Evaluating mineral biomarkers as mediators and moderators of behavioural improvements in a randomised controlled trial of multinutrients for children with attention-deficit/hyperactivity disorder.

Hayleigh K Ast, Martina Ralle, Ryan D Bradley, Jeanette M Johnstone, Priya Srikanth, Lisa M Robinette, Alisha M Bruton, L Eugene Arnold, Irene E Hatsu, Brenda Leung

Journal: The British journal of nutrition 2024;132(3):315-329

PMID: 38818718

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Plain Language Summary

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common condition in children that affects attention, self-control, and behaviour. While medications are often used to manage symptoms, there is growing interest in nutritional therapies, such as healthy diets and vitamin/mineral supplements, which may have fewer side effects. This study aimed to understand how minerals may play a role in improving ADHD symptoms by examining biological samples from children who took part in an earlier clinical trial. This research analysed samples from children with ADHD and emotional dysregulation who participated in an 8-week, randomised, double-blind, placebo-controlled trial. Children either received a multinutrient supplement containing 14 essential minerals or a placebo. The results showed that children who took the multinutrients showed significant improvements in behaviour. The supplement improved blood levels of 6 out of 13 measured minerals and all 3 of the minerals measured in urine, regardless of the child’s starting mineral levels. The authors concluded that multinutrient supplementation may be a useful treatment option for children with ADHD and emotional challenges, offering a non-pharmacological alternative. These findings are clinically relevant for healthcare practitioners because they support the use of targeted nutritional strategies, like multinutrient supplements, as a safe and effective intervention to help manage ADHD symptoms and emotional regulation in children.

Abstract

Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind randomised controlled trial of multinutrients for attention-deficit/hyperactivity disorder (ADHD) demonstrated three times as many children (age 6-12) had significantly improved behaviour ('treatment responders') on multinutrients (54 %) compared with placebo (18 %). The aim of this secondary study was to evaluate changes in fasted plasma and urinary mineral concentrations following the intervention and their role as mediators and moderators of treatment response. Fourteen essential or trace minerals were measured in plasma and/or urine at baseline and week eight from eighty-six participants (forty-nine multinutrients, thirty-seven placebos). Two-sample tests/Mann-Whitney tests compared 8-week change between treatment and placebo groups, which were also evaluated as potential mediators. Baseline levels were evaluated as potential moderators, using logistic regression models with clinical treatment response as the outcome. After 8 weeks, plasma boron, Cr (in females only), Li, Mo, Se and vanadium and urinary iodine, Li and Se increased more with multinutrients than placebo, while plasma phosphorus decreased. These changes did not mediate treatment response. However, baseline urinary Li trended towards moderation: participants with lower baseline urinary Li were more likely to respond to multinutrients ( = 0·058). Additionally, participants with higher baseline Fe were more likely to be treatment responders regardless of the treatment group ( = 0·036.) These results show that multinutrient treatment response among children with ADHD is independent of their baseline plasma mineral levels, while baseline urinary Li levels show potential as a non-invasive biomarker of treatment response requiring further study.

Address: Department of Human Sciences, The Ohio State University, Columbus, OH, USA.; Center for Mental Health Innovation, Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.; National University of Natural Medicine, Helfgott Research Institute, Portland, OR, USA.; Oregon Health & Science University, Portland, OR, USA.; Center for Mental Health Innovation, Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.; Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.; National University of Natural Medicine, Helfgott Research Institute, Portland, OR, USA.; Herbert Wertheim School of Public Health, University of California San Diego, San Diego, CA, USA.; Faculty of Health Sciences, University of Lethbridge, Lethbridge, AB, Canada.; Department of Psychiatry & Behavioral Health, The Ohio State University, Columbus, OH, USA.; Department of Human Sciences, The Ohio State University, Columbus, OH, USA.; OSU Extension, The Ohio State University, Columbus, OH, USA.

DOI: 10.1017/S0007114524001132

Patient Centred Factor

Mediators: Attention-deficit hyperactivity disorder

Clinical Imbalances

Neurological

Laboratory Testing

Blood Urine

Modifiable Lifestyle Factors

Diet Psychological

Nutrition Evidence Keywords

Supplements Amino acids Antioxidants Multivitamin Multimineral

Bioactive Substances

Micronutrients

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MeSH Terms: Humans, Attention Deficit Disorder with Hyperactivity, Child, Female, Male, Biomarkers, Minerals, Dietary Supplements, Treatment Outcome, Trace Elements