How the placenta-brain lipid axis impacts the nutritional origin of child neurodevelopmental disorders: Focus on attention deficit hyperactivity disorder and autism spectrum disorder.

Dietary fish is a rich source of omega-3 (n-3) fatty acids, and as such, is believed to have played an important role in the evolution of the human brain and its advanced cognitive function. The long chain polyunsaturated fatty acids, particularly the n-3 docosahexanoic acid (DHA), are critical for proper neurological development and function. Both low plasma DHA and obesity in pregnancy are associated with neurodevelopmental disorders such as attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in childhood, and n-3 supplementation has been shown to improve symptoms, as reviewed herein. The mechanisms underlying the connection between maternal obesity, n-3 fatty acid levels and offspring's neurological outcomes are poorly understood, but we review the evidence for a mediating role of the placenta in this relationship. Despite promising data that n-3 fatty acid supplementation mitigates the effect of maternal obesity on placental lipid metabolism, few clinical trials or animal studies have considered the neurological outcomes of offspring of mothers with obesity supplemented with n-3 FA in pregnancy.

The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder common from childhood to adulthood, affecting 5% to 12% among the general population in developed countries. Potential etiological factors have been identified, including genetic causes, environmental elements and epigenetic components. Nutrition is currently considered an influencing factor, and several studies have explored the contribution of restriction and dietary supplements in ADHD treatments. Iron is an essential cofactor required for a number of functions, such as transport of oxygen, immune function, cellular respiration, neurotransmitter metabolism (dopamine production), and DNA synthesis. Zinc is also an essential trace element, required for cellular functions related to the metabolism of neurotransmitters, melatonin, and prostaglandins. Epidemiological studies have found that iron and zinc deficiencies are common nutritional deficits worldwide, with important roles on neurologic functions (poor memory, inattentiveness, and impulsiveness), finicky appetite, and mood changes (sadness and irritability). Altered levels of iron and zinc have been related with the aggravation and progression of ADHD. OBJECTIVE: This is a systematic review focused on the contribution of iron and zinc in the progression of ADHD among children and adolescents, and how therapies including these elements are tolerated along with its effectiveness (according to PRISMA guidelines). METHOD: The scientific literature was screened for randomized controlled trials published between January 2000 to July 2021. The databases consulted were Medline, PsycINFO, Web of Science, and Google Scholar. Two independent reviewers screened studies, extracted data, and assessed quality and risk of bias (CONSORT, NICE, and Cochrane checklists used). CONCLUSION: Nine studies met the eligibility criteria and were selected. Evidence was obtained regarding the contribution of iron-zinc supplementation in the treatment of ADHD among young individuals. The discussion was focused on how the deficits of these elements contribute to affectation on multiple ADHD correlates, and potential mechanisms explaining the mediational pathways. Evidence also suggested that treating ADHD with diet interventions might be particularly useful for specific subgroups of children and adolescents, but further investigations of the effects of these diet interventions are needed.

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.

Does Diet Affect the Symptoms of ADHD?

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric diagnosis in childhood and adolescence, with an estimated worldwide-pooled prevalence of 5,29%. The type of treatment depends on several factors. Psychopharmacological treatment entails undesirable side effects, with unclear long-term benefits, which has led the scientific community to investigate other therapeutic approaches, such as dietary interventions. METHOD: The authors conducted a classical review on the current treatment recommended in individuals with ADHD diagnosis, their dietary patterns, as well as dietary factors possibly implicated in the etiology and treatment of this disorder. An extensive bibliographic research was carried out in the databases PubMed, The Cochrane Library and the National Guideline Clearinghouse. DISCUSSION: The most common dietary interventions in the case of ADHD are food supplementation diets (e.g. PUFAs, vitamins) and elimination diets. Supplementation with omega-3 PUFAs lacks further studies that can validate them as an effective therapeutic approach in this disorder. Also, regarding vitamin supplementation, studies are not consistent as to their role in the etiology of ADHD. Elimination diets are unclear as to the benefits provided in individuals with ADHD. Children with ADHD are less likely to engage in healthy lifestyle behaviors than non-ADHD youth. CONCLUSION: There is no clear evidence that supports dietary interventions for the treatment of ADHD. The effects of unhealthy diet patterns in ADHD individuals are not yet fully understood and, like the general population, children with ADHD may benefit from a healthy lifestyle.

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.

Supplementation with polyunsaturated fatty acids (PUFAs) in the management of attention deficit hyperactivity disorder (ADHD).

While pharmacotherapy and psychosocial interventions are recommended as the primary frontline treatment for attention deficit hyperactivity disorder (ADHD), alternative approaches to managing ADHD are becoming increasingly popular among patients and their families. Supplementation with polyunsaturated fatty acids (PUFAs) is an example of this. PUFA supplementation is not recommended by guidelines for managing ADHD; however, patients may still decide to use it. To provide direction to healthcare professionals (HCPs) managing ADHD, eight international experts in the field of adult and child ADHD came together for the Continuum Education Board: Omega Supplements in ADHD meeting. This commentary summarises the panel's consensus that current evidence suggests PUFA supplementation has a small beneficial effect on behaviour in children with ADHD, and that further high-quality research is needed to clearly evaluate and define its role in the management of ADHD of children, adolescents and adults. The panel concluded that in cases where patients use PUFA supplementation, HCPs should be comfortable explaining the potential gains that they may have and their possible side effects. The panel also concluded HCPs should not reinforce the idea that PUFA supplementation should replace treatment approaches with a more robust evidence base for managing ADHD.

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 vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized, double blind, placebo-controlled trial.

OBJECTIVES: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD. METHODS: Sixty-two children aged 5-12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed. RESULTS: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P < 0.05). Evening symptoms and total score of WPREMB scale were significantly different at weeks 4 and 8 between the two groups (P = 0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales. DISCUSSION: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism. The trial was registered in www.irct.ir is (IRCT201404222394N10).

A case series on the potential effect of omega-3-fatty acid supplementation on 24-h heart rate variability and its circadian variation in children with attention deficit (hyperactivity) disorder.

Attention deficit disorder with and without hyperactivity (ADHD) in children is associated with decreased 24-h heart rate variability (HRV). Previous research has shown that supplementation of omega-3-fatty acid increases HRV. Here, we aimed to investigate whether the supplementation of omega-3-fatty acids would increase 24-h HRV in an uncontrolled case series of children with ADHD. HRV was recorded in 18 children and adolescents (age 13.35 ± 2.8 years) before and after omega-3 supplementation. Preliminary results indicate that omega-3 supplementation in children with AD(H)D may reduce mean heart rate and increase its variability. Future studies would do well to implement randomized, placebo-controlled designs with greater methodological rigor.

Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder: a Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies.

The role of omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) in the pathogenesis and treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD) is unclear. A systematic review followed by meta-analysis was conducted on: (1) randomized controlled trials (RCTs) assessing the effects of n-3 PUFAs on clinical symptoms and cognition in children and adolescent with ADHD; and (2) case-control studies assessing the levels of n-3 PUFAs in blood and buccal tissues of children and adolescents with ADHD. In seven RCTs, totalling n=534 randomized youth with ADHD, n-3 PUFAs supplementation improves ADHD clinical symptom scores (g=0.38, p<0.0001); and in three RCTs, totalling n=214 randomized youth with ADHD, n-3 PUFAs supplementation improves cognitive measures associated with attention (g=1.09, p=0.001). Moreover, children and adolescents with ADHD have lower levels of DHA (seven studies, n=412, g=-0.76, p=0.0002), EPA (seven studies, n=468, g=-0.38, p=0.0008), and total n-3 PUFAs (six studies, n=396, g=-0.58, p=0.0001). In summary, there is evidence that n-3 PUFAs supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD, and that these youth have a deficiency in n-3 PUFAs levels. Our findings provide further support to the rationale for using n-3 PUFAs as a treatment option for ADHD.

Dietary supplements in child and adolescent psychiatry.

Complementary and alternative treatments, including dietary supplements, are very popular and increasingly used in developed countries. Some features such as accessibility, ease of use, the possibility of self-administration and the belief they are safe without side effects, have led to an increase in their consumption. However, there is limited evidence of the effectiveness and safety of these treatments because of methodological issues. The level of scientific evidence is particularly low and weak in the field of child and adolescent Psychiatry. The purpose of this article is to give an updated overview of dietary treatments in this area. We make a brief introduction about general questions, including legal aspects, and propose general practical recommendations for a proper management by the families that choose these treatments. We focus on reviewing the current state of research into dietary treatments in some childhood and juvenile psychiatric disorders, highlighting current evidence of specific treatments. The final purpose of this article is to describe the level of current evidence on dietary treatments and to provide professionals involved in the care of children and adolescents with a useful tool to help, guide and educate families about their use in order to achieve the greatest benefit to patients.

Nutritional interventions to reduce symptoms in children and adults with attention deficit hyperactivity disorder: a scoping review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this scoping review is to examine and map reported nutritional interventions and their outcomes in relieving symptoms of attention deficit hyperactivity disorder (ADHD) in the daily lives of children and adults. A further objective is to determine if experiences of people diagnosed with ADHD, their relatives or staff in being on a diet or having to eat or avoid eating specific food items have been reported in the existing literature.Specifically the scoping review questions are.

Dietary factors in the etiology and therapy of attention deficit/hyperactivity disorder.

PURPOSE OF REVIEW: The purpose of this study is to discuss the role of dietary factors in the etiology and therapy of attention deficit/hyperactivity disorder (ADHD). Relevant literature published from January 2016 to January 2017 was included in this review. RECENT FINDINGS: Unhealthy prenatal diet may be associated with ADHD in the offspring through an increase in epigenetic changes. The few-foods diet may have some efficacy, but requires further investigation before firm conclusions can be drawn. The efficacy of the supplementation of polyunsaturated fatty acids in the therapy of ADHD is probably small and may be confined to patient subgroups. It is unclear whether vitamin deficiency plays a role in the etiology of ADHD. SUMMARY: There is no clear evidence supporting a role of food or nutrient-based intervention strategies in the etiology and therapy of ADHD. The investigation of the inter-relationship between diet and other lifestyle interventions may be a promising approach.

The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. METHODS AND FINDINGS: We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution. CONCLUSIONS: Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.

Nutritional Psychiatry: Where to Next?

The nascent field of 'Nutritional Psychiatry' offers much promise for addressing the large disease burden associated with mental disorders. A consistent evidence base from the observational literature confirms that the quality of individuals' diets is related to their risk for common mental disorders, such as depression. This is the case across countries and age groups. Moreover, new intervention studies implementing dietary changes suggest promise for the prevention and treatment of depression. Concurrently, data point to the utility of selected nutraceuticals as adjunctive treatments for mental disorders and as monotherapies for conditions such as ADHD. Finally, new studies focused on understanding the biological pathways that mediate the observed relationships between diet, nutrition and mental health are pointing to the immune system, oxidative biology, brain plasticity and the microbiome-gut-brain axis as key targets for nutritional interventions. On the other hand, the field is currently limited by a lack of data and methodological issues such as heterogeneity, residual confounding, measurement error, and challenges in measuring and ensuring dietary adherence in intervention studies. Key challenges for the field are to now: replicate, refine and scale up promising clinical and population level dietary strategies; identify a clear set of biological pathways and targets that mediate the identified associations; conduct scientifically rigorous nutraceutical and 'psychobiotic' interventions that also examine predictors of treatment response; conduct observational and experimental studies in psychosis focused on dietary and related risk factors and treatments; and continue to advocate for policy change to improve the food environment at the population level.

Suplementos nutricionales en psiquiatría del niño y del adolescente / Dietary supplements in child and adolescent psychiatry

Los tratamientos de la medicina complementaria y alternativa, incluyendo los tratamientos con suplementos nutricionales, son muy populares en los países desarrollados y su uso continúa creciendo. La facilidad de uso, su accesibilidad y posibilidad de autoadministración y la percepción como seguros y carentes de efectos secundarios han conducido a un incremento de su consumo. Sin embargo, la evidencia de la efectividad y seguridad de estos tratamientos es limitada a causa de los problemas metodológicos. En el caso de la psiquiatría del niño y del adolescente, el nivel de evidencia científica es particularmente escaso y débil. El propósito de este artículo es dar una visión general actualizada de los tratamientos nutricionales en psiquiatría del niño y del adolescente. Realizamos una breve introducción que expone cuestiones generales sobre este tema, incluyendo aspectos legales. Proponemos recomendaciones generales prácticas para un manejo adecuado de las familias que escogen estos tratamientos. Nos centramos en la revisión del estado actual de la investigación de los tratamientos nutricionales en varios trastornos psiquiátricos infanto-juveniles, y describimos la evidencia actual de tratamientos específicos. El objetivo último de este artículo es proporcionar a los profesionales implicados en la atención de niños y adolescentes la información sobre el nivel de la evidencia actual de los tratamientos nutricionales para que puedan orientar, ayudar y educar a las familias sobre su uso y procurar de esta manera el mayor beneficio de los pacientes (AU)

Complementary and alternative treatments, including dietary supplements, are very popular and increasingly used in developed countries. Some features such as accessibility, ease of use, the possibility of self-administration and the belief they are safe without side effects, have led to an increase in their consumption. However, there is limited evidence of the effectiveness and safety of these treatments because of methodological issues. The level of scientific evidence is particularly low and weak in the field of child and adolescent Psychiatry. The purpose of this article is to give an updated overview of dietary treatments in this area. We make a brief introduction about general questions, including legal aspects, and propose general practical recommendations for a proper management by the families that choose these treatments. We focus on reviewing the current state of research into dietary treatments in some childhood and juvenile psychiatric disorders, highlighting current evidence of specific treatments. The final purpose of this article is to describe the level of current evidence on dietary treatments and to provide professionals involved in the care of children and adolescents with a useful tool to help, guide and educate families about their use in order to achieve the greatest benefit to patients (AU)

Integrative Nutrition for Pediatrics.

Food is essential for life. Yet, poor food choices may cause poor health. Dietary manipulation is frequently integrated into the management of common chronic pediatric conditions. Parents seek dietary information to have more control over child's condition and to avoid side effects of medicine. This article reviews selected diets for a few common pediatric disorders including eczema, attention deficit hyperactivity disorder, headache and migraine, non-celiac gluten sensitivity, and irritable bowel syndrome.

The effect of omega-3 polyunsaturated fatty acid supplementation on emotional dysregulation, oppositional behaviour and conduct problems in ADHD: A systematic review and meta-analysis.

BACKGROUND: A number of randomised controlled trials report a beneficial effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on emotional lability (EL) and related domains (e.g. oppositional behaviour, conduct problems). Given that n-3 PUFA supplementation shows a significant effect on reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) and that EL and related behaviours commonly co-occurs with ADHD, it is important that there is a more conclusive picture as to the effect of n-3 PUFA on these co-occurring clinical domains. METHODS: Databases (Ovid Medline, Embase, Psychinfo) were searched for trials assessing the effects of n-3 PUFA on EL, oppositional behaviour, aggression and conduct problems. We included trials in children who had ADHD or a related neurodevelopmental disorder. RESULTS: Of the 1775 identified studies, 10 were included in the meta-analysis. In the primary analyses n-3 PUFA supplementation did not show improvements in measures of EL, oppositional behaviour, conduct problems or aggression. However subgroup analyses of higher quality studies and those meeting strict inclusion criteria found a significant reduction in EL and oppositional behaviour. LIMITATIONS: A number of treatment effects may have failed to reach statistical significance due to small sample sizes and within and between study heterogeneity in terms of design and study participants. CONCLUSIONS: These results exclude the possibility of moderate to large effects. They provide suggestive evidence of small effects of n-3 PUFA on reducing EL and oppositional behaviour in subgroups of children with ADHD.

Micronutrient treatment for children with emotional and behavioral dysregulation: a case series.

INTRODUCTION: In clinical studies of adults and children, broad-spectrum micronutrients (minerals and vitamins) have proven beneficial for improving mood regulation and attention. We report here pilot work whose primary objective was to evaluate the feasibility of studying micronutrient treatment in school-aged children with emotional and behavioral problems. Issues examined included feasibility of participant recruitment from a culturally diverse population, probability of sample retention for a 12-week trial, acceptability of the outcome measures, supplement adherence, as well as trends in treatment benefit. CASE PRESENTATION: The families of two boys (ages 5 and 6) and one girl (age 14) were invited to participate in a 12-week pilot trial of micronutrients carried out during the summer months. All children were enrolled in the private school at which future research was being considered. During the previous school year, all three had been extremely difficult to educate due to their inability to pay attention and learn, as well as their behavior problems. Although the two younger children had not been formally diagnosed, parents and teachers provided reports of hyperactivity and inability to focus on education in the classroom. The oldest child was often aggressive, and had been diagnosed with bipolar disorder, attention deficit hyperactivity disorder, and oppositional defiant disorder. All three children were Hispanic and spoke both Spanish and English. For 12 weeks, after signing consent forms, the children's parents provided weekly ratings on the parent-report Child Mania Rating Scale; the children consumed the micronutrient formula daily and provided a daily rating of how they felt. The parent ratings revealed significantly improved behavior, p = .002. Children's ratings approached the ideal level of 7, indicating "happy" self-reports. Parent interviews confirmed the weekly scores. Several feasibility questions were answered: all three children completed the 12-week trial, all scores were completed by parents and children, adherence to the protocol was excellent, and no adverse reactions emerged. CONCLUSIONS: Family physicians and pediatricians are often confronted with the challenge of improving the lives of families whose children experience school crises due to emotional and behavioral dysregulation. Three children, who participated in pilot work to determine the feasibility of further investigations, experienced impressive changes that clearly warrant both research and clinical exploration.