College Papers

A the study to boys to reduce “confounding

A
double blind, randomized controlled trial studied the effects of adding omega-3
polyunsaturated fatty acids (PUFAs) to the diet of young males with ADHD and
those without ADHD over a 16-week period. 
Forty boys between the ages of 8-14 with a confirmed diagnosis of ADHD
were enrolled via the Department of Psychiatry at the University Medical Center
in Utrecht.  Advertising was
also used to enroll participants.  A
qualified researcher through the “Diagnostic Interview Schedule for
Children-Parent Version” (DISC-P) authenticated the ADHD diagnosis. When
determining the inclusion criteria, the researchers decided to limit the study
to boys to reduce “confounding variables”.  The participants were either on no medications
or only taking methylphenidate, a psychostimulant.  They were to hold their medication 24 hours
before undergoing a fMRI scan.  Thirty-nine boys were selected to be part of a
reference group (RG) because they matched certain criteria that were similarly
seen in the treatment group (age, body mass index (BMI), hand preference). 1

                  The authors hypothesized that
adding Omega-3 PUFAs to the diet would mitigate symptoms of ADHD, increase
phospholipid PUFA levels, and increase “dopamine turnover.”  In addition, the authors expected to see an
increase in “cognitive control in ADHD” and further activated prefrontal and
striatal areas in the brain.  In the end,
participants were randomly sorted into either of 4 groups in the study:
Children with diagnosed ADHD getting placebo (N=20) or omega-3 PUFAs infused margarine
(N=20) and children in the RGs without ADHD also either receiving placebo
(N=19) or fortified margarine (N=20).  The participants were told to take 10 g of either
regular margarine or margarine supplemented with omega-3 containing 650 mg DHA
and 650 mg EPA per serving. Adherence was measured by weighing the remaining
product left on a monthly basis. Parents also recorded daily intake. Cheek
swabs were taken to measure fatty acid levels, samples of urine were used to
measure “HVA to creatinine ratio” to determine dopamine turnover, and fMRI
scans 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 79
participants, 1 was excluded due to non-compliance and 2 failed to follow up.
 No changes were seen among the
children 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 higher on these "CBCL subscales" at baseline. During follow-up, those that received the fortified margarine had a lower mean score on the CBCL scale for attention problems (RGACTIVE : 2.4, +/-2.6; ADHDACTIVE: 7.7, +/-3.0).  However, only the ADHDACTIVE group showed significance in this category with a p<0.001.  Furthermore, unfortunately, significance was not seen in the rule breaking and aggressive behavior subscales or SWAN test in the treatment groups.  There was no significance seen in phospholipid PUFA levels between all the groups (p=0.135).  However, it is important to note that some of the cheek samples were too small to render conclusive results.  Even though, there was significance in the HVA ratio at baseline (p=0.059) in children with ADHD who received active treatment, there was no significance seen at follow-up.  Finally, there were no effects seen on the pre-frontal and striatal areas of the brain in the fMRI scans. The authors concluded 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 pervious research and using that to formulate a study to demonstrate the effects of adding omega-3 PUFAs to the diet.1 However, despite having showed positive results of omega-3 PUFA supplementation, their sample size was not big enough to demonstrate the effects on a larger scale.1 Furthermore, the study never mentioned what ethnicity/race the participants were, so it is not known whether the results can be replicated at a larger scale.1 The researchers did, however, do their best to eliminate confounding variables by only including one gender in the study (boys), especially because ADHD is seen more commonly in boys.1 The length of the study was also a bit concerning (16 weeks) because measuring behavior and other psychological outcomes takes time.1  Furthermore the degree of ADHD a participant had was not taken into account.1  It is also important to note that Unilever Research & Development paid for this study and 2 of the authors of this study are employees of Unilever.1 Unilever is a huge company who controls many brands, some of which also make margarine and other food-based products.2                    Another "randomized, placebo-controlled" study conducted by Matsudaira et al, looked the effects of omega 3 and 6 supplements in male teens over the course of 12 weeks. The study's primary aim was to see if long chain PUFA supplements (LC-PUFAs) would improve symptoms of ADHD. The secondary aim was to test for an increase in fatty acids by testing a blood sample of the participants.  Safety was also assessed by recording adverse events that may have originated from taking the active treatment.  Seventy-six teens were enrolled in the study from either "day" school (12-14 years od age) or boarding school (15-17 years of age).   The sample size was determined using 0.7 as the effect size. There were 38 participants in each group. Inclusion was determined using the "Conners' Teacher Rating Scales (CTRS-L) and the Conners' Parent Rating Scales."  Only participants who scored a mean greater than 65 on these scales and who were aged 12-17 were included.  The ADHD diagnosis was also confirm using the "Diagnostic and Statistical Manual of Mental Disorders, DSM-IV."  The ADHD group was further divided based on severity of the disorder. These groups included participants who had inattentive type, combined type, or hyperactive/impulsive type.  The group who received the active treatment got LC-PUFA capsules called Equazen Eye Q.  Each participant was instructed to take 6 capsules each day and each daily dose contained 558 mg of EPA and 174 mg DHA.  The placebo capsules had similar shape and color as the active capsules and were provided in identical bottles.  Adherence was assessed at the end of the 12-week trial by gathering the bottles and counting the capsules.3                   In terms of the primary outcome, "linear regression of the CTRS" ADHD score at baseline and type of school did not show a difference after the trial period with a p-value of 0.671.  However, significant changes were seen in the secondary outcome.  For instance, 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 participants from the control group and 3 from the treatment group experienced an adverse effect. Furthermore, 4 of the 5 participants who experienced an even had more than 1 to report.  Ten out of the 12 adverse events were determined to be mild and 1 participant in the treatment reported experiencing a moderate event (bone fracture), but it was concluded as not 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 adverse events.  The researchers concluded there was no significant difference seen between the control group and treatment group receiving LC-PUFA supplementation over the 12-week trial period.3                   This article was a randomized, placebo-controlled clinical trial and approved by the Research Ethics Committee in the UK.  Furthermore, the researchers did their best to keep the study double blinded by ensuring that the placebo and treatment capsules were indistinguishable and that they were placed in identical bottles.  One thing this study also included, which the previous study failed to take into account, was the varying degrees/subtypes of ADHD that participants had. However, the study never mentioned what ethnicity/race the participants were, so it is not known whether the results can be replicated in a different population.  Even though, the study talked about effect size, they failed to mention what alpha and power was for the study.