mannose‐Binding Lectin Complement Activity Is Associated With Improved Outcome in Patients With Advanced Pancreatic Cancer Treated With Gemcitabine and Intravenous ω‐3 Fish Oil

Background: Pancreatic cancer has an extremely poor clinical outcome. Surrogate biomarkers for outcome are scarce. There is mixed evidence for the association of high mannose‐binding lectin (MBL) complement activity with cancer outcomes, including reduced survival and increased infectious complications. ω‐3–rich fatty acids (ω‐3FA) attenuate production of proinflammatory cytokines and potentially manipulate complement activity. Materials and Methods: As part of a single‐arm phase II trial in a university hospital, patients with advanced pancreatic adenocarcinoma were treated with weekly ω‐3FA–rich intravenous infusion (Lipidem [B. Braun Melsungen AG, Melsungen, Germany]: up to 100 g/wk) plus gemcitabine chemotherapy until withdrawal or tumor progression. Primary outcome measure was objective response rate. Changes in complement activity, which were a secondary outcome measure, were analyzed and relation to clinical outcome determined. Results: Twenty‐three patients were assessable for time to progression (TTP), overall survival (OS), and complement activity. No hypoactivity in alternative and classical pathways was demonstrated. Baseline MBL was low in 10 of 23 patients (43.5%). There was no difference in OS or TTP between low‐ and high‐baseline MBL patients. Of these 10 patients, 5 were classified as MBL responders. MBL responders had a tendency toward improved OS over nonresponders (8.9 vs 4.4 months, P = .07). MBL responders had significantly improved TTP over nonresponders (10.6 vs 5.3 months, P = .03). Conclusion: MBL restoration had an association with improved outcome in the cohort of patients with low MBL activity at baseline. The independent contribution of ω‐3FA to this effect warrants further investigation in the form of randomized clinical trials.     

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.     

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.     

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.     

Pilot Experimental Study on the Effect of Arginine,Glutamine, and β‐Hydroxy β‐Methylbutyrate on Secondary Wound Healing

Background: Wound healing is a complex process, dependent on available nutrition substrates. When used together with β‐hydroxy β‐methylbutyrate, arginine and glutamine have been shown to increase collagen deposition in human subjects. However, there are no experimental investigations on the influence of this amino acid mixture with regard to secondary wound healing. The aim of this study is to investigate the effects of the supplementation of these 3 amino acids on the healing of open wounds in otherwise healthy animals. Materials and Methods: Twelve rats were divided into control and treatment groups. Two 2‐cm × 1‐cm full‐thickness skin defects were prepared on each subject. The rats in both groups received a diet containing 1.2 g of protein per 100 g of body weight per day. The treatment group, in addition, received 200 mg/kg L‐arginine, 200 mg/kg L‐glutamine, and 40 mg/kg β‐hydroxy β‐methylbutyrate every day. Wound sizes were measured every 2 days. On the 10th day, tissue samples were taken for histopathologic evaluation and also for the measurement of hydroxyproline concentrations. Results: There was no statistically significant difference between mean wound sizes for the 2 groups (P > .05). There was also no statistically significant difference between the groups with regard to histological healing parameters (reepithelialization [P = 1.00], granulation tissue [P = 1.00], collagen accumulation [P = .455], inflammatory cell accumulation [P = .455], angiogenesis [P = .242]) or tissue hydroxyproline concentrations (P = .240). Conclusion: Diet supplemented with arginine, glutamine, and β‐hydroxy β‐methylbutyrate is not beneficial in enhancing secondary healing of open wounds in rats. Further research regarding this topic is warranted.     

Characterization of Fatty Acid Profiles in Infants With Intestinal Failure–Associated Liver Disease

Background

The purpose of this study was to characterize fatty acid profiles (FAPs) in parenteral nutrition (PN)‐dependent infants with intestinal failure–associated liver disease (IFALD) receiving soybean oil–based lipid emulsion (SO) doses of ～3 and ～1 g/kg/d.

Methods

Prospectively collected data were retrospectively reviewed. Serum FAPs of patients <1 year old who experienced development of IFALD while receiving standard PN with SO were examined before transitioning to a fish oil–based lipid emulsion for IFALD treatment. Time on SO, dose, gestational age, and weight‐ and length‐for‐age z scores were also reviewed.

Results

Among the 49 patients analyzed, there were no differences in demographics or anthropometrics between patients who received standard SO (SO‐S) (n = 14, range of dosage 2.06–3.31 g/kg/d) and reduced SO (SO‐R) (n = 35, range of dosage 0.90–1.34 g/kg/d). Patients received SO for a median of 53 days (interquartile range 39, 73) before FAP measurement. Patients who received SO‐R had significantly higher Mead acid and lower α‐linolenic, eicosapentaenoic, linoleic, stearic, total ω‐3, and total ω‐6 fatty acid levels than patients who received SO‐S (P < .01). Triene:tetraene ratios were higher in patients who received SO‐R (P = .0009), and no patients experienced biochemical essential fatty acid deficiency (EFAD).

Conclusion

PN‐dependent infants with IFALD receiving SO‐R have different FAPs than patients receiving SO‐S. No patients in either group had biochemical EFAD.     

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.