The database searches, reviews of bibliographies, and contact with experts yielded 143 potentially relevant articles. Six articles satisfied all inclusion and no exclusion criteria and are included in this systematic review. Reasons for exclusion of other articles are shown in Fig. .
Reason for exclusion of studies
The characteristics of the six included studies are shown in Table .
Characteristics of studies of omega-3 fatty acids in autistic spectrum disorder
Only one study was a randomized controlled trial (Amminger et al. 2007
). This study enrolled 13 children with autism (based on DSM-IV criteria and the ADI-R) and randomly assigned them to the daily use of 1.5 gms of omega-3 fatty acids or an identical placebo for 6 weeks. The outcome measure was the Aberrant Behavior Checklist. The difference in the change in each of the subscales between groups is shown in Table .
Table 2 Results of the one randomized controlled trial of omega-3 fatty acids (Amminger et al. 2007)
Each subscale showed a greater improvement in the omega-3 group compared to the placebo group, but none of these changes reached statistical significance. The largest changes were in the hyperactivity and stereotypy subscales. The study was methodologically sound, and received a four out of five point rating on the Jadad score (the score was reduced by one point because the method of randomization was not described).
Four studies were uncontrolled, open-label studies that enrolled children or young adults with autism or Asperger’s. Politi et al. 2008
conducted an open-label study of 19 young adults (mean age 29) with severe autism, moderate to profound mental retardation, and severe maladaptive behaviors. All subjects were given 0.93 gms of omega-3 fatty acids (DHA + EPA) and a vitamin supplement containing 5 mg of vitamin E daily for 6 weeks. The frequency and severity of problematic behaviors was assessed using an instrument (the Rossago Behavioral Checklist) for 6 weeks before, during, and after treatment (18 week total study period). The authors found no improvement in the mean severity score of problematic behaviors between the pre-treatment and treatment periods. Interestingly, there appeared to be an improvement in both the frequency and severity of symptoms in the post-treatment period, though it is not clear if this was due to beneficial effects of omega-3 fatty acids or other factors (as there was no control group).
Meguid et al. 2008
treated 30 children with autism from a National Research Center in Egypt for 3 months with a combination of omega-3 (240 mg DHA + 52 mg EPA daily) and omega-6 fatty acids (68 mg) and Vitamin E. They reported that 20 of 30 children improved on the Childhood Autism Rating Scale, but they did not report the mean change in the overall group of 30 children.
Patrick et al. enrolled 22 children who were all treated in an open-label manner with one daily capsule containing 247 mg per day of omega-3 fatty acids for 90 days (Patrick and Salik 2005
). The authors reported that there was a statistically significant increase from day 0 to 90 in each of the subscales of the assessment of basic language and learning skills. However, no raw data were presented.
Bell et al. 2004
included a very brief description of an open-label study where nine children with autism or Asperger’s were given one of two different omega-3 supplements of varying dose for at least 6 months. No structured outcomes were assessed, but parents reported improvements in general health and a variety of outcome measures (Table ).
The sixth study was a case report involving an 11 year-old child who had been diagnosed with autism at age 2.5 and was having problems with high levels of anxiety and agitation associated with compulsive rituals (Johnson and Hollander 2003
). Fish oils were initiated and advanced to 3 g/day (540 mg EPA). The parents and the clinician reported complete elimination of anxiety and agitation after 1 week, and the improvement was stable over 8 months of follow-up.
Only the randomized controlled trial reported the details of the method of ascertaining adverse medication effects (UKU Side Effect Rating Scale) (Amminger et al. 2007
). In this study, one child withdrew due to gastrointestinal complaints and lack of perceived benefit. The authors noted that a mild adverse event of fever was reported in the omega-3 group (but the number of patients reporting this was not shown). In one uncontrolled study, 2/22 children withdrew due to reports of increased physical activity, but no other adverse effects were noted (Patrick and Salik 2005
). In another uncontrolled study, a “few parents” reported “increased hyperactivity and behavioral problems” (Bell et al. 2004
). Two uncontrolled studies (Meguid et al. 2008
; Politi et al. 2008
) and the case report (Johnson and Hollander 2003
) did not discuss whether adverse events were assessed.
Based on the evidence summarized above, two independent raters agreed that the evidence for efficacy of omega-3 fatty acids for the treatment of autism should be rated as “I,” indicating that there is insufficient evidence to determine if it is effective.