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Background  The pathogenesis of autism spectrum disorder (ASD) is under investigation and one of the main alterations relates to the metabolic and inflammatory system dysfunctions. Indeed, based on a possible deficit of omega-3 fatty acids (FAs) of patients with ASD and looking for an anti-inflammatory effect, dietary supplements with omega-3 fatty acids have been proposed. We aimed to evaluate differences in plasma and erythrocyte FA profiles and plasma cytokines in patients with infantile ASD after supplementation with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids or placebo and both compared at baseline with a reference healthy group.    Methods  A double-blind, randomized placebo-controlled intervention with DHA/EPA for 6 months was carried out in 54 children between 2 and 6 years diagnosed with ASD. They were selected and randomly assigned into two groups: 19 children received 800 mg/day of DHA and 25 mg/day of EPA, or placebo. In addition, another reference group of 59 healthy children of the same age was included. Plasma lipids and cytokines, and FA profiles in plasma and erythrocytes were measured at baseline and after 6 months of treatment in ASD children, and at baseline in the reference group.    Results  There were no differences in demographic, anthropometric characteristics, and omega-3 intake between the healthy reference group and the ASD children at baseline. Children with ASD showed the higher plasma percentages of palmitic acid and total saturated FA and lower total omega-6 polyunsaturated FA (PUFA) compared with healthy children. An increased level of DHA and reduced EPA level in erythrocytes were detected in the ASD group vs. the reference group. After 6 months of treatment, the ASD group that received DHA enriched product significantly increased the plasma and erythrocyte percentages of DHA, but no differences were observed in the clinical test scores and other parameters as plasma cytokines between the two groups of ASD related to the intervention.    Conclusion  Spanish children with ASD exhibit an appropriate omega-3 FA status in plasma and erythrocytes. Neither a clinical improvement of ASD children nor a better anti-inflammatory or fatty acid state has been found after an intervention with DHA/EPA for 6 months. So, the prescription of n-3 LC-PUFA and other dietary supplements in ASD should be only indicated after a confirmed alteration of FA metabolism or omega-3 LC-PUFA deficiency evaluated by specific erythrocyte FA.    Clinical Trial Registration  [ www.ClinicalTrials.gov ], identifier [NCT03620097].

frontiers in nutrition

Docosahexaenoic and Eicosapentaenoic Intervention Modifies Plasma and Erythrocyte Omega-3 Fatty Acid Profiles But Not the Clinical Course of Children With Autism Spectrum Disorder: A Randomized Control Trial