Contents lists available at ScienceDirect Prostaglandins, Leukotrienes and Essential Fatty Acids journal homepage: www.elsevier.com/locate/plefa Moderate intake of docosahexaenoic acid raises plasma and platelet vitamin E levels in cystic fibrosis patients Evelyne Véricel a, ⁎ , Stéphane Mazur b , Romain Colas a , Véronique Delaup b , Catherine Calzada a , Philippe Reix b , Isabelle Durieu c , Michel Lagarde a , Gabriel Bellon b a Univ-Lyon, CarMeN laboratory, Inserm U1060, INRA U1397, Université Claude Bernard Lyon 1, INSA-Lyon, IMBL, 69621 Villeurbanne, France b Centre de Référence pédiatrique Mucoviscidose de Lyon, Hôpital Femme Mère Enfant, F-69500 Bron, France c Centre de Référence adulte Mucoviscidose de Lyon, Centre Hospitalier Lyon-Sud, F-69310 Pierre-Bénite, France ARTICLE INFO Keywords: Docosahexaenoic acid Antioxidant status Plasma Platelet lipids Oxidative stress ABSTRACT Patients with cystic fibrosis have increased oxidative stress and impaired antioxidant systems. Moderate intake of docosahexaenoic acid (DHA) may favor the lowering of oxidative stress. In this randomized, double-blind, cross-over study, DHA or placebo capsules, were given daily to 10 patients, 5 mg/kg for 2 weeks then 10 mg/kg DHA for the next 2 weeks (or placebo). After 9 weeks of wash-out, patients took placebo or DHA capsules. Biomarkers of lipid peroxidation and vitamin E were measured at baseline, and after 2 and 4 weeks of treatment in each phase. The proportions of DHA increased both in plasma and platelet lipids after DHA supplementa- tions. The lipid peroxidation markers did not significantly decrease, in spite of a trend, after the first and/or the second dose of DHA but plasma and platelet vitamin E amounts increased significantly after DHA supplementation. Our findings reinforce the antioxidant potential of moderate DHA intake in subjects displaying increased oxidative stress. 1. Introduction Cystic fibrosis (CF), a common autosomal recessive disorder, caused by mutations in the Cystic Fibrosis Trans-membrane conduc- tance Regulator (CFTR) gene, is characterized by defective cAMP- dependent chloride ion conductance. Numerous mutations (more than 1900) for the CFTR gene have been reported in the Cystic Fibrosis Mutation Database but the deletion of phenylalanine 508 in the CFTR protein remains the most frequent [1]. In CF patients, abnormal CFTR protein impairs function of a number of organs and tissues where CFTR is expressed. Moreover, severity of CF could be influenced by an abnormal generation of reactive oxygen species [2,3]. Acute and chronic inflammations can explain, among many factors, high levels of oxidative stress. Moreover, malabsorption of antioxidant vitamins has been described in these patients [2,4]. Accordingly, markers of lipid peroxidation have been shown to be increased in plasma of CF patients [4,5]. Within the inflammation process, the major fatty acid involved is arachidonic acid (20:4n-6, ArA), a fatty acid from the n-6 polyunsatu- rated fatty acids (PUFA) family whose the essential precursor is linoleic acid (18:2n-6). The other family is the n-3 PUFA which mainly includes eicosapentaenoic (20:5n-3, EPA), docosapentaenoic (22:5n-3) and docosahexaenoic (22:6n-3, DHA) acids, from the essential precursor alpha-linolenic acid (18:3n-3). A pathophysiological role in CF has also been attributed to the abnormal PUFA metabolism. Indeed, previous investigations [3,6] described abnormal levels of plasma fatty acids in patients with a decreased 18:2n-6 and DHA [7]. Moreover, alterations of some plasma lipids could be correlated to disease severity [8]. While the alteration of lipid metabolism is well established, the mechanisms have not been completely known, although an increased release of ArA from phospholipids is observed explaining an increase of eicosanoids and inflammatory mediators [9]. In addition to their major role in haemostasis and thrombosis, platelets can initiate and modulate inflammatory responses [10,11]. In 2010, Mattoscio et al. [12] showed that human platelets are affected by molecular defect of CFTR. Moreover, microorganisms, present in lungs of CF patients, are able to activate platelets [13]. Numerous studies have shown platelet dysfunctions in patients with CF [14], as reflected by increased ex-vivo platelet aggregability and increased release of thromboxane A 2 , (TxA 2 ) [15], a pro-aggregatory prostanoid formed by http://dx.doi.org/10.1016/j.plefa.2016.10.008 Received 27 June 2016; Received in revised form 17 October 2016; Accepted 17 October 2016 ⁎ Correspondence to: UMR Inserm U.1060, Université de Lyon, INSA-Lyon, Cardiovasculaire, Métabolisme, diabétologie et Nutrition (CarMeN), IMBL, Bât Louis Pasteur, INSA, 20 Ave A. Einstein, 69621 Villeurbanne Cedex, France. E-mail address: evelyne.vericel@insa-lyon.fr (E. Véricel). Abbreviations: CF, cystic fibrosis; CFTR, cystic fibrosis trans-membrane conductance regulator; TxB 2 , thromboxane B 2 Prostaglandins, Leukotrienes and Essential Fatty Acids 115 (2016) 41–47 0952-3278/ © 2016 Elsevier Ltd. All rights reserved. crossmark