A study by researchers from King’s College London and China Medical University in Taichung, Taiwan, has found that omega-3 fish oil supplements may have equivalent or even greater beneficial effects on attention in children with attention deficit hyperactivity disorder (ADHD) than do conventional drugs, but only among individuals who have otherwise low levels of omega-3 in their blood. The study results indicated that for individuals with already high blood levels of the omega-3 fatty acid eicosapentaenoic acid (EPA), further omega-3 supplementation may have “detrimental” effects on certain measures of ADHD. The scientists say the study is the first that they know of to report the effects of monotherapy using EPA in individuals with ADHD.

“Our results suggest that fish oil supplements are at least as effective for attention as conventional pharmacological treatments among those children with ADHD who have omega-3 deficiency,” said Jane Chang, MD, co-lead researcher from the Institute of Psychiatry, Psychology & Neuroscience at King’s. “On the other hand, it is possible to have too much of a good thing, and parents should always consult with their children’s psychiatrists since our study suggests there could be negative effects for some children.”

The scientists report their findings in Translational Psychiatry, in a paper titled, “High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels.”

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), including EPA and docosahexaenoic acid (DHA), are essential fatty acids (EFA) that have been closely associated with cognitive function and academic performance, the authors explained. Their previous meta-analysis of studies had indicated a link between a deficiency of n-3 PUFAs and ADHD, and suggested that n-3 PFA treatment may improve the clinical symptoms of ADHD in youth.

To investigate directly whether EPA may impact on ADHD, the team carried out a 12-week placebo-controlled trial to evaluate the effects of high dose EPA, compared with placebo, in 92 children and adolescents, aged 6–18 years, who had been referred to the China Medical University Hospital department of psychiatry between July 2016 and December 2017 with a DSM-5 diagnosis of ADHD. All the participants were either drug-naïve or had received no medication for the previous six months.

The main outcome measures of the trial were focused attention, impulsivity, sustained attention, and vigilance, as assessed by the Continuous Performance Test (CPT). Secondary measures were assessed using additional, recognized scoring systems. Blood levels of PUFAs were measured at baseline, and also at the end of the trial. The trial results confirmed that children with the lowest baseline blood levels of EPA showed improvements in focused attention and vigilance after taking the omega-3 supplements for 12 weeks. However, these improvements weren’t seen in children with normal or high baseline blood-levels of EPA. In addition, for children with high pre-existing EPA, omega-3 supplements had negative effects on impulsivity symptoms.

“Overall, EPA improves (more than placebo) focused attention at the CPT test, one of our main outcome measures,” the authors reported. “… we find that youth with the lowest levels of baseline endogenous EPA show the largest improvement in cognitive function.” Conversely, they stated, “We also find that children with the highest baseline EPA levels perform better on placebo than on EPA, in impulsivity and in parental and teachers’ reports of ADHD and emotional symptoms … To our knowledge, this is the first study to report the effects of EPA monotherapy in ADHD, and the first study ever to use endogenous baseline PUFAs levels to stratify subjects in a PUFAs clinical trial.”

Previous studies have reported inconsistent results with respect to the potential impact of omega-3 supplementation on ADHD symptoms, with overall effect sizes being relatively small. Standard treatments offered to parents whose children have ADHD include stimulants such as methylphenidate. The effect size of improvement in attention and vigilance from methylphenidate is 0.22–0.42. In comparison, the effect sizes in the newly reported trial of omega-3 supplementation for those children with low blood levels of EPA were larger, at 0.89 for focused attention and 0.83 for vigilance.

The researchers pointed out that while there are no other studies similar to their study, previous research in healthy children, as well as children and adults with ADHD and other neurodevelopmental disorders, has found that PUFAs improve cognitive function more when the participants also have low n-3 PUFAs status, “i.e., in those with evidence of low dietary intake of fish, or if they present symptoms of aforementioned EFA deficiency … Moreover, EFA deficiency (a measure of symptoms such as excessive thirst, dry skin, brittle nails, and small skin bumps) has been described in children with ADHD, and the severity of EFA deficiency has been associated with ADHD symptom severity.”

The researchers note that their study does have some limitations, and caution that parents should consult with medical professionals before opting to give their children omega-3 supplements. “The omega-3 supplements only worked in children that had lower levels of EPA in their blood, as if the intervention was replenishing a lack of this important nutrient,” said Carmine Pariante, PhD, MD, senior researcher from the Institute of Psychiatry, Psychology & Neuroscience at King’s. “For those children with omega-3 deficiency, fish oil supplements could be a preferable option to standard stimulant treatments. Our study sets an important precedent for other nutritional interventions, and we can start bringing the benefits of ‘personalized psychiatry’ to children with ADHD.”

The study was carried out in Taiwan where diets often contain plenty of fish compared to diets in Europe and North America. Most studies of children with ADHD, conducted largely in Western countries, have shown average blood-levels of EPA that are lower than in the current study. “Nevertheless, with fish intake and other natural sources of omega-3 being constantly advocated as part of a healthy diet, it is important to be aware that supplementing those who already have high levels of EPA may be detrimental,” the authors stated.

Kuan-Pin Su, PhD, co-lead researcher from China Medical University, added, “High blood levels of EPA without using supplements can be achieved through a good diet with plenty of fish, which is common in some Asian countries like Taiwan and Japan. It is possible that EPA deficiency is more common among children with ADHD in countries with less fish consumption, such as in North America and many countries in Europe, and that fish oil supplementation could therefore have more widespread benefits for treating the condition than in our study.”

The authors also suggest that while their results show some benefits of EPA monotherapy on cognitive symptoms of ADHD, “ … it is possible that a combined EPA + DHA strategy might have been more beneficial, and as such we support the recent recommendation by a panel of ADHD experts that patients who prefer omega-3 supplements over stimulants should take a combination of DHA and EPA at doses ≥ 750 mg per day for at least 12 weeks. However, we additionally recommend that this strategy should be even more strongly advocated for children with evidence of low endogenous PUFAs levels, as indicated by direct measurement, dietary habits, or symptoms of EFA deficiency.”

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