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Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial

Johnstone J, Hatsu I, Tost G, Srikanth P, Eiterman L, Bruton A, Ast H, Robinette L, Stern M, Millington E, Gracious B, Hughes A, Leung B, Arnold L (2022) Journal of the American Academy of Child and Adolescent Psyhiatry May;61(5):647-661 doi: 10.1016/j.jaac.2021.07.005 

Web URL: Read this and related articles on PubMed



To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample.


A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores.


Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained.

For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001).

CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70).

The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred.


Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed.

This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level.


This study examined the efficacy of a broad-spectrum micronutrient supplement in reducing ADHD symptoms and emotional dysregulation, in a diverse group of 135 unmedicated children betwee 6-12 years of age, who all met DSM-5 criteria for ADHD and also displayed at least one symptom of irritability or anger.

Results showed:

  • Micronutrients showed significant benefit over placebo based on blinded clinician rating (p < 0.001)
    • 54% of supplemented children were 'responders' (i.e. showed pre-specified improvement in their symptoms) versus 18% in the placebo group.
  • Parent ratings reported improvements in both groups - but the differences between them were not significant.
  • Children taking the micronutrients grew 6mm taller, on average, than children taking a placebo - suggeting correction of undetected nutrient insufficiency
  • No significant adverse side effects were reported.

These results support the findings of smaller ADHD trials showing supplementation to be both safe and effective for similar formulations, containing all vitamins and known essential minerals, in quantities between the Recommended Dietary Allowance (RDA) and Upper Tolerable Intake Level.

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And the recent book 'The Better Brain' – by leading researchers in this field – which provides an accessible and practical but evidence-based guide to nutritional and dietary treatments for ADHD, Anxiety, Stress and related conditions.

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  • Date:  9th June at 18.00-19.30 BST

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  • How food and diet can affect symptoms of ADHD and related developmental conditions - including Dyslexia, Dyspraxia and the Autistic Spectrum 
  • Links between these conditions and Anxiety, Depression and other Mood Disorders, as well as physical health and wellbeing.

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