Omega-3/6 supplementation for mild to moderate inattentive ADHD: a randomised, double-blind, placebo-controlled efficacy study in Italian children.

Recently there has been a growing interest in non-pharmacological treatments for ADHD. We evaluated the efficacy of a specific Omega-3/6 dietary supplement (two capsules containing 279 mg eicosapentaenoic acid [EPA], 87 mg Docosahexaenoic Acid [DHA], 30 mg gamma linolenic acid [GLA] each) in ameliorating inattentive symptoms in inattentive-ADHD children (6-12 years) with a baseline ADHD-RS-Inattention score ≥ 12. Secondary objectives included changes in global functioning, severity of illness, depression, and anxiety symptoms, learning disorders and in the fatty acids blood levels. The study was a randomised, double-blind, placebo-controlled efficacy and safety trial with a 6-month double-blind evaluation of Omega-3/6 vs placebo (Phase-I) and a further 6-month-open-label treatment with Omega-3/6 on all patients (Phase-II). In total 160 subjects were enrolled. No superiority of Omega-3/6 supplement to placebo was observed on the primary outcome (ADHD-RS-inattention score) after the first 6-months, with 46.3% of responders in the Omega-3/6 group and 45.6% in the placebo group; a slight (not statistically significant) reduction in Omega-6/3 ratio blood levels was measured in the active treatment group. Twelve months after enrolment, percentages of responders were similar between groups. A mild statistical, although not clinically significant, improvement was observed on the ADHD-RS-total score in the Omega-3/6 group but not on the ADHD-RS-Inattention score; a slight (not-statistically significant) reduction in Omega-6/3 ratio was observed in the group taking active treatment only during Phase II. In conclusion, no clinical beneficial effects of Omega-3/6 were detected on inattentive symptoms, suggesting a limited role of Omega-3/6 dietary products in children with mild ADHD-I.Trial registration: At the time of the Ethical submission, according to the clinical trial Italian law, registration was not mandatory for food additive as Omega 3/6 were then classified. The trial was approved by the Ethical Committee of the Cagliari University Hospital (resolution n. 662; September 22nd, 2011).

Use of Nutritional Supplements Based on L-Theanine and Vitamin B6 in Children with Tourette Syndrome, with Anxiety Disorders: A Pilot Study.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and co-occurring disorders. It has been suggested that anxiety occurs in 2-45% patients affected by Tourette syndrome. Despite dietary and nutritional factors have been found to affect a range of neurological conditions, no more studies have investigated the relationship between nutritional supplements and tics. OBJECTIVE: To evaluate the effectiveness of supplementation of both L-Theanine and Vitamin B6 in reducing tics and co-occurring disorders in a sample of youth with chronic tic disorder (CTD) or Tourette syndrome with anxiety symptoms. DESIGN: A open-label trial. Patients affected by Tourette syndrome were randomized to receive nutritional supplements based on L-Theanine and vitamin B6, or psychoeducation (PE). PARTICIPANTS: 34 children (30 boys and 4 girls) aged between 4 and 17 years affected by Tourette syndrome or chronic tic disorder, associated with anxiety symptoms. RESULTS: Patients in both groups showed a reduction in the severity of tic and anxiety symptoms. Supplementation with L-Theanine and vitamin B6 was significantly more effective than psychoeducation in reducing tics and co-occurring disorders, as measured by neuropsychological findings. CONCLUSIONS: Supplementation of both L-Theanine and Vitamin B6 may help in the treatment of tic disorders associated with anxious symptoms. Between-group differences in clinician-rated severity did reach statistical significance only for tics. Despite this finding, further placebo-controlled trials are needed.

Use of Nutraceutical Ingredient Combinations in the Management of Tension-Type Headaches with or without Sleep Disorders.

Headache is the most common pain complaint in the pediatric population, with tension type headache (TTH) having a prevalence of 10-15% in children. Up to 70% of pediatric patients with chronic headache also experience sleep disruption, with a likely bidirectional relationship between headache and poor sleep. Treatment options include specific pharmacological approaches as well as non-pharmacological alternatives; nutraceuticals have the advantage of a relative lack of side effects. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and quality of sleep in children, helping to regulate the circadian rhythm, with a secondary positive impact on headache. Supplementation with other nutraceutical ingredients, such as tryptophan, magnesium, and B vitamins, can have significant additional effects in children with primary headache, with or without sleep disorders. Tryptophan may reduce night awakenings and improve the efficiency of sleep. Primary headache has been related to low amounts of magnesium in serum, and integration with magnesium appears to be effective in reducing headache attacks without adverse effects. There are different observational reports and uncontrolled studies suggesting a possible synergistic effect for these nutraceuticals, but there is now a need for high-quality randomized controlled trials in order to confirm these positive preliminary findings.

TrASDition Training: An online parental training for transition-age youth with autism spectrum disorder.

Transition to the adult age represents a rather challenging period of life for youth with Autism Spectrum Disorder (ASD) and for their families. Given the actual lack of integrated healthcare systems for autistic young-adults, enhancing parental skills could represent a feasible program to improve skills preparatory for transition in adult life. The online approach, providing easy access to services which otherwise would burden a daily family organization, already strenuous for a family with an autistic person, can represent an innovative way of delivering intervention. Therefore, we developed an online psychoeducational parental training, named TrASDition Training, with a 6 months duration, addressed to parents of autistic youth with and without Intellectual Disability during the transition age. The aim of this study was to longitudinally evaluate the impact of the online parental training on the adaptive functioning, on the repetitive and problematic behaviors of ASD youth (n = 23) and on parental stress. After 6 months of Training, we found a significant improvement in adaptive functioning of ASD participants and a reduction of parental stress.

Vitamin D Deficiency and Autism Spectrum Disorder.

Vitamin D is a neurosteroid hormone crucially involved in neurodevelopment. Neural cell proliferation, neurotransmission, oxidative stress and immune function represent the main mechanisms mediated by vitamin D in the Central Nervous System. Therefore, its deficiency during pregnancy and early childhood may significantly impact on a developing brain, leading to possible adverse neuropsychological outcomes including Autism Spectrum Disorder (ASD). Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. We reviewed the actual literature on the potential contributing role of prenatal and early postnatal vitamin D deficiency in ASD etiopathogenesis, at both genetic and environmental levels, and the possible effect of vitamin D supplementation in autistic children. Conflicting but promising results emerged on the topic. Further Randomized Controlled Trials studies carried out during pregnancy and early infancy are necessary for better understanding the possible contribution of vitamin D deficiency in the etiopathogenesis of autism and the potential efficacy of the hormone supplementation in the improvement of ASD core symptoms.

Use of nutritional supplements based on melatonin, tryptophan and vitamin B6 (Melamil Tripto®) in children with primary chronic headache, with or without sleep disorders: a pilot study.

BACKGROUND: Headache is one of the main complaints in pediatric neurology. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and sleep quality in children. Tryptophan as well plays a key role in sleep regulation. So far, no studies tried to analyze the effects of a combination of both melatonin and tryptophan in treating chronic headache in children affected also by night-time awakenings. METHODS: Thirty-four children with a diagnosis of chronic headache (with or without sleep disorders) have been enrolled. The study was articulated in two steps: 1) each child was observed for one month without any intervention; 2) children have been then randomized into two groups: the "ME-group", which received the nutritional supplement melatonin for two months and the "MET-group", which received the nutritional supplements melatonin, tryptophan, and vitamin B6 for two months. RESULTS: In terms of changes in number of headache events, responders in the ME-group were 91.7% and those in the MET-group were 66.7% (P=0.113). In terms of changes in number of night awakenings, in the ME group, mean number at baseline, after 30 days, and after 60 days were 3.6±3.2, 3.2±3.5, and 2.7±3.4 (P=0.495). In the MET group, mean number of night awakenings was 7.4±8.1, 4.0±4.4, and 3.3±2.9 (P=0.041). CONCLUSIONS: Using either nutritional supplement for two months can help in decreasing the monthly number of headache episodes and night awakenings. The addition of tryptophan and vitamin B6 appears to have stronger influence on night awakenings reduction than melatonin only.

Effects of oral administration of common antioxidant supplements on the energy metabolism of red blood cells. Attenuation of oxidative stress-induced changes in Rett syndrome erythrocytes by CoQ10.

Nutritional supplements are traditionally employed for overall health and for managing some health conditions, although controversies are found concerning the role of antioxidants-mediated benefits in vivo. Consistently with its critical role in systemic redox buffering, red blood cell (RBC) is recognized as a biologically relevant target to investigate the effects of oxidative stress. In RBC, reduction of the ATP levels and adenylate energy charge brings to disturbance in intracellular redox status. In the present work, several popular antioxidant supplements were orally administrated to healthy adults and examined for their ability to induce changes on the energy metabolism and oxidative status in RBC. Fifteen volunteers (3 per group) were treated for 30 days per os with epigallocatechin gallate (EGCG) (1 g green tea extract containing 50% EGCG), resveratrol (325 mg), coenzyme Q10 (CoQ10) (300 mg), vitamin C (1 g), and vitamin E (400 U.I.). Changes in the cellular levels of high-energy compounds (i.e., ATP and its catabolites, NAD and GTP), GSH, GSSG, and malondialdehyde (MDA) were simultaneously analyzed by ion-pairing HPLC. Response to oxidative stress was further investigated through the oxygen radical absorptive capacity (ORAC) assay. According to our experimental approach, (i) CoQ10 appeared to be the most effective antioxidant inducing a high increase in ATP/ADP, ATP/AMP, GSH/GSSG ratio and ORAC value and, in turn, a reduction of NAD concentration, (ii) EGCG modestly modulated the intracellular energy charge potential, while (iii) Vitamin E, vitamin C, and resveratrol exhibited very weak effects. Given that, the antioxidant potential of CoQ10 was additionally assessed in a pilot study which considered individuals suffering from Rett syndrome (RTT), a severe X-linked neuro-developmental disorder in which RBC oxidative damages provide biological markers for redox imbalance and chronic hypoxemia. RTT patients (n = 11), with the typical clinical form, were supplemented for 12 months with CoQ10 (300 mg, once daily). Level of lipid peroxidation (MDA production) and energy state of RBCs were analyzed at 2 and 12 months. Our data suggest that CoQ10 may significantly attenuate the oxidative stress-induced damage in RTT erythrocytes.

Mechanistic target of rapamycin (mTOR) in tuberous sclerosis complex-associated epilepsy.

BACKGROUND: Tuberous sclerosis complex is a multiorgan disease resulting from a mutation of one of two TSC genes. The two gene products form a functional complex that regulates the mTOR signaling pathway (mTOR initially represented mammalian target of rapamycin, but increasingly the term mechanistic target of rapamycin is used to reflect the ubiquitous occurrence of mTOR). Epilepsy is the most common neurological symptom of tuberous sclerosis complex, occurring in 80% to 90% of affected individuals over the course of their lifetimes and causing significant morbidity and mortality. The mechanistic target of rapamycin (mTOR) signaling pathway is intricately involved in multiple cellular functions--including protein synthesis, cell growth and proliferation, and synaptic plasticity--which may influence neuronal excitability and precipitate epileptogenesis. Recent preclinical and clinical studies have increased interest in the potential role of mTOR inhibitors for the treatment of tuberous sclerosis complex-related epilepsy. METHODS: Medline and PubMed database searches were used to identify relevant studies and other information on tuberous sclerosis complex-related epilepsies, the mTOR pathway, and current advances in treatment approaches. RESULTS: Although current management strategies that provide symptomatic relief are effective at reducing the frequency of seizures in individuals with tuberous sclerosis complex, there is further room for the exploration of therapies that directly address hyperactive mTOR signaling--the underlying etiology of the disease. The role of the antiepileptic effect of mTOR inhibition was first demonstrated in knockout TSC1 mouse models. Additionally, several case studies demonstrated a positive effect on seizure frequency and severity in patients with pharmacoresistant epilepsy. In a phase 1/2 clinical trial with 28 patients, clinically relevant reduction in overall seizure frequency was documented in individuals treated with the mTOR inhibitor everolimus. In a phase 3 trial evaluating the role of everolimus in subependymal giant cell astrocytoma, seizures were a secondary end point. Because the median seizure frequency was zero in this study, the analysis was inconclusive. CONCLUSION: Various preclinical models provide substantial evidence for the role of mTOR inhibition in the treatment of epilepsy in individuals with tuberous sclerosis complex. Preliminary clinical studies provide supportive evidence for a role of mTOR inhibition in the management of tuberous sclerosis complex-associated epilepsy and pave the way for new randomized placebo-controlled studies. This article reviews current treatment recommendations for the management of tuberous sclerosis complex-associated epilepsy as well as the rationale and evidence to support the use of mTOR inhibitors.