Clinical practice reveals the need to develop alternative treatments for children with ADHD who do not respond to standard psychostimulant treatment or whose families deprive them of treatment, fearful of the short- and long-term side effects of medication. Consequently, there is a significant percentage of parents who prefer alternative treatments for the management of ADHD symptoms in their children. The present study was, therefore, designed to investigate the effects of n-3 PUFA supplements, compared with the n-6 PUFA placebo, on the core ADHD symptoms in children following a 16-week, double-blind, one-way, crossover randomized study, using the SWAN and Conners’ rating scales completed by the parents or caregivers and the teachers.
An important issue of the present investigation was to determine whether n-3 PUFA can improve behavioural parameters in ADHD subjects. For behaviour assessment, we used the Conners’ parent rating scale that has been extensively used in various investigations and represents a suitable tool for behaviour evaluation in youths. The results from the parent version of the Conners’ questionnaire revealed that from baseline (time 0) to the end of phase 1 (time 1), the subjects’ ADHD symptoms showed a statistically significant improvement in several of the Conners’ subscales in both groups. Within this time frame, subjects in group A showed a greater, but not statistically significant, improvement in comparison with subjects in group B. From time 1 to time 2, further improvement was seen in both groups, which was more significant in patients from group B, although only statistically significant for subscale L in this group.
Moreover, our analysis of the teacher-completed SWAN questionnaire indicated no significant differences in ADHD symptoms during the duration of the study among subjects in groups A and B. In contrast, an improvement in the different scales and, in particular, scale A (inattention) was seen in the parent SWAN questionnaire, although the improvement was not statistically significant. Altogether, these data suggest that n-3 PUFA supplementation may result in improvements in ADHD symptomatology, but a positive effect of n-6 PUFA cannot be excluded according to our findings. It is possible that n-3 PUFA supplementation at higher levels may be necessary to achieve clear-cut improvements in ADHD symptomatology.
Based on the data relative to behaviour and academic performance in 26 subjects who completed the study, no significant improvement was recorded in six subjects, whereas 12 subjects reported minimal improvement. However, eight subjects (four each in groups A and B) exhibited a significant clinical improvement following the administration of the n-3 PUFA supplement, particularly for the inattention and global DSM-IV total Conners’ subscales. This improvement, particularly important in the attention dimensions, is limited in scope compared with two other studies (47
) that reported an amelioration for all dimensions, including attention, hyperactivity and impulsivity. However, our cohort consisted of more children with ADHD, in which the inattentive type (20 of 37 [54%]) was more elevated than what is typically observed in ADHD, which may in part explain the observations.
The literature to date indicates variable effects on different mental health disorders and particularly on ADHD following treatment with n-3 PUFA. For example, two studies (49
) comparing the use of a DHA supplement with a placebo showed no significant improvement in the symptoms of inattention in a group of children receiving DHA.
Improvements were seen in ADHD symptoms in several studies in which children were given a placebo or an n-3 PUFA supplement, which included EPA (51
). However, these results are not always conclusive. Some of the studies that were performed were only based on parents’ (39
) or teachers’ evaluation (47
). This is important because a statistically significant improvement in ADHD symptoms was seen in our work and also in the study by Sinn and Bryan (48
), only in the parent rating scales but not in the teacher rating scales. Similarly, Stevens et al (25
) concluded that marked improvements were noted in multiple outcomes (rated by parents) in both groups, but a clear benefit was not observed from PUFA supplementation in all ADHD behaviour characteristics.
Thus, our results indicate a statistically significant trend toward improvement in the core symptoms of ADHD as assessed by Conners’ parent rating scales in children given an n-3 PUFA supplement. A clear clinical improvement was seen in eight of the 37 children (21.6%) in our study. However, if we take into consideration only the 26 children who completed our study, as per Sinn and Bryan’s study (48
), we can note an improvement of approximately 30.7%, which is quite similar to their results. The amelioration of ADHD symptoms in both placebo and n-3 PUFA groups in the first eight weeks of the study (phase 0 to phase 1) also suggests the presence of a placebo effect. Nevertheless, the improvement measured in group A patients receiving the supplement is greater than in group B patients who were given the placebo. Moreover, further improvement during phase 2 was, in general, more evident and statistically significant for inattention in children from group B who received the n-3 PUFA supplement during eight weeks. Finally, based on clinical and statistical evaluations, we observed that eight of the 26 subjects (approximately 30%) who completed the study had a significant clinical improvement following the administration of the n-3 PUFA supplement.
Importantly, our young patients were not deficient in EFA. They did not display lower levels in arachidonic acid, EPA or DHA. Only the ALA proportion was somewhat decreased compared with controls. Therefore, future trials should attempt to include ALA in their n-3 PUFA supplements, in addition to EPA and DHA. This is particularly important because the symptoms of ADHD, including attention and behaviour, were improved after the administration of a combination of vitamin C and flax oil containing ALA – a precursor of DHA and EPA – in an open-label study (52
There are a number of limitations regarding the present study that should be taken into account when interpreting the behavioural data. The high attrition rate resulted in a smaller sample size, which did not allow us to reach statistical significance for various variables. Moreover, the response of subjects to an n-3 PUFA supplement was monitored using parent and teacher behaviour rating scales. Although DSM-IV ADHD symptom rating scales constitute the most common method to estimate the response to medication as a primary outcome measure given its reliability and validity, clinical studies have started using measures of overall impairment and quality of life to assess the impact of treatment on patients with ADHD.
Our clinical evaluation with the families of the subjects revealed that at the end of the study, most families preferred to continue the use of the n-3 PUFA supplement rather than medication. One of the reasons may be attributed to the safety profile of the supplements because none of the subjects reported significant adverse effects. Another reason may be related to improved functioning as a result of a decrease in the deviant behaviours in day-to-day living. Although the present investigation did not assess quality of life, functional impairment and its correlation to DSM-IV ADHD symptoms, other studies have shown that, in patients with ADHD, the correlation between measures of functional impairments and symptoms of ADHD is modest (53
Therapy with n-3 PUFA supplements was well tolerated in the current study. Furthermore, no differences were detected in the CPT scores of subjects at baseline or during the study. This is consistent with reports in the literature that CPT scores are not specific to the diagnosis of ADHD, and there is no significant correlation between the results on the behaviour rating scales and scores on CPT (54
This is one of the few studies that included a detailed biochemical analysis of the lipid profile of children with ADHD. Unlike reports in the literature, abnormalities in plasma EFA, including the deficiency of DHA and EPA, were not observed in our cohort. On the contrary, the concentrations of the latter were higher, but the relative proportion of ALA was lower compared with normal controls, which suggests that French Canadian patients have satisfactory EFA consumption and intestinal fat absorption.