Index
Symptoms of inattention were reduced after dietary supplementation with this type of fatty acid in children with attention-deficit.
The attention deficit these children presented was with or without hyperactivity.
The headlines of significant research journals sometimes feature reports that there seems to be nothing omega-3s can’t do. Other times, they seem overrated.
Omega-3 fatty acids are named after their double bond (which makes the fatty acid “unsaturated” since it has fewer hydrogen atoms than the maximum), three carbons of the omega, or the end of the chain.
Omega-3s are found in fish and plants, such as flax and walnuts.
The two omega-3s used in this study, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), come from fish sources rather than plants and are critical for early brain development.
These fatty acids are added to many commercial baby formulas to mimic the high levels found in breast milk.
The study under review examined the effects of omega-3 supplementation on the symptoms of attention deficit/hyperactivity disorder (ADHD).
Formerly known as ADD or Attention Deficit Disorder, the 1987 revision of the Gold Standard for Psychiatric and Mental Disorders, known as the Diagnostic and Statistical Manual, relabelled ADHD.
A further review in 1994 classified patients into the ‘hyperactive-impulsive’ subtype, the ‘inattentive’ subtype, or the ‘combined’ subtype based on their specific symptoms. ADHD is one of the most commonly diagnosed childhood disorders.
Medications for ADHD are primarily (and perhaps paradoxically) central nervous system stimulants, with methylphenidate being the most commonly prescribed drug.
One of the hypothetical causes of ADHD is decreased dopamine production, which can cause the unnecessary firing of neurons unrelated to the task the brain is trying to complete.
The drug decreases dopamine and norepinephrine levels in the brain to be used more effectively because it blocks reuptake receptors, thus improving the functionality of neurons in the prefrontal cortex responsible for cognitive function.
Mechanism of action of methylphenidate
Prescribing a stimulant for someone who is already hyperactive seems counterintuitive.
Methylphenidate (which has a variety of names, including Ritalin and Concerta) and other similar stimulants were prescribed for ADHD for decades before a mechanism of action was determined.
Usually, only in doses higher than those prescribed for ADHD do the stimulant effects gain control.
In lower doses, the drug helps coordinate the actions of dopamine, norepinephrine, and, to a lesser extent, serotonin by preventing receptors in the brain from reactivating it.
The increased effect of dopamine helps the brain focus on tasks, while the effects of norepinephrine can enhance the brain’s normal reward cycle to complete tasks.
Stabilized serotonin can also help produce a sense of well-being and calm.
Who and what was studied?
Forty children living in the Netherlands, aged between eight and 15, diagnosed with ADHD, were recruited for the study and are from now on referred to as the ADHD group.
Most of the participants were taking methylphenidate at enrollment. They were allowed to continue taking the drug as prescribed for the duration of the study, except for a 24-hour washout period before the functional MRI scans.
An additional 39 children without ADHD were also enrolled as matched participants by age, BMI, and hand preference,
The study referred to these as the Reference Group (RG).
Within each group, half of the participants were randomly assigned to consume 10 grams daily of a margarine product with added omega-3 fatty acids, with 650 milligrams each of DHA and EPA per serving.
This was denoted as the “active” arm of each group. The other half of each group was assigned to the “placebo” arm and consumed 10 grams of margarine that contained monounsaturated fatty acids instead of omega-3 fatty acids.
The two products were identical in saturated fatty acid and omega-6 fatty acid contents.
Participants consumed their assigned margarine product for a total of 16 weeks. They were told to avoid other omega-3 supplements or fortified products and limit fatty fish to one serving per week to prevent additional consumption of omega-3 from interfering with the study intervention.
Two behavioral assessments for ADHD symptoms were used in this study, both completed by the participants’ parents.
The first asks parents on a scale of zero to two to assess the various negative behaviors of their children. This is used as a diagnostic and evaluation tool for several disorders, including ADHD.
The CBCL was used as the primary outcome measure throughout the study. The second test was the strengths and weaknesses of ADHD symptoms and the standard behavior scale (SWAN).
This assessment was performed approximately every four weeks throughout the study and was used as a secondary measure to assess changes in behavior over time.
Parents are asked to rate the frequency of a child’s positive behaviors, such as paying attention to detail, waiting their turn, and playing quietly.
Participants completed an fMRI task to assess response inhibition at the start of the study and the follow-up appointment at the end of the study.
Participants were asked to alternately press and hold a button when prompted or not to press a button when asked not to.
This test measures whether the button is pressed at the correct times to assess the participant’s ability to control their motor impulses, one of the symptoms of ADHD.
Participants also provided urine and cheek swab samples and completed a dietary questionnaire to assess existing fatty acid deficiencies.
The urine samples were used to analyze markers of dopamine levels in the brain to measure dopamine turnover, and the cheek swabs were analyzed to determine the levels of omega-3 in the fatty acids of the cell membranes as a compliance measure.
In addition to the CBCL and SWAN behavioral assessments described above, we also attempted to collect data from the participants’ teachers before and after the study. However, the data could not be used due to a low response rate.
Parents completed the SWAN behavioral assessment and a dietary checklist to assess compliance at three intervals during the study.
To further assess compliance throughout the study, the remaining margarine product was weighed at the end of the research. The amount of DHA incorporation into the cell membranes collected in the cheek swab samples was measured and compared. Initials.
Forty children with ADHD and 39 children without any diagnosed disorder were randomly assigned to consume margarine or regular margarine with 650 milligrams each of DHA and EPA added for 16 weeks.
At the beginning and end of the study, they completed a functional MRI task to assess impulse control, and their parents completed the behavioral questionnaires.
What were the findings?
The researchers discussed three sets of study findings: behavioral, as assessed by the CBCL and SWAN questionnaires.
Physiological, analyzing the dietary evaluation of the presence of fatty acid deficiencies, the data from the urinalysis, and the incorporation of omega-3 fatty acids into the cheek cells of the “active” groups.
Finally, the neurological from fMRI data. There were no differences in fMRI performance in either group compared to their baseline results.
Based on behavioral data, both ADHD and RG participants improved their overall CBCL scores after consuming the omega-3-supplemented margarine product for 16 weeks.
However, only participants with ADHD showed improvements in the Attention Problems subset of behaviors, with an average decrease of 1.83 points in their checklist score.
There were no differences in either group’s Rule Blocking or Aggressive Behavior subsets.
The data was then re-analyzed without the seven participants who had increased their medication dose throughout the study to rule out the possible effects of a higher medication dose, and the decrease remained statistically significant.
No statistically significant differences were reported in SWAN scores.
Physiological data showed that children in the ADHD group were more likely to show symptoms of fatty acid deficiencies at the start of the study. However, only four of the 79 participants met the cutoff for a defined lack.
Analysis of cell membranes from cheek cells collected after the treatment showed higher DHA levels in the group that consumed omega-3 margarine compared to the group that consumed regular margarine.
There was a slight but statistically significant correlation between CBCL scores and DHA levels before and after omega-3 treatment in the ADHD group.
The lower the level of DHA measured in the cheek cells, the higher the child’s score on negative behavioral assessments.
The urine samples were analyzed for homovanillic acid, a marker of dopamine levels in the brain, but no differences were seen in either group.
This finding refutes the hypothesis that changes in dopamine metabolism caused the effects of omega-3 supplements.
Both groups experienced some behavioral improvements after consuming added DHA and EPA for 16 weeks, but only the ADHD participants specifically experienced improvements in attention.
Omega-3 supplementation did not affect the performance of a functional magnetic resonance imaging task that measures the control of cognitive responses. It did not affect dopamine levels in the brain, as measured by a marker in urine samples.
What does the study tell us?
There are two significant limitations to consider in this study.
First, a participant only had to consume two-thirds or more of the assigned margarine product (based on comparing the weight of the returned product to the initial weight) and was allowed to skip consuming the product for up to seven days while it was still being considered. Complies with the study protocol.
This lack of rigor in the study protocol may have contributed to the more minor effects observed.
Second, the researchers observed after further statistical analysis that the study sample size should have been nearly ten times larger to show the effects of treatment on the functional MRI task.
This study was supported by manufacturers of several nutrition, health, and food products worldwide.
In addition to producing the supplemented margarine for the study, Unilever also funded the trial (including funding for the investigators conducting the test), participated in the study’s design and employed two of the article’s co-authors.
Many companies produce rigorous science, and the complete lack of corporate interests is no guarantee that the reported results are valid or valuable, so it is something to keep in mind when evaluating any study.
Since the study was double-blind, none of the researchers knew which child had received which product until after the study was completed.
However, the primary outcome, which is an overall improvement in behavioral measures in both groups and a specific improvement in attention problems in the ADHD group (both on the order of about 15%), provides some evidence of the efficacy of the measures. EPA and DHA supplements for children with ADHD.
These effects were probably only seen in conjunction with medication: 95% of the ADHD participants took methylphenidate during the trial. No conclusions can be drawn about the impact of omega-3s on ADHD symptoms in the absence of therapies standard.
Two limitations of the study include the relatively low threshold for compliance and the lack of power for the functional MRI task.
In addition, the study had significant corporate support. Industry researchers were involved in the study’s overall design, but the fact that the study was double-blind reduces the risk of bias in the data analysis.
The panorama
Several observational studies have previously reported lower omega-3 fatty acid levels in children with ADHD.
However, clinical trials in which omega-3s are administered as an intervention have shown little or no benefit for supplementation of selected ADHD symptoms.
Meta-analysis of relevant trials suggests that the effects, if any, are minor and that supplementation can only be helpful in conjunction with medication.
A separate study indicated that when children took omega-3 medications and supplements, they needed lower doses of drugs to improve symptoms.
The ratio of DHA to EPA can also be critical to the success of treatment, as previous studies had a low percentage of DHA to EPA, whereas this study used equal amounts.
In this context, it is also worth mentioning that omega-3 fatty acid supplementation, in general, appears to have positive effects on brain development.
Therefore, it is not surprising that behavioral improvements were observed in both the ADHD arm and the GR group.
Whether these behavioral improvements are mediated by changes in the level or effects of dopamine in the brain requires further study.
Urinary levels of homovanillic acid, the dopamine metabolite, measured in this study point to a different mechanism, but a more direct evaluation of the effects in the brain would be required to disprove this hypothesis.
Instead, it is possible that the effects that were specific to the ADHD participants could be due to improved neural function, as previously shown.
The magnitude of the effects observed in the study under review was relatively low. This is in line with previous meta-analysis results indicating minor treatment effects.
This study is also consistent with previous research suggesting that omega-3 supplementation may only be effective with medications for treating ADHD symptoms.
Frequent questions
Why was the study conducted only on children?
The authors chose to recruit only children for the study for two reasons. The prevalence of ADHD is two to three times higher in boys than in girls, so enrollment was more straightforward.
The researchers also wanted to eliminate gender as a confounder for fMRI studies. However, the study results cannot be extrapolated to girls with ADHD.
It would be interesting to see a separate study done on girls, as diagnosed girls tend to have different symptoms than boys.
Girls tend to show more ‘internalizing’ symptoms such as separation anxiety, while boys show more ‘externalizing’ symptoms such as aggression and impulsivity so that omega-3 supplements may cause them. Affect in very different ways.
Why didn’t the treatment affect the dopamine pathway when there is so much evidence that dopamine is dysregulated in ADHD?
Dopamine has been implicated in controlling cognitive functions, particularly in children with ADHD. Mechanistic evidence in rats has provided clues as to what may be happening in humans.
One of the challenges in this study may lie in the measurement of homovanillic acid, which can sometimes produce unreliable results on dopamine and its effects. The effects may have been overlooked when an indirect marker of dopamine activity was measured.
The brain is a complex system, and omega-3s may also play a more critical role in the cell membranes of neurons than in the signaling pathways themselves.
What should I know?
Supplementation with omega-3 fatty acids in margarine resulted in some moderate behavioral improvements in children with and without diagnosed ADHD.
Only the children with ADHD (who were also primarily medicated) experienced specific improvements in attention. Based on the data from the study under review, this effect was not mediated by the dopamine results in cognitive control.
