Do Omega-3/6 Fatty Acids Have a Therapeutic Role in Children and Young People with ADHD?

Table 2

Information extracted from trials looking at LC3PUFAs and ADHD.

Reference and country	Subjects; M/F and sample size	Mean age	Study design and methods	Dose of supplement	Main findings
[31]; Mexico	90 children; (60 M, 30 F)	6–12 years; Mean age 8.27 years	12-month trial (unblinded); MPH, omega-3/6 or a combination	Equazen: 558 mg EPA, 174 mg DHA, and 60 mg GLA (9 : 3 : 1 ratio)	Significantly better scores on ADHD. Adverse events were numerically less frequent with omega-3/6 or MPH + omega-3/6 than MPH alone.
[41]; Netherlands	40 boys with ADHD and 39 matched, typically developing controls	Aged 8–14 years	16-week trial	10 g of margarine daily, enriched with either 650 mg of EPA/DHA or placebo	EPA/DHA supplementation improved parent-rated attention in both children with ADHD and typically developing children. Phospholipid DHA level at follow-up was higher for children receiving EPA/DHA supplements than placebo.
[32]; United Kingdom	76 M adolescents with ADHD	12–16 years, mean = 13.7 years	12-week trial	Equazen: 558 mg EPA, 174 mg DHA, and 60 mg GLA (9 : 3 : 1 ratio)	In the treatment group, supplementation enhanced EPA, DHA, and total omega-3 fatty acid levels.
[26]; Australia	90 Australian children with ADHD symptoms higher than the 90th percentile on the Conners’ Rating Scales	7 to 12 years	4-month crossover study evaluating literacy and behaviour up to 12 months	Supplements rich in EPA, DHA, or LA	Increased erythrocyte EPA + DHA was associated with improved spelling () and attention (), reduced oppositional behaviour (), hyperactivity (), cognitive problems (), DSM-IV hyperactivity (), and DSM-IV inattention ().
[27]; China	179 children with lower IQs or ADHD to receive	7 to 12 years	3-month trial: evaluated effects on visual acuity	Ordinary eggs or eggs rich in EPA and DHA	Both groups of children showed a significant improvement in visual acuity (); however, visual acuity in the study group was significantly better than that of the control group ().
[37]; Germany	95 children diagnosed with ADHD according to DSM-IV criteria	6–12 years	16-week trial	Omega-3 fatty acid mix	Improved working memory correlated significantly with increased EPA, DHA, and decreased ARA.
[39]; Israel	200 children diagnosed with ADHD	6–13 years	15-week trial followed by an open-label extension	300 mg PS-omega-3/day	Study results demonstrate that consumption of PS-omega-3 by children with ADHD, is safe and well tolerated, without any negative effect on body weight or growth.
[38]; Malaysia	103 children	6–12 years	8-week trial	635 mg EPA, 195 mg DHA	Significant reduction in levels of CRP in the omega-3 group and significant increase in SOD and glutathione reductase. Significant improvement in ASQ-P score (measure of hyperactivity).
[33]; Sweden	75 children and adolescents with DSM-IV ADHD	8–18 years	3-month trial. Omega-3/6 (Equazen) or placebo, followed by 3 months of open phase	Omega-3/6 (Equazen) or placebo; Equazen: 558 mg EPA, 174 mg DHA, and 60 mg gamma linoleic acid (9 : 3 : 1 ratio)	Subjects with more than 25% reduction in ADHD symptoms were classified as responders. Compared to nonresponders, the 6-month responders had significantly greater n-3 increase at 3 months and decrease in n-6/n-3 ratio at 3 and 6 months ().
[28]; Australia	90 Australian children with ADHD symptoms higher than the 90th percentile on the Conners’ Rating Scales	7 to 12 years	4-month trial	Supplements rich in EPA, DHA, or safflower oil	Increased erythrocyte DHA was associated with improved word reading and lower parent ratings of oppositional behaviour. These effects were more evident in a subgroup of 17 children with learning difficulties.
[29]; Sri Lanka	Children with ADHD active group, placebo	6–12 years	6-month trial	Capsule; containing n3 and n6 (fish oil) and cold-pressed evening primrose oil	Statistically significant improvement was not found at 3 months of treatment between groups but was evident at 6 months of treatment () with inattention, impulsiveness, and cooperation with parents and teachers.
[40]; Norway	92 children with ADHD	7–12 years	15-week RCT	0.5 g EPA versus placebo	EPA improved CTRS, inattention/cognitive subscale (), but not Conners’ total score.
[34]; Sweden	75 children and adolescents with DSM-IV ADHD	8–18 years	3-month trial. Omega-3/6 (Equazen) or placebo, followed by 3 months of open phase	Equazen: 558 mg EPA, 174 mg DHA, and 60 mg GLA (9 : 3 : 1 ratio)	A subgroup of 26% responded with more than 25% reduction of ADHD symptoms and a drop of Clinical Global Impression scores to the near-normal range. After 6 months, 47% of all showed such improvement. Responders tended to have ADHD inattentive subtype and comorbid neurodevelopmental disorders.
[30]; Israel	73 unmedicated children with a diagnosis of ADHD	7–13 years	7-week trial	480 mg LA, 120 mg ALA, placebo: 1000 mg of vitamin C	Both treatments ameliorated some of the symptoms, but no significant differences were found between the groups in any of the treatment effects.
[35]; Japan	40 AD/HD (including eight AD/HD-suspected) children who were mostly without medication	6–12 years	2-month trial	Foods containing fish oil (fermented soybean milk, bread rolls, and steamed bread; 3.6 g DHA/week from these foods)	DHA-containing foods did not improve ADHD-related symptoms. Visual short-term memory and errors of commission (continuous performance) significantly improved in the control group compared with the changes over time in the DHA group.
[36]; USA	63 children with ADHD, all receiving effective maintenance therapy with stimulant medication	6–12 years	4-month trial	345 mg DHA	No statistically significant improvement in any objective or subjective measure of ADHD symptoms.

Key. ADHD, attention deficit hyperactivity disorder; ALA, alpha-linolenic acid; ARA, arachidonic acid; CRP, C-reactive protein; CTRS, Connor Teacher Rating Scale; DHA, docosahexaenoic acid; DSM-IV; Diagnostic and Statistical Manual of Mental Disorders; EPA, eicosapentaenoic acid; F, female; GLA, gamma linoleic acid; LA, linoleic acid; M, male; MPH, methylphenidate; PS, phosphatidylserine; SOD, superoxide dismutase.