Do Changes in Blood Nutrient Levels Mediate Treatment Response in Children and Adults With ADHD Consuming a Vitamin-Mineral Supplement?

Objective: We investigated whether changes in serum nutrient levels mediate clinical response to a micronutrient intervention for ADHD. Method: Data were compiled from two ADHD trials (8-10 weeks), one in adults (n = 53) and one in children (n = 38). Seven outcomes included change in ADHD symptoms, mood, overall functioning (all clinician-rated) as well as response status. Change in serum/plasma nutrient levels (vitamins B12 and D, folate, ferritin, iron, zinc, and copper) were considered putative mediators. Results: A decrease in ferritin and an increase in copper were weakly associated with greater likelihood of being identified as an ADHD responder; none of the other nutrient biomarkers served as mediators. Conclusion: Further research looking at nutrients more broadly from other tissues are required to confirm these initial observations of the limited value of nutrient levels in deciphering mechanism of action. Monitoring these biomarkers on their own is unlikely helpful in understanding clinical response to a broad-spectrum micronutrient approach.

Vitamin-Mineral Treatment of ADHD in Adults.

OBJECTIVE: Despite widespread use, there is little data investigating the long-term impact of micronutrients on psychiatric disorders. This study investigated the naturalistic outcome 1-year post-baseline of a randomized controlled trials (RCT) that compared micronutrients with placebo in 80 adults with ADHD. METHOD: All participants were contacted and clinician-rated questionnaires completed. RESULTS: A total of 72 (90%) of the sample participated; although there was significant regression in psychiatric functioning from the end-of-trial on all measures, outcomes remained significantly improved from baseline. Dominant treatment from the end-of-treatment to follow-up was investigated as a mediator of outcome; those staying on the micronutrients performed better than those who switched to medications or discontinued micronutrients. Cost was the most substantial reason why people stopped micronutrient treatment. CONCLUSION: For the small number of participants who stayed on micronutrients, the benefits conferred through the controlled trial were maintained. The results are limited by small sample, lack of blinding, expectation, and reliance on self-report of symptoms.

Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial.

BACKGROUND: The role of nutrition in the treatment of attention-deficit hyperactivity disorder (ADHD) is gaining international attention; however, treatments have generally focused only on diet restriction or supplementing with one nutrient at a time. AIMS: To investigate the efficacy and safety of a broad-based micronutrient formula consisting mainly of vitamins and minerals, without omega fatty acids, in the treatment of ADHD in adults. METHOD: This double-blind randomised controlled trial assigned 80 adults with ADHD in a 1:1 ratio to either micronutrients (n = 42) or placebo (n = 38) for 8 weeks (trial registered with the Australian New Zealand Clinical Trials Registry: ACTRN12609000308291). RESULTS: Intent-to-treat analyses showed significant between-group differences favouring active treatment on self- and observer- but not clinician-ADHD rating scales. However, clinicians rated those receiving micronutrients as more improved than those on placebo both globally and on ADHD symptoms. Post hoc analyses showed that for those with moderate/severe depression at baseline, there was a greater change in mood favouring active treatment over placebo. There were no group differences in adverse events. CONCLUSIONS: This study provides preliminary evidence of efficacy for micronutrients in the treatment of ADHD symptoms in adults, with a reassuring safety profile.

Moderators of treatment response in adults with ADHD treated with a vitamin-mineral supplement.

BACKGROUND: To date there has been no research investigating moderators of response to micronutrient treatment of mental illness, specifically baseline nutrient levels. METHOD: We conducted analyses of data from a randomized placebo-controlled trial (RCT) of 80 adults (≥16years) with Attention-Deficit/Hyperactivity Disorder (ADHD), whereby participants were treated acutely (8weeks) with micronutrients or placebo followed by an open-label (OL) phase of 8weeks whereby all participants received micronutrients. To ensure that all participants had been exposed to the micronutrients for 8weeks, only those 64 who had adhered to the treatment protocol and completed 8weeks on nutrients were included in the data analysis: 34 from the group that had been randomized to the micronutrient arm, and 30 from the group that had been randomized to the placebo group and hence had only received nutrients in the OL phase. Six outcomes were examined: change in ADHD symptoms (self/clinician), ADHD responder, Clinical Global Impression-Improvement (CGI-I), change in mood, and change in Global Assessment of Functioning (GAF). Demographic, developmental and psychiatric history, current clinical characteristics, and baseline nutrient levels were all considered as putative predictors. RESULTS: There were significant changes in all outcome variables after 8weeks exposure to the micronutrients. Among the nutrients recorded at baseline, substantial deficiencies (27%) were only observed for vitamin D. However, other than an association showing that higher iron at baseline was correlated with higher baseline depression scores, baseline nutrient levels were not correlated with baseline psychiatric variables/current clinical characteristics. Regression analyses revealed that higher baseline ferritin and lower baseline copper and vitamin D levels were associated with a better response to treatment for some but not all outcomes. None of the other nutrient levels was found to be associated with outcome, including zinc, vitamin B12, iron, and folate. There were no childhood risk factors, demographic variables or clinical correlates that contraindicated micronutrient treatment; more severe symptoms at baseline and greater number of developmental risk factors predicted greater treatment response. CONCLUSIONS: Further research looking at nutrients more broadly is required to confirm these initial observations about ferritin, vitamin D and copper; however, the results suggest that serum nutrient levels have limited value for identifying who will respond to treatment.

Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses.

OBJECTIVE: To compare two micronutrient (vitamins and minerals) formulas (Berocca™ and CNE™) and assess their impact on emotions and stress related to the 6.3 earthquake on February 22(nd) 2011 in Christchurch, New Zealand. METHODS: 91 adults experiencing heightened anxiety or stress 2-3 months following the earthquake were randomized to Berocca™, CNE™ low dose (CNE4), or CNE™ high dose (CNE8), for 28 days and monitored weekly via on-line questionnaires and followed 1 month post-trial. A nonrandomized control group (n = 25) completed questionnaires at baseline and 4 weeks. RESULTS: All treatment groups experienced significant declines in psychological symptoms (p < .001). CNE™ groups experienced greater reduction in intrusive thoughts as compared with Berocca™ (p = .05), with no group differences on other measures of psychological symptoms. However, CNE8 group reported greater improvement in mood, anxiety, and energy (p < .05) with twice as many reporting being "much" to "very much" improved and five times more likely to continue taking CNE™ post-trial than Berocca™ group. Treated participants had better outcomes on most measures over 4 weeks as compared to controls. CONCLUSIONS: This study supports micronutrients as an inexpensive and practical treatment for acute stress following a natural disaster with a slight advantage to higher doses ACTRN 12611000460909.

Micronutrients reduce stress and anxiety in adults with Attention-Deficit/Hyperactivity Disorder following a 7.1 earthquake.

The role of good nutrition for resilience in the face of stress is a topic of interest, but difficult to study. A 7.1 earthquake took place in the midst of research on a micronutrient treatment for Attention-Deficit/Hyperactivity Disorder (ADHD), providing a unique opportunity to examine whether individuals with ADHD taking micronutrients demonstrated more emotional resilience post-earthquake than individuals with ADHD not taking micronutrients. Thirty-three adults with ADHD were assessed twice following the earthquake using a measure of depression, anxiety and stress also completed at some point pre-earthquake (baseline). Seventeen were not taking micronutrients at the time of the earthquake (control group), 16 were (micronutrient group). While there were no between-group differences one week post-quake (Time 1), at two weeks post-quake (Time 2), the micronutrient group reported significantly less anxiety and stress than the controls (effect size 0.69). These between group differences could not be explained by other variables, such as pre-earthquake measures of emotions, demographics, psychiatric status, and personal loss or damage following the earthquake. The results suggest that micronutrients may increase resilience to ongoing stress and anxiety associated with a highly stressful event in individuals with ADHD and are consistent with controlled studies showing benefit of micronutrients for mental health.