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Front. Immunol. | doi: 10.3389/fimmu.2018.00336


 Sheylla Felau1, Lucas Sales1, Marina Solis1, Ana Paula Hayashi1,  Hamilton Roschel1, Ana Lucia Sá-Pinto1,  Danieli C. Andrade1, Keyla Katayama2, Maria Claudia Irigoyen2, Fernanda Consolim-Colombo2, Eloisa Bonfá1,  Bruno Gualano1 and  Fabiana B. Benatti1, 3*
  • 1Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, Brazil
  • 2Heart Institute (InCor), Faculdade de Medicina, Universidade de São Paulo, Brazil
  • 3School of Applied Sciences, Universidade Estadual de Campinas, Brazil

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, n=11) or n-3 PUFA (ω-3, n=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%, p=0.06, ES=0.9; and +23% vs. -22%, p=0.02, ES=1.0). No changes were observed for e-selectin, VCAM-1 and fibrinogen levels (p>0.05). Additionally, ω-3 group showed decreased circulating levels of IL-10 (-4% vs. +45%, p=0.04, ES=-0.9) and TNF (-13% vs. +0.3%, p=0.04, ES=-0.95) and a tendency towards a lower ICAM-1 response (+3% vs. +48%, p=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 as NCT01956188.

Keywords: Antiphospholipid Syndrome, n-3 PUFA, Endothelial Function, coagulation, Inflammation

Received: 30 Nov 2017; Accepted: 06 Feb 2018.

Edited by:

Niccolo Terrando, Duke University, United States

Reviewed by:

Joan Clària, Hospital Clínic de Barcelona, Spain
Jesmond Dalli, Queen Mary University of London, United Kingdom  

Copyright: © 2018 Felau, Sales, Solis, Hayashi, Roschel, Sá-Pinto, Andrade, Katayama, Irigoyen, Consolim-Colombo, Bonfá, Gualano and Benatti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Fabiana B. Benatti, Faculdade de Medicina, Universidade de São Paulo, Laboratory of Assessment and Conditioning in Rheumatology, São Paulo, Brazil,