The impact of an omega-3 fatty acid rich lipid emulsion on fatty acid profiles in critically ill septic patients

Hall, Thomas C.; Bilku, D.; Neal, Christopher P.; Cooke, Jill; Fisk, Helena L.; Calder, Philip C.; Dennison, Ashley R.

doi:10.1016/j.plefa.2016.07.001

Cited by 25 publications

(25 citation statements)

References 39 publications

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“…For example, lipoprotein APOE largely influences DHA half-life, suggesting that fish oil supplementation of APOE4 carriers (at risk of AD) is less efficient to increase DHA in the brain (Chouinard-Watkins and . Parenteral administration of DHA (Omegaven, LipoPlus, SMOFLipid containing 10%-15% fish oil) is also useful to rapidly increase plasma DHA but has been poorly researched in the context of neuroinflammatory diseases, but more commonly in peripheral inflammatory diseases (Hall et al, 2016;Klek, 2016).…”

Section: A Lc-pufa Dietary Interventions To Limit Neuroinflammation mentioning

confidence: 99%

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Layé¹,

Nadjar²,

Joffre³

et al. 2017

Pharmacol Rev

313

190

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Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain.

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Section: A Lc-pufa Dietary Interventions To Limit Neuroinflammation mentioning

confidence: 99%

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Layé¹,

Nadjar²,

Joffre³

et al. 2017

Pharmacol Rev

313

190

View full text Add to dashboard Cite

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“…Several RCTs have also investigated omega-3 supplementation in sepsis over the past two decades; most recently, Hall et al [21] suggested that a reduced ratio of arachidonic acid (AA) to eicosapentaenoic acid and docosahexaenoic acid [AA/(EPA + DHA)] after treatment with omega-3 fatty acids may be associated with improved survival in critically ill patients with sepsis. However, a comprehensive synthesis of these data has not been conducted, and the evidence for benefit remains unclear [2].…”

Section: Introductionmentioning

confidence: 99%

Omega-3 supplementation in patients with sepsis: a systematic review and meta-analysis of randomized trials

Sharma

McIntyre

et al. 2017

Ann. Intensive Care

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BackgroundNutritional supplementation of omega-3 fatty acids has been proposed to modulate the balance of pro- and anti-inflammatory mediators in sepsis. If proved to improve clinical outcomes in critically ill patients with sepsis, this intervention would be easy to implement. However, the cumulative evidence from several randomized clinical trials (RCTs) remains unclear.MethodsWe searched the Cochrane Library, MEDLINE, and EMBASE through December 2016 for RCTs on parenteral or enteral omega-3 supplementation in adult critically ill patients diagnosed with sepsis or septic shock. We analysed the included studies for mortality, intensive care unit (ICU) length of stay, and duration of mechanical ventilation, and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the quality of the evidence for each outcome.ResultsA total of 17 RCTs enrolling 1239 patients met our inclusion criteria. Omega-3 supplementation compared to no supplementation or placebo had no significant effect on mortality [relative risk (RR) 0.85; 95% confidence interval (CI) 0.71, 1.03; P = 0.10; I 2 = 0%; moderate quality], but significantly reduced ICU length of stay [mean difference (MD) −3.79 days; 95% CI −5.49, −2.09; P < 0.0001, I 2 = 82%; very low quality] and duration of mechanical ventilation (MD −2.27 days; 95% CI −4.27, −0.27; P = 0.03, I 2 = 60%; very low quality). However, sensitivity analyses challenged the robustness of these results.ConclusionOmega-3 nutritional supplementation may reduce ICU length of stay and duration of mechanical ventilation without significantly affecting mortality, but the very low quality of overall evidence is insufficient to justify the routine use of omega-3 fatty acids in the management of sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0282-5) contains supplementary material, which is available to authorized users.

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“…N-3 PUFA supplementation was shown to decrease organ dysfunction in septic shock patients, ICU and hospital lengths of stay [ 15 , 22 ]. In the present study, we have shown that DHA significantly reduced norepinephrine needs to maintain the MAP target in septic rats, while EPA did not.…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid, but not eicosapentaenoic acid, improves septic shock-induced arterial dysfunction in rats

et al. 2017

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IntroductionLong chain n-3 fatty acid supplementation may modulate septic shock-induced host response to pathogen-induced sepsis. The composition of lipid emulsions for parenteral nutrition however remains a real challenge in intensive care, depending on their fatty acid content. Because they have not been assessed yet, we aimed at determining the respective effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) during septic shock-induced vascular dysfunction.MethodsIn a peritonitis-induced septic shock model, rats were infused with EPA, DHA, an EPA/DHA mixture or 5% dextrose (D5) during 22 hours. From H18, rats were resuscitated and monitored during 4 hours. At H22, plasma, aorta and mesenteric resistance arteries were collected to perform ex vivo experiments.ResultsWe have shown that septic rats needed an active resuscitation with fluid challenge and norepinephrine treatment, while SHAM rats did not. In septic rats, norepinephrine requirements were significantly decreased in DHA and EPA/DHA groups (10.6±12.0 and 3.7±8.0 μg/kg/min respectively versus 17.4±19.3 μg/kg/min in D5 group, p<0.05) and DHA infusion significantly improved contractile response to phenylephrine through nitric oxide pathway inhibition. DHA moreover significantly reduced vascular oxidative stress and nitric oxide production, phosphorylated IκB expression and vasodilative prostaglandin production. DHA also significantly decreased polyunsaturated fatty acid pro-inflammatory mediators and significantly increased several anti-inflammatory metabolites.ConclusionsDHA infusion in septic rats improved hemodynamic dysfunction through decreased vascular oxidative stress and inflammation, while EPA infusion did not have beneficial effects.

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The impact of an omega-3 fatty acid rich lipid emulsion on fatty acid profiles in critically ill septic patients

Cited by 25 publications

References 39 publications

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Omega-3 supplementation in patients with sepsis: a systematic review and meta-analysis of randomized trials

Docosahexaenoic acid, but not eicosapentaenoic acid, improves septic shock-induced arterial dysfunction in rats

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