Behavioral effects of omega 3 fatty acid

Archives of Medical Research 39 (2008) 682e685

ORIGINAL ARTICLE

Behavioral Effects of Omega-3 Fatty Acid Supplementation in Young
Adults with Severe Autism: An Open Label Study
Pierluigi Politi,a Hellas Cena,b Mario Comelli,c Gaetano Marrone,c Chiara Allegri,b
Enzo Emanuele,a and Stefania Ucelli di Nemia
a
Department of Health Applied Sciences, Section of Psychiatry
Department of Health Applied Sciences, Section of Human Nutrition
c
Department of Health Applied Sciences, Section of Statistics, University of Pavia, Pavia, Italy
b

Received for publication April 14, 2008; accepted June 30, 2008 (ARCMED-D-08-00158).

Background. Pilot findings seem to suggest a potential beneficial effect of omega-3 fatty
acid (FA) supplementation on behavioral alterations in children with autism. However,
data on the potential benefits of omega-3 supplements in young adults with severe autism
are lacking. In the present study, we sought to explore this issue in an open label study.

Methods. Nineteen young adults with severe autism (CARS O40), aged 18e40 years,
received two fish oil capsules per day [0.93 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plus 5 mg of vitamin E to avoid lipid peroxidation] for 6 weeks.
Subjects were assessed with an ad hoc caregiver questionnaire, the Rossago Behavioral
Checklist, for the assessment of behavioral anomalies.
Results. No significant improvements were observed with regard to the severity and frequency of problematic behaviors either during the active treatment period or during the
post-treatment 6-week observation period. Moreover, no effect on the number of episodes
and severity of behavior aberrations was observed.
Conclusions. Our negative findings do not point toward a major effect of omega-3 FA
supplementation on behavioral abnormalities in adults with severe autism. Further studies
on larger sample sizes are warranted to shed more light on this important issue. Ó 2008
IMSS. Published by Elsevier Inc.
Key Words: Autism, Behavior, Omega-3 fatty acids.

Introduction
Autism is characterized by impairments in social interaction,
difficulty with communication, and restrictive and repetitive
behaviors (1). This condition is traditionally considered as
a stable neuropsychiatric disorder and improvements in core
autistic features are uncommon. However, preliminary evidences mainly derived from clinical studies seem to suggest
that specific pharmacological or nutraceutical interventions

may improve behavioral problems in this patient group (2e5).
There is growing evidence that deficiencies of omega-3
fatty acids (FA) may be involved in numerous psychiatric
disorders (6). Interestingly, a recent double-blind study by
Address reprint requests to: Pierluigi Politi, MD, PhD, Department of
Health Applied Sciences, Section of Psychiatry, University of Pavia, Via
Bassi 21, Ie27100, Pavia, Italy; E-mail: [email protected]

Amminger et al. (7) found that omega-3 FA supplements
were superior to placebo for reducing hyperactivity and stereotypy in autistic children. However, there were significant
shortcomings in this study including the small sample size
(n 5 12), the large baseline differences between patients
with autism and controls, the fluctuating nature of the outcomes, and problems inherent in the effect sizes (8).
To our knowledge, there are no published data on the efficacy of omega-3 FA supplementation in young adults with
severe autism. The issue of pharmacological treatment of adult
autistic patients is not trivial inasmuch as severe cases of autism usually persist into adulthood, and the majority of cases
diagnosed in childhood continue to meet the criteria for the
disorder in early adult life (9,10). We therefore conducted
this open label trial to examine the safety and behavioral effects of omega-3 FA supplementation in this patient group.


0188-4409/08 $esee front matter. Copyright Ó 2008 IMSS. Published by Elsevier Inc.
doi: 10.1016/j.arcmed.2008.06.005

Omega-3 Fatty Acids in Severe Autism

683

Materials and Methods

Table 1. Rossago Behavioral Checklist

Study Participants

1. Plays with or eats mucus, saliva, stools, or earth (includes picacism)
2. Excessive or deficient hygiene
3. No sphincteric control
4. Urinates or defecates in inappropriate places
5. Excessive or deficient food intake
6. Improper sexual behavior
7. Undresses him/herself in the public

8. Shuts him/herself in the room or bathroom. Refuses to go out
9. Absconds or runs away from the caregiver
10. Damages objects
11. Cries, shouts, sings, or laughs in an excessive manner or with no reason
12. Disturbs others
13. Picks at healing wounds and scars
14. Hits, pinches, bites, scratches him/herself
15. Hits, pinches, bites, scratches others
16. Irritates, quarrels verbally with others
17. Disobeys caregivers’ orders
18. Throws objects at others
19. Obsessive, repetitive, compulsive behaviors
20. Intense fear or anxiety without cause
21. Steals food or objects
22. Does not sleep and disturbs others

This open label trial was conducted from April 2007 to June
2007 in a single farm community center specifically designed
for individuals with autism (Cascina Rossago, Pontenizza,
Pavia, Italy). The sample included 19 adults (15 males, 4

females) aged 18 to 40 years (mean  SD: 28.9  4.9 years)
with severe autistic disorder (CARS O40) (11). The sampling design followed previously established selection criteria:
(a) a physician and a psychologist, both experienced in autism,
confirmed that the subject diagnosis met the DSM-IV-Text Revised; (b) the patients manifested moderate to profound mental
retardation as assessed by standardized tests of intelligence,
including the Wechsler Adult Intelligence Scale (12); (c) all
subjects had a positive history of severe maladaptive behaviors; (d) all subjects had no medical contraindications.
Design
An open label design extending over three 6-week periods
was used. All patients initially took part in a prebaseline
period (from February to March 2007). During this interval,
behaviors targeted for observation were selected and operationalized. Inter-rater reliability was established at or above
90%. The prebaseline period was followed by a 6-week pretreatment period (from March 14, 2007 to April 24, 2007)
when subjects did not receive any unusual treatment. During
the following 6-week treatment period (from April 25, 2007
to June 5, 2007) all subjects were given two gelatin capsules
of fish oil supplements containing 0.93 g of eicosapentaenoic
acid (EPA) and dososahexaenoic acid (DHA). Moreover, all
subjects received two multimineral and vitamin supplements
containing 5 mg of vitamin E in order to avoid lipid peroxidation. During the post-treatment 6-week period (from June

6, 2007 to July 17, 2007) the experimental treatment was
stopped. Throughout all phases, all subjects were assessed
daily with the Rossago Behavioral Checklist (see below).
Outcome Measure

computed for the three study periods were plotted. Individual pretreatment severity score means were compared with
their treatment period counterparts using the Wilcoxon test
for paired observations.
Statistical packages R (2.5.1; Foundation for Statistical
Computing, Vienna, Austria) and SPSS (15.0; SPSS Inc., Chicago, IL) were used for all statistical analyses. A two-tailed
p value of !0.05 was considered statistically significant.

Results
Severity and frequency of problematic behaviors during
the study periods are depicted in Figures 1 and 2. Between
the pretreatment period (mean severity score: 18.73,
SD 5 13.06) and the treatment period (mean severity score:
19.75, SD 5 11.58), the severity of symptoms worsened
slightly but not significantly ( p 5 0.054). During the posttreatment period the mean severity score decreased to 14.46


In the present study, an ad hoc caregiver questionnaire, the
Rossago Behavioral Checklist (personal communication)
was used (Table 1). This instrument consists of a 22-item rating scale focusing on behavioral problems. Each item was
rated on a 5-point Likert scale from 0 (none) to 4 (extremely
severe). In this study, we analyzed problematic behaviors
assessed during an 18-week period (6 week pretreatment observational period, 6-week treatment period, 6-week posttreatment period). Primary endpoint of the trial is the severity score
as measured by the Rossago Behavioral Checklist.
Data Analysis
The whole sample averages and standard deviations of the
severity score and the number of problematic behaviors

Figure 1. Evolution of the weekly average severity score.

684

Politi et al./ Archives of Medical Research 39 (2008) 682e685

Figure 2. Evolution of the weekly average problem frequency.

(SD 5 7.55). The patients’ weekly average frequency of

problematic events did not show any improvement between
pretreatment and treatment period (results not shown). No
clear trend was detectable when severity and frequency of
problematic behaviors were computed taking into account
only the hyperactivity-related items of the Rossago Behavioral Checklist (data not shown).

Discussion
Epidemiological data have shown the beneficial effects that
a diet rich in fish oils can have on several psychiatric disorders (13,14). Pilot findings by Amminger et al. (7) seemed
to suggest the effectiveness of fish oil supplementation to
reduce hyperactivity in children with autism. The primary
outcome measure used in the study was the change in the
Aberrant Behavior Checklist (ABC) at 6 weeks (6). However, there are caveats in the study of Amminger et al. (7) that
merit consideration. The sample size was small (n 5 12) and
the authors’ use of repeated measures statistical analysis may
have led to misleading interpretation of results related to stereotypy and hyperactivity scores (8). We thus designed this
study to test the hypothesis that omega-3 FA supplementation
could exert beneficial behavioral effects in adult patients with
severe autism.
Our results failed to convincingly demonstrate a beneficial effect of omega-3 FA supplementation in a group of

young adults with severe autism. In an attempt to confirm
the effect of omega-3 FA on several behavior problems in
persons with autism, we performed a comprehensive analysis of several aberrant behaviors commonly found in autistic individuals. Not only were differences in outcome
between the intervention groups in our study small, but also
the results of our study were inconsistent with those of Amminger et al. (7) and do not support such a positive effect on
hyperactivity reduction. Thus, overall effect of supplementation with omega-3 PUFAs on the incidence of behavioral
problems in this population of adult patients with severe autism seems more modest than that observed for hyperactivity in a trial conducted in children.

Although our open label study and the trial by Amminger
et al. (7) differed with respect to the study population, we do
not think that this explains the apparent divergence of results.
We chose a treatment time and dosage of omega-3 PUFAs
similar to the dose in the previous trial (6), which showed significant effects on hyperactivity scores. Furthermore, the
length of our treatment and the follow-up schedule is such
that we were able to perform a sufficient number of clinical
observations to judge the potential effect of treatment.
There may be some methodological concerns about this
study in adult patients. With respect to limitations of this
investigation, we must consider two issues. Firstly, this is
a single-center study and the number of patients is small.

This limited sample size may have obscured a possible effect of omega-3 FA on aberrant behaviors. Second, behavioral problems were evaluated with a different instrument
compared with the study by Amminger et al. (7). Strengths
of our study rely on our assessment of multiple measures of
behavior and on close follow-up assessments.
In conclusion, in this open label trial we did not find evidence of strong behavioral effects of intake of omega-3
PUFAs from fish oil against problematic behaviors in adult
patients with autism. Fluctuations of the behavioral scores
as observed during our study are likely to represent random
fluctuations, not real treatment effects. In light of our results
and based on the methodological limitations of the study by
Amminger et al., we conclude that caution should be exercised on the potential usefulness of omega-3 supplementations to reduce hyperactivity or other problematic behaviors
in autistic individuals.

Acknowledgments
We are grateful to Sigma Tau Italia and Wyeth Italia for their kind
gift of omega-3 capsules and multivitamin supplementation. We
gratefully acknowledge the excellent nursing assistance of Roberto Albasi.

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