The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 children and adolescents aged 7–18 years (36 boys, 5 girls; mean age=11.66, s.d.=3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P<0.01) and the Social and Attention Problems syndrome scales of the Child Behavior Checklist (P<0.05). Blood fatty acid levels were significantly correlated with changes in the core symptoms of ASD. Baseline levels of blood fatty acid levels were also predictive of response to the omega-3 treatment. Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted.
Autism Spectrum Disorders (ASD) are neuropsychiatric disorders characterized by difficulties in reciprocal social interaction/communication, and the presence of stereotypic, obsessive, or repetitive behaviors, interests and activities.1 Omega-3 fatty acids supplementation received attention in light of the reports that suggest possible links between deficiencies or imbalances of omega-3 fatty acids and behaviors in ASD that may be overcome with supplementation.2 Although the potential mechanism of action by which omega-3 fatty acids improve symptoms of ASD is still unknown, studies suggest that neural tissue contains high concentrations of docosahexaenoic acid (DHA), and that this fatty acid is essential for the growth and functional development of the human brain.3 Studies (e.g., randomized controlled trials (RCT) and uncontrolled, open-label trials) have reported improvements in general health, sleeping patterns, cognitive ability, motor skills, concentration, eye contact, and sociability, as well as reductions in irritability, aggression, and hyperactivity among children with ASD following omega-3 supplementation.4, 5, 6 For instance, Amminger et al.4 conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (0.84 g/d eicosapentaenoic acid (EPA), 7 g/d DHA) supplementation in 13 children (aged 5–17 years) with ASD and found that omega-3 was associated with improvements in stereotypy and hyperactivity. However, there are also inconsistent reports as to whether omega-3 fatty acids are an effective treatment for ASD.7 Clearly, there is a need for more research in this area. Therefore, the goal of our present study was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children with ASD in the Asian (Singapore) context. We assessed: (i) the efficacy of omega-3 fatty acid supplementation in reducing core and comorbid symptoms of ASD and (ii) the relationship between blood fatty acids level, treatment response, and ASD symptomatology. We hypothesized that omega-3 fatty acids supplementation would be associated with significant improvements on core ASD symptoms and comorbidities, and that the changes in blood fatty acid levels would be associated with a greater treatment response.
Materials and Methods
The 12-week open-label pilot study was approved by the National Healthcare Group Domain Specific Review Board. Participants were referred to the present pilot study by their attending psychiatrist. Participation in the study was voluntary. Written informed consent to participate was obtained from the parents. Forty-one children and adolescents aged 7–18 years (36 boys, 5 girls; mean age=11.66; s.d.=3.05) diagnosed with ASD from an outpatient child psychiatric clinic in Singapore participated in this study. They received their ASD diagnosis from a licensed child psychiatrist based on the DSM-IV criteria.8 Information on cognitive functioning (assessed using standardized Wechsler Intelligence Scales such as the Wechsler Intelligence Scale for Children-IV (WISC-IV)9 and Wechsler Preschool and Primary Scale of Intelligence (WPPSI)10) was obtained from the participants’ medical records. All participants did not receive any concurrent behavioral interventions during the study period as reported by the parents at each study visit. However, they had access to standard routine care provided by their attending psychiatrists, which consisted of medication treatment and parent support. Table 1 presents the demographics of the participants.
Participants were given 15 ml liquid (Efamol Efalex) twice daily, which consisted of 1 g/day of omega-3 fatty acids (840 mg DHA, 192 mg EPA, 1278 mg pure evening primrose oil of which: 66 mg arachidonic acid (AA) and 144 mg gamma linolenic acid, 60 mg vitamin E, and 3 mg thyme oil) for 12 weeks. This dosage and DHA/EPA ratio were chosen based on prior studies.7 Compliance was monitored through unused bottles at mid-treatment and post-treatment. The Social Responsiveness Scale–Parent (SRS-P)11 and the Child Behavior Checklist (CBCL)12 were completed by the parents and were used to assess the core and comorbid symptoms of ASD. A non-fasting blood sample (2x50 μl per spot of blood) was collected via the finger-prick method at pre-treatment and post-treatment. The samples (i.e., red blood cells methylated by 1% H2SO4/methanol) were analyzed by the Institute of Aquaculture at the University of Stirling, UK.
A series of paired sample t-tests were conducted to compare the pre- and post-treatment scores of the outcome measures. Bonferroni's correction was applied. Pearson’s correlational analyzes were conducted to assess changes in levels of fatty acids and its relationship to core ASD symptoms. Effect sizes were reported using Cohen’s d (0.8=large, 0.5=medium, and 0.2=small).13
At post-treatment, parents reported significant improvements on core symptoms of ASD as assessed by the SRS-Parent: Social Awareness, Social Cognition, Social Communication, Social Motivation, Autistic Mannerisms, and Total SRS. In addition, parents also reported improvements on two comorbid symptoms as assessed by the CBCL: social problems and attention problems (see Table 2).
Participants showed a significant decrease in percentage of AA:EPA and an increase in percentage of omega-3 fatty acids, suggesting that the 12-week omega-3 supplementation led to significant differences in the fatty acid profiles (see Table 2). Positive changes in omega-3: total highly unsaturated fatty acids (r=−0.37, P=0.03) and DHA (r=−0.38, P=0.02) were associated with decreases in the severity of autism mannerisms. In addition, higher baseline percentage of omega-6:EPA was correlated with an increase in social awareness (r=0.38, P=0.02). No serious adverse events were reported.
Our findings indicated significant improvements on the core symptoms of ASD and attention problems as reported by parents. These findings are in line with three RCT studies that document improvements in the core and comorbid symptoms of ASD following omega-3 supplementation.4, 5, 6 Our findings were also supported by an analysis of blood fatty acids showing significant differences in fatty acid profiles following supplementation. In addition, positive changes in omega-3:total highly unsaturated fatty acids and DHA were associated with decreases in the severity of the autistic mannerisms (i.e., stereotypical behaviors or highly restricted interests). Baseline levels of blood fatty acid levels were also predictive of response to omega-3 treatment as measured by the SRS-P, which may allow clinicians to identify candidates with potential for treatment response. Our findings add to the existing literature, suggesting that specific blood fatty acid levels correlate with changes in the core symptoms of ASD.4 The omega-6:omega-3 ratio has been found to influence the immune status, for example, omega-3 fatty acids are known to exert an anti-inflammatory effect whereas omega-6 fatty acids exert pro-inflammatory effects.14 Therefore, an optimal ratio of omega-6:omega-3 fatty acids may be beneficial in decreasing the risk of chronic diseases.15 Our study was feasible because of the relatively simple study procedures, such as blood-taking using a simple finger-prick method, and the intake of omega-3 supplement in liquid form. The intake of omega-3 supplement in liquid form is advantageous for children with ASD, who may have difficulties in swallowing the capsules. Future RCT studies may adopt omega-3 in liquid form, with the placebo masked by adding a small amount of fish oil to give it a fishy taste.
Despite these preliminary encouraging findings, caution is needed in interpreting the results from the present study. As our study was an open-label study, we cannot be certain whether improvements were due solely to the omega-3 supplementation or owing to other factors, such as existing standard routine care and/or parent’s positive expectation of the treatment benefit. Clearly, RCTs of omega-3 fatty acids with blood fatty acids measurements on a larger ASD sample with longer follow-up is warranted to ascertain the efficacy of omega-3 fatty acids supplementation.
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We thank Efamol for providing the omega-3 fatty acids supplementation and for partially sponsoring the study. We also thank Chee Yu Yan and Lim Ee Wen for their contribution to the study and the families of the persons who participated in the study.
Efamol had no role in the design or conduct of the study, data collection, management, analysis and interpretation of the findings, and the preparation and approval of this manuscript.
The authors declare no conflict of interest.
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Ooi, Y., Weng, S., Jang, L. et al. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore. Eur J Clin Nutr 69, 969–971 (2015). https://doi.org/10.1038/ejcn.2015.28
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