Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany.
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Am J Clin Nutr. 2019 May 1;109(5):1251-1263. doi: 10.1093/ajcn/nqz016.
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.
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.
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.
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.
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.
长链ω-3 多不饱和脂肪酸（n-3 PUFA）的健康影响部分是由其氧化代谢物介导的，即类二十烷酸和其他氧化脂类。一些干预研究表明，二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）会增加体内 n-3 PUFA 衍生氧化脂类的浓度，并适度降低花生四烯酸衍生氧化脂类的浓度。关于 n-3 PUFA 摄入后氧化脂类浓度的剂量反应，目前尚无信息。
本研究旨在定量分析接受 n-3 PUFA 干预 12 个月的健康成年人血浆样本中的氧化脂类。
低习惯性鱼类摄入的健康成年男女（n=121）被随机分配，每天摄入不同剂量的 EPA 和 DHA，持续 12 个月。分别提供反映三种不同鱼类摄入模式的胶囊[每周 1、2 或 4 份，每份含 3.27 克 EPA+DHA（1:1.2，wt:wt）]或安慰剂。在 3 个月和 12 个月后定量分析血浆中的氧化脂类。计算个体氧化脂类的相对和绝对变化，并将浓度与血液脂质池中的 EPA 和 DHA 剂量和含量相关联。
共定量了 73 种氧化脂类，主要是羟基、二羟基和环氧化 PUFAs。在 3 个月和 12 个月后，所有 EPA 和 DHA 衍生的氧化脂类都呈现出剂量依赖性的线性增加。细胞色素 P450 衍生的抗炎和心脏保护环氧 PUFAs 随 n-3 PUFA 剂量呈线性增加，个体间差异较小（r2>0.95）。同样，5、12 和 15-脂氧合酶衍生的羟基 PUFAs 以及自动氧化形成的 PUFAs 也呈线性增加。其中包括所谓的专门的促解决脂质介质（SPM）的前体，例如 17-羟基-DHA 和 18-羟基-EPA。
n-3 PUFA 衍生的生物活性氧化脂类，包括环氧 PUFAs 和 SPM 前体，血浆浓度随 EPA 和 DHA 摄入量的增加而呈线性增加。个体间血浆浓度的差异较小。本试验在 controlled-trials.com 上注册为 ISRCTN48398526。
