Magnesium, Iron, Zinc, Copper and Selenium Status in Attention-Deficit/Hyperactivity Disorder (ADHD).

In this study, we critically review the literature concerning the relation of Mg, Fe, Zn, Cu and Se and attention-deficit/hyperactivity disorder (ADHD). Elemental status is estimated using peripheral blood parameters, hair, urine, daily intake and response to supplementation. The observed associations between concentration levels of the elements Mg, Fe, Zn, Cu and Se and ADHD symptoms are contradictory. This is partly due to the heterogeneity and complexity of the disorder. As a trend, lower ferritin and zinc levels can be observed. However, this correlation is not causative, as illustrated by placebo-controlled trials reporting conflicting evidence on the efficacy of supplementation. Well-defined studies on changes in concentration levels of the elements in relation to ADHD symptoms before and after treatment with therapeutics it will be possible to shed more light on the significance of these elements in this behavioral disorder. The discussion on whether a change in concentration of an element is cause or consequence of ADHD is not within the scope of this article.

Rationale for Dietary Antioxidant Treatment of ADHD.

Increasing understanding arises regarding disadvantages of stimulant medication in children with ADHD (Attention-Deficit Hyperactivity Disorder). This review presents scientific findings supporting dietary antioxidant treatment of ADHD and describes substantial alterations in the immune system, epigenetic regulation of gene expression, and oxidative stress regulation in ADHD. As a result, chronic inflammation and oxidative stress could develop, which can lead to ADHD symptoms, for example by chronic T-cell-mediated neuroinflammation, as well as by neuronal oxidative damage and loss of normal cerebral functions. Therefore, modulation of immune system activity and oxidant-antioxidant balance using nutritional approaches might have potential in ADHD treatment. The use of natural antioxidants against oxidative conditions is an emerging field in the management of neurodegenerative diseases. Dietary polyphenols, for example, have antioxidant capacities as well as immunoregulatory effects and, therefore, appear appropriate in ADHD therapy. This review can stimulate the development and investigation of dietary antioxidant treatment in ADHD, which is highly desired.

Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial.

BACKGROUND: Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. METHODS: This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. DISCUSSION: This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT02700685 . Registered on 18 January 2016. EudraCT 2016-000215-32 . Registered on 4 October 2016.