在患有重度抑郁症和慢性炎症的患者中，补充二十碳五烯酸后，循环中抗炎和促解决的脂质介质呈剂量和时间依赖性增加。
Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation.
机构信息
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
出版信息
Prostaglandins Leukot Essent Fatty Acids. 2021 Jan;164:102219. doi: 10.1016/j.plefa.2020.102219. Epub 2020 Dec 5.
BACKGROUND
Eicosapentaenoic acid (EPA) supplementation is an effective treatment option in major depressive disorder (MDD) associated with chronic low-grade inflammation. EPA is the precursor of specialized pro-resolving lipid mediators (SPMs) termed resolvins (Rv), that serve important roles in the resolution of inflammation. The objective of this study was to assess the effects of different doses of EPA on plasma concentrations of EPA metabolites and SPMs in MDD patients.
METHODS
In a 2-site study, 61 MDD patients with body mass index >25 kg/m and serum high-sensitivity C-reactive protein ≥3 μg/mL were enrolled in a 12-week randomized trial comparing EPA 1, 2, and 4 g/d to placebo. Plasma EPA (mol%) and SPMs (pg/mL) were measured in 42 study completers at baseline and at the end of treatment by liquid chromatography/mass spectrometry.
RESULTS
Plasma EPA and SPM concentrations did not change in the placebo group during 12 weeks of treatment. Plasma EPA and EPA-derived metabolites increased significantly and dose-dependently in all EPA supplementation arms. The increase in 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of RvE1-3, was significantly greater with the 4 g/d EPA dose than the other doses from week 4 to 12. RvE1 was undetected in all treatment groups, while RvE2 was detected in half of the subjects both at baseline and after treatment, with dose-dependent increases. RvE3 was detected only after supplementation, dose-dependently. A significant reduction in plasma arachidonic acid (AA), relative to baseline, was observed in all EPA arms. This was in contrast with an increase in AA-derived SPM lipoxin B4 (LXB4) in the 4 g/d arm.
CONCLUSIONS
Our results show a robust effect of EPA 4 g/d supplementation in increasing plasma EPA and 18-HEPE levels, associated with improved conversion to RvE2-3, and LXB4 levels.
背景
二十碳五烯酸（EPA）补充剂是治疗与慢性低度炎症相关的重度抑郁症（MDD）的有效治疗选择。EPA 是特化的促解决脂质介质（SPM）即消退素（Rv）的前体，在炎症消退中发挥重要作用。本研究旨在评估不同剂量 EPA 对 MDD 患者血浆 EPA 代谢物和 SPM 浓度的影响。
方法
在一项 2 个地点的研究中，61 名 BMI>25kg/m2 和血清高敏 C 反应蛋白≥3μg/mL 的 MDD 患者入组了一项为期 12 周的随机试验，比较了 EPA 1、2 和 4g/d 与安慰剂的疗效。42 名研究完成者在基线和治疗结束时通过液相色谱/质谱法测量了血浆 EPA（mol%）和 SPM（pg/mL）。
结果
安慰剂组在 12 周的治疗过程中，血浆 EPA 和 SPM 浓度没有变化。在所有 EPA 补充组中，血浆 EPA 和 EPA 衍生代谢物均显著且剂量依赖性增加。18-羟基二十碳五烯酸（18-HEPE）的增加，即 RvE1-3 的前体，在第 4 周至 12 周期间，4g/d EPA 剂量组的增加明显大于其他剂量组。所有治疗组均未检测到 RvE1，而 RvE2 在基线和治疗后均有一半受试者检测到，且剂量依赖性增加。仅在补充后才检测到 RvE3，剂量依赖性增加。与基线相比，所有 EPA 组的血浆花生四烯酸（AA）均显著减少。与之相反，在 4g/d EPA 组中，AA 衍生的 SPM 脂氧素 B4（LXB4）增加。
结论
我们的结果显示，EPA 4g/d 补充具有增加血浆 EPA 和 18-HEPE 水平的强大作用，与改善向 RvE2-3 和 LXB4 水平的转化相关。
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