November 20, 2019

expert reaction to study looking at Omega-3 fish oil and ADHD in children

Research, published in the journal Translational Psychiatry, reports that Omega-3 fish oil may be beneficial for the treatment of ADHD for those children that have the condition, and are deficient in Omega-3. 

Dr Bernadka Dubicka, chair of the Royal College of Psychiatrists’ child and adolescent faculty, said:

“This is a small study with mixed findings and the omega-3 fatty acid EPA (eicosapentaenoic acid) may not be helpful for impulsivity, which can be very debilitating for people with ADHD.

“More research is needed before fish oil supplements can be recommended as a treatment for ADHD.”

Dr Kate Langley, Senior Lecturer, School of Psychology, Cardiff University, said:

“This paper reports on a randomised control trial of omega-3 fatty acid EPA supplementation compared to a placebo in children with ADHD.  The main outcome for this study was measures of cognitive tasks related to sustained attention, impulsivity and vigilance.  Their main analyses found limited support for EPA supplementation on a single cognitive measure.

“The authors also report secondary analyses looking at those with low levels of EPA at the start of the study, thus stratifying the sample by initial omega-3 levels.  In these analyses, they found statistically significant improvements in two of a number of cognitive measures.

“These analyses stratifying the sample, whilst interesting, were not the main aim of the original study and should therefore be considered exploratory, especially as only a third of the original sample were in this low EPA group (29 children, split between the EPA and placebo conditions).  The authors note that they looked at a number of different measures and did not take this into account in their statistical analysis – this may mean that there is a greater likelihood of significant findings by chance and highlights the need to be cautious when interpreting these findings and the need for replication.

“Of note, there were no significant improvements in the core ADHD symptoms of inattention, hyperactivity or impulsivity as measured by parents or teachers in either the main or stratified sample.

“The paper presents the data in a considered manner, but the press release broadens the implications further to suggest that, in those with low baseline levels, treatment by omega-3 supplementation may be as effective as conventional pharmacological treatments.  This takes the findings of the study too far as they are exploratory findings in a small sample and relate to cognitive improvements rather than the core ADHD symptoms which are the main focus of most treatments for ADHD.  The suggestions that the effect size improvements here are bigger than those in other treatments should also be treated with caution because they are on a small sample with large margins for error.”

Prof Graham Burdge, Professor of Nutritional Biochemistry, University of Southampton, said:

“There is no child in the UK who is at risk of being deficient in omega-3 fatty acids (the only reported cases are in patients receiving artificial feeding in hospital).  However, nobody can define what ‘low’, as opposed to deficient, EPA actually is because there is no defined level of deficiency or of a normal range.  So we can only look within a cohort at levels by comparing two groups and seeing whether levels are lower in one group than the other.  There is marked variation in EPA levels between normal healthy people in the population, but we can’t put a number on what ‘low’ means, and even if levels are lower in one group than the other anyone in the UK is very unlikely to be deficient.

“It should be noted that there is a potential flaw in the study design because the ‘placebo’ was soybean oil which contains an omega-3 fatty acid (alpha-linolenic acid) that can be converted to EPA.  This confounds the findings of the study being interpreted as due to EPA since both the test oil and the placebo were sources, albeit the placebo indirectly, of EPA.  The article does not meet the usual standards of reporting and it doesn’t appear to have been registered on a clinical trials database, which is the norm for all such studies.  There is no information about the children who took part.  For example, were the groups matched to eliminate possible confounding factors (e.g. were the numbers of boys and girls the same in each group?).  The age range is huge, but there does not appear to be any adjustment for this.  Intuitively, a child of 6 years is very different physically and mentally from an 18 year old and so these ages cannot be considered together.  There is no information to indicate whether the behavioural assessments were adjusted for the children’s ages.  There is no mention of the socioeconomic background of the children.  Their background can have a substantial impact on their cognition and behaviour.  There’s no information about the supplements e.g. the source of the EPA isn’t disclosed, which is important because if it was derived from fish oil, then it would be difficult to blind the study because of residual odour.  It is also important to know the composition of the EPA and placebo oils in order to eliminate the possibility that there were differences between the interventions that could suggest and alternative explanation for the findings.”

Prof John Stein, Emeritus Professor of Physiology, University of Oxford, said:

“The Chang et al study shows that EPA supplements can help some ADHD children improve their ability to concentrate.  This is a subject of great controversy but this paper speaks to many of the problems that bedevil the study of nutrition in psychiatry.  First they measured baseline levels of EPA so that they could see whether their supplement actually changed blood levels which many studies have not, and they stratified the children according to their baseline levels.  This confirmed that the lower their initial level the greater the beneficial effect on attention.  Second they gave large doses of EPA and measured both EPA and DHA, so that they could distinguish the effect of each.  Again many studies have made no such distinction.  Third they recognised that psychiatric diagnoses are broad and overlapping.  They analysed a subgroup of the ADHD children with opposition and defiance and showed that these benefited even more from the EPA.

“Of course there are many caveats.  Numbers were small, one could quarrel with the stats and they failed to show any effects on markers of inflammation.  But the study begins to answer why omega 3 studies in this area are so contradictory.”

Prof Emily Simonoff, Chair of the European ADHD Guidelines Group, and Professor of Child and Adolescent Psychiatry, Institute of Psychiatry Psychology & Neuroscience, King’s College London, said:

“This paper reports findings from an RCT of omega-3-fatty acids in children with a clinical diagnosis of DSM-5 ADHD.  The primary outcome measure is a continuous performance task, where several subscales are reported, none of which has been pre-specified as the primary outcome measure, either in the Clinical Trials.Gov registration and there also does not appear to be a subsequent pre-registered statistical analysis plan.  The secondary outcome measuring ADHD behaviour pre-specified in the trial registration, the SNAP-IV, is not reported here.  There was no systematic evaluation of possible adverse effects reported.  The sample was divided into tertiles based on EPA levels and report that those with the lowest levels (29 participants, randomized to either active medication or placebo) appeared to show the greatest benefit from EPA, but these group differences were not formally statistically tested.

“The National Institute of Health and Clinical Excellence (2018) does not recommend the use of omega-3 fatty acids in ADHD, based on a systematic review of the available randomized controlled trials.  While the current study is intriguing, more evidence on large, adequately powered samples, using pre-specified statistical analysis plans and particularly with robust behavioural outcomes (which are the ultimate target of interest) are required before changing practice.”

Dr Jessica Agnew-Blais, MRC Skills Development Fellow and Honorary Lecturer, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, said:

“The findings from this study offer the interesting suggestion that benefits of fish oil supplementation for performance on some neuropsychological measures of attention may be specific to those with lower levels of eicosapentaenoic acid (EPA) at baseline.  However, these findings remain suggestive given the small number of participants (n=29) with low baseline EPA levels (so, about 15 people in the fish oil group compared to about 15 in the placebo group).

“It is very important to keep in mind that this study did not find any benefit of fish oil supplementation over placebo on ADHD symptom levels or emotional problems among participants.  These are outcomes that many studies find do improve with conventional pharmacological treatments for ADHD.  Therefore, these findings do not suggest that fish oil supplementation is better – or as effective – as stimulant medication in treating ADHD symptoms.”

‘High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels’ by Jane Pei-Chen Chang et al. was published in Translational Psychiatry at 01:00 UK time on Wednesday 20 November 2019. 

DOI: 10.1038/s41398-019-0633-0

Declared interests

Dr Kate Langley: “I have no conflicts of interest.”

Prof Graham Burdge: “Prof Burdge has received research funding from Nestle, Abbott Nutrition and Danone.  He has served as member of the Scientific Advisory Board of BASF and is member of the BASF Asia Grant Panel.”

Prof John Stein: “I am a Trustee of the Inst food, brain & behaviour.  No conflicts of interest.”

Prof Emily Simonoff: “No conflicts of interest.”

Dr Jessica Agnew-Blais: “No financial disclosures.  My fellowship is funded by the MRC.”  Jessica was not on the research team for this study.

None others received.