Background: Estimation of the intake of oily fish at a population level is difficult. The measurement of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in biological samples may provide a useful biomarker of intake.Objective: We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological samples that represent roles in fatty acid transport, function, and storage.Design: This was a double-blind, randomized, controlled intervention trial in 204 men and women that lasted 12 mo. EPA and DHA capsules were provided in a manner to reflect sporadic consumption of oily fish (ie, 1, 2, or 4 times/wk). EPA and DHA were assessed at 9 time points over 12 mo in 9 sample types (red blood cells, mononuclear cells, platelets, buccal cells, adipose tissue, plasma phosphatidylcholine, triglycerides, cholesteryl esters, and nonesterified fatty acids).Results: A dose response (P < 0.05) was observed for EPA and DHA in all pools except for red blood cell EPA (P = 0.057). EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes (P < 0.0001). The rate of incorporation varied between sample types, with the time to maximal incorporation ranging from days (plasma phosphatidylcholine) to months (mononuclear cells) to >12 mo (adipose tissue).Conclusions: Plasma phosphatidylcholine EPA plus DHA was identified as the most suitable biomarker of acute changes in EPA and DHA intake, and platelet and mononuclear cell EPA plus DHA were the most suitable biomarkers of habitual intake. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN48398526.

Supplements providing EPA+DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile. The results of the current trial, which used a prospective recruitment approach to examine the responses in population subgroups, are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females.

Background-Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported to reduce the risk of sudden cardiac death presumed to be due to fatal ventricular arrhythmias, but their effect on atrial arrhythmias is unclear. Methods and Results-Patients (nϭ108) undergoing coronary artery bypass graft surgery were randomly assigned to receive 2 g/d n-3 PUFA or placebo (olive oil) for at least 5 days before surgery (median, 16 days; range, 12 to 21 days). Phospholipid n-3 PUFA were measured in serum at study entry and at surgery and in right atrial appendage tissue at surgery. Echocardiography was used to assess left ventricular function and left atrial dimensions. Postoperative continuous ECG monitoring (Lifecard CF) for 5 days or until discharge, if earlier, was performed with a daily 12-lead ECG and clinical review if patients remained in the hospital beyond 5 days. Lifecard recordings were analyzed for episodes of atrial fibrillation (AF) Ն30 seconds (primary outcome). Clinical AF, AF burden (% time in AF), hospital stay, and intensive care/high dependency care stay were measured as secondary outcomes. One hundred three patients completed the study (51 in the placebo group and 52 in the n-3 PUFA group). There were no clinically relevant differences in baseline characteristics between groups. n-3 PUFA levels were higher in serum and right atrial tissue in the active treatment group. There was no significant difference between groups in the primary outcome of AF (95% confidence

*WELCOME, Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy.

Background The health effects of long-chain omega-3 polyunsaturated fatty acids (n–3 PUFAs) are partly mediated by their oxidized metabolites, i.e., eicosanoids and other oxylipins. Some intervention studies have demonstrated that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase systemic concentrations of n–3 PUFA–derived oxylipins and moderately decrease arachidonic acid–derived oxylipins. There is no information on the dose-response of oxylipin concentrations after n–3 PUFA intake. Objective The aim of this study was to quantify oxylipins in human plasma samples from an intervention study in which participants were randomly assigned to different daily intakes of EPA and DHA for 12 mo. Methods Healthy adult men and women with low habitual fish consumption (n = 121) were randomly assigned to receive capsules providing doses of n–3 PUFAs reflecting 3 patterns of consumption of oily fish [1, 2, or 4 portions/wk with 3.27 g EPA + DHA (1:1.2, wt:wt) per portion] or placebo. Oxylipins were quantified in plasma after 3 and 12 mo. Relative and absolute changes of individual oxylipins were calculated and concentrations were correlated with the dose and the content of EPA and DHA in blood lipid pools. Results Seventy-three oxylipins, mostly hydroxy-, dihydroxy-, and epoxy-PUFAs, were quantified in the plasma samples. After 3 and 12 mo a linear increase with dose was observed for all EPA- and DHA-derived oxylipins. Cytochrome-P450-derived anti-inflammatory and cardioprotective epoxy-PUFAs increased linearly with n–3 PUFA dose and showed low interindividual variance (r2 > 0.95). Similarly, 5, 12-, and 15-lipoxygenase–derived hydroxy-PUFAs as well as those formed autoxidatively increased linearly. These include the precursors of so-called specialized pro-resolving lipid mediators (SPMs), e.g., 17-hydroxy-DHA and 18-hydroxy-EPA. Conclusions Plasma concentrations of biologically active oxylipins derived from n–3 PUFAs, including epoxy-PUFAs and SPM-precursors, increase linearly with elevated intake of EPA and DHA. Interindividual differences in resulting plasma concentrations are low. This trial was registered at controlled-trials.com as ISRCTN48398526.

BackgroundReady-to-use therapeutic foods (RUTF) are lipid-based pastes widely used in the treatment of acute malnutrition. Current specifications for RUTF permit a high n-6 polyunsaturated fatty acid (PUFA) content and low n-3 PUFA, with no stipulated requirements for preformed long-chain n-3 PUFA. The objective of this study was to develop an RUTF with elevated short-chain n-3 PUFA and measure its impact, with and without fish oil supplementation, on children’s PUFA status during treatment of severe acute malnutrition.MethodsThis randomized controlled trial in children with severe acute malnutrition in rural Kenya included 60 children aged 6 to 50 months who were randomized to receive i) RUTF with standard composition; ii) RUTF with elevated short chain n-3 PUFA; or iii) RUTF with elevated short chain n-3 PUFA plus fish oil capsules. Participants were followed-up for 3 months. The primary outcome was erythrocyte PUFA composition.ResultsErythrocyte docosahexaenoic acid (DHA) content declined from baseline in the two arms not receiving fish oil. Erythrocyte long-chain n-3 PUFA content following treatment was significantly higher for participants in the arm receiving fish oil than for those in the arms receiving RUTF with elevated short chain n-3 PUFA or standard RUTF alone: 3 months after enrolment, DHA content was 6.3% (interquartile range 6.0–7.3), 4.5% (3.9–4.9), and 3.9% (2.4–5.7) of total erythrocyte fatty acids (P <0.001), respectively, while eicosapentaenoic acid (EPA) content was 2.0% (1.5–2.6), 0.7% (0.6–0.8), and 0.4% (0.3–0.5) (P <0.001). RUTF with elevated short chain n-3 PUFA and fish oil capsules were acceptable to participants and carers, and there were no significant differences in safety outcomes.ConclusionsPUFA requirements of children with SAM are not met by current formulations of RUTF, or by an RUTF with elevated short-chain n-3 PUFA without additional preformed long-chain n-3 PUFA. Clinical and growth implications of revised formulations need to be addressed in large clinical trials.Trial registrationClinicaltrials.gov NCT01593969. Registered 4 May 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0315-6) contains supplementary material, which is available to authorized users.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%–64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.

The aim of the present study was to determine whether age and sex influence both the status and incorporation of EPA and DHA into blood plasma, cells and tissues. The study was a double-blind, randomised, controlled intervention trial, providing EPA plus DHA equivalent to 0, 1, 2 or 4 portions of oily fish per week for 12 months. The participants were stratified by age and sex. A linear regression model was used to analyse baseline outcomes, with covariates for age or sex groups and by adjusting for BMI. The change in outcomes from baseline to 12 months was analysed with additional adjustment for treatment and average compliance. Fatty acid profiles in plasma phosphatidylcholine, cholesteryl esters, NEFA and TAG, mononuclear cells (MNC), erythrocyte membranes, platelets, buccal cells (BU) and adipose tissue (AT) were determined. At baseline, EPA concentrations in plasma NEFA and DHA concentrations in MNC, BU and AT were higher in females than in males (all P,0·05). The concentrations of EPA in AT (P¼ 0·003) and those of DHA in plasma TAG (P, 0·01) and AT (P,0·001) were higher with increasing age. Following 12-month supplementation with EPA plus DHA, adjusted mean difference for change in EPA concentrations in plasma TAG was significantly higher in females than in males (P,0·05) and was greater with increasing age (P¼ 0·02). Adjusted mean difference for change in DHA concentrations in AT was significantly smaller with increasing age (P¼ 0·02). Although small differences in incorporation with age and sex were identified, these were not of sufficient magnitude to warrant a move away from population-level diet recommendations for n-3 PUFA.