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Effects of Large Doses of Arachidonic Acid Added to Docosahexaenoic Acid on Social Impairment in Individuals With Autism Spectrum Disorders: A Double-Blind, Placebo-Controlled, Randomized Trial

Yui, Kunio MD, PhD*†; Koshiba, Mamiko PhD; Nakamura, Shun PhD; Kobayashi, Yuji PhD§

Journal of Clinical Psychopharmacology: April 2012 - Volume 32 - Issue 2 - p 200–206
doi: 10.1097/JCP.0b013e3182485791
Original Contributions

Autism spectrum disorders are a neurodevelopmental disorders with reduced cortical functional connectivity relating to social cognition. Polyunsaturated fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) may have key role in brain network maturation. In particularly, ARA is important in signal transduction related to neuronal maturation. Supplementation with larger ARA doses added to DHA may therefore mitigate social impairment. In a 16-week, double-blind, randomized, placebo-controlled trial, we evaluated the efficacy of supplementation with large doses of ARA added to DHA (n = 7) or placebo (n = 6) in 13 participants (mean age, 14.6 [SD, 5.9] years). To examine underlying mechanisms underlying the effect of our supplementation regimen, we examined plasma levels of antioxidants transferrin and superoxide dismutase, which are useful markers of signal transduction. The outcome measures were the Social Responsiveness Scale and the Aberrant Behavior Checklist–Community. Repeated-measures analysis of variance revealed that our supplementation regimen significantly improved Aberrant Behavior Checklist–Community–measured social withdrawal and Social Responsiveness Scale–measured communication. Treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: treatment groups, 0.87 vs, placebo, 0.44; social withdrawal: treatment groups, 0.88, vs placebo, 0.54). There was a significant difference in the change in plasma transferrin levels and a trend toward a significant difference in the change in plasma superoxide dismutase levels between the 2 groups. This preliminary study suggests that supplementation with larger ARA doses added to DHA improves impaired social interaction in individuals with autism spectrum disorder by up-regulating signal transduction.

Supplemental Digital Content is available in the text.

From the *Research Institute of Progressive Developmental Disorders, Ashiya University Graduate School of Education, Ashiya; †Department of Psychiatry, Sawa Hospital, Osaka; and ‡Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology; and §Information and Planning Department, SRL, Inc, Tokyo, Japan.

Received November 9, 2010; accepted after revision October 18, 2011.

Reprints: Kunio Yui, MD, PhD, Research Institute of Progressive Developmental Disorders, Ashiya University Graduate School of Clinical Education, Rokurokusomachi, Ashiya, Hyougo 659-8511, Japan (e-mail:

This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (grant no. 21200017) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and a Clinical Research grant of the Sawa Hospital in Osaka, Japan.

This trial has been registered at as NCT01154894, ClinicalTrials (; no: NCT01154894).

Supplemental digital contents are available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (

© 2012 Lippincott Williams & Wilkins, Inc.