Omega-3 (n-3) Fatty Acid-Statin Interaction: Evidence for a Novel Therapeutic Strategy for Atherosclerotic Cardiovascular Disease.

Managing atherosclerotic cardiovascular disease (ASCVD) often involves a combination of lifestyle modifications and medications aiming to decrease the risk of cardiovascular outcomes, such as myocardial infarction and stroke. The aim of this article is to discuss possible omega-3 (n-3) fatty acid-statin interactions in the prevention and treatment of ASCVD and to provide evidence to consider for clinical practice, highlighting novel insights in this field. Statins and n-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) are commonly used to control cardiovascular risk factors in order to treat ASCVD. Statins are an important lipid-lowering therapy, primarily targeting low-density lipoprotein cholesterol (LDL-C) levels, while n-3 fatty acids address triglyceride (TG) concentrations. Both statins and n-3 fatty acids have pleiotropic actions which overlap, including improving endothelial function, modulation of inflammation, and stabilizing atherosclerotic plaques. Thus, both statins and n-3 fatty acids potentially mitigate the residual cardiovascular risk that remains beyond lipid lowering, such as persistent inflammation. EPA and DHA are both substrates for the synthesis of so-called specialized pro-resolving mediators (SPMs), a relatively recently recognized feature of their ability to combat inflammation. Interestingly, statins seem to have the ability to promote the production of some SPMs, suggesting a largely unrecognized interaction between statins and n-3 fatty acids with relevance to the control of inflammation. Although n-3 fatty acids are the major substrates for the production of SPMs, these signaling molecules may have additional therapeutic benefits beyond those provided by the precursor n-3 fatty acids themselves. In this article, we discuss the accumulating evidence that supports SPMs as a novel therapeutic tool and the possible statin-n-3 fatty acid interactions relevant to the prevention and treatment of ASCVD.

A health technology assessment of personalized nutrition interventions using the EUnetHTA HTA Core Model.

OBJECTIVES: Poor nutrition links to chronic diseases, emphasizing the need for optimized diets. The EU-funded project PREVENTOMICS, introduced personalized nutrition to address this. This study aims to perform a health technology assessment (HTA) comparing personalized nutrition interventions developed through this project, with non-personalized nutrition interventions (control) for people with normal weight, overweight, or obesity. The goal is to support decisions about further development and implementation of personalized nutrition. METHODS: The PREVENTOMICS interventions were evaluated using the European Network for HTA Core Model, which includes a methodological framework that encompasses different domains for value assessment. Information was gathered via [1] different statistical analyses and modeling studies, [2] questions asked of project partners and, [3] other (un)published materials. RESULTS: Clinical trials of PREVENTOMICS interventions demonstrated different body mass index changes compared to control; differences ranged from -0.80 to 0.20 kg/m2. Long-term outcome predictions showed generally improved health outcomes for the interventions; some appeared cost-effective (e.g., interventions in UK). Ethical concerns around health inequality and the lack of specific legal regulations for personalized nutrition interventions were identified. Choice modeling studies indicated openness to personalized nutrition interventions; decisions were primarily affected by intervention's price. CONCLUSIONS: PREVENTOMICS clinical trials have shown promising effectiveness with no major safety concerns, although uncertainties about effectiveness exist due to small samples (n=60-264) and short follow-ups (10-16 weeks). Larger, longer trials are needed for robust evidence before implementation could be considered. Among other considerations, developers should explore financing options and collaborate with policymakers to prevent exclusion of specific groups due to information shortages.

Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles: a randomized, controlled crossover trial.

BACKGROUND: Extracellular vesicles (EVs) are proposed to play a role in the development of cardiovascular diseases (CVDs) and are considered emerging markers of CVDs. n-3 PUFAs are abundant in oily fish and fish oil and are reported to reduce CVD risk, but there has been little research to date examining the effects of n-3 PUFAs on the generation and function of EVs. OBJECTIVES: We aimed to investigate the effects of fish oil supplementation on the number, generation, and function of EVs in subjects with moderate risk of CVDs. METHODS: A total of 40 participants with moderate risk of CVDs were supplemented with capsules containing either fish oil (1.9 g/d n-3 PUFAs) or control oil (high-oleic safflower oil) for 12 wk in a randomized, double-blind, placebo-controlled crossover intervention study. The effects of fish oil supplementation on conventional CVD and thrombogenic risk markers were measured, along with the number and fatty acid composition of circulating and platelet-derived EVs (PDEVs). PDEV proteome profiles were evaluated, and their impact on coagulation was assessed using assays including fibrin clot formation, thrombin generation, fibrinolysis, and ex vivo thrombus formation. RESULTS: n-3 PUFAs decreased the numbers of circulating EVs by 27%, doubled their n-3 PUFA content, and reduced their capacity to support thrombin generation by >20% in subjects at moderate risk of CVDs. EVs derived from n-3 PUFA-enriched platelets in vitro also resulted in lower thrombin generation, but did not alter thrombus formation in a whole blood ex vivo assay. CONCLUSIONS: Dietary n-3 PUFAs alter the number, composition, and function of EVs, reducing their coagulatory activity. This study provides clear evidence that EVs support thrombin generation and that this EV-dependent thrombin generation is reduced by n-3 PUFAs, which has implications for prevention and treatment of thrombosis. CLINICAL TRIAL REGISTRY: This trial was registered at clinicaltrials.gov as NCT03203512.

Combining proteins with n-3 PUFAs (EPA + DHA) and their inflammation pro-resolution mediators for preservation of skeletal muscle mass.

The optimal feeding strategy for critically ill patients is still debated, but feeding must be adapted to individual patient needs. Critically ill patients are at risk of muscle catabolism, leading to loss of muscle mass and its consequent clinical impacts. Timing of introduction of feeding and protein targets have been explored in recent trials. These suggest that "moderate" protein provision (maximum 1.2 g/kg/day) is best during the initial stages of illness. Unresolved inflammation may be a key factor in driving muscle catabolism. The omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are substrates for synthesis of mediators termed specialized pro-resolving mediators or SPMs that actively resolve inflammation. There is evidence from other settings that high-dose oral EPA + DHA increases muscle protein synthesis, decreases muscle protein breakdown, and maintains muscle mass. SPMs may be responsible for some of these effects, especially upon muscle protein breakdown. Given these findings, provision of EPA and DHA as part of medical nutritional therapy in critically ill patients at risk of loss of muscle mass seems to be a strategy to prevent the persistence of inflammation and the related anabolic resistance and muscle loss.

Omega-3 fatty acid supplementation affects tryptophan metabolism during a 12-week endurance training in amateur runners: a randomized controlled trial.

The effects of long-term omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation during endurance training on tryptophan (Trp) metabolism and mental state of healthy individuals have not been evaluated so far. Concentrations of plasma Trp, its metabolites and IL-6 were assessed in 26 male runners before and after a 12-week training program combined with supplementation of n-3 PUFAs (O-3 + TRAIN group) or medium chain triglycerides (MCTs; TRAIN group). After the 12-week program participants' mood before and after stress induction was also assessed. The effects of the same supplementation protocol were evaluated also in 14 inactive subjects (O-3 + SEDEN group). Concentrations of 3-hydroxykynurenine (3-HK) and picolinic acid (PA) significantly increased only in the O-3 + TRAIN group (p = 0.01; [Formula: see text] = 0.22 and p = 0.01; [Formula: see text]= 0.26). Favorable, but not statistically significant changes in the concentrations of kynurenic acid (KYNA) (p = 0.06; [Formula: see text]= 0.14), xanthurenic acid (XA) (p = 0.07; [Formula: see text]= 0.13) and 3-hydroxyanthranilic acid (3-HAA) (p = 0.06; [Formula: see text]= 0.15) and in the ratio of neurotoxic to neuroprotective metabolites were seen also only in the O-3 + TRAIN group. No changes in mood and IL-6 concentrations were observed in either group. Supplementation with n-3 PUFAs during endurance training has beneficial effects on Trp's neuroprotective metabolites.Trial registry: This study was registered at ClinicalTrials.gov with identifier NCT05520437 (14/07/2021 first trial registration and 2018/31/N/NZ7/02962 second trial registration).

LC-ESI-HRMS - lipidomics of phospholipids : Characterization of extraction, chromatography and detection parameters.

Lipids are a diverse class of molecules involved in many biological functions including cell signaling or cell membrane assembly. Owing to this relevance, LC-MS/MS-based lipidomics emerged as a major field in modern analytical chemistry. Here, we thoroughly characterized the influence of MS and LC settings - of a Q Exactive HF operated in Full MS/data-dependent MS2 TOP N acquisition mode - in order to optimize the semi-quantification of polar lipids. Optimization of MS-source settings improved the signal intensity by factor 3 compared to default settings. Polar lipids were separated on an ACQUITY Premier CSH C18 reversed-phase column (100 × 2.1 mm, 1.7 µm, 130 Å) during an elution window of 28 min, leading to a sufficient number of both data points across the chromatographic peaks, as well as MS2 spectra. Analysis was carried out in positive and negative ionization mode enabling the detection of a broader spectrum of lipids and to support the structural characterization of lipids. Optimal sample preparation of biological samples was achieved by liquid-liquid extraction using MeOH/MTBE resulting in an excellent extraction recovery > 85% with an intra-day and inter-day variability < 15%. The optimized method was applied on the investigation of changes in the phospholipid pattern in plasma from human subjects supplemented with n3-PUFA (20:5 and 22:6). The strongest increase was observed for lipids bearing 20:5, while 22:4 bearing lipids were lowered. Specifically, LPC 20:5_0:0 and PC 16:0_20:5 were found to be strongest elevated, while PE 18:0_22:4 and PC 18:2_18:2 were decreased by n3-PUFA supplementation. These results were confirmed by targeted LC-MS/MS using commercially available phospholipids as standards.

The impact of fish oil and/or probiotics on serum fatty acids and the interaction with low-grade inflammation in pregnant women with overweight and obesity: secondary analysis of a randomised controlled trial.

N-3 long-chain PUFA (LC-PUFA) and probiotics are generally considered to induce health benefits. The objective was to investigate (1) the impact of fish oil and/or probiotics on serum fatty acids (sFA), (2) the interaction of sFA with low-grade inflammation and (3) the relation of sFA to the onset of gestational diabetes mellitus (GDM). Pregnant women with overweight/obesity were allocated into intervention groups with fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo in early pregnancy (fish oil: 1·9 g DHA and 0·22 g EPA, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 CFU, each daily). Blood samples were collected in early (n 431) and late pregnancy (n 361) for analysis of fatty acids in serum phosphatidylcholine (PC), cholesteryl esters (CE), TAG and NEFA with GC and high-sensitivity C-reactive protein and GlycA by immunoassay and NMR spectroscopy, respectively. GDM was diagnosed according to 2 h 75 g oral glucose tolerance test. EPA in PC, CE and TAG and DHA in PC, CE, TAG and NEFA were higher in fish oil and fish oil + probiotics groups compared with placebo. EPA in serum NEFA was lower in women receiving probiotics compared with women not receiving. Low-grade inflammation was inversely associated with n-3 LC-PUFA, which were related to an increased risk of GDM. Fish oil and fish oil + probiotics consumption increase serum n-3 LC-PUFA in pregnant women with overweight/obesity. Although these fatty acids were inversely related to inflammatory markers, n-3 LC-PUFA were linked with an increased risk for GDM.

Risk assessment of nutrients: There must be a threshold for their effects.

Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety Authority (EFSA). EFSA concluded in 2022 that the intake of added and free sugars should be "as low as possible in the context of a nutritionally adequate diet". That conclusion of EFSA is based on the effects on two surrogate endpoints for an adverse effect found in randomized controlled trials with high sugars intake levels: fasting glucose and fasting triglycerides. The lowest intake levels in these trials were around 10 energy% and at this intake level there were no adverse effects on the two outcomes. This indicates that the adverse effects of sugars have an observable threshold value for these two endpoints. The most appropriate interpretation from the vast amount of data is that currently no definitive conclusion can be drawn on the tolerable upper intake level for dietary sugars. Therefore, EFSA's own guidance would lead to the conclusion that the available data do not allow the setting of an upper limit for added sugars and hence, that more robust data are required to identify the threshold value for intake of sugars.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. METHODS: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. RESULTS: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. CONCLUSION: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Markers of adipose tissue fibrogenesis associate with clinically significant liver fibrosis and are unchanged by synbiotic treatment in patients with NAFLD.

BACKGROUND AND AIMS: Subcutaneous adipose tissue (SAT) dysfunction contributes to NAFLD pathogenesis and may be influenced by the gut microbiota. Whether transcript profiles of SAT are associated with liver fibrosis and are influenced by synbiotic treatment (that changes the gut microbiome) is unknown. We investigated: (a) whether the presence of clinically significant, ≥F2 liver fibrosis associated with adipose tissue (AT) dysfunction, differential gene expression in SAT, and/or a marker of tissue fibrosis (Composite collagen gene expression (CCGE)); and (b) whether synbiotic treatment modified markers of AT dysfunction and the SAT transcriptome. METHODS: Sixty-two patients with NAFLD (60 % men) were studied before and after 12 months of treatment with synbiotic or placebo and provided SAT samples. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. RNA-sequencing and histological analysis of SAT were performed to determine differential gene expression, CCGE and the presence of collagen fibres. Regression modelling and receiver operator characteristic curve analysis were used to test associations with, and risk prediction for, ≥F2 liver fibrosis. RESULTS: Patients with ≥F2 liver fibrosis (n = 24) had altered markers of AT dysfunction and a SAT gene expression signature characterised by enrichment of inflammatory and extracellular matrix-associated genes, compared to those with

Effect of Roux-en-Y Gastric Bypass on circulating oxylipin profile in women with obesity and type 2 diabetes.

BACKGROUND & AIMS: Chronic inflammation associated with obesity directly contributes to metabolic comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for obesity-associated T2D. We investigated the effect of RYGB on the circulating profile of oxylipins derived from arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids as a potential mechanism underlying the metabolic benefits of the surgery. METHODS: Plasma samples were collected from 28 women with obesity and T2D before and 3 months after RYGB. Circulating levels of oxylipins and their precursors, along with biochemical markers of glucose homeostasis, were evaluated using untargeted mass spectrometry and routine biochemical techniques, respectively. RESULTS: No significant changes were observed in the levels of oxylipins derived from EPA and DHA. However, there was an increase in ARA and its derived oxylipins, TXB2 (an inert derivative of TXA2) and PGD2 (Wilcoxon, p ≤ 0.05). Positive correlations were observed between hemoglobin A1c levels and TXB2 as well as ARA levels (Spearman, p ≤ 0.05). CONCLUSIONS: Our data suggest that the anti-inflammatory oxylipins derived from EPA and DHA may not be involved in the metabolic benefits associated with RYGB. However, the findings indicate that the pro-inflammatory oxylipin TXA2 and its precursor ARA may negatively impact glucose homeostasis both before and after RYGB.

Athletes Can Benefit from Increased Intake of EPA and DHA-Evaluating the Evidence.

Fatty fish, which include mackerel, herring, salmon and sardines, and certain species of algae (e.g., Schizochytrium sp., Crytthecodiniumcohnii and Phaeodactylumtricornutum) are the only naturally rich sources of the omega-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are the most biologically active members of the n-3 PUFA family. Limited dietary sources and fluctuating content of EPA and DHA in fish raise concerns about the status of EPA and DHA among athletes, as confirmed in a number of studies. The beneficial effects of EPA and DHA include controlling inflammation, supporting nervous system function, maintaining muscle mass after injury and improving training adaptation. Due to their inadequate intake and beneficial health-promoting effects, athletes might wish to consider using supplements that provide EPA and DHA. Here, we provide an overview of the effects of EPA and DHA that are relevant to athletes and discuss the pros and cons of supplements as a source of EPA and DHA for athletes.

Nutrition and immunity: lessons from coronavirus disease-2019.

This review will provide an overview of the immune system and then describe the effects of frailty, obesity, specific micronutrients and the gut microbiota on immunity and susceptibility to infection including data from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic where relevant. A key role for the immune system is providing host defence against pathogens. Impaired immunity predisposes to infections and to more severe infections and weakens the response to vaccination. A range of nutrients, including many micronutrients, play important roles in supporting the immune system to function. The immune system can decline in later life and this is exaggerated by frailty. The immune system is also weakened with obesity, generalised undernutrition and micronutrient deficiencies, which all result in increased susceptibility to infection. Findings obtained during the SARS-CoV-2 pandemic support what was already known about the effects of ageing, frailty and obesity on immunity and susceptibility to infection. Observational studies conducted during the pandemic also support previous findings that multiple micronutrients including vitamins C, D and E, zinc and selenium and long-chain n-3 fatty acids are important for immune health, but whether these nutrients can be used to treat those already with coronavirus disease discovered in 2019 (COVID-19), particularly if already hospitalised, is uncertain from current inconsistent or scant evidence. There is gut dysbiosis in patients with COVID-19 and studies with probiotics report clinical improvements in such patients. There is an inverse association between adherence to a healthy diet and risk of SARS-CoV-2 infection and hospitalisation with COVID-19 which is consistent with the effects of individual nutrients and other dietary components. Addressing frailty, obesity and micronutrient insufficiency will be important to reduce the burden of future pandemics and nutritional considerations need to be a central part of the approach to preventing infections, optimising vaccine responses and promoting recovery from infection.

Gut microbiology of UK care home residents: a cross-sectional analysis from a randomised controlled trial.

OBJECTIVE: To describe the prevalence of potentially clinically relevant gut pathogens and associations with the carriage of resistant organisms in UK care home residents. METHODS: Stool samples were collected pre-randomisation from care home residents participating in a randomised placebo-controlled trial. Cultivable clinically relevant bacteria were analysed. Antimicrobial susceptibility testing was performed by agar dilution (amoxicillin, co-amoxiclav, gentamicin, trimethoprim, nitrofurantoin, and ciprofloxacin). We also aimed to detect resistance to third-generation cephalosporins, carbapenems, and vancomycin. RESULTS: Stool samples were available for 159/310 residents participating in the trial (51%) from 23 care homes between 2016 and 2018. In total, 402 bacterial isolates were cultured from 158 stool samples and 29 different species were cultured. The five most common species were Escherichia coli (155/158, 98%), Pseudomonas aeruginosa (40/158, 25%), Enterococcus faecalis (35/158, 22%), Enterococcus faecium (30/158, 19%), and Proteus mirabilis (25/158, 16%). Enterobacterales isolates were cultured from 157 samples (99%), and resistance to at least one of the tested antimicrobials was found in 119 of these (76%). There were high levels of variation in outcomes by care home. DISCUSSION: We demonstrated that care home residents harbour significant levels of antimicrobial-resistant organisms in their stool. This work emphasises the importance of both enhanced infection control practices and antimicrobial stewardship programmes to support the appropriate use of antimicrobials in this setting.

The Impact of Linoleic Acid on Infant Health in the Absence or Presence of DHA in Infant Formulas.

Both linoleic acid (LA) and α-linolenic acid (ALA) are essential dietary fatty acids, and a balanced dietary supply of these is of the utmost importance for health. In many countries across the globe, the LA level and LA/ALA ratio in breast milk (BM) are high. For infant formula (IF), the maximum LA level set by authorities (e.g., Codex or China) is 1400 mg LA/100 kcal ≈ 28% of total fatty acid (FA) ≈ 12.6% of energy. The aims of this study are: (1) to provide an overview of polyunsaturated fatty acid (PUFA) levels in BM across the world, and (2) to determine the health impact of different LA levels and LA/ALA ratios in IF by reviewing the published literature in the context of the current regulatory framework. The lipid composition of BM from mothers living in 31 different countries was determined based on a literature review. This review also includes data from infant studies (intervention/cohort) on nutritional needs regarding LA and ALA, safety, and biological effects. The impact of various LA/ALA ratios in IF on DHA status was assessed within the context of the current worldwide regulatory framework including China and the EU. Country averages of LA and ALA in BM range from 8.5-26.9% FA and 0.3-2.65% FA, respectively. The average BM LA level across the world, including mainland China, is below the maximum 28% FA, and no toxicological or long-term safety data are available on LA levels > 28% FA. Although recommended IF LA/ALA ratios range from 5:1 to 15:1, ratios closer to 5:1 seem to promote a higher endogenous synthesis of DHA. However, even those infants fed IF with more optimal LA/ALA ratios do not reach the DHA levels observed in breastfed infants, and the levels of DHA present are not sufficient to have positive effects on vision. Current evidence suggests that there is no benefit to going beyond the maximum LA level of 28% FA in IF. To achieve the DHA levels found in BM, the addition of DHA to IF is necessary, which is in line with regulations in China and the EU. Virtually all intervention studies investigating LA levels and safety were conducted in Western countries in the absence of added DHA. Therefore, well-designed intervention trials in infants across the globe are required to obtain clarity about optimal and safe levels of LA and LA/ALA ratios in IF.

ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit.

Following the new ESPEN Standard Operating Procedures, the previous 2019 guideline to provide best medical nutritional therapy to critically ill patients has been shortened and partially revised. Following this update, we propose this publication as a practical guideline based on the published scientific guideline, but shortened and illustrated by flow charts. The main goal of this practical guideline is to increase understanding and allow the practitioner to implement the Nutrition in the ICU guidelines. All the items discussed in the previous guidelines are included as well as special conditions.

Oxylipin secretion by human CD3+ T lymphocytes in vitro is modified by the exogenous essential fatty acid ratio and life stage.

Immune function changes across the life stages; for example, senior adults exhibit a tendency towards a weaker cell-mediated immune response and a stronger inflammatory response than younger adults. This might be partly mediated by changes in oxylipin synthesis across the life course. Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that modulate immune function and inflammation. A number of PUFAs are precursors to oxylipins, including the essential fatty acids (EFAs) linoleic acid (LA) and α-linolenic acid (ALA). LA and ALA are also substrates for synthesis of longer chain PUFAs. Studies with stable isotopes have shown that the relative amounts of LA and ALA can influence their partitioning by T lymphocytes between conversion to longer chain PUFAs and to oxylipins. It is not known whether the relative availability of EFA substrates influences the overall pattern of oxylipin secretion by human T cells or if this changes across the life stages. To address this, the oxylipin profile was determined in supernatants from resting and mitogen activated human CD3+ T cell cultures incubated in medium containing an EFA ratio of either 5:1 or 8:1 (LA : ALA). Furthermore, oxylipin profiles in supernatants of T cells from three life stages, namely fetal (derived from umbilical cord blood), adults and seniors, treated with the 5:1 EFA ratio were determined. The extracellular oxylipin profiles were affected more by the EFA ratio than mitogen stimulation such that n-3 PUFA-derived oxylipin concentrations were higher with the 5:1 EFA ratio than the 8:1 ratio, possibly due to PUFA precursor competition for lipoxygenases. 47 oxylipin species were measured in all cell culture supernatants. Extracellular oxylipin concentrations were generally higher for fetal T cells than for T cells from adult and senior donors, although the composition of oxylipins was similar across the life stages. The contribution of oxylipins towards an immunological phenotype might be due to the capacity of T cells to synthesize oxylipins rather than the nature of the oxylipins produced.