Effect of Supplementation on Levels of Homovanillic and Vanillylmandelic Acids in Children with Autism Spectrum Disorders.

Autism Spectrum Disorders (ASD) are characterized by numerous comorbidities, including various metabolic and nutritional abnormalities. In many children with ASD, problems with proper nutrition can often lead to inadequate nutrient intake and some disturbances in metabolic profiles, which subsequently correlate with impaired neurobehavioural function. The purpose of this study was to investigate and compare the relationship between supplementation, levels of homovanillic acid (HVA) and vanillylmandelic acid (VMA) and the behaviour of children with ASD using quantitative urinary acid determination and questionnaires provided by parents/caregivers. The study was carried out on 129 children between 3 and 18 years of age. HVA and VMA were extracted and derivatized from urinary samples and simultaneously analyzed by gas chromatography-mass spectrometry (GC-MS). In addition, parents/caregivers of children with ASD were asked to complete questionnaires containing information about their diet and intake/non-intake of supplements. The application of the Mann-Whitney U test showed a statistically significant difference between the level of HVA and vitamin B supplementation (p = 1.64 × 10-2) and also omega-6 fatty acids supplementation and the levels of HVA (p = 1.50 × 10-3) and VMA (p = 2.50 × 10-3). In some children, a reduction in the severity of autistic symptoms (better response to own name or better reaction to change) was also observed. These results suggest that supplementation affects the levels of HVA and VMA and might also affect the children's behaviour. Further research on these metabolites and the effects of supplementation on their levels, as well as the effects on the behaviour and physical symptoms among children with ASD is needed.

Nutritional aspects in Parkinson's disease.

The links between diet and Parkinson's disease (PD) are unclear and incomprehensible. However, numerous studies have demonstrated the correlation between diet, nutrients and health condition in PD patients. They indicate the possibility of management of the disease, which might be possible through nutrition. Pharmaceutical treatment as well as a complementary holistic approach to the patients should be considered. It is of critical importance to understand how the diet and nutrients might influence PD. A better understanding of the relationship between diet and PD could help to better manage the disease explain promising therapeutic approaches, minimize motor and nonmotor symptoms and disease progression based on a personalized diet. In this review, the recent literature on the observed nutrition disorders and the possible role of diet and nutrients in the prevention and potential regression of PD, as well as dietary interventions and supplementation used to manage the disease is revised.

Effect of Zinc Supplementation on the Serum Metabolites Profile at the Early Stage of Breast Cancer in Rats.

The cytotoxic properties of zinc nanoparticles have been evaluated in vitro against several types of cancer. However, there is a lack of significant evidence of their activity in vivo, and a potential therapeutic application remains limited. Herein we report the effective inhibition of tumor growth by zinc nanoparticles in vivo, as the effect of the dietary intervention, after the chemical induction in a rodent model of breast cancer. Biopsy images indicated grade 1 tumors with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, a moderately differentiated grade 2 adenocarcinoma was identified. Moreover, after the supplementation with zinc nanoparticles, the levels of several metabolites associated with cancer metabolism, important to its survival, were found to have been altered. We also revealed that the biological activity of zinc in vivo depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.

Oxidative Stress in Autism Spectrum Disorder.

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

The Role of Vitamins in Autism Spectrum Disorder: What Do We Know?

Vitamin or mineral supplementation is considered to be the most commonly used medical treatment for autism spectrum disorder (ASD), in addition to other interventions such as neurological and psychological interventions. There is not much evidence of therapeutic efficacy between vitamin and mineral supplementation and improvements in ASD. However, several researchers have noted that patients with ASD have various metabolic and nutritional abnormalities including issues with sulfation, methylation, glutathione redox imbalances, oxidative stress, and mitochondrial dysfunction. There is some evidence that vitamin and mineral supplementation may support these basic physiologic processes. Recently, the nutritional status of ASD patients has been gaining focus in this particular area. Pointing out the nutritional status as a potential etiological factor for attention/communication disorders, more importance has been given to this particular point. Moreover, autistic specific considerations like the feature and behavior of ASD might be increased or at least fall in the higher risk due to the sub-optimal nutritional status.

How important is tryptophan in human health?

Tryptophan (Trp) is an amino acid and an essential component of the human diet. It plays a crucial role in many metabolic functions. Clinicians can use Trp levels in the course of diagnosing various metabolic disorders and the symptoms associated with those diseases. Furthermore, supplementation with this amino acid is considered in the treatment of depression and sleep disorders, mainly due to the Trp relationship with the synthesis of serotonin (5-HT) and melatonin. It is also used in helping to resolve cognitive disorders, anxiety, or neurodegenerative diseases. Reduced secretion of serotonin is associated with autism spectrum disorder, obesity, anorexia and bulimia nervosa, and other diseases presenting peripherals symptoms. The literature strongly suggests that Trp has a significant role in the correct functionality of the brain-gut axis and immunology. This information leads to the consideration of Trp as an essential dietary component due to its role in the serotonin pathway. A reduced availability of Trp in diet and nutraceutical supplementation should be considered with greater concern than one might expect. This paper constitutes a review of the more salient aspects gleaned from the current knowledge base about the role of Trp in diseases, associated nutritional disorders, and food science, in general.

Tryptophan status in autism spectrum disorder and the influence of supplementation on its level.

Recent reports show that the worldwide incidence of autism spectrum disorder (ASD) is dramatically increasing, although ASD etiology and pathogenesis are still far to be fully elucidated. Some dietary-derived essential compounds, such as the amino acid tryptophan, appear to be impaired in patients with ASD. Tryptophan (Trp) plays a significant role in the human organism and serves as a precursor for a wide range of bioactive compounds, including major neurotransmitters. Research indicates that tryptophan might be deficient in subjects with ASD. Deficiency in the tryptophan level can be retrieved by investigating Trp levels or its major metabolite kynurenine in urines. The purpose of the present study is to quantify tryptophan content in urine samples (n = 236) of ASD patients, who underwent a supplemented dietary panel with B vitamins and magnesium, compared to controls (without this diet regimen). The samples were analyzed with gas chromatography-mass spectrometry. Additionally, the correlation between body mass index (BMI) and the level of this amino acid in urine was accomplished. Basic parameters of urine samples were also evaluated. Statistical evaluations in the concentration of tryptophan in ASD patients with different severity of symptoms were reported. A significant difference in tryptophan levels in all groups was observed. Supplementation with B vitamins and magnesium has an influence on the Trp concentration. Furthermore, no correlation between BMI and tryptophan levels was found. These results assess that the Trp level in ASD subjects is critical and that intake of B vitamins and magnesium with diet might influence its metabolic homeostasis.

Chromatographic determination of harmalans in the urine of autistic children.

This paper presents a new approach to autism - a complex and still enigmatic condition. We present the results of our preliminary research which was based on the detection of the hallucinogenic substance 6- (or 10-)methoxyharmalan in the urine samples of autistic children with the use of chromatographic methods. Additionally, we aim to describe the relationship between the level of tryptophan and harmalan, and the influence of supplementation on the level of this compound. We applied HPLC-UV/vis, HPLC-DAD and LC-MS in order to determine McIsaac's compound in the urine samples obtained from autistic children (n = 132) and healthy individuals (n = 10). The level of tryptophan was quantified with the use of GC-MS. Our research shows the presence of the McIsaac's compound in 110 samples of ASD children contrary to healthy children, where it was not found. No relationship between the level of tryptophan and 6-methoxyharmalan was noticed. The study shows a strong influence of melatonin supplementation on the presence of the McIsaac's compound. We believe that the results of our research can contribute to a better understanding of autism spectrum disorders. Moreover, our findings can form the basis for other studies focused on autism, eventually making it possible to understand its etiology.

A focus on homocysteine in autism.

Homocysteine is an amino acid, which plays several important roles in human physiology. A wide range of disorders, including neuropsychiatric disorders and autism, are associated with increased homocysteine levels in biological fluids. Various B vitamins: B6 (pyridoxine), B12 (cobalamin), and B9 (folic acid) are required as co-factors by the enzymes involved in homocysteine metabolism. Therefore, monitoring of homocysteine levels in body fluids of autistic children can provide information on genetic and physiological diseases, improper lifestyle (including dietary habits), as well as a variety of pathological conditions. This review presents information on homocysteine metabolism, determination of homocysteine in biological fluids, and shows abnormalities in the levels of homocysteine in the body fluids of autistic children.

The level of arabinitol in autistic children after probiotic therapy.

OBJECTIVE: The level of D-arabinitol (DA) and the ratio of D-/L-arabinitol (DA/LA) in the urine of children with autism were investigated. The changes in DA/LA after probiotic treatment in urine samples of children with autism were studied. METHODS: DA and LA and the DA/LA ratio were identified by capillary gas chromatography/mass spectrometry in urine before and after the probiotic therapy. RESULTS: The level of DA is significantly higher (P < 0.05) in the urine of autistic children before (A) and after probiotic supplementation (A1) (160.04 ± 22.88 µmol/mmol creatinine and 89.53 ± 37.41 µmol/mmol creatinine, respectively). Nonetheless, the probiotic supplementation let to a significant decrease in DA and DA/LA and to a significant improvement in ability of concentration and carrying out orders. CONCLUSION: The use of probiotics seems to be helpful in reducing the level of DA and the ratio of DA/LA in the urine of children with autism.

B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children.

Urinary dicarboxylic acids are an important source of information about metabolism and potential problems especially connected with energy production, intestinal dysbiosis, and nutritional individuality in autistic children. A diet rich in vitamins and macroelements is a new idea of intervention in autism. The objective of the present study was to test the hypothesis that vitamin B2, vitamin B6, and magnesium supplementation is effective in reducing the level of dicarboxylic acids in the urine of autistic children. We examined the levels of succinic, adipic, and suberic acids in the urine of autistic children before and after vitamin supplementation. Thirty children with autism received magnesium (daily dose, 200 mg), vitamin B6 (pyridoxine; daily dose, 500 mg), and vitamin B2 (riboflavin; daily dose, 20 mg). The treatment was provided for a period of 3 months. Organic acids were determined using gas chromatography/mass spectrometry. Before supplementation, the levels of succinic, adipic, and suberic acids in the urine of autistic children were 41.47 ± 50.40 µmol/mmol creatinine, 15.61 ± 15.31 µmol/mmol creatinine, 8.02 ± 6.08 µmol/mmol creatinine; and after supplementation, the levels were 9.90 ± 8.26 µmol/mmol creatinine, 2.92 ± 2.41 µmol/mmol creatinine, and 2.57 ± 3.53 µmol/mmol creatinine, respectively. The results suggest that the supplementation reduces the level of dicarboxylic acid in the urine of autistic children.

Vitamin supplementation reduces the level of homocysteine in the urine of autistic children.

Significant differences in homocysteine levels in the urine of autistic children are observed. We hypothesized that vitamin supplementation might reduce the level of urinary homocysteine. To rationalize such a hypothesis, analyses were performed using the gas chromatography/mass spectrometry method. The homocysteine level in the urine of autistic children was measured twice: (1) before vitamin supplementation (group C, 30 autistic children) and (2) after supplementation, with either folic acid and vitamins B(6) and B(12) (group A1, 24 autistic children) or vitamins B(6) and B(12) alone (group A2, 6 autistic children). The homocysteine level in the urine of autistic children before vitamin supplementation was 2.41 ± 1.10 mmol/mol creatinine (mean ± SD difference). After treatment, the homocysteine level was reduced to 1.13 ± 0.44 and 1.33 ± 0.39 mmol/mol creatinine for A1 and A2 groups, respectively. The intake of vitamins B(6) and B(12), together with folic acid, was found to be more effective in lowering the levels of urinary homocysteine than the intake of vitamins B(6) and B(12) alone. Our findings may lead to the recommendation of including vitamins B(6) and B(12) together with folic acid supplementation in the diets of children with autism.