The effects of a sleep/recovery supplement: 'Night Time Recharge' on sleep parameters in young adults.

BACKGROUND: Concentrated cherry juice reportedly contains melatonin which, in turn, has been highlighted as an important regulator in initiating sleep. AIM: The present investigation aims to clarify whether Night Time Recharge (NTR), a marketed sleep aid containing cherry extract, improves key sleep parameters in young, active adults with mildly poor sleep. METHODS: A double-blind, randomized, placebo-controlled, cross-over study design was employed. Twenty participants (nine female) consumed either NTR or a placebo for seven days. Accelerometers were used to assess sleep quality and physical activity levels. Urinary levels of 6-sulphatoxymelatonin (6-SMT), a marker of melatonin synthesis, was assessed via enzyme-linked immunosorbent assay. RESULTS: 6-SMT levels increased following NTR treatment (28.95 ng/ml) compared with placebo (4.0 ng/ml) (p < 0.001). There was also a significant difference (p = 0.047) in dietary tryptophan consumption during the NTR treatment (1236 mg) versus placebo (1149 mg). No trace of melatonin was detected from our analysis of the supplement. NTR had no significant effect on any sleep parameters with the exception of sleep latency (p = 0.001). CONCLUSIONS: As chemical analysis of NTR by liquid-chromatography mass-spectrometry identified no detectable melatonin, the tryptophan content of the supplement is a likely reason for improvement in sleep latency. These results are in contrast to previous studies which have found a positive effect on sleep following cherry supplementation. Future work should focus on sleep latency and investigating whether cherry juice is effective in participants with problems in initiating sleep.

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.

No Tryptophan, Tyrosine and Phenylalanine Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: The aim of the current study was to explore the role of aromatic amino acids (AAAs) in blood in relation to attention-deficit/hyperactivity disorder (ADHD). Given their impact on the synthesis of serotonin and dopamine, decreased concentrations of the AAAs tryptophan, tyrosine and phenylalanine in blood may contribute to the expression of ADHD symptoms. Decreased AAA blood concentrations, in turn, may be related to lowered dietary protein intake or to abnormal AAA catabolism, as evidenced by increased urinary AAA concentrations. METHODS: Eighty-three children with ADHD (75% males) and 72 typically developing (TD) children (51% males), aged 6 to 13 years, participated in the study. AAA concentrations were assessed in blood spots and an 18-hour urinary sample. A nutritional diary was filled out by parents to calculate dietary protein intake. Parent and teacher questionnaires assessed symptoms of ADHD, oppositional defiant disorder, conduct disorder, and autism spectrum disorder. RESULTS: Children with ADHD showed normal AAA concentrations in blood spots and urine, as well as normal protein intake compared to controls. No associations between AAA concentrations and symptoms of ADHD or comorbid psychiatric disorders were found. CONCLUSIONS: This study is the first to explore AAA metabolism in children with ADHD using a well-defined and relatively large sample. We found that AAA deficiencies are not related to ADHD. The results do not support treatment with AAA supplements in children with ADHD. Future studies regarding the cause of serotonin and dopamine alterations in ADHD should focus on other explanations, such as effects of altered transport of AAAs.

Metabonomic study of biochemical changes in the rat urine induced by Pinellia ternata (Thunb.) Berit.

We adopted an ultra performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC Q-TOF/MS) metabonomics approach to study metabonomic features of rats induced by orally administered Pinellia ternata (Thunb.) Berit. (BX). The integrated urinary MS data were analyzed via principal component analysis (PCA) and partial least squares-discriminant analysis (OPLS-DA) to identify the differential metabolites. Ten potential biomarkers were identified within complex sample matrix of urine. The identified biomarkers indicated the perturbations of tryptophan, phenylacetylglycine and pantothenic acid metabolism in BX-induced rats. The biomarkers that were found to be changed with the passage of time were explained tentatively based on previous study.

An investigation of the antidepressant action of xiaoyaosan in rats using ultra performance liquid chromatography-mass spectrometry combined with metabonomics.

A rapid, highly sensitive, and selective method was applied in a non-invasive way to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and chemometrics. Many significantly altered metabolites were used to explain the mechanism. Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs with a relatively clear mechanism of action to evaluate the efficiency and to predict the mechanism of action of XYS. Urine obtained from rats subjected to chronic unpredictable mild stress (CUMS) was analyzed by UPLC-MS. Distinct changes in the pattern of metabolites in the rat urine after CUMS production and drug intervention were observed using partial least squares-discriminant analysis. The results of behavioral tests and multivariate analysis showed that CUMS was successfully reproduced, and a moderate-dose XYS produced significant therapeutic effects in the rodent model, equivalent to those of the positive control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant changes induced by CUMS were identified, and 17 biomarker candidates for stress and drug intervention were identified. The therapeutic effect of XYS on depression may involve regulation of the dysfunctions of energy metabolism, amino acid metabolism, and gut microflora changes. Metabonomic methods are valuable tools for measuring efficacy and mechanisms of action in the study of traditional Chinese medicines.

Dietary quinic acid supplied as the nutritional supplement AIO + AC-11® leads to induction of micromolar levels of nicotinamide and tryptophan in the urine.

Hippuric acid is synthesized and produced primarily by the gastrointestinal (GI) microflora. However, there is no known health benefit for hippuric acid except its catabolic conjugation of benzene-type compounds via glycine and subsequent excretion in the urine. For years the GI tract microflora were known to metabolize quinic acid to hippuric acid. Recently it was also proposed that DNA repair was strongly enhanced by quinic acid. In order to explain these quinic acid effects, Pero and colleagues have examined whether tryptophan and nicotinamide were also enhanced by quinic acid levels in urine. They were indeed, and so another study was designed using a natural supplement source of quinic acid called AIO + AC-11®, and then the effects of intervention were measured after only 21 days. It was possible to show profound increases in quinic acid that were again paralleled by increases in tryptophan and nicotinamide urinary levels. Because the high pressure liquid chromatography (HPLC) methods differed greatly between the two studies, differences in chemical analyses probably did not contribute to the data base.

Antioxidant metabolism induced by quinic acid. Increased urinary excretion of tryptophan and nicotinamide.

For over 50 years, hippuric/quinic acids were believed to have no biological efficacy. Here data are presented to support the hypothesis that quinic acid is not responsible for any efficacy, but rather that quinic acid nutritionally supports the synthesis of tryptophan and nicotinamide in the gastrointestinal (GI) tract, and that this in turn leads to DNA repair enhancement and NF-kB inhibition via increased nicotinamide and tryptophan production.Moreover, it is shown that quinic acid is a normal constituent of our diet, capable of conversion to tryptophan and nicotinamide via the GI tract microflora, thus providing an in situ physiological source of these essential metabolic ingredients to humans. The concentrations of quinic and hippuric acids in the diet were dependent on each other when analysed in urine, as was evidenced by a significant linear regression analysis that included unsupplemented control subjects (n = 45, p < 0.001). Thus, these ingredients were identified as major dietary components, and not simply originating from environmental pollution as previously had been thought.

Free amino acids during chronic cyclosporine A toxicity in intact and partially nephrectomized rats.

The effects of 40 days of treatment with Cyclosporine A (CSA) on plasma and urine free amino acids were investigated in sham-operated (C) and partially nephrectomized (Pnx) female Fischer 344 rats. High Dose CSA (30 mg/kg/day ip) was associated with reduced weight gain, increased plasma urea nitrogen, and hypoproteinemia in C and Pnx animals. These animals also demonstrated increased plasma levels of alanine, markedly reduced levels of tryptophan, and an increase in urinary excretion of methylhistidines. C but not Pnx animals also showed a significant increase in plasma serine and a decrease in plasma taurine. CSA treatment of group C resulted in a progressive aminoaciduria involving substrates of the neutral and acidic renal amino acid transport systems; however, the renal excretion of taurine and beta-alanine by these animals was markedly reduced as compared to vehicle treated controls. High dose CSA exacerbated aminoaciduria in Pnx animals, but in this group, the excretion of beta amino acids was also increased. Our findings demonstrate that chronic CSA toxicity in rodents with normal renal function is characterized by increased muscle protein catabolism, significant reductions in plasma tryptophan, and an apparent decrease in whole body taurine pools. With the exception of the taurine abnormalities. CSA treatment had similar effects on Pnx animals; however, in this group, CSA-induced pathological changes were superimposed on the changes due to renal insufficiency per se. CSA toxicity as identified by the parameters investigated in this study was no more severe in Pnx animals with moderate chronic renal insufficiency than in controls with intact renal function.

High doses of vitamin B6 in the rat are associated with inhibition of hepatic tryptophan metabolism and increased uptake of tryptophan into the brain.

Acute administration of vitamin B6 to rats (10 mg/kg body weight) led to reduced urinary excretion of N1-methyl nicotinamide and methyl pyridone carboxamide, indicating inhibition of the oxidative metabolism of tryptophan. There was a considerable reduction in the production of 14CO2 from [ring-2-14C]tryptophan, and a significant inhibition of hepatic tryptophan oxygenase when measured in liver homogenates, together with an increase in the concentration of tryptophan in plasma. There was an increase in both the concentration of tryptophan in the brain and the uptake into the brain of peripherally administered [3H]tryptophan, accompanied by a small increase in the rate of synthesis of 5-hydroxytryptamine in the brain. It is suggested that this increase in the uptake of tryptophan into the brain following a relatively large dose of vitamin B6 may explain the beneficial action of the vitamin in some cases of depressive illness.

Utilization of dietary tryptophan in iron-deficient rats.

Excretion of urinary tryptophan in iron-deficient rats increased threefold while the excretion of N-methyl nicotinamide, a catabolic product of tryptophan, decreased by one-half compared to control rats. The activity of hepatic tryptophan oxygenase, the first enzyme of tryptophan metabolism, was not affected by iron deficiency. It is concluded that tryptophan supplementation in severe iron deficiency would not be beneficial.

Effect of phototherapy on the urinary excretion of tryptophan metabolites in neonatal hyperbilirubinemia.

The 24 hours urinary excretion of tryptophan metabolites after an aminoacid loading (50 mg/Kg body-weight) was studied in a group of hyperbilirubinemic infants with or without light exposure treatment, in comparison to normal newborn babies. Kynurenine was the main metabolite in the urine of the control subjects. In the hyperbilirubinemic infants a high urinary excretion of kynurenine and 3-hydroxyanthranilic acid was observed. In the ones treated with phototherapy these two substances were markedly decreased. Besides 3-hydroxykynurenine was almost always absent. The effect of the light exposure was studied on kynurenine and 3-hydroxykynurenine "in vitro". Kynurenine did not present any photodecomposition. On the contrary, 3-hydroxykynurenine was easily decomposed. This fact can explain the decreased excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid observed in urine of hyperbilirubinemic newborn infants treated with phototherapy. The decrease of kynurenine in these infants probably is a consequence of the photodecomposition of 3-hydroxykynurenine.