Randomized trial of omega-3 for autism spectrum disorders: Effect on cell membrane composition and behavior Mara Parellada a,b,c,n , Cloe Llorente a , Rosa Calvo e , Silvia Gutierrez f , Luisa Lázaro e , Montserrat Graell f , Maria Guisasola c,d , Maria Luisa Dorado a , Leticia Boada a,b , Jose Romo a , Elena Dulin g , Inmaculada Sanz g , Celso Arango a,b,c , Carmen Moreno a,b,c a Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain b IiSGM, CIBERSAM, Spain c School of Medicine, Universidad Complutense, Madrid, Spain d Experimental Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain e Hospital Clínic of Barcelona, CIBERSAM, Spain f Hospital Infantil Niño Jesus (Madrid), CIBERSAM, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, UCM, Madrid, Spain g Biochemistry Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Received 9 July 2016; received in revised form 17 July 2017; accepted 20 August 2017 KEYWORDS Randomized controlled trials; Autism Spectrum Disorder; Fatty acids, omega-3; Fatty acids, unsaturated; Biomarkers Abstract A high ω6/ω3 ratio [fatty acid (FA) index] in the cell membrane has been associated with inadequate brain development. It has started to be used as a biomarker of treatment efficacy in human diseases. The aim of this study was to investigate if omega-3 supplementation improves erythrocyte membrane ω6/ω3, plasma antioxidant status (TAS) and autistic behaviors. A randomized, crossover, placebo-controlled study was designed to investigate the effect of 8 weeks of supplementation with ω3 (962 mg/d and 1155 mg/d for children and adolescents, respectively). Sixty-eight children and adolescents with Autism Spectrum Disorders (ASD) completed the full protocol. Primary outcome measures were erythrocyte membrane FA composition and TAS. Secondary outcome measures were Social Responsiveness Scale and Clinical Global Impression-Severity. Treatment with ω3 improved the erythrocyte membrane ω6/ω3 ratio (treatment effect po0.008, d = 0.66; within subjects effect po0.007, d = 0.5) without changing TAS. There was a within subjects significant improvement in Social Motivation www.elsevier.com/locate/euroneuro http://dx.doi.org/10.1016/j.euroneuro.2017.08.426 0924-977X/& 2017 Elsevier B.V. and ECNP. All rights reserved. n Correspondence to: Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, UCM, Ibiza 43, Madrid 28009, Spain. Fax: + 34 91 4265004. E-mail address: parelladahggm@gmail.com (M. Parellada). European Neuropsychopharmacology (]]]]) ], ]]]–]]] Please cite this article as: Parellada, M., et al., Randomized trial of omega-3 for autism spectrum disorders: Effect on cell membrane composition and behavior. European Neuropsychopharmacology (2017), http://dx.doi.org/10.1016/j.euroneuro.2017.08.426