Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: A randomized controlled trial (original) (raw)

Applied nutritional investigation

Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: A randomized controlled trial

Abstract

Objective

Methods

Supplements rich in EPA, DHA, or safflower oil were randomly allocated for 4 mo to 90 Australian children 7 to 12 y old with ADHD symptoms higher than the 90th percentile on the Conners Rating Scales. The effect of supplementation on cognition, literacy, and parent-rated behavior was assessed by linear mixed modeling. Pearson correlations determined associations between the changes in outcome measurements and the erythrocyte fatty acid content (percentage of total) from baseline to 4 mo.

Results

There were no significant differences between the supplement groups in the primary outcomes after 4 mo. However, the erythrocyte fatty acid profiles indicated that an increased proportion of DHA was associated with improved word reading (r = 0.394) and lower parent ratings of oppositional behavior (r = 0.392). These effects were more evident in a subgroup of 17 children with learning difficulties: an increased erythrocyte DHA was associated with improved word reading (r = 0.683), improved spelling (r = 0.556), an improved ability to divide attention (r = 0.676), and lower parent ratings of oppositional behavior (r = 0.777), hyperactivity (r = 0.702), restlessness (r = 0.705), and overall ADHD symptoms (r = 0.665).

Conclusion

Increases in erythrocyte ω-3 polyunsaturated fatty acids, specifically DHA, may improve literacy and behavior in children with ADHD. The greatest benefit may be observed in children who have comorbid learning difficulties.

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is commonly diagnosed in childhood and has a high comorbidity with other disorders of behavior and mood such as conduct disorder and developmental coordination disorder [1]. At least one-fourth of children with ADHD also have a learning disorder resulting in difficulties with reading, spelling, and writing [2].

The ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and, to a lesser extent, the ω-6 PUFA arachidonic acid (AA) constitute a large proportion of the lipid in the brain [3]. The ω-3 PUFAs DHA and eicosapentaenoic acid (EPA) are involved in many aspects of brain function including cell growth, neural signaling, and gene expression [4]. The low intake of ω-3 PUFAs in children from Western societies such as Australia is therefore of concern [5], [6], not only for physical health such as blood pressure [7] but also for brain function, with implications for developmental disorders such as ADHD.

Some randomized controlled trials have investigated effects of ω-3 PUFA supplementation on behavior in volunteers with ADHD, with varying success [8]. The inconsistent results seen in these trials could be attributed to methodologic differences including variations in the type of supplement used [9]. Most studies have used supplements containing a combination of EPA and DHA in varying ratios. One study used pure DHA 345 mg [10] in medicated boys with ADHD and reported no effects; another study used a supplement containing only EPA 500 mg and reported improved ADHD symptoms [11], suggesting that pure EPA supplementation will assist in alleviating ADHD symptoms. The effects of the long-chain ω-3 PUFAs, EPA and DHA, on behavior, cognition, and literacy in children with ADHD have not been compared within a single randomized, controlled, intervention trial.

Variations among trials could also be attributed to the choice of volunteers recruited and the outcomes assessed. In the UK, improvements in cognitive and behavioral symptoms were observed after PUFA supplementation in children with dyslexia and ADHD symptoms [12] and in children with dyspraxia (one-third with ADHD symptoms in the clinical range) who were also on average 1 y behind in reading and spelling [13]. An Australian study found improved parent ratings of attention and behavior in children with ADHD symptoms in the clinical range [14], [15]. A more recent Swedish study with children diagnosed with ADHD found that the subgroup with reading and writing difficulties were among the strongest responders [16]. In contrast, a study that included only boys who met strict Diagnostic and Statistical Manual, Fourth Revision criteria for ADHD and excluded comorbid disorders failed to find a treatment effect [10]. Therefore, the effects of ω-3 PUFA supplementation on behavior and literacy in children with ADHD symptoms and comorbidities need further investigation.

Importantly, few of these trials have included blood PUFA analysis [10], [17]. Serum, plasma, or erythrocyte PUFA contents are biomarkers of PUFA intake and bioavailability [18], with the latter being most indicative of long term consumption and tissue incorporation. In the present sample of children, we found that higher ω-6 PUFA and lower ω-3 PUFA levels in erythrocytes were predictive of poorer outcomes at baseline, particularly word reading [19]. The inclusion of PUFA status in supplementation trials could be used to determine if the treatment is efficacious in children with a lower baseline ω-3 PUFA intake or in those who exhibit the greatest increase in PUFA levels over the supplementation period.

The aim of this study was to investigate effects of a selective supplementation with EPA or DHA versus the ω-6 PUFA linoleic acid (LA) on behavior, cognition, and literacy in children 7 to 12 y old with ADHD symptoms in a randomized, placebo-controlled trial. The erythrocyte PUFA status (percentage of total fatty acids) was used to determine if those with lower ω-3 PUFA levels were the greatest responders. In addition, the changes in PUFA levels and their correlation with changes in behavior and literacy/cognition were examined over 4 mo.

Section snippets

Materials and methods

A 4-mo parallel comparison of effects of a DHA-rich or an EPA-rich fish oil with an LA-rich safflower oil was undertaken as stage 1 of a 12-mo randomized, controlled, three-way crossover trial in children 7 to 12 y old with ADHD symptoms. The study was conducted in Adelaide and Brisbane, Australia and was approved by the human research ethics committees of the University of South Australia and the Queensland University of Technology. It was registered with the Australian New Zealand Clinical

Description

Of the 90 children 6 to 13 y old who commenced the study (52 at the University of South Australia and 38 at the Queensland University of Technology), three were excluded owing to a lack of an ADHD diagnosis or ADHD symptom severity scores below the 90th percentile on the Conners Global Scale. Seventy children completed the 4-mo assessments. Blood samples were obtained from 75 volunteers at baseline and 52 volunteers at 4 mo and from 48 children at the two time points. There were no differences

Discussion

This study investigated the effects of supplementation with EPA- or DHA-rich oil on literacy, cognition, and behavior of children with ADHD symptoms. No treatment effects were observed with the EPA or DHA-rich supplements compared with the LA control. However, an increased erythrocyte DHA over 4 mo was associated with improved word reading and oppositional behavior in the entire sample, and this effect was much stronger in the subgroup with learning difficulties, who also showed associations

Conclusion

An increase over 4 mo in erythrocyte ω-3 PUFAs, particularly DHA, was associated with improvements in literacy and the behavior of some children with ADHD. The greatest benefit was observed in children who had comorbid learning difficulties.

Acknowledgments

The authors acknowledge the assistance of Jacqueline Boon, Shelley Appleton, Suzanne Hegarty, and Liz Anderson with the recruitment and data collection in Brisbane and all the children and their parents for their participation.

References (33)

et al.

Developmental coordination disorder: associated problems in attention, learning, and psychosocial adjustment

Hum Mov Sci

(2002)

B.J. Meyer et al.

Australian children are not consuming enough long-chain omega-3 polyunsaturated fatty acids for optimal health

Nutrition

(2011)

T.A. O'Sullivan et al.

Dietary intake and food sources of fatty acids in Australian adolescents

Nutrition

(2011)

A. Ramel et al.

Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction

Nutrition

(2010)

R.G. Voigt et al.

J Pediatr

(2001)

A.J. Richardson et al.

Prog Neuropsychopharmacol Biol Psychiatry

(2002)

N. Sinn et al.

Cognitive effects of polyunsaturated fatty acids in children with attention deficit hyperactivity disorder symptoms: a randomised controlled trial

Prostaglandins Leukot Essent Fatty Acids

(2008)

N. Vaisman et al.

Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids

Am J Clin Nutr

(2008)

P. Rise et al.

Fatty acid composition of plasma, blood cells and whole blood: Relevance for the assessment of the fatty acid status in humans

Prostaglandins Leukot Essent Fatty Acids

(2007)

C.M. Milte et al.

Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls

Prostaglandins Leukot Essent Fatty Acids

(2011)

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While it has been suggested that EPA may be more effective than DHA in managing these disorders, for reasons not completely understood (Jazayeri et al., 2008; Song and Zhao, 2007; Peet and Stokes, 2005), others reported similar effects on mood between EPA and DHA or even an advantage of DHA compared to EPA (Sinn et al., 2012). Milte et al. (2012) observed DHA to be more effective than EPA in improving cognition in ADHD-afflicted subjects. The EPA vs DHA debate on mental function is an important one and largely underinvestigated. View all citing articles on Scopus

Ms. Milte is supported by a Ph.D. scholarship from the South Australian Health Department. Drs. Sinn, Young, and Howe are recipients of an Australian Research Council Linkage Project grant (LP0776922) in partnership with Novasel Australia (“Cognitive and Behavioral Benefits of Omega-3 Fatty Acids Across the Lifespan”).

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