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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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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)., (© 2024. The Author(s).)

Delayed wound healing is a devastating complication of diabetes and supplementation with fish oil, a source of anti-inflammatory omega-3 (ω-3) fatty acids including eicosapentaenoic acid (EPA), seems an appealing treatment strategy. However, some studies have shown that ω-3 fatty acids may have a deleterious effect on skin repair and the effects of oral administration of EPA on wound healing in diabetes are unclear. We used streptozotocin-induced diabetes as a mouse model to investigate the effects of oral administration of an EPA-rich oil on wound closure and quality of new tissue formed. Gas chromatography analysis of serum and skin showed that EPA-rich oil increased the incorporation of ω-3 and decreased ω-6 fatty acids, resulting in reduction of the ω-6/ω-3 ratio. On the tenth day after wounding, EPA increased production of IL-10 by neutrophils in the wound, reduced collagen deposition, and ultimately delayed wound closure and impaired quality of the healed tissue. This effect was PPAR-γ-dependent. EPA and IL-10 reduced collagen production by fibroblasts in vitro . In vivo , topical PPAR-γ-blockade reversed the deleterious effects of EPA on wound closure and on collagen organization in diabetic mice. We also observed a reduction in IL-10 production by neutrophils in diabetic mice treated topically with the PPAR-γ blocker. These results show that oral supplementation with EPA-rich oil impairs skin wound healing in diabetes, acting on inflammatory and non-inflammatory cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Burger, Sagiorato, Silva, Candreva, Pacheco, White, Castelucci, Pral, Fisk, Rabelo, Elias-Oliveira, Osório, Consonni, Farias, Vinolo, Lameu, Carlos, Fielding, Whyte, Martinez, Calder and Rodrigues.)

Purpose: This study aimed to investigate the effects of 12 wk of omega-3 fatty acid supplementation during endurance training on omega-3 index (O3I) and indicators of running performance in amateur long-distance runners., Methods: Twenty-six amateur male long-distance runners ≥29 yr old supplemented omega-3 fatty acid capsules (OMEGA group, n = 14; 2234 mg of eicosapentaenoic acid and 916 mg of docosahexaenoic acid daily) or medium-chain triglycerides capsules as placebo (medium-chain triglyceride [MCT] group, n = 12; 4000 mg of MCT daily) during 12 wk of endurance training. Before and after intervention, blood samples were collected for O3I assessment, and an incremental test to exhaustion and a 1500-m run trial were performed., Results: O3I was significantly increased in the OMEGA group (from 5.8% to 11.6%, P < 0.0001). A significant increase in V̇O 2peak was observed in the OMEGA group (from 53.6 ± 4.4 to 56.0 ± 3.7 mL·kg -1 ⋅min -1 , P = 0.0219) without such change in MCT group (from 54.7 ± 6.8 to 56.4 ± 5.9 mL·kg -1 ⋅min -1 , P = 0.1308). A positive correlation between the change in O3I and the change in running economy was observed when data of participants from both groups were combined (-0.1808 ± 1.917, P = 0.0020), without such an effect in OMEGA group alone ( P = 0.1741). No effect of omega-3 supplementation on 1500-m run results was observed., Conclusions: Twelve weeks of omega-3 fatty acid supplementation at a dose of 2234 mg of eicosapentaenoic acid and 916 mg of docosahexaenoic acid daily during endurance training resulted in the improvement of O3I and running economy and increased V̇O 2peak without improvement in the 1500-m run trial time in amateur runners., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: the effect on liver function markers and inflammation of the different content of phytosterols in lipid emulsions (LEs) used in the parenteral nutrition (PN) regimen of adult home PN (HPN) patients is not clear., Methods: plasma phytosterol and cytokine concentrations, fatty acid composition, liver function markers, and triglycerides were measured in 58 adult HPN patients receiving one of three different LEs (soybean oil-based: Intralipid; olive oil-based: ClinOleic; containing fish oil: SMOFLipid)., Results: patients receiving Intralipid had higher plasma campesterol and stigmasterol concentrations than those receiving ClinOleic or SMOFLipid. Plasma sterol concentrations were not different between patients receiving ClinOleic and SMOFLipid. Differences in plasma fatty acids reflected the fatty acid composition of the LEs. Markers of liver function did not differ among the three groups. Blood triglycerides were higher with ClinOleic than with Intralipid or SMOFLipid. Total bilirubin correlated positively with the plasma concentrations of two of the phytosterols, ALT correlated positively with one, AST with one, and GGT with three., Conclusions: liver function markers correlate with plasma plant sterol concentrations in adult HPN patients. Adult HPN patients receiving SMOFLipid are more likely to have liver function markers and triglycerides within the normal range than those receiving ClinOleic or Intralipid. The omega-3 fatty acids in SMOFLipid may act to mitigate the adverse effects of plant sterols on liver function.

It is not fully understood how supplementation with omega-3 fatty acids affects the metabolism of amino acids required for the bioavailability/synthesis of NO, i.e., L-arginine (L-arg), asymmetric dimethylarginine (ADMA), their metabolites, and the L-arg/ADMA ratio and their impact on running economy (RE) in runners. Thus, 26 male amateur endurance runners completed a twelve-week study in which they were divided into two supplemented groups: the OMEGA group (n = 14; 2234 mg and 916 mg of eicosapentaenoic and docosahexaenoic acid daily) or the MCT group (n = 12; 4000 mg of medium-chain triglycerides daily). At the same time, all participants followed an endurance training program. Before and after the 12-week intervention, blood was collected from participants at two time points (at rest and immediately post-exercise) to determine EPA and DHA in red blood cells (RBCs) and plasma levels of L-arg, ADMA, and their metabolites. RBC EPA and DHA significantly increased in the OMEGA group (p < 0.001), which was related to the resting increase in L-arg (p = 0.001) and in the L-arg/ADMA ratio (p = 0.005) with no changes in the MCT group. No differences were found in post-exercise amino acid levels. A total of 12 weeks of omega-3 fatty acid supplementation at a dose of 2234 mg of EPA and 916 mg of DHA daily increased levels of L-arg and the L-arg/ADMA ratio, which indirectly indicates increased bioavailability/NO synthesis. However, these changes were not associated with improved RE in male amateur endurance runners.

Introduction: Substantial response heterogeneity is commonly seen in dietary intervention trials. In larger datasets, this variability can be exploited to identify predictors, for example genetic and/or phenotypic baseline characteristics, associated with response in an outcome of interest., Objective: Using data from a placebo-controlled crossover study (the FINGEN study), supplementing with two doses of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), the primary goal of this analysis was to develop models to predict change in concentrations of plasma triglycerides (TG), and in the plasma phosphatidylcholine (PC) LC n-3 PUFAs eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), after fish oil (FO) supplementation. A secondary goal was to establish if clustering of data prior to FO supplementation would lead to identification of groups of participants who responded differentially., Methods: To generate models for the outcomes of interest, variable selection methods (forward and backward stepwise selection, LASSO and the Boruta algorithm) were applied to identify suitable predictors. The final model was chosen based on the lowest validation set root mean squared error (RMSE) after applying each method across multiple imputed datasets. Unsupervised clustering of data prior to FO supplementation was implemented using k-medoids and hierarchical clustering, with cluster membership compared with changes in plasma TG and plasma PC EPA + DHA., Results: Models for predicting response showed a greater TG-lowering after 1.8 g/day EPA + DHA with lower pre-intervention levels of plasma insulin, LDL cholesterol, C20:3 n -6 and saturated fat consumption, but higher pre-intervention levels of plasma TG, and serum IL-10 and VCAM-1. Models also showed greater increases in plasma PC EPA + DHA with age and female sex. There were no statistically significant differences in PC EPA + DHA and TG responses between baseline clusters., Conclusion: Our models established new predictors of response in TG (plasma insulin, LDL cholesterol, C20:3n-6, saturated fat consumption, TG, IL-10 and VCAM-1) and in PC EPA + DHA (age and sex) upon intervention with fish oil. We demonstrate how application of statistical methods can provide new insights for precision nutrition, by predicting participants who are most likely to respond beneficially to nutritional interventions., Competing Interests: Authors AW and EZ were employed by the Unilever Foods Innovation Centre Wageningen, which markets food products. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Potter, Horgan, Wanders, Zandstra, Zock, Fisk, Minihane, Calder, Mathers and de Roos.)

Introduction: Sore throat is a common reason for overuse of antibiotics. The value of inflammatory or biomarkers in throat swab or saliva samples in predicting benefit from antibiotics is unknown., Methods: We used the 'person-based approach' to develop an online tool to support self-swabbing and recruited adults and children with sore throats through participating general practices and social media. Participants took bacterial and viral swabs and a saliva sponge swab and passive drool sample. Bacterial swabs were cultured for streptococcus (Group A, B, C, F and G). The viral swab and saliva samples were tested using a routine respiratory panel PCR and Covid-19 PCR testing. We used remaining viral swab and saliva sample volume for biomarker analysis using a panel of 13 biomarkers., Results: We recruited 11 asymptomatic participants and 45 symptomatic participants. From 45 symptomatic participants, bacterial throat swab, viral throat swab, saliva sponge and saliva drool samples were returned by 41/45 (91.1%), 43/45 (95.6%), 43/45 (95.6%) and 43/45 (95.6%) participants respectively. Three saliva sponge and 6 saliva drool samples were of insufficient quantity. Two adult participants had positive bacterial swabs. Six participants had a virus detected from at least one sample (swab or saliva). All of the biomarkers assessed were detectable from all samples where there was sufficient volume for testing. For most biomarkers we found higher concentrations in the saliva samples. Due to low numbers, we were not able to compare biomarker concentrations in those who did and did not have a bacterial pathogen detected. We found no evidence of a difference between biomarker concentrations between the symptomatic and asymptomatic participants but the distributions were wide., Conclusions: We have demonstrated that it is feasible for patients with sore throat to self-swab and provide saliva samples for pathogen and biomarker analysis. Typical bacterial and viral pathogens were detected but at low prevalence rates. Further work is needed to determine if measuring biomarkers using oropharyngeal samples can help to differentiate between viral and bacterial pathogens in patients classified as medium or high risk using clinical scores, in order to better guide antibiotic prescribing and reduce inappropriate prescriptions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lown, Miles, Fisk, Smith, Muller, Maund, Rogers, Becque, Hayward, Moore, Little, Glogowska, Hay, Stuart, Mantzourani, Butler, Bostock, Davies, Dickerson, Thompson and Francis.)

Background: Disturbances in protein metabolism and impaired muscle health have been observed in chronic obstructive pulmonary disease (COPD). The ω-3 (n-3) PUFAs EPA and DHA are known for their anti-inflammatory and muscle health-enhancing properties., Objectives: We examined whether daily EPA + DHA supplementation can improve daily protein homeostasis in patients with COPD by reducing postabsorptive whole-body protein breakdown (PB) and enhancing the anabolic response to feeding in a dose-dependent way., Methods: Normal-weight participants with moderate to severe COPD (n = 32) received daily for 4 wk, according to a randomized double-blind placebo controlled 3-group design, a high dose (3.5 g, n = 10) of EPA + DHA, a low dose (2.0 g, n = 10) of EPA + DHA, or placebo (olive oil, n = 12) via gel capsules. At pre- and postintervention, stable isotope tracers were infused to assess postabsorptive netPB [postabsorptive PB - protein synthesis (PS)] and the anabolic response (prandial netPS = prandial PS-PB) to a protein meal. In addition, muscle mass and function were measured., Results: Plasma phosphatidylcholine EPA and DHA concentrations were higher after 4 wk of supplementation in both EPA + DHA groups (P < 0.004), and there was a trend toward higher values for plasma EPA after the high compared with the low dose of EPA + DHA (P = 0.065). Postabsorptive PB was lower after 4 wk of the high dose of EPA + DHA, whereas netPB was lower independent of the dose of EPA + DHA (low dose, P = 0.037; high dose, P = 0.026). Prandial netPS was increased only after the high dose of EPA + DHA (P = 0.03). Extremity lean mass but not muscle function was increased, independent of the EPA + DHA dose (P < 0.05)., Conclusions: Daily n-3 PUFA supplementation for 4 wk induces a shift toward a positive daily protein homeostasis in patients with COPD in part in a dose-dependent way. Daily doses up to 3.5 g EPA and DHA are still well tolerated and lead to protein gain in these patients. This trial was registered at clinicaltrials.gov as NCT01624792., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Obesity is associated with enhanced lipid accumulation and the expansion of adipose tissue accompanied by hypoxia and inflammatory signalling. Investigation in human subcutaneous white adipose tissue (scWAT) in people living with obesity in which metabolic complications such as insulin resistance are yet to manifest is limited, and the mechanisms by which these processes are dysregulated are not well elucidated. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have been shown to modulate the expression of genes associated with lipid accumulation and collagen deposition and reduce the number of inflammatory macrophages in adipose tissue from individuals with insulin resistance. Therefore, these lipids may have positive actions on obesity associated scWAT hypertrophy and inflammation., Methods: To evaluate obesity-associated tissue remodelling and responses to LC n-3 PUFAs, abdominal scWAT biopsies were collected from normal weight individuals and those living with obesity prior to and following 12-week intervention with marine LC n-3 PUFAs (1.1 g EPA + 0.8 g DHA daily). RNA sequencing, qRT-PCR, and histochemical staining were used to assess remodelling- and inflammatory-associated gene expression, tissue morphology and macrophage infiltration., Results: Obesity was associated with scWAT hypertrophy ( P < 0.001), hypoxia, remodelling, and inflammatory macrophage infiltration ( P = 0.023). Furthermore, we highlight the novel dysregulation of Wnt signalling in scWAT in non-insulin resistant obesity. LC n-3 PUFAs beneficially modulated the scWAT environment through downregulating the expression of genes associated with inflammatory and remodelling pathways ( P < 0.001), but there were altered outcomes in individuals living with obesity in comparison to normal weight individuals., Conclusion: Our data identify dysregulation of Wnt signalling, hypoxia, and hypertrophy, and enhanced macrophage infiltration in scWAT in non-insulin resistant obesity. LC n-3 PUFAs modulate some of these processes, especially in normal weight individuals which may be preventative and limit the development of restrictive and inflammatory scWAT in the development of obesity. We conclude that a higher dose or longer duration of LC n-3 PUFA intervention may be needed to reduce obesity-associated scWAT inflammation and promote tissue homeostasis., Clinical Trial Registration: www.isrctn.com, identifier ISRCTN96712688., Competing Interests: PCC undertakes unpaid voluntary work as the current President of the Federation of European Nutrition Societies (FENS) and as Past President of ILSI Europe. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fisk, Childs, Miles, Ayres, Noakes, Paras-Chavez, Antoun, Lillycrop and Calder.)

Background: Obesity is associated with enhanced inflammation. However, investigation in human subcutaneous white adipose tissue (scWAT) is limited and the mechanisms by which inflammation occurs have not been well elucidated. Marine long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and may reduce scWAT inflammation., Methods: Subcutaneous white adipose tissue (scWAT) biopsies were collected from individuals living with obesity (n=45) and normal weight individuals (n=39) prior to and following a 12-week intervention with either 3 g/day of a fish oil concentrate (providing 1.1 g eicosapentaenoic acid (EPA) + 0.8 g docosahexaenoic acid (DHA)) or 3 g/day of corn oil. ScWAT fatty acid, oxylipin, and transcriptome profiles were assessed by gas chromatography, ultra-pure liquid chromatography tandem mass spectrometry, RNA sequencing and qRT-PCR, respectively., Findings: Obesity was associated with greater scWAT inflammation demonstrated by lower concentrations of specialised pro-resolving mediators (SPMs) and hydroxy-DHA metabolites and an altered transcriptome with differential expression of genes involved in LC n-3 PUFA activation, oxylipin synthesis, inflammation, and immune response. Intervention with LC n-3 PUFAs increased their respective metabolites including the SPM precursor 14-hydroxy-DHA in normal weight individuals and decreased arachidonic acid derived metabolites and expression of genes involved in immune and inflammatory response with a greater effect in normal weight individuals., Interpretation: Downregulated expression of genes responsible for fatty acid activation and metabolism may contribute to an inflammatory oxylipin profile and limit the effects of LC n-3 PUFAs in obesity. There may be a need for personalised LC n-3 PUFA supplementation based on obesity status., Funding: European Commission Seventh Framework Programme (Grant Number 244995) and Czech Academy of Sciences (Lumina quaeruntur LQ200111901)., Competing Interests: Declaration of interests P.C. Calder undertakes unpaid voluntary work as the current President of the Federation of European Nutrition Societies (FENS) and as Past President of ILSI Europe. P.C Calder received funding from the European Commission Seventh Framework Programme (Grant Number 244995). O. Kuda received funding from the Czech Academy of Sciences (Lumina quaeruntur LQ200111901). K.A. Lillycrop holds a contract with Benevolent AI Ltd. E.A. Miles received payment from Abbott Nutrition to present at The British Society for Allergy & Clinical Immunology (BSACI) conference in 2019. There are no other declarations of interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

PUFA modulate immune function and have been associated with the risk of childhood atopy and asthma. We investigated the effect of maternal fat intake in mice on PUFA status, elongase and desaturase gene expression, inflammatory markers and lung function in the offspring. C57BL/6J mice (n 32) were fed either standard chow (C, 20·4 % energy as fat) or a high-fat diet (HFD, 39·9 % energy as fat) for 4 weeks prior to conception and during gestation and lactation. At 21 d of age, offspring were weaned onto either the HFD or C, generating four experimental groups: C/C, C/HF, HF/C and HF/HF. Plasma and liver fatty acid composition were measured by GC and gene expression by quantitative PCR. Lung resistance to methacholine was assessed. Arachidonic acid concentrations in offspring plasma and liver phospholipids were increased by HFD; this effect was greater in the post-natal HFD group. DHA concentration in offspring liver phospholipids was increased in response to HFD and was higher in the post-natal HFD group. Post-natal HFD increased hepatic fatty acid desaturase (FADS) 2 and elongation of very long-chain fatty acid 5 expression in male offspring, whereas maternal HFD elevated expression of FADS1 and FADS2 in female offspring compared with males. Post-natal HFD increased expression of IL-6 and C-C motif chemokine ligand 2 (CCL2) in perivascular adipose tissue. The HFD lowered lung resistance to methacholine. Excessive maternal fat intake during development modifies hepatic PUFA status in offspring through regulation of gene expression of enzymes that are involved in PUFA biosynthesis and modifies the development of the offspring lungs leading to respiratory dysfunction.

A glyceride mixture of monoglyceride, diglyceride and TAG increases solubilisation and enhances emulsification of n-3 fatty acid (FA)-containing lipids in the stomach. This allows for better access of digestive enzymes, pivotal for the release of bioactive n-3 FA. The objective was to compare the effect of a glyceride formulation and an ethyl ester formulation of EPA + DHA on concentrations of EPA and DHA in plasma following single dosing. We conducted a double-blind crossover trial in which twenty healthy adults aged 50-70 years consumed a single dose (2·8 g EPA + DHA) of each EPA + DHA formulation without a meal in random order separated by a 2-week washout period. EPA and DHA were measured in plasma total lipid over the following 12 h. EPA and DHA in plasma total lipid increased over 12 h with both formulations. A 10-fold greater Δ concentration of EPA, 3-fold greater Δ concentration of DHA and 5-fold greater Δ concentration of EPA + DHA were seen with the glyceride-EPA + DHA. The time at which the maximal concentrations of n-3 FA occurred was 4 h earlier for EPA, 1 h earlier for DHA and 2 h earlier for EPA + DHA when consuming glyceride-EPA + DHA. A mixture of monoglyceride, diglyceride and TAG results in greater and faster incorporation of EPA and DHA into blood plasma lipid in the absence of a fatty meal. This may provide benefit to individuals on a low-fat diet or with digestive impairments and could result in greater efficacy in clinical trials using n-3 FA.

Background & Aims: Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs)., Methods: Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18-65 years with type-2 diabetes mellitus and body mass index 30-50 kg/m 2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group., Results: Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group., Conclusion: One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation., Trial Registration: ClinicalTrials.gov Identifier NCT02459561., Competing Interests: Conflict of interest AR reports personal fees from GI Dynamics during the conduct of the study. AG reports funding supported by UK Medical Research Council and Wellcome Trust outside of the submitted work. JPT received travel fees support from GI Dynamics. The remaining authors report no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aging is associated with changes to the immune system, collectively termed immunosenescence and inflammageing. However, the relationships among age, frailty, and immune parameters in older people resident in care homes are not well described. We assessed immune and inflammatory parameters in 184 United Kingdom care home residents aged over 65 years and how they relate to age, frailty index, and length of care home residence. Linear regression was used to identify the independent contribution of age, frailty, and length of care home residence to the various immune parameters as dependent variables. Participants had a mean age (±SD) of 85.3 ± 7.5 years, had been residing in the care home for a mean (±SD) of 1.9 ± 2.2 years at the time of study commencement, and 40.7% were severely frail. Length of care home residence and frailty index were correlated but age and frailty index and age and length of care home residence were not significantly correlated. All components of the full blood count, apart from total lymphocytes, were within the reference range; 31% of participants had blood lymphocyte numbers below the lower value of the reference range. Among the components of the full blood count, platelet numbers were positively associated with frailty index. Amongst plasma inflammatory markers, C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1ra), soluble E-selectin and interferon gamma-induced protein 10 (IP-10) were positively associated with frailty. Plasma soluble vascular cell adhesion molecule 1 (sVCAM-1), IP-10 and tumor necrosis factor receptor II (TNFRII) were positively associated with age. Plasma monocyte chemoattractant protein 1 was positively associated with length of care home residence. Frailty was an independent predictor of platelet numbers, plasma CRP, IL-1ra, IP-10, and sE-selectin. Age was an independent predictor of activated monocytes and plasma IP-10, TNFRII and sVCAM-1. Length of care home residence was an independent predictor of plasma MCP-1. This study concludes that there are independent links between increased frailty and inflammation and between increased age and inflammation amongst older people resident in care homes in the United Kingdom. Since, inflammation is known to contribute to morbidity and mortality in older people, the causes and consequences of inflammation in this population should be further explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Castro-Herrera, Lown, Fisk, Owen-Jones, Lau, Lowe, Hood, Gillespie, Hobbs, Little, Butler, Miles and Calder.)

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [ Lacticaseibacillus (previously known as Lactobacillus ) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis , BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67-97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3-1.6 × 10 9 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly ( p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%)., Competing Interests: PC has acted as a consultant to Chr. Hansen, but not in the context of this trial. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Castro-Herrera, Fisk, Wootton, Lown, Owen-Jones, Lau, Lowe, Hood, Gillespie, Hobbs, Little, Butler, Miles and Calder.)

The fatty acid composition of human follicular fluid is important for oocyte development and for pregnancy following in vitro fertilization (IVF). This study investigated whether a dietary intervention that included an increase in marine omega-3 fatty acids, olive oil and vitamin D alters the fatty acid composition of human follicular fluid. The association of lifestyle factors with follicular fluid fatty acid composition was also investigated. Fifty-five couples awaiting IVF were randomized to receive the 6-week treatment intervention of olive oil for cooking, an olive oil-based spread, and a daily supplement drink enriched with vitamin D and the marine omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and 56 couples were randomized to receive placebo equivalents. Dietary questionnaires were completed, and samples of blood were taken before and after the intervention. Follicular fluid was collected at oocyte retrieval and the fatty acid profile assessed using gas chromatography. In the control group, individual fatty acids in red blood cells and follicular fluid were significantly correlated. Furthermore, a healthier diet was associated with a lower percentage of follicular fluid arachidonic acid. The follicular fluid of women in the treatment group contained significantly higher amounts of EPA and DHA compared to the control group, while the omega-6 fatty acids linoleic, γ-linolenic, dihomo-γ-linolenic, and arachidonic were lower. This is the first report of a dietary intervention altering the fatty acid composition of follicular fluid in humans. Further research is required to determine whether this intervention improves oocyte quality., (© 2020 The Authors. Lipids published by Wiley Periodicals LLC on behalf of American Oil Chemists' Society.)

Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5-25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30-40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background and Aims: Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes)., Methods: In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22)., Results: On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04)., Conclusions: It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. CLINICALTRIALS., Gov Number: NCT01745861., Eu Clinical Trials Register: EudraCT (2010-018660-16)., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To study the impact of increased dietary intake of omega-3 fatty acids, vitamin D, and olive oil for 6 weeks before in vitro fertilization (IVF) or IVF-intracytoplasmic sperm injection (ICSI) on morphokinetic markers of early embryo development., Design: A double-blinded randomized controlled trial., Setting: Academic IVF unit., Patient(s): A total of 111 couples undergoing IVF or IVF-ICSI were recruited., Interventions(s): Fifty-five couples received the 6-week study intervention of a daily supplement drink enriched with omega-3 fatty acids and vitamin D plus additional olive oil and olive oil-based spread, and 56 couples received the control intervention., Main Outcome Measure(s): The primary end point for the study was the time taken for completion of the second cell cycle after fertilization (CC2). Secondary end points included time to complete the third and fourth cell cycles (CC3 and CC4), the synchrony of the second and third cell cycles (S2 and S3), and the day 3 and day 5 Known Implantation Data Scores (KIDScores)., Result(s): There was no difference in CC2 between the two groups. However, CC4 was accelerated in the study group compared with the control group, and a significantly shortened S3 as well as an increase in KIDScore on day 3 were observed, indicating improved embryo quality in the study group., Conclusion(s): This study demonstrates that a short period of dietary supplementation alters the rate of embryo cleavage. Further research is required to investigate the mechanisms that regulate this effect, and whether the impact on embryo development translates into improved clinical outcomes., Clinical Trial Registration Number: ISRCTN50956936., (Copyright © 2019 American Society for Reproductive Medicine. All rights reserved.)

Compared with omnivorous mothers, vegetarian mothers have lower intakes of some nutrients required for neurological development. However, there is a lack of information about the impact of vegetarianism during pregnancy on subsequent cognitive function in children. The aim of this study was to investigate whether vegetarianism during pregnancy is associated with altered maternal nutritional status and with cognitive function in children at six to seven years of age. Women aged 20-34 years participating in a prospective observational study who provided dietary data and blood samples in early pregnancy (11 weeks; 78 vegetarians and 2144 omnivores) or late pregnancy (34 weeks; 91 vegetarians and 2552 omnivores). Compared with omnivorous women, vegetarian women had lower blood concentrations of arachidonic acid, docosahexaenoic acid, and cobalamin in early and late pregnancy. Vegetarianism in pregnancy was linked to higher maternal educational attainment, longer breastfeeding duration, lower incidence of smoking during pregnancy and a tendency towards higher IQ in the mothers. Concentrations of some nutrients required for neurodevelopment were lower in maternal blood during gestation; however, after controlling for confounders consuming a vegetarian diet during pregnancy was not associated with poorer neurocognitive development of the children in this study., Competing Interests: K.M.G. and G.C.B. have received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and are, or have been, part of an academic consortium that received research funding from Abbott Nutrition, Nestec and Danone. P.C.C. is a consultant to Danone/Nutricia, DSM, Pronova BioPharma, Cargill and Smartfish and has received speaking honoraria from Danone, DSM, Smartfish and Abbott Nutrition. G.C.B. has been an advisor to BASF. None of the other authors had disclosures to report. None of the authors has any conflicts of interest to declare.

There is no consensus on the effects of omega-3 (ω-3) fatty acids (FA) on cutaneous repair. To solve this problem, we used 2 different approaches: (1) FAT-1 transgenic mice, capable of producing endogenous ω-3 FA; (2) wild-type (WT) mice orally supplemented with DHA-enriched fish oil. FAT-1 mice had higher systemic (serum) and local (skin tissue) ω-3 FA levels, mainly docosahexaenoic acid (DHA), in comparison with WT mice. FAT-1 mice had increased myeloperoxidase (MPO) activity and content of CXCL-1 and CXCL-2, and reduced IL-10 in the skin wound tissue three days after the wound induction. Inflammation was maintained by an elevated TNF-α concentration and presence of inflammatory cells and edema. Neutrophils and macrophages, isolated from FAT-1 mice, also produced increased TNF-α and reduced IL-10 levels. In these mice, the wound closure was delayed, with a wound area 6-fold bigger in relation with WT group, on the last day of analysis (14 days post-wounding). This was associated with poor orientation of collagen fibers and structural aspects in repaired tissue. Similarly, DHA group had a delay during late inflammatory phase. This group had increased TNF-α content and CD45+F4/80+ cells at the third day after skin wounding and increased concentrations of important metabolites derived from ω-3, like 18-HEPE, and reduced concentrations of those from ω-6 FA. In conclusion, elevated DHA content, achieved in both FAT-1 and DHA groups, slowed inflammation resolution and impaired the quality of healed skin tissue., (© 2019 The Author(s).)

Wound healing is an essential process for organism survival. Some fatty acids have been described as modulators of wound healing. However, the role of omega-3 fatty acids is unclear. In the present work, we investigate the effects of oral administration of eicosapentaenoic acid (EPA)-rich oil on wound healing in mice. After 4 weeks of EPA-rich oil supplementation (2 g/kg of body weight), mice had increased serum concentrations of EPA (20:5ω-3) (6-fold) and docosahexaenoic acid (DHA; 22:6ω-3) (33%) in relation to control mice. Omega-3 fatty acids were also incorporated into skin in the EPA fed mice. The wound healing process was delayed at the 3 rd and 7 th days after wounding in mice that received EPA-rich oil when compared to control mice but there was no effect on the total time required for wound closure. Collagen reorganization, that impacts the quality of the wound tissue, was impaired after EPA-rich oil supplementation. These effects were associated with an increase of M2 macrophages (twice in relation to control animals) and interleukin-10 (IL-10) concentrations in tissue in the initial stages of wound healing. In the absence of IL-10 (IL-10 -/- mice), wound closure and organization of collagen were normalized even when EPA was fed, supporting that the deleterious effects of EPA-rich oil supplementation were due to the excessive production of IL-10. In conclusion, oral administration of EPA-rich oil impairs the quality of wound healing without affecting the wound closure time likely due to an elevation of the anti-inflammatory cytokine IL-10.

Background: The effect of different lipid emulsions (LEs) within the parenteral nutrition (PN) regimen of adult home PN (HPN) patients is not clear. This study investigated the effect of changing adult HPN patients from a soybean oil based LE (Intralipid) to either a fish oil containing LE (providing n-3 fatty acids) (SMOFLipid) or an olive oil based LE (ClinOleic)., Methods: Thirty two adults receiving long-term HPN with Intralipid as the LE were transferred to receive either SMOFLipid (n = 13) or ClinOleic (n = 19) for 60 days. Liver function markers, cholesterol, triglycerides, a full profile of fatty acids, and several cytokines were measured at study entry and after 60 days., Results: SMOFLipid did not affect liver function markers, blood lipids or plasma cytokines. ClinOleic lowered both gamma-glutamyltranspeptidase (P = 0.044) and interleukin-8 (P = 0.030) concentrations. Both LEs induced marked changes in the fatty acid profile of plasma. SMOFLipid resulted in significant decreases in the proportions of linoleic acid, several other n-6 fatty acids and the essential fatty acid (EFA) deficiency indicator mead acid and significant increases in the proportions of the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. ClinOleic resulted in significant decreases in the proportions of some saturated fatty acids, linoleic acid, several n-6 fatty acids, all n-3 fatty acids and mead acid and a significant increase in the proportion of oleic acid. The ratio of mead to arachidonic acid in plasma was not altered by either SMOFLipid or ClinOleic. No patient had a mead acid to arachidonic acid ratio of >0.2, the cut-off used to indicate EFA deficiency., Conclusion: Both SMOFLipid and ClinOleic significantly alter the fatty acid profile of plasma in adult HPN patients previously using Intralipid. Neither LE induces EFA deficiency in these patients. SMOFLipid did not alter liver function markers or inflammation. In contrast, ClinOleic decreased some, though not all, markers of liver function and inflammation. SMOFLipid and ClinOleic may both be considered for use in adult HPN patients., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone gastrointestinal surgery. Limited information, however, is available on the benefits of nutritional supplementation enriched with arginine and n-3 fatty acids in patients undergoing liver resection., Aim: To evaluate the effects of preoperative nutritional supplementation enriched with arginine and n -3 fatty acids on inflammatory and immunologic markers and clinical outcome in patients undergoing liver resection., Methods: Thirty-four patients undergoing liver resection were randomized to either five days of preoperative Impact ® [1020 kcal/d, immunonutrition (IMN) group], or standard care [no supplementation, standard care (STD) group]. Nutritional status was measured at study entry by subjective global assessment (SGA). Functional assessments (grip strength, fatigue and performance status) were carried out at study entry, on the day prior to surgery, and on postoperative day (POD) 7 and 30. Inflammatory and immune markers were measured at study entry, on the day prior to surgery, and POD 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively until POD30., Results: A total of 32 patients (17 IMN and 15 STD) were analysed. All except four patients were SGA class A. The plasma ratio of (eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid was higher in IMN patients on the day prior to surgery and POD 1, 3, 5 and 7 ( P < 0.05). Plasma interleukin (IL)-6 concentrations were elevated in the IMN group ( P = 0.017 for POD7). No treatment effect was detected for functional measures, immune response (white cell count and total lymphocytes) or markers of inflammation (C-reactive protein, tumour necrosis factor-α, IL-8, IL-10). There were 10 patients with infectious complications in the IMN group and 4 in the STD group ( P = 0.087). Median hospital stay was 9 (range 4-49) d in the IMN group and 8 (3-34) d in the STD group ( P = 0.476)., Conclusion: In well-nourished patients undergoing elective liver resection, this study failed to show any benefit of preoperative immunonutrition., Competing Interests: Conflict-of-interest statement: None of the authors has any conflicts of interest related to this study.

n-3 Fatty acids are associated with better cardiovascular and cognitive health. However, the concentration of EPA, DPA and DHA in different plasma lipid pools differs and factors influencing this heterogeneity are poorly understood. Our aim was to evaluate the association of oily fish intake, sex, age, BMI and APOE genotype with concentrations of EPA, DPA and DHA in plasma phosphatidylcholine (PC), NEFA, cholesteryl esters (CE) and TAG. Healthy adults (148 male, 158 female, age 20-71 years) were recruited according to APOE genotype, sex and age. The fatty acid composition was determined by GC. Oily fish intake was positively associated with EPA in PC, CE and TAG, DPA in TAG, and DHA in all fractions (P≤0·008). There was a positive association between age and EPA in PC, CE and TAG, DPA in NEFA and CE, and DHA in PC and CE (P≤0·034). DPA was higher in TAG in males than females (P<0·001). There was a positive association between BMI and DPA and DHA in TAG (P<0·006 and 0·02, respectively). APOE genotype×sex interactions were observed: the APOE4 allele associated with higher EPA in males (P=0·002), and there was also evidence for higher DPA and DHA (P≤0·032). In conclusion, EPA, DPA and DHA in plasma lipids are associated with oily fish intake, sex, age, BMI and APOE genotype. Such insights may be used to better understand the link between plasma fatty acid profiles and dietary exposure and may influence intake recommendations across population subgroups.

Objectives: Findings relating to dietary intake of n-3 polyunsaturated fatty acids (PUFA) and risk of rheumatoid arthritis (RA) are mixed. Erythrocyte membrane PUFA is an accurate objective biomarker of PUFA status; however, there are little data on erythrocyte membrane PUFA and risk of RA. The objective was therefore to compare erythrocyte membrane PUFA between pre-RA individuals and matched controls from a population-based sample, and specifically to test the hypothesis that higher levels of longer chain n-3 PUFA are associated with lower risk of RA., Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC) is a large European prospective cohort study of apparently healthy populations. We undertook a nested case-control study by identifying RA cases with onset after enrolment (pre-RA) in four EPIC cohorts in Italy and Spain. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. Conditional logistic regression analysis was used to estimate associations of PUFA with the development of RA, adjusting for potential confounders including body mass index, waist circumference, education level, physical activity, smoking status and alcohol intake., Results: The study analysed samples from 96 pre-RA subjects and 258 matched controls. In this analysis, the median time to diagnosis (defined as time between date of blood sample and date of diagnosis) was 6.71 years (range 0.8-15). A significant inverse association was observed with n-6 PUFA linoleic acid (LA) levels and pre-RA in the fully adjusted model (highest tertile: OR 0.29; 95% CI 0.12 to 0.75; P for trend 0.01). No association was observed with any individual n-3 PUFA, total n-3 PUFA or total n-3:n-6 ratio., Conclusions: Erythrocyte levels of the n-6 PUFA LA were inversely associated with risk of RA, whereas no associations were observed for other n-6 or n-3 PUFA. Further work is warranted to replicate these findings and to investigate if lower LA levels are a bystander or contributor to the process of RA development., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6-7 years in 724 mother-child pairs from the Southampton Women's Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children's cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6-7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6-7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6-7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.

Objective: The aims of this study were to test whether yeast-derived β-1,3/1,6 glucan can prevent the occurrence or reduce the severity of upper respiratory tract infection (URTI) and modulate innate immune responses during winter months in community-dwelling older adults., Methods: This was a double-blind placebo-controlled trial of community-dwelling adults ages 50 to 70 y randomized to once-daily β-1,3/1,6 glucan (Wellmune 250 mg/d; n = 50) or identical placebo capsule (n = 50) over 90 d during winter. URTI episodes were medically confirmed. Symptom severity was recorded via self-reported daily Wisconsin Upper Respiratory Tract Infection Score 21. Blood and saliva samples were collected at days 0, 45, and 90 for measurements of innate immune parameters., Results: Forty-nine participants completed the trial in each group. Supplementation was well tolerated. Forty-five URTIs were confirmed: 28 in the placebo group and 17 in the Wellmune group (odds ratio, 0.55; 95% confidence interval, 0.24-1.26; P = 0.149). There was a strong trend for Wellmune to decrease the number of symptom days (P = 0.067). Symptom severity did not differ significantly between groups. Compared with the placebo group, lipopolysaccharide-stimulated blood from participants in the Wellmune group showed an increase in interferon-γ concentration from baseline at day 45 (P = 0.016) and smaller decreases in monokine induced by interferon-γ concentration from baseline at days 45 and 90 (P = 0.032 and 0.046, respectively). No difference was seen in serum or nonstimulated blood cytokines and chemokines or in salivary immunoglobulin A., Conclusion: Daily oral β-1,3/1,6 glucan may protect against URTIs and reduce the duration of URTI symptoms in older individuals once infected. This may be linked to effects on innate immune function. Larger studies are needed to confirm the benefits of β-1,3/1,6 glucan on URTIs in this older population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF-driven Th17 cell differentiation., Methods: Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured. CD4+CD25- T cells and monocytes were purified from the blood of healthy donors and cocultured in the presence of anti-CD3, with or without etanercept (ETN), eicosapentaenoic acid (EPA), or the control fatty acid, linoleic acid (LA). Expression of interleukin 17 and interferon-γ was measured by intracellular staining and flow cytometry., Results: Plasma PC EPA levels and the EPA/arachidonic acid ratio correlated inversely with change in the Disease Activity Score at 28 joints (DAS28) at 3 months (-0.51, p = 0.007 and -0.48, p = 0.01, respectively), indicating that higher plasma EPA was associated with a greater reduction in DAS28. Plasma PC EPA was positively associated with European League Against Rheumatism response (p = 0.02). An increase in Th17 cells post-therapy has been associated with nonresponse to anti-TNF. ETN increased Th17 frequencies in vitro . Physiological concentrations of EPA, but not LA, prevented this., Conclusion: EPA status was associated with clinical improvements to anti-TNF therapy in vivo and prevented the effect of ETN on Th17 cells in vitro . EPA supplementation might be a simple way to improve anti-TNF outcomes in patients with RA by suppressing Th17 frequencies.

Background: 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., Methods: 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 2 ml/kg body weight for 4 h 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., Results: 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., Conclusion: 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., Trial Registration: Clinical Trials.Gov NCT01870791., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Death from sepsis in the intensive therapy unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with omega-3 (n-3) fatty acids (FAs), principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial in reducing mortality from organ dysfunction. Fish oil (FO) is a source of EPA and DHA., Methods: A randomized trial investigating the effects of parenteral (intravenous) nutrition providing FO (0.092g EPA+DHA/kg body weight/day) was conducted. Sixty consecutive ITU patients diagnosed with sepsis were randomised to receive either once daily parenteral FO and standard medical care or standard medical care only., Results: Forty one patients (21 received fish oil; 20 controls) consented to blood sampling and blood was taken on days 0, 1, 2, 3, 5, 7, 10 and 13; because of deaths, patient discharge and withdrawal of consent, the number of blood samples available for analysis diminished with time. FA composition of plasma phosphatidylcholine (PC), plasma non-esterified FAs (NEFAs) and peripheral blood mononuclear cells (PBMCs) was determined by gas chromatography. EPA and DHA were rapidly incorporated into all 3 lipid pools investigated. There was a reduction in the arachidonic acid (AA) to EPA+DHA ratio in plasma PC and NEFAs. Fewer patients died in the FO group (13.3% (n=4)) compared with the control group (26.7% (n=8)) but this difference was not significant. A reduction in the AA/(EPA+DHA) ratio in PBMCs and plasma PC was associated with significantly improved survival. Plasma PC, plasma NEFA and PBMC FA profiles are rapidly altered by FO infusion in critically ill septic patients., Conclusion: The provision of high dose n-3 FAs resulted in a rapid and significant increase in EPA and DHA and a reduction in AA/(EPA+DHA) ratio. This latter reduction is associated with improved survival., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

Background: Home parenteral nutrition (HPN) patients depend on lipid emulsions as part of their parenteral nutrition regimen to provide essential fatty acids (EFAs). Mixed-oil sources are used in modern lipid emulsions to decrease the amount of proinflammatory EFAs, mainly linoleic acid, which is present in large amounts in soybean oil. It is unknown whether patients who fully depend on such mixed lipids have adequate EFA supply. We therefore evaluated whether HPN patients who depend on mixed olive oil- and soybean oil-based HPN show clinical or biochemical evidence of EFA deficiency., Materials and Methods: Fatty acid status was assessed in plasma phosphatidylcholine (PC) and peripheral blood mononuclear cells from 30 patients receiving mixed olive oil- and soybean oil-based HPN (>3 months, ≥5 times per week) and 30 healthy controls. Innate immune cell functions were evaluated by assessing expression of surface membrane molecules, and reactive oxygen species, and cytokine production., Results: None of the patients or controls showed clinical evidence (skin rash) or biochemical evidence (increased Holman index [>0.2]) for EFA deficiency. The Holman index in plasma PC (median [25th-75th percentile]) was significantly higher in patients (0.019 [0.015-0.028]) compared with controls (0.015 [0.011-0.017]). No differences were found in innate immune cell functions between groups, except for a 3.6-fold higher tumor necrosis factor-α production in patients., Conclusion: We found no clinical or biochemical evidence that HPN patients who fully and long-term depend on mixed olive oil- and soybean oil-based lipids have an increased risk for EFA deficiency., (© 2015 American Society for Parenteral and Enteral Nutrition.)

Objective: Studies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health., Method: At 26-28 weeks' gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months' postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression., Results: In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (β = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (β = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression., Conclusions: No association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality., Trial Registration: ClinicalTrials.gov identifier: NCT01174875., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother-offspring cohort were assayed at 26-28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.

Gas chromatography (GC) is a highly sensitive method used to identify and quantify the fatty acid content of lipids from tissues, cells, and plasma/serum, yielding results with high accuracy and high reproducibility. In metabolic and nutrition studies GC allows assessment of changes in fatty acid concentrations following interventions or during changes in physiological state such as pregnancy. Solid phase extraction (SPE) using aminopropyl silica cartridges allows separation of the major lipid classes including triacylglycerols, different phospholipids, and cholesteryl esters (CE). GC combined with SPE was used to analyze the changes in fatty acid composition of the CE fraction in the livers of virgin and pregnant rats that had been fed various high and low fat diets. There are significant diet/pregnancy interaction effects upon the omega-3 and omega-6 fatty acid content of liver CE, indicating that pregnant females have a different response to dietary manipulation than is seen among virgin females.