Reviewers Find Mixed Evidence for Nutritional Supplements in ADHD

According to a recent review of individual trials and meta-analyses, the evidence for using nutritional supplements of polyunsaturated fatty acids (PUFAs) or of minerals in treatment of attention-deficit/hyperactivity disorder (ADHD) was described as "marginal".
 
While 12% of children with ADHD had used complementary or alternative medicines including nutritional supplements according to a survey cited in the review, they did so "despite minimal or non-existent evidence of efficacy and possible side effects," observed Klaus Lange, PhD (photo), Department of Experimental Psychology, University of Regensburg, Regensburg, Germany and colleagues.
 
To examine current evidence for nutritional supplements that have been used in ADHD, like the long-chain PUFAs, and the minerals zinc, iron and magnesium, Lange and colleagues reviewed the relevant literature published from 2014 to April 2016.
 
The rationale for supplementing omega-3 and omega-6 PUFAs was based on their importance in neuronal development and central nervous system functioning. They were considered to be essential fatty acids, which are not synthesized in the body yet still must be consumed.  In addition, several studies have found reduced levels of omega-3 PUFA levels in children with ADHD.
 
However, the trials conducted since 2014 provide a mixed picture of clinical effects from PUFA supplementation. Although concentrations of long chain PUFA levels were increased in the neuronal and erythrocyte membranes, change in cognitive measures or ADHD symptoms were not consistent across different trials.
 
The reviewers suggested that the disparate results could reflect methodological differences between the studies, including diverse diagnostic criteria for the ADHD, varied forms and doses of PUFA supplementation, and different instruments to assess clinical outcomes. The team suspected that the conclusions from meta-analyses differed as a result of having included studies of ADHD populations with co-occurring conditions.
 
According to Lange, "The treatment response in patients with ADHD has been demonstrated to vary depending on the presence of comorbid conditions. These factors may explain differences between the meta-analytical reviews which emphasizes the sensitivity of these analyses to variations in protocol."
 
Although zinc has been of interest as an endogenous neuromodulator in synaptic neurotransmission, studies with zinc as either a stand-alone supplement or an adjunct to psychostimulant medication for ADHD have also yielded conflicting evidence of efficacy. Lange and colleagues found the most compelling indication for their use to be in patients who have, or are at risk for zinc deficiency. They noted there aren’t enough adequate studies to recommend a particular dose or dosage form.
 
The reviewers did not find evidence that iron supplementation can benefit ADHD, but noted that the possibility is based on its action as a cofactor for tyrosine hydroxylase, the rate-limiting enzyme of monoamine synthesis and regulation of the dopamine and noradrenaline systems.  In addition, studies have shown lower levels of serum feritin in patients with ADHD, and magnetic resonance imaging (MRI) has indicated that children with ADHD may have lower brain iron levels, in both the right and left thalamus, than the healthy controls.
 
Magnesium levels in children with ADHD have also been reported to be lower in case-control trials than in health controls.  A relationship between the reduced levels and ADHD was not found in the meta-analysis of these studies, however, and the reviewers found no trials to have demonstrated the efficacy of magnesium supplementation.
 
"There is marginal evidence that nutritional supplementation of omega-3 PUFAs or minerals zinc, iron, magnesium influences symptoms and/or cognition in individuals with ADHD," Lange concluded.
 
The review of evidence for nutritional supplementation for ADHD, “The Role of Nutrional Supplments in the Treatment of ADHD: What the Evidence Says,” was published in the February issue of Current Psychiatry Reports
 
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