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1.
Effects of single-dose L-theanine on motor cortex excitability.
Yuan, S, Brown, JC, Gold, M, Tirrell, E, Jones, RN, Carpenter, LL
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2021;(9):2062-2064
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Protective effect of the oral administration of cystine and theanine on oxaliplatin-induced peripheral neuropathy: a pilot randomized trial.
Kobayashi, M, Sato, R, Komura, T, Ichikawa, H, Hirashima, T, Otake, S, Akazawa, N, Yazawa, T, Abe, T, Okada, T, et al
International journal of clinical oncology. 2020;(10):1814-1821
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Abstract
BACKGROUND Oxaliplatin, one of the key cytotoxic drugs for colorectal cancer, frequently causes peripheral neuropathy which leads to dose modification and decreased patients' quality of life. However, prophylactic or therapeutic measures have not yet been established. Orally administered amino acids, cystine and theanine, promoted the synthesis of glutathione which was one of the potential candidates for preventing the neuropathy. The aim of this study was to determine whether daily oral administration of cystine and theanine attenuated oxaliplatin-induced peripheral neuropathy (OXLIPN). METHODS Twenty-eight colorectal cancer patients who received infusional 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) therapy were randomly and evenly assigned to the cystine and theanine group and the control group. OXLIPN was assessed up to the sixth course using original 7-item questionnaire as well as Common Terminology Criteria for Adverse Events (CTCAE) grading scale. RESULTS Neuropathy scores according to our original questionnaire were significantly smaller in the cystine and theanine group at the fourth (p = 0.026), fifth (p = 0.029), and sixth course (p = 0.038). Furthermore, significant differences were also observed in CTCAE neuropathy grades at the fourth (p = 0.037) and the sixth course (p = 0.017). There was one patient in each group who required dose reduction due to OXLIPN. Except for neurotoxicity, no significant differences were noted in the incidence of adverse events, and the total amount of administered oxaliplatin. CONCLUSION The results demonstrated the daily oral administration of cystine and theanine attenuated OXLIPN.
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Efficient fermentative production of L-theanine by Corynebacterium glutamicum.
Ma, H, Fan, X, Cai, N, Zhang, D, Zhao, G, Wang, T, Su, R, Yuan, M, Ma, Q, Zhang, C, et al
Applied microbiology and biotechnology. 2020;(1):119-130
Abstract
L-Theanine is a unique non-protein amino acid found in tea plants that has been shown to possess numerous functional properties relevant to food science and human nutrition. L-Theanine has been commercially developed as a valuable additive for use in food and beverages, and its market is expected to expand substantially if the production cost can be lowered. Although the enzymatic approach holds considerable potential for use in L-theanine production, demand exists for developing more tractable methods (than those currently available) that can be implemented under mild conditions and will reduce operational procedures and cost. Here, we sought to engineer fermentative production of L-theanine in Corynebacterium glutamicum, an industrially safe host. For L-theanine synthesis, we used γ-glutamylmethylamide synthetase (GMAS), which catalyzes the ATP-dependent ligation of L-glutamate and ethylamine. First, distinct GMASs were expressed in C. glutamicum wild-type ATCC 13032 strain and GDK-9, an L-glutamate overproducing strain, to produce L-theanine upon ethylamine addition to the hosts. Second, the L-glutamate exporter in host cells was disrupted, which markedly increased the L-theanine titer in GDK-9 cells and almost eliminated the accumulation of L-glutamate in the culture medium. Third, a chromosomally gmasMm-integrated L-alanine producer was constructed and used, attempting to synthesize ethylamine endogenously by expressing plant-derived L-serine/L-alanine decarboxylases; however, these enzymes showed no L-alanine decarboxylase activity under our experimental conditions. The optimal engineered strain that we ultimately created produced ~ 42 g/L L-theanine, with a yield of 19.6%, in a 5-L fermentor. This is the first report of fermentative production of L-theanine achieved using ethylamine supplementation.
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Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.
Kahathuduwa, CN, Wakefield, S, West, BD, Blume, J, Dassanayake, TL, Weerasinghe, VS, Mastergeorge, A
Scientific reports. 2020;(1):13072
Abstract
We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task ~ 1 h post-dose. NIH Cognition Toolbox was administered ~ 2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. L-Theanine improved total cognition composite in NIH Cognition Toolbox (p = 0.040) vs. placebo. Caffeine worsened and L-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p = 0.031 and p = 0.053 respectively). L-Theanine-caffeine combination improved total cognition composite (p = 0.041), d-prime in the Go/NoGo task (p = 0.033) and showed a trend of improvement of inhibitory control (p = 0.080). L-Theanine-caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). L-Theanine-caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.
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Time-series transcriptomic analysis reveals novel gene modules that control theanine biosynthesis in tea plant (Camellia sinensis).
Cao, H, He, X, Du, J, Zhang, R, Chen, Y, Ma, Y, Chen, Q, Fang, C, Ho, CT, Zhang, S, et al
PloS one. 2020;(9):e0238175
Abstract
Theanine (thea) is a unique non-protein amino acid in tea plant (Camellia sinensis) and one of the most important small molecular compounds for tea quality and health effects. The molecular mechanism that maintains thea biosynthesis is not clear but may be reflected in complicated biological networks as other secondary metabolites in plants. We performed an integrative transcriptomic analysis of tea seedlings bud and leave over the time-course of ethylamine (EA) treatment that activated thea pathway. We identified 54 consistent differentially expressed genes (cDEGs, 25 upregulated and 29 downregulated) during thea activation. Gene Ontology (GO) functional enrichment analysis of upregulated genes and downregulated genes showed that they may function as a cascade of biological events during their cooperative contribution to thea biosynthesis. Among the total cDEGs, a diversity of functional genes (e.g., enzymes, transcription factors, transport and binding proteins) were identified, indicating a hierarchy of gene control network underlying thea biosynthesis. A gene network associated with thea biosynthesis was modeled and three interconnected gene functional modules were identified. Among the gene modules, several topologically important genes (e.g., CsBCS-1, CsRP, CsABC2) were experimentally validated using a combined thea content and gene expression analysis. Collectively, we presented here for the first time a comprehensive landscape of the biosynthetic mechanism of thea controlled by a underling gene network, which might provide a theoretical basis for the identification of key genes that contribute to thea biosynthesis.
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Effects of acute caffeine, theanine and tyrosine supplementation on mental and physical performance in athletes.
Zaragoza, J, Tinsley, G, Urbina, S, Villa, K, Santos, E, Juaneza, A, Tinnin, M, Davidson, C, Mitmesser, S, Zhang, Z, et al
Journal of the International Society of Sports Nutrition. 2019;(1):56
Abstract
BACKGROUND A limited amount of research has demonstrated beneficial effects of caffeine and theanine supplementation for enhancement of mental performance. The purpose of this investigation was to determine whether the acute ingestion of a supplement containing caffeine, theanine and tyrosine improves mental and physical performance in athletes. METHODS Twenty current or former male collegiate athletes (age: 20.5 ± 1.4 y; height: 1.82 ± 0.08 m; weight: 83.9 ± 12.6 kg; body fat: 13.8 ± 5.6%) completed this randomized, double-blind, placebo-controlled crossover trial. After familiarization, each participant completed two identical testing sessions with provision of a proprietary dietary supplement (SUP) containing caffeine theanine and tyrosine or a placebo (PL). Within each testing session, participants completed assessments of mental and physical performance before and after provision of SUP or PL, as well as after two rounds of exercise. Assessments were performed using a performance testing device (Makoto Arena) that evaluated multiple aspects of mental and physical performance in response to auditory and visual stimuli. Testing was performed both with the body in a static position and during dynamic movement. General linear models were used to evaluate the effects of SUP and PL on performance. RESULTS Changes in movement accuracy during performance assessment were greater following SUP ingestion as compared to PL for both static and dynamic testing (SUP: + 0.4 to 7.5%; PL: - 1.4 to 1.4% on average; p < 0.05). For dynamic testing, the change in number of targets hit was higher and the change in average hit time was lower with SUP as compared to PL (p < 0.05). However, there were no differences between conditions for the changes in number of targets hit or average hit time during static testing. There were no differences in changes of subjective variables during either condition, and performance measures during the two rounds of exercise did not differ between conditions (p > 0.05). DISCUSSION The present results indicate that a combination of a low-dose of caffeine with theanine and tyrosine may improve athletes' movement accuracy surrounding bouts of exhaustive exercise without altering subjective variables. Based on this finding, supplementation with caffeine, theanine and tyrosine could potentially hold ergogenic value for athletes in sports requiring rapid and accurate movements. TRIAL REGISTRATION NCT03019523. Registered 24 January 2017.
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Formation and stability of the mixed-chelator complexes of Sr2+, Mg2+, Ca2+, Ba2+, and Y3+ in solution with bio-relevant chelators.
Begum, ZA, Rahman, IMM, Takase, T, Hasegawa, H
Journal of inorganic biochemistry. 2019;:141-148
Abstract
The formation and equilibria of Sr2+, Mg2+, Ca2+, Ba2+, and Y3+ (M) complexes with a mixed-chelator comprising two biodegradable chelators (GLDA, LG, 2-[bis(carboxymethyl)amino] pentanedioic acid; HIDS, LH, 2-(1,2-dicarboxyethylamino)-3-hydroxy-butanedioic acid) in an aqueous matrix was evaluated. The potentiometric measurement results (ionic strength, 0.10 M; temperature, 25 ± 0.1 °C) confirmed the formation of 1:1:1 (M:LG:LH) complexes and the experimental data sets were further used to derive the equilibrium constants for the ternary complexes. The [MHLGLH]5- complex was the dominant ternary complex with Sr2+, Mg2+, Ca2+, and Ba2+, while Y3+ formed [M(OH)2LGLH]7- as the principal ternary species. The trend in the overall formation constants of the MLmix (Lmix, LG:LH = 1:1) complexes was in the order: Y3+ > Ca2+ > Mg2+ > Sr2+ > Ba2+. The ternary complexation trend was interpreted using the corresponding atomic radii and solution-phase electronegativities of the elements. The modes of interaction between the chelators and cations in the MLmix systems were subsequently deduced, and evaluated by using Gaussian 16W program. The relative stabilities of the ternary complexes (ΔlogK) were interpreted by comparison with the stabilities of the corresponding binaries, with negative ΔlogK values observed for all the MLmix complexes.
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Exploration of nitrate-to-glutamate assimilation in non-photosynthetic roots of higher plants by studies of 15N-tracing, enzymes involved, reductant supply, and nitrate signaling: A review and synthesis.
Yoneyama, T, Suzuki, A
Plant physiology and biochemistry : PPB. 2019;:245-254
Abstract
Roots of the higher plants can assimilate inorganic nitrogen by an enzymatic reduction of the most oxidized form (+6) nitrate to the reduced form (-2) glutamate. For such reactions, the substrates (originated from photosynthates) must be imported to supply energy through the reductant-generating systems within the root cells. Intensive studies over last 70 years (reviewed here) revealed the precise mechanisms of nitrate-to-glutamate transformation in roots with elaborate searches of 15N-tracing, enzymes involved, the reductant-supplying system, and nitrate signaling. In the 1970s, the tracing of 15N-labeled nitrate and ammonia in the roots demonstrated the sequential reduction and assimilation of nitrate to nitrite, ammonia, glutamine amide, and then glutamate. These reactions involve nitrate reductase (NADH-NR, EC 1.7.1.1) in the cytosol, nitrite reductase (ferredoxin [Fd]-NiR, EC 1.7.7.1), glutamine synthetase (GS2, EC 6.3.1.2), and glutamate synthase (Fd-GOGAT, EC 1.4.7.1) in the plastids. NADH for NR is generated by glycolysis in the cytosol, and NADPH for Fd-NIR and Fd-GOGAT are produced by the oxidative pentose phosphate pathway (OPPP). Electrons from NADPH are conveyed to reduce NIR and Fd-GOGAT through Fd-NADP+ reductase (FNR, EC 1.6.7.1) specifically in the roots. Physiological and molecular analyses showed the parallel inductions of NR, NIR, GS2, Fd-GOGAT, OPPP enzymes, FNR, and Fd in response to a short-term nitrate supply. Recent studies proposed a molecular mechanism of nitrate-induction of these genes and proteins. Roots can also assimilate the reduced form of inorganic ammonia by the combination of cytosolic GS1 and plastidic NADH-GOGAT.
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l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study.
Kahathuduwa, CN, Dhanasekara, CS, Chin, SH, Davis, T, Weerasinghe, VS, Dassanayake, TL, Binks, M
Nutrition research (New York, N.Y.). 2018;:67-78
Abstract
Oral intake of l-theanine and caffeine supplements is known to be associated with faster stimulus discrimination, possibly via improving attention to stimuli. We hypothesized that l-theanine and caffeine may be bringing about this beneficial effect by increasing attention-related neural resource allocation to target stimuli and decreasing deviation of neural resources to distractors. We used functional magnetic resonance imaging (fMRI) to test this hypothesis. Solutions of 200mg of l-theanine, 160mg of caffeine, their combination, or the vehicle (distilled water; placebo) were administered in a randomized 4-way crossover design to 9 healthy adult men. Sixty minutes after administration, a 20-minute fMRI scan was performed while the subjects performed a visual color stimulus discrimination task. l-Theanine and l-theanine-caffeine combination resulted in faster responses to targets compared with placebo (∆=27.8milliseconds, P=.018 and ∆=26.7milliseconds, P=.037, respectively). l-Theanine was associated with decreased fMRI responses to distractor stimuli in brain regions that regulate visual attention, suggesting that l-theanine may be decreasing neural resource allocation to process distractors, thus allowing to attend to targets more efficiently. l-Theanine-caffeine combination was associated with decreased fMRI responses to target stimuli as compared with distractors in several brain regions that typically show increased activation during mind wandering. Factorial analysis suggested that l-theanine and caffeine seem to have a synergistic action in decreasing mind wandering. Therefore, our hypothesis is that l-theanine and caffeine may be decreasing deviation of attention to distractors (including mind wandering); thus, enhancing attention to target stimuli was confirmed.
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Efficacy of oral administration of cystine and theanine in patients with colorectal cancer undergoing capecitabine-based adjuvant chemotherapy after surgery: study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled, phase II trial.
Hamaguchi, R, Tsuchiya, T, Miyata, G, Sato, T, Takahashi, K, Ariyoshi, K, Oyamada, S, Iwase, S
BMJ open. 2018;(7):e021442
Abstract
INTRODUCTION Although adjuvant capecitabine therapy for patients with colorectal cancer after surgery often causes adverse events (AEs), such as diarrhoea, stomatitis, anorexia and hand-foot syndrome (HFS), there are no standard prevention therapies. Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and are also expected to attenuate the AEs caused by capecitabine treatment. Therefore, our present study aimed to determine the safety and efficacy of cystine/theanine therapy in patients with colorectal cancer undergoing capecitabine-based adjuvant chemotherapy after surgery. METHODS AND ANALYSIS A multi-institutional, prospective, randomised, double-blinded, placebo-controlled, phase II trial is being planned. Patients with colorectal cancer treated with capecitabine as an adjuvant chemotherapy will be randomised into either the cystine/theanine group (n=50) or placebo group (n=50). Data will be collected during four courses of capecitabine therapy. The primary endpoint will be incidence rate of diarrhoea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints are incidence rates of other AEs (CTCAE v.4.0-JCOG), scores of the Japanese version of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire module for all patients with cancer (QLQ-C30) and for patients with colorectal cancer (QLQ-CR29), incidence rate of HFS according to the HFS grading scale, protocol adherence, completion rate of four courses of capecitabine therapy and the proportion of completion without delay or dose reduction, time to completion of four courses of capecitabine and total dose of capecitabine. A sample size of 100 patients will be analysed between November 2016 and April 2018. ETHICS AND DISSEMINATION Ethical approval was obtained at all participating institutions. The results of this study will be submitted for publication in international peer-reviewed journals. TRIAL REGISTRATION NUMBER UMIN000024784; Pre-results.