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Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial.
Johnstone, JM, Hatsu, I, Tost, G, Srikanth, P, Eiterman, LP, Bruton, AM, Ast, HK, Robinette, LM, Stern, MM, Millington, EG, et al
Journal of the American Academy of Child and Adolescent Psychiatry. 2022;61(5):647-661
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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects about 5-7% of children. Characteristics of ADHD are age-inappropriate hyperactivity, impulsivity, and difficulties in focusing attention which arise from an impaired ability to regulate executive and emotional functions. The condition often persists into adulthood, where it presents an increased risk for poor educational achievements, substance abuse, incarceration, and mental health problems. In many cases, drug treatment can improve ADHD symptoms, yet concern remains about the side effects of these treatments. Some research has investigated the impact of nutrient supplementation on ADHD management, as many nutrients are essential for healthy brain function and are also involved in the production of neurotransmitters. In previous studies, supplementation with nutrients has shown some benefits but likewise also inconsistent results. This eight-week randomised placebo-controlled clinical trial evaluated the effects of a multi-nutrient supplement in 135 children with ADHD, aged 6-12 years. The study specifically focused on irritable mood symptoms. The multi-nutrient formula contained vitamins, minerals, amino acids, and antioxidants. Outcomes were measured by scores rated by clinicians (Clinical Global Impression-Improvement aka CGI-I) and scores rated by parents (Child and Adolescent Symptom Inventory-5 aka CASI-5). The multi-nutrient formula showed overall benefit in the blinded clinician rating but not by parental reports. According to the parents, overall improvement was reported, both in the placebo and intervention groups. The authors discussed how this absence of difference can be explained. Yet, on a subscale, the multi-nutrient group parents were more likely to report improvements. In addition, children with the additional micronutrients demonstrated greater height growth during the intervention. The supplement was well tolerated with good adherence and the monitored blood markers demonstrated safety of use.
Expert Review
Conflicts of interest:
None
Take Home Message:
This fully-blinded RCT of micronutrients addresses several concerns related to existing ADHD treatment, including the possibility of counteracting height suppression and treating associated irritable mood, emotional dysregulation, and aggression.
Although further research is needed, multinutrient supplementation should be considered for children with ADHD.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric condition that can result in low educational performance and achievement. Around 5-7% of children are believed to be affected. Alongside inattention and hyperactivity, emotional dysregulation is a common feature of ADHD. Psychiatric problems can continue into adulthood and an increased risk of incarceration and substance abuse have been reported.
Treatment with prescription medications may improve symptoms of ADHD, however, potential side effects include mild growth suppression, and mood and emotional dysregulation. Non-pharmacological treatments are therefore being investigated.
Previous research on single nutrients have shown mixed results for emotional dysregulation and mood issues in ADHD. The aim of this study was to test whether supplementation with a multi-nutrient could be beneficial to children aged 6-12 years with ADHD and irritability.
Methods
126 unmedicated children from North America with ADHD (mean age 9.8 years) completed this 8-week study. All participants had at least 1 symptom of anger, irritability, peer conflict or Disruptive Mood Dysregulation Disorder (DMDD).
Randomisation was into an intervention (n=71) or placebo (N=55) group with a 3:2 ratio to promote enrolment. Participants were required to take 6-12 capsules daily, depending on age and tolerance, of micronutrients or a placebo. Micronutrient dosages were above the recommended dietary allowance (RDA). Outcomes were measured using clinician and parent rated assessments and by a further adult who knew the child well.
The trial was blinded to all participants, parents and study staff.
Results
The clinician-rated results found 54% of the micronutrient group and 18% of the placebo group had improvements in irritability symptoms (Risk ratio =2.97, 97.5% CI: 1.5, 5.90, p<0.001). This was not replicated in the parent/adult rated results. Children in the micronutrient group grew on average 6mm more than the placebo group (p=0.002). No serious adverse treatment effects were reported. Adherence to protocol was met by >74% of participants (n=93).
Conclusions
In this study, clinicians reported that micronutrients showed greater benefits than placebo for treating irritability and supporting growth in children with ADHD.
The study and authors received funding from several research and association bodies. However, no funder was involved in the study design or reporting. No conflicts of interest were declared.
Clinical practice applications:
- Multinutrient supplementation including vitamins, minerals, amino acids, and antioxidants may support height growth in children who take pharmacologic treatment
- Multi nutrient supplementation may also help with irritable mood, emotional dysregulation, and aggression in ADHD children
- Micronutrients given at doses between the Recommended Dietary Allowance and Upper Tolerable Intake Level appear safe and may be developed into an alternative or complementary treatment for ADHD.
Considerations for future research:
- Further large scale research is needed into the potential benefits of micronutrients for children with ADHD and irritability
Abstract
OBJECTIVE To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD 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. RESULTS 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. CONCLUSION 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. CLINICAL TRIAL REGISTRATION INFORMATION Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.
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Comparing eating behaviours, and symptoms of depression and anxiety between Spain and Greece during the COVID-19 outbreak: Cross-sectional analysis of two different confinement strategies.
Papandreou, C, Arija, V, Aretouli, E, Tsilidis, KK, Bulló, M
European eating disorders review : the journal of the Eating Disorders Association. 2020;28(6):836-846
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Stress and mental health problems which may be induced by restrictions imposed during the Covid-19 pandemic can lead to unhealthy eating habits. Restrictions have varied amongst countries and this cross-sectional analysis aimed to compare eating behaviours and symptoms of stress experienced by 1841 individuals in countries with differing lockdown measures. The results showed that individuals in the country with higher lockdown measures showed lower restraint in eating, they were more likely to overeat if they saw or smelt food and reported increased anxiety. However, they did not display depression or overeating when experiencing negative feelings. It was concluded that both countries had a high frequency of depression and anxiety. Higher restrictions were associated with greater anxiety, lower restraint and overeating when confronted with food. This paper could be used by healthcare professionals to recognise the need to include dietary advice when dealing with patients who are reporting anxiety during the current Covid-19 pandemic.
Abstract
OBJECTIVE We compared eating behaviours, and depressive and anxiety symptoms in two countries with different confinement strictness strategies and different levels of COVID-19 pandemic. METHOD A web-based cross-sectional survey was administered during and shortly after the COVID-19 related lockdown in Spain and Greece. Multivariable linear regression analyses were performed to identify country differences associated with eating behaviour, and symptoms of depression and anxiety. RESULTS This study included 1,002 responders in Spain and 839 in Greece. The mean ± SD of restraint, emotional and external eating was 2.5 ± 0.79, 2.1 ± 0.81 and 2.6 ± 0.65 in Spain, whereas 2.7 ± 0.85, 2.3 ± 0.99 and 2.9 ± 0.74 in Greece. Spanish participants had lower average scores of restraint and external eating compared to Greek participants (p < .001), but no difference was seen for emotional eating. In Spain, 13.6%, and 12.3% of the survey respondents reported moderate to severe depressive and anxiety symptoms, respectively, whereas in Greece the respective values were 18.8 and 13.2%. After adjusting for several risk factors, a higher prevalence of anxiety symptoms was observed in Spain compared to Greece (p = .001), but no difference was seen for depressive symptoms. CONCLUSIONS This study demonstrated high scores of inappropriate eating behaviours and a high frequency of depressive and anxiety symptoms in two Mediterranean countries during the COVID-19 outbreak. Our findings revealed that compared to Greek participants, Spanish participants, that faced more severe COVID-19 pandemic and stricter lockdown measures, were associated with lower restraint and external eating and increased anxiety symptoms, but not with depressive symptoms or emotional eating.
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Key Risk Factors Affecting Farmers' Mental Health: A Systematic Review.
Daghagh Yazd, S, Wheeler, SA, Zuo, A
International journal of environmental research and public health. 2019;16(23)
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The prevalence of psychological stress among farmers and farm workers is greater than that of non-farmers. The mental health of farmers can be affected by several factors, including pesticide exposure, financial problems, climate issues, and poor physical health. A total of 167 studies are included in this systematic review incorporating data from the studies conducted in 34 countries, including the United Kingdom, the United States and Australia. There is a need for risk assessment that influences farmers' mental health, according to this systematic review. There is a need for more robust studies to evaluate the impact of climate change and pesticide exposure on farmers' mental health and to determine which strategies can be used to help them find therapies. Using the results of this systematic review, healthcare professionals can raise awareness about mental health issues and assist farmers in identifying the symptoms, allowing them to seek help.
Abstract
Recently, concern has increased globally over farmers' mental health issues. We present a systematic review of the outcomes, locations, study designs, and methods of current studies on farmers' mental health. In particular, this review aims to fill an important gap in understanding of the potential key risk factors affecting farmers' mental health around the world. 167 articles on farmer mental health were included in a final systematic review using a standardized electronic literature search strategy and PRISMA guidelines. The four most-cited influences on farmers' mental health in the reviewed literature respectively were pesticide exposure, financial difficulties, climate variabilities/drought, and poor physical health/past injuries. The majority of studies were from developed countries, most specifically from the United States, Australia, and the United Kingdom. Comparative studies on the mental health of farmers and other occupational workers showed mixed results, with a larger portion identifying that psychological health disturbances were more common in farmers and farm-workers. Knowledge of farmer psychological disorder risk factors and its impacts are essential for reducing the burden of mental illness. Further research will be required on climate change impacts, developing country farmers' mental health, and information on how to reduce help-seeking barriers amongst farmers.
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Patterns of Eating Disorder Pathology are Associated with Weight Change in Family-Based Behavioral Obesity Treatment.
Balantekin, KN, Hayes, JF, Sheinbein, DH, Kolko, RP, Stein, RI, Saelens, BE, Hurst, KT, Welch, RR, Perri, MG, Schechtman, KB, et al
Obesity (Silver Spring, Md.). 2017;25(12):2115-2122
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Children who are overweight or obese have higher rates of eating disorder pathology (extreme dietary restraint, loss of control eating and emotional eating) than their peers who are not overweight or obese, thus having an increased risk of developing a clinical eating disorder. The aim of the study is to classify overweight or obese children entering family-based treatment into groups with distinct patterns of eating disorder pathology and then examine eating disorder pattern differences in 3 categories. The study includes data from a multi-site randomised controlled trial. The analysis focused on data from the initial weight loss phase which included 241 obese or overweight children aged between 7 to 11 years. Results showed that eating disorders are more common among females than males, yet males also experience high levels of eating disorder pathology. Levels of eating disorder pathology decreased after family-based behavioural weight-loss treatment and so decreased the risk of the development of a clinical eating disorder. Authors conclude that eating disorder pathology is prevalent among children with overweight or obesity but has varying presentations.
Abstract
OBJECTIVE Children with overweight or obesity have elevated eating disorder (ED) pathology, which may increase their risk for clinical EDs. The current study identified patterns of ED pathology in children with overweight or obesity entering family-based behavioral weight loss treatment (FBT) and examined whether children with distinct patterns differed in their ED pathology and BMI z score (zBMI) change across FBT. METHODS Before participating in a 16-session FBT, children (N = 241) completed surveys or interviews assessing ED pathology (emotional eating, shape/weight/eating concerns, restraint, and loss of control [LOC]). Shape and weight concerns (SWC) and LOC were also assessed post treatment. Child height and weight were measured at baseline and post treatment. Latent class analysis identified patterns of ED pathology. Repeated-measures ANOVA examined changes in zBMI and ED pathology. RESULTS Four patterns of ED pathology were identified: low ED pathology, SWC, only loss of control, and high ED pathology. SWC decreased across treatment, with the highest decreases in patterns characterized by high SWC. All groups experienced significant decreases in zBMI; however, children with the highest ED pathology did not achieve clinically significant weight loss. CONCLUSIONS ED pathology decreased after FBT, decreasing ED risk. While all children achieved zBMI reductions, further research is needed to enhance outcomes for children with high ED pathology.