Applied Physiology and Nutrition Research Group, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
Heart Institute (InCor), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
Front Immunol. 2018 Mar 2;9:336. doi: 10.3389/fimmu.2018.00336. eCollection 2018.
Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, = 11) or n-3 PUFA (ω-3, = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, = 0.06, ES = 0.9; and +23 vs. -22%, = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels ( > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.
内皮细胞被认为在抗磷脂综合征（APS）的发病机制中起核心作用。研究表明，ω-3 多不饱和脂肪酸（n-3 PUFA）补充剂可改善多种疾病中的内皮功能；因此，它在 APS 中具有很高的临床相关性。本研究旨在评估 n-3 PUFA 补充剂对原发性 APS（PAPS）患者内皮功能（主要结局）的疗效。这是一项为期 16 周的随机临床试验，纳入了 22 名成年女性 PAPS 患者。患者按 1:1 随机分配（n=11）接受安慰剂（PL）或 n-3 PUFA（ω-3）补充剂。在干预前（pre）和干预后（post）16 周，患者均接受内皮功能（外周动脉张力测定）评估（主要结局）。患者还接受了系统内皮细胞活化标志物、炎症标志物、饮食摄入、国际标准化比值（INR）和不良反应的评估。与 PL 组相比，ω-3 组在反应性充血指数（RHI）和 RHI 的对数转换（LnRHI）的内皮功能估计值在 post 时呈现出显著的增加（+13% vs. -12%， = 0.06，ES = 0.9；和+23% vs. -22%， = 0.02，ES = 1.0）。E-选择素、血管细胞黏附分子-1 和纤维蛋白原水平无变化（ > 0.05）。此外，与 PL 组相比，ω-3 组在 post 时循环中白细胞介素-10（-4% vs. +45%， = 0.04，ES = -0.9）和肿瘤坏死因子（-13% vs. +0.3%， = 0.04，ES = -0.95）的水平降低，细胞间黏附分子-1 的反应呈下降趋势（+3% vs. +48%， = 0.1，ES = -0.7）。饮食摄入、INR 或自述不良反应无变化。总之，16 周的 n-3 PUFA 补充剂改善了经良好控制的 PAPS 患者的内皮功能。这些结果支持 n-3 PUFA 补充剂作为 APS 的辅助治疗。在 ClinicalTrials.gov 注册，编号为 NCT01956188。
