Food and Behaviour Research

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Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivity disorder?

Arnold LE, Pinkham SM and Votolato N. (2000) J Child Adolesc Psychopharmacol 10 111-117 

Web URL: PubMed Abstract can be viewed online here


Zinc is an important co-factor for metabolism relevant to neurotransmitters, fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine metabolism, believed intimately involved in attention-deficit/hyperactivity disorder (ADHD).

To explore the relationship of zinc nutrition to essential fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data from an 18-subject double-blind, placebo-controlled crossover treatment comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma-linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc levels; for each category, placebo-active difference means were calculated on teachers' ratings.

Placebo-controlled d-amphetamine response appeared linear with zinc nutrition, but the relationship of Efamol response to zinc appeared U-shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc and dropped to 0.3-0.7 with mild zinc deficiency.

If upheld by prospective research, this post-hoc exploration suggests that zinc nutrition may be important for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it likely does so by improving or compensating for borderline zinc nutrition.


This study found that the response to stimulant medication in ADHD children was directly related to their zinc status - i.e. treatment response was poorest in children with the lowest, and best in those with the highest zinc levels.

These findings obviously require further investigation, but if better zinc status really does improve the response to stimulant medication, this would have important implications for clinical practice.

As previously reported, fatty acid supplements had little overall effect on ADHD symptoms in this study. They did appear to have some benefit over placebo in children with borderline zinc status, but did not help children with the lowest or highest zinc levels.  

Zinc is needed as a co-factor in order to convert shorter-chain omega-3 and omega-6 fatty acids into the longer-chain versions that are most important for brain function.

These findings suggest that measurements of zinc status would be useful in future studies of fatty acid supplementation in ADHD.