Expert consensus report on lipid mediators: Role in resolution of inflammation and muscle preservation.

This meeting report presents a consensus on the biological aspects of lipid emulsions in parenteral nutrition, emphasizing the unanimous support for the integration of lipid emulsions, particularly those containing fish oil, owing to their many potential benefits beyond caloric provision. Lipid emulsions have evolved from simple energy sources to complex formulations designed to improve safety profiles and offer therapeutic benefits. The consensus highlights the critical role of omega-3 polyunsaturated fatty acids (PUFAs), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil and other marine oils, for their anti-inflammatory properties, muscle mass preservation, and as precursors to the specialized pro-resolving mediators (SPMs). SPMs play a significant role in immune modulation, tissue repair, and the active resolution of inflammation without impairing host defense mechanisms. The panel's agreement underscores the importance of incorporating fish oil within clinical practices to facilitate recovery in conditions like surgery, critical illness, or immobility, while cautioning against therapies that might disrupt natural inflammation resolution processes. This consensus not only reaffirms the role of specific lipid components in enhancing patient outcomes, but also suggests a shift towards nutrition-based therapeutic strategies in clinical settings, advocating for the proactive evidence-based use of lipid emulsions enriched with omega-3 PUFAs. Furthermore, we should seek to apply our knowledge concerning DHA, EPA, and their SPM derivatives, to produce more informative randomized controlled trial protocols, thus allowing more authoritative clinical recommendations.

Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients - a randomized controlled trial. (OxaNeuro).

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. METHODS: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. DISCUSSION: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023.

The role of lipid emulsions containing omega-3 fatty acids for medical and surgical critical care patients.

In critical illness the regulation of inflammation and oxidative stress can improve patient outcomes, and thus omega-3 polyunsaturated fatty acids (PUFAs) have been used as part of parenteral nutrition (PN) owing to their potential anti-inflammatory effects. The international lipids in PN Summit, encompassed discussions and the production of consensus guidelines concerning PN intravenous lipid emulsion (ILE) use in critical care. The Lipid Summit participants agreed that the inclusion of fish oil in ILEs is associated with meaningful clinical benefits without signals of harm, based on a strong biological rationale and current clinical evidence. Decisions concerning ILE choice should be made based on current evidence, thus addressing clinical requirements for guidance, particularly as further definitive evidence seems unlikely to occur. In addition, a future of individualized ICU care is envisioned, yielding better clinical outcomes. This approach will require the greater use of intelligent study designs incorporating the use of biomarkers of omega-3 derivatives, inflammatory-resolving processes, and/or muscle protein breakdown.

Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

Assessing the Potential of an Enzymatically Liberated Salmon Oil to Support Immune Health Recovery from Acute SARS-CoV-2 Infection via Change in the Expression of Cytokine, Chemokine and Interferon-Related Genes.

Cytokines, chemokines, and interferons are released in response to viral infection with the ultimate aim of viral clearance. However, in SARS-CoV-2 infection, there is an imbalanced immune response, with raised cytokine levels but only a limited interferon response with inefficient viral clearance. Furthermore, the inflammatory response can be exaggerated, which risks both acute and chronic sequelae. Several observational studies have suggested a reduced risk of progression to severe COVID-19 in subjects with a higher omega-3 index. However, randomized studies of omega-3 supplementation have failed to replicate this benefit. Omega-3 fats provide important anti-inflammatory effects; however, fatty fish contains many other fatty acids that provide health benefits distinct from omega-3. Therefore, the immune health benefit of whole salmon oil (SO) was assessed in adults with mild to moderate COVID-19. Eleven subjects were randomized to best supportive care (BSC) with or without a full spectrum, enzymatically liberated SO, dosed at 4g daily, for twenty-eight days. Nasal swabs were taken to measure the change in gene expression of markers of immune response and showed that the SO provided both broad inflammation-resolving effects and improved interferon response. The results also suggest improved lung barrier function and enhanced immune memory, although the clinical relevance needs to be assessed in longer-duration studies. In conclusion, the salmon oil was well tolerated and provided broad inflammation-resolving effects, indicating a potential to enhance immune health.

Amelioration of obesity induction by a high-fat diet and related inflammation by Phasa fish (Setipinna phasa) oil in BALB/c mice.

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement.

Supplementation With Fish Oil in Pregnancy Reduces Gastroenteritis in Early Childhood.

BACKGROUND: We hypothesized that insufficient intake of fish oil-derived omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy is a contributing factor to gastroenteritis in early childhood. We examined the effect of n-3 LCPUFA supplementation on gastroenteritis symptoms in the offspring's first 3 years of life. METHODS: This was a double-blinded, randomized controlled trial whereby 736 mothers were administered n-3 LCPUFA or control from pregnancy week 24 until 1 week after birth. We measured the number of days with gastroenteritis, number of episodes with gastroenteritis, and the risk of having a gastroenteritis episode in the first 3 years of life. RESULTS: A median reduction of 2.5 days with gastroenteritis (P = .018) was shown, corresponding to a 14% reduction in the n-3 LCPUFA group compared with controls in the first 3 years of life (P = .037). A reduction in the number of gastroenteritis episodes (P = .027) and a reduced risk of having an episode (hazard ratio, 0.80 [95% confidence interval, .66-.97]; P = .023) were also shown. CONCLUSIONS: Fish oil supplementation from the 24th week of pregnancy led to a reduction in the number of days and episodes with gastroenteritis symptoms in the first 3 years of life. The findings suggest n-3 LCPUFA supplementation as a preventive measure against gastrointestinal infections in early childhood. CLINICAL TRIALS REGISTRATION: NCT00798226.

Atopic and non-atopic effects of fish oil supplementation during pregnancy.

BACKGROUND: We recently conducted a double-blinded randomised controlled trial showing that fish-oil supplementation during pregnancy reduced the risk of persistent wheeze or asthma in the child by 30%. Here, we explore the mechanisms of the intervention. METHODS: 736 pregnant women were given either placebo or n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the third trimester in a randomised controlled trial. Deep clinical follow-up of the 695 children in the trial was done at 12 visits until age 6 years, including assessment of genotype at the fatty acid desaturase (FADS) locus, plasma fatty acids, airway DNA methylation, gene expression, microbiome and metabolomics. RESULTS: Supplementation with n-3 LCPUFA reduced the overall risk of non-atopic asthma by 73% at age 6 (relative risk (RR) 0.27 (95% CI 0.06 to 0.85), p=0.042). In contrast, there was no overall effect on asthma with atopic traits (RR 1.42 (95% CI 0.63 to 3.38), p=0.40), but this was significantly modified by maternal FADS genotype and LCPUFA blood levels (interaction p<0.05), and supplementation did reduce the risk of atopic asthma in the subgroup of mothers with FADS risk variants and/or low blood levels of n-3 LCPUFA before the intervention (RR 0.31 (95% CI 0.11 to 0.75), p=0.016). Furthermore, n-3 LCPUFA significantly reduced the number of infections (croup, gastroenteritis, tonsillitis, otitis media and pneumonia) by 16% (incidence rate ratio 0.84 (95% CI 0.74 to 0.96), p=0.009). CONCLUSIONS: n-3 LCPUFA supplementation in pregnancy showed protective effects on non-atopic asthma and infections. Protective effects on atopic asthma depended on maternal FADS genotype and n-3 LCPUFA levels. This indicates that the fatty acid pathway is involved in multiple mechanisms affecting the risk of asthma subtypes and infections. TRIAL REGISTRATION NUMBER: NCT00798226.

Lipid emulsions in parenteral nutrition: does it matter?

PURPOSE OF REVIEW: Recently, clinicians have shown interest in switching patients to nonsoybean-based intravenous lipid emulsion (ILE) formulas for parental nutrition (PN) due to adverse outcomes related to high Omega-6 content in soybean oil (SO) ILE's. This review summarizes recent literature on improved clinical outcomes with new Omega-6 lipid-sparing ILE's in PN management. RECENT FINDINGS: Although there is a paucity of large-scale studies directly comparing Omega-6 lipid sparing ILE's with SO-based lipid emulsion use in PN in ICU patients, there is strong translational and meta-analysis evidence to suggest that lipid formulations containing fish oil (FO) and/or olive oil (OO) have favorable effects on immune function and improve clinical outcomes in ICU populations. SUMMARY: More research is needed to directly compare omega-6-sparing PN formulas with FO and/or OO versus traditional SO ILE's. However, current evidence is promising for improved outcomes using newer ILE's including reduced infections, shorter lengths of stay, and reduced costs.

Fish Oil And/Or Probiotics Intervention in Overweight/Obese Pregnant Women and Overweight Risk in 24-Month-Old Children.

OBJECTIVES: To evaluate whether a fish oil and/or probiotics intervention in pregnant women with overweight or obesity would influence the tendency of their 24-month-old children to become overweight and alter their body fat percentage. METHODS: Women (n = 439) were double-blindly randomized into 4 intervention groups: fish oil+placebo, probiotics+placebo, probiotics+fish oil, and placebo+placebo (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). The intervention lasted from early pregnancy until 6 months postpartum. Children's (n = 330) growth data (height, weight, head circumference), a secondary outcome of the trial, were evaluated at birth, 3, 6, 12, and 24 months of age and compared to Finnish growth charts. Body fat percentage was measured with air displacement plethysmography (24 months). Logistic regression and general linear models were used to analyze the data. RESULTS: Probiotics+placebo [weight-for-height% adj. Odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.14-0.95] and probiotics+fish oil [weight-for-age standard deviation score (SD-score) adj. OR = 0.22, 95% CI = 0.07-0.71] associated with lower overweight odds in 24-month-old children compared to placebo+placebo. Results remained essentially the same, when probiotics' main effect (combined probiotics+placebo and probiotics+fish oil) was estimated; that is, lower overweight odds (weight-for-height% adj. OR = 0.48, 95% CI = 0.25-0.95 and weight-for-age SD-score adj. OR = 0.42, 95% CI = 0.20-0.88) compared to non-probiotics. No fish oil main effect (combined fish oil+placebo and probiotics+fish oil) was seen. The intervention did not influence body fat percentage. CONCLUSIONS: The administration of probiotics solely and in combination with fish oil during pregnancy to women with overweight or obesity lowered the overweight odds of their 24-month-old children.

Interplay between fish oil, obesity and cardiometabolic diabetes.

Diabetes, dyslipidemia, obesity, and cardiac dysfunction are the hallmarks of the cardiometabolic syndrome. Pathogens include hypercoagulability, inflammation, endothelial dysfunction, and oxidative stress. Increased white fat, nonalcoholic fatty liver disease, diabetes, and cardiovascular disease are caused by obesity. Depression increases the risk of future obesity, a surprising link between obesity and neuropathology. High glucose levels, abnormal lipids, and metabolic syndrome are the root causes of CVD associated with diabetes. Diets high in fat induce insulin resistance and liver fat. Inflammation, diminished insulin signaling, and ectopic lipid accumulation are the causes of ectopic lipid accumulation. Polyunsaturated fatty acids with eicosapentaenoic acid and docohexasonoic acid inhibit the synthesis of triglycerides and increase their clearance. Omega-3 regulates the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammation. However, anxiety and depression can cause cardiovascular disease. It has been shown that PUFAs found in fish oil can improve glucose and lipid metabolism, cardiac membrane composition, and inflammation in the body. By repairing the dysregulation of metabolic syndrome, fish oil is a potential therapeutic target for cardiovascular diseases.

Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events.

OBJECTIVE: To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD). STUDY DESIGN: In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73). RESULTS: When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT00910104 and NCT00738101.

Fish oil supplementation alters emotion-generated corticolimbic functional connectivity in depressed adolescents at high-risk for bipolar I disorder: A 12-week placebo-controlled fMRI trial.

OBJECTIVE: To evaluate the effects of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on emotion-generated corticolimbic functional connectivity in depressed youth at high risk for developing bipolar I disorder. METHODS: Thirty-nine antidepressant-free youth with a current depressive disorder diagnosis and a biological parent with bipolar I disorder were randomized to 12-week double-blind treatment with FO or placebo. At baseline and endpoint, fMRI (4 Tesla) scans were obtained while performing a continuous performance task with emotional and neutral distractors (CPT-END). Seed-to-voxel functional connectivity analyses were performed using bilateral orbitofrontal cortex (OFC) and amygdala (AMY) seeds. Measures of depression, mania, global symptom severity, and erythrocyte fatty acids were obtained. RESULTS: Erythrocyte EPA+DHA composition increased significantly in the FO group (+47%, p ≤ 0.0001) but not in the placebo group (-10%, p = 0.11). Significant group by time interactions were found for functional connectivity between the left OFC and the left superior temporal gyrus (STG) and between the right AMY and right inferior temporal gyrus (ITG). OFC-STG connectivity increased in the FO group (p = 0.0001) and decreased in the placebo group (p = 0.0019), and AMY-ITG connectivity decreased in the FO group (p = 0.0014) and increased in the placebo group (p < 0.0001). In the FO group, but not placebo group, the decrease in AMY-ITG functional connectivity correlated with decreases in Childhood Depression Rating Scale-Revised and Clinical Global Impression-Severity Scale scores. CONCLUSIONS: In depressed high-risk youth FO supplementation alters emotion-generated corticolimbic functional connectivity which correlates with changes in symptom severity ratings.

Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence.

Whether marine omega-3 fatty acid (n-3 FA) or vitamin D supplementation can prevent cardiovascular disease (CVD) in general populations at usual risk for this outcome is unknown. A major goal of VITAL (Vitamin D and Omega-3 Trial) was to fill this knowledge gap. In this article, we review the results of VITAL, discuss relevant mechanistic studies regarding n-3 FAs, vitamin D, and vascular disease, and summarize recent meta-analyses of the randomized trial evidence on these agents. VITAL was a nationwide, randomized, placebo-controlled, 2×2 factorial trial of marine n-3 FAs (1 g/d) and vitamin D3 (2000 IU/d) in the primary prevention of CVD and cancer among 25 871 US men aged ≥50 and women aged ≥55 years, including 5106 blacks. Median treatment duration was 5.3 years. Supplemental n-3 FAs did not significantly reduce the primary cardiovascular end point of major CVD events (composite of myocardial infarction, stroke, and CVD mortality; hazard ratio [HR], 0.92 [95% CI, 0.80-1.06]) but were associated with significant reductions in total myocardial infarction (HR, 0.72 [95% CI, 0.59-0.90]), percutaneous coronary intervention (HR, 0.78 [95% CI, 0.63-0.95]), and fatal myocardial infarction (HR, 0.50 [95% CI, 0.26-0.97]) but not stroke or other cardiovascular end points. For major CVD events, a treatment benefit was seen in those with dietary fish intake below the cohort median of 1.5 servings/wk (HR, 0.81 [95% CI, 0.67-0.98]) but not in those above (P interaction=0.045). For myocardial infarction, the greatest risk reductions were in blacks (HR, 0.23 [95% CI, 0.11-0.47]; P interaction by race, 0.001). Vitamin D supplementation did not reduce major CVD events (HR, 0.97 [95% CI, 0.85-1.12]) or other cardiovascular end points. Updated meta-analyses that include VITAL and other recent trials document coronary risk reduction from supplemental marine n-3 FAs but no clear CVD risk reduction from supplemental vitamin D. Additional research is needed to determine which individuals may be most likely to derive net benefit from supplementation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01169259.

The effect of Omega-3 fatty acid supplementation in systemic lupus erythematosus patients: A systematic review.

OBJECTIVE: Many rheumatologists are inundated with questions about what "natural remedies" and "anti-autoimmune diets" exist for decreasing Systemic Lupus Erythematosus (SLE) disease activity. Over the last three decades, there has been an abundance of data from several different trials about omega-3 fatty acids sourced from fish oil, but the findings have been contradictory. This review seeks to present this data so that evidence-based recommendations can be given to patients, supporting the use of an adjuvant regimen with their present immunosuppression. METHODS: A literature search was conducted using the PubMed, Google Scholar, MEDLINE, and Scopus electronic databases to retrieve relevant articles for this review. Trials conducted on human subjects with SLE with full publications in English were included from 1 January 1980 to 1 April 2021. The impact of fish oil-derived omega-3 fatty acid supplementation on specific clinical features, the innate and adaptive immune response, biomarkers, and disease activity measures were assessed. The initial search yielded 7519 articles, but only 13 met our criteria and were eligible for this review. RESULTS: Data from thirteen articles were assessed. Ten trials assessed disease activity as an outcome, with eight trials demonstrating an improvement in patients in the omega-3 fatty acid group as assessed by a validated clinical tool or individual patient criteria. There was a significant improvement in Systemic Lupus Activity Measure-Revised (SLAM-R) scores at week 12 (p = .009) and week 24 (p < .001). Additionally, a reduction of urinary 8-isoprostane, a non-invasive marker of disease activity, was observed. There was no treatment benefit seen with respect to renal parameters such as serum creatinine or 24-hour urine protein; or systemic parameters such as C3, C4, or anti-double stranded DNA (anti-dsDNA) levels regardless of the dose of the omega-3 LUPUS fatty acids or duration of the trial. CONCLUSION: While there is conflicting evidence about the benefits of omega-3 fatty acid supplementation on SLE disease activity, specific measures have demonstrated benefits. Current data show that there is a potential benefit on disease activity as demonstrated by SLAM-R, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and British Isles Lupus Assessment Group (BILAG) scores and plasma membrane arachidonic acid composition and urinary 8-isoprostane levels, with minimal adverse events.

Omega-6 sparing effects of parenteral lipid emulsions-an updated systematic review and meta-analysis on clinical outcomes in critically ill patients.

BACKGROUND: Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed. RESULTS: 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care. CONCLUSION: Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact. Trial registration PROSPERO international prospective database of systematic reviews (CRD42021259238).

Hospital change to mixed lipid emulsion from soybean oil-based lipid emulsion for parenteral nutrition in hospitalized and critically ill adults improves outcomes: a pre-post-comparative study.

INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes. METHODS: We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort. RESULTS: We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95-0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87-0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82-0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (- 1.6, 95% CI - 2.8 to - 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26-0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients. CONCLUSION: 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.

Associations of baseline use of fish oil with progression of cardiometabolic multimorbidity and mortality among patients with hypertension: a prospective study of UK Biobank.

PURPOSE: The role of fish oil in the prognosis of hypertensive patients is unknown. This study investigated the associations of fish oil supplementation with the progression of cardiometabolic multimorbidity (CMM) and mortality among patients with hypertension. METHODS: Based on UK Biobank, we enrolled participants with hypertension and free of other cardiometabolic diseases. The exposure was baseline use of fish oil derived from questionnaires at baseline. The primary outcomes were the incidence of CMM and all-cause mortality. Competing risk models and flexible parametric proportion-hazards models were fitted to assess the adjusted hazard ratios (HRs) for the risk of CMM and mortality outcomes, respectively. RESULTS: Among 81,579 participants involved [50.37%, men; mean age, 59.38 years (standard deviation, 7.23 years)], 15,990 CMM events and 6456 all-cause deaths were reported (median follow-up, 12.23 years). In multivariable-adjusted models, baseline use of fish oil was associated with 8% lower risk of CMM [95% confidence interval (95% CI) 0.89-0.96, P < 0.001] and 10% lower risk of all-cause mortality (95% CI 0.85-0.95, P < 0.001). CONCLUSION: In individuals with hypertension, baseline use of fish oil was associated with a reduced risk of CMM and all-cause mortality, and further clinical trials are needed to prove this hypothesis.

Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors.

Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. The expression of signaling molecules in tumors was determined by measuring either mRNA or protein expression. Compared with doxorubicin alone, combination treatment resulted in lower tumor sizes and fewer overall metastasis, lower GPR-40 mRNA levels, and higher expression of all selenoproteins. Doxorubicin-FO/Se combination treatment decreased expression of membrane EGFR and FGFR, down-regulated downstream PI3K/AKT/mTOR, MAPK/ERK, and JAK2/c-Src/STAT3 signaling, increased tumor suppressor PTEN/TSC1/TSC2 expression and P53 activation, and suppressed oncogenic transcription factor expression. Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.

Effects of marine-derived and plant-derived omega-3 polyunsaturated fatty acids on erythrocyte fatty acid composition in type 2 diabetic patients.

BACKGROUND: Dietary fatty acids intake affects the composition of erythrocyte fatty acids, which is strongly correlated with glycolipid metabolism disorders. This study aimed at investigating the different effects of marine-derived and plant-derived omega-3 polyunsaturated fatty acid (n-3 PUFA) on the fatty acids of erythrocytes and glycolipid metabolism in patients with type 2 diabetes mellitus (T2DM). METHODS: The randomized double-blinded trial that was performed on 180 T2DM patients. The participants were randomly assigned to three groups for the six-month intervention. The participants were randomly assigned to three groups for the six-month intervention. The fish oil (FO) group was administered with FO at a dose of 3 g/day containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the perilla oil (PO) group was administered with PO at a dose of 3 g/day containing α-linolenic (ALA), the linseed and fish oil (LFO) group was administered with mixed linseed and fish oil at a dose of 3 g/day containing EPA, DHA and ALA. Demographic information were collected and anthropometric indices, glucose and lipid metabolism indexes, erythrocyte fatty acid composition were measured. Statistical analyses were performed using two-way ANOVA. RESULTS: A total of 150 patients finished the trial, with 52 of them in the FO group, 50 in the PO group and 48 in the LFO group. There were significant effects of time × treatment interaction on fast blood glucose (FBG), insulin, HOMA-IR and C-peptide, TC and triglyceride (TG) levels (P < 0.001). Glucose and C-peptide in PO and LFO groups decreased significantly and serum TG in FO group significantly decreased (P < 0.001) after the intervention. Erythrocyte C22: 5 n-6, ALA, DPA, n-6/n-3 PUFA, AA/EPA levels in the PO group were significantly higher than FO and LFO groups, while EPA, total n-3 PUFA and Omega-3 index were significantly higher in the FO and LFO groups compared to PO group. CONCLUSION: Supplementation with perilla oil decreased FBG while fish oil supplementation decreased the TG level. Marine-based and plant-based n-3 PUFAs exhibit different effects on fatty acid compositions of erythrocytes and regulated glycolipid metabolism. TRIAL REGISTRATION: This trial was recorded under Chinese Clinical Trial Registry Center (NO: ChiCTR-IOR-16008435 ) on May 28 2016.