Toward 'element balance' in ADHD: an exploratory case control study employing hair analysis.

Background: Head hair analysis has been used for decades to clarify mineral relationships to symptoms of ADHD, but there is little consensus among findings. We sought to explore 33 hair element concentrations and their 528 calculated ratios among two groups of boys, one with ADHD and one without.Method: 107 boys aged 7-12 years were recruited; 55 with ADHD and 52 non-ADHD Controls. Hair minerals were compared using Mann-Whitney U tests, p<0.01 was used for significance. Dietary data were obtained using a 138 item food frequency questionnaire (FFQ).Results: There were three group differences on individual elements: bismuth/Bi: 8 fold higher in ADHD, chromium/Cr: 15% lower in ADHD and germanium/Ge: 11% lower in ADHD, Cr level being the strongest predictor of ADHD symptoms. We found thirty significant group differences in element ratios, two thirds involving Bi and eight of these showing that as ADHD severity increased, the ratios with Bi as the denominator decreased (r ranging from -0.263 to -0.433, p<0.01). From the FFQ, tinned fruit was consumed more often in the ADHD group. Hair arsenic levels were somewhat elevated across both ADHD and Control groups.Discussion: While element 'imbalance' appears to be associated with ADHD, we did not replicate any previous study results of group differences on individual elements. We have raised the possibility that the ratios may be far more important than any one individual element in better elucidating the effects that minerals may have on the pathogenesis of ADHD. These are cautionary findings requiring replication.

Author Correction: Human gut microbiome changes during a 10 week Randomised Control Trial for micronutrient supplementation in children with attention deficit hyperactivity disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Resting-state networks and neurometabolites in children with ADHD after 10 weeks of treatment with micronutrients: results of a randomised placebo-controlled trial.

Children with attention-deficit/hyperactivity disorder (ADHD) show significant abnormalities on MR imaging in network communication and connectivity. The prefrontal-striatal-cerebella circuitry, involved in attention is particularly disrupted. Neurometabolites, the biochemical structures that support neurological structural integrity, particularly in the prefrontal cortex and striatum are associated with symptoms. This study aimed to explore changes in neurometabolite levels through treatment with vitamins and minerals (micronutrients), hypothesising that treatment would impact neural circuitry and correspond to a reduction in symptoms. Twenty-seven non-medicated children (M = 10.75 years) with DSM5 diagnosed ADHD were randomised to receive daily micronutrients or placebo for 10 weeks. Main outcome measures included the Clinical Global Impression-Improvement Scale and ADHD-RS-IV Clinician Ratings of ADHD symptoms. Magnetic resonance spectroscopy of the bilateral pre-frontal cortex and bilateral striatum, resting state fMRI and structural images were acquired 1 week pre-treatment, and in the last week of intervention. Results did not show any significant differences in the measured brain metrics and the levels of neurometabolites between treatment and placebo groups after ten weeks of treatment with micronutrients. In the treatment group there was a trend for: decreased choline in the striatum; decreased glutamate in the prefrontal cortex; increased grey matter in the anterior thalamus; increased white matter in the fornix and improved network integrity of the default mode network, dorsal attention network and frontal executive network. The small sample size of the current study limits results, future studies with higher power are warranted to explore any association between micronutrient treatment and neurological changes.

Mineral-Vitamin Treatment Associated with Remission in Attention-Deficit/Hyperactivity Disorder Symptoms and Related Problems: 1-Year Naturalistic Outcomes of a 10-Week Randomized Placebo-Controlled Trial.

Objective: This article presents 1-year follow-up of a randomized placebo-controlled trial with open-label extension evaluating the efficacy of a broad-spectrum micronutrient (vitamins and minerals) intervention. The object was to determine if dominant treatment at follow-up was associated with differential psychological outcomes. Methods: Ninety percent of the original sample of 93 children with attention-deficit/hyperactivity disorder (ADHD) were followed 52 weeks postbaseline. Assessments included measures of ADHD, mood, anxiety, and general function based on parent/clinician report. Outcome was considered based on dominant therapy at 52 weeks (trial micronutrients [n = 19], medications [n = 21], and no treatment [n = 35]). Nine children were not categorized due to inconsistent therapies. Results: Based on dominant treatment, more of those who stayed on trial micronutrients (84%) were identified as "Much" or "Very Much" improved overall relative to baseline functioning, compared to 50% of those who switched to psychiatric medications and only 21% of those who discontinued treatment [χ2(2) = 19.476, p < 0.001]. Fifteen (79%) of those still taking micronutrients, 8 (42%) of those using medications, and 7 (23%) of those who discontinued treatment were considered remitters based on parent-reported ADHD [χ2(2) = 15.3, p < 0.001]. Those who stayed on micronutrients were more likely to have failed medication treatment in the past. The micronutrient group also displayed better outcomes on measures of parent-rated hyperactivity and anxiety, and clinician-rated general function and mood, with moderate to large between-group effect sizes (micronutrients vs. medication: ES = 0.73-1.01; micronutrients vs. no treatment: ES = 0.54-1.01). Most common reasons for stopping trial micronutrients were cost and number of pills to swallow. No continued side effects were associated with micronutrients. Conclusions: Children who benefitted from micronutrients in the short term maintained changes at follow-up, without side effects. While both those who continued micronutrients and those who switched to medication showed improved ADHD symptoms, psychiatric medication use was associated with deterioration in mood and anxiety. Inherent selection bias limits generalizability.

Human gut microbiome changes during a 10 week Randomised Control Trial for micronutrient supplementation in children with attention deficit hyperactivity disorder.

It has been widely hypothesized that both diet and the microbiome play a role in the regulation of attention-deficit/hyperactivity disorder (ADHD) behaviour. However, there has been very limited scientific investigation into the potential biological connection. We performed a 10-week pilot study investigating the effects of a broad spectrum micronutrient administration on faecal microbiome content, using 16S rRNA gene sequencing. The study consisted of 17 children (seven in the placebo and ten in the treatment group) between the ages of seven and 12 years, who were diagnosed with ADHD. We found that micronutrient treatment did not drive large-scale changes in composition or structure of the microbiome. However, observed OTUs significantly increased in the treatment group, and showed no mean change in the placebo group. The differential abundance and relative frequency of Actinobacteria significantly decreased post- micronutrient treatment, and this was largely attributed to species from the genus Bifidobacterium. This was compensated by an increase in the relative frequency of species from the genus Collinsella. Further research is required to establish the role that Bifidobacterium contribute towards neuropsychiatric disorders; however, these findings suggest that micronutrient administration could be used as a safe, therapeutic method to modulate Bifidobacterium abundance, which could have potential implications for modulating and regulating ADHD behaviour. Our pilot study provides an initial observation into this area of research, and highlights an interesting avenue for further investigation in a larger cohort. Furthermore, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome.

Can we predict treatment response in children with ADHD to a vitamin-mineral supplement? An investigation into pre-treatment nutrient serum levels, MTHFR status, clinical correlates and demographic variables.

BACKGROUND: Intent-to-treat analyses from a randomized controlled trial showed significant between-group differences favouring micronutrient treatment on the Clinical Global Impression-Improvement, but no group differences on clinician, parent and teacher ratings of overall ADHD symptoms. There was an advantage of micronutrients over placebo in improving overall function, emotional regulation, aggression, and reducing impairment as well as improving inattention based on clinician but not parent observation. No group differences were observed on hyperactive-impulsive symptoms. We investigated predictors of response defined by pre-treatment variables. METHOD: We conducted analyses of data from a clinical trial of children (7-12 years) with ADHD, whereby participants were randomized to receive micronutrients or placebo for 10 weeks followed by a 10 week open-label (OL) phase. We included only children who had been exposed to micronutrients for a full 10 week period and demonstrated satisfactory adherence, either in RCT phase (n = 40) or OL phase (those who received placebo during RCT phase; n = 31). Seven outcomes were examined: change in ADHD symptoms (clinician/parent), ADHD responder, overall responder, change in mood, change in functioning, and change in aggression. Demographic, developmental variables, current clinical and physical characteristics, MTHFR genotype at two common variants, and pre-treatment serum/plasma levels (vitamin D, B12, folate, zinc, copper, iron, ferritin, potassium, calcium, magnesium, and homocysteine) were all considered as putative predictors. RESULTS: Substantial nutrient deficiencies pre-treatment were observed only for vitamin D (13%) and copper (15%), otherwise most children entered the trial with nutrient levels falling within expected ranges. Regression analyses showed varying predictors across outcomes with no one predictor being consistently identified across different variables. Lower pre-treatment folate and B12 levels, being female, greater severity of symptoms and co-occurring disorders pre-treatment, more pregnancy complications and fewer birth problems were identified as possible predictors of greater improvement for some but not all outcome measures although predictive values were weak. Lower IQ and higher BMI predicted greater improvement in aggression. CONCLUSIONS: This study replicates Rucklidge et al. (2014b) showing the limited value of using serum nutrient levels to predict treatment response although we cannot rule out that other non-assayed nutrient levels may be more valuable. Additionally, no specific demographic or clinical characteristics, including MTHFR genetic status, were identified that would preclude children with ADHD from trying this treatment approach.

Methylomic changes in response to micronutrient supplementation and MTHFR genotype.

Exposure times and dosage required for dietary components to modify DNA methylation patterns are largely unknown. AIM: This exploratory research represents the first genome-wide analysis of DNA methylation changes during a randomized-controlled-trial (RCT) for dietary supplementation with broad spectrum vitamins, minerals and amino acids in humans. METHODS: Genome-wide changes in methylation from paired, peripheral blood samples were assessed using the Infinium Methylation EPIC 850 K array. RESULTS: Methylation increased at 84% of the most significant differentially methylated CpGs; however, none showed significance after adjustment for genome-wide testing. CONCLUSION: Micronutrient supplementation is unlikely to have a substantial biological effect on DNA methylation over 10 weeks; however, the trend toward hypermethylation that we observed is likely to become more marked with longer exposure periods.

Dual-task interference between climbing and a simulated communication task.

Climbers often need to maintain communication with other people. Previous research indicates that climbers remember less of the information communicated to them while climbing than when not climbing. In the present research, we investigated at what stage of memory the source of this impairment occurs. Participants were required to respond to words presented to them by saying out loud an associated word. This enforced encoding of the words, and was completed alone, as well as while climbing. Participants then recalled as many words as possible. A separate single-task condition had participants climb without making word associations. Word recall was reduced in the dual-task compared with the single word association task, but there was no difference in the number of word associations made. This indicates that the reduction in word recall was not a result of reduced encoding in the dual-task condition. Concurrent climbing may have reduced word recall by interfering with rehearsal and maintenance of words in memory.