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.

A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods.

BACKGROUND: Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD. METHODS: A total of N = 162 children (5-12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm including N = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only. DISCUSSION: This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD. TRIAL REGISTRATION: www.trialregister.nl, NTR5434. Registered at October 11th, 2015.

Treating impulsivity with probiotics in adults (PROBIA): study protocol of a multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota-gut-brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity. METHODS/DESIGN: This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebo-controlled phase (response defined as a Clinical Global Impression-Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18-65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up. DISCUSSION: This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03495375. Registered on 26 February 2018.

Food Color and Autism: A Meta-Analysis.

Autism has been increasing dramatically since its description by Leo Kanner in 1943. The Centers for Disease Control and Prevention (CDC) in 2018 has identified 1 in 59 children (1 in 37 boys and 1 in 151 girls) has autism spectrum disorder (ASD). Autistic spectrum disorders and ADHD are complex conditions in which nutritional and environmental factors play major roles. It is important to understand how food can have an impact on their current and future health. Appealing food colors stimulate the consumption of different food products. Since 2011, it is evident that dyes are linked to harmful effects in children. Artificial dyes have neurotoxic chemicals that aggravate mental health problems. Many families with autistic children avoid food dyes in their diet in order to avoid behavioral issues. A study reported that there is a correlation between yellow dye and sleep disturbance. Food colors Blue 1 and 2, Green 3, Red 3, Yellow 5 and 6, Citrus Red 2, and Red 40 can trigger many behaviors in most kids. Artificial food color usually contains petroleum and is manufactured in a chemical process that includes formaldehyde, aniline, hydroxides, and sulfuric acids. Most impurities in the food color are in the form of salts or acids. Sometimes lead, arsenic, and mercury may be present as impurities. The U.S. FDA is yet to study the effects of synthetic dyes on behavior in children. A study conducted at Southampton University in England found a link between food dyes and hyperactive behavior in children. The research does not prove that food coloring actually causes autism spectrum disorder, but there seems to be a link. This chapter attempts to provide a broad review of the available literature on food color and the epidemiology, etiology, prevention, and treatment of autistic spectrum disorder.

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.

Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) - study protocol of an open-label trial to investigate the mechanisms underlying the effects of a few-foods diet on ADHD symptoms in children.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common childhood behavioural disorder, causing significant impediment to a child's development. It is a complex disorder with numerous contributing (epi)genetic and environmental factors. Currently, treatment consists of behavioural and pharmacological therapy. However, ADHD medication is associated with several side effects, and concerns about long-term effects and efficacy exist. Therefore, there is considerable interest in the development of alternative treatment options. Double-blind research investigating the effects of a few-foods diet (FFD) has demonstrated a significant decrease in ADHD symptoms following an FFD. However, an FFD requires a considerable effort of both child and parents, limiting its applicability as a general ADHD treatment. To make FFD intervention less challenging or potentially obsolete, we need to understand how, and in which children, an FFD affects ADHD behaviour and, consequently, the child's well-being. We hypothesise that an FFD affects brain function, and that the nutritional impact on ADHD is effectuated by a complex interplay between the microbiota, gut and brain, that is, the microbiota-gut-brain axis. METHODS AND ANALYSIS: The Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) study is an open-label trial with researchers blinded to changes in ADHD symptoms during sample processing and initial data analyses. ETHICS AND DISSEMINATION: The Medical Research and Ethics Committee of Wageningen University has approved this study (NL63851.081.17, application 17/24). Results will be disseminated through peer-reviewed journal publications, conference presentations, (social) media and the BRAIN study website. A summary of the findings will be provided to the participants. TRIAL REGISTRATION NUMBER: NCT03440346. STUDY DATES: Collection of primary outcome data started in March 2018 and will be ongoing until 100 children have participated in the study. Sample data analysis will start after all samples have been collected.

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.

Attention deficit and hyperactivity disorder symptoms respond to gluten-free diet in patients with coeliac disease.

Introduction: Patients with coeliac disease commonly report symptoms of 'brain fog'. The aim of this study was to assess self-reported symptoms of impaired concentration in coeliac disease before and after treatment with gluten-free diet, compared with healthy controls and patient controls. Methods: Patients with newly diagnosed coeliac disease were included consecutively from two out-patient clinics. The patients completed the questionnaires Adult ADHD Self-Report Scale v1.1 Symptoms Checklist (ASRS), Hospital Anxiety and Depression Scale (HADS) and Gastrointestinal Symptom Rating Scale (GSRS) prior to start of a gluten-free diet and after at least 12 months on the diet. Patients with an established diagnosis of inflammatory bowel disease served as patient controls (n = 36). Health care personnel at Oslo University Hospital served as healthy controls (n = 60) and filled out ASRS and HADS. Results: A total of 31 newly diagnosed coeliac patients were included in the study. Of these, 26 patients met for follow-up and repeated the questionnaires. Prior to treatment, patients with coeliac disease had significantly higher scores than healthy controls on both the ASRS (p = .0014) and HADS (p=.0004). After a gluten-free diet, their scores improved and were not significantly different from healthy controls. There were no significant differences between patients with coeliac disease prior to treatment and patient controls with inflammatory bowel disease. Conclusion: Prior to treatment, coeliac disease patients reported significantly more symptoms than healthy controls on ASRS and HADS. The differences disappeared after a minimum of 12 months on a gluten-free diet.

Treatment strategies for ADHD: an evidence-based guide to select optimal treatment.

Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing disorder affecting children, adolescents, and adults. Several treatment strategies are available that can successfully ameliorate symptoms, ranging from pharmacological to dietary interventions. Due to the increasing range of available options, an informed selection or prioritization of treatments is becoming harder for clinicians. This review aims to provide an evidence-based appraisal of the literature on ADHD treatment, supplemented by expert opinion on plausibility. We outline proposed mechanisms of action of established pharmacologic and non-pharmacologic treatments, and we review targets of novel treatments. The most relevant evidence supporting efficacy and safety of each treatment strategy is discussed. We review the individualized features of the patient that should guide the selection of treatments in a shared decision-making continuum. We provide guidance for optimizing initiation of treatment and follow-up of patients in clinical settings.

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.

The effectiveness of omega-3 supplementation in reducing ADHD associated symptoms in children as measured by the Conners' rating scales: A systematic review of randomized controlled trials.

Omega-3 supplements are considered to have anti-inflammatory effects which may be beneficial as inflammation has been linked to ADHD. The aim of this review is to examine the effectiveness of omega-3 supplementation at reducing ADHD symptoms in children and adolescents. Medline, Cinahl+, PsycINFO, Cochrane and Embase were searched for trials investigating the effects of omega-3 supplementation in children and adolescents with ADHD. The primary outcome measure was a mean difference in Conners' rating scale (CRS) between the intervention and placebo group. Search terms used include ADHD, omega-3, fish oils, eicosapentaenoic acid, docosahexaenoic acids, alpha-linolenic acid and Conners' rating scale. Randomized controlled trials examining the efficacy of omega-3 supplementation in children and adolescents as measured by CRS were included. Studies using a combination of polyunsaturated fatty acids or any other rating scale were excluded. Seven trials were included in this review, totalling 926 participants. We found no evidence of publication bias or heterogeneity between trials. Overall, there was a slightly greater reduction in CRS score in favour of the experiment group. One study found a greater reduction in score in favour of the placebo group. Neither findings were statistically significant. There is little supportive evidence to validate the claim of omega-3 supplementation to reduce the degree of ADHD symptoms experienced by children and adolescents. Both experiment and control groups saw similar reductions in Conners rating scale score.

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.

Associations between attention-deficit/hyperactivity disorder symptoms and dietary habits in elementary school children.

OBJECTIVE: The aim of the present study was to investigate the associations between dietary habits and attention deficit/hyperactivity disorder (ADHD) symptoms in elementary school children. METHODS: The parents of 16,831 participating children assessed the ADHD symptoms of their children by responding to the Korean version of the ADHD rating scale (K-ARS). Parents also responded to the food habit questionnaire, which consists of 8 items regarding the eating pace, the frequency of overeating, and patterns of eating six types of food: fast food, soft drinks, instant noodles, fruit and vegetables, and milk. RESULTS: K-ARS scores were positively associated with higher consumption of foods categorized as unhealthy, including fast food, soft drinks, and instant noodles, and negatively associated with higher consumption of fruit and vegetables categorized as healthy foods. K-ARS scores were also higher in the groups who overate more frequently and ate faster or slower compared to other family members. CONCLUSION: Our findings may provide useful clinical information for dietary interventions in children with 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.

Dietary patterns are associated with attention-deficit/hyperactivity disorder (ADHD) symptoms among preschoolers in mainland China.

BACKGROUND/OBJECTIVES: To identify the major dietary patterns among preschoolers and assess the relation of major dietary patterns to attention-deficit/hyperactivity disorder (ADHD). SUBJECTS/METHODS: A cross-sectional survey was conducted comprising a large sample of 14,912 children aged 3-6 years old in Ma'anshan city of Anhui Province in China. A semi-quantitative food frequency questionnaire and the 10-item Chinese version of the Conners' abbreviated symptom questionnaire were administered to assess usual dietary intakes and ADHD. Social-demographic information was also collected. Major dietary patterns were identified by principal components analysis. Logistic regression was employed to explore the association of dietary patterns with ADHD. RESULTS: Five dietary patterns were identified explaining 47.96% of the total diet variation. The "processed" dietary component was the principal pattern that explained the higher percentage of variability, 24.69%. After controlling for potential confounders, preschoolers in the top quintile of the "processed" (odds ratio (OR) = 1.56, 95% confidence interval (CI): 1.31-1.86) and "snack" (OR = 1.76, 95% CI = 1.49-2.07) dietary pattern score had greater odds for having ADHD symptoms compared with those in the lowest quintile. Lowest scores on the "vegetarian" were associated with significantly a higher likelihood of indications of ADHD symptoms (OR = 0.67, 95% CI = 0.56-0.79). CONCLUSIONS: This study showed that preschoolers tend to choose unhealthy dietary pattern in Ma'anshan, China. "Processed" and "snack" dietary patterns were significantly and positively correlated with ADHD symptoms, while "vegetarian" dietary patterns were negatively correlated with ADHD symptoms.

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.