Adouble blind, randomized controlled trial studied the effects of adding omega-3polyunsaturated fatty acids (PUFAs) to the diet of young males with ADHD andthose without ADHD over a 16-week period. Forty boys between the ages of 8-14 with a confirmed diagnosis of ADHDwere enrolled via the Department of Psychiatry at the University Medical Centerin Utrecht. Advertising wasalso used to recruit participants. Aqualified researcher through the “Diagnostic Interview Schedule forChildren-Parent Version” (DISC-P) authenticated the ADHD diagnosis. Whendetermining the inclusion criteria, the researchers decided to limit the studyto boys to reduce “confounding variables”.
The participants were either on no medicationsor only taking methylphenidate, a psychostimulant. They were to hold their medications 24 hoursbefore undergoing an fMRI scan. Thirty-nine boys were selected to be part of areference group (RG) because they matched certain criteria that were similarlyseen in the treatment group (age, body mass index (BMI), hand preference). 1 The authors hypothesized thatadding Omega-3 PUFAs to the diet would mitigate symptoms of ADHD, increasephospholipid PUFA levels, and increase dopamine turnover. In addition, the authors expected to see anincrease in “cognitive control in ADHD” and further activated prefrontal andstriatal areas. In the end, participantswere randomly sorted into either of 4 groups in the study: Children withdiagnosed ADHD getting placebo (N=20) or omega-3 PUFAs infused margarine (N=20)and children in the reference groups without ADHD also either receiving placebo(N=19) or fortified margarine (N=20). The participants were told to take 10 g of eitherregular margarine or margarine supplemented with omega-3 containing 650 mg DHAand 650 mg EPA per serving.
Adherence was measured by weighing the remainingproduct left on a monthly basis. Parents also recorded daily intake. Cheekswabs were taken to measure fatty acid levels, samples of urine were used tomeasure “HVA to creatinine ratio” to determine dopamine turnover, and fMRIscans were done to look at the previously mentioned areas of the brain. Lastly, the “Child Behavior Checklist (CBCL)and Strengths and Weaknesses of ADHD symptoms and Normal behavior scale (SWAN)”were used to assess symptoms and extent of ADHD in participants.1 Of the original 79participants, 1 was excluded due to non-compliance and 2 failed to follow up. No changes were seen among thechildren in either the treatment groups or reference groups in Age, hand preference,BMI, and adherence percentage as shown by the p-values of 0.
163, 0.422, 0.122,and 0.573 respectively. With a p-value of <000.
1 in “rule breaking behavior”,”attention problems” and “aggressive behavior,” young boys with ADHD scored higheron these “CBCL subscales” at baseline. During follow-up, those that receivedthe fortified margarine had a lower mean score on the CBCL scale for attentionproblems (RGACTIVE : 2.4, +/-2.
6; ADHDACTIVE: 7.7,+/-3.0). However, only the ADHDACTIVEgroup showed significance in this category with a p<0.001. Furthermore, unfortunately, significance wasnot seen in the rule breaking and aggressive behavior subscales or SWAN test inthe treatment groups. There was nosignificance seen in phospholipid PUFA levels between all the groups(p=0.135).
However, it is important tonote that some of the cheek samples were too small to render conclusiveresults. Even though, there was significancein the HVA ratio at baseline (p=0.059) in children with ADHD who receivedactive treatment, there was no significance seen at follow-up. Finally, there were no effects seen on thepre-frontal and striatal areas of the brain in the fMRI scans.
The authorsconcluded that there might be benefits to introducing omega-3 PUFAs to the diet,but research is required.1 Overall, the study did a good job in looking at perviousresearch and using that to formulate a study to demonstrate the effects of addingomega-3 PUFAs to the diet. However, their sample size was not big enough todemonstrate the effects on a bigger scale. The researchers did, however, do their best to eliminate confoundingvariable by only including one gender in the study (boys), especially becauseADHD is seen more commonly in boys.1 Furthermore, the children inthe study were either “medication naïve” or taking only methylphenidate and thechildren taking this medication were told to hold it for 24 hours before a fMRIscan.
The length ofthe study was also a bit concerning, measuring behavior and other psychologicaloutcomes takes time. 1 Furthermore the degree of ADHD a participant had was nottaken into account. It is also importantto note that Unilever Research & Development paid for this study and 2 ofthe authors of this study are employees of Unilever. Furthermore, the study nevermentioned what ethnicity/race the participants were, so it is not known whetherthe results can be replicated at a larger scale. Another “randomized,placebo-controlled” study conducted by Matsudaira et al, looked the effects ofomega 3 and 6 supplements in male teens over the course of 12 weeks.
Thestudy’s primary aim was to see if long chain PUFA supplements (LC-PUFAs) wouldimprove symptoms of ADHD. The secondary aim was to test for an increase infatty acids by testing the blood of the participants. Safety was also assessed by recording adverseevents that may have originated from taking the active treatment. Seventy-six teens were enrolled in the studyfrom either “day” school (12-14 years od age) or boarding school (15-17 yearsof age). The sample size was determinedusing 0.
7 as the effect size. There were 38 participants in each group.Inclusion was determined using the “Conners’ Teacher Rating Scales (CTRS-L) andthe Conners’ Parent Rating Scales.” Onlyparticipants who scored a mean greater than 65 on these scales and who wereaged 12-17 were included. The ADHDdiagnosis was also confirm using the “Diagnosticand Statistical Manual of Mental Disorders, DSM-IV.
” The ADHD group was further divided based onseverity of the disorder. These groups included participants who had combinedtype, inattentive type, or hyperactive/impulsive type. The group who received the active treatment gotLC-PUFA capsules called Equazen Eye Q. Each participant was instructed to take 6 capsules each day and eachdaily dose contained 558 mg of EPA and 174 mg DHA. The placebo capsules had similar shape andcolor as the active capsules and were provided in identical bottles. Adherence was assessed at the end of the12-week trial by gathering the bottles and counting the capsules.2 In terms of the primaryoutcome, “linear regression of the CTRS” ADHD score at baseline and type ofschool did not show a difference after the trial period with a p-value of0.671.
However, significant changes wereseen in the secondary outcome. Forinstance, the levels of omega 3 in the blood sample increased from 2.60(+/-1.16) to 3.
62 (+/-1.21) in the treatment group and in the control group,the mean rose from 2.57 (+/-0.75) to 2.
73 (+/-0/73); p<0.001. In reference to the safety outcome, 2 participantsfrom the control group and 3 from the treatment group experienced an adverseeffect. Furthermore, 4 of the 5 participants who experienced an even had morethan 1 to report. Ten out of the 12adverse events were determined to be mild and 1 participant in the treatmentreported experiencing a moderate event (bone fracture), but it was concluded asnot being caused by the intervention. Using the Fisher's exact test, there was no significance seen at the 5%level due to a p-value of 1.000 among the treatment and the reported adverseevents.
The researchers concluded therewas no significant difference seen between the control group and treatmentgroup receiving LC-PUFA supplementation over the 12-week trial period.2 The researchers did their best to keep the study doubleblinded by ensuring that the placebo and treatment capsules wereindistinguishable and that they were placed in identical bottles. One thing this study also included, which theprevious study failed to take into account, was the varying degrees/subtypes ofADHD that participants had. Furthermore, the study never mentioned whatethnicity/race the participants were, so it is not known whether the resultscan be replicated at a larger scale.