The impact of micronutrient supplementation on ADHD in children.
Prior research has demonstrated that children with ADHD are more likely than peers to be deficient in levels of certain minerals and fatty acids. And, supplementation with single nutrients (eg, zinc, magnesium) and with omega-3 fatty acids have yielded some promising results in randomized-controlled studies. In open-label trials examining supplementation with broad-spectrum micronutrients – as opposed to supplementing a specific micronutrient in isolation – modest effects in adults and children with ADHD and co-occurring mood issues or emotional dysregulation (irritability, aggression, and anger) have been reported. The scientific rationale for micronutrient supplementation is based on their function in brain processes, including their role in the synthesis of essential neurotransmitters. These promising results point to the need for a randomized-controlled study of broad-spectrum micronutrient supplementation in children with ADHD.A study published recently in the Journal of the American Academy of Child and Adolescent Psychiatry [Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial. 61(5), 647-661.] provides helpful new data on the potential utility of this approach. Participants were 126 6-12-year old children diagnosed with ADHD (73% male); all participants also had some symptoms of oppositional behavior and/or emotional irritability. While nearly 50% had been treated previously with medication, none were on medication during the study or during the 2 weeks leading up to it. Children were randomly assigned to receive micronutrient supplementation or a placebo that they remained on for 8 weeks. The micronutrient supplement consisted of capsules containing a blend of vitamins and known essential minerals, plus amino acids and antioxidants; the capsules were provided by Hardy Nutritionals (I have no relationship whatsoever with this company.). Participants received 9 to 12 capsules per day to achieve daily doses above the Recommended Dietary Allowance (RDA) but below the Upper Tolerable Intake Level (UL) for all micronutrients. Participants in the control group were given visually identical capsules containing inert cellulose filler. This blinding process was effective – at the end of the 8-weeks, neither children, parents, or research staff could guess which condition the child was in at a rate exceeding chance.
Outcome measures – The primary study outcome measure was a measure of Clinical Global Improvement (CGI) made by research staff blind to children’s status. CGI ratings are made on a 1 ‘very much improved’ to 7 ‘very much worse’ scale and were based on all available data including behavior rating scales and comments made by parents and children at each visit.. Children were considered treatment responders if they received CGI ratings of 1 or 2, signifying very much or much improved. Clinicians also rated the severity of children’s symptoms on a 1 ‘normal’ to 7 ‘among the most extremely ill’ scale. Children whose symptom rating declined by more than one category, e.g., from 5 to 3 but not from 5 to 4, were considered to have had the severity of their symptoms reduced. Secondary outcome measure included parent ratings on a standardized behavior rating scale. This scale was also completed by the child’s teacher or by an adult besides the parent(s) who knew the child well.
– 54% of children in the micronutrient group were considered responders based on the CGI ratings compared to only 18% of control participants. This difference in response rate was statistically significant. For symptom severity ratings, 56% of children receiving micronutrients compared to only 22% of the control group were reported to show a reduction. Parents reported significant reductions in ADHD symptoms for both groups, with no incremental benefits for the micronutrient intervention. There was a trend towards greater reductions in dysregulated mood for the micronutrient group, but this did not reach statistical significance. Ratings provided by teachers/other adults also yielded similar results for both groups, with equivalent improvements generally seen. However, children receiving micronutrients were reported to show a significantly larger reduction in peer conflict ratingsReports of adverse effects did not differ significantly between groups and the micronutrient intervention was generally well tolerated; no concerning urine or blood values were detected. During the 8 weeks, participants in the micronutrient group (n = 67) grew 6 mm more on average than those in the placebo group
Summary and implications – Results from this well-designed study highlight the potential benefits of broad spectrum micronutrient supplementation in children with ADHD. Compared to controls, those receiving the active supplements were 3 times more likely to be rated as very much or much improved by blinded research staff. This is a noteworthy finding. And, taking micronutrients was also associated with a small but statistically significant gain in height. At the same time. 46% of children receiving the micronutrients did not show this level of improvement and 44% had ratings of symptom severity that either declined by only a single level or not at all on the 7-point severity rating scale. And, ratings provided by parents and teachers showed largely equivalent changes in both groups. The authors suggest that the measures used to assess parent and teacher perceptions of change may not have been sufficiently sensitive to capture group differences if they were there. They also suggest that because parents were responsible for administering the capsules to their child, their investment, it may have resulted in a robust placebo response that served to diminish treatment group differences. Even if this explanation were correct, however, it would not apply to teacher ratings. Overall, these are promising findings in suggesting the broad spectrum supplementation of micronutrients can be helpful to a significant percentage of children with ADHD. Ultimately, however, it will be essential to show that improvements are reported not only by research staff, but also by parents and teachers. The absence of differential benefits of active treatment as reported by these groups speaks to the importance of caution when assessing the value of this approach based on currently available data. In future studies, it would be interesting to test whether preselecting participants based on assessed micronutrient deficiencies – something that was not done here – would yield even more robust findings given the positive findings that have been reported for omega-3 fatty acid supplementation, testing micronutrient supplementation in conjunction with fatty acid supplementation to see whether synergistic effects are found would also be worth pursuing.
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