Table 1 Characteristics of included Randomized Controlled Trials

Amminger, 2007 [44]

Austria

Autistic disorder

DSM-IV; ADI-R; ADOS

EPA 0.84 g/day, DHA 0.7 g/day, and vitamin E (7 mg/day) (7)

Placebo (6)

6

10.4 (3.2); range: 5–17 years

0 (0%)

ABC, adverse events

Omega Protein Cooperation, Houston, Texas

Bent, 2011 [45]

USA

Autistic spectrum disorder

DSM-IV-TR; ADOS; SCQ

EPA 0.7 g/day and DHA 0.46 g/day (14)

Placebo (13)

12

5.8 (1.7); range: 3–8 years

3 (11.1%)

ABC, Communication (PPVT, EVT), Social interaction (SRS); Behaviours (BASC); Global changes (CGI-I)

Autism Speaks; the Higgins Family Foundation; The Emch Foundation; The Taube Foundation; NIH/NCRR UCSF-CTSI UL1RR024131; MIND Institute

Bent, 2014 [43]

USA

Autistic spectrum disorder

Parent-report; Social Communication Questionnaire (SCQ)

EPA 0.7 g/day and DHA 0.46 g/day (29)

Placebo (28)

6

7.2 (1.1); range: 5–8 years

7 (12.3%)

ABC, parent and teacher ratings, Social interaction (SRS), Global changes (CGI-I)

Simons Foundation (SFARI 206484)

Johnson, 2010 [49]

USA

Autistic spectrum disorder; Pervasive Developmental Disorder, NOS

DSM-IV; ADOS

DHA 0.4 g/day (10)

Healthy diet (no treatment) (13)

12

3.4 (0.7); range: NR

NR

Child Behavior Checklist, MSEL AGS edition, direct behaviour observation measure, adverse events

John F. & Nancy A. Emmerling Fund / The Pittsburgh Foundation

Mankad, 2015 [46]

Canada

Autistic spectrum disorder

DSM-IV; ADOS; Autism Diagnostic Interview - Revised (ADI-R)

EPA and DHA (0.75 to 1.5 g/day) (18)

Placebo (19)

24

3.7 (1.5); range: 2–5 years

10 (26.3%)

Behaviors (BASC-2, PDDBI); Adaptive skills (VABS-II); language (PLS-4); global improvement (CGI-I); adverse events

Alva Foundation

Mazahery, 2018 [42]

New Zealand

Autistic spectrum disorder

DSM-V

DHA (0.722 g/day) (28) Vitamin D (2000 IU/day) (30) DHA (0.722 g/day) plus Vitamin D (2000 IU/day) (25)

Placebo (28)

52

5.3 (1.4); range: 2.5–8 years

13 (17.8%)

ABC

Massey University Strategic Innovation Fund, Massey University, New Zealand; Douglas Nutrition, Pty. Ltd

Parellada, 2017 [47]

Spain

Autistic spectrum disorder

DSM-IV-TR (Pervasive Developmental Disorder)

EPA (0.578 to 0.693 g/day), DHA (0.385 to 0.462 g/day) and vitamin E (1.6 to 2.10 mg/day) (40)

Placebo (37)

8 (crossover)

9.7 (3.6); range: 5–17 years

11 (16.2%)

Communication (SRS); Global severity (CGI-S); Proportion of ω3 PUFAs in erythrocyte (RBC) membranes [the ratio of AA to DHA and EPA (AA/DHA, AA/EPA) and ω3/ω6]; Plasma total antioxidant oxidative status (TAS);

Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (FIS EC07/90076); (CB/07/09/0023), and the Alicia Koplowitz Foundation(FAK 2017)

Voigt, 2014 [48]

USA

Autistic spectrum disorder

DSM-IV; CARS

DHA (0.2 g/day) (24)

Placebo (24)

26

6.1 (2.0); range: 3–10 years

8 (16.7%)

ABC; Global improvement (CGI-I); behaviour (BASC), depression (CDI)

Mayo Foundation; Martek Biosciences Corporation (Columbia, MD)

Yui, 2012 [9]

Japan

Autistic disorder or Asperger disorder

DSM-IV; ADI-R

DHA (0.24 g/day), arachidonic acid (0.24 g/day), astaxanthin (0.96 mg/day) (7)

Placebo (6)

16

14.6 (6.0); range: 6–28 years

1 (7.7%)

ABC; Social interaction (Social Responsiveness Scale)

Ministry of Education, Culture, Sports, Science and Technology, Japan; Sawa Hospital, Osaka, Japan.