DHA supplementation appears to offer a safe and effective way to improve reading and behavior in healthy but underperforming children from mainstream schools. Replication studies are clearly warranted, as such children are known to be at risk of low educational and occupational outcomes in later life.

ITT analyses showed no effect of DHA on reading in the full sample, but significant effects in the pre-planned subgroup of 224 children whose initial reading performance was ≤20 th centile (the target population in our original study design). Parent-rated behavior problems (ADHD-type symptoms) were significantly reduced by active treatment, but little or no effects were seen for either teacher-rated behaviour or working memory.

Omega-3 fatty acids are dietary essentials, and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems. Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning, although most previous trials have involved children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) or developmental coordination disorder (DCD). Here we investigated whether such benefits might extend to the general child population.

Competing interests: The authors have read the journal's policy and have the following conflicts: Funding for the trial was provided by Martek Biosciences Inc., who also provided product and placebo. PM, JRB, and RPS declare that no other competing interests exist. AJR acts as an occasional paid consultant (lectures and advisory work) for companies and organisations involved in producing, selling, or promoting foods or supplements containing ω-3. None of these issues alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Funding: The study was funded by Martek Biosciences Inc. ( http://www.lifesdha.com/ ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © Richardson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Introduction

Omega-3 fatty acids are dietary essentials, but intakes are low by historical standards in most modern developed countries [1]. The longer-chain omega-3 found in fish, seafood and some algae – known as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) – are the most biologically important forms, not only for cardiovascular and immune system health, but also for normal development and functioning of the brain and nervous system [2]. Accumulating evidence from epidemiological, biochemical and intervention studies suggests that low dietary intakes of these long-chain omega-3 may have a detrimental effect on children's behavior and cognitive development [3], [4].

Prior to this study there was already some evidence from randomized, controlled trials (RCTs) that dietary supplementation with omega-3 long-chain, polyunsaturated fatty acids (LC-PUFAs) may have benefits for child behavior and learning [5], [6]. However, almost all such studies had involved populations with specific developmental conditions such as attention-deficit/hyperactivity disorder (ADHD), dyslexia or developmental coordination disorder (DCD). They were also small trials with considerable differences between the populations studied, treatment formulations used, and outcomes assessed. Findings from these RCTs had therefore been mixed, but the most consistently reported benefits in children of school age had included improvements in attention and concentration, and reductions in other ‘ADHD-type’ symptoms such as impulsive and oppositional behaviour, as well as anxiety and emotional lability [5], [6]. Highly significant improvements in both reading and spelling performance were also found in the one study that assessed these outcomes [7].

These findings raised the important question of whether such results might have broader applicability. A systematic review of the effects of omega-3 intake on child behavior and learning, carried out in 2006 for the UK Food Standards Agency, emphasized that findings from groups of children with varying levels of clinically reported neurodevelopmental disorder could not reliably be used to assess the potential effects of omega-3 fatty acids on the educational performance of mainstream UK school children [8]. There was thus a clear need for RCTs involving healthy children from the general school population. In designing such a study, however, we reasoned that any benefits from omega-3 supplementation would more likely be demonstrable in children who were initially underperforming on the outcomes of interest. Official figures show that 20% of all children in mainstream UK schools are in need of additional learning support [9]. Given the importance of literacy skills to children's educational progress, reading achievement was chosen as a primary outcome in this study; and we decided to focus simply on those children whose current reading performance placed them within the bottom 20% of the general population distribution.

Treatment formulations were another important issue. Most previous research had used varying mixtures of EPA and DHA (the two main omega-3 LC-PUFAs found in fish oils) and sometimes other ingredients, making it difficult to identify which component(s) might be responsible for any treatment effects. DHA is an essential structural component of neuronal membranes, and therefore the main omega-3 found in brain and nerve tissue. Furthermore, the ability of humans to synthesize DHA in-vivo from shorter-chain, plant-derived omega-3 such as alpha-linolenic acid, is very limited, making a direct dietary supply of DHA particularly important [2].

This study was therefore designed to investigate the importance of DHA for behavior and learning in healthy but underperforming children from the mainstream school population. The study outcomes were selected for their relevance to children's educational progress and future life chances, and involved simple, practical measures of reading, working memory and behavior.

(a) Reading: Literacy skills are fundamental to educational and occupational success. Only 85 per cent of UK adults had a basic level of functional literacy in 2005, and in 2006, five million adults were judged to be under-functioning in this domain [10]. These statistics are an issue of major public concern; and given the dynamic and cumulative nature of the development of literacy skills in children, early intervention is known to be more cost-effective than later remediation [11].

(b) Working memory: The ability to hold and manipulate information in the short-term is important for many aspects of everyday life as well as educational performance; and furthermore, working memory problems (particularly the accurate processing and retrieval of auditory/verbal sequential information), are commonly associated with reading difficulties [12], [13]. (c) Behavior: Difficulties with behavior in childhood are one of the best predictors of poor educational and occupational achievements in later life. Such problems affect an increasing proportion of UK schoolchildren, and again early intervention is key to minimising the adverse consequences to individuals, families and wider society [14].