Fish Oil-based Lipid Emulsion Research Articles

Fish oil-based lipid emulsion in the treatment of parenteral nutrition-associated cholestasis

BackgroundParenteral nutrition-associated cholestasis (PNAC) is a serious complication in preterm infants receiving prolonged parenteral nutrition. Soybean lipid emulsion (SLE) seems to have a role in its pathogenesis, whereas fish oil-based emulsion (FOLE) seems to be able to reverse cholestasis. This study aimed to evaluate the effectiveness of a FOLE in reversing PNAC.MethodsThe effectiveness in reversing PNAC was evaluated in prospective cohort study of very preterm infants when compared to historical controls: twenty-six infants (27.0 ± 2.6 weeks GA; 724 ± 204 g) who developed cholestasis while receiving SLE were shifted to receive FOLE and were compared with 30 infants (27.3 ± 2.5 weeks GA¸ 838 ± 277 g) who continued to receive SLE at diagnosis of cholestasis.ResultsTime to reversal of cholestasis was the same in the two study groups (45 ± 21 vs 43 ± 32 days).ConclusionsFOLE does not seem to be superior to SLE in reversing cholestasis. Considering that definitive data on the actual efficacy of FOLE to reverse PNAC are lacking, larger randomized trials are required, mainly to asses if FOLE may have a role in PNAC prevention rather than PNAC treatment.

PNALD related to the type of initial intravenous lipid emulsion in preterm infants: LCT/MCT vs. SMOF lipid

Rationale: Peterm infants often have long-term parenteral nutrition (PN), so they are vulnerable to parenteral nutrition-associated liver disease (PNALD). The present study was aimed to verify benefits of fish oil-based lipid emulsions in prevention of PNALD.

Effects of fish oil-based lipid emulsion on inflammation and kidney injury in mice subjected to unilateral hind limb ischemia/reperfusion

This study investigated the effects of a fish oil-based lipid emulsion (FO) on local skeletal muscle and remote renal damage at 72 h post-reperfusion in a murine model of hind limb ischemia-reperfusion (IR) injury. Mice were assigned to 1 sham group and 3 IR groups. The IR groups were treated daily with either saline or FO from 3 days prior to limb ischemia till 3 days after reperfusion. Limb IR was induced by applying a 4.5-oz orthodontic rubber band above the left greater trochanter for 120 min followed by band-released reperfusion for 72 h. Mice were then sacrificed to harvest blood, muscle, and kidney for analysis. The results showed that IR injury led to upregulation of pro-inflammatory monocytes in blood, infiltration of leukocytes into injured muscle, and over-expression of pro-inflammatory genes in muscle and kidney tissues. Supplementing FO either before or after IR injury alleviated IR-induced inflammatory gene expressions in muscle and kidney tissues. Furthermore, FO given after IR injury reduced circulating pro-inflammatory monocytes, limited muscle leukocytic infiltration, and improved renal histology. These results suggest that FO may protect the muscles from IR injury. FO given after IR injury can better downregulate the inflammation seen in IR-induced remote kidney injury.

Dispelling myths about intravenous fish oil-based lipid emulsions: a clinical perspective.

Intravenous lipid emulsions (IVLEs) are an essential component of parenteral nutrition. With the recent incorporation of new lipid emulsions into the Canadian and American market, the clinician responsible for prescribing these lipids should be educated regarding the different fatty acid (FA) profiles of these lipids, as well as their metabolic and functional effects. New IVLEs contain a mix of soybean oil and olive oil, or a mix of soybean oil, coconut oil, olive oil and fish oil. These new lipid emulsions provide less essential fatty acids (FAs) (linoleic and alpha linolenic acids) than in pure soybean oil, yet incorporation of fish oil into an IVLE may decrease the amount of essential FAs required. Fish oil is a treatment for hypertriglyceridemia, and therefore, IVLEs that include fish oil may decrease serum triglycerides. Historical perspective is that fish oil can be associated with increased bleeding time. Evidence suggests that there is no association between fish oil and increased bleeding in patients, even those who are using anticoagulants. New IVLEs provide less vitamin K than soybean oil alone. Patients, or the parenteral nutrition solutions that include these new IVLEs should be supplemented with vitamin K. Canadian and American Guidelines for IVLEs were based on soybean oil. Current practice should be tailored to which IVLE is being prescribed.

Effect of a fish oil-based lipid emulsion on intestinal failure-associated liver disease in children

The aim of this study was to assess the effects of a fish oil-based lipid emulsion on intestinal failure-associated liver disease (IFALD) in children. From January 2014 through June 2017, we enrolled 32 children with IF on long-term parenteral nutrition (PN). When the levels of any three of seven liver indicators (TBA, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, gamma glutamyl transferase (γ-GT), total bilirubin (TB), or direct bilirubin (DB)) were two times higher than normal levels, we switched a 50:50 mix of soybean oil and medium-chain triglycerides (MCT) lipid emulsion (with an average dose of 1.30 g/kg/day) to a fish oil-based lipid emulsion (1 g/kg/day) and measured liver function in the children. Meanwhile, inflammation and oxidative stress-related markers were also measured. The average fish oil therapy duration was 26 ± 21 days, and the median duration of PN support was 84 days. With fish oil therapy, levels of TBA, ALT, AST, γ-GT, TB, and DB all significantly decreased. Enteral nutrition was introduced following fish oil resulting in higher energy intake (99.88 ± 31.06 kcal/kg/day) compared with before fish oil (67.90 ± 27.31 kcal/kg/day, P = 0.001). No significant difference was found in average PN energy (P = 0.147). In addition, levels of inflammatory indicators like tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and white blood cell (WBC) significantly decreased. Fish oil therapy alleviates IFALD in children.

Parenteral Nutrition Associated Liver Toxicity: Prevention, Diagnosis and Management

Long-term parenteral nutrition (PN) treatment is limited by parenteral nutrition–associated liver disease (PNALD), which is characterized initially by intrahepatic cholestasis, typically defined as a direct bilirubin greater than 2 mg/dL in the absence of other causes of liver disease. PNALD is typically less common and less severe and progresses more slowly in older children and adults than in infants. The etiology of PNALD is multifactorial. Key factors include immature liver function, sepsis, and a lack of enteral nutrition. Additionally, nearly every component of PN has been attributed to or exacerbated hepatotoxicity. PN preparations must be carefully individualized and monitored to minimize hepatotoxicity from its various components. Although many hepatotoxic components or imbalances have been recognized, soybean oil–based lipid emulsions continue to be widely used as they are the only lipid emulsions currently approved for PN by the Food and Drug Administration. Fish oil–based lipid emulsions have been shown to reverse PNALD, with an associated decrease in mortality. As such, fish oil therapy should be considered early once biochemical cholestasis is detected in PN-dependent patients. Studies investigating the use of novel lipid emulsions for prevention and treatment of PNALD are ongoing. This review contains 5 figures, 5 tables, and 114 references.

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

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

Parenteral Nutrition Associated Liver Toxicity: Prevention, Diagnosis and Management

Long-term parenteral nutrition (PN) treatment is limited by parenteral nutrition–associated liver disease (PNALD), which is characterized initially by intrahepatic cholestasis, typically defined as a direct bilirubin greater than 2 mg/dL in the absence of other causes of liver disease. PNALD is typically less common and less severe and progresses more slowly in older children and adults than in infants. The etiology of PNALD is multifactorial. Key factors include immature liver function, sepsis, and a lack of enteral nutrition. Additionally, nearly every component of PN has been attributed to or exacerbated hepatotoxicity. PN preparations must be carefully individualized and monitored to minimize hepatotoxicity from its various components. Although many hepatotoxic components or imbalances have been recognized, soybean oil–based lipid emulsions continue to be widely used as they are the only lipid emulsions currently approved for PN by the Food and Drug Administration. Fish oil–based lipid emulsions have been shown to reverse PNALD, with an associated decrease in mortality. As such, fish oil therapy should be considered early once biochemical cholestasis is detected in PN-dependent patients. Studies investigating the use of novel lipid emulsions for prevention and treatment of PNALD are ongoing. This review contains 5 figures, 5 tables, and 114 references.

Nutritional practices in very low birth weight infants: a national survey.

Significant efforts have been made to improve the nutritional support of very preterm infants. Large surveys may help to know the nutritional practices for preterm infants in neonatal units and identify if they are in line with the current guidelines. A multicentre nationwide web-based survey on clinical feeding practices in very low birth weight (VLBW) infants was conducted in tertiary neonatal hospitals that admit infants with a birth weight < 1,500 g and/or a gestational age of < 32 weeks. The questionnaire was completed by 53 units (response rate, 59%). Over 90% of the units surveyed start amino-acid administration immediately after birth and more than half use novel intravenous fish oil-based lipid emulsions. Enteral nutrition is started within 24 hours of birth in 65% of units and 86% of these are medium-sized or large. Feeding volumes are increased at a rate of 10-30 ml/kg/day in > 90% of units. Monitoring of serum phosphorus was measured more frequently than albumin (p = 0.009) or triglycerides (p = 0.037), but only 28% of centres regularly measure pre-albumin as a nutritional biomarker. Human milk fortification and iron supplementation, starting at four weeks of age, are almost universal. However, only 30% of units administer 800 IU/day of vitamin D. Nearly 50% of the units discharge infants on preterm formula. Most Spanish neonatology units use early amino-acid supplementation and over half use novel fish oil-based lipid emulsions. Post-discharge nutrition practices and vitamin administration vary greatly.

Management of parenteral nutrition in critically ill patients.

Artificial nutrition (AN) is necessary to meet the nutritional requirements of critically ill patients at nutrition risk because undernutrition determines a poorer prognosis in these patients. There is debate over which route of delivery of AN provides better outcomes and lesser complications. This review describes the management of parenteral nutrition (PN) in critically ill patients. The first aim is to discuss what should be done in order that the PN is safe. The second aim is to dispel “myths” about PN-related complications and show how prevention and monitoring are able to reach the goal of “near zero” PN complications. Finally, in this review is discussed the controversial issue of the route for delivering AN in critically ill patients. The fighting against PN complications should consider: (1) an appropriate blood glucose control; (2) the use of olive oil- and fish oil-based lipid emulsions alternative to soybean oil-based ones; (3) the adoption of insertion and care bundles for central venous access devices; and (4) the implementation of a policy of targeting “near zero” catheter-related bloodstream infections. Adopting all these strategies, the goal of “near zero” PN complications is achievable. If accurately managed, PN can be safely provided for most critically ill patients without expecting a relevant incidence of PN-related complications. Moreover, the use of protocols for the management of nutritional support and the presence of nutrition support teams may decrease PN-related complications. In conclusion, the key messages about the management of PN in critically ill patients are two. First, the dangers of PN-related complications have been exaggerated because complications are uncommon; moreover, infectious complications, as mechanical complications, are more properly catheter-related and not PN-related complications. Second, when enteral nutrition is not feasible or tolerated, PN is as effective and safe as enteral nutrition.

Pretreatment with Fish Oil-Based Lipid Emulsion Modulates Muscle Leukocyte Chemotaxis in Murine Model of Sublethal Lower Limb Ischemia

This study investigated the effects of a fish oil- (FO-) based lipid emulsion on muscle leukocyte chemotaxis and inflammatory responses in a murine model of limb ischemia-reperfusion (IR) injury. Mice were assigned randomly to 1 sham (sham) group, 2 ischemic groups, and 2 IR groups. The sham group did not undergo the ischemic procedure. The mice assigned to the ischemic or IR groups were pretreated intraperitoneally with either saline or FO-based lipid emulsion for 3 consecutive days. The IR procedure was induced by applying a 4.5 oz orthodontic rubber band to the left thigh above the greater trochanter for 120 min and then cutting the band to allow reperfusion. The ischemic groups were sacrificed immediately while the IR groups were sacrificed 24 h after reperfusion. Blood, IR-injured gastrocnemius, and lung tissues were collected for analysis. The results showed that FO pretreatment suppressed the local and systemic expression of several IR-induced proinflammatory mediators. Also, the FO-pretreated group had lower blood Ly6ChiCCR2hi monocyte percentage and muscle M1/M2 ratio than the saline group at 24 h after reperfusion. These findings suggest that FO pretreatment may have a protective role in limb IR injury by modulating the expression of proinflammatory mediators and regulating the polarization of macrophage.

Fish oil-based lipid emulsions versus standard lipid emulsions for prevention of parenteral nutrition-associated liver disease in children

Fish oil-based lipid emulsions versus standard lipid emulsions for prevention of parenteral nutrition-associated liver disease in children

Fish oil-based lipid emulsions versus standard lipid emulsions for treatment of parenteral nutrition-associated liver disease in children

Fish oil-based lipid emulsions versus standard lipid emulsions for treatment of parenteral nutrition-associated liver disease in children

Plasma and erythrocyte uptake of omega-3 fatty acids from an intravenous fish oil based lipid emulsion in patients with advanced oesophagogastric cancer

It has been demonstrated that short term intravenous (IV) administration of omega-3 polyunsaturated fatty acids (PUFAs) is more effective than oral supplementation at promoting incorporation of the bioactive omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma, blood cells and tissues. The effect of repeated short term IV infusion of omega-3 PUFAs was investigated in patients with advanced oesophagogastric cancer during palliative chemotherapy. Patients with advanced oesophagogastric cancer (n=21) were recruited into a phase II pilot clinical trial. All patients were scheduled for an intravenous infusion of Omegaven® (fish oil supplement containing EPA and DHA) at a rate of 2ml/kg body weight for 4h once a week for up to six months. Blood samples were collected to assess omega-3 PUFA uptake into plasma non-esterified fatty acids (NEFAs) and phosphatidylcholine (PC) and into red blood cell (RBC) membranes. Fatty acid profiles were analysed by gas chromatography. Twenty patients received at least one Omegaven® treatment and were included in the analysis. Each infusion of omega-3 PUFAs resulted in increased EPA and DHA in plasma NEFAs, but there was little effect on PUFAs within plasma PC during the infusions. However, with repeated weekly infusion of omega-3 PUFAs, the EPA content of plasma PC and of RBC membranes increased. Repeated weekly omega-3 PUFA infusion is effective in enriching plasma PC and RBC membranes in EPA in patients with advanced oesophagogastric cancer receiving palliative chemotherapy. Clinical Trials.Gov NCT01870791.

Fish oil- and soy oil-based lipid emulsions in neonatal parenteral nutrition: a systematic review and meta-analysis.

The precise role of fish oil-based lipid emulsions (FBL=any lipid emulsion containing any amount of fish oil) and soy oil-based lipid emulsions (SBL=any lipid emulsion not containing fish oil or containing at least 50% soy oil) in neonatal parenteral nutrition (PN) needs to be explored. The PubMed, MedLine and Google Scholar databases were searched for randomised control trials in which PN with FBL and SBL was the only difference between intervention and control groups. Methodological quality was assessed based on the Cochrane handbook for systemic reviews and Jadad's score. Revman 5.2 software was used for meta-analysis. Of 420 trials, 25 met the inclusion criteria. The aggregate results showed that both FBLs and SBLs are beneficial. FBLs were associated with significantly lower incidences of cholestasis (relative risk (RR)=0.50; 95% confidence interval (CI)=0.27-0.92, P=0.03) compared with SBLs. FBLs also had a tendency to improve the rates of weight gain, increase in head circumference and the time to regain birth weight (mean difference (MD)=0.24; 95% CI=-0.63-0.15). SBLs were associated with reduced duration of respiratory support (MD=2.22, 95% CI=0.35-4.09, P=0.02) and mortality rate in the first 28 days (RR=1.24, 95% CI=-0.72-2.13). Both FBLs and SBLs are beneficial for neonatal PN. FBLs reduce cholestasis, and SBLs reduce the duration of respiratory support.

Effect of Fish Oil-based Intravenous Fat Emulsion with Parenteral Nutrition in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Omega-3 fatty acid is known for immunonutrition in that it has anti-inflammatory properties and improves the patients’ immune function. The objective of this study was to determine the effects of a fish oil-based lipid emulsion for adult patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Differential Impacts of Soybean and Fish Oils on Hepatocyte Lipid Droplet Accumulation and Endoplasmic Reticulum Stress in Primary Rabbit Hepatocytes.

Parenteral nutrition-associated liver disease (PNALD) is a severe ailment associated with long-term parenteral nutrition. Soybean oil-based lipid emulsions (SOLE) are thought to promote PNALD development, whereas fish oil-based lipid emulsions (FOLE) are thought to protect against PNALD. This study aimed to investigate the effects of SOLE and FOLE on primary rabbit hepatocytes. The results reveal that SOLE caused significant endoplasmic reticulum (ER) and mitochondrial damage, ultimately resulting in lipid droplets accumulation and ER stress. While these deleterious events induce hepatocyte injury, FOLE at high doses cause only minor ER and mitochondrial damage, which has no effect on hepatic function. SOLE also significantly upregulated glucose-regulated protein 94 mRNA and protein expression. These data indicate that SOLE, but not FOLE, damage the ER and mitochondria, resulting in lipid droplets accumulation and ER stress and, finally, hepatocyte injury. This likely contributes to the differential impacts of SOLE and FOLE on PNALD development and progression.

The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants.

Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53 ± 5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants.

Effect of parenteral infusion of fish oil-based lipid emulsion on systemic inflammatory cytokines and lung eicosanoid levels in experimental acute pancreatitis

We evaluated the effect of short-term FOLE infusion before experimental induction of AP on systemic cytokine and lung eicosanoid profiles. Lewis rats (n=72) received parenteral infusion of FOLE (FO group) or saline (SS group), or remained without parenteral infusion (CG group) for 48h. Thereafter, AP was induced by retrograde injection of sodium taurocholate into the pancreatic duct. Animals were sacrificed after 2, 12 and 24h. Blood and lung samples were collected to assess serum inflammatory cytokines (Luminex) and tissue eicosanoids (ELISA), respectively. Serum TNF-α increased over time and serum IL-10 decreased from 12 to 24h in CG group. In SS group serum TNF-α increased from 12 to 24h (p=0.039) and serum IL-10 decreased over time. Both CG and SS groups exhibited increased IL-6/IL-10 ratio (p=0.040). From 12 to 24h animals from FO group showed decreased serum IL-1 (p<0.001), IL-4 (p<0.002) and IL-6 (p=0.050), and a trend towards increased IL-10 (p=0.060). All experimental groups showed a trend towards increased PGE2 and decreased LTB4 in the lung at 24 compared with 12h CONCLUSION: Parenteral infusion of FOLE for 48h before the induction of experimental AP appears to favorably influence the cytokine response without affecting lung eicosanoids at the time points measured. The use of FOLE to prevent and treat AP following major surgery needs to be further explored.

Fish oil-based lipid emulsion: current updates on a promising novel therapy for the management of parenteral nutrition-associated liver disease.

Intestinal failure is characterized by loss of enteral function to absorb necessary nutrients and water to sustain life. Parenteral nutrition (PN) is a lifesaving therapeutic modality for patients with intestinal failure. Lifelong PN is also needed for patients who have short bowel syndrome due to extensive resection or a dysmotility disorder with malabsorption. However, prolonged PN is associated with short-term and long-term complications. Parenteral nutrition-associated liver disease (PNALD) is one of the long-term complications associated with the use of an intravenous lipid emulsion to prevent essential fatty acid deficiency in these patients. PNALD affects 30–60% of the adult population on long-term PN. Further, PNALD is one of the indications for isolated liver or combined liver and intestinal transplantation. There is no consensus on how to manage PNALD, but fish oil-based lipid emulsion (FOBLE) has been suggested to play an important role both in its prevention and reversal. There is significant improvement in liver function in those who received FOBLE as lipid supplement compared with those who received soy-based lipid emulsion. Studies have also demonstrated that FOBLE reverses hepatic steatosis and reduces markers of inflammation in patients on long-term PN. Future prospective studies with larger sample sizes are needed to further strengthen the positive role of FOBLE in PNALD.