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The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Lyon Michael R,Kapoor Mahendra P,Juneja Lekh R Alternative medicine review : a journal of clinical therapeutic INTRODUCTION:The purpose of this study was to investigate the efficacy and safety of L-theanine as an aid to the improvement of objectively measured sleep quality in a population of 98 male children formally diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHODS:A randomized, double-blind, placebo-controlled trial was conducted involving boys, ages 8-12 years, who had been previously diagnosed with ADHD. An experienced physician confirmed the diagnosis of ADHD in each subject. Randomization was stratified based upon current use of stimulant medication to ensure an equal distribution of stimulant/non-stimulant treated subjects into active and placebo treated groups. Participants consumed two chewable tablets twice daily (at breakfast and after school), with each tablet containing 100 mg of L-theanine (total 400 mg daily Suntheanine®, Taiyo Kagaku, Yokkaichi, Japan) or identical tasting chewable placebo for six weeks. Subjects were evaluated for five consecutive nights using wrist actigraphy at baseline, and again at the end of the six-week treatment period. The Pediatric Sleep Questionnaire (PSQ) was completed by parents at baseline and at the end of the treatment period. RESULTS:Actigraph watch data findings indicated that boys who consumed L-theanine obtained significantly higher sleep percentage and sleep efficiency scores, along with a non-significant trend for less activity during sleep (defined as less time awake after sleep onset) compared to those in the placebo group. Sleep latency and other sleep parameters were unchanged. The PSQ data did not correlate significantly to the objective data gathered from actigraphy, suggesting that parents were not particularly aware of their children's sleep quality. L-theanine at relatively high doses was well tolerated with no significant adverse events. CONCLUSIONS:This study demonstrates that 400 mg daily of L-theanine is safe and effective in improving some aspects of sleep quality in boys diagnosed with ADHD. Since sleep problems are a common co-morbidity associated with ADHD, and because disturbed sleep may be linked etiologically to this disorder, L-theanine may represent a safe and important adjunctive therapy in childhood ADHD. Larger, long-term studies looking at the wider therapeutic role of this agent in this population are warranted.
Alteration of Mevalonate Pathway in Rat Splenic Lymphocytes: Possible Role in Cytokines Secretion Regulated by L-Theanine. Li Chengjian,Yan Qiongxian,Tang Shaoxun,Xiao Wenjun,Tan Zhiliang BioMed research international L-Theanine is a nonprotein amino acid in tea, and its immunomodulatory function has been confirmed. This study aimed to investigate the effect of L-theanine addition on cytokines secretion in rat splenic lymphocytes and explore its potential immunomodulatory effects on the mevalonate biosynthetic pathway. Our results showed that L-theanine treatment did not influence the proliferation and division indexes of the splenic lymphocytes subsets. Interestingly, L-theanine treatment had regulated the contents of IFN-, IL-2, IL-4, IL-10, IL-12, and TNF-  ( < 0.001) except IL-6 and upregulated the mRNA and protein expression of Ras-related protein Rap-1A (Rap1A), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and farnesyl diphosphate synthase (FDPs) ( < 0.001). Additionally, there was a positive correlation between Rap1A and HMGCR proteins expression and IFN-, IL-4, and IL-6 levels. In conclusion, L-theanine regulated the secretion of cytokines probably by activating expression of Rap1A and HMGCR proteins involved in the mevalonate biosynthetic pathway in rat splenic lymphocytes. Therefore, L-theanine might be a promising potential drug candidate as immunopotentiator. 10.1155/2018/1497097
Role of Epigallocatechin Gallate in Glucose, Lipid, and Protein Metabolism and L-Theanine in the Metabolism-Regulatory Effects of Epigallocatechin Gallate. Nutrients Epigallocatechin gallate (EGCG) and L-theanine (LTA) are important bioactive components in tea that have shown promising effects on nutrient metabolism. However, whether EGCG alone or combined with LTA can regulate the glucose, lipid, and protein metabolism of healthy rats remains unclear. Therefore, we treated healthy rats with EGCG or the combination of EGCG and LTA (EGCG+LTA) to investigate the effects of EGCG on nutrient metabolism and the role of LTA in the metabolism-regulatory effects of EGCG. The results showed that compared with the control group, EGCG activated insulin and AMP-activated protein kinase (AMPK) signals, thus regulating glucose, lipid, and protein metabolism. Compared with EGCG, EGCG+LTA enhanced hepatic and muscle glycogen levels and suppressed phosphorylation of AMPK, glycogen synthase 2, mammalian target of rapamycin, and ribosomal protein S6 kinase. In addition, EGCG+LTA inhibited the expression of liver kinase B1, insulin receptor and insulin receptor substrate, and promoted the phosphorylation level of acetyl-CoA carboxylase. Furthermore, both EGCG and EGCG+LTA were harmless for young rats. In conclusion, EGCG activated AMPK and insulin pathways, thereby promoting glycolysis, glycogen, and protein synthesis and inhibiting fatty acid (FA) and cholesterol synthesis. However, LTA cooperated with EGCG to promote glycogen metabolism and suppressed the effect EGCG on FA and protein synthesis via AMPK signals. 10.3390/nu13114120
Effects of (L)-cystine and (L)-theanine supplementation on the common cold: a randomized, double-blind, and placebo-controlled trial. Journal of amino acids The common cold is one of the most frequent illnesses caused by viral infection. Recently, we have reported that oral administration of cystine and theanine (CT) to mice enhanced the humoral immune response associated with antibody production. Based on this mouse study, we investigated the effects of CT supplementation on the common cold in humans as a pilot study. A total of 176 healthy male volunteers were randomized to receive either placebo or CT (490 mg) tablets twice daily for 35 days. The incidence outcome was assessed using the definition in our laboratory based on questionnaires regarding cold symptoms. The incidence of subjects with colds during the trial was significantly lower in the CT group than in the placebo group, although the duration of the colds was not significantly different between the groups. These results suggest that CT supplementation may be useful for the prevention of the common cold. 10.4061/2010/307475
Reinventing the nutraceutical value of gluten: The case of l-theanine-gluten as a potential alternative to the gluten exclusion diet in celiac disease. Ribeiro Miguel,Lopes Sandra,Picascia Stefania,Gianfrani Carmen,Nunes Fernando M Food chemistry Functional foods have created an open environment for the development of new solutions to health-related issues. In celiac disease, there is still no therapeutic alternative other than the observance of a gluten-free diet. In this context, we developed a wheat flour enriched in l-theanine aimed to be a potential alternative to the gluten-free diet. Through microbial transglutaminase-catalysed transamidation of gluten proteins using ethylamine as amine nucleophile, substantial amounts of glutamine residues were converted in theanine residues. Furthermore, using T-cell lines generated from intestinal biopsy specimens of celiac disease patients, this treatment showed the potential to strongly reduce the ability of gluten proteins to stimulate a T-cell-mediated immune response. From a rheological point of view, the functionality of gluten was retained. Considering L-theanine's evidence-based health benefits, a novel functional food is presented here and for celiac disease can be a path towards the development of an alternative to the gluten-free diet. 10.1016/j.foodchem.2020.126840
Validation of a reversed-phase high-performance liquid chromatographic method for the determination of free amino acids in rice using l-theanine as the internal standard. Liyanaarachchi G V V,Mahanama K R R,Somasiri H P P S,Punyasiri P A N Food chemistry The study presents the validation results of the method carried out for analysis of free amino acids (FAAs) in rice using l-theanine as the internal standard (IS) with o-phthalaldehyde (OPA) reagent using high-performance liquid chromatography-fluorescence detection. The detection and quantification limits of the method were in the range 2-16μmol/kg and 3-19μmol/kg respectively. The method had a wide working range from 25 to 600μmol/kg for each individual amino acid, and good linearity with regression coefficients greater than 0.999. Precision measured in terms of repeatability and reproducibility, expressed as percentage relative standard deviation (% RSD) was below 9% for all the amino acids analyzed. The recoveries obtained after fortification at three concentration levels were in the range 75-105%. In comparison to l-norvaline, findings revealed that l-theanine is suitable as an IS and the validated method can be used for FAA determination in rice. 10.1016/j.foodchem.2017.07.038
Serum Ethylamine Levels as an Indicator of l-Theanine Consumption and the Risk of Type 2 Diabetes in a General Japanese Population: The Hisayama Study. Ninomiya Toshiharu,Kanzaki Noriyuki,Hirakawa Yoichiro,Yoshinari Masahito,Higashioka Mayu,Honda Takanori,Shibata Mao,Sakata Satoko,Yoshida Daigo,Teramoto Takanori,Takemoto Susumu,Nishimoto Shozo,Hata Jun,Kitazono Takanari Diabetes care OBJECTIVE:This study investigated the association between serum ethylamine levels as an indicator of l-theanine consumption and the development of type 2 diabetes in a Japanese community. RESEARCH DESIGN AND METHODS:A total of 2,253 community-dwelling Japanese individuals aged 40-79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87-2.10, 2.11-5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed after ingestion of l-theanine-rich green tea products containing 8 mg of l-theanine by 12 healthy volunteers. RESULTS:During follow-up, 282 subjects developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes decreased significantly with elevating levels of serum ethylamine ( for trend = 0.04). This association remained unchanged after adjusting for potential confounding factors. The multivariable-adjusted hazard ratio (HR) for type 2 diabetes was significantly lower in the fourth quartile of serum ethylamine than in the first quartile (HR 0.69, 95% CI 0.49-0.98). This trend of decrease in diabetic risk across serum ethylamine levels was more prominent in middle-aged subjects and in subjects with prediabetes, obesity, or insulin resistance. Kinetic analysis estimated that the minimum concentration at the steady state was >5.90 ng/mL in the case of twice-daily ingestion with an interval of 12 h. CONCLUSIONS:Higher serum ethylamine was significantly associated with lower risk of the development of type 2 diabetes in a general Japanese population. The measurement of serum ethylamine concentration would be a useful biomarker for the objective estimation of l-theanine consumption. 10.2337/dc18-2655
Theogallin and L-theanine as active ingredients in decaffeinated green tea extract: I. electrophysiological characterization in the rat hippocampus in-vitro. Dimpfel Wilfried,Kler Adolf,Kriesl Erwin,Lehnfeld Romanus The Journal of pharmacy and pharmacology The in-vitro hippocampus slice preparation was used to mimic a physiological situation where nervous tissue is exposed directly to the water soluble extract of green tea and some of its constituents. This investigation provides evidence that L-theanine- and theogallin-enriched decaffeinated green tea extract is able to change the physiological pattern of electrical hippocampus activity in a concentration dependent manner (EC50 3 mg L(-1)). Of the seven fractions or single components tested (fraction containing all amino acids without L-theanine, fractions containing all amino acids plus L-theanine, glutamic acid, theogallin, its metabolites quinic acid and gallic acid, and L-theanine alone), glutamic acid produced the strongest changes in terms of increased population spike amplitude after single stimuli and increased long-term potentiation, commonly taken as representative for enhancement of spatial and time dependent memory. The presence of theogallin alone shifted the activity in the same direction. Similar results as with theogallin were obtained in the presence of quinic acid. No effect was seen with gallic acid. Opposite changes (decrease of population spike amplitude and attenuated long-term potentiation) were observed in the presence of L-theanine alone. No effects were detected during the addition of the amino acid mixture unless L-theanine was added, leading to a decrease of the responses as observed for the action of L-theanine alone. The results provide evidence for the involvement of several active principles in the action of enriched green tea extract on electrical brain activity. The overall enhancement of hippocampal pyramidal cell responses as observed for the crude extract seems to be due to the combined action of glutamic acid and theogallin (or its presumable metabolite quinic acid), whereas L-theanine seems to have an opposite effect. However, this action was not strong enough to antagonize the effects of glutamic acid and theogallin. The results are in line with the observation that the tested green tea extract improves cognition at concomitant mental relaxation in man. 10.1211/jpp.59.8.0011
Effects of L-theanine on posttraumatic stress disorder induced changes in rat brain gene expression. Ceremuga Tomás Eduardo,Martinson Stephanie,Washington Jason,Revels Robert,Wojcicki Jessica,Crawford Damali,Edwards Robert,Kemper Joshua Luke,Townsend William Luke,Herron Geno M,Ceremuga George Allen,Padron Gina,Bentley Michael TheScientificWorldJournal Posttraumatic stress disorder (PTSD) is characterized by the occurrence of a traumatic event that is beyond the normal range of human experience. The future of PTSD treatment may specifically target the molecular mechanisms of PTSD. In the US, approximately 20% of adults report taking herbal products to treat medical illnesses. L-theanine is the amino acid in green tea primarily responsible for relaxation effects. No studies have evaluated the potential therapeutic properties of herbal medications on gene expression in PTSD. We evaluated gene expression in PTSD-induced changes in the amygdala and hippocampus of Sprague-Dawley rats. The rats were assigned to PTSD-stressed and nonstressed groups that received either saline, midazolam, L-theanine, or L-theanine + midazolam. Amygdala and hippocampus tissue samples were analyzed for changes in gene expression. One-way ANOVA was used to detect significant difference between groups in the amygdala and hippocampus. Of 88 genes examined, 17 had a large effect size greater than 0.138. Of these, 3 genes in the hippocampus and 5 genes in the amygdala were considered significant (P < 0.05) between the groups. RT-PCR analysis revealed significant changes between groups in several genes implicated in a variety of disorders ranging from PTSD, anxiety, mood disorders, and substance dependence. 10.1155/2014/419032
Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain - histopathological, and biochemical approach. Sumathi Thangarajan,Shobana Chandrasekar,Thangarajeswari Mohan,Usha Ramakrishnan Drug and chemical toxicology L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions. 10.3109/01480545.2014.900068
Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Tian Xia,Sun Lingyan,Gou Lingshan,Ling Xin,Feng Yan,Wang Ling,Yin Xiaoxing,Liu Yi Brain research The present work was aimed to study the protective effect of l-theanine on chronic restraint stress (CRS)-induced cognitive impairments in mice. The stress was produced by restraining the animals in well-ventilated polypropylene tubes (3.2 cm in diameter ×10.5 cm in length) for 8h once daily for 21 consecutive days. L-theanine (2 and 4 mg/kg) was administered 30 min before the animals subjected to acute immobilized stress. At week 4, mice were subjected to Morris water maze and step-through tests to measure the cognitive function followed by oxidative parameters and corticosterone as well as catecholamines (norepinephrine and dopamine) subsequently. Our results showed that the cognitive performances in CRS group were markedly deteriorated, accompanied by noticeable alterations in oxidative parameters and catecholamine levels in the hippocampus and the cerebral cortex as well as corticosterone and catecholamine levels in the serum. However, not only did l-theanine treatment exhibit a reversal of the cognitive impairments and oxidative damage induced by CRS, but also reversed the abnormal level of corticosterone in the serum as well as the abnormal levels of catecholamines in the brain and the serum. This study indicated the protective effect of l-theanine against CRS-induced cognitive impairments in mice. 10.1016/j.brainres.2013.01.048
Studies on the Biochemical Formation Pathway of the Amino Acid l-Theanine in Tea (Camellia sinensis) and Other Plants. Cheng Sihua,Fu Xiumin,Wang Xiaoqin,Liao Yinyin,Zeng Lanting,Dong Fang,Yang Ziyin Journal of agricultural and food chemistry Tea (Camellia sinensis) is the most widely consumed beverage aside from water. The flavor of tea is conferred by certain metabolites, especially l-theanine, in C. sinensis. To determine why more l-theanine accumulates in C. sinensis than in other plants, we compare l-theanine contents between C. sinensis and other plant species (Camellia nitidissima, Camellia japonica, Zea mays, Arabidopsis thaliana, and Solanum lycopersicum) and use a stable isotope labeling approach to elucidate its biosynthetic route. We quantify relevant intermediates and metabolites by mass spectrometry. l-Glutamic acid, a precursor of l-theanine, is present in most plants, while ethylamine, another precursor of l-theanine, specifically accumulates in Camellia species, especially C. sinensis. Most plants contain the enzyme/gene catalyzing the conversion of ethylamine and l-glutamic acid to l-theanine. After supplementation with [H]ethylamine, all the plants produce [H]l-theanine, which suggests that ethylamine availability is the reason for the difference in l-theanine accumulation between C. sinensis and other plants. 10.1021/acs.jafc.7b02437
Anxiolytic effects of L-theanine--a component of green tea--when combined with midazolam, in the male Sprague-Dawley rat. Heese Traci,Jenkinson Jack,Love Cheryl,Milam Ronald,Perkins Lillian,Adams Cynthia,McCall Suzanne,Ceremuga Thomas E AANA journal The purpose of the study was to investigate the anxiolytic effects of L-theanine and its potential interaction with the GABAA receptor in Sprague-Dawley rats. L-theanine is a major component of green tea, which has traditionally been used as an herbal remedy in the treatment of many medical conditions, including anxiety. Herbals and supplements and their potential interactions perioperatively are a concern to anesthetists. Fifty-five rats were divided into 5 groups: control (saline); L-theanine (positive control); flumazenil (a known benzodiazepine receptor antagonist) and L-theanine; and midazolam and L-theanine. The behavioral component of anxiety was evaluated using the elevated plus-maze and calculated by the time spent in the open arm of the maze divided by total time in the maze. Data were analyzed using a 2-tailed multivariate analysis of variance and Sheffé posthoc test. The data suggest that L-theanine does not produce anxiolysis by modulation of the GABAA receptor; however, in combination with midazolam, a synergistic or additive effect was demonstrated by decreased anxiety and both fine and basic motor movements. These data may provide direction for further studies examining L-theanine and its effects on anxiety and motor activity.
Enhancement of antigen-specific immunoglobulin G production in mice by co-administration of L-cystine and L-theanine. Kurihara Shigekazu,Shibahara Susumu,Arisaka Harumi,Akiyama Yukio The Journal of veterinary medical science Supplementation with both cystine and glutamic acid increases the synthesis of glutathione (GSH), which has a marked effect on immune cell function, as compared with supplementation with either amino acid alone in human macrophages in vitro. As dietary glutamic acid is metabolized during intestinal transport, oral administration of L-theanine (gamma-glutamylethylamide), which is metabolized to glutamic acid mainly in the liver, may act as a glutamic acid donor in vivo. The present study was performed to investigate the effects of oral administration of L-cystine and/or L-theanine on GSH levels and immune responses. Co-administration of L-cystine (200 mg/kg) and L-theanine (80 mg/kg) for 11 days before immunization significantly increased the levels of total GSH in the liver 6 hr after immunization as compared with the levels in control mice. To examine the effects of administration of L-cystine and/or L-theanine on the balance of T helper (Th) 1/Th2 cell responses, the serum ratios of the Th1 cytokine, interferon (IFN)-gamma, and the Th2 cytokine, interleukin IL-10, were investigated. At 24 hr after immunization, co-administration significantly increased the IL-10/IFN-gamma ratio compared with the ratios of the control and single-administration mice. Furthermore, co-administration before primary immunization significantly enhanced serum antigen-specific IgG levels. Taken together, these findings suggest that co-administration of L-cystine and L-theanine enhances antigen-specific IgG production partly through augmentation of GSH levels and Th2-mediated responses. 10.1292/jvms.69.1263
16S ribosomal RNA sequencing reveals a modulation of intestinal microbiome and immune response by dietary L-theanine supplementation in broiler chickens. Saeed Muhammad,Yatao Xu,Tiantian Zhang,Qian Ren,Chao Sun Poultry science Despite the availability of abundant literature on green tea, studies on the use of L-theanine (an amino acid found only in green tea) as a feed additive in poultry especially broiler are limited. So, this study was conducted to explore the effects of L-theanine on the intestinal microbiome and immune response in a broiler. A total of 400-d-old chicks were randomly divided into four treatment groups (A, B, C, and D) using a complete randomized design. Treatments were as follows: A, control (basal diet); B, basal diet + 100 mg L-theanine/kg diet; C, basal diet + 200 mg L-theanine/kg diet; and D, basal diet + 300 mg L-theanine/kg diet. Mucosal samples from ileum and jejunum of broiler chicken were extracted at 21 and 42 d of age. Extraction of genomic DNA was followed by amplification of V3 and V4 hypervariable regions of 16S ribosomal RNA. After Illumina sequencing, results revealed that treatment with L-theanine significantly increased the population of Lactobacillus in ileum and jejunum as compared to a control group, but the higher population was observed in jejunum at both 21 and 42 d of age. The overall diversity of the jejunum microbiome in the treatment group was significantly lower than that of the ileum and control group (P < 0.05). Results of this study revealed that mRNA expression of TLRs (TLR-2 and TLR-4) and cytokines (TNF-α, IFN-γ, and IL-2) was decreased in response to treatment with L-theanine. Moreover, the negative correlation of abundance of Lactobacillus was observed with expression of IL-2 and IFN-γ in the intestine and these effects were highly significant (P < 0.01). In summary, our finding revealed that dietary supplementation of L-theanine exhibited a positive influence on intestinal bacteria by supporting beneficial microbes like Lactobacillus while decreasing harmful microbes like Clostridium. 10.3382/ps/pey394
The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Giesbrecht T,Rycroft J A,Rowson M J,De Bruin E A Nutritional neuroscience The non-proteinic amino acid L-theanine and caffeine, a methylxanthine derivative, are naturally occurring ingredients in tea. The present study investigated the effect of a combination of 97 mg L-theanine and 40 mg caffeine as compared to placebo treatment on cognitive performance, alertness, blood pressure, and heart rate in a sample of young adults (n = 44). Cognitive performance, self-reported mood, blood pressure, and heart rate were measured before L-theanine and caffeine administration (i.e. at baseline) and 20 min and 70 min thereafter. The combination of moderate levels of L-theanine and caffeine significantly improved accuracy during task switching and self-reported alertness (both P < 0.01) and reduced self-reported tiredness (P < 0.05). There were no significant effects on other cognitive tasks, such as visual search, choice reaction times, or mental rotation. The present results suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task. 10.1179/147683010X12611460764840
L-theanine (suntheanin): effects of L-theanine, an amino acid derived from Camellia sinensis (green tea), on stress response parameters. Ross Stephanie Maxine Holistic nursing practice 10.1097/HNP.0000000000000009
Novel Therapeutic Approach for the Management of Mood Disorders: In Vivo and In Vitro Effect of a Combination of L-Theanine, L. and Rehder & E.H. Wilson. Borgonetti Vittoria,Governa Paolo,Biagi Marco,Galeotti Nicoletta Nutrients Mood disorders represent one of the most prevalent and costly psychiatric diseases worldwide. The current therapies are generally characterized by several well-known side effects which limit their prolonged use. The use of herbal medicine for the management of several psychiatric conditions is becoming more established, as it is considered a safer support to conventional pharmacotherapy. The aim of this study was to investigate the possible anxiolytic and antidepressant activity of a fixed combination of L-theanine, , and (TMM) in an attempt to evaluate how the multiple modulations of different physiological systems may contribute to reducing mood disorders. TMM showed an anxiolytic-like and antidepressant-like activity in vivo, which was related to a neuroprotective effect in an in vitro model of excitotoxicity. The effect of TMM was not altered by the presence of flumazenil, thus suggesting a non-benzodiazepine-like mechanism of action. On the contrary, a significant reduction in the effect was observed in animals and neuronal cells co-treated with AM251, a cannabinoid receptor type 1 (CB1) antagonist, suggesting that the endocannabinoid system may be involved in the TMM mechanism of action. In conclusion, TMM may represent a useful and safe candidate for the management of mood disorders with an innovative mechanism of action, particularly as an adjuvant to conventional therapies. 10.3390/nu12061803
Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice. Yin Cui,Gou Lingshan,Liu Yi,Yin Xiaoxing,Zhang Ling,Jia Genguang,Zhuang Xuemei Phytotherapy research : PTR L-theanine (γ-glutamylethylamide), an amino acid component of green tea, has been shown to reduce mental and physical stress, and to improve memory function. In this study, the antidepressant effect of L-theanine was investigated in mice using the forced swim test, tail suspension test, open-field test and reserpine test. L-theanine produced an antidepressant-like effect, since the administration of L-theanine at doses of 1, 4 and 20 mg/kg for 10 successive days significantly reduced the immobility time in both the forced swim test and tail suspension test, compared with the control group, without accompanying changes in ambulation in the open-field test. Moreover, L-theanine significantly antagonized reserpine-induced ptosis and hypothermia. Taken together, these results indicate that L-theanine possessed an antidepressant-like effect in mice, which may be mediated by the central monoaminergic neurotransmitter system. 10.1002/ptr.3456
Rapid and selective quantification of L-theanine in ready-to-drink teas from Chinese market using SPE and UPLC-UV. Chen Guoqiang,Wang Yun,Song Weiqi,Zhao Bo,Dou Yuling Food chemistry An ultra performance liquid chromatography (UPLC) method combined with solid phase extraction (SPE) sample pre-treatment was developed and validated for the rapid quantification of L-theanine in ready-to-drink (RTD) teas. UPLC analysis of twenty-seven RTD teas from the Chinese market revealed that the L-theanine levels in various types of RTD teas were significantly different. RTD green teas were found to contain highest mean L-theanine level (37.85±20.54 mg/L), followed by jasmine teas (36.60±12.08 mg/L), Tieguanying teas (18.54±3.46 mg/L) black teas (16.89±6.56), Pu-erh teas (11.31±0.90 mg/L) and oolong teas (3.85±2.27 mg/L). The ratio of total polyphenols content to L-theanine content could be used as a featured parameter for differentiating RTD teas. L-theanine in RTD teas could be a reliable quality parameter that is complementary to total polyphenols. 10.1016/j.foodchem.2012.04.084
Effect of Alpha-S1-Casein Tryptic Hydrolysate and L-Theanine on Poor Sleep Quality: A Double Blind, Randomized Placebo-Controlled Crossover Trial. Nutrients This randomized, placebo-controlled, crossover and double-blind study investigates the effects of RLX2™ containing alpha-s1-casein tryptic hydrolysate and L-theanine in working adults affected by poor sleep quality. The supplement or placebo was randomly and blindly assigned to 39 subjects for four weeks and the changes in the subjective sleep assessment via the Pittsburgh Sleep Quality Index (PSQI), heart rate, blood pressure, salivary cortisol by high-performance liquid chromatography method and alpha power of awake electroencephalogram (EEG) were studied. The data were analyzed in two ways, by crossover and crossover summed up. The latter depicted that RLX2™ improved PSQI total score, sleep latency, sleep duration, sleep habitual efficiency, daytime dysfunction, and increased total and frontal alpha power significantly (p < 0.05). The supplement prolonged the total sleeping time by 45 min in the supplement receiving group compared to the placebo group (p < 0.001). However, only sleep duration and sleep habitual efficiency showed a profound effect in both analyses (p < 0.05). In conclusion, being given its beneficial effects without notable adverse events, it would be advantageous to use these nutraceutical ingredients to promote better sleep quality. Further studies with a larger number participants are warranted to support these findings. 10.3390/nu14030652
The combination of luteolin and l-theanine improved Alzheimer disease-like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-β-infused rats. Park Sunmin,Kim Da Sol,Kang Suna,Kim Hyun Jin Nutrition research (New York, N.Y.) Luteolin and l-theanine have anti-inflammatory, antioxidant, and possible antidiabetic activities, and they may synergistically protect against dementia. Here, we hypothesized that a combination of luteolin and l-theanine would synergistically act to improve memory function and glucose disturbances in rats infused with amyloid-β, and the mechanisms underlying these actions were investigated. Rats that received an amyloid-β(25-35) infusion into the CA1 region of the hippocampus were fed dextrin (AD-CON), 0.1% luteolin (AD-Lut), 0.2% l-theanine (AD-Thea), or both 0.05% luteolin and 0.1% l-theanine (AD-LuTh) in conjunction with a high-fat diet over 8 weeks. AD-LuTh improved memory function, as determined by water maze and passive avoidance tests, by potentiating the hippocampal insulin signaling and reducing inflammation: Luteolin mainly potentiated insulin signaling via the pAkt➔pGSK➔pTau pathway, and l-theanine primarily reduced tumor necrosis factor-α. In the metabolomics analysis of the hippocampus lysates, the concentration of proline, phenylpyruvic acid, and normetanephrine decreased in the AD-LuTh compared to AD-CON. Norepinephrine contents were lower in the AD-CON than non-AD rats with a high fat diet with 0.2% dextrin, whereas AD-Thea and AD-LuTh inhibited the decrease. Both the AD-Lut and AD-LuTh increased glucose infusion rates and decreased hepatic glucose output under basal and hyperinsulinemic conditions, indicating improved whole-body and hepatic insulin sensitivity. Disturbances in glucose-stimulated insulin secretion during hyperglycemic clamp were most effectively corrected by the AD-Lut and AD-LuTh treatments. In conclusion, the hypothesis of the study was accepted. The combination of luteolin and l-theanine prevented Alzheimer disease-like symptom, possibly by improving hippocampal insulin signaling, norepinephrine metabolisms, and decreasing neuroinflammation. The combination of luteolin and l-theanine may be a useful therapeutic option for preventing and/or delaying the progression of memory dysfunction. 10.1016/j.nutres.2018.09.010
Behavioral and molecular evidence for psychotropic effects in L-theanine. Wakabayashi Chisato,Numakawa Tadahiro,Ninomiya Midori,Chiba Shuichi,Kunugi Hiroshi Psychopharmacology RATIONALE:L-Theanine (N-ethyl-L: -glutamine) is an amino acid uniquely found in green tea and historically considered to be a relaxing agent. It is a glutamate derivative and has an affinity for glutamatergic receptors. However, its psychotropic effects remain unclear. OBJECTIVES:To elucidate effects of L: -theanine on psychiatric disease-related behaviors in mice and its molecular basis focusing on brain-derived neurotrophic factor (BDNF) and N-methyl-D: -aspartate (NMDA) receptor. METHODS:We examined the effects of L: -theanine on behaviors in mice by using the open-field test (OFT), forced swim test (FST), elevated plus-maze test (EPMT), and prepulse inhibition (PPI) of acoustic startle. By western blot analysis, we looked at the effect of L: -theanine on the expression of BDNF and related proteins in the hippocampus and cerebral cortex. To determine whether L: -theanine has agonistic action on the NMDA receptor, we performed Fluo-3 intracellular Ca(2+) imaging in cultured cortical neurons. RESULTS:Single administration of L: -theanine significantly attenuated MK-801-induced deficits in PPI. Subchronic administration (3-week duration) of L: -theanine significantly reduced immobility time in the FST and improved baseline PPI. Western blotting analysis showed increased expression of BDNF protein in the hippocampus after subchronic administration of L: -theanine. In cultured cortical neurons, L: -theanine significantly increased the intracellular Ca(2+) concentration, and this increase was suppressed by competitive and non-competitive NMDA receptor antagonists (AP-5 and MK-801, respectively). CONCLUSIONS:Our results suggest that L: -theanine has antipsychotic-like and possibly antidepressant-like effects. It exerts these effects, at least in part, through induction of BDNF in the hippocampus and the agonistic action of L: -theanine on the NMDA receptor. 10.1007/s00213-011-2440-z
[Efficient synthesis of L-theanine by recombinant strain Corynebacterium glutamicum SYPA5-5]. He Fei,Yang Taowei,Xu Meijuan,Zhang Xian,Rao Zhiming,Tang Lei Wei sheng wu xue bao = Acta microbiologica Sinica Objective:To construct a Corynebacterium glutamicum strain system for L-theanine production by the secretion expression of γ-glutamyltranspeptidase. Methods:Two genes ggt and △sp ggt (without signal peptide fragment) from Bacillus subtilis were cloned and expressed in C. glutamicum. Then the recombinant GGT was used for L-theanine production under the optimal conditions: GGT enzyme 0.9 U/mL, pH 10, 37℃, and 20 mmol/L L-glutamine and 60 mmol/L ethylamine were fed every two hours. Supplementation was ceased after 12 h to minimize the substrates residue in the final broth. Results:Firstly, two different recombinant C. glutamicum strains C. glutamicum SYPA5-5/pXMJ19-△sp ggt (without signal peptide), C. glutamicum SYPA5-5/pXMJ19-ggt (with signal peptide) were successfully constructed. In comparison to C. glutamicum SYPA5-5/pXMJ19-△sp ggt, C. glutamicum SYPA5-5/pXMJ19-ggt showed the ability to secret GGT into the medium and 5-fold higher enzyme activity than that in the former strain. This finding suggested that the signal peptide of GGT was responsible for the secretion and could work in C.glutamicum strain system. Furthermore, the glucose concentration and the adding time of inducer IPTG on GGT production were optimized in shake-flask. The batch transformation conditions were also investigated. The optimal ratio of L-glutamine to ethylamine was 1:3, and optimal enzyme amount was 0.06 U/mL. The highest L-theanine production reached at 104.36 mmol/L at 12 h with the conversion rate of 86.9%. Conclusion:This is the first time to use the C. glutamicum system for the efficient synthesis of L-theanine. Furthermore, the signal peptide of GGT is identified to function well in C. glutamicum, providing a possible strategy for constructing a secretion expression system in C. glutamicum.
The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Lu Kristy,Gray Marcus A,Oliver Chris,Liley David T,Harrison Ben J,Bartholomeusz Cali F,Phan K Luan,Nathan Pradeep J Human psychopharmacology L-Theanine (delta-glutamylethylamide) is one of the predominant amino acids ordinarily found in green tea, and historically has been used as a relaxing agent. The current study examined the acute effects of L-theanine in comparison with a standard benzodiazepine anxiolytic, alprazolam and placebo on behavioural measures of anxiety in healthy human subjects using the model of anticipatory anxiety (AA). Sixteen healthy volunteers received alprazolam (1 mg), L-theanine (200 mg) or placebo in a double-blind placebo-controlled repeated measures design. The acute effects of alprazolam and L-theanine were assessed under a relaxed and experimentally induced anxiety condition. Subjective self-reports of anxiety including BAI, VAMS, STAI state anxiety, were obtained during both task conditions at pre- and post-drug administrations. The results showed some evidence for relaxing effects of L-theanine during the baseline condition on the tranquil-troubled subscale of the VAMS. Alprazolam did not exert any anxiolytic effects in comparison with the placebo on any of the measures during the relaxed state. Neither L-theanine nor alprazalam had any significant anxiolytic effects during the experimentally induced anxiety state. The findings suggest that while L-theanine may have some relaxing effects under resting conditions, neither L-theanine not alprazolam demonstrate any acute anxiolytic effects under conditions of increased anxiety in the AA model. 10.1002/hup.611
Influence of Graded Levels of l-Theanine Dietary Supplementation on Growth Performance, Carcass Traits, Meat Quality, Organs Histomorphometry, Blood Chemistry and Immune Response of Broiler Chickens. Saeed Muhammad,Yatao Xu,Hassan Faiz-Ul,Arain Muhammad Asif,Abd El-Hack Mohamed E,Noreldin Ahmed E,Sun Chao International journal of molecular sciences l-theanine is a water-soluble non-proteinous amino acid mainly found in green tea leaves. Despite the availability of abundant literature on green tea, studies on the use of l-theanine as a feed additive in animals, and especially broilers are limited. The objective of this study was, therefore, to evaluate the effect of different dietary levels of l-theanine on meat quality, growth performance, immune response, and blood metabolites in broilers. A total of 400 day-old broiler chicks were randomly divided into four treatment groups using a completely randomized design; C-control, basal diet; 100LT-basal diet + 100 mg l-theanine/kg diet; 200LT-basal diet + 200 mg l-theanine/kg diet; and 300LT-basal diet + 300 mg l-theanine/kg diet. Results revealed that the intermediate level of l-theanine (200 mg/kg diet) showed better results in terms of body weight gain (BWG), feed consumed (FC), and feed conversion ratio (FCR) as compared with the other supplemented groups and the control. The live weight eviscerated weight and gizzard weight were higher in all l-theanine levels as compared to those of the control group. Increased weight ( ≤ 0.05) of spleen and bursa were found in group 200LT (200 mg l-theanine/kg diet). Concerning meat color parameters, values for yellowness (), and redness () were greater in l-theanine-supplemented groups than the control. Supplementing broiler diet with l-theanine reduced ( = 0.02) total serum cholesterol contents while increased HDL. Further analysis revealed lower relative serum cytokines ( and ) and reduced mRNA expression of and in thymus, and and in spleen in the treated group. Moreover, supplementation with 200 mg/kg of l-theanine improved antioxidant status in blood by increasing SOD, GSH-Px, and relative CAT levels. It is concluded that the optimum supplementation level of l-theanine is 200 mg/kg of diet because it resulted in improved performance parameters in broilers. However, higher levels of l-theanine (300 mg/kg diet) may have deleterious effects on performance and health of broiler chickens. 10.3390/ijms19020462
L-theanine synthesis using γ-glutamyl transpeptidase from Bacillus licheniformis ER-15. Bindal Shruti,Gupta Rani Journal of agricultural and food chemistry Recombinant γ-glutamyl transpeptidase (rBLGGT) from Bacillus licheniformis ER-15 was purified to homogeneity by ion-exchange chromatography. Molecular masses of large and small subunits were 42 and 22 kDa, respectively. The enzyme was optimally active at pH 9.0 and 60 °C and was alkali stable. K(m) and V(max) for γ-glutamyl-p-nitroanilide hydrochloride were 45 μM and 0.34 mM/min, respectively. L-Theanine synthesis was standardized using a one variable at a time approach followed by response surface methodology, which resulted in approximately 85-87% conversion of L-glutamine to L-theanine within 4 h. The standardized reaction contained 80 mM L-glutamine, 600 mM ethylamine, and 1.0 U/mL rBLGGTin 50 mM Tris-Cl (pH 9.0) at 37 °C. Similar conversions were also obtained with the enzyme immobilized in calcium alginate. Using immobilized enzyme, 35.2 g of L-theanine was obtained in three cycles of 1 L each. The product was purified by Dowex 50W X 8 hydrogen form resin and was confirmed by HPLC and proton NMR spectroscopy. 10.1021/jf5022913
L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance. The Journal of nutrition Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8-14 Hz) activity. We found an increase in hit rate and target discriminability (d') for the combined treatment relative to placebo, and an increase in d' but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea. 10.1093/jn/138.8.1572S
The effects of L-theanine on alpha-band oscillatory brain activity during a visuo-spatial attention task. Gomez-Ramirez Manuel,Kelly Simon P,Montesi Jennifer L,Foxe John J Brain topography Background/Objectives Ingestion of the non-proteinic amino acid L-theanine (gamma-glutamylethylamide) has been shown to influence oscillatory brain activity in the alpha band (8-14 Hz) in humans during resting electroencephalographic (EEG) recordings and also during cognitive task performance. We have previously shown that ingestion of a 250-mg dose of L-theanine significantly reduced tonic (background) alpha power during a demanding intersensory (auditory-visual) attentional cueing task. Further, cue-related phasic changes in alpha power, indexing the shorter-term anticipatory biasing of attention between modalities, were stronger on L-theanine compared to placebo. This form of cue-contingent phasic alpha activity is also known to index attentional biasing within visual space. Specifically, when a relevant location is pre-cued, anticipatory alpha power increases contralateral to the location to be ignored. Here we investigate whether the effects of L-theanine on tonic and phasic alpha activity, found previously during intersensory attentional deployment, occur also during a visuospatial task. Subjects/Methods 168-channel EEG data were recorded from thirteen neurologically normal individuals while engaged in a highly demanding visuo-spatial attention task. Participants underwent testing on two separate days, ingesting either a 250-mg colorless and tasteless solution of L-theanine mixed with water, or a water-based solution placebo on each day in counterbalanced order. We compared the alpha-band activity when subjects ingested L-Theanine vs. Placebo. Results We found a significant reduction in tonic alpha for the L-theanine treatment compared to placebo, which was accompanied by a shift in scalp topography, indicative of treatment-related changes in the neural generators of oscillatory alpha activity. However, L-theanine did not measurably affect cue-related anticipatory alpha effects. Conclusions This pattern of results implies that L-theanine plays a more general role in attentional processing, facilitating longer-lasting processes responsible for sustaining attention across the timeframe of a difficult task, rather than affecting specific moment-to-moment phasic deployment processes. 10.1007/s10548-008-0068-z
The effect of L-theanine supplementation on the immune system of athletes exposed to strenuous physical exercise. Juszkiewicz A,Glapa A,Basta P,Petriczko E,Żołnowski K,Machaliński B,Trzeciak J,Łuczkowska K,Skarpańska-Stejnborn A Journal of the International Society of Sports Nutrition BACKGROUND:The aim of this study was to analyze the response of selected components of the immune system in rowers to maximal physical exercise, and to verify if this response could be modulated by supplementation with L-theanine. METHOD:The double-blind study included 20 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group (n = 10), receiving 150 mg of L-theanine extract for 6 weeks, or to the placebo group (n = 10). The participants performed a 2000-m test on a rowing ergometer at the beginning (1st examination) and at the end of the supplementation period (2nd examination). Blood samples were obtained from the antecubital vein before each exercise test, 1 min after completing the test, and after a 24-h recovery. Subpopulations of T regulatory lymphocytes (Tregs) (CD4+/CD25+/CD127-), cytotoxic lymphocytes (CTLs) (CD8+/TCRαβ+), natural killer (NK) cells (CD3-/CD16+/CD56+) and TCRδγ-positive (Tδγ) cells were determined by means of flow cytometry. The levels of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 10 (IL-10), interferon gamma (INF-ɤ) and total antioxidant capacity (TAC) were determined with commercially available diagnostic kits. RESULTS:Supplementation with L-theanine contributed to a significant post-exercise decrease in IL-10 concentration, which was reflected by higher values of IL-2 to IL-10 and IFN-γ to IL-10 ratios. Moreover, a significant post-recovery decrease in CTL count, Treg to NK and Treg to CTL ratios was observed in the supplemented group. CONCLUSION:Despite the decrease in the number of some cytotoxic cells (CTLs) and an increase in the proportion of Tregs to CTLs, supplementation with LTE seems to exert a beneficial effect on a disrupted Th1/Th2 balance in elite athletes, as shown by the decrease in IL-10 concentration. 10.1186/s12970-019-0274-y
Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. Yoto Ai,Motoki Mao,Murao Sato,Yokogoshi Hidehiko Journal of physiological anthropology BACKGROUND:L-theanine, an amino acid contained in green tea leaves, is known to block the binding of L-glutamic acid to glutamate receptors in the brain, and has been considered to cause anti-stress effects by inhibiting cortical neuron excitation. Both L-theanine and caffeine, which green tea contains, have been highlighted for their beneficial effects on cognition and mood. METHODS:In this study, we investigated the effects of orally administered L-theanine or caffeine on mental task performance and physiological activities under conditions of physical or psychological stress in humans. Fourteen participants each underwent three separate trials, in which they orally took either L-theanine + placebo, caffeine + placebo, or placebo only. RESULTS:The results after the mental tasks showed that L-theanine significantly inhibited the blood-pressure increases in a high-response group, which consisted of participants whose blood pressure increased more than average by a performance of a mental task after placebo intake. Caffeine tended to have a similar but smaller inhibition of the blood-pressure increases caused by the mental tasks. The result of the Profile of Mood States after the mental tasks also showed that L-theanine reduced the Tension-Anxiety scores as compared with placebo intake. CONCLUSIONS:The findings above denote that L-theanine not only reduces anxiety but also attenuates the blood-pressure increase in high-stress-response adults. 10.1186/1880-6805-31-28
Effect of L-theanine on meat quality, muscle amino acid profiles, and antioxidant status of broilers. Animal science journal = Nihon chikusan Gakkaiho This study investigated the effect of L-theanine on carcass traits, meat quality, muscle antioxidant capacity, and amino acid (AA) profiles of broilers. Three hundred 1-day-old Ross 308 male broilers were randomly allotted to five groups with six replicates. Birds were fed the basal diet or basal diet with 300, 600, 900, or 1,500 mg/kg L-theanine for 42 consecutive days. The results showed that L-theanine quadratically increased dressing percentage, eviscerated percentage, and leg muscle yield (p < .05). Meanwhile, drip loss, cooking loss, shear force, L* and muscle lactate content decreased quadratically in response to dietary L-theanine supplementation (p < .05), while pH and muscle glycogen content were quadratically improved by L-theanine (p < .05). Notably, the contents of muscle malondialdehyde and protein carbonyl, and the activities of muscle total antioxidant capacity, catalase, and glutathione peroxidase decreased quadratically in response to dietary L-theanine supplementation (p < .05), suggesting that the oxidative stress level of muscle was decreased quadratically. Moreover, L-theanine quadratically increased the concentrations of most of muscle essential AA, nonessential AA, and flavor AA (p < .05). In conclusion, L-theanine can be used as a valuable feed additive to modulate carcass traits, meat quality, muscle antioxidant status, and AA profiles of boilers, and its optimum addition level is 600 mg/kg based on the present study. 10.1111/asj.13351
γ-Glutamyltranspeptidase from Bacillus amyloliquefaciens: transpeptidation activity enhancement and L-theanine production. Li Zelong,Zhu Runtao,Liu Yongqi,Li Jiaqi,Gao Haofeng,Hu Nan Enzyme and microbial technology L-theanine, a unique amino acid in green tea with health benefits, can be enzymatically synthesized by γ-glutamyltranspeptidase (γ-GT; EC 2.3.2.2). Here, a salt-tolerant γ-glutamyltranspeptidase from a marine bacterium Bacillus amyloliquefaciens was expressed in Escherichia. coli BL21 (DE3) and was shown to be optimally active at 55 °C, pH 8.5 and alkali stable. A mutant, with higher transpeptidation activity, was obtained following two rounds of directed evolution using error-prone PCR and site-saturation mutagenesis. The mutation increased the ratio of transpeptidation to hydrolysis from 1.6 to 35.6. Additionally, Kinetic analysis exhibited 17.5% decrease of K, 13.0-fold increase of K, and 16.3-fold increase of K/K in mutant V319A/S437 G versus the wild-type. The 3-D modelling analysis revealed a tighter binding pocket in mutant V319A/S437 G. The frequency of hydrogen bond between donor substrate and two residues in the catalytic pocket (Gly437 and Thr375) was enhanced, which stabilized the ligand binding and thus improved the catalytic efficiency. The optimal conditions for the biocatalytic synthesis were determined as pH 10.0, 20 μg mLBaGT, 200 mM L-glutamine, 2 M ethylamine, and a reaction time of 5 h. The V319A/S437 G mutant was shown to increase the percentage yield of L-theanine from 58% to 83%. These results indicate the great potential of V319A/S437 G in L-theanine production after further study. 10.1016/j.enzmictec.2020.109644
An imaging approach for determining the mechanism of enhancement of intestinal absorption of an L-theanine supplement. Sato Yuki,Yamaguchi Kazuki,Ogawa Mikako,Takekuma Yoh,Sugawara Mitsuru PloS one BACKGROUND & OBJECTIVE:Theanine (L-glutamylethylamide) contained in green tea is a functional food component that has been attracting attention due to its relaxation effect. It was shown that the ingredients added to the theanine formulations increased the absorption of theanine. If this mechanism can be elucidated, it would be possible to contribute to development of evidence-based formulations. In this study, we investigated the effect of ingredients in the formulations on the absorption of theanine in detail. MAIN METHODS:After oral administration of a mixture of theanine and additional components to Wistar rats the plasma concentration was determined by an HPLC and the pharmacokinetic parameters were calculated. In addition, a new system for evaluating intestinal blood flow was developed since the involvement of intestinal blood flow was considered as a factor that increased absorption of theanine. KEY FINDINGS:Plasma concentration of theanine increased significantly in the combined use group with eight ingredients containing piperine as compared with theanine only group. Piperine would increase theanine absorption by increased blood flow, not an inhibition of metabolism. We succeeded to develop a visual and quantitative system to evaluate the effect of these ingredients directly including piperine on the intestinal blood flow using indocyanine green while maintaining physiological conditions. SIGNIFICANCE:Increased intestinal blood flow by these ingredients including piperine enhanced the absorption of theanine. Other mechanisms may also be considered as the mechanism by which theanine absorption is increased in addition to increased blood flow. 10.1371/journal.pone.0253066
Kinetics of L-theanine uptake and metabolism in healthy participants are comparable after ingestion of L-theanine via capsules and green tea. The Journal of nutrition L-Theanine, an amino acid in green tea, is suggested to improve cognition and mood. Therefore, L-theanine is available as a supplement and is now used as an ingredient in functional drinks. Because data on the metabolic fate of L-theanine from human studies are lacking, we investigated the kinetics of L-theanine uptake and its metabolites, ethylamine and glutamic acid, in healthy participants. Within a randomized crossover study, 12 participants ingested a bolus of 100 mg L-theanine via capsules or green tea. On further occasions, 3 participants received 50 and 200 mg L-theanine via capsules. Blood and urine were collected before and up to 24 h postconsumption to determine the concentrations of L-theanine, proteinogenic amino acids, and ethylamine in plasma, erythrocytes, and urine by HPLC. L-Theanine increased in plasma, erythrocytes, and urine with comparable results after both treatments. The maximum plasma concentration of L-theanine occurred 0.8 h after intake of 100 mg L-theanine via capsules (24.3 ± 5.7 μmol/L) and tea (26.5 ± 5.2 μmol/L), respectively. The AUC of L-theanine in plasma increased dose dependently after intake of 50, 100, and 200 mg L-theanine via capsules. Moreover, ethylamine and glutamic acid increased in plasma and were excreted by urine after intake of capsules and tea. In conclusion, L-theanine is rapidly absorbed and seems to be hydrolyzed to ethylamine and glutamic acid. A minor part of L-theanine is retained in erythrocytes. Kinetics and urinary excretion of L-theanine, ethylamine, and glutamic acid are comparable after both treatments. Thus, functional effects of L-theanine intake may result from L-theanine, ethylamine, or glutamic acid. 10.3945/jn.112.166371
Physicochemical, antioxidant and sensory properties of Mango Sorbet containing L-theanine as a potential functional food product. Journal of food science and technology The non-proteinous amino acid L-theanine (L-THE) is associated with a range of health benefits including improvements in immune function, cardiovascular outcomes and cognition. The aims of this study were to develop a food product (mango sorbet; ms-L-THE) containing physiologically relevant doses of L-THE (0.2/100 g w/w) and determine its antioxidant, physicochemical and sensory properties in comparison to a mango sorbet without L-THE (ms). Total phenolic and flavanol content, and antioxidant analysis (DPPH, FRAP and ABTS) were determined spectrophotometrically. Both products were also evaluated for acceptability and likeability in healthy participants using the 9-point hedonic scale. Any differences that could be caused by the addition of L-THE were examined using the triangle test. Results indicated no significant differences between ms-L-THE and ms in taste of the products (p > 0.05), and the ms-L-THE was well received and accepted as a potential commercial product. Findings of the DPPH assay indicated significant difference between the two products (p < 0.05). In conclusion, we have successfully created a mango sorbet that contains a potentially physiologically relevant concentration of L-THE with antioxidant properties that could be used as a novel method of L-THE delivery to clinical and healthy populations. 10.1007/s13197-022-05570-6
Alterations in nutrient digestibility and performance of heat-stressed dairy cows by dietary L-theanine supplementation. Animal nutrition (Zhongguo xu mu shou yi xue hui) The purpose of this study was to investigate the effects of dietary L-theanine supplementation on apparent nutrient digestibility, milk yield, milk composition, and blood biochemical indices of dairy cows under heat stress. Thirty Chinese Holstein cows (19.84 ± 2.42 kg milk/d, 192.36 ± 40.77 d in milk and 2 ± 0.93 parities) were divided into 3 groups of 10 animals each. The control group was fed a basal total mixed ration (TMR) diet, while treatment 1 (LTA16) and treatment 2 (LTA32) groups were fed a basal TMR diet supplemented with L-theanine at 16 and 32 g/cow per day, respectively. The results showed that feeding the dairy cows with LTA16 treatment decreased ( < 0.05) their rectal temperature, whereas feeding with LTA32 treatment decreased ( < 0.05) their rumen fluid ammonia nitrogen content. In comparison to the control group, the supplementation of L-theanine had no significant effect ( > 0.05) on the dry matter intake, nutrient digestibility, total volatile fatty acid (TVFA) concentration and molar proportion of volatile fatty acid, milk yield, milk composition, feed efficiency and antioxidant capacity of the dairy cows. The triglyceride (TG) content of the LTA32 group was significantly greater ( = 0.014) than that of the control group. With the increase in L-theanine dosage, the serum cholesterol (CHOL) content significantly increased ( = 0.013). The serum albumin (ALB;  = 0.067), low-density lipoprotein cholesterol (LDL-C;  = 0.053), and high-density lipoprotein cholesterol (HDL-C;  = 0.067) contents showed an upward trend as L-theanine dosage increased. Ultimately, the results of this study show that supplementing dairy cow diet with L-theanine could decrease dairy cow rectal temperature, affect lipid metabolism, and potentially relieve the heat stress of dairy cows to some extent. 10.1016/j.aninu.2022.08.002
Co-administration of l-cystine and l-theanine enhances efficacy of influenza vaccination in elderly persons: nutritional status-dependent immunogenicity. Miyagawa Koichi,Hayashi Yoshimitsu,Kurihara Shigekazu,Maeda Akiko Geriatrics & gerontology international AIM:The immune response to influenza vaccine is attenuated in elderly persons, though they are at greatest risk for morbidity and mortality by influenza virus infection. Experimental studies demonstrate that co-administration of l-cystine and l-theanine enhanced antigen-specific production of immunoglobulin in aged mice infected with influenza virus. We thus investigated the effect of l-cystine and l-theanine on antibody induction by influenza vaccines in elderly persons. METHODS:Residents in a nursing home were randomly allocated to l-cystine and l-theanine (n = 32) or placebo (n = 33). The test substances were administered p.o. for 14 days before immunization. Serum influenza virus antibody titers were measured before and 4 weeks after vaccination. RESULTS:Vaccination significantly elevated hemagglutination inhibition (HI) titers for all the three strains of influenza viruses (A/New Caledonia [H1N1], A/New York [H3N2] and B/Shanghai) in both groups. HI titers after vaccination were not significantly different between the two groups for either strain. Also, the seroconversion rate was not significantly different between the two groups in the aggregate. A stratified analysis showed that the rate of seroconversion was significantly greater in the l-cystine and l-theanine group compared with the placebo group for influenza virus A (H1N1) among subjects with low serum total protein (63% vs 10%, P < 0.05) or low hemoglobin (71% vs 9%, P < 0.05). CONCLUSION:Co-administration of l-cystine and l-theanine before vaccination may enhance the immune response to influenza vaccine in elderly subjects with low serum total protein or hemoglobin. 10.1111/j.1447-0594.2008.00483.x
Combined administration of (L)-cystine and (L)-theanine enhances immune functions and protects against influenza virus infection in aged mice. Takagi Yasuhiro,Kurihara Shigekazu,Higashi Natsumi,Morikawa Saeko,Kase Tetsuo,Maeda Akiko,Arisaka Harumi,Shibahara Susumu,Akiyama Yukio The Journal of veterinary medical science Cell-mediated and humoral immune responses are attenuated with aging. Intracellular glutathione (GSH) levels also decrease with aging. Previously, we have reported that combined administration of (L)-cystine and (L)-theanine enhances antigen-specific IgG production, partly through augmentation of GSH levels and T helper 2-mediated responses in 12-week-old mice. These findings suggest that combined administration of (L)-cystine and (L)-theanine to aged mice improves immune responses via increase of GSH synthesis. Here, we examined the effects of combined administration of (L)-cystine and (L)-theanine on antigen-specific antibody production and influenza virus infection in aged mice. Combined administration of these amino acids for 14 days before primary immunization significantly enhanced the serum antigen-specific IgM and IgG levels in 24-month-old mice. Furthermore, 13-month-old mice co-treated with these amino acids orally for 10 days had significantly lower lung viral titers than controls at 6 days after influenza virus infection. In addition, this co-treatment also significantly prevented the weight loss associated with infection. Enhancement of anti-influenza-virus IgG antibodies by combined administration of (L)-cystine and (L)-theanine was seen 10 days after infection. The significantly elevated serum interleukin-10/interferon-gamma ratio and gamma-glutamylcysteine synthetase mRNA expression, which is the rate-limiting enzyme of GSH synthesis, in the spleen 3 days after infection may have contributed to the observed beneficial effects. These results suggest that combined administration of (L)-cystine and (L)-theanine enhances immune function and GSH synthesis which are compromised with advanced age, and may become a useful strategy in healthy aging. 10.1292/jvms.09-0067
Neuroprotective effect of -theanine in a rat model of chronic constriction injury of sciatic nerve-induced neuropathic pain. Chen Shu-Mei,Wang Mao-Hsien,Soung Hung-Sheng,Tseng Hsiang-Chien,Fang Chih-Hsiang,Lin Yi-Wen,Yang Chih-Chuan,Tsai Cheng-Chia Journal of the Formosan Medical Association = Taiwan yi zhi BACKGROUND/PURPOSE:We investigated the protective efficacy of -theanine (LT), the major amino acid components of green tea, on chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain (NP) development and neuronal functional changes in rats. METHODS:Rats with NP induced by CCI of the left sciatic nerve and sham-operated rats received LT or saline solution, with pain sensitive tests of thermal hyperalgesia and mechanical allodynia. Motor and sensory nerve conduction velocities were measured after surgery. Subsequently, the rats were sacrificed; the sciatic nerve was excised, homogenized, prepared and subjected for estimation of nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), myeloperoxidase (MPO), and caspase-3. RESULTS:CCI produced a significant increase in hyperalgesia and allodynia, an increase in SFI, a decrease in nerve conduction velocity, increases in NO, MDA, TNF-α, IL-1β, IL-6, MPO, and caspase-3 levels, as well as reduction of GSH, SOD, and CAT in the rat sciatic nerve. LT treatment significantly and dose-dependently alleviated CCI-induced nociceptive pain thresholds and ameliorated abnormal nerve conduction and functional loss in rats with CCI. Moreover, LT treatment reduced NO and MDA levels, increased antioxidative strength, and markedly suppressed the levels of neuroinflammatory and apoptotic markers in injured sciatic nerves. CONCLUSION:This is the first report on the ameliorative effect of LT in CCI-induced NP in rats. This effect might be attributed to its anti-oxidative, anti-inflammatory, anti-apoptotic, and neuroprotective, thus making it potentially useful as an adjuvant to conventional treatment. 10.1016/j.jfma.2021.08.023
Dynamic Observation of the Effect of L-Theanine on Cerebral Ischemia-Reperfusion Injury Using Magnetic Resonance Imaging under Mathematical Model Analysis. Journal of healthcare engineering This study was to use the partial differential mathematical model to analyze the magnetic resonance imaging (MRI) images of cerebral ischemia-reperfusion injury (CIRI) and to dynamically observe the role of L-theanine in CIRI based on this. 30 patients with cerebral ischemia in a hospital in a certain area were selected and divided into a cerebral ischemia group and a L-theanine treatment group. The two groups of patients were examined by MRI within 48 hours, and the relative apparent diffusion coefficient (rADC) of the cerebral ischemic part of the patients was determined. The partial differential mathematical model was used for data processing to obtain the function of cerebral ischemia time and infarct area, and the data of patients in the cerebral ischemia group and L-theanine treatment group were compared and analyzed. The results showed that the partial differential mathematical model could effectively analyze the linear relationship between the rADC value and time in the treatment of CIRI using L-theanine. The rADC values of the four points of interest in the L-theanine treatment group all increased with time, and there was a positive correlation between the variables and . In observing the efficacy indicators of L-theanine, the L-theanine treatment group showed a significant advantage in the neurospecific enolase (NSE) content compared with the cerebral ischemia group ( < 0.01), and the neurological function score of the L-theanine treatment group gradually decreased and showed a statistically obvious difference on the 7 day of treatment ( < 0.05). In summary, it was verified in this study that the role of L-theanine in the treatment of CIRI was of a great and positive significance for the subsequent treatment of patients with cerebral ischemia, providing reliable theoretical basis and data basis for clinical treatment of CIRI. 10.1155/2021/5679665
The Effect of L-Theanine Incorporated in a Functional Food Product (Mango Sorbet) on Physiological Responses in Healthy Males: A Pilot Randomised Controlled Trial. Williams Jackson,McKune Andrew J,Georgousopoulou Ekavi N,Kellett Jane,D'Cunha Nathan M,Sergi Domenico,Mellor Duane,Naumovski Nenad Foods (Basel, Switzerland) Consumption of L-Theanine (L-THE) has been associated with a sensation of relaxation, as well as a reduction of stress. However, these physiological responses have yet to be elucidated in humans where L-THE is compared alongside food or as a functional ingredient within the food matrix. The aim of this study was to determine the physiological responses of a single intake of a potential functional food product (mango sorbet) containing L-THE (ms-L-THE; 200 mgw/) in comparison to a flavour and colour-matched placebo (ms). Eighteen healthy male participants were recruited in this randomised, double-blind, placebo-controlled trial. The participants were required to consume ms-L-THE or placebo and their blood pressure (BP) (systolic and diastolic), heart rate (HR), and heart rate variability (HRV) were monitored continuously over 90 minutes. Eleven males (age 27.7 ± 10.8 years) completed the study. Changes in area under the curve for systolic and diastolic blood pressure and HRV over the 90 minute observation period indicated no differences between the three conditions (all > 0.05) or within individual groups (all 0.05). The values for heart rate were also not different in the placebo group ( = 0.996) and treatment group ( = 0.066), while there was a difference seen at the baseline ( = 0.003). Based on the findings of this study, L-THE incorporated in a food matrix (mango sorbet) demonstrated no reduction in BP or HR and showed no significant parasympathetic interaction as determined by HRV high-frequency band and low-frequency/high-frequency ratio. Further studies should be focussed towards the comparison of pure L-THE and incorporation within the food matrix to warrant recommendations of L-THE alongside food consumption. 10.3390/foods9030371
Potential role of green tea amino acid l-theanine in the activation of innate immune response by enhancing expression of cytochrome b responsible for the reactive oxygen species-generating ability of leukocytes. Microbiology and immunology l-Theanine (N-ethyl- l-glutamine) is an analog of l-glutamine and l-glutamic acid, accounts for up to 50% of all free amino acids in green tea, and elicits an umami taste. As l-theanine also shows various physiological activities including immune response-modifying activities, it is expected to be an excellent health-promoting phytochemical agent. To know the influences of l-theanine on the human innate immune response, we investigated the effect of l-theanine on the superoxide anion (O )-generating system of leukocytes using U937 cells. The O -generating system in leukocytes consists of membrane cytochrome b protein (a complex of p22-phox and gp91-phox proteins) and cytosolic p40-phox, p47-phox, and p67-phox proteins. Addition of 500 μM l-theanine caused remarkable enhancement of the all-trans retinoic acid (ATRA)-induced O -generating activity (to ~470% of ATRA-treated cells), but not l-glutamine and l-glutamic acid. Semiquantitative RT-PCR showed that the transcription level of gp91-phox is significantly increased in ATRA and l-theanine-co-treated cells. Chromatin immunoprecipitation revealed that l-theanine enhances acetylations of Lys-9 and Lys-14 residues of histone H3 within the chromatin surrounding the promoter region of the gp91-phox gene. Immunoblotting demonstrated that membrane cytochrome b proteins remarkably accumulate in ATRA +  l-theanine-treated cells. These results suggested that l-theanine brings about a remarkable accumulation of cytochrome b protein via upregulating the transcription of the gp91-phox gene during leukocyte differentiation, resulting in marked augmentation of the O -generating ability, which is one of the most important functions of leukocytes responsible for the innate immune system. 10.1111/1348-0421.12977
Effect of l-theanine tablets in reducing stress-related emotional signs in cats: an open-label field study. Dramard V,Kern L,Hofmans J,Rème C A,Nicolas C S,Chala V,Navarro C Irish veterinary journal BACKGROUND:L-theanine is an aminoacid found in tea leaves which has relaxing effects in humans and animals. It is a structural analogue of glutamate which can bind glutamate receptors. Although the relaxing action of L-theanine has been shown in humans, laboratory animals and dogs, it has never been published in cats. The goal of this open-label, multicentre and prospective trial was to determine whether an L-theanine based oral supplement (Anxitane®, Virbac, France) could attenuate manifestations of stress in cats under field conditions. CASE PRESENTATION:Thirty-three privately owned cats presenting signs associated with stress or fear (inappropriate urination/defecation, fear-induced aggressiveness, hypervigilance/tenseness or physical/functional manifestations of stress) for at least 1 month, were included in the study. They were given L-theanine (Anxitane®, 25 mg twice a day) for 30 days and 20 stress-related parameters were scored at Days 0, 15 and 30. The evolution of some parameters was also rated relative to Day 0. All median scores of the 20 parameters were significantly reduced at D30, and 30/33 cats (91%) had a reduced global score at the end of the study, including 21/33 with ≥50% score reduction. The median (IQR) global scores went from 18 (13-23) at D0 to 11 (8-13) at D15 and 5 (3-12) at D30 ( < 0.0001; Friedman test; significant reduction starting from D15). All the stress-related signs were significantly improved compared to D0, according to the owners, especially inappropriate elimination. Tablet palatability was judged good or very good in 94% of cases with spontaneous intake by cats when given by hand or in food. Tolerance was satisfactory as well, and no side effects were reported, so that most owners (27/33; 82%) were satisfied with the product. CONCLUSIONS:Despite the lack of a placebo group, it can be concluded that L-theanine (Anxitane®) helped to improve the undesirable manifestations of stress in cats in as soon as 15 days, though better results could be seen after 30 days of administration. These encouraging results show that L-theanine can help manage stress-related behaviour, but additional trials with a placebo group should be run to confirm this effect. 10.1186/s13620-018-0130-4
Synaptic modification by L-theanine, a natural constituent in green tea, rescues the impairment of hippocampal long-term potentiation and memory in AD mice. Zhu Guoqi,Yang Sanjuan,Xie Zhongwen,Wan Xiaochun Neuropharmacology Synaptic refinement improves synaptic efficiency, which provides a possibility to improve memory in Alzheimer's disease (AD). In the current study, we aimed to investigate the role of L-theanine, a natural constituent in green tea, in hippocampal synaptic transmission and to assess its potential to improve memory in transgenic AD mice. Initially, we found that L-theanine bath application facilitated hippocampal synaptic transmission and reduced paired-pulse facilitation (PPF). These effects were blocked by antagonists of N-methyl-D-aspartic acid receptors and the dopamine D1/5 receptor, and a selective protein kinase A (PKA) inhibitor. Moreover, L-theanine enhanced PKA phosphorylation via dopamine D1/5 receptor activation. L-theanine did not influence hippocampal long-term potentiation (LTP) in the slices obtained from wild-type mice, but rescued the impairment of hippocampal LTP in AD mice. Importantly, systemic application of L-theanine also improved memory and hippocampal LTP in AD mice. Our results demonstrate that L-theanine administration promotes hippocampal dopamine and noradrenaline release, and stimulates PKA phosphorylation. Moreover, the rescued hippocampal LTP in AD mice could be impaired by a PKA inhibitor. Our data reveal that L-theanine ameliorates the impairment of memory and hippocampal LTP in AD mice, likely through dopamine D1/5 receptor-PKA pathway activation. These data warrant the consideration of L-theanine as a candidate for the treatment of AD. 10.1016/j.neuropharm.2018.06.030
Nonaqueous fractionation and overexpression of fluorescent-tagged enzymes reveals the subcellular sites of L-theanine biosynthesis in tea. Fu Xiumin,Liao Yinyin,Cheng Sihua,Xu Xinlan,Grierson Don,Yang Ziyin Plant biotechnology journal l-Theanine is a specialized metabolite in the tea (Camellia sinensis) plant which can constitute over 50% of the total amino acids. This makes an important contribution to tea functionality and quality, but the subcellular location and mechanism of biosynthesis of l-theanine are unclear. Here, we identified five distinct genes potentially capable of synthesizing l-theanine in tea. Using a nonaqueous fractionation method, we determined the subcellular distribution of l-theanine in tea shoots and roots and used transient expression in Nicotiana or Arabidopsis to investigate in vivo functions of l-theanine synthetase and also to determine the subcellular localization of fluorescent-tagged proteins by confocal laser scanning microscopy. In tea root tissue, the cytosol was the main site of l-theanine biosynthesis, and cytosol-located CsTSI was the key l-theanine synthase. In tea shoot tissue, l-theanine biosynthesis occurred mainly in the cytosol and chloroplasts and CsGS1.1 and CsGS2 were most likely the key l-theanine synthases. In addition, l-theanine content and distribution were affected by light in leaf tissue. These results enhance our knowledge of biochemistry and molecular biology of the biosynthesis of functional tea compounds. 10.1111/pbi.13445
RNA-Sequencing Analysis Reveals l-Theanine Regulating Transcriptional Rhythm Alteration in Vascular Smooth Muscle Cells Induced by Dexamethasone. Wang Ruru,Xiao Menchao,Zhang Yujing,Ho Chi-Tang,Wan Xiaochun,Li Daxiang,Xie Zhongwen Journal of agricultural and food chemistry l-Theanine, a unique amino acid in tea leaves, is known to have beneficial effects on stress relief, tumor suppression, and prevention of hypertension and cardiovascular diseases (CADs). The disruption of the circadian rhythm has been implied in the pathogenesis of CADs. However, it is unknown whether l-theanine has a modulatory effect on the vascular circadian rhythm. In this research, we have established a circadian gene expression model in rat vascular smooth muscle cells by dexamethasone induction. l-Theanine treatment enhanced the expression amplitude of clock genes, including Bmal1, Cry1, Rev-erbα, and Per2. Moreover, pairwise comparisons of the RNA-sequencing data showed that l-theanine is able to upregulate a ray of the rhythm genes and differentially expressed genes that are involved in vasoconstriction and actin cytoskeleton regulation pathways. Our data suggest that l-theanine changes the circadian gene rhythm involving in the process of vascular smooth muscle restructure. 10.1021/acs.jafc.8b05057
Development and Application of a Fast Gas Chromatographic Method Offer New Insights into l-theanine Production Regulation in L. Chen Yanni,Liu Shuoqian,Ferreira Jorge Freire da Silva,Xiao Lizheng,Gu Meiyi,Luo Yiping,Zhang Tiantian,Zhang Xiangqin,Liu Zhonghua,Huang Jianan,Tian Na Journal of agricultural and food chemistry Tea is the most consumed beverage worldwide, and l-theanine in tea leaves significantly affects their flavor and market quality. We have developed and validated a fast and reliable gas chromatographic method with flame ionization detection (GC-FID) to quantify l-theanine after its extraction from (tea plant) and derivatization. The procedure was completed in 40 min, from extraction to chromatographic analysis, with a recovery rate of more than 93% and allowing a high sample throughput. The GC-FID intraday precision was within 0.57-2.28%, while the interday precision ranged from 1.57 to 13.48%. The intraday accuracy ranged from -6.84 to 5.26%, while the interday accuracy ranged from -1.08 to 3.12%. The limit of detection was 2.28 μg/mL, and the limit of quantification was 6.47 μg/mL. The GC-FID method was validated by high-performance liquid chromatography with UV detection (HPLC-UV) and was used to investigate the biosynthesis and regulation of l-theanine in tea plants. We found that plants fed with ethylamine significantly increased l-theanine concentrations in roots, while exogenous supplementation of glutamic acid, carbamide, and glutamine did not significantly affect the l-theanine level in roots. Our results also indicated that roots were not indispensable for the biosynthesis of l-theanine, which was detected in undifferentiated embryonic calluses in concentrations (g/100 g dry weight) as high as in leaves of whole plants (1.67 and 1.57%, respectively) and without any exogenous theanine precursor supplementation. 10.1021/acs.jafc.1c04093
Effects of Dietary L-Theanine on Growth Performance, Antioxidation, Meat Quality, and Intestinal Microflora in White Feather Broilers With Acute Oxidative Stress. Frontiers in veterinary science In order to reduce the negative effects caused by oxidative stress on broilers, it is particularly important to find ways to alleviate oxidative stress. As a natural plant extract, L-theanine has a variety of biological effects, such as improving antioxidant capacity, promoting growth, and enhancing immunity and antitumor. This trial evaluated the effects of dietary supplementation of L-theanine on growth performance, antioxidation, meat quality, and intestinal microflora in 817 White Feather Broilers. A total of 108 21-day-old 817 broilers with similar body weight (BW) were randomly divided into three groups with six replicates per group and six chickens within each replicate. The three groups were corn-soybean-based diet (NC group); basal diet plus drinking water with 30 mg hydrocortisone/kg (PC group); and basal diet supplemented with 400 mg L-theanine/kg plus drinking water with 30 mg hydrocortisone/kg (LT group). Compared with the NC group, from 21 to 24 days of age, the PC and LT groups had decreased BW, average daily gain (ADG), and average daily feed intake (ADFI), and increased feed to gain ratio (F/G; < 0.05). At 24 days of age, the LT group had improved superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum as compared to the NC group ( < 0.05). The LT group broilers also had significantly higher concentrations of malondialdehyde (MDA) in serum and liver ( < 0.05). On the 42nd days, the PC group had lower PH ( < 0.05) than the NC and LT groups and higher cooking loss and shear force ( < 0.05). Moreover, the villi height of the PC group was significantly lower in jejunum than the NC group ( < 0.05). The LT group had a higher ZO-1 content in duodenum than the NC and PC groups ( < 0.05). The activity of GSH-Px in the liver of the LT group was increased than in the PC group ( < 0.05). The relative abundance of in the LT group was significantly higher than in the NC and PC groups ( < 0.05). These results suggested that the effects of acute oxidative stress on growth performance and meat quality of broilers are continuous, and dietary supplementation of L-theanine could improve the growth performance and meat quality, enhance the intestinal mucosal barrier and antioxidant capacity, and improve the composition of the intestinal flora of broilers caused by acute oxidative stress. 10.3389/fvets.2022.889485
Synergistic effects of epigallocatechin gallate and l-theanine in nerve repair and regeneration by anti-amyloid damage, promoting metabolism, and nourishing nerve cells. Frontiers in nutrition Green tea has significant protective activity on nerve cells, but the mechanism of action is unclear. Epigallocatechin gallate (EGCG) and -ethyl-L-glutamine (L-theanine) are the representative functional components of green tea (). In this study, an AD model of Aβ-induced differentiated neural cell line PC12 cells was established to study the synergistic effect of EGCG and L-theanine in protecting neural cells. The results showed that under Aβ stress conditions, mitochondria and axons degenerated, and the expression of cyclins was up-regulated, showing the gene and protein characteristics of cellular hyperfunction. EGCG + L-theanine inhibited inflammation and aggregate formation pathways, significantly increased the percentage of G0/G1 in the cell cycle, downregulated the expression of proteins such as p-mTOR, Cyclin D1, and Cyclin B1, upregulated the expression of GAP43, Klotho, p-AMPK, and other proteins, promoted mitochondrial activity and energy metabolism, and had repair and regeneration effects on differentiated nerve cells. The synergistic mechanism study showed that under the premise that EGCG inhibits amyloid stress and inflammation and promotes metabolism, L-theanine could play a nourish nerve effect. EGCG + L-theanine keeps differentiated nerve cells in a quiescent state, which is beneficial to the repair and regeneration of nerve cells. In addition, EGCG + L-theanine maintains the high-fidelity structure of cellular proteins. This study revealed for the first time that the synergistic effect of EGCG with L-theanine may be an effective way to promote nerve cell repair and regeneration and slow down the progression of AD. Our findings provide a new scientific basis for the relationship between tea drinking and brain protection. 10.3389/fnut.2022.951415
Contribution of l-theanine to the formation of 2,5-dimethylpyrazine, a key roasted peanutty flavor in Oolong tea during manufacturing processes. Guo Xiangyang,Song Chuankui,Ho Chi-Tang,Wan Xiaochun Food chemistry l-Theanine, the most abundant amino acid in tea, is widely believed to be associated with the tea taste, however, its contribution to the formation of tea aroma is still unknown. Volatiles were determined and nitrogen-containing compounds formed during manufacturing processes were quantified. Lower levels of total sugar and l-theanine were detected in the Oolong tea product undergoing full fire processing (FFOT) suggesting that l-theanine probably involved in the volatile formation during manufacturing processes. Methylpyrazine and 2,5-dimethylpyrazine, two newly formed compounds in FFOT, together with other volatiles were successfully detected in a model thermal reaction of d-glucose and l-theanine (GT-MTR) but not detectable in thermal reactions with single d-glucose (G-MTR) or l-theanine (T-MTR). The concentration of 2,5-dimethylpyrazine increased significantly by adding additional l-theanine to 2nd roasted tea. Our study demonstrated that l-theanine, at least partly, contributed to the formation of 2,5-dimethylpyrazine, a key roasted peanutty flavor in Oolong tea. 10.1016/j.foodchem.2018.04.117
Protective effect of L-theanine on carbon tetrachloride-induced acute liver injury in mice. Jiang Wei,Gao Min,Sun Shuai,Bi Aijing,Xin Yinqiang,Han Xiaodong,Wang Liangbin,Yin Zhimin,Luo Lan Biochemical and biophysical research communications We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level as well as liver histopathological changes induced by CCl(4) in mice. L-theanine significantly prevented CCl(4)-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities. Our further studies demonstrated that L-theanine inhibited metabolic activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a consequence, L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-α and IL-1β in sera, and expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers. CCl(4)-induced activation of apoptotic related proteins including caspase-3 and PARP in mouse livers was also prevented by L-theanine treatment. In summary, L-theanine protects mice against CCl(4)-induced acute liver injury through inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis. 10.1016/j.bbrc.2012.05.022
Physiological effects of L-theanine on Drosophila melanogaster. Yang Hui,Li Wenzhe,Yu Huiyi,Yuan Ruiqi,Yang Yang,Pung Kingston,Li Ping,Xue Lei Molecules (Basel, Switzerland) Green tea has been consumed as the most popular drink in East Asia for centuries, and is believed to have a wide range of health benefits. L-Theanine, the major component of the free amino acids in green tea, has been reported to display neuronal protection and tumor inhibition in vitro, but its physiological effects on animal development and behavior remain elusive. In this report, we used Drosophila melanogaster, the fruit fly, as a model organism to investigate the physiological effects of L-theanine. Flies were fed with three different concentrations of theanine as a dietary supplement after eclosion, and were examined for a variety of physiological parameters at different time points. We found theanine treatment results in significantly increased locomotion and courtship ability, and decreased resistance against wet and dry starvation in males, but not in females. Furthermore, theanine application diminished UV tolerance in females, but not in males. However, we did not perceive distinguishable effect of theanine on animal development, life span, weight, and tolerance of heat and anoxia. This work represents the first comprehensive physiological investigation of L-theanine at the whole animal level, and shall shed light on the mechanistic study of theanine in the future. 10.3390/molecules181113175
l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways. Kim Tae Il,Lee Yong Kyung,Park Sang Gi,Choi Im Seop,Ban Jung Ok,Park Hyoung Kook,Nam Sang-Yoon,Yun Young Won,Han Sang Bae,Oh Ki Wan,Hong Jin Tae Free radical biology & medicine Amyloid beta (Abeta)-induced neurotoxicity is a major pathological mechanism of Alzheimer disease (AD). In this study, we investigated the inhibitory effect of l-theanine, a component of green tea (Camellia sinensis), on Abeta(1-42)-induced neuronal cell death and memory impairment. Oral treatment of l-theanine (2 and 4 mg/kg) for 5 weeks in the drinking water of mice, followed by injection of Abeta(1-42) (2 microg/mouse, icv), significantly attenuated Abeta(1-42)-induced memory impairment. Furthermore, l-theanine reduced Abeta(1-42) levels and the accompanying Abeta(1-42)-induced neuronal cell death in the cortex and hippocampus of the brain. Moreover, l-theanine inhibited Abeta(1-42)-induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase as well as the activity of nuclear factor kappaB (NF-kappaB). l-Theanine also significantly reduced oxidative protein and lipid damage and the elevation of glutathione levels in the brain. These data suggest that the positive effects of l-theanine on memory may be mediated by suppression of ERK/p38 and NF-kappaB as well as the reduction of macromolecular oxidative damage. Thus, l-theanine may be useful in the prevention and treatment of AD. 10.1016/j.freeradbiomed.2009.09.008
Protective Effect of L-Theanine on Cadmium-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondria-Mediated Pathway. Ben Peiling,Zhang Zhengping,Xuan Chunxia,Sun Shasha,Shen Lei,Gao Yanhong,Cao Xiang,Zhou Yi,Lan Lei,Yin Zhimin,Luo Lan Neurochemical research L-Theanine is an amino acid derivative from green tea. The present work was aimed at the effect of L-theanine on neuron-like rat pheochromocytoma (PC12) cells stimulated with cadmium chloride. Treatment with L-theanine before cadmium exposure increased cell viability; the experiments of Annexin V/PI staining indicated that L-theanine inhibited cadmium-induced cell apoptosis. Meanwhile, L-theanine decreased ROS production and protected from cadmium-induced disruption of mitochondrial transmembrane potential. Compared with cadmium-treated cells, L-theanine could also decrease the ratio of Bax/Bcl-2, as well as the level of cleaved caspase-9, caspase-3 and poly(ADP-ribose) polymerase. Furthermore, L-theanine depresses cadmium-induced up regulation of phosphorylations of PI3K/Akt, MAPK ERK1/2, and JNK signaling. These data suggest that L-theanine pretreatment reduces severity of cadmium toxicity probably via antioxidant action. Therefore, it may be concluded that L-theanine could be exploited for prevention of cadmium-induced diseases. 10.1007/s11064-015-1648-4
A high-throughput dual system to screen polyphosphate kinase mutants for efficient ATP regeneration in L-theanine biocatalysis. Biotechnology for biofuels and bioproducts ATP, an important cofactor, is involved in many biocatalytic reactions that require energy. Polyphosphate kinases (PPK) can provide energy for ATP-consuming reactions due to their cheap and readily available substrate polyphosphate. We determined the catalytic properties of PPK from different sources and found that PPK from Cytophaga hutchinsonii (ChPPK) had the best catalytic activity for the substrates ADP and polyP. An extracellular-intracellular dual system was constructed to high-throughput screen for better catalytic activity of ChPPK mutants. Finally, the specific activity of ChPPK mutant was increased by 4.3 times. Therefore, we focused on the production of L-theanine catalyzed by GMAS as a model of ATP regeneration. Supplying 150 mM ATP, GMAS enzyme could produce 16.8 ± 1.3 g/L L-theanine from 100 mM glutamate. When 5 mM ATP and 5 U/mL ChPPK were added, the yield of L-theanine was 16.6 ± 0.79 g/L with the conversion rate of 95.6 ± 4.5% at 4 h. Subsequently, this system was scaled up to 200 mM and 400 mM glutamate, resulting in the yields of L-theanine for 32.3 ± 1.6 g/L and 62.7 ± 1.1 g/L, with the conversion rate of 92.8 ± 4.6% and 90.1 ± 1.6%, respectively. In addition, we also constructed an efficient ATP regeneration system from glutamate to glutamine, and 13.8 ± 0.2 g/L glutamine was obtained with the conversion rate of 94.4 ± 1.4% in 4 h after adding 6 U/ mL GS enzyme and 5 U/ mL ChPPK, which further laid the foundation from glutamine to L-theanine catalyzed by GGT enzyme. This proved that giving the reaction an efficient ATP supply driven by the mutant enzyme enhanced the conversion rate of substrate to product and maximized the substrate value. This is a positively combination of high yield, high conversion rate and high economic value of enzyme catalysis. The mutant enzyme will further power the ATP-consuming biocatalytic reaction platform sustainably. 10.1186/s13068-023-02361-9
The R2R3-MYB transcription factor CsMYB73 negatively regulates l-Theanine biosynthesis in tea plants (Camellia sinensis L.). Wen Beibei,Luo Yong,Liu Dongmin,Zhang Xiangna,Peng Zhong,Wang Kunbo,Li Juan,Huang Jianan,Liu Zhonghua Plant science : an international journal of experimental plant biology l-Theanine, a non-proteinaceous amino acid abundantly present in tea (Camellia sinensis), contributes to the umami flavor of tea and has beneficial effects on human health. While key l-theanine biosynthetic genes have been well documented, their transcriptional regulation remains poorly understood. In this study, we determined the l-theanine contents in tea leaves of two cultivars at three developmental stages and investigated the expression patterns of the l-theanine biosynthetic genes CsGS1 and CsGS2. Additionally, we identified an R2R3-MYB transcription factor, CsMYB73, belonging to subgroup 22 of the R2R3-MYB family. CsMYB73 expression negatively correlated with l-theanine accumulation during leaf maturation. We found that CsMYB73, as a nuclear protein, binds to the promoter regions of CsGS1 and CsGS2 via MYB recognition sequences and represses the transcription of CsGS1 and CsGS2 in tobacco leaves. Collectively, our results demonstrate that CsMYB73 is a transcriptional repressor involved in l-theanine biosynthesis in tea plants. Our findings might contribute to future tea plant breeding strategies. 10.1016/j.plantsci.2020.110546
Fabrication of poly(D, L-lactic acid) nanoparticles as delivery system for sustained release of L-theanine. Ravi Chandrika,Zaved Ahmed Khan,Abul Kalam Azad Mandal IET nanobiotechnology L-theanine is present in tea as a unique, free, non-protein amino acid. Due to various beneficial effects on brain activity, it is widely used as a nutraceutical. After consumption, it is rapidly absorbed and metabolised followed by excretion through urine. Therefore, the authors developed an L-theanine delivery system by encapsulating into polymeric nanoparticles to release it slowly and make it available for a longer period of time. Poly(D, L-lactic acid) nanoparticle (PLANP) was fabricated by the double emulsion method and L-theanine was encapsulated into it (PLANP-T). Spherical nanoparticles with a hydrodynamic diameter of 247 and 278 nm and surface charge of -14.5 and -25.7 mV for PLANP and PLANP-T, respectively, were fabricated. The Fourier transform infrared spectroscopic data indicated encapsulation of L-theanine into PLANP. The PLANP showed high L-theanine encapsulation capacity (71.65%) with a sustained release character. The maximum release (66.3%) of L-theanine was recorded in pH 7.3 at 48 h. The release kinetics followed the Higuchi model and the release mechanism was determined as super case-II transport (erosion). This slow release will make it available to the target tissue for a longer period of time (sustain release effect) and will also avoid immediate metabolism and clearance from the circulation. 10.1049/iet-nbt.2018.5248
Effects of L-theanine on anxiety-like behavior, cerebrospinal fluid amino acid profile, and hippocampal activity in Wistar Kyoto rats. Ogawa Shintaro,Ota Miho,Ogura Jun,Kato Koichi,Kunugi Hiroshi Psychopharmacology RATIONALE AND OBJECTIVES:The amino acid L-theanine (N-ethyl-L-glutamine) has historically been considered a relaxing agent. In the present study, we examined the effects of repeated L-theanine administration on behavior, levels of amino acids in the cerebrospinal fluid (CSF), and hippocampal activity in Wistar Kyoto (WKY) rats, an animal model of anxiety and depressive disorders. METHODS:Behavioral tests were performed after 7-10 days of L-theanine (0.4 mg kg day) or saline administration, followed by CSF sampling for high-performance liquid chromatography (HPLC) analysis. An independent set of animals was subjected to [F]fluorodeoxyglucose positron emission tomography (PET) scanning after the same dose of L-theanine or saline administration for 7 days. RESULTS:In the elevated plus maze test, the time spent in the open arms was significantly longer in the L-theanine group than in the saline group (P = 0.035). In addition, significantly lower CSF glutamate (P = 0.039) and higher methionine (P = 0.024) concentrations were observed in the L-theanine group than in the saline group. A significant increase in the standard uptake value ratio was observed in the hippocampus/cerebellum of the L-theanine group (P < 0.001). CONCLUSIONS:These results suggest that L-theanine enhances hippocampal activity and exerts anxiolytic effects, which may be mediated by changes in glutamate and methionine levels in the brain. Further study is required to more fully elucidate the mechanisms underlying the effects of L-theanine. 10.1007/s00213-017-4743-1
L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness. Einöther Suzanne J L,Martens Vanessa E G,Rycroft Jane A,De Bruin Eveline A Appetite Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of L-theanine (97 mg) and caffeine (40 mg) to a placebo on two attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption. The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo, while subjective alertness and intersensory attention were not improved significantly. The results support previous evidence that L-theanine and caffeine in combination can improve attention. 10.1016/j.appet.2010.01.003
Effect of dietary L-theanine supplementation on skeletal muscle fiber type transformation in weaning piglets. Animal biotechnology The aim of this study was to explore the effect of dietary L-theanine (LT) supplementation on skeletal muscle fiber type transformation in weaning piglets. Our data showed that LT significantly increased the slow-twitch fiber-related genes expression and the percentage of slow oxidative fiber, and decreased the MyHC IIb mRNA expression and the percentage of fast glycolytic fiber. In addition, LT significantly increased the succinic dehydrogenase (SDH) and malate dehydrogenase (MDH) activities and increased the LDH activities. In addition, LT significantly affected mitochondrial biogenesis and function and antioxidative related genes expression, and increased the protein expression of p-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear factor E2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) and decreased the Keap1 protein levels. Furthermore, our data indicated that LT significantly increased the mRNA and protein expression of prospero-related homeobox 1 (Prox1), calcineurin A (CnA), and NFATc1, suggesting that dietary LT supplementation promoted skeletal muscle fiber transition from types II to I might be via activation of calcineurin signaling pathway. Taken together, these findings suggested that LT promoted the transformation of muscle fiber types from slow oxidative to fast glycolytic by increasing antioxidant capacity and improving mitochondrial biogenesis and function and activation of calcineurin signaling pathway. 10.1080/10495398.2022.2078725
L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. Ritsner Michael S,Miodownik Chanoch,Ratner Yael,Shleifer Tatyana,Mar Maria,Pintov Leonid,Lerner Vladimir The Journal of clinical psychiatry OBJECTIVE:L-theanine is a unique amino acid present almost exclusively in the tea plant. It possesses neuroprotective, mood-enhancing, and relaxation properties. This is a first study designed to evaluate the efficacy and tolerability of L-theanine augmentation of antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder. METHOD:60 patients with DSM-IV schizophrenia or schizoaffective disorder participated in an 8-week, double-blind, randomized, placebo-controlled study. 400 mg/d of L-theanine was added to ongoing antipsychotic treatment from February 2006 until October 2008. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), the Hamilton Anxiety Rating Scale (HARS), the Cambridge Neuropsychological Test Automated Battery (CANTAB) for neurocognitive functioning, and additional measures of general functioning, side effects, and quality of life. RESULTS:40 patients completed the study protocol. Compared with placebo, L-theanine augmentation was associated with reduction of anxiety (P = .015; measured by the HARS scale) and positive (P = .009) and general psychopathology (P < .001) scores (measured by the PANSS 3-dimensional model). According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive (P = .004) and activation factor (P = .006) scores compared to placebo. The effect sizes (Cohen d) for these differences ranged from modest to moderate (0.09-0.39). PANSS negative and CANTAB task scores, general functioning, side effect, and quality of life measures were not affected by L-theanine augmentation. L-theanine was found to be a safe and well-tolerated medication. CONCLUSIONS:L-theanine augmentation of antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. Further long-term studies of L-theanine are needed to substantiate the clinically significant benefits of L-theanine augmentation. 10.4088/JCP.09m05324gre
Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Hidese Shinsuke,Ota Miho,Wakabayashi Chisato,Noda Takamasa,Ozawa Hayato,Okubo Tsutomu,Kunugi Hiroshi Acta neuropsychiatrica OBJECTIVE:l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. METHODS:Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). RESULTS:HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. CONCLUSION:Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects. 10.1017/neu.2016.33
Determination of l-theanine in tea water using fluorescence-visualized paper-based sensors based on CdTe quantum dots/corn carbon dots and nano-porphyrin with chemometrics. Chen Hengye,Wei Liuna,Guo Xiaoming,Hai Chengying,Xu Lu,Zhang Lei,Lan Wei,Zhou Chunsong,She Yuanbin,Fu Haiyan Journal of the science of food and agriculture BACKGROUND:The quality of tea is influenced by numerous factors, especially l-theanine, which is one of the important markers used to evaluate the sweetness and freshness of tea. Sensitive, rapid, and accurate detection of l-theanine is therefore useful to identify the grade and quality of tea. RESULTS:A high-sensitivity, paper-based fluorescent sensor combined with chemometrics was established to detect l-theanine in tea water based on CdTe quantum dots / corn carbon dots and nano tetra pyridel-porphine zinc (ZnTPyP). To verify the reliability of this method, fluorescence spectra and fluorescence-visualized paper-based sensors were compared. The fluorescence spectrum method demonstrated a linear range of 1 to 10 000 nmol L and a limit of detection (LOD) of 0.19 nmol L . In the fluorescence-visualized paper-based sensors there was a linear range of 10-1000 nmol L , and the LOD was 10 nmol L . Partial least squares discriminant analysis (PLSDA) and partial least squares regression analysis (PLSR) were used successfully to determine l-theanine accurately in tea water with this approach. The accuracy of the PLSDA model was 100% both in the training set and the predicting set, and the correlation coefficient between the actual concentration and the predicted concentration was greater than 0.9997 in the PLSR model. CONCLUSION:This fluorescence-visualized paper-based sensor, combined with chemometrics, could be applied efficiently to the practical analysis of tea water samples, which provides a new idea to ensure the flavor and quality of tea. © 2020 Society of Chemical Industry. 10.1002/jsfa.10882
L-theanine elicits an umami taste with inosine 5'-monophosphate. Narukawa Masataka,Morita Kanako,Hayashi Yukako Bioscience, biotechnology, and biochemistry We investigated the taste synergy between L-theanine and the flavour enhancer, inosine 5'-monophosphate (IMP), by using a human sensory evaluation. When L-theanine was added to IMP, only the umami taste was enhanced. We then investigated this synergistic effect of L-theanine in mice by gustatory nerve recording. We confirmed the synergism between L-theanine and IMP for the umami taste. 10.1271/bbb.80328
Redesign of γ-glutamyl transpeptidase from Bacillus subtilis for high-level production of L-theanine by cavity topology engineering. Applied microbiology and biotechnology L-Theanine is a multifunctional nonprotein amino acid found naturally in tea leaves. It has been developed as a commercial product for a wide range of applications in the food, pharmaceutical, and healthcare industries. However, L-theanine production catalyzed by γ-glutamyl transpeptidase (GGT) is limited by the low catalytic efficiency and specificity of this class of enzymes. Here, we developed a strategy for cavity topology engineering (CTE) based on the cavity geometry of GGT from B. subtilis 168 (CGMCC 1.1390) to obtain an enzyme with high catalytic activity and applied it to the synthesis of L-theanine. Three potential mutation sites, M97, Y418, and V555, were identified using the internal cavity as a probe, and residues G, A, V, F, Y, and Q, which may affect the shape of the cavity, were obtained directly by computer statistical analysis without energy calculations. Finally, 35 mutants were obtained. The optimal mutant Y418F/M97Q showed a 4.8-fold improvement in catalytic activity and a 25.6-fold increase in catalytic efficiency. The recombinant enzyme Y418F/M97Q exhibited a high space-time productivity of 15.4 g L h by whole-cell synthesis in a 5 L bioreactor, which was one of the highest concentrations reported so far at 92.4 g L. Overall, this strategy is expected to enhance the enzymatic activity associated with the synthesis of L-theanine and its derivatives.Key points • Cavity topology engineering was used to modify the GGT for L-theanine biocatalysis. • The catalytic efficiency of GGT was increased by 25.6-fold. • Highest productivity of L-theanine reached 15.4 g L h (92.4 g L) in a 5 L bioreactor. 10.1007/s00253-023-12544-x
Characterization of L-theanine in tea extracts and synthetic products using stable isotope ratio analysis. Journal of food and drug analysis L-theanine involves a great number of health benefits and dietary supplements containing this molecule are becoming increasingly popular. There is, therefore, a growing need to find ways to discriminate between natural L-theanine extracted from tea leaves and the cheaper, synthetic one obtained using specific bacterial enzymes. A first attempt of stable isotope ratio analysis characterization of the possible synthetic adulterant L-theanine (δC of -14.3 ± 1.5‰), obtained from vegetable substrates with C4 photosynthetic cycle, and of the more expensive natural L-theanine (δC of -24.4 ± 1.3‰), extracted from Camellia sinensis plants with C3 photosynthetic cycle, is reported here. 10.38212/2224-6614.3349
L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway. Di X,Yan J,Zhao Y,Zhang J,Shi Z,Chang Y,Zhao B Neuroscience As a natural analogue of glutamate, l-theanine is the unique amino acid derivative in green tea. Although its underlining mechanisms are not yet clear, it has been suggested that l-theanine treatment may prove beneficial to patients with neurodegenerative diseases. In this study, we investigated the neuroprotective effect and its mechanism of l-theanine in an in vitro model of Alzheimer's disease by using the human APP (Swedish mutation) transgenic SH-SY5Y cell. Amyloid beta (Abeta) neurotoxicity was triggered by l-glutamate in this cell line. Additionally, l-theanine significantly attenuated l-glutamate-induced apoptosis at similar levels to those seen with the NMDA receptor inhibitor MK-801 in the stably expressing APP Swedish mutation SH-SY5Y cells which over-generated Abeta. Meanwhile, the activation of c-Jun N-terminal kinase and caspase-3 induced by l-glutamate was suppressed by l-theanine. We also found that cells treated with l-theanine showed decreased production of nitric oxide resulting from the down-regulated protein levels of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). These results indicate that the inhibition of the NMDA subtype of glutamate receptors and its related pathways is the crucial point of the neuroprotective effect of l-theanine in the cell model. Thus, our present study supports the notion that l-theanine may provide effective prophylaxis and treatment for Alzheimer's disease. 10.1016/j.neuroscience.2010.04.019
Protective Effects of L-Theanine on IPEC-J2 Cells Growth Inhibition Induced by Dextran Sulfate Sodium via p53 Signaling Pathway. Molecules (Basel, Switzerland) L-theanine is a nonprotein amino acid found in tea leaves and has been widely used as a safe food additive in beverages or foods because of its varied bioactivities. The aim of this study was to reveal the in vitro gastrointestinal protective effects of L-theanine in DSS-induced intestinal porcine enterocyte (IPEC-J2) cell models using molecular and metabolic methods. Results showed that 2.5% dextran sulfate sodium (DSS) treatment inhibited the cell proliferation of IPEC-J2 and blocked the normal operation of the cell cycle, while L-theanine pretreatment significantly preserved these trends to exert protective effects. L-theanine pre-treatment also up-regulated the EGF, CDC2, FGF2, Rb genes and down-regulated p53, p21 proliferation-related mRNA expression in DSS-treated cells, in accompany with p53 signaling pathway inhibition. Meanwhile, metabolomics analysis revealed that L-theanine and DSS treated IPEC-J2 cells have different metabolomic profiles, with significant changes in the key metabolites involved in pyrimidine metabolism and amino acid metabolism, which play an important role in nucleotide metabolism. In summary, L-theanine has a beneficial protection in DSS-induced IPEC-J2 cells via promoting proliferation and regulating metabolism disorders. 10.3390/molecules26227002
L-Theanine intake increases threshold for limbic seizures but decreases threshold for generalized seizures. Schallier Anneleen,Vermoesen Katia,Loyens Ellen,Van Liefferinge Joeri,Michotte Yvette,Smolders Ilse,Massie Ann Nutritional neuroscience L-Theanine, an ethylamide derivate of glutamate found in abundance in green tea, has been shown to exert beneficial actions in animal models for several neurological disorders. We here investigated for the first time the effect of L-theanine intake on seizure susceptibility using acute pilocarpine and pentylenetetrazol (PTZ) mouse models for studying, respectively, limbic seizures or primarily generalized seizures. Moreover, we studied the effect of l-theanine intake on extracellular hippocampal and cortical glutamate and gamma-aminobutyric acid (GABA) levels, using in vivo microdialysis. Feeding mice with a 4% L-theanine solution significantly decreased their susceptibility to pilocarpine-induced seizures whereas susceptibility to PTZ-induced seizures was increased. The latter effect was linked to decreased extracellular GABA concentrations in frontal cortex. 10.1179/1476830512Y.0000000033
The effects of L-theanine, caffeine and their combination on cognition and mood. Haskell Crystal F,Kennedy David O,Milne Anthea L,Wesnes Keith A,Scholey Andrew B Biological psychology L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone. 10.1016/j.biopsycho.2007.09.008
L-Theanine affects intestinal mucosal immunity by regulating short-chain fatty acid metabolism under dietary fiber feeding. Xu Wei,Lin Ling,Liu An,Zhang Tuo,Zhang Sheng,Li Yinhua,Chen Jinhua,Gong Zhihua,Liu Zhonghua,Xiao Wenjun Food & function To investigate the effects of l-Theanine (LTA) on intestinal mucosal immunity and the regulation of short-chain fatty acid (SCFA) metabolism under dietary fiber feeding, a 28-day feeding experiment was performed in Sprague-Dawley rats. The results show that LTA increased the proportion of Prevotella, Lachnospira, and Ruminococcus while increasing the total SCFA, acetic acid, propionic acid, and butyric acid contents in the feces. LTA also increased IgA, IgE, and IgG levels in the ileum, and increased villi height and crypt depth. Moreover, LTA upregulated the mRNA and protein expression of acetyl-CoA carboxylase 1, sterol element-binding protein 1c, fatty acid synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver, while downregulating the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the colon. Our study suggests that LTA can affect intestinal mucosal immunity by regulating SCFA metabolism under dietary fiber feeding. 10.1039/d0fo01069c
L-Theanine Improves Immunity by Altering TH2/TH1 Cytokine Balance, Brain Neurotransmitters, and Expression of Phospholipase C in Rat Hearts. Li Chengjian,Tong Haiou,Yan Qiongxian,Tang Shaoxun,Han Xuefeng,Xiao Wenjun,Tan Zhiliang Medical science monitor : international medical journal of experimental and clinical research BACKGROUND This study aimed to investigate the regulatory effects of L-theanine on secretion of immune cytokines, hormones, and neurotransmitters, and mRNA expression of phospholipase C (PLC) in rats, and to explore its regulatory mechanism in immune function. MATERIAL AND METHODS Sixty-four Sprague-Dawley rats received daily intragastric infusion of different doses of L-theanine solution [0, 50 (LT), 200 (MT), and 400 (HT) mg/kg BW]. Cytokines, immunoglobulins, and hormones in the serum, neurotransmitters, and mRNA expression of PLC in the relevant tissues were assayed. RESULTS L-theanine administration increased the splenic organ index and decreased the contents of ILs-4/6/10 and the ratio of IL-4/IFN-γ in the serum. High-dose L-theanine administration increased the levels of dopamine and 5-hydroxytryptamine in the pituitary and hippocampus, resulting in decrease in corticosterone level in the serum. L-theanine administration decreased the mRNA expressions of PLC isomers in the liver and PLC-γ1 and PLC-δ1 in the spleen. Interestingly, mRNA expressions of PLC-β1 in the spleen and PLC isomers mRNA in the heart were up-regulated by L-theanine administration. CONCLUSIONS Administration of 400 mg/kg BWL-theanine improved immune function of the rats by increasing the splenic weight, altering the Th2/Th1 cytokine balance, decreasing the corticosterone level in the serum, elevating dopamine and 5-hydroxytryptamine in the brain, and regulating the mRNA expression of PLC isomers in the heart. 10.12659/msm.897077
Protective Effect of L-Theanine on Haloperidol-Induced Orofacial. Chen Cheng-Neng,Chang Kuo-Chi,Wang Mao-Hsien,Tseng Hsiang-Chien,Soung Hung-Sheng The Chinese journal of physiology Tardive dyskinesia (TD) is a severe side effect of chronic neuroleptic treatment consisting ofabnormal involuntary movements, characterized by orofacial dyskinesia (OD). Haloperidol (HAL)-induced OD has been widely used as an animal model to study the neuropathophysiology of humanTD with its pathophysiology strongly associated with striatal oxidative stress. L-Theanine (LT), oneof the major amino acid components in green tea, has potent antioxidative effects and is able to protectagainst various oxidative injuries. In this study, we examined the potential protective effects of LTon HAL-induced behavioral and neurochemical dysfunction in rats. HAL treatment (1 mg/kg i.p.for 21 days) induced significant increases (P < 0.001) in the frequency of vacuous chewing movement(VCM) and tongue protrusion (TP) as well as the duration of facial twitching (FT). LT treatment (100,300 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of theHAL-induced OD. LT treatment was also able to reduce the lipid peroxidation (LPO) production, andenhance the antioxidation power in striatum from rats with HAL treatment. The above results indicatethat LT has a protective role against HAL-induced OD, probably via its powerful antioxidative properties.Thus, LT may have a clinically relevant therapeutic effect in delaying or treating TD. 10.4077/CJP.2018.BAG529
Effect of l-theanine on growth performance, intestinal development and health, and peptide and amino acid transporters expression of broilers. Zhang Cheng,Wang Chi,Chen Kaikai,Zhao Xiaohui,Geng Zhaoyu Journal of the science of food and agriculture BACKGROUND:l-Theanine has multiple beneficial biological activities. However, there is little information about the use of l-theanine in broiler production. Therefore, this study investigated the effect of l-theanine on growth performance, intestinal development and health, and the mRNA levels of intestinal peptide and amino acid (AA) transporters of broilers. RESULTS:Body weight and average daily gain were increased by l-theanine, whereas feed to gain ratio was decreased (quadratic, P < 0.05). Notably, the relative weight of duodenum, jejunum and ileum, villus height, villus height to crypt depth ratio, the jejunal activities of glutathione peroxidase, total antioxidant capacity, catalase and total superoxide dismutase were increased linearly and/or quadratically by l-theanine (P < 0.05), whereas crypt depth, serum d-lactic acid, and jejunal protein carbonyls and malondialdehyde content were decreased linearly and/or quadratically (P < 0.05). Moreover, l-theanine enhanced the jejunal mRNA levels of occludin, claudin-1, E-cadherin, zona occludens-1, di- and tripeptide transporter, excitatory AA transporter 3, Na -independent cationic AA transporter 1, Na -independent cationic and zwitterionic AA transporter, Na - and Cl -dependent neutral and cationic AA transporter, Na -independent cationic and Na -dependent neutral AA transporter (y+LAT) 1, y+LAT2, Na -independent branched-chain and aromatic AA transporter, and heavy chain corresponding to the b° transport system (linear and/or quadratic, P < 0.05). CONCLUSIONS:l-Theanine beneficially affected the growth performance of broilers by improving intestinal development and health, and the intestinal mRNA levels of AA and peptide transporters. Therefore, l-theanine has the potential to be a promising feed additive for broilers. © 2020 Society of Chemical Industry. 10.1002/jsfa.10192
Differential accumulation of specialized metabolite l-theanine in green and albino-induced yellow tea (Camellia sinensis) leaves. Cheng Sihua,Fu Xiumin,Liao Yinyin,Xu Xinlan,Zeng Lanting,Tang Jinchi,Li Jianlong,Lai Jianhong,Yang Ziyin Food chemistry l-Theanine is a specialized metabolite in tea (Camellia sinensis) leaves that contributes to tea function and quality. Yellow tea leaves (albino) generally have higher l-theanine contents than green tea leaves (normal), but the reason is unknown. The objective of this study was to investigate why l-theanine is accumulated in yellow tea leaves. We compared original normal leaves (green) and light-sensitive albino leaves (yellow) of cv. Yinghong No. 9. The l-theanine content was significantly higher in yellow leaves than in green leaves (p ≤ 0.01). After supplementation with [H]-l-theanine, yellow leaves catabolized less [H]-l-theanine than green leaves (p ≤ 0.05). Furthermore, most plants contained the enzyme catalyzing l-theanine conversion to ethylamine and l-glutamic acid. In conclusion, l-theanine accumulation in albino-induced yellow tea leaves was due to weak l-theanine catabolism. The differential accumulation mechanism differed from the l-theanine accumulation mechanism in tea and other plants. 10.1016/j.foodchem.2018.10.010
Stable Isotope-Labeled Precursor Tracing Reveals that l-Alanine is Converted to l-Theanine l-Glutamate not Ethylamine in Tea Plants . Fu Xiumin,Liao Yinyin,Cheng Sihua,Deng Rufang,Yang Ziyin Journal of agricultural and food chemistry Tea plants () specifically produce l-theanine, which contributes to tea function and taste. Ethylamine is a limiting factor differentiating l-theanine accumulation between tea and other plants. Ethylamine has long been assumed to be derived from l-alanine in tea. In this study, the l-alanine content in tea root cells was mainly located in vacuoles and mitochondria using a nonaqueous fractionation technique, while alanine decarboxylase in tea (CsADC) was located in the cytoplasm. Although CsADC was able to catalyze l-alanine decarboxylation to produce ethylamine , it may not provide the same enzyme activity in tea plants. Stable isotope-labeled precursor tracing in tea plants discovered that l-alanine is not a direct precursor of ethylamine but a precursor of l-glutamate, which is involved in l-theanine biosynthesis in tea. Cortex with epidermis from root tissue was the main location of ethylamine. In summary, l-alanine is converted to l-theanine l-glutamate not ethylamine in tea plants . 10.1021/acs.jafc.1c06660
Characterization of l-Theanine Excitatory Actions on Hippocampal Neurons: Toward the Generation of Novel N-Methyl-d-aspartate Receptor Modulators Based on Its Backbone. Sebih Fatiha,Rousset Matthieu,Bellahouel Salima,Rolland Marc,de Jesus Ferreira Marie Celeste,Guiramand Janique,Cohen-Solal Catherine,Barbanel Gérard,Cens Thierry,Abouazza Mohammed,Tassou Adrien,Gratuze Maud,Meusnier Céline,Charnet Pierre,Vignes Michel,Rolland Valérie ACS chemical neuroscience l-Theanine (or l-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient, and environmentally friendly chemical synthesis of l-theanine and l-γ-N-propyl-Gln and their corresponding d-isomers. l-Theanine, and its derivatives obtained so far, exhibited partial coagonistic action at N-methyl-d-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons. This activity was retained on NMDA receptors expressed in Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors were equally modulated by l-theanine. The stereochemical change from l-theanine to d-theanine along with the substitution of the ethyl for a propyl moiety in the γ-N position of l- and d-theanine significantly enhanced the biological efficacy, as measured on cultured hippocampal neurons. l-Theanine structure thus represents an interesting backbone to develop novel NMDA receptor modulators. 10.1021/acschemneuro.7b00036
l-theanine alleviates liver and kidney dysfunction in septic rats induced by cecal ligation and puncture. Malkoç Meltem,Patan Huriye,Yaman Serap Özer,Türedi Süleyman,Kerimoğlu Gökçen,Kural Birgül Vanizor,Örem Asım Life sciences AIMS:Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response against infection that triggers systemic inflammatory response syndrome. l-theanine (LT), a glutamate derivative, is a non-protein amino acid derived from tea (Camellia sinensis), and a valuable nutraceutical product used as an additive in the food industry. This study we aimed to investigate whether LT would exert any therapeutic effect on liver and kidney tissues in Sprague Dawley rats with sepsis induced with cecal ligation and puncture (CLP). MAIN METHODS:Rats were divided into four groups; sham, CLP, CLP+LT1 (2x250 mg/kg) and CLP+LT2 (2 × 750 mg/kg). Liver and kidney tissues were subjected to histopathological examination. Apoptotic index percentages (AI%) were examined using the TUNEL method. The oxidized glutathione to total glutathione (GSSG/TGSH) ratio (as a marker of oxidative stress, levels of caspase-3 (a marker of apoptosis), glutathione peroxidase (GPx) and glutathione S-transferase (GST) (as antioxidant enzymes), inducible nitric oxide synthase (iNOS) and the tumor necrosis factor-α to Interleukin-10 ratio (TNF-α/IL-10) (as markers of inflammation) were investigated using commercial kits. Levels of malondialdehyde (MDA) (a marker of oxidative stress) were determined spectrophotometrically. KEY FINDINGS:A high dose of LT exhibited more significant effects in reducing oxidative stress, inflammation and apoptosis than a low dose of LT in liver and kidney tissues with CLP-induced sepsis (p < 0.05). SIGNIFICANCE:Our results indicated that LT significantly and dose-dependently inhibited sepsis induced liver and kidney injury. This effect may be attributed to the antioxidant, anti-inflammatory, and anti-apoptotic activities of LT. 10.1016/j.lfs.2020.117502
L-Theanine Content and Related Gene Expression: Novel Insights into Theanine Biosynthesis and Hydrolysis among Different Tea Plant ( L.) Tissues and Cultivars. Liu Zhi-Wei,Wu Zhi-Jun,Li Hui,Wang Yong-Xin,Zhuang Jing Frontiers in plant science L-Theanine content has tissues and cultivars specificity in tea plant ( L.), the correlations of theanine metabolic related genes expression profiles with theanine contents were explored in this study. L-theanine contents in the bud and 1st leaf, 2nd leaf, 3rd leaf, old leaf, stem, and lateral root were determined by HPLC from three . cultivars, namely 'Huangjinya', 'Anjibaicha', and 'Yingshuang', respectively. The theanine contents in leaves and root of 'Huangjinya' were the highest, followed by 'Anjibaicha', and 'Yingshuang'. The theanine contents in the leaves reduced as the leaf mature gradually, and in stem were the least. Seventeen genes encoding enzymes involved in theanine metabolism were identified from GenBank and our tea transcriptome database, including , and . The transcript profiles of those seventeen genes in the different tissues of three tea plant cultivars were analyzed comparatively. Among the different cultivars, the transcript levels of most selected genes in 'Huangjinya' were significantly higher than that in the 'Anjibaicha' and 'Yingshuang'. Among the different tissues, the transcript levels of , and almost showed positive correlation with the theanine contents, while the other genes showed negative correlation with the theanine contents in most cases. The theanine contents showed correlations with related genes expression levels among cultivars and tissues of tea plant, and were determined by the integrated effect of the metabolic related genes. 10.3389/fpls.2017.00498
Effect of L-theanine on sensorimotor gating in healthy human subjects. Ota Miho,Wakabayashi Chisato,Matsuo Junko,Kinoshita Yukiko,Hori Hiroaki,Hattori Kotaro,Sasayama Daimei,Teraishi Toshiya,Obu Satoko,Ozawa Hayato,Kunugi Hiroshi Psychiatry and clinical neurosciences AIM:l-Theanine (N-ethyl-l-glutamine) is an amino acid uniquely found in green tea. Growing evidence has suggested the possible effects of l-theanine on cognition. Previously, we found that l-theanine attenuates MK-801-induced deficit in prepulse inhibition (PPI) in mice. In this study, we examined the effect of l-theanine in increasing the PPI in healthy humans. METHODS:The subjects were 14 healthy adults who underwent PPI testing as a measure of sensorimotor gating 90 min after an oral intake of l-theanine (0, 200, 400, or 600 mg). PPI tests were done by examiners who were blind to the dose. RESULTS:The administration of 200 mg of l-theanine and that of 400 mg, but not 600 mg, significantly increased the % PPI compared to the baseline (0 mg). There was no significant relation between the dose of l-theanine and the startle magnitude or the habituation of startle response. The plasma concentrations of l-theanine correlated with the dose of l-theanine. CONCLUSION:The observed effect with 200-400 mg of l-theanine on PPI suggested that l-theanine at a particular dose range increases sensorimotor gating in humans. 10.1111/pcn.12134
L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway. Di Xiaojing,Yan Jingqi,Zhao Yan,Chang Yanzhong,Zhao Baolu Science China. Life sciences In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a conditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DHβE). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the α(4), β(2) and α(7) nicotine acetylcholine receptor (nAChR) subunits induced by nicotine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction. 10.1007/s11427-012-4401-0
L-theanine attenuates transport stress-induced impairment of meat quality of broilers through improving muscle antioxidant status. Zhang C,Geng Z Y,Chen K K,Zhao X H,Wang C Poultry science This study was to investigate the effect of dietary L-theanine (THE) supplementation (0, 600 mg/kg) on growth performance, carcass traits, immune organ indexes, meat quality, and muscle antioxidant status of transported broilers. A total of 180 one-day-old male Ross 308 broilers were randomly allotted to 2 treatment groups including a THE-free group with 12 replicates of 10 birds each and a THE group with 6 replicates of 10 birds each. On the morning of day 42, after a 9-h fast, the birds of THE-free group were divided into 2 equal groups, and then all birds in the 3 groups were placed into 18 crates and were transported according to the following protocols: 0-h transport of birds in the THE-free group (control group), 3-h transport of birds in the THE-free group (T group), and 3-h transport of birds in the THE group (T + THE group). Results showed that dietary THE supplementation improved feed conversion ratio and birds' final body weight (P < 0.05), while transport and dietary THE supplementation did not affect carcass traits of broilers (P > 0.05). Transport increased bird live weight loss, drip loss, L*24 h, muscle malondialdehyde (MDA), protein carbonyl (PC) and lactate contents, while it decreased thymus, spleen, and bursa of Fabricius indexes, pH24h, a*, and muscle total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase (GSH-PX) activities and glycogen content (P < 0.05). Nevertheless, compared with birds in the T group, birds in the T + THE group exhibited increased thymus, spleen, and bursa of Fabricius indexes, pH24h, a*24 h, and muscle T-AOC, CAT, and GSH-PX activities and glycogen content, and decreased drip loss, L*24 h, and muscle MDA, PC, and lactate contents (P < 0.05). This study provided the first evidence that dietary THE supplementation prevented transport-stress-impaired immune organ indexes and meat quality of broilers, and the reason for maintenance of meat quality by supplementation of THE may be partly ascribed to the changed muscle glycolysis metabolism and antioxidant status. 10.3382/ps/pez164
L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion. Zukhurova Mavdzhuda,Prosvirnina Maria,Daineko Anastasia,Simanenkova Anna,Petrishchev Nikolay,Sonin Dmitry,Galagudza Michael,Shamtsyan Mark,Juneja Lekh R,Vlasov Timur Phytotherapy research : PTR While the neuroprotective effect of green tea (Camellia sinensis) might be explained by the presence of amino acid L-theanine in the tea leaves, it is not known whether postischemic administration of L-theanine could also provide neuroprotection. In the present study, we investigated the neuroprotective effect of L-theanine (1 and 4 mg/kg) administered at 3, 12, and 24 h after reperfusion in the rat model of stroke. We also studied the effect of L-theanine on brain injury caused by exogenous administration of N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate/kainate receptor agonists during reperfusion. Rats were subjected to 30-min middle cerebral artery occlusion followed by 48-h reperfusion. Neurological deficit and infarct size were determined at the end of reperfusion. At 3 and 12 h, but not at 24 h of reperfusion, L-theanine substantially reduced the size of brain infarct. Neurological status was improved when L-theanine was administered 3, 12, and 24 h after reperfusion. Repeated intrastriatal injections of L-theanine at a total dose of 800 µg/kg during reperfusion prevented brain injury caused by glutamate receptor agonists. In conclusion, L-theanine at reperfusion exerts neuroprotective effect in the in vivo rat model of stroke. Local treatment with L-theanine at reperfusion prevents glutamate receptor agonist-mediated brain injury. 10.1002/ptr.4868
Protective Effect of l-Theanine against DSS-Induced Colitis by Regulating the Lipid Metabolism and Reducing Inflammation via the NF-κB Signaling Pathway. Journal of agricultural and food chemistry The present study revealed the phylactic effects of l-theanine on a DSS-induced colitis mice model. The results showed that 3% DSS treatment significantly induced intestinal damage as reflected by DAI, histopathological feature, and colon length, while l-theanine pretreatment markedly prevented these trends to exert protective effects. Meanwhile, l-theanine pretreatment decreased the levels of TNF-α, IL-1β, IL-6, iNOS, and COX2 on DSS-induced colitis. Notably, DSS inhibited the proliferation and promoted the apoptosis of intestinal epithelial cells, thereby damaging the integrity of the intestinal epithelial barrier, whereas l-theanine also played a protective role by attenuating these deteriorated effects. It was also observed that l-theanine treatment downregulated the levels of p-p65, p65, p-p53, p53, and p-AKT protein expression in acute DSS-induced colitis, which showed the protective function of l-theanine, mainly via the NF-κB signaling pathway. Furthermore, the results of lipid analysis and transcriptome analysis show that l-theanine reversed transcriptional profiles and lipid profiles of colitis models, mainly via the inflammatory reactivity-related pathway. Interestingly, the correlation analysis between transcriptional profiles and lipid profiles showed that inflammatory response-related genes were almost significantly correlated with differential lipid metabolites. In summary, l-theanine plays a protective role in DSS-induced colitis via downregulating the NF-κB signaling pathway and regulating lipid metabolism disorders. 10.1021/acs.jafc.1c05839
Effect of l-theanine on the growth performance, immune function, and jejunum morphology and antioxidant status of ducks. Zhang C,Chen K K,Zhao X H,Wang C,Geng Z Y Animal : an international journal of animal bioscience l-theanine is a unique nonproteinogenic amino acid found in tea, and has recently received considerable attention because of its various biological activities. However, there is no available research report on the use of l-theanine as a feed additive in ducks. This study was conducted to investigate the potential benefits and appropriate dosages of l-theanine on the growth performance, immune function, serum biochemical parameters, and jejunum morphology and antioxidant capacity of ducks. A total of 600 1-day-old Chaohu ducks were randomly allocated into five dietary treatment groups supplemented with 0 (control group), 300, 600, 900 and 1500 mg/kg of l-theanine. Each group included five replicates of 24 birds each. Body weight at day 28 was increased (P&lt;0.05) by l-theanine. From days 15 to 28, l-theanine elevated cumulative BW gain (BWG) and cumulative feed intake (FI), and decreased feed to gain ratio. From days 1 to 28, l-theanine elevated (P&lt;0.05) cumulative BWG and cumulative FI. l-theanine elevated (P&lt;0.05) the relative weight of bursa of Fabricus (day 14), thymus (day 14), spleen (day 28) and liver (day 28). On day 28, l-theanine decreased (P&lt;0.05) serum glucose, uric acid, triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, insulin, interleukin-2 (IL-2) and IL-6 contents, and elevated (P&lt;0.05) serum total protein, globulin (GLB), immune globulin A (IgA) and IgG contents, but only serum insulin, interferon-γ, tumor necrosis factor-α and IL-6 contents was decreased (P&lt;0.05) and serum GLB and IgM content was elevated (P&lt;0.05) by l-theanine on day 14. On day 14, l-theanine decreased (P&lt;0.05) jejunum crypt depth, and elevated (P&lt;0.05) jejunum villus height, villus height to crypt depth ratio (V/C), goblet cell number and total superoxide dismutase (T-SOD) activity. On day 28, l-theanine decreased (P&lt;0.05) jejunum malondialdehyde content, and elevated (P&lt;0.05) jejunum villus height, V/C, goblet cell number, and T-SOD, catalase and glutathione peroxidase activities. l-theanine levels caused quadratic effect on the growth performance, relative organ weight, serum parameters, jejunum morphology and antioxidant capacity. In conclusion, l-theanine can be used as a promising feed additive for ducks, and its optimal supplementation level was 600 to 900 mg/kg based on the current experimental condition. 10.1017/S1751731118002884
Dose-response effect of L-theanine on psychomotor speed, sustained attention, and inhibitory control: a double-blind, placebo-controlled, crossover study. Nutritional neuroscience BACKGROUND:L-theanine is a non-protein-forming amino acid found in tea. Previous research shows high doses (100-400 mg) of L-theanine enhances attention, mainly by reducing mind wandering and distracter processing. We hypothesized that these indirect mechanisms could significantly improve the performance of low-level attentional tasks, whereas the relative contribution could be less in complex attentional tasks that require active, higher-order processing of target stimuli. METHODS:To test this hypothesis, we conducted a double-blind, placebo-controlled, counterbalanced, four-way crossover study in 32 healthy young adults, where we compared the effects of three doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water), administered before and 50 min after dosing, on three attentional tasks from the Cambridge Neuropsychological Test Automated Battery [viz. Reaction Time (RTI)-visuomotor speed, Rapid Visual Information Processing (RVP)-sustained attention, and Stop Signal Task (SST)-inhibitory control]. Results were analyzed in dose × time repeated measures ANOVA models, with subsequent pairwise comparisons. RESULTS:Active doses significantly improved reaction times in the RTI (100-200 mg) and RVP (200-400 mg) tasks from baseline ( < 0.05), but once controlled for the change-from-baseline caused by placebo, only the RTI simple reaction times showed significant improvements, following 100 mg (Δ = 16.3 ms,  = 0.009) and 200 mg (Δ = 16.9 ms,  = 0.009) of L-theanine. CONCLUSIONS:Consistent with our hypothesis, these findings suggest that L-theanine significantly improves attention in simple visuomotor tasks, but not in more complex sustained attention tasks, or executive control tasks that require top-down inhibition of pre-active responses. 10.1080/1028415X.2022.2136884
l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats. Tsai Wen-Hsin,Wu Chung-Hsin,Yu Hong-Jeng,Chien Chiang-Ting Neurourology and urodynamics AIMS:Upregulation of substance P (SP) and neurokinin-1 receptor (NK1R) activation induces pro-inflammatory bladder hyperactivity through the PKC/ERK/NF-κB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. l-Theanine is a unique non-protein-forming amino acid present in tea (Camellia sinensis [L.] O. Kuntze) with its antioxidant, anti-inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of l-theanine on SP-induced bladder hyperactivity. METHODS:In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/poly-(ADP-ribose)-polymerase (PARP), and autophagy-mediated LC3 II expression by Western blot, electrophoretic-mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP-evoked hyperactive bladder. RESULTS:l-Theanine dose-dependently depressed H O and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intra-arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, Caspase 3/PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical l-theanine (15 mg/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP-treated hyperactive bladder. CONCLUSIONS:In conclusion, l-theanine through antioxidant and anti-inflammatory actions ameliorates SP-induced bladder hyperactivity via the inhibition of proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, oxidative stress, bladder nerve hyperactivity, apoptosis, and autophagy. Neurourol. Urodynam. 36:297-307, 2017. © 2016 Wiley Periodicals, Inc. 10.1002/nau.22965
Application of Cell-Free Protein Synthesis System for the Biosynthesis of l-Theanine. Feng Junchen,Yang Chen,Zhao Zhehao,Xu Junjian,Li Jian,Li Ping ACS synthetic biology l-Theanine, as an active component of the leaves of the tea plant, possesses many health benefits and broad applications. Chemical synthesis of l-theanine is possible; however, this method generates chiral compounds and needs further isolation of the pure l-isoform. Heterologous biosynthesis is an alternative strategy, but one main limitation is the toxicity of the substrate ethylamine on microbial host cells. In this study, we introduced a cell-free protein synthesis (CFPS) system for l-theanine production. The CFPS expressed l-theanine synthetase 2 from (CsTS2) could produce l-theanine at a concentration of 11.31 μM after 32 h of the synthesis reaction. In addition, three isozymes from microorganisms were expressed in CFPS for l-theanine biosynthesis. The γ-glutamylcysteine synthetase from could produce l-theanine at the highest concentration of 302.96 μM after 24 h of reaction. Furthermore, CFPS was used to validate a hypothetical two-step l-theanine biosynthetic pathway consisting of the l-alanine decarboxylase from (CsAD) and multiple l-theanine synthases. Among them, the combination of CsAD and the l-glutamine synthetase from (PtGS) could synthesize l-theanine at the highest concentration of 13.42 μM. Then, we constructed an engineered strain overexpressed CsAD and PtGS to further confirm the l-theanine biosynthesis ability in living cells. This engineered strain could convert l-alanine and l-glutamate in the medium to l-theanine at a concentration of 3.82 mM after 72 h of fermentation. Taken together, these results demonstrated that the CFPS system can be used to produce the l-theanine through the two-step l-theanine biosynthesis pathway, indicating the potential application of CFPS for the biosynthesis of other active compounds. 10.1021/acssynbio.0c00618
Characterization of l-Theanine Hydrolase and Subcellular Distribution of Its Specific Product Ethylamine in Tea (). Fu Xiumin,Cheng Sihua,Liao Yinyin,Xu Xinlan,Wang Xinchao,Hao Xinyuan,Xu Ping,Dong Fang,Yang Ziyin Journal of agricultural and food chemistry l-Theanine has a significant role in the taste of tea () infusions. Our previous research indicated that the lower l-theanine metabolism in ethylamine and l-glutamate is a key factor that explains the higher content of l-theanine in albino tea with yellow or white leaves, compared with that of normal tea with green leaves. However, the specific genes encoding l-theanine hydrolase in tea remains unknown. In this study, was cloned together with the homologous gene and the recombinant protein was shown to catalyze l-theanine hydrolysis into ethylamine and l-glutamate . There were higher transcript levels in leaf tissue and lower transcripts in the types of albino (yellow leaf) teas compared with green controls. The subcellular location of ethylamine in tea leaves was shown to be in the mitochondria and peroxisome using a nonaqueous fractionation method. This study identified the l-theanine hydrolase gene and subcellular distribution of ethylamine in tea leaves, which improves our understanding of the l-theanine metabolism and the mechanism of differential accumulation of l-theanine among tea varieties. 10.1021/acs.jafc.0c01796
L-Theanine healed NSAID-induced gastric ulcer by modulating pro/antioxidant balance in gastric ulcer margin. Chatterjee Sirshendu,Chatterjee Ananya,Roy Surmi,Bera Biswajit,Bandyopadhyay Sandip K Journal of natural medicines L-Theanine is a unique non-protein-forming amino acid present in tea [Camellia sinensis (L.) O. Kuntze]. In the present work, we evaluated the healing effect of L-theanine on NSAID (indomethacin)-induced gastric ulcer. Histology of the stomach tissues revealed maximum ulceration on the third day after indomethacin administration (18 mg/kg, single dose p.o.) which was accompanied by increased lipid peroxidation; protein carbonylation; Th1 cytokine synthesis, and depletion of thiol, mucin, prostaglandin (PG) E, Th2 cytokine synthesis; and total antioxidant status in mice. L-Theanine healed gastric ulcer at a dose of 10 mg/kg b.w. but aggravated the ulcerated condition at a higher dose of 40 mg/kg b.w. At 10 mg/kg b.w., L-theanine significantly alleviated the adverse oxidative effect of indomethacin through enhanced synthesis of PGE2 by modulation of cyclo-oxygenase-1 and 2 [COX-1 and COX-2] expression, Th1/Th2 cytokine balance, and restoration of cellular antioxidant status at the gastric ulcer margin. The present study revealed for the first time the dose-dependent biphasic effect of a natural neuroprotective agent, L-theanine, on gastric ulcer disease. 10.1007/s11418-014-0852-x
Transcription factor CsWRKY40 regulates L-theanine hydrolysis by activating the CsPDX2.1 promoter in tea leaves during withering. Horticulture research L-Theanine is a crucial secondary metabolite in tea and positively determines the potential quality and health benefits of tea products. Previous work found the content of L-theanine decreased during withering process, while the specific mechanism is still unknown. Here, weighted gene co-expression network analysis (WGCNA) was performed based on the transcriptome data obtained previously. The key hydrolysis gene CsPDX2.1 in L-theanine metabolism and seven candidate transcription factors were screened out. Among those transcription factors, CsWRKY40 presented the strongest activation on the CsPDX2.1 promoter (373.18-fold) by binding to W box element based on the dual luciferase assay and EMSA results. Meanwhile, CsWRKY40 protein was located in the nucleoplasm, while CsPDX2.1 was found in both the nucleoplasm and cytoplasm. Furthermore, it was confirmed that the water loss of tea leaves was the critical factor affecting the contents of ABA and L-theanine by activating the expression of CsPDX2.1 and CsPDX2.1 based on the analysis of the withering model, water-retention model and water-loss model. Our results provide a new insight into revealing the regulation mechanism of L-theanine hydrolysis metabolism. 10.1093/hr/uhac025
L-theanine prevent quinolinic acid induced motor deficit and striatal neurotoxicity: Reduction in oxido-nitrosative stress and restoration of striatal neurotransmitters level. Jamwal Sumit,Singh Shamsher,Gill Jaskamal Singh,Kumar Puneet European journal of pharmacology L-theanine has been documented to possess anti-oxidant, anti-inflammatory and neuroprotective potential in various animal models of neurological disorders. The present study was anticipated to investigate the effect of L-theanine against quinolinic acid induced motor deficits, oxido-nitrosative stress, neuro-inflammation and neurotransmitters alteration in rats. Rats were stereotaxically injected QA (200nmol/2µl saline; intrastriatal); bilaterally on 0 day and L-theanine (25 & 50mg/kg; p.o.) was administered for 21 days starting from day 1 of QA injection. Either, L-NAME (10mg/kg; i.p.), a nitric oxide synthase inhibitor and L-arginine (50mg/kg; i.p.), a nitric oxide synthase precursor were administered with L-theanine in respective groups. Behavioral observations were evaluated on weekly basis using rota-rod, grip strength, narrow beam walking and open field test. QA treatment induces significant alteration in body weight, motor coordination, oxidative defense, pro-inflammatory cytokines and striatal neurotransmitters level. L-theanine treatment alone, at both the tested doses, significantly attenuated QA induced alterations. In addition, treatment of L-theanine with L-NAME significantly enhances the protective effect of L-theanine whereas treatment of L-theanine with L-arginine significantly ameliorated the protective effect of L-theanine. The protective effect of L-theanine is attributed to its anti-oxidant, anti-inflammatory and modulatory effect on nitric oxide pathway and neurotransmitters level in striatum. This suggests use of L-theanine in the clinical settings of HD. 10.1016/j.ejphar.2017.06.016
Ultrasound enhanced biosynthesis of L-theanine from L-glutamine and ethylamine by recombinant γ-glutamyltranspeptidase. Xu Lisheng,Han Fangkai,Zhang Xingtao,Yu Qiaoling Bioresource technology A mutant library of the key amino acid residue site E387 in γ-glutamyltranspeptidase was constructed to screen the mutant enzymes with significantly improved thermal stability (E387Q). The reaction temperature of the mutant enzyme (E387Q) was 10℃ higher than that of the parent enzyme. Ultrasound-assisted synthesis of L-theanine by γ-glutamyltranspeptidase was investigated. The effects of ultrasonic power, reaction pH and substrate concentration on the enzymatic synthesis of L-theanine were studied by the response surface method. The results showed that the optimal process conditions are ultrasonic power of 100 W, reaction pH of 9, substrate L-glutamine concentration of 120 mmol/L, reaction temperature of 45℃, and L-theanine yield of 89.1%. The yield of L-theanine is 2.61 times higher than that obtained without ultrasound. Ultrasound can significantly promote the synthesis of L-theanine by γ-glutamyltranspeptidase. 10.1016/j.biortech.2020.123251
Combining protein and metabolic engineering strategies for high-level production of L-theanine in Corynebacterium glutamicum. Bioresource technology L-theanine is a natural non-protein amino acid with wide applications. Thus, a high yield of L-theanine production is required on an industrial scale. Herein, an efficient L-theanine-producing strain of Corynebacterium glutamicum was constructed by combining protein and metabolic engineering. Firstly, a γ-glutamylmethylamide synthetase from Paracoccus aminovorans (PaGMAS) was isolated and engineered by computer-aided design, the resulting mutant E179K/N105R improved L-theanine yield by 36.61 %. Subsequently, to increase carbon flux towards L-theanine production, the gene ggt which degrades L-theanine, the gene alaT which participated in L-alanine synthesis, and the gene NCgl1221 which encodes glutamate-exporting protein were deleted. Finally, ppk gene was overexpressed to enhance intracellular ATP production. The reprogramed strain produced 44.12 g/L L-theanine with a yield of 57.11 % and productivity of 1.16 g/L/h, which is the highest L-theanine titer reported by Corynebacterium glutamicum. This study provides an efficient and economical biosynthetic pathway for the industrial production of L-theanine. 10.1016/j.biortech.2023.130200
Effect of L-theanine on glutamatergic function in patients with schizophrenia. Ota Miho,Wakabayashi Chisato,Sato Noriko,Hori Hiroaki,Hattori Kotaro,Teraishi Toshiya,Ozawa Hayato,Okubo Tsutomu,Kunugi Hiroshi Acta neuropsychiatrica OBJECTIVES:Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. Previous studies suggested that L-theanine affects the glutamatergic neurotransmission and ameliorates symptoms in patients with schizophrenia. The aims of the present study were twofold: to examine the possible effects of L-theanine on symptoms in chronic schizophrenia patients and to evaluate the changes in chemical mediators, including glutamate + glutamine (Glx), in the brain by using 1H magnetic resonance spectroscopy (MRS). METHOD:The subjects were 17 patients with schizophrenia and 22 age- and sex-matched healthy subjects. L-theanine (250 mg/day) was added to the patients' ongoing antipsychotic treatment for 8 weeks. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index scores and MRS results. RESULTS:There were significant improvements in the PANSS positive scale and sleep quality after the L-theanine treatment. As for MRS, we found no significant differences in Glx levels before and after the 8 week L-theanine treatment. However, significant correlations were observed between baseline density of Glx and change in Glx density by l-theanine. CONCLUSIONS:Our results suggest that L-theanine is effective in ameliorating positive symptoms and sleep quality in schizophrenia. The MRS findings suggest that L-theanine stabilises the glutamatergic concentration in the brain, which is a possible mechanism underlying the therapeutic effect. 10.1017/neu.2015.22
l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice. Wise Laura E,Premaratne Ishani D,Gamage Thomas F,Lichtman Aron H,Hughes Larry D,Harris Louis S,Aceto Mario D Pharmacology, biochemistry, and behavior l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine's stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether l-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether l-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. l-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5h. l-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that l-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors. 10.1016/j.pbb.2012.08.008
l-Theanine and NEP1-40 promote nerve regeneration and functional recovery after brachial plexus root avulsion. Guo Wen-Lai,Qu Wen-Rui,Zeng Li-Ni,Qi Zhi-Ping,Huang Chao,Zhu Zhe,Li Rui Biochemical and biophysical research communications Brachial plexus root avulsion causes severe sequelae Treatments and prognosis face many problems, including inflammatory reaction, oxidative damage, and myelin related inhibitory effect. l-Theanine has anti-inflammatory, anti-oxidative, and neuroprotective effects. NEP1-40 competitively inhibits Nogo-66 receptor (NgR1) promotes axonal regeneration. Forty-eight Sprague-Dawley rats were randomly assigned into four groups to establish an animal model of brachial plexus root avulsion. Inflammation and oxidative damage were evaluated by spectrophotometry and motor function of the upper limbs was assessed via Terzis grooming test after modeling. Immunofluorescence and hematoxylin and eosin staining were utilized to determine the content of reactive oxygen species, activation of microglial cells, neuroprotection, and nerve regeneration. Compared with the control group, the L-Theanine + NEP1-40 group had significantly decreased myeloperoxidase, malondialdehyde, interleukin-6, reactive oxygen species, and microglial cells, significantly increased score on the Terzis grooming test, increased motor neuron content, and thickened muscle fibers, increased area, and appearance of large and clear motor endplate structures. The results of this study suggest that l-Theanine combined with NEP1-40significantly promoted nerve regeneration after brachial plexus root avulsion, and may be a potential treatment for promoting nerve regeneration. Possible mechanisms underlying these results are alleviation of oxidative damage and inflammatory responses in the injured area and antagonism of myelin inhibition. 10.1016/j.bbrc.2018.11.124
Effects of single-dose L-theanine on motor cortex excitability. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 10.1016/j.clinph.2021.07.003
L-Theanine Administration Modulates the Absorption of Dietary Nutrients and Expression of Transporters and Receptors in the Intestinal Mucosa of Rats. Yan Qiongxian,Tong Haiou,Tang Shaoxun,Tan Zhiliang,Han Xuefeng,Zhou Chuanshe BioMed research international L-theanine has various advantageous functions for human health; whether or not it could mediate the nutrients absorption is unknown yet. The effects of L-theanine on intestinal nutrients absorption were investigated using rats ingesting L-theanine solution (0, 50, 200, and 400 mg/kg body weight) per day for two weeks. The decline of insulin secretion and glucose concentration in the serum was observed by L-theanine. Urea and high-density lipoprotein were also reduced by 50 mg/kg L-theanine. Jejunal and ileac basic amino acids transporters and , neutral and , and acidic expression were upregulated. The expression of intestinal and responsible for carbohydrates uptake and and associated with fatty acids transport were inhibited. These results indicated that L-theanine could inhibit the glucose uptake by downregulating the related gene expression in the small intestine of rats. Intestinal gene expression of transporters responding to amino acids absorption was stimulated by L-theanine administration. 10.1155/2017/9747256
l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study. Kahathuduwa Chanaka N,Dhanasekara Chathurika S,Chin Shao-Hua,Davis Tyler,Weerasinghe Vajira S,Dassanayake Tharaka L,Binks Martin Nutrition research (New York, N.Y.) 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. 10.1016/j.nutres.2017.11.002
-Theanine Decreases Orofacial Dyskinesia Induced by Reserpine in Rats. Soung Hung-Sheng,Wang Mao-Hsien,Chang Kuo-Chi,Chen Cheng-Neng,Chang Yi,Yang Chih-Chuan,Tseng Hsiang-Chien Neurotoxicity research Reserpine (RES)-induced orofacial dyskinesia (OD) has been used as an animal model for human tardive dyskinesia (TD) for decades, due to its strong pathophysiological association with striatal oxidative stress and neural cytoarchitecture alteration. -Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative, anti-inflammatory, and neuroprotective effects. In this study, we examined the potential protective effects of LT on RES-induced behavioral and neurochemical dysfunction in rats. RES treatment (1 mg/kg s.c., 3 injections 1 day apart) induced significant increases (p < 0.001) in the frequency of vacuous chewing movements (VCM), tongue protrusion (TP), as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 14 days, starting 10 days before RES injection) was able to prevent most of the RES-induced OD. Moreover, LT treatment reduced the RES-induced lipid peroxidation (LPO) production, increased the antioxidation power and catecholamines in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results indicated that LT was able to counteract the increased oxidative damage, neurotransmitter deficiency, neuroinflammation, and apoptosis induced by RES, and these results have demonstrated the possible neuroprotective effects of LT against RES-induced OD, including antioxidation, neurochemical deficiency prevention, antineuroinflammation, and antiapoptosis. These findings, therefore, suggest a potential role for LT to have a clinically relevant therapeutic effect in delaying or treating human TD. 10.1007/s12640-018-9897-z
L-Theanine extends lifespan of adult Caenorhabditis elegans. Zarse Kim,Jabin Saskia,Ristow Michael European journal of nutrition PURPOSE:Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of L-theanine, a putative anti-cancer, anti-obesity, blood pressure-lowering, and neuroprotective compound contained in green tea (Camellia sinensis), are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. METHODS:Adult C. elegans roundworms were maintained on agar plates, were fed E. coli strain OP50 bacteria, and L-theanine was applied to agar to test (1) whether it may increase survival upon paraquat exposure and (2) whether it may promote longevity by quantifying survival in the presence and absence of the compound. RESULTS:L-Theanine increases survival of C. elegans in the presence of paraquat at a concentration of 1 micromolar. L-theanine extends C. elegans lifespan when applied at concentrations of 100 nM, as well as 1 and 10 micromolar. CONCLUSIONS:In the model organism C. elegans, L-theanine is capable of promoting paraquat resistance and longevity suggesting that this compound may as well promote healthy lifespan in mammals and possibly humans. 10.1007/s00394-012-0341-5
Metabolic Engineering of for Fermentative Production of l-Theanine. Benninghaus Leonie,Walter Tatjana,Mindt Melanie,Risse Joe Max,Wendisch Volker F Journal of agricultural and food chemistry -alkylated amino acids are intermediates of natural biological pathways and can be found incorporated in peptides or have physiological roles in their free form. The -ethylated amino acid l-theanine shows taste-enhancing properties and health benefits. It naturally occurs in green tea as major free amino acid. Isolation of l-theanine from shows low efficiency, and chemical synthesis results in a racemic mixture. Therefore, biochemical approaches for the production of l-theanine gain increasing interest. Here, we describe metabolic engineering of KT2440 for the fermentative production of l-theanine from monoethylamine and carbon sources glucose, glycerol, or xylose using heterologous enzymes from for l-theanine production and heterologous enzymes from for growth with xylose. l-Theanine (15.4 mM) accumulated in shake flasks with minimal medium containing monoethylamine and glucose, 15.2 mM with glycerol and 7 mM with xylose. Fed-batch bioreactor cultures yielded l-theanine titers of 10 g L with glucose plus xylose, 17.2 g L with glycerol, 4 g L with xylose, and 21 g L with xylose plus glycerol, respectively. To the best of our knowledge, this is the first l-theanine process using and the first compatible with the use of various alternative carbon sources. 10.1021/acs.jafc.1c03240
Retracted: Dynamic Observation of the Effect of L-Theanine on Cerebral Ischemia-Reperfusion Injury Using Magnetic Resonance Imaging under Mathematical Model Analysis. Journal of healthcare engineering [This retracts the article DOI: 10.1155/2021/5679665.]. 10.1155/2023/9793832
L-Theanine Down-Regulates the JAK/STAT3 Pathway to Attenuate the Proliferation and Migration of Vascular Smooth Muscle Cells Induced by Angiotensin II. Ben Peiling,Hu Monong,Wu Huizhen,Zhang Zhengping,Gao Yanhong,Luo Lan,Yin Zhimin Biological & pharmaceutical bulletin L-Theanine, a green tea amino acid derivative, has cardiovascular qualities. The focus of the current evaluation was to examine the suppression of L-theanine on cultured vascular smooth muscle cell (VSMC) proliferation and migration that is prompted by angiotensin II (Ang II). The VSMCs were treated with non-cytotoxic concentrations of L-theanine and then stimulated with Ang II. The CCK-8 and Transwell chamber assays were monitored on the proliferation and migration rate, respectively. We discovered that L-theanine (50 and 100 µM) significantly halted Ang II-induced VSMC proliferation and migration. This was joined by a decline in the amount of cyclin D1. An additional discovery was that L-theanine lowered the proportion of S-phase cells, whereas the number of G1/G0-phase cells in Ang II-stimulated VSMCs was elevated, based on flow cytometry. Western blotting analyses indicated that L-theanine had no impact on extracellular-signal-regulated kinase 1/2 (ERK1/2) activation prompted by Ang II. Nevertheless, L-theanine significantly lowered Ang II-prompted phosphorylation of Janus kinase 2 (JAK2), c-Src tyrosine kinase, and signal transducer and activators of transcription 3 (STAT3). The outcomes revealed that L-theanine subdued the Ang II-prompted proliferation and migration of VSMC, partly via the obstruction of the JAK/STAT3 pathway instead of via just the ERK pathway. 10.1248/bpb.b18-00387
L-theanine promotes nitric oxide production in endothelial cells through eNOS phosphorylation. Siamwala Jamila H,Dias Paul M,Majumder Syamantak,Joshi Manoj K,Sinkar Vilas P,Banerjee Gautam,Chatterjee Suvro The Journal of nutritional biochemistry Consumption of tea (Camellia sinensis) improves vascular function and is linked to lowering the risk of cardiovascular disease. Endothelial nitric oxide is the key regulator of vascular functions in endothelium. In this study, we establish that l-theanine, a non-protein amino-acid found in tea, promotes nitric oxide (NO) production in endothelial cells. l-theanine potentiated NO production in endothelial cells was evaluated using Griess reaction, NO sensitive electrode and a NO specific fluorescent probe (4-amino-5-methylamino-2',7'-difluororescein diacetate). l-Theanine induced NO production was partially attenuated in presence of l-NAME or l-NIO and completely abolished using eNOS siRNA. eNOS activation was Ca(2+) and Akt independent, as assessed by fluo-4AM and immunoblotting experiments, respectively and was associated with phosphorylation of eNOS Ser 1177. eNOS phosphorylation was inhibited in the presence of ERK1/2 inhibitor, PD-98059 and partially inhibited by PI3K inhibitor, LY-294002 and Wortmanin suggesting PI3K-ERK1/2 dependent pathway. Increased NO production was associated with vasodilation in ex ovo (chorioallantoic membrane) model. These results demonstrated that l-theanine administration in vitro activated ERK/eNOS resulting in enhanced NO production and thereby vasodilation in the artery. The results of our experiments are suggestive of l-theanine mediated vascular health benefits of tea. 10.1016/j.jnutbio.2012.02.016
Development of a highly efficient and specific L-theanine synthase. Yao Jun,Li Jing,Xiong Dandan,Qiu Yuanyuan,Shi Guizhi,Jin Jian-Ming,Tao Yong,Tang Shuang-Yan Applied microbiology and biotechnology γ-Glutamylcysteine synthetase (γ-GCS) from Escherichia coli, which catalyzes the formation of L-glutamylcysteine from L-glutamic acid and L-cysteine, was engineered into an L-theanine synthase using L-glutamic acid and ethylamine as substrates. A high-throughput screening method using a 96-well plate was developed to evaluate the L-theanine synthesis reaction. Both site-saturation mutagenesis and random mutagenesis were applied. After three rounds of directed evolution, 13B6, the best-performing mutant enzyme, exhibited 14.6- and 17.0-fold improvements in L-theanine production and catalytic efficiency for ethylamine, respectively, compared with the wild-type enzyme. In addition, the specific activity of 13B6 for the original substrate, L-cysteine, decreased to approximately 14.6% of that of the wild-type enzyme. Thus, the γ-GCS enzyme was successfully switched to a specific L-theanine synthase by directed evolution. Furthermore, an ATP-regeneration system was introduced based on polyphosphate kinases catalyzing the transfer of phosphates from polyphosphate to ADP, thus lowering the level of ATP consumption and the cost of L-theanine synthesis. The final L-theanine production by mutant 13B6 reached 30.4 ± 0.3 g/L in 2 h, with a conversion rate of 87.1%, which has great potential for industrial applications. 10.1007/s00253-020-10482-6
L-theanine, a Component of Green Tea Prevents 3-Nitropropionic Acid (3-NP)-Induced Striatal Toxicity by Modulating Nitric Oxide Pathway. Jamwal Sumit,Kumar Puneet Molecular neurobiology L-theanine is unique amino acid which readily crosses blood brain barrier and possesses neuroprotective potential against neurodegenerative disorders including Huntington disease (HD). HD is characterized by selective loss of GABAergic medium spiny neurons. 3-nitropropionic acid (3-NP) induces a spectrum of HD-like neuropathology in rat striatum and widely used as experimental tool to study HD. Therefore, the present study was intended to investigate the effect of L-theanine against 3-NP-induced striatal toxicity and to explore its possible mechanism. Rats were administered with 3-NP for 21 days. L-theanine was given once a day, 1 h prior to 3-NP treatment for 21 days and L-NAME (10 mg/kg, i.p.), NO inhibitor and L-arginine (50 mg/kg; i.p.), NO precursor were administered 1 h prior to L-theanine treatment. Body weight and behavioral observation were made on weekly basis. On the 22nd day, animals were sacrificed, and the striatum was isolated for biochemical (LPO, GSH, and nitrite), pro-inflammatory cytokines and neurochemical analysis. 3-NP treatment significantly altered body weight, locomotor activity, motor coordination, mitochondrial complex-II activity, oxidative defense, pro-inflammatory mediators, and striatal neurotransmitters level. L-theanine pre-treatment (25 and 50 mg/kg/day, p.o.) significantly prevented these alterations. In addition, concurrent treatment of L-NAME with L-theanine (25 mg/kg/day, p.o.) significantly enhanced protective effect of L-theanine (25 mg/kg/day, p.o.) whereas concurrent treatment of L-arginine with L-theanine (50 mg/kg/day, p.o.) significantly ameliorated the protective effect of L-theanine (50 mg/kg/day, p.o.). The neuroprotective potential of L-theanine involves inhibition of detrimental nitric oxide production and prevention of neurotransmitters alteration in the striatum. 10.1007/s12035-016-9822-5
Protective effects of L-theanine against doxorubicin-induced nephrotoxicity in rats. Altınkaynak Yahya,Kural Birgül,Akcan Buket A,Bodur Akın,Özer Serap,Yuluğ Esin,Munğan Sevdegül,Kaya Cansu,Örem Asım Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie BACKGROUND/AIM:L-theanine is the unique amino acid found in tea plants, has antioxidant and antiinflammatory activities, and functions in mental concentration and sleep quality. In this study, it is aimed to investigate the effects of L-theanine on doxorubicin (DOX, a chemotherapeutic agent) induced nephrotoxicity in rats, especially via GSH related enzymes. MATERIALS AND METHODS:32 male Sprague Dawley rats weighing 300-400 g were randomly assigned into 4 groups (n = 8) and the substances were given intraperitoneally to them: Control group (saline for 5 days); Theanine group (200 mg/kg/day theanine for 5 days); DOX group (single dose of 20 mg/kg DOX); DOX + Theanine group (20 mg/kg DOX at first day and 200 mg/kg/day theanine for 5 days). Kidney tissues were evaluated by histopathological analysis. Serum levels of blood urea nitrogen (BUN) and creatinine by spectrophotometrically; percentage of apoptosis indexes (AI%) in the tissues by TUNEL method; caspase-3 levels, reduced and oxidized glutathione (GSH and GSSG), gamma-glutamyltransferase 1 (GGT1), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST), nuclear factor kappa B p65 (NF-kB p65) by commercial kits; malondialdehyde (MDA) by spectrophotometrically were determined in plasma and kidney tissues. RESULTS:According to DOX group, the DOX + Theanine group has much lower tissue and plasma GSSG, GGT1, NF-κB p65 levels and tissue AI%, whereas significantly higher GSH levels and GPx, GR, GST activities (P < 0.05). CONCLUSION:It is suggested that L-theanine may have protective effects by enhancing effects on the antioxidant system of GSH and GSH-related enzymes against DOX-induced nephrotoxicity in rats. But this finding needs to be supported with further studies. 10.1016/j.biopha.2018.09.171
Protective effects of L-theanine on rats with dextran sulfate sodium-induced inflammatory bowel disease. Chen Ling,Xiao Wen-Jun,Yan Qiong-Xian,Gong Zhi-Hua,Zhang Sheng,Zeng Li,Yang Ming,Zhou Yan-He Archives of pharmacal research The aim of this study is to evaluate the anti-inflammatory and protective effects of L-theanine in inflammatory bowel disease (IBD) and to identify the underlying molecular mechanisms. Rats were pre-treated with L-theanine at 0, 50, 200, or 800 mg/kg/day. IBD was induced in rats using dextran sulfate sodium (DSS). Histopathological analysis suggests that L-theanine can suppress DSS-induced IBD with significant inhibition of inflammation in large and small intestinal tissues. Moreover, the 200 mg/kg/day L-theanine-treated DSS group had higher body and small intestine weights, a lower disease activity index and expression of inflammatory factors than the DSS group without pre-treatment. In RNA sequencing and tandem mass tag labeling analyses, large number of mRNAs and proteins expression level differed when compared with the DSS-induced rats with and without 200 mg/kg/day L-theanine pre-treatment. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicates the anti-inflammatory activities of L-theanine in DSS-induced IBD, with a high representation of genes in "Cholesterol metabolism" and "Retinol metabolism" pathways. Analysis of protein-protein interaction networks further indicates the involvement of these two pathways. These studies suggest that medium-dose L-theanine pre-treatment could ameliorate DSS-induced IBD through molecular mechanisms involving cholesterol and retinol metabolism. 10.1007/s12272-020-01248-9
Through Its Powerful Antioxidative Properties, L-Theanine Ameliorates Vincristine-Induced Neuropathy in Rats. Antioxidants (Basel, Switzerland) L-theanine (LT), which is a major amino acid found in green tea, was shown to alleviate Vincristine (VCR)-induced peripheral neuropathy and associated neuronal functional changes in rats. To induce peripheral neuropathy, rats were administered VCR at a dose of 100 mg/kg/day intraperitoneally on days 1-5 and 8-12, while control rats received LT at doses of 30, 100, and 300 mg/kg/day intraperitoneally for 21 days or saline solution. Electrophysiological measurements were taken to evaluate the nerve functional loss and recovery through motor and sensory nerve conduction velocities. The sciatic nerve was examined for several biomarkers, including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total calcium, IL-6, IL-10, MPO, and caspase-3. The results showed that VCR caused significant hyperalgesia and allodynia in rats; decreased nerve conduction velocity; increased NO and MDA levels; and decreased GSH, SOD, CAT, and IL-10 levels. LT was found to significantly reduce VCR-induced nociceptive pain thresholds, decrease oxidative stress levels (NO, MDA), increase antioxidative strength (GSH, SOD, CAT), and reduce neuroinflammatory activity and apoptosis markers (caspase-3). LT's antioxidant, calcium homeostasis, anti-inflammatory, anti-apoptotic, and neuroprotective properties make it a potential adjuvant to conventional treatment in VCR-induced neuropathy in rats. 10.3390/antiox12040803
L-theanine . Monograph. Alternative medicine review : a journal of clinical therapeutic
L-Theanine elicits umami taste via the T1R1 + T1R3 umami taste receptor. Narukawa Masataka,Toda Yasuka,Nakagita Tomoya,Hayashi Yukako,Misaka Takumi Amino acids L-Theanine is a unique amino acid present in green tea. It elicits umami taste and has a considerable effect on tea taste and quality. We investigated L-theanine activity on the T1R1 + T1R3 umami taste receptor. L-Theanine activated T1R1 + T1R3-expressing cells and showed a synergistic response with inosine 5'-monophosphate. The site-directed mutagenesis analysis revealed that L-theanine binds to L-amino acid binding site in the Venus flytrap domain of T1R1. This study shows that L-theanine elicits an umami taste via T1R1 + T1R3. 10.1007/s00726-014-1713-3
Adsorption Behavior of the L-Theanine onto Cation Exchange Resin ZGSPC106Na and D001SD. Foods (Basel, Switzerland) Adsorption is an important technology for the separation of different tea components. The adsorption behavior of L-theanine onto adsorbents was comprehensively studied in this paper. Among tested adsorbents, cation exchange resin ZGSPC106Na and D001SD were suitable for separating L-theanine, PVPP and PA-6 for catechins and macroporous resin HPD-400 for caffeine. Adsorption of L-theanine onto the cation resins was significantly influenced by the acidity, contact time and temperature. The adsorption behavior could be described by the pseudo-second-order rate equation and fitted to Langmuir and Freundlich models. ZGSPC106Na exhibited higher adsorption capacity, while D001SD showed higher adsorption selectivity. These might be attributed to the distinctive structure of the two resins and different ionization of the adsorbates. A method for simultaneous preparation of decaffeinated polyphenols, caffeine-enriched extract and decaffeinated L-theanine was established through successive separation on the columns fulfilled with PA-6, HPD-400 and D001SD, respectively. 10.3390/foods11223625
l-Theanine improves functional recovery after traumatic spinal cord injury in rats. Yang Chih-Chuan,Chang Kuo-Chi,Wang Mao-Hsien,Tseng Hsiang-Chien,Soung Hung-Sheng,Fang Chih-Hsiang,Lin Yi-Wen,Li Keng-Yuan,Tsai Cheng-Chia Journal of the Formosan Medical Association = Taiwan yi zhi BACKGROUND/PURPOSE:Spinal cord injury (SCI) is a devastating medical condition for which no effective pharmacological interventions exist. l-Theanine (LT), a major amino acid component of green tea, exhibits potent antioxidative and anti-inflammatory activities and protects against various neural injuries. Here, we evaluated the potential therapeutic effects of LT on the recovery of behavioral motor functions after SCI in rats and the underlying neuroprotective mechanisms. METHODS:SCI was induced by applying vascular clips to the dura through a four-level T5-T8 laminectomy, and saline or LT (10/30 mg/kg) was intrathecally administered at 1-, 6-, and 24-h post-SCI. At 72-h post-SCI, half of the rats from each group for each parameter were sacrificed, and their spinal cord was excised for measurement of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase, catalase, tumor necrosis factor-α, interleukin-1β/-6, myeloperoxidase, and caspase-3. The remaining rats from each group were subjected to Bresnahan locomotor-rating scale (BBB), inclined-plane, toe-spread, and hindfoot bar-grab tests at 1-, 4-, 7-, 10-, and 14-days post-SCI. RESULTS:LT treatment reduced NO and MDA levels, increased antioxidative strength, and markedly suppressed the levels of neuroinflammatory and apoptotic markers in the spinal cord after SCI. Moreover, LT treatment drastically promoted the recovery of behavioral motor functions post-SCI. CONCLUSION:Our findings revealed that LT can enhance the recovery of behavioral motor functions after SCI in rats, which related to the suppression of post-traumatic oxidative response, neural inflammation, and apoptosis. This evidence indicates that LT holds considerable potential for use in the clinical treatment/prevention of SCI-induced motor dysfunction. 10.1016/j.jfma.2019.11.009
L-theanine improves neurophysiological measures of attention in a dose-dependent manner: a double-blind, placebo-controlled, crossover study. Dassanayake Tharaka L,Kahathuduwa Chanaka N,Weerasinghe Vajira S Nutritional neuroscience L-theanine, a non-proteinic amino acid found in tea, is known to enhance attention particularly in high doses, with no reported adverse effects. We aimed to determine whether oral administration of L-theanine acutely enhances neurophysiological measures of selective attention in a dose-dependent manner. In a double-blind, placebo-controlled, counterbalanced, 4-way crossover study in a group of 27 healthy young adults, we compared the effects of 3 doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water) on latencies of amplitudes of attentive and pre-attentive cognitive event-related potentials (ERPs) recorded in an auditory stimulus discrimination task, before and 50 min after dosing. Compared to the placebo, 400 mg of theanine showed a significant reduction in the latency of the parietal P3b ERP component ( < 0.05), whereas no significant changes were observed with lower doses. A subsequent exploratory regression showed that each 100-mg increase in dose reduces the P3b latency by 4 ms ( < 0.05). No dose-response effect was observed in P3b amplitude, pre-attentive ERP components or reaction time. The findings indicate L-theanine can increase attentional processing of auditory information in a dose-dependent manner. The linear dose-response attentional effects we observed warrant further studies with higher doses of L-theanine. 10.1080/1028415X.2020.1804098
The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. Nathan Pradeep J,Lu Kristy,Gray M,Oliver C Journal of herbal pharmacotherapy L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found in green tea. L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been shown to exert neuroprotective effects in animal models possibly through its antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural studies in animals suggest improvement in learning and memory. Overall, L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent and warrants further investigation in animals and humans.
Neuroprotective attributes of L-theanine, a bioactive amino acid of tea, and its potential role in Parkinson's disease therapeutics. Deb Satarupa,Dutta Ankumoni,Phukan Banashree Chetia,Manivasagam Thamilarasan,Justin Thenmozhi Arokiasamy,Bhattacharya Pallab,Paul Rajib,Borah Anupom Neurochemistry international Meta-analyses of tea consumption and reduced risk of Parkinson's disease have thrown light in the pathway of exploring beneficial properties of tea components. On the basis of dry mass, a typical black or green tea beverage contains approximately 6% of free amino acids, which impart high quality, taste and distinctive aroma to the tea infusion. L-theanine (chemically known as γ-glutamylethylamide) is a non-proteinogenic amino acid of tea that takes part in the biosynthesis of its polyphenols. Recently discovered neuroprotective effects of L-theanine can be attributed to its structural analogy with glutamate, the principal excitatory neurotransmitter in brain. This unique amino acid also bears a potential to ameliorate the pathophysiological changes associated with Parkinson's disease as it displays antioxidant and anti-inflammatory properties, improves motor behavioral abnormalities, increases dopamine availability and may cause a favorable downshift in neurodegeneration due to glutamate excitotoxicity. To gain an explicit understanding of the role of L-theanine, this review article is the first one to focus on its mechanism of neuromodulatory action and to critically evaluate the possibilities of employing this bioactive amide in the forage of anti-Parkinsonian medication. We also hypothesize the idea of L-theanine being a potent natural agent against L-DOPA induced dyskinesia, since long-term reliance on dopamine replacement therapy is linked with elevation in glutamate receptor activity. 10.1016/j.neuint.2019.104478
L-theanine combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: A placebo-controlled, double-blind, randomized trial. Psychiatry and clinical neurosciences AIM:The main aim of this study was to investigate the additional effects of L-theanine, an amino acid in tea and an analog of glutamate with neuroprotective and anti-depressant properties, on obsessive-compulsive disorder (OCD) symptoms in combination with fluvoxamine. METHODS:Patients from either sex aged between 18 and 60 years diagnosed with OCD, based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of more than 21 were enrolled in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either L-theanine (100 mg twice daily) and fluvoxamine (100 mg daily initially followed by 200 mg daily after week 5) or placebo and fluvoxamine. The primary outcome of interest in this study was the Y-BOCS total score decrease from baseline. RESULTS:From a total of 95 evaluated patients, 50 completed our study; 30 were randomly assigned to each group. Multivariate analysis (ANOVA) showed a significant effect of time treatment for L-theanine in obsession subscale (F = 5.51, P = 0.008) of the Y-BOCS score but not in the total and compulsion scores. Our results showed significantly more improvement in obsession subscale scores in L-theanine compared to placebo group (P = 0.007, Cohen's d = 0.82). Also, total Y-BOCS scores were lower in L-theanine compared to placebo group at week 5 (P = 0.039, Cohen's d = 0.60) and 10 (P = 0.008, Cohen's d = 0.80). However, there was no significant between-group differences in compulsion subscale scores. Complete response was also more frequent in the L-theanine group (P = 0.0001). CONCLUSION:Findings in this study suggest L-theanine as a relatively safe and effective adjuvant therapy for moderate to severe OCD. 10.1111/pcn.13565
The combined effects of L-theanine and caffeine on cognitive performance and mood. Owen Gail N,Parnell Holly,De Bruin Eveline A,Rycroft Jane A Nutritional neuroscience The aim of this study was to compare 50 mg caffeine, with and without 100 mg L-theanine, on cognition and mood in healthy volunteers. The effects of these treatments on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood were compared to placebo in 27 participants. Performance was measured at baseline and again 60 min and 90 min after each treatment (separated by a 7-day washout). Caffeine improved subjective alertness at 60 min and accuracy on the attention-switching task at 90 min. The L-theanine and caffeine combination improved both speed and accuracy of performance of the attention-switching task at 60 min, and reduced susceptibility to distracting information in the memory task at both 60 min and 90 min. These results replicate previous evidence which suggests that L-theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks. 10.1179/147683008X301513
Production of L-Theanine Using Whole-Cell Overexpressing γ-Glutamylmethylamide Synthetase with Bakers Yeast. Journal of microbiology and biotechnology L-Theanine, found in green tea leaves has been shown to positively affect immunity and relaxation in humans. There have been many attempts to produce L-theanine through enzymatic synthesis to overcome the limitations of traditional methods. Among the many genes coding for enzymes in the L-theanine biosynthesis, glutamylmethylamide synthetase (GMAS) exhibits the greatest possibility of producing large amounts of production. Thus, GMAS from No. 9 was overexpressed in several strains including vectors with different copy numbers. BW25113(DE3) cells containing the pET24ma:: was selected for strains. The optimal temperature, pH, and metal ion concentration were 50°C, 7, and 5 mM MnCl, respectively. Additionally, ATP was found to be an important factor for producing high concentration of L-theanine so several strains were tested during the reaction for ATP regeneration. Bakers yeast was found to decrease the demand for ATP most effectively. Addition of potassium phosphate source was demonstrated by producing 4-fold higher L-theanine. To enhance the conversion yield, GMAS was additionally overexpressed in the system. A maximum of 198 mM L-theanine was produced with 16.5 mmol/l/h productivity. The whole-cell reaction involving GMAS has greatest potential for scale-up production of L-theanine. 10.4014/jmb.1910.10044
l-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways. Gong Zhihua,Liu Qiuling,Lin Ling,Deng Yanli,Cai Shuxian,Liu Zunying,Zhang Sheng,Xiao Wenjun,Xiong Shuo,Chen Dong European journal of pharmacology l-Theanine (LTA; γ-glutamylethylamide), a peculiar non-protein-derived amino acid isolated from tea, is widely used as a functional ingredient and dietary supplement. l-Theanine has been confirmed to have hepatoprotective effects, but the underlying mechanism remains unknown. This study investigated the protective effect of l-Theanine-in vivo, using an enterotoxigenic Escherichia coli (ETEC)-infected mouse model. l-Theanine significantly decreased the elevated serum activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT), two biomarkers of hepatic impairment. This was consistent with histopathological images from the microscopic observation of liver tissue. In addition, l-theanine significantly increased the mRNA and protein expression of Bcl-2 and decreased the expression of Bax, anti- and pro-apoptotic molecules, respectively, compared with levels in the ETEC control group. The expression of cleaved caspase-3 protein in the group pre-treated with l-theanine was significantly lower than that in the ETEC group. Additionally, decreases in extracellular signal-regulated kinase (ERK1/2) and c-Jun NH-terminal kinase(JNK1/2) MAPK phosphorylation were observed in the l-theanine pre-treated group. Our study demonstrates that l-theanine possesses anti-apoptotic activity, which can be attributed to suppression of the intrinsic mitochondria-mediated apoptosis and MAPK phosphorylation signaling pathways. 10.1016/j.ejphar.2017.10.050
l-Theanine attenuates liver aging by inhibiting advanced glycation end products in d-galactose-induced rats and reversing an imbalance of oxidative stress and inflammation. Zeng Li,Lin Ling,Peng Yingqi,Yuan Dongyin,Zhang Sheng,Gong Zhihua,Xiao Wenjun Experimental gerontology Redox and inflammation imbalances are associated with increased levels of advanced glycation end products (AGEs), leading to the degeneration of body function. l-Theanine, derived from tea, reportedly inhibits AGE formation in vitro. We investigated the effects on AGE content, oxidative stress, and inflammatory factors in d-galactose-induced aging rats for prevention and treatment of age-related liver dysfunction. l-Theanine increased activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, thus enhancing total antioxidant capacity, and decreasing malondialdehyde and nitric oxide synthase levels in serum and liver. Levels of the pro-inflammatory factors, interleukin (IL)-1β, tumour necrosis factor-alpha, and IL-6 were decreased in serum and liver, whereas those of anti-inflammatory factors, IL-4 and IL-10, were increased in the serum. Further, l-theanine inhibited AGE production and decreased the levels of the liver function markers, alanine aminotransaminase and aspartate aminotransferase. It also significantly increased the mRNA expression levels of FoxO1 and downregulated NF-κB(p65) but suppressed the phosphorylation of both FOXO1 and NF-κB (p65). Moreover, l-theanine effectively attenuated d-galactose-induced oedema and vacuole formation, thus protecting the liver. Overall, l-theanine reversed the d-galactose-induced imbalance in oxidative stress and inflammatory responses, reduced AGEs content in aging rats, maintained homeostasis in the body, and ameliorated liver aging. 10.1016/j.exger.2019.110823
L-theanine partially counteracts caffeine-induced sleep disturbances in rats. Jang Hwan-Soo,Jung Ji Young,Jang Il-Sung,Jang Kwang-Ho,Kim Sang-Hyun,Ha Jeoung-Hee,Suk Kyoungho,Lee Maan-Gee Pharmacology, biochemistry, and behavior L-theanine has been reported to inhibit the excitatory effects of caffeine. The present study examined the effects of L-theanine on caffeine-induced sleep disturbances in rats. Rats received the following drug pairings: saline and saline (Control), 7.5 mg/kg caffeine and saline, or 7.5 mg/kg of caffeine followed by various doses of L-theanine (22.5, 37.5, 75, or 150 mg/kg). Vigilance states were divided into: wakefulness (W), transition to slow-wave sleep (tSWS), slow-wave sleep (SWS), and rapid-eye-movement sleep (REMS). Caffeine significantly increased the duration of W and decreased the duration of SWS and REMS compared to the Control. Although L-theanine failed to reverse the caffeine-induced W increase, at 22.5 and 37.5 mg/kg (but not at 75 and 150 mg/kg), it significantly reversed caffeine-induced decreases in SWS. In conclusion, low doses of L-theanine can partially reverse caffeine-induced reductions in SWS; however, effects of L-theanine on caffeine-induced insomnia do not appear to increase dose-dependently. 10.1016/j.pbb.2012.01.011
L-Theanine Regulates the Abundance of Amino Acid Transporters in Mice Duodenum and Jejunum via the mTOR Signaling Pathway. Nutrients The intestine is a key organ for the absorption of amino acids. L-theanine (LTA) is a structural analog of glutamine and a characteristic non-protein amino acid found in tea () that regulates lipid and protein metabolism. The present study explored the role of LTA in intestinal amino acid absorption, protein synthesis, and its mechanisms. Overall, our findings suggest that LTA supplementation not only affects serum alkaline phosphatase (AKP), total protein (TP), and urea nitrogen (BUN) levels, but it also upregulates the mRNA and protein expression of amino acid transporters (EAAT3, EAAT1, 4F2hc, yLAT1, CAT1, ASCT2, and BAT1), and activates the mTOR signaling pathway. The downstream S6 and S6K1 proteins are regulated, and the expression of amino acid transporters is regulated. These findings suggest that LTA increases intestinal AA absorption, promotes protein metabolism, and increases nitrogen utilization by upregulating AAT expression, activating the mTOR signaling pathway, and phosphorylating the mTOR downstream proteins S6 and S6K1. 10.3390/nu15010142
Dietary L-theanine supplementation improves lipid metabolism and antioxidant capacity in weaning piglets. Animal biotechnology The aim of this study was to explore the effects of dietary L-theanine (LT) supplementation on lipid metabolism and antioxidant capacity in weaned piglets. Twenty-one castrated DLY weaning piglets were randomly divided into three groups: a basal diet, a basal diet supplemented with 0.05% and 0.1% LT, respectively. Our data showed that dietary LT supplementation decreased T-CHO, TG, LDL-C and apoB levels and increased apoA and HDL-C levels in serum, but decreased the hepatic TG and T-CHO contents. Dietary LT supplementation increased the antioxidant capacity in serum and liver, and significantly increased the mRNA level and the nucleus Nrf2 protein level, but decreased the mRNA level of in the liver. In addition, dietary LT supplementation significantly increased HSL enzyme activity and the levels of CPT1 and TBA, while decreasing the enzyme activities of LPL and FAS in the liver. Furthermore, the mRNA levels , and and the protein levels of phosphorylated-AMPK and PGC-1α were increased by LT. Together, our data provide the first evidence that dietary supplementation of LT could improve lipid metabolism and antioxidant capacity in the liver of weaned piglets, and the effect might be mediated by activation of AMPK and Nrf2 signaling, respectively. 10.1080/10495398.2022.2099883
l-Theanine Ameliorates d-Galactose-Induced Brain Damage in Rats via Inhibiting AGE Formation and Regulating Sirtuin1 and BDNF Signaling Pathways. Zeng Li,Lin Ling,Chen Ling,Xiao Wenjun,Gong Zhihua Oxidative medicine and cellular longevity The maintenance of homeostasis is essential for mitigating stress and delaying degenerative diseases such as Alzheimer's disease (AD). AD is generally defined as the abnormal production of -amyloid (A) and advanced glycation end products (AGEs). The effects of l-theanine on A and AGE generation were investigated in this study. Decreased AGEs and A levels were reflected by increased acetylcholine (ACh) concentration and acetylcholinesterase AChE activity inhibition compared to model rats. l-Theanine also inhibited nuclear factor-B (p65) protein expression by activating sirtuin1 (SIRT1), reducing inflammatory factor expression, and downregulating the mRNA and protein expression of AGE receptors (RAGE). Superoxide dismutase 2 and catalase protein expressions were markedly upregulated by l-theanine, whereas oxidative stress-related injury was alleviated. The expression of peroxisome proliferator-activated receptor- coactivator 1 (PGC-1) was also found to be increased. H&E staining showed that the apoptosis of hippocampal neurons was mitigated by decreased Bax and cleaved-caspase-3 protein expression and the increase of Bcl-2 protein expression. Moreover, l-theanine increased the gene and protein expression of brain-derived neurotrophic factor (BDNF). These findings suggest that the potential preventive effects of l-theanine against AD may be attributed to its regulation of SIRT1 and BDNF proteins and its mitigation of AGEs/RAGE signaling pathways in the brain tissue of AD model rats. 10.1155/2021/8850112
Psychological effects of dietary components of tea: caffeine and L-theanine. Bryan Janet Nutrition reviews This review summarizes the literature on the association between two dietary components of tea, caffeine and L-theanine, and the psychological outcomes of consumption; it also identifies areas for future research. The studies reviewed suggest that caffeinated tea, when ingested at regular intervals, may maintain alertness, focused attention, and accuracy and may modulate the more acute effects of higher doses of caffeine. These findings concur with the neurochemical effects of L-theanine on the brain. L-theanine may interact with caffeine to enhance performance in terms of attention switching and the ability to ignore distraction; this is likely to be reflective of higher-level cognitive activity and may be sensitive to the detrimental effects of overstimulation. Further research should investigate the interactive effects of caffeine, L-theanine, and task complexity, utilize a range of ecologically valid psychological outcomes, and assess the neuroprotective effects of L-theanine using epidemiological or longer-term intervention studies among individuals at risk of neurodegenerative disease. 10.1111/j.1753-4887.2007.00011.x
Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis. Camfield David A,Stough Con,Farrimond Jonathon,Scholey Andrew B Nutrition reviews A systematic review and meta-analysis was conducted on 11 randomized placebo-controlled human studies of acute effects of tea constituents L-theanine and epigallocatechin gallate, administered alone or in combination with caffeine, on cognitive function and mood. The outcome measures of mood were alertness, calmness, and contentedness, derived from the Bond-Lader scales, and state anxiety, from the State-Trait Anxiety Inventory. Cognitive measures assessed were attentional switch, intersensory attention, and rapid visual information processing. Standardized mean differences between placebo and treatment groups are presented for each study and outcome measure. Meta-analysis using a random-effects model was conducted when data were available for three or more studies. Evidence of moderate effect sizes in favor of combined caffeine and L-theanine in the first 2 hours postdose were found for outcome measures Bond-Lader alertness, attentional switching accuracy, and, to a lesser extent, some unisensory and multisensory attentional outcomes. Moderator analysis of caffeine and L-theanine doses revealed trends toward greater change in effect size for caffeine dose than for L-theanine dose, particularly during the first hour postdose. 10.1111/nure.12120
Caution may be required in using l-theanine in diabetes mellitus: A study on the rats. Biochemical and biophysical research communications BACKGROUND:The study aimed to identify the effects of l-theanine on kidney and heart tissues in diabetic rats. 24 male rats included in the study were divided into 4 groups (n = 6/group): SHAM, LTEA, DM and DM + LTEA. For 28 days, drinking water was given to SHAM and DM, and LTEA (200 mg/kg/day) to LTEA and DM + LTEA groups, intragastrically. DM was induced by 120 mg/kg nicotinamide (NA) + 60 mg/kg streptozotocin (STZ). The levels of cystatin C (CysC) and angiotensin-converting enzyme 2 (ACE2) were determined by ELISA kits, homocysteine, electrolytes and iron by an autoanalyzer, the ratio of oxidized/total reduced glutathione (GSSG/TGSH) by assay kits. The tissues were histopathologically analyzed. RESULTS:LTEA alleviated histopathological degenerations. However, it decreased significantly serum iron and homocysteine levels (p < 0.05). CONCLUSION:LTEA did not exhibit significant protective effects on kidney and heart tissues; it may have affected the homocysteine and iron metabolisms in diabetics. 10.1016/j.bbrc.2023.04.095
Nutritional applications and beneficial health applications of green tea and l-theanine in some animal species: A review. Alagawany Mahmoud,Abd El-Hack Mohamed E,Saeed Muhammad,Naveed Muhammad,Arain Muhammad A,Arif Muhammad,Tiwari Ruchi,Khandia Rekha,Khurana Sandip K,Karthik Kumaragurubaran,Yatoo Mohd I,Munjal Ashok,Bhatt Prakash,Sharun Khan,Iqbal Hafiz M N,Sun Chao,Dhama Kuldeep Journal of animal physiology and animal nutrition Green tea (Camellia sinensis) is a popular herbal plant with abundant health benefits, and thus, it has been used as a potent antioxidant for a long time. Based on the available literature, the diversity and the availability of multifunctional compounds in green tea offer its noteworthy potential against many diseases such as liver and heart diseases, inflammatory conditions and different metabolic syndromes. Owing to its bioactive constituents including caffeine, amino acids, l-theanine, polyphenols/flavonoids and carbohydrates among other potent molecules, green tea has many pharmacological and physiological effects. The effects of green tea include anti-oxidative, anti-inflammatory, anti-arthritic, anti-stress, hypolipidaemic, hypocholesterolaemic, skin/collagen protective, hepatoprotective, anti-diabetic, anti-microbial, anti-infective, anti-parasitic, anti-cancerous, inhibition of tumorigenesis and angiogenesis, anti-mutagenic, and memory and bone health-improving activities. Apart from its utilization in humans, green tea has also played a significant role in livestock production such as in dairy, piggery, goatry and poultry industries. Supplementation of animal feeds with green tea and its products is in line with the modern concepts of organic livestock production. Hence, incorporating green tea or green tea by-products into the diet of poultry and other livestock can enhance the value of the products obtained from these animals. Herein, an effort is made to extend the knowledge on the importance and useful applications of green tea and its important constituents in animal production including poultry. This review will be a guideline for researchers and entrepreneurs who want to explore the utilization of feeds supplemented with green tea and green tea by-products for the enhancement of livestock production. 10.1111/jpn.13219
l-Theanine ameliorates motor deficit, mitochondrial dysfunction, and neurodegeneration against chronic tramadol induced rats model of Parkinson's disease. Drug and chemical toxicology Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disease, characterized by loss of dopaminergic neurons in substantia nigra, with deficiency of dopamine in the striatum. Tramadol is safe analgesic but long-term use confirmed to elevate oxidative stress, neuroinflammation, mitochondrial dysfunction, in brain leads to motor deficits. l-Theanine is an active constituent of green tea which prevents neuronal loss, mitochondrial failure and improves dopamine, gamma-aminobutyric acid (GABA), serotonin levels and in the central nervous system (CNS) via antioxidant, anti-inflammatory, and neuromodulatory properties. In the present study, tramadol was injected intraperitoneally to Wister rats for 28 days at a dose of 50 mg/kg. l-Theanine (25, 50, and 100 mg/kg) was administered orally 3 h before tramadol administration from day 14 to day 28. Behavioral analyses including rotarod, narrow beam walk, open field, and grip strength were used to evaluate motor coordination on a weekly basis. On the day 29, all Wistar rats were sacrificed and striatum homogenates were used for biochemical (lipid peroxidation, nitrite, glutathione, glutathione peroxidase activity, superoxide dismutase, catalase, mitochondrial complex I, IV, and cyclic adenosine monophosphate), neuroinflammatory markers (tumor necrosis factor-α, interleukin-1β, and interleukin-17), and neurotransmitters (dopamine, norepinephrine, serotonin, GABA, and glutamate) analysis. Chronic tramadol treatment caused motor deficits reduced antioxidant enzymes level, increased striatal proinflammatory cytokines release, dysbalanced neurotransmitters, and reduced mitochondrial complex activity I, IV, and cAMP activity. However, l-theanine administration attenuated behavioral, biochemical, neuroinflammatory, neurotransmitters, and mitochondrial activity indicated it as a promising neuroprotective potential against degenerative changes in experimental model of PD. 10.1080/01480545.2021.1907909
L-Theanine attenuates heat stress-induced proteotoxicity and alterations in carbohydrate and lipid metabolism heat shock factor 1. Food & function Extreme heat caused by global warming accelerated the frequency of heat stress (HS). Proteotoxic stress induced by the aggregation of misfolded proteins and metabolic stress triggered by alterations in the metabolism were observed during HS. The activation of heat shock factor 1 (Hsf1) and its interaction with adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) are critical in addressing proteotoxicity and metabolic stress in heat-stressed organisms. Previous studies have shown that L-theanine (LTA) can regulate nutrient metabolism through the AMPK pathway and can alleviate HS. Therefore, we hypothesize that LTA may help in restoring homeostasis by regulating nutrient metabolism under HS. Here, we investigated the effects of LTA on nutrient metabolism in heat-stressed rats and characterized the underlying mechanisms using RNA sequencing and metabonomics. The results showed that LTA alleviated HS-induced liver damage, promoted body weight gain, decreased serum cortisol and enhanced the total protein content. Besides, it regulated the expression of genes related to carbohydrate, lipid and amino acid metabolism and altered metabolite levels. Moreover, LTA inhibited the expression of Hsf1 and heat shock protein 70 (Hsp70), promoted AMPK phosphorylation and the expression of glucose-6-phosphatase catalytic subunit 1 (), and inhibited the phosphorylation of acetyl-CoA carboxylase 1 (ACC1) in heat-stressed rats. Mechanistically, LTA alleviated HS-induced proteotoxic stress by acting on Hsf1/Hsp70; simultaneously, it promoted AMPK phosphorylation by suppressing Hsf1 expression, which in turn inhibited fatty acid synthesis and hepatic gluconeogenesis, thus alleviating HS-induced metabolic stress. These results suggest that LTA regulates nutrient metabolism through Hsf1/AMPK and alleviates HS-induced proteotoxicity Hsf1/Hsp70. 10.1039/d3fo01001e
Regulatory Effects and Mechanisms of L-Theanine on Neurotransmitters via Liver-Brain Axis Under a High Protein Diet. Molecular neurobiology Excessive protein intake causes liver and brain damage and neurotransmitter disorders, thereby inducing cognitive dysfunction. L-theanine can regulate the neurotransmitter content and show great potential in liver and brain protection. However, it remains unclear whether l-theanine effectively regulates neurotransmitter content under high-protein diet. A 40-day feeding experiment was performed in Sprague Dawley rats to investigate the regulatory effects and mechanisms of l-theanine on neurotransmitters via liver-brain axis in high-protein diets. The results showed that a 30% protein diet increased the liver and brain neurotransmitter content while maintaining the normal structure of liver and the hippocampal CA1 of brain and improving the autonomous behavior of rats. In contrast, 40% and 50% protein diets decreased the content of neurotransmitters, affected autonomous behavior, destroyed the hippocampal CA1 of brain structure, increased hepatic inflammatory infiltration, lipid degeneration, and hepatocyte eosinophilic change in liver, increased liver AST, ALT, MDA, CRP, and blood ammonia level, and decreased liver SOD and CAT level. However, l-theanine improved liver and brain neurotransmitter content, autonomous behavior, liver and hippocampal brain structure, and liver biochemical indicators in 40% and 50% protein diets. To explore how LTA can eliminate the adverse effects of a high-protein diet, we analyzed different metabolites and proteomes and using western blotting for validate quantitatively. We found that l-theanine regulates the activity of PF4 and G protein subunit alpha i2, increases the content of brain-derived neurotrophic factor and dopamine under a 20% protein diet. In addition, l-theanine can activate the adenylate cyclase-protein kinase A pathway through the protein alpha/beta-hydrolase domain protein 12 to regulate the content of neurotransmitters under a 40% protein diet, thereby exerting a neuroprotective effect. 10.1007/s12035-023-03608-0
l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes. Li Guilan,Ye Yin,Kang Jingjing,Yao Xiangyang,Zhang Yizhou,Jiang Wei,Gao Min,Dai Yudong,Xin Yinqiang,Wang Qi,Yin Zhimin,Luo Lan Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association l-Theanine is a unique amino acid in green tea. We here evaluated the protective effects of l-theanine on ethanol-induced liver injury in vitro and in vivo. Our results revealed that l-theanine significantly protected hepatocytes against ethanol-induced cell cytotoxicity which displayed by decrease of viability and increase of LDH and AST. Furthermore, the experiments of DAPI staining, pro-caspase3 level and PARP cleavage determination indicated that l-theanine inhibited ethanol-induced L02 cell apoptosis. Mechanically, l-theanine inhibited loss of mitochondrial membrane potential and prevented cytochrome c release from mitochondria in ethanol-treated L02 cells. l-Theanine also prevented ethanol-triggered ROS and MDA generation in L02 cells. l-Theanine restored the antioxidant capability of hepatocytes including GSH content and SOD activity which were reduced by ethanol. In vivo experiments showed that l-theanine significantly inhibited ethanol-stimulated the increase of ALT, AST, TG and MDA in mice. Histopathological examination demonstrated that l-theanine pretreated to mice apparently diminished ethanol-induced fat droplets. In accordance with the in vitro study, l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities. 10.1016/j.fct.2011.10.036
L-Theanine Modulates Intestine-Specific Immunity by Regulating the Differentiation of CD4+ T Cells in Ovalbumin-Sensitized Mice. Journal of agricultural and food chemistry Ovalbumin (OVA), a common food protein, can cause deadly allergies with intestine-specific immune reactions. L-Theanine (LTA) shows great potential for regulating intestinal immunity. To investigate the regulatory effect of LTA intervention on intestine-specific immunity, a 41 day experiment was performed on BALB/c OVA-sensitized mice. The results show that injecting female mice intraperitoneally with 50 μg of OVA and administering 30 mg of OVA 4 times can successfully establish an OVA-sensitized mouse model. LTA intervention significantly increased weight gain and thymus index ( < 0.05), decreased allergy and diarrhea scores ( < 0.05), and improved jejunum structure. Meanwhile, the histological score and degranulation of mast cells decreased. LTA intervention increased , , , , and abundance while decreasing abundance Flow cytometry and Western blotting results indicated that 200 and 400 mg/kg of LTA upregulated the expression of T-bet and Foxp3 proteins ( < 0.05), thus promoting the differentiation of jejunum CD4+ T cells to Th1 and Tregs and increasing the cytokines IFN-γ, IL-10, and TGF-β ( < 0.05). We found that 200 and 400 mg/kg of LTA downregulated the expression of RORγt and GATA3, thus inhibiting the differentiation of Th2 and Th17 cells and decreasing cytokines IL-4, IL-5, IL-13 TNF-α, IL-6, and IL-17A ( < 0.05). LTA inhibited the degranulation of mast cells and significantly decreased the serum levels of OVA-IgE, HIS, and mouse MCPT-1 ( < 0.05). Therefore, LTA intervention alleviated OVA allergy by improving intestine-specific immunity. 10.1021/acs.jafc.2c06171
The protective effect of L-theanine addition to a cryoprotectant on the storage viability of lactic acid bacteria. International microbiology : the official journal of the Spanish Society for Microbiology Lactic acid bacteria (LAB) that metabolize sugars to obtain energy and produce a large amount of lactate through the process are well known for their benefits. However, they can be used on a large scale only when good storage stability is guaranteed. The vitality and stability of several LAB strains were effectively protected in this investigation by L-theanine at 1% of the appropriate concentration (Lactiplantibacillus plantarum MG5023, Enterococcus faecium MG5232, Lactococcus lactis MG4668, Streptococcus thermophilus MG5140, and Bifidobacterium animalis subsp. lactis MG741). The inclusion of L-theanine as a protective agent significantly enhanced the viability of all strains throughout the freeze-drying process compared to that of the non-coated probiotics. The efficacy of L-theanine in improving bacterial stability and survivability was evaluated using accelerated stability tests, gastrointestinal (GI) tract survivability tests, and adhesion assays with intestinal epithelial cells. The cell surface was covered with substances including L-theanine, according to morphological findings, providing efficient defense against a variety of external stresses. Therefore, by exerting anti-freezing and anti-thawing properties, the adoption of L-theanine as a new and efficient protective agent may improve the stability and viability of a variety of probiotics. 10.1007/s10123-023-00444-z
L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes. Biological chemistry The aim of this study was to investigate the effect and mechanism of L-theanine (LT) on muscle fiber type transformation in C2C12 myotubes. Our data showed that LT exhibited significantly higher slow oxidative muscle fiber expression and lower glycolytic fibers expression. In addition, LT significantly increased the activities of malate dehydrogenase (MDH) and succinic dehydrogenase (SDH), and decreased lactate dehydrogenase (LDH) activity, the calcineurin (CaN) activity and the protein expressions of nuclear factor of activated T cell 1 (NFATc1), prospero-related homeobox1 (prox1), and calcineurin A (CnA) were significantly increased. However, inhibition of CaN activity by cyclosporine A (CsA) abolished LT-induced increase of slow oxidative muscle fiber expression and decrease of glycolytic fibers expression. Moreover, inhibition of prox1 expression by prox1-siRNA disrupted LT-induced activation of CaN signaling pathway and muscle fiber type transformation. Taken together, these results indicated that LT could promote skeletal muscle fiber type transformation from type II to type I via activation of prox1/CaN signaling pathway. 10.1515/hsz-2022-0165
l-Theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Ben Peiling,Zhang Zhengping,Zhu Yanyan,Xiong Aiying,Gao Yanhong,Mu Jianyun,Yin Zhimin,Luo Lan Neurotoxicology Cadmium (Cd) has long been known to induce neurological degenerative disorders. We studied effects of l-theanine, one of the major amino acid components in green tea, on Cd-induced brain injury in mice. Male ICR mice were intraperitoneally injected with l-theanine (100 or 200mg/kg/day) or saline and after one hour these mice were orally administrated with CdCl (3.75-6mg/kg). The treatment was conducted for 8 weeks. l-Theanine significantly reduced Cd level in the mouse brain and plasma. Cd-induced neuronal cell death in the mouse cortex and hippocampus were apparently inhibited by l-theanine treatment. l-Theanine also decreased the levels of malondialdehyde (MDA) and ROS, and obviously elevated the levels of glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the mouse brain. Hyperphosphorylation of tau protein is proposed to be an early event for the evolution of tau pathology, and may play an important role in Cd-induced neurodegeneration. Our results showed that l-theanine significantly suppressed Cd-induced tau protein hyperphosphorylation at Ser199, Ser202, and Ser396. Mechanism study showed that l-theanine inhibited the activation of glycogen synthase kinase-3β (GSK-3β) which contributed to the hyperphosphorylation of tau and Cd-induced cytotoxicity. Furthermore, l-theanine reduced Cd-induced cytotoxicity possibly by interfering with the Akt/mTOR signaling pathway. In conclusion, our study indicated that l-theanine protected mice against Cd-induced neurotoxicity through reducing brain Cd level and relieved oxidative damage and tau hyperphosphorylation. Our foundings provide a novel insight into the potential use of l-theanine as prophylactic and therapeutic agents for Cd-induced neurodegenerative diseases. 10.1016/j.neuro.2016.09.010
Dietary L-theanine alleviated lipopolysaccharide-induced immunological stress in yellow-feathered broilers. Li Rui,Song Zehe,Zhao Jianfei,Huo Dongxiao,Fan Zhiyong,Hou De-Xing,He Xi Animal nutrition (Zhongguo xu mu shou yi xue hui) L-theanine, a natural nonprotein amino acid with a high biological activity, is reported to exert anti-stress properties. An experiment with a 3 × 2 factorial arrangement was conducted to investigate the effects of dietary L-theanine on growth performance and immune function in lipopolysaccharide (LPS)-challenged broilers. A total of 432 one-day-old male yellow-feathered broilers were randomly assigned to 3 dietary treatments (control, antibiotic and L-theanine diets) with 2 subgroups of each (6 replicate cages; 12 birds/cage). Birds from each subgroup of the 3 dietary treatments were intra-abdominally injected with the same amount of LPS or saline at 24, 25, 26 d of age. Both dietary L-theanine and antibiotic improved ( < 0.05) the growth performance of birds before LPS injection (d 1 to 21). The effect of dietary L-theanine was better ( < 0.05) than that of antibiotic. Lipopolysaccharide decreased feed intake (FI) and body weight gain (BWG) from d 22 to 28 ( < 0.05), BWG and feed to gain ratio (F:G) from d 29 to 56 ( < 0.05), increased mortality in different growth periods ( < 0.05), elevated the levels of serum cortisol, α1-acid glycoprotein (α1-AGP), interleukin-6 (IL-6) on d 24 and 25 ( < 0.05), reduced immune organ indexes and contents of jejunal mucosal secretory immunoglobulin A (sIgA) on d 28 ( < 0.05). The decreased FI and BWG, as well as increased F:G and mortality in LPS-challenged birds, were alleviated by dietary L-theanine or antibiotic from d 29 to 56 and from d 1 to 56. Dietary L-theanine mitigated the elevated serum α1-AGP level on d 25, serum IL-6 concentration on d 24 and 26, and the decreased jejunal mucosal sIgA content on d 28 of the LPS-challenged birds. The results indicated that L-theanine had potential to alleviate LPS-induced immune stress in broilers. 10.1016/j.aninu.2018.05.002
L-Theanine-Treated Adipose-Derived Mesenchymal Stem Cells Alleviate the Cytotoxicity Induced by N-Nitrosodiethylamine in Liver. Tissue engineering and regenerative medicine BACKGROUND:Liver inflammation is the main cause of severe liver diseases, including liver fibrosis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Cell therapy topics are receiving increasingly more attention. The therapeutic applications of mesenchymal stem cells (MSC) have become one of the most discussed issues. While other stem cells have therapeutic effects, they have only one or two clinical applications. MSCs are responsible for repairing a variety of tissue injuries. Moreover, MSCs could be derived from several sources, including adipose tissue. MSCs are usually more abundant and easier to obtain compared to other stem cells. METHODS:To prove the concept that MSCs have homing ability to the injured tissue and assist in tissue repair, we examined the effects of intravenous injected adipose-derived mesenchymal stem cells (ADSCs) in a N-nitrosodiethylamine (DEN)-induced liver injury rat model. RESULTS:The significant repairing ability of ADSCs was observed. The levels of fibrosis, apoptosis, and tumorigenesis in the DEN-injured liver tissues all decreased after ADSC treatment. Furthermore, to enhance the therapeutic effects of ADSCs, we pretreated them with L-theanine, which promotes the hepatocyte growth factor secretion of ADSC, and therefore improved the healing effects on injured liver tissue. CONCLUSION:ADSCs, especially L-theanine-pretreated ADSCs, have anti-inflammation, anti-apoptosis, and anti-tumorigenesis effects on the N-nitrosodiethylamine-induced liver injury rat model. 10.1007/s13770-022-00472-2
L-theanine ameliorate depressive-like behavior in a chronic unpredictable mild stress rat model via modulating the monoamine levels in limbic-cortical-striatal-pallidal-thalamic-circuit related brain regions. Shen Manjun,Yang Yi,Wu Ying,Zhang Beibei,Wu Haishan,Wang Lu,Tang Hui,Chen Jindong Phytotherapy research : PTR L-theanine, originally found in green tea, elicits various physiological effects, such as promoting relaxation, improving concentration and learning ability, and providing antianxiety-like and antidepressant-like properties. This study aims to investigate the effects of L-theanine (2 mg/kg) on monoamine levels in an animal model of depression. The effect of l-theanine on the symptoms of depression was examined through the open-field test, sucrose preference test, and forced swim test. The monoamine neurotransmitters that involve serotonin (5-HT), norepinephrine (NE), and dopamine (DA) were measured in the limbic-cortical-striatal-pallidal-thalamic (LCSPT)-circuit related brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (ST), amygdala, and hippocampus (HIP). L-theanine ameliorated the depressive-like behaviors in the chronic unpredictable mild stress (CUMS) rat model. In the PFC, NAC, and HIP, L-theanine administration significantly increased the levels of 5-HT, NE, and DA. In the ST, the levels of 5-HT and DA were increased after the administration of L-theanine. However, in the HIP, only the level of DA significantly changed after the treatment of L-theanine. Taken together, these results indicated that L-theanine has possibly antidepressant-like effects in the CUMS rat model, which could be mediated by the monoamine neurotransmitters in the LCSPT-circuit related brain regions. 10.1002/ptr.6237
Efficient fermentative production of L-theanine by Corynebacterium glutamicum. Ma Hongkun,Fan Xiaoguang,Cai Ningyun,Zhang Dezhi,Zhao Guihong,Wang Ting,Su Rui,Yuan Meng,Ma Qian,Zhang Chenglin,Xu Qingyang,Xie Xixian,Chen Ning,Li Yanjun Applied microbiology and biotechnology 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 gmas-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. 10.1007/s00253-019-10255-w
Diet and Psychosis: A Scoping Review. Neuropsychobiology INTRODUCTION:Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for intervention in many physical illnesses and more recently in mental illnesses such as unipolar depression; however, no dietary guidelines exist for patients with SSD. OBJECTIVE:This review sought to systematically scope the existing literature in order to identify nutritional interventions for the prevention or treatment of mental health symptoms in SSD as well as gaps and opportunities for further research. METHODS:This review followed established methodological approaches for scoping reviews including an extensive a priori search strategy and duplicate screening. Because of the large volume of results, an online program (Abstrackr) was used for screening and tagging. Data were extracted based on the dietary constituents and analyzed. RESULTS:Of 55,330 results identified by the search, 822 studies met the criteria for inclusion. Observational evidence shows a connection between the presence of psychotic disorders and poorer quality dietary patterns, higher intake of refined carbohydrates and total fat, and lower intake or levels of fibre, ω-3 and ω-6 fatty acids, vegetables, fruit, and certain vitamins and minerals (vitamin B12 and B6, folate, vitamin C, zinc, and selenium). Evidence illustrates a role of food allergy and sensitivity as well as microbiome composition and specific phytonutrients (such as L-theanine, sulforaphane, and resveratrol). Experimental studies have demonstrated benefit using healthy diet patterns and specific vitamins and minerals (vitamin B12 and B6, folate, and zinc) and amino acids (serine, lysine, glycine, and tryptophan). DISCUSSION:Overall, these findings were consistent with many other bodies of knowledge about healthy dietary patterns. Many limitations exist related to the design of the individual studies and the ability to extrapolate the results of studies using dietary supplements to dietary interventions (food). Dietary recommendations are presented as well as recommendations for further research including more prospective observational studies and intervention studies that modify diet constituents or entire dietary patterns with statistical power to detect mental health outcomes. 10.1159/000493399
Effects of dietary l-theanine supplementation on pork quality and muscle fiber type transformation in finishing pigs. Journal of the science of food and agriculture BACKGROUND:This experiment aimed to investigate effects of dietary l-theanine supplementation on pork quality and muscle fiber type transformation in finishing pigs. In a 30-day experiment, 18 healthy Duroc × Landrace × Yorkshire (DLY) pigs with an average body weight of 86.03 ± 0.83 kg were randomly divided into three groups (a basal diet or a basal diet supplemented with 500 and 1000 ppm l-theanine, respectively), with six duplicates and one pig per replicate. RESULTS:The results showed that dietary 1000 ppm l-theanine supplementation significantly reduced (P < 0.05) b* and drip loss. Dietary 1000 ppm l-theanine supplementation significantly increased (P < 0.05) slow myosin heavy chain (MyHC) protein expression and the percentage of slow-twitch fibers, as well as significantly decreased (P < 0.05) fast MyHC protein expression and the percentage of fast-twitch fibers, accompanied by an increase in succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) activities and a decrease in lactate dehydrogenase (LDH) activity. In addition, the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway was activated by l-theanine. CONCLUSION:Together, this study demonstrated for the first time that dietary supplementation of 1000 ppm l-theanine can improve pork color and drip loss and promote muscle fiber type transformation from fast-twitch to slow-twitch in finishing pigs. © 2022 Society of Chemical Industry. 10.1002/jsfa.12368
The effect of L-theanine and S-ketamine on d-serine cellular uptake. Lakatos Péter P,Vincze István,Nyariki Noel,Bagaméry Fruzsina,Tábi Tamás,Szökő Éva Biochimica et biophysica acta. Proteins and proteomics Decreased extracellular level of d-Serine (D-Ser), a co-agonist of the N-methyl-d-aspartate (NMDA) receptors was connected to receptor hypofunction in the brain and the related deficit of cognitive functions. Extracellular D-Ser concentration is modulated by ASCT neutral amino acid transporters. L-Theanine (L-Tea), a neutral amino acid component of green tea was reported to improve cognitive functions. We thus intended to investigate the possible inhibitory effect of L-Tea on the D-Ser uptake of SH-SY5Y neuroblastoma cells, which was previously found as a good model of D-Ser transport into astrocytes. Cells were incubated with D-Ser and various concentrations of L-Tea or the reference compound S-ketamine (S-Ket). The effect on the uptake was assessed by measuring the intracellular D-Ser concentration using a capillary electrophoresis - laser induced fluorescence detection method. L-Tea competitively inhibited D-Ser uptake into SH-SY5Y cells with an IC50 value of 9.68 mM. Having previously described as an inhibitor of ASCT-2 transporter, S-Ket was intended to be used as a positive control. However, no acute inhibition of D-Ser transport by S-Ket was observed. Its long-term effect on the transport was also examined. No significant difference in D-Ser uptake in control and S-Ket-treated cells was found after 72 h treatment, although the intracellular D-Ser content of the 50 μM S-Ket pre-treated cells was significantly higher. L-Tea was found to be a weak competitive inhibitor of the ASCT transporters, while S-Ket did not directly affect D-Ser uptake or modify the uptake kinetics after a long-term incubation period. 10.1016/j.bbapap.2020.140473
Variability of antioxidant properties, catechins, caffeine, L-theanine and other amino acids in different plant parts of Azorean . Paiva Lisete,Lima Elisabete,Motta Madalena,Marcone Massimo,Baptista José Current research in food science During tea processing, manufacturers usually remove the internodes, which are classified as waste. This study presents the first determination of plant part contribution, particularly internodes, to green tea quality, in order to find the best blend to maximize impact on human health. Catechins, caffeine and free amino acid (FAA) profiles were determined by RP-HPLC/DAD, total phenolics (TPC) and total flavonoids (TFC) by Folin-Ciocalteu and colorimetric methodologies, respectively, and antioxidant activities by free radical-scavenging activity (FRSA), ferric-reducing antioxidant power (FRAP) and ferrous ion-chelating (FIC) methods. Individual esterified catechins content decreased as follows: epicatechin-3-gallate > epigallocatechin-3-gallate ≫ gallocatecin-3-gallate, and epicatechin derivatives content ranged from 63.91 to 91.22% of total catechins. Caffeine content was higher in internodes. L-theanine, histidine, asparagine, phenylalanine, glutamic acid and methionine were the major FAAs, and internodes contained the highest amounts of L-theanine and histidine (17 and 13.73 mg/g of sample, respectively). TPC ranged from 201.51 to 265.48 mg gallic acid equivalents/g dry extract (DE) and TFC ranged from 23.84 to 72.02 mg rutin equivalents/g DE. Internodes presented the lowest FRSA (EC = 6.10-13.50 μg/mL), FRAP (EC = 5.70-11.40 μg/mL) and FIC activity (36.96-79.21%). Bud presented the highest FRSA and FRAP, and bud+1st+2leaves + internodes the highest FIC activity. The results revealed the potential contribution of the internodes to green tea quality and, consequently, to human health. 10.1016/j.crfs.2020.07.004
Green tea effects on cognition, mood and human brain function: A systematic review. Mancini Edele,Beglinger Christoph,Drewe Jürgen,Zanchi Davide,Lang Undine E,Borgwardt Stefan Phytomedicine : international journal of phytotherapy and phytopharmacology BACKGROUND:Green tea (Camellia sinensis) is a beverage consumed for thousands of years. Numerous claims about the benefits of its consumption were stated and investigated. As green tea is experiencing a surge in popularity in Western culture and as millions of people all over the world drink it every day, it is relevant to understand its effects on the human brain. PURPOSE:To assess the current state of knowledge in the literature regarding the effects of green tea or green tea extracts, l-theanine and epigallocatechin gallate both components of green tea-on general neuropsychology, on the sub-category cognition and on brain functions in humans. METHODS:We systematically searched on PubMed database and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data. We structured our effort according to the PRISMA statement. OUTCOME:We reviewed and assessed 21 studies, 4 of which were randomised controlled trials, 12 cross-over studies (both assessed with an adapted version of the DELPHI-list), 4 were cross-sectional studies and one was a cohort study (both assessed with an adapted version of the Newcastle-Ottawa assessment scale). The average study quality as appraised by means of the DELPHI-list was good (8.06/9); the studies evaluated with the Newcastle-Ottawa-scale were also good (6.7/9). CONCLUSIONS:The reviewed studies presented evidence that green tea influences psychopathological symptoms (e.g. reduction of anxiety), cognition (e.g. benefits in memory and attention) and brain function (e.g. activation of working memory seen in functional MRI). The effects of green tea cannot be attributed to a single constituent of the beverage. This is exemplified in the finding that beneficial green tea effects on cognition are observed under the combined influence of both caffeine and l-theanine, whereas separate administration of either substance was found to have a lesser impact. 10.1016/j.phymed.2017.07.008
l-Theanine protects against excess dopamine-induced neurotoxicity in the presence of astrocytes. Takeshima Mika,Miyazaki Ikuko,Murakami Shinki,Kita Taizo,Asanuma Masato Journal of clinical biochemistry and nutrition l-Theanine (γ-glutamylethylamide), a component of green tea, is considered to have regulatory and neuroprotective roles in the brain. The present study was designed to determine the effect of l-theanine on excess dopamine-induced neurotoxicity in both cell culture and animal experiments. The primary cultured mesencephalic neurons or co-cultures of mesencephalic neurons and striatal astrocytes were pretreated with l-theanine for 72 h, and then treated with excess dopamine for further 24 h. The cell viability of dopamine neurons and levels of glutathione were evaluated. Excess dopamine-induced neurotoxicity was significantly attenuated by 72 h preincubation with l-theanine in neuron-astrocyte co-cultures but not in neuron-rich cultures. Exposure to l-theanine increased the levels of glutathione in both astrocytes and glial conditioned medium. The glial conditioned medium from l-theanine-pretreated striatal astrocytes attenuated dopamine-induced neurotoxicity and quinoprotein formation in mesencephalic neurons. In addition, replacement of l-glutamate with l-theanine in an cell-free glutathione-synthesis system produced glutathione-like thiol compounds. Furthermore, l-theanine administration (4 mg/kg, p.o.) for 14 days significantly increased glutathione levels in the striatum of mice. The results suggest that l-theanine provides neuroprotection against oxidative stress-induced neuronal damage by humoral molecules released from astrocytes, probably including glutathione. 10.3164/jcbn.16-15
Effects of L-theanine on intestinal morphology, barrier function, and MAPK signaling pathways in diquat-challenged piglets. Animal biotechnology This study aimed to explore the protective effects of L-theanine supplementation on the diquat-challenged weaned piglets. A total of 160 weaned piglets were randomly divided into 4 groups using a 2 × 2 two-factor design, there were 4 replicates per group and 10 pigs per replicate. Piglets were fed diets (with 1000 mg/kg L-theanine addition or not), then challenged with diquat or saline on day 7. 21 days after challenge, two pigs from each replicate were selected for sample collection. Results showed that supplement with 1000 mg/kg L-theanine down-regulated the diarrhea rate, serum D-lactate level, tumor necrosis factor-α, and phosphorylation of extracellular regulated protein kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signaling in pigs without diquat challenge ( < 0.05). While for diquat-challenged piglets, L-theanine addition increased average daily gain, jejunum villus height, and interferon-γ level ( < 0.05). Meanwhile, L-theanine addition decreased the diarrhea rates and mortality, serum D-lactate level, and phosphorylation of ERK and JNK in diquat-challenged pigs ( < 0.05). These results demonstrate that L-theanine pretreatment could alleviate diquat-induced oxidative stress and improve intestinal barrier function in diquat-challenged weaned piglets, which can be attributed to suppression of MAPK phosphorylation signaling pathways. 10.1080/10495398.2021.2013857
l-Theanine improves emulsification stability and antioxidant capacity of diacylglycerol by hydrophobic binding β-lactoglobulin as emulsion surface stabilizer. Xue Xiuheng,He Haiyong,Liu Cunjun,Wang Li,Wang Lu,Wang Yueji,Wang Luping,Yang Chen,Wang Juhua,Hou Ruyan Food chemistry Diacylglycerol (DAG) is commonly used as fat substitute in food manufacture due to its functional properties, but DAG has poor emulsification and oxidation stability, which limits its wide application in food industry. In this work, fluorescence quenching data and thermodynamic parameters were analyzed to investigate the interaction mechanism between l-theanine (L-Th) and β-lactoglobulin (β-LG). DAG emulsion was prepared by using β-lactoglobulin-theanine (β-LG-Th) as surface stabilizer, and its emulsification and oxidation stability were evaluated. The results showed that the hydrophobic interaction played an important role on the conjugate of β-LG and L-Th due to the negative values for ΔG, positive values for ΔH and ΔS at pH 4.0, pH 6.0 and pH 8.0. The DAG has been better embedded by using β-LG-Th as surface stabilizer, and the droplet size was about 0.2 µm to 1.5 µm when the pH was 6.0, the ratio of L-Th to β-LG was 1:1. β-LG-Th as surface stabilizer for DAG can increase the ζ-potential and emulsion index, make the emulsion droplet size distribution more uniform. The l-theanine was better to be used to improve the emulsification stability and antioxidant capacity of DAG by binding β-LG as surface stabilizer. 10.1016/j.foodchem.2021.130557
L-Theanine Protects H9C2 Cells from Hydrogen Peroxide-Induced Apoptosis by Enhancing Antioxidant Capability. Li Chengjian,Yan Qiongxian,Tang Shaoxun,Xiao Wenjun,Tan Zhiliang Medical science monitor : international medical journal of experimental and clinical research BACKGROUND L-theanine is a non-protein amino acid in green tea, and its hepatoprotection and neuroprotection have been verified. However, whether L-theanine can prevent cardiomyocytes from apoptosis is unclear yet. This study evaluated the protective effects of L-theanine on H2O2-induced heart injury in vitro. MATERIAL AND METHODS The certified H9C2 cells were pretreated with L-theanine (0 mM, 4 mM, 8 mM, and 16 mM) for 24 h, followed by 160 µM H2O2 solution for 4 h. The cell viability and antioxidant indices were assayed. Quantitative evaluation of apoptosis was performed by flow cytometric analysis. Nuclear morphology of the cells was monitored by 4',6-diamidino-2-phenylindole staining. Expression of Caspase-3, poly ADP-ribose polymerase (PARP), c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase p38 was assayed by Western blot. RESULTS Compared to the H2O2 treatment, all doses of L-theanine treatments increased the cell viability, glutathione level, and the activities of glutathione peroxidase and superoxide dismutase (P<0.001). The contents of reactive oxygen species, nitric oxide, and oxidized glutathione were decreased by L-theanine treatments (P<0.001). Meanwhile, L-theanine treatments decreased the apoptosis ratio of H2O2-induced H9C2 cells (P<0.001). Pro-Caspase-3 expression was upregulated and cleavaged-PARP expression was inhibited by L-theanine (P<0.001). However, the phosphorylation of JNK and p38 was not affected by L-theanine treatments (P>0.05). CONCLUSIONS These data indicate that L-theanine pretreatment prevents H2O2-induced apoptosis in H9C2 cells, probably via antioxidant capacity improvement. Therefore, it might be a promising potential drug candidate for prophylaxis of ischemia/reperfusion-induced heart diseases. 10.12659/msm.907660
L-Theanine Attenuates Isoflurane-Induced Injury in Neural Stem Cells and Cognitive Impairment in Neonatal Mice. Chen Yong,Lian Fang,Lu Qiang,Peng Shengliang,Li Jiahao,Huang Song,Du Xiaohong Biological & pharmaceutical bulletin The neurodevelopmental toxicity of isoflurane has been proved by many studies, which makes it essential to explore the underline mechanisms and search for protective agents to attenuate its neurotoxcity. Accumulating evidence showed that L-theanine had neuroprotective effects on injured neurons and the developing brain. The present study was designed to investigate whether L-theanine could attenuate isoflurane-induced damage in neural stem cells and cognitive impairment in young mice, and to discuss the role of protein kinase B (Akt)-glycogen synthase kinase 3β (GSK-3β) signaling pathway in this process. Multipotential neural stem cells (NSCs) and C57BL/6J mice were treated with either gas mixture, isoflurane, or L-theanine 30 min prior to isoflurane exposure, respectively. NSC viability was detected by CCK-8 assay. NSC proliferation and apoptosis were assessed by immunofluorescence and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, respectively. The levels of cleaved caspase-3 and phosphorylated (p)-Akt and p-GSK-3β in NSCs were tested by Western blotting. Cognitive function of mice was tested by Morris Water Maze at postnatal day (P) 30-35. The results indicated that isoflurane exposure inhibited NSC viability and proliferation, promoted NSC apoptosis as well as increased caspase-3 activation and down-regulated the expressions of p-Akt and p-GSK-3β in NSCs, and that isoflurane exposure on neonatal mice would induce late cognitive impairment. Pretreatment with L-theanine could attenuate isoflurane-caused damage in NSCs and cognitive deficits in young mice. Addinonally, the protective effects of L-theanine on isoflurane-injured NSCs could be reversed by Akt inhibitor Triciribine. Our data showed that pretreatment with L-theanine eliminated the NSC damage and cognitive impairment induced by isoflurane exposure, and that the neuroprotective effect of L-theanine was associated with the Akt-GSK-3β signaling pathway. 10.1248/bpb.b19-00790
l-Theanine regulates glucose, lipid, and protein metabolism via insulin and AMP-activated protein kinase signaling pathways. Lin Ling,Zeng Li,Liu An,Peng Yingqi,Yuan Dongyin,Zhang Sheng,Li Yinhua,Chen Jinhua,Xiao Wenjun,Gong Zhihua Food & function l-Theanine is an important component found in tea and has positive effects on nutrient absorption and transport. However, whether l-theanine can regulate glucose, lipid, and protein metabolism remains unknown. This study aims to investigate the effects of l-theanine on glucose, lipid, and protein metabolism in male Sprague-Dawley rats and characterize the underlying mechanisms. Compared to the control group, l-theanine increased the contents of hepatic and muscle glycogen, serum total protein (TP), and albumin (Alb), lowered the serum low-density lipoprotein cholesterol (LDL-C) level, decreased the activity of acetyl-CoA carboxylase (ACC), and enhanced carnitine palmitoyl transferase-1 (CPT-1) activity in the liver. Additionally, l-theanine upregulated the mRNA expression of phosphofructokinase (PFKL), CPT-1, insulin receptor (INSR), insulin receptor substrate (IRS), and liver kinase B1 (LKB1) and downregulated the mRNA expression of phosphoenolpyruvate carboxykinase 1 (PCK1), glucose-6-phosphatase catalytic subunit (G6PC), fatty acid synthase (FAS), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Moreover, l-theanine upregulated the expression of PFKL, glycogen synthase 2 (GYS2), ribosomal protein S6 (S6), INSR, IRS, and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) proteins; downregulated the expression of FAS, sterol regulatory element binding protein-1c (SREBP-1c), and HMGCR proteins; enhanced the phosphorylation of the mammal target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), protein kinase B (AKT), and AMP-activated protein kinase (AMPK); and decreased the phosphorylation of glycogen synthase kinase 3β (GSK-3β) and ACC1. Furthermore, 100 mg kg-1l-theanine was more effective at eliciting these effects than 200 and 400 mg kg-1l-theanine. In conclusion, l-theanine can regulate glucose, lipid, and protein metabolism via insulin and AMPK and their downstream signaling pathways. 10.1039/c9fo02451d
Effect of dietary L-theanine supplementation on skeletal muscle fiber type transformation in vivo. Chen Xiaoling,Zhang Man,Xue Yonghong,Liang Dahui,An Wenting,Jia Gang,Zhao Hua,Liu Guangmang,Huang Zhiqing The Journal of nutritional biochemistry The aim of this study was to investigate the effect of dietary L-theanine supplementation on skeletal muscle fiber type transition in mice. Our data indicated that dietary 0.15% L-theanine supplementation significantly increased the mRNA expression levels of muscle fiber type related genes (MyHC I, MyHC IIa, PGC-1α, Sirt1, Tnnt1, Tnnc1, Tnni1, MEF2C) and the protein expression levels of MyHC IIa, myoglobin, PGC-1α, Sirt1 and Troponin I-SS, but significantly decreased the mRNA and protein expression levels of MyHC IIb. Dietary 0.15% L-theanine supplementation significantly increased the activities of SDH and MDH and decreased the activity of LDH. Furthermore, immunofluorescence demonstrated that dietary 0.15% L-theanine supplementation significantly increased the percentage of type I fibers, and significantly decreased the percentage of type II fibers. In addition, we found that dietary 0.15% L-theanine supplementation increased the fatigue-resistant, antioxidant capacity, mitochondrial biogenesis, and function in skeletal muscle of mice. Furthermore, dietary 0.15% L-theanine supplementation significantly increased the mRNA levels of prox1, CaN and NFATc1, the protein levels of prox1, CNA and NFATc1 and the activity of CaN in GAS muscle when compared with the control group. These results indicated that dietary L-theanine supplementation promoted skeletal muscle fiber transition from type II-type I, which might be via activation of CaN and/or NFATc1 signaling pathway. 10.1016/j.jnutbio.2021.108859
Medicinal herbs for the treatment of anxiety: A systematic review and network meta-analysis. Pharmacological research BACKGROUND:Anxiety disorder is a common psychiatric illness. Medicinal herbs have become a field of interest in the treatment of anxiety. This study aimed to evaluate and compare the efficacy and acceptability of all possible medicinal herbs for the treatment of anxiety. METHODS:A Bayesian network meta-analysis was conducted for adults with diagnosed or subthreshold anxiety in randomized controlled trials identified in PubMed, EMBASE, the Cochrane Library, and Web of Science, searched between Jan 1, 1987, and Dec 31, 2021. The outcomes included efficacy (measured by endpoint Hamilton Anxiety Scale [HAMA] Scores) and acceptability (discontinuation by ineffectiveness, worsening of the symptoms, or adverse events). RESULTS:A total of 29 trials were reviewed, comparing 12 medicinal herbs. Silexan (mean difference [MD]: -3.84, 95% credible interval [CrI]: -6.31 to -1.34) displayed a significant effect on anxiety, and possibly benefitted the treatment of depression (standard mean difference [SMD]: -0.37, 95% confidence interval [CI]: -0.53 to -0.20) and insomnia (SMD: -0.48, 95% CI: -0.76 to -0.21). Kava was found to be an effective anxiolytic (MD: -2.46, 95% CrI: -4.47 to -0.32) but possibly ineffective in patients with generalized anxiety disorder (MD: -0.17, 95% CrI: -2.55 to -1.97). Ginkgo biloba (MD: -4.63, 95% CrI: -9.01 to -0.23) and Withania somnifera (MD: -4.90, 95% CrI: -9.70 to -0.17) were efficacious, as measured by HAMA scores but the trials were limited by their small sample sizes. Galphimia glauca (MD: -1.23, 95% CrI: -4.68 to 2.23) and Manasamitravn Vataka (MD: -1.35, 95% CrI: -7.39 to 4.68) exhibited the same anxiolytic effect as standard treatments, but both were absent from trials that were rated low risk, highlighting that confidence in their ability to provide an anxiolytic effect requires additional study. Conversely, although Passionflower (MD: -4.20, 95% CrI: -8.82 to 0.16) and Saffron (MD: -2.71, 95% CrI: -6.06 to 0.57) did not reduce HAMA scores significantly in the summary network, both were worthy of further study because of support from separate networks. There was insufficient evidence to confirm the effectiveness of Valerian (MD: 0.95, 95% CrI: -6.57 to 8.42) in standard-controlled estimation or the ineffectiveness of Chamomile (MD: 0.54, 95% CrI: -5.13 to 6.25) compared with a placebo for anxiety. Gamisoyo-san (MD: -0.98, 95% CrI: -6.48 to 4.54) and L-theanine (MD: -0.49, 95% CrI: -6.54 to 5.57) did not outperform a placebo for the treatment of anxiety in terms of statistical certainty. All medicinal herbs were well-tolerated and exhibited a good safety profile compared with control groups. When all herbs were compared, there was no statistical evidence to suggest any comparison significantly reduced HAMA scores except Ginkgo biloba vs Kava (MD: -4.41, 95% CrI: -8.32 to -0.35), although Ginkgo biloba was ranked as worst due to its poor tolerability. CONCLUSION:Medicinal herbs may be promising for the treatment of anxiety. However, these results should be considered preliminary because of the unconvincing sample sizes, together with the potential effectiveness of placebos. 10.1016/j.phrs.2022.106204
l-Theanine Prevents Long-Term Affective and Cognitive Side Effects of Adolescent Δ-9-Tetrahydrocannabinol Exposure and Blocks Associated Molecular and Neuronal Abnormalities in the Mesocorticolimbic Circuitry. The Journal of neuroscience : the official journal of the Society for Neuroscience Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. l-Theanine is an amino acid analog of l-glutamate and l-glutamine derived from various plant sources, including green tea leaves. l-Theanine has previously been shown to modulate levels of GABA, DA, and glutamate in various neural regions and to possess neuroprotective properties. Using a preclinical model of adolescent THC exposure in male rats, we report that l-theanine pretreatment before adolescent THC exposure is capable of preventing long-term, THC-induced dysregulation of both PFC and VTA DAergic activity states, a neuroprotective effect that persists into adulthood. In addition, pretreatment with l-theanine blocked THC-induced downregulation of local GSK-3 (glycogen synthase kinase 3) and Akt signaling pathways directly in the PFC, two biomarkers previously associated with cannabis-related psychiatric risk and subcortical DAergic dysregulation. Finally, l-theanine powerfully blocked the development of both affective and cognitive abnormalities commonly associated with adolescent THC exposure, further demonstrating functional and long-term neuroprotective effects of l-theanine in the mesocorticolimbic system. With the increasing trend of cannabis legalization and consumption during adolescence, it is essential to expand knowledge on the potential effects of adolescent cannabis exposure on brain development and identify potential pharmacological strategies to minimize Δ-9-tetrahydrocannabinol (THC)-induced neuropathology. Previous evidence demonstrates that adolescent THC exposure induces long-lasting affective and cognitive abnormalities, mesocorticolimbic dysregulation, and schizophrenia-like molecular biomarkers that persist into adulthood. We demonstrate for the first time that l-theanine, an amino acid analog of l-glutamate and l-glutamine, is capable of preventing long-term THC side effects. l-Theanine prevented the development of THC-induced behavioral aberrations, blocked cortical downregulation of local GSK-3 (glycogen synthase kinase 3) and Akt signaling pathways, and normalized dysregulation of both PFC and VTA DAergic activity, demonstrating powerful and functional neuroprotective effects against THC-induced developmental neuropathology. 10.1523/JNEUROSCI.1050-20.2020
Over the Counter Supplements for Memory: A Review of Available Evidence. CNS drugs In 2021, the Global Brain Health Supplement Industry Market size was valued at US$7.6 billion. It is predicted to increase to US$15.59 billion by 2030. Memory and its enhancement are a segment of the market that comprised the highest global revenue share in 2021. In the USA alone, dietary supplement sales reached US$18 billion in 2018. The US Food and Drug Administration (FDA) does not have the authority to approve dietary supplements' safety, effectiveness, or labeling before products go on the market. The FDA often does not even review supplements before they go to market. Supplement manufacturers are thus responsible for ensuring their products are safe and that their claims are truthful. An extensive review of current supplements on the market was performed by surveying memory products for sale at local and national pharmacies and grocery stores. A list of 103 supplements was compiled and the ingredients in these memory supplements were reviewed. The 18 most common ingredients in these supplements were identified. Each of the supplements included at least one of the 18 most common ingredients. Scientific data relative to these ingredients and their effect on memory was searched using PubMed and Cochrane library databases. Currently, there is no compelling evidence for use of apoaequorin, coenzyme Q10, coffee extracts, L-theanine, omega-3 fatty acids, vitamin B6, vitamin B9, or vitamin B12 supplementation for memory. On the other hand, there is some current evidence for memory benefit from supplementation with ashwagandha, choline, curcumin, ginger, Lion's Mane, polyphenols, phosphatidylserine, and turmeric. There are current studies with mixed results regarding the benefit of carnitine, gingko biloba, Huperzine A, vitamin D, and vitamin E supplementation for memory. Dietary supplements geared toward improving cognition are a billion-dollar industry that continues to grow despite lacking a solid scientific foundation for their marketing claims. More rigorous studies are needed relative to the long-term use of these supplements in homogenous populations with standardized measurements of cognition. Health care providers need to be aware of any and all supplements their older adult patients may be consuming and be educated about their side effects and interactions with prescription medications. Lastly, the FDA needs to take an active position relative to monitoring marketed supplements regarding safety, purity and claims of efficacy. 10.1007/s40263-023-01031-6
L-theanine protects rat kidney from D-galactose-induced injury via inhibition of the AGEs/RAGE signaling pathway. European journal of pharmacology As the irreversible products of the non-enzymatic reduction of sugars and the amino groups of proteins or peptides, advanced glycation end products (AGEs) are metabolized and excreted via the kidneys. However, if AGEs are not metabolized, they are deposited in the kidneys and bind to AGE receptors (RAGE), which can induce various pathological changes, including oxidative stress, apoptosis, and inflammation. This study used the D-galactose (DG)-induced rat model to explore the potential role and mechanism of L-theanine in inhibiting AGEs/RAGE-related signaling pathways in renal tissues. L-theanine increased the activities of glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) while downregulating the contents of malondialdehyde (MDA) and AGEs in renal tissues induced by DG (P < 0.05). By inhibiting the upregulation of RAGE protein expression attributed to AGEs accumulation (P < 0.05), L-theanine downregulated phosphorylated nuclear factor (p-NF-κB (p65)), Bax, and cleaved-caspase-3 expression and increased Bcl-2 protein expression (P < 0.05), thereby alleviating the oxidative stress damage and reducing the inflammation and cell injury induced by DG. In addition, the Congo red staining section of renal tissue also showed that the natural product L-theanine can protect against AGEs-induced renal damage in DG-induced rat model. 10.1016/j.ejphar.2022.175072
l-Theanine Protects Bladder Function by Suppressing Chronic Sympathetic Hyperactivity in Spontaneously Hypertensive Rat. Matsuoka Kanako,Akaihata Hidenori,Hata Junya,Tanji Ryo,Honda-Takinami Ruriko,Onagi Akifumi,Hoshi Seiji,Koguchi Tomoyuki,Sato Yuichi,Kataoka Masao,Ogawa Soichiro,Kojima Yoshiyuki Metabolites Chronic sympathetic hyperactivity is known to affect metabolism and cause various organ damage including bladder dysfunction. In this study, we evaluated whether l-theanine, a major amino acid found in green tea, ameliorates bladder dysfunction induced by chronic sympathetic hyperactivity as a dietary component for daily consumption. Spontaneously hypertensive rats (SHRs), as an animal model of bladder dysfunction, were divided into SHR-water and SHR-theanine groups. After 6 weeks of oral administration, the sympathetic nervous system, bladder function, and oxidative stress of bladder tissue were evaluated. The mean blood pressure, serum noradrenaline level, and media-to-lumen ratio of small arteries in the suburothelium were significantly lower in the SHR-theanine than in the SHR-water group. Micturition interval was significantly longer, and bladder capacity was significantly higher in the SHR-theanine than in the SHR-water group. Bladder strip contractility was also higher in the SHR-theanine than in the SHR-water group. Western blotting of bladder showed that expression of malondialdehyde was significantly lower in the SHR-theanine than in the SHR-water group. These results suggested that orally administered l-theanine may contribute at least partly to the prevention of bladder dysfunctions by inhibiting chronic sympathetic hyperactivity and protecting bladder contractility. 10.3390/metabo11110778
Production of l-Theanine by Escherichia coli in the Absence of Supplemental Ethylamine. Hagihara Ryota,Ohno Shoto,Hayashi Mikiro,Tabata Kazuhiko,Endo Hirofumi Applied and environmental microbiology l-Theanine is a nonproteinogenic amino acid present almost exclusively in tea plants and is beneficial for human health. For industrial production, l-theanine is enzymatically or chemically synthesized from glutamine/glutamate (or a glutamine/glutamate derivative) and ethylamine. Ethylamine is extremely flammable and toxic, which complicates and increases the cost of operational procedures. To solve these problems, we developed an artificial biosynthetic pathway to produce l-theanine in the absence of supplemental ethylamine. For this purpose, we identified and selected a novel transaminase (NCBI:protein accession number AAN70747) from KT2440, which catalyzes the transamination of acetaldehyde to produce ethylamine, as well as γ-glutamylmethylamide synthetase (NCBI:protein accession number AAY37316) from pv. syringae B728a, which catalyzes the condensation of l-glutamate and ethylamine to produce l-theanine. Expressing these genes in W3110S3GK and enhancing the production capacity of acetaldehyde and l-alanine achieved successful production of l-theanine without ethylamine supplementation. Furthermore, the deletion of , which encodes γ-glutamyltranspeptidase (EC 2.3.2.2), achieved large-scale production of l-theanine by attenuating its decomposition. We show that an alanine decarboxylase-utilizing pathway represents a promising route for the fermentative production of l-theanine. Our study reports efficient methods to produce l-theanine in the absence of supplemental ethylamine. l-Theanine is widely used in food additives and dietary supplements. Industrial production of l-theanine uses the toxic and highly flammable precursor ethylamine, raising production costs. In this study, we used to engineer two biosynthetic pathways that produce l-theanine from glucose and ammonia in the absence of supplemental ethylamine. This study establishes a foundation for safely and economically producing l-theanine. 10.1128/AEM.00031-21
L-theanine and Neumentix mixture improves sleep quality and modulates brain neurotransmitter levels in mice. Zhang Ying,Jia Xiuzhen,Chen Ximin,Liu Yajuan,Zhao Zifu,Hao Jingyu,Wu Rui,Feng Haotian,Ren Xiangnan Annals of palliative medicine BACKGROUND:L-theanine (L-THE), a natural amino acid found in green tea, has been shown to improve anxiety and sleep. Neumentix proprietary spearmint extract (PSE), which is commonly found in beverage flavoring a pharmaceutical, also has a wide range of health benefits, including cognitive performance improvement. METHODS:Four experiments tested the effects of L-THE and PSE on sleep: a direct sleeping test, pentobarbital-induced sleeping test, sub-hypnotic pentobarbital-induced sleeping test, and sodium barbital-induced sleeping test. Presence of neurotransmitters in brain tissue was detected by liquid chromatography mass spectroscopy (HP LC-MS) during these studies. RESULTS:Pentobarbital-induced sleeping and sodium barbital-induced sleeping tests examined the potential effect of L-THE/PSE mixture on synergistic sleep, while neurotransmitter levels in the brain were determined by the high performance liquid chromatography/mass spectroscopy (HPLC/MS) method. L-THE and L-THE/PSE mixture showed increased sleep duration and shortened sleep latency when co-administrated with pentobarbital or sodium barbital. The mixture also increased sleeping rate when co-administrated with the pentobarbital at sub-hypnotic dose. Additionally, the L-THE, PSE and L-THE/PSE mixture significantly increased the concentrations of acetylcholine (Ach), γ-aminobutyric acid (GABA), and decreased the concentration of serotonin (5-HT) in the brain. CONCLUSIONS:These data demonstrated that L-THE/PSE mixture regulates sleep disorders via the GABA receptor and neurotransmitter systems. 10.21037/apm-21-663
An L-theanine derivative targets against SARS-CoV-2 and its Delta and Omicron variants. Heliyon Recent research efforts have shown that tea has activities against SARS-CoV-2. However, the active compounds and the action mechanisms are largely unknown. Here we study the inhibitory potential of L-theanine from tea and its semi-synthesized derivative, a small-molecule fluorescent compound, ethyl 6-bromocoumarin-3-carboxylyl L-theanine (TBrC) against infection and replication of SARS-CoV-2 and the underlying mechanisms of action. We reveal that TBrC has potential activities against SARS-CoV-2 in addition to its activity against lung cancer. TBrC showed extracellular inhibition of SARS-CoV-2 M/3CL and the host cell receptor ACE2 while interacting with the viral spike glycoproteins (wild-type, Delta, and Omicron mutants). Moreover, TBrC and L-theanine significantly suppressed growth and TNFα-induced nuclear transcriptional activation of NF-κB in human lung cancer cells without affecting the viability of normal lung cells, suggesting a potential protection of TBrC and L-theanine from pulmonary damages in SARS-CoV-2 infected patients, especially for lung cancer patients with SARS-CoV-2 infection. 10.1016/j.heliyon.2022.e09660
L-Theanine adjunct to risperidone in the treatment of chronic schizophrenia inpatients: a randomized, double-blind, placebo-controlled clinical trial. Psychopharmacology RATIONALE:Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches. OBJECTIVES:This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia. METHODS:Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS:Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05). CONCLUSIONS:L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies. TRIAL REGISTRATION:The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials ( http://www.irct.ir ; registration number: IRCT20090117001556N133) on 2020-12-12. 10.1007/s00213-023-06458-9
L-Theanine alleviates heat stress through modulation of gut microbiota and immunity. Journal of the science of food and agriculture BACKGROUND:Heat stress (HS) damages the intestines, disrupting gut microbiota and immune balance. l-Theanine (LTA), found in tea, alleviates oxidative stress and cell apoptosis under HS; however, its effects on gut microbiota and immunity under HS remain unclear. To investigate this, we administered LTA doses of 100, 200, and 400 mg·kg ·d to C57BL/6J mice. On day 44, the model group and LTA intervention group were subjected to continuous 7-day HS treatment for 2 h per day. RESULTS:The results demonstrated that LTA intervention improved food intake, body weight, and intestinal epithelium, and reduced the water intake of heat-stressed mice. It increased the abundance of Turicibacter, Faecalibaculum, Bifidobacterium, and norank_f_Muribaculaceae, while reducing that of Lachnoclostridium and Desulfovibrio. LTA intervention also increased the concentrations of amino acid and lipid metabolites, regulated macrophage differentiation stimulated by gut microbiota and metabolites, reduced the antigen presentation by macrophages to the specific immune system, promoted B-cell differentiation and sIgA secretion, inhibited pro-inflammatory factors, and enhanced intestinal defense. Mechanistically, LTA downregulated heat shock protein 70 expression and the TLR4/NF-κB/p38 MAPK signaling pathway, restoring gut microbiota and immune balance. CONCLUSION:We suggest that LTA can alleviate HS by modulating gut microbiota, metabolites, and immunity, indicating its potential as a natural active ingredient for anti-HS food products. © 2023 Society of Chemical Industry. 10.1002/jsfa.13095
L-Theanine promotes cultured human Sertoli cells proliferation and modulates glucose metabolism. Dias Tânia R,Bernardino Raquel L,Alves Marco G,Silva Joaquina,Barros Alberto,Sousa Mário,Casal Susana,Silva Branca M,Oliveira Pedro F European journal of nutrition PURPOSE:L-Theanine is the major free amino acid present in tea (Camellia sinensis L.). The effects of several tea constituents on male reproduction have been investigated, but L-theanine has been overlooked. Sertoli cells (SCs) are essential for the physical and nutritional support of germ cells. In this study, we aimed to investigate the ability of L-theanine to modulate important mechanisms of human SCs (hSCs) metabolism, mitochondrial function and oxidative profile, which are essential to prevent or counteract spermatogenesis disruption in several health conditions. METHODS:We evaluated the effect of a dose of L-theanine attained by tea intake (5 μM) or a pharmacological dose (50 μM) on the metabolism (proton nuclear magnetic resonance and Western blot), mitochondrial functionality (protein expression of mitochondrial complexes and JC1 ratio) and oxidative profile (carbonyl levels, nitration and lipid peroxidation) of cultured hSCs. RESULTS:Exposure of hSCs to 50 µM of L-theanine increased cell proliferation and glucose consumption. In response to this metabolic adaptation, there was an increase in mitochondrial membrane potential, which may compromise the prooxidant-antioxidant balance. Still, no alterations were observed regarding the oxidative damages. CONCLUSIONS:A pharmacological dose of L-theanine (50 µM) prompts an increase in hSCs proliferation and a higher glucose metabolization to sustain the pool of Krebs cycle intermediates, which are crucial for cellular bioenergetics and biosynthesis. This study suggests an interplay between glycolysis and glutaminolysis in the regulation of hSCs metabolism. 10.1007/s00394-019-01999-2
L-theanine prevents progression of nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway. Nutrition & metabolism BACKGROUND:L-theanine, a non-protein amino acid was found principally in the green tea, has been previously shown to exhibit potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism. METHODS:In vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high-fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of triglycerides (TG), accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo. RESULTS:Our data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced nonalcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK through its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ). CONCLUSIONS:Taken together, our findings suggested that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway. 10.1186/s12986-022-00664-6
L-theanine exuded from Camellia sinensis roots regulates element cycling in soil by shaping the rhizosphere microbiome assembly. The Science of the total environment Root exudate metabolites are a key medium for the interaction between plants and soil microbiota. L-theanine is a unique non-protein amino acid critical for the flavor and potential health benefits of tea products; however, its biological function in tea plants is not well understood. As L-theanine is mainly synthesized in the roots of tea plants, we hypothesized that L-theanine could affect the function of the rhizosphere microbiota by modulating microbial assembly. In the present study, L-theanine was detected in the exudates of tea plant roots using liquid chromatography-mass spectrometry. Additionally, 16S rRNA gene sequencing revealed that L-theanine significantly altered the structure of the rhizosphere microbiota and selectively shaped rhizosphere microbial assembly. Moreover, metagenomic data showed that L-theanine affected the abundance of genes encoding element cycling in soil. Interestingly, the denitrification and complete nitrification pathways were significantly inhibited by L-theanine by decreasing the narH, napA, and napB genes abundance. These findings provide new insights into the biological function of L-theanine, as well as the implications of interactions between tea plant root exudates and the rhizosphere microbiome. 10.1016/j.scitotenv.2022.155801
L-Theanine alleviates heat stress-induced impairment of immune function by regulating the p38 MAPK signalling pathway in mice. Food & function With the current trend of global warming, heat stress-induced impairment could seriously endanger human health. L-Theanine is a non-protein amino acid in tea with various biological activities, including immunoregulatory, anti-anxiety, and anti-oxidation. However, its effect on immune function under heat stress and the underlying mechanism are currently unclear. In this study, male BALB/c mice were used as experimental objects to explore the effect of L-theanine on heat stress-induced changes in immune function and its mechanism. Three doses of L-theanine were used: low (100 mg kg d), medium (200 mg kg d), and high (400 mg kg d). Treatment with L-theanine could attenuate the heat stress-induced reductions in body weight and feed intake in mice, alleviate damage in the liver and jejunum, and inhibit the inflammatory factors IL-6, IL-1β, and TNF-α. Aspartate aminotransferase and alanine transaminase activity levels and the malondialdehyde content decreased, while the IgA, IgM, and IgG contents increased in response to L-theanine. It is possible that L-theanine affects the P38 signalling pathway and inhibits the increase in p-P65/P65 caused by the overexpression of HSP27 and regulation of PPAR-γ and Foxp3 proteins, thereby alleviating immune dysfunction caused by heat stress. 10.1039/d2fo02775e
Effect of single or combined caffeine and L-Theanine supplementation on shooting and cognitive performance in elite curling athletes: a double-blind, placebo-controlled study. Journal of the International Society of Sports Nutrition PURPOSE:Previous studies have investigated the effect of single or combined caffeine (CAF) and L-theanine (THE) intake on attention performance. However, its effect on shooting performance and cognitive performance in a sport is unknown. The aim of this study was to investigate the hypothesis "Does single or combined CAF and THE supplementation have an effect on shooting and cognitive performance in elite curling athletes?." It is predicted that over the next decade, studies based on nutritional ergogenic supplements in the developing sport of curling will continue to increase, leading to a significant increase in studies examining the effects of CAF and THE supplementation, alone or in combination, on throwing and cognitive performance in elite curling athletes. METHODS:In this double-blind, randomized controlled crossover study, twenty-two elite national curling athletes (age 20.20 ± 1.61 and sports age 6.20 ± 0.51 years, height 174.10 ± 7.21 cm, BMI 21.80 ± 3.47 kg/m) were randomly assigned to CAF (6 mg/kg single dose CAF), THE (6 mg/kg single dose THE), CAF*THE (6 mg/kg CAF and 6 mg/kg THE combined) and PLA (400 mg maltodextrin) groups at each of four sessions. 60 minutes after taking the supplement, the athletes were first given the Stroop test and then asked to shoot. RESULTS:Our main findings have shown that the performance of athletes in guard (F=,  < .001, η = .842), draw (F=,  < .001, η = .485), and take-out (F=,  < .001, η = .743) shot styles significantly improved when comparing the combined intake of CAF and THE to the PLA. Regarding cognitive performance evaluation through the Stroop test, during the NR task (F=,  = .001, η = .653), the combined intake of CAF and THE significantly improved reaction times compared to the intake of single CAF, THE, or PLA. The best reaction times during the CR and ICR (respectively; F=,  = .004, η = .328; F = 1.632,  < .001, η = .625) tasks were achieved with the combined CAF and THE intake, showing a significant improvement compared to PLA. During the NER (F=,  < .001, η = .741), task, the combined intake of CAF and THE significantly improved error rates compared to the intake of CAF, THE, or PLA single. The best accuracy rates during the CER and ICER (respectively; F=,  < .001, η = .396; F=,  < .001, η = .710) tasks were achieved with the combined CAF and THE intake, leading to a significant reduction in error rates compared to PLA. Based on these findings, it has been demonstrated in this study that the best shooting scores and cognitive performance were achieved, particularly with the combined intake of CAF and THE. CONCLUSIONS:Based on these findings, it has been demonstrated in this study that the best shooting scores and cognitive performance were achieved, particularly with the combined intake of CAF and THE. The combined use of these supplements has been found to be more effective on shooting and cognitive performance than their single use. 10.1080/15502783.2023.2267536
In Search of a Safe Natural Sleep Aid. Rao Theertham P,Ozeki Motoko,Juneja Lekh R Journal of the American College of Nutrition Sleep deprivation is associated with an elevated risk of various diseases and leads to a poor quality of life and negative socioeconomic consequences. Sleep inducers such as drugs and herbal medicines may often lead to dependence and other side effects. L-Theanine (γ-glutamylethylamide), an amino acid naturally found abundant in tea leaves, has anxiolytic effects via the induction of α brain waves without additive and other side effects associated with conventional sleep inducers. Anxiolysis is required for the initiation of high-quality sleep. In this study, we review the mechanism(s), safety, and efficacy of L-theanine. Collectively, sleep studies based on an actigraph, the obstructive sleep apnea (OSA) sleep inventory questionnaire, wakeup after sleep onset (WASO) and automatic nervous system (ANS) assessment, sympathetic and parasympathetic nerve activities, and a pediatric sleep questionnaire (PSQ) suggest that the administration of 200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis. Because L-theanine does not induce daytime drowsiness, it may be useful at any time of the day. The no observable adverse effect level (NOAEL) for the oral administration of L-theanine was determined to be above 2000 mg/kg bw/day. KEY TEACHING POINTS: Sleep deprivation-associated morbidity is an increasing public health concern posing a substantial socioeconomic burden. Chronic sleep disorders may seriously affect quality of life and may be etiological factors in a number of chronic diseases such as depression, obesity, diabetes, and cardiovascular diseases. Most sleep inducers are sedatives and are often associated with addiction and other side effects. L-Theanine promotes relaxation without drowsiness. Unlike conventional sleep inducers, L-theanine is not a sedative but promotes good quality of sleep through anxiolysis. This review suggests that L-theanine is a safe natural sleep aid. 10.1080/07315724.2014.926153
l-Theanine Goes Greener: A Highly Efficient Bioprocess Catalyzed by the Immobilized γ-Glutamyl Transferase from Bacillus subtilis. ChemSusChem l-Theanine (l-Th) was synthesized by simply mixing the reactants (l-glutamine and ethylamine in water) at 25 °C and Bacillus subtilis γ-glutamyl transferase (BsGGT) covalently immobilized on glyoxyl-agarose according to a methodology previously reported by our research group; neither buffers, nor other additives were needed. Ratio of l-glutamine (donor) to ethylamine (acceptor), pH, enzymatic units (IU), and reaction time were optimized (molar ratio of donor/acceptor=1 : 8, pH 11.6, 1 IU mL , 6 h), furnishing l-Th in 93 % isolated yield (485 mg, 32.3 g L ) and high purity (99 %), after a simple filtration of the immobilized biocatalyst, distillation of the volatiles (unreacted ethylamine) and direct lyophilization. Immobilized BsGGT was re-used (four reaction cycles) with 100 % activity retention. This enzymatic synthesis represents a straightforward, fast, high-yielding, and easily scalable approach to l-Th preparation, besides having a favorable green chemistry metrics. 10.1002/cssc.202202108
International society of sports nutrition position stand: energy drinks and energy shots. Journal of the International Society of Sports Nutrition Position Statement: The (ISSN) bases the following position stand on a critical analysis of the literature regarding the effects of energy drink (ED) or energy shot (ES) consumption on acute exercise performance, metabolism, and cognition, along with synergistic exercise-related performance outcomes and training adaptations. The following 13 points constitute the consensus of the Society and have been approved by the Research Committee of the Society: Energy drinks (ED) commonly contain caffeine, taurine, ginseng, guarana, carnitine, choline, B vitamins (vitamins B1, B2, B3, B5, B6, B9, and B12), vitamin C, vitamin A (beta carotene), vitamin D, electrolytes (sodium, potassium, magnesium, and calcium), sugars (nutritive and non-nutritive sweeteners), tyrosine, and L-theanine, with prevalence for each ingredient ranging from 1.3 to 100%. Energy drinks can enhance acute aerobic exercise performance, largely influenced by the amount of caffeine (> 200 mg or >3 mg∙kg bodyweight [BW]) in the beverage. Although ED and ES contain several nutrients that are purported to affect mental and/or physical performance, the primary ergogenic nutrients in most ED and ES based on scientific evidence appear to be caffeine and/or the carbohydrate provision. The ergogenic value of caffeine on mental and physical performance has been well-established, but the potential additive benefits of other nutrients contained in ED and ES remains to be determined. Consuming ED and ES 10-60 minutes before exercise can improve mental focus, alertness, anaerobic performance, and/or endurance performance with doses >3 mg∙kg BW. Consuming ED and ES containing at least 3 mg∙kg BW caffeine is most likely to benefit maximal lower-body power production. Consuming ED and ES can improve endurance, repeat sprint performance, and sport-specific tasks in the context of team sports. Many ED and ES contain numerous ingredients that either have not been studied or evaluated in combination with other nutrients contained in the ED or ES. For this reason, these products need to be studied to demonstrate efficacy of single- and multi-nutrient formulations for physical and cognitive performance as well as for safety. Limited evidence is available to suggest that consumption of low-calorie ED and ES during training and/or weight loss trials may provide ergogenic benefit and/or promote additional weight control, potentially through enhanced training capacity. However, ingestion of higher calorie ED may promote weight gain if the energy intake from consumption of ED is not carefully considered as part of the total daily energy intake. Individuals should consider the impact of regular coingestion of high glycemic index carbohydrates from ED and ES on metabolic health, blood glucose, and insulin levels. Adolescents (aged 12 through 18) should exercise caution and seek parental guidance when considering the consumption of ED and ES, particularly in excessive amounts (e.g. > 400 mg), as limited evidence is available regarding the safety of these products among this population. Additionally, ED and ES are not recommended for children (aged 2-12), those who are pregnant, trying to become pregnant, or breastfeeding and those who are sensitive to caffeine. Diabetics and individuals with preexisting cardiovascular, metabolic, hepatorenal, and/or neurologic disease who are taking medications that may be affected by high glycemic load foods, caffeine, and/or other stimulants should exercise caution and consult with their physician prior to consuming ED. The decision to consume ED or ES should be based upon the beverage's content of carbohydrate, caffeine, and other nutrients and a thorough understanding of the potential side effects. Indiscriminate use of ED or ES, especially if multiple servings per day are consumed or when consumed with other caffeinated beverages and/or foods, may lead to adverse effects. The purpose of this review is to provide an update to the position stand of the (ISSN) integrating current literature on ED and ES in exercise, sport, and medicine. The effects of consuming these beverages on acute exercise performance, metabolism, markers of clinical health, and cognition are addressed, as well as more chronic effects when evaluating ED/ES use with exercise-related training adaptions. 10.1080/15502783.2023.2171314
L-theanine intervention enhances human gammadeltaT lymphocyte function. Bukowski Jack F,Percival Susan S Nutrition reviews Human gammadeltaT lymphocytes are a subset of T cells and are a first line of defense against microbes and tumors. These gammadeltaT cells can be primed by nitrogen-containing bisphosphonates, and certain short-chain alkylamines. These primed gammadeltaT cells have an enhanced capacity to proliferate and to secrete cytokines upon ex vivo exposure to a wide variety of microbes and tumor cells. The largest dietary source of alkylamines is L-theanine, an amino acid unique to tea beverages that is catabolized to ethylamine. Supplementation of subjects with capsules containing L-theanine and catechins has recently been shown to decrease the incidence of cold and flu symptoms, while enhancing gammadeltaT cell function. 10.1111/j.1753-4887.2007.00013.x
Psychotropic effects of -theanine and its clinical properties: From the management of anxiety and stress to a potential use in schizophrenia. Lopes Sakamoto Filipe,Metzker Pereira Ribeiro Rodrigo,Amador Bueno Allain,Oliveira Santos Heitor Pharmacological research Anxiety disorders are highly prevalent in modern societies, and are ranked the sixth most important contributor of non-fatal negative health outcomes. -theanine is an amino acid naturally found in green tea (Camellia sinensis) and some other plant extracts, and recent clinical studies have proposed promising adjuvant effects of -theanine for the negative impact of anxiety and psychological stress on health. In this integrative narrative review, we aimed to appraise and further discuss the effects of -theanine administration on anxiety disorders and psychological stress. Published data suggests that -theanine administered at daily doses ranging from 200 to 400 mg for up to 8 weeks are safe and induce anxiolytic and anti-stress effects in acute and chronic conditions. -theanine at doses lower and higher than these may also show promising therapeutic potential; however, a more thorough investigation through randomized double-blind placebo-controlled crossover clinical trials are necessary to elucidate its effects for longer periods, providing further insights for meta-analyses and the development of recommendation guidelines. Additionally, animal studies investigating a higher dosage, its combination with other pharmacological compounds and associated metabolic comorbidities are recommended, as cases of hepatotoxicity associated with the consumption of green tea extract have been reported. 10.1016/j.phrs.2019.104395
An overview of biological production of L-theanine. Mu Wanmeng,Zhang Tao,Jiang Bo Biotechnology advances L-Theanine (γ-glutamylethylamide) is a unique non-protein amino acid that is naturally found in tea plants. It contributes to the umami taste and unique flavor to green tea infusion, and thus its content in tea leaves highly impacts the tea quality and price. In addition to the graceful taste, it has been proved to have many beneficial physiological effects, especially promoting relaxation and improving concentration and learning ability. Based on these promising advantages, L-theanine has been commercially developed as a valuable ingredient for use in food and beverages to improve and/or maintain human health. L-Theanine can be obtained by chemical synthesis or isolation from tea, while chemical synthesis of L-theanine is hard to be accepted by consumers and is not allowed to use in food industry, and isolation of L-theanine in high purity generally involves time-consuming, cost-ineffective, and complicated operational processes. Accordingly, the biological production of L-theanine has recently attracted much attention. Four kinds of bacterial enzymes, including L-glutamine synthetase, γ-glutamylmethylamide synthetase, γ-glutamyltranspeptidase, and L-glutaminase, have been characterized to have L-theanine-producing ability. Herein, an overview of recent studies on the biological production of L-theanine was presented. 10.1016/j.biotechadv.2015.04.004
An L-Glutamine Transporter Isoform for Neurogenesis Facilitated by L-Theanine. Yoneda Yukio Neurochemical research L-Theanine (=γ-glutamylethylamide) is an amino acid ingredient in green tea with a structural analogy to L-glutamine (L-GLN) rather than L-glutamic acid (L-GLU), with regards to the absence of a free carboxylic acid moiety from the gamma carbon position. L-theanine markedly inhibits [H]L-GLN uptake without affecting [H]L-GLU uptake in cultured neurons and astroglia. In neural progenitor cells with sustained exposure to L-theanine, upregulation of the L-GLN transporter isoform Slc38a1 expression and promotion of both proliferation and neuronal commitment are seen along with marked acceleration of the phosphorylation of mammalian target of rapamycin (mTOR) and relevant downstream proteins. Stable overexpression of Slc38a1 leads to promotion of cellular growth with facilitated neuronal commitment in pluripotent embryonic carcinoma P19 cells. In P19 cells stably overexpressing Slc38a1, marked phosphorylation is seen with mTOR and downstream proteins in a fashion insensitive to the additional stimulation by L-theanine. The green tea amino acid L-theanine could thus elicit pharmacological actions to up-regulate Slc38a1 expression for activation of the mTOR signaling pathway required for cell growth together with accelerated neurogenesis after sustained exposure in undifferentiated neural progenitor cells. In this review, I summarize a novel pharmacological property of the green tea amino acid L-theanine for embryonic and adult neurogenesis with a focus on the endogenous amino acid analog L-GLN. A possible translational strategy is also discussed on the development of dietary supplements and nutraceuticals enriched of L-theanine for the prophylaxis of a variety of untoward impairments and malfunctions seen in patients with different neurodegenerative and/or neuropsychiatric disorders. 10.1007/s11064-017-2317-6
Functional roles of taurine, L-theanine, L-citrulline, and betaine during heat stress in poultry. Uyanga Victoria Anthony,Oke Emmanuel O,Amevor Felix Kwame,Zhao Jingpeng,Wang Xiaojuan,Jiao Hongchao,Onagbesan Okanlawon M,Lin Hai Journal of animal science and biotechnology Heat stress (HS) is an important environmental stress factor affecting poultry production on a global scale. With the rise in ambient temperature and increasing effects of global warming, it becomes pertinent to understand the effects of HS on poultry production and the strategies that can be adopted to mitigate its detrimental impacts on the performance, health, welfare, immunity, and survival of birds. Amino acids (AAs) have been increasingly adopted as nutritional modifiers in animals to ameliorate the adverse effects of HS. They are essential for protein synthesis, growth, maintenance, reproduction, immunity, stress response, and whole-body homeostasis. However, HS tends to adversely affect the availability, transport, absorption, and utilization of these AAs. Studies have investigated the provision of these AAs to poultry during HS conditions, and variable findings have been reported. Taurine, L-theanine, and L-citrulline are non-essential amino acids that are increasingly gaining attention as nutritional supplements in HS animals. Similarly, betaine is an amino acid derivative that possesses favorable biological properties which contributes to its role as a functional additive during HS. Of particular note, taurine is negligible in plants, while betaine, L-theanine, and L-citrulline can be found in selected plants. These nutrients are barely found in feed ingredients, but their supply has been shown to elicit important physiological roles including anti-stress effects, anti-oxidative, anti-inflammatory, gut promoting, and immunomodulatory functions. The present review provides information on the use of these nutritionally and physiologically beneficial nutrients as functional additives to poultry diets during HS conditions. Presently, although several studies have reported on the positive effects of these additives in human and murine studies, however, there is limited information regarding their utilization during heat stress in poultry nutrition. Therefore, this review aims to expound on the functional properties of these nutrients, their potentials for HS alleviation, and to stimulate further researches on their biological roles in poultry nutrition. 10.1186/s40104-022-00675-6
Use of Nutritional Supplements Based on L-Theanine and Vitamin B6 in Children with Tourette Syndrome, with Anxiety Disorders: A Pilot Study. Rizzo Renata,Prato Adriana,Scerbo Miriam,Saia Federica,Barone Rita,Curatolo Paolo Nutrients 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. 10.3390/nu14040852
The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review. Plant foods for human nutrition (Dordrecht, Netherlands) The green tea amino acid, L-theanine (L-THE) is associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms. This systematic review evaluated the effect of pure L-THE intake, in the form of orally administered nutritional supplements, on stress responses and anxiety levels in human randomised controlled trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 9 peer-reviewed journal articles were identified where L-THE as a supplement was compared to a control. Our findings suggest that supplementation of 200-400 mg/day of L-THE may assist in the reduction of stress and anxiety in people exposed to stressful conditions. Despite this finding, longer-term and larger cohort clinical studies, including those where L-THE is incorporated into the diet regularly, are needed to clinically justify the use of L-THE as a therapeutic agent to reduce stress and anxiety in people exposed to stressful conditions. 10.1007/s11130-019-00771-5
L-theanine attenuates nicotine reward and withdrawal signs in mice. Neuroscience letters BACKGROUND:L-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid detected in green tea leaves, is used as a dietary supplement to attenuate stress and enhance mood and cognition. Furthermore, L-theanine induces anxiolytic effects in humans. Recently, L-theanine was reported to reduce morphine physical dependence in primates, suggesting the potential usefulness of L-theanine for drug dependence intervention. OBJECTIVE:The aim of this study is to determine whether L-theanine attenuates nicotine-withdrawal (somatic and affective signs) and nicotine reward in mice. We also investigated the effects of L-theanine on nicotinic receptors binding and function. METHODS:ICR male mice rendered dependent to nicotine through implanted subcutaneous osmotic minipumps for 14 days undertook precipitated nicotine withdrawal by mecamylamine on day 15. Anxiety-like behaviors using LDB, somatic signs observation and hot plate latency were assessed consecutively after treatment with L-theanine. Furthermore, we examined the effect of L-theanine on acute nicotine responses and nicotine conditioned reward in mice and on expressed nicotinic receptors in oocytes. KEY FINDINGS:L-theanine reduced in a dose-dependent manner anxiety-like behavior, hyperalgesia and somatic signs during nicotine withdrawal. Also, L-theanine decreased the nicotine CPP, but it did not affect the acute responses of nicotine. Finally, L-theanine did not alter the binding or the function of expressed α4β2 and α7 nAChRs. CONCLUSION:Our results support the potential of L-theanine as a promising candidate for treating nicotine dependence. 10.1016/j.neulet.2023.137279
Effect of Combined Ingestion of L-Theanine and L-Arginine for Short-Term Psychological Stress in Young Adults: A Randomized Placebo-Controlled Study. Journal of nutritional science and vitaminology l-Theanine, the most abundant amino acid component in green tea, has anti-stress effects and refreshes the mental state. A recent study demonstrated that l-arginine, the second most abundant amino acid in green tea, might enhance the anti-stress effects of l-theanine. The aim of this study was to evaluated the effects of combined ingestion of l-theanine and l-arginine on psychological stress in humans. A randomized placebo-controlled trial was conducted including 120 healthy young adults (mean age 22.4 y, 63.3% female). Subjects were randomly assigned to theanine (200 mg l-theanine), combined theanine/arginine (200 mg l-theanine, 50 mg l-arginine), or placebo groups. After consuming a test beverage, we administered a stress-loading test (Uchida-Kraepelin performance test) and performed salivary alpha-amylase activity (sAA) measurements to assess the physiological stress response at 0 min (immediately after), 5 min, and 15 min. The changes in sAA at 15 min after the stress-loading test were -2.75 (11.2) kIU/L in the theanine/arginine group, -0.40 (11.5) kIU/L in the theanine group, and 6.95 (18.6) kIU/L in the placebo group. The values in the theanine/arginine (p=0.007) and theanine (p=0.02) groups differed significantly from those in the placebo group. However, the difference between theanine/arginine and theanine groups, was not statistically significant (p=0.74). From this study, no clear conclusion could be drawn regarding the potentiating effect of theanine and arginine combined ingestion on anti-stress effects in human. 10.3177/jnsv.68.540
Immune-boosting role of L-theanine in broiler poultry production under stress conditions. Open veterinary journal Theanine is a naturally occurring amino acid, including two forms: D-theanine and L-theanine. L-theanine is the most common nonprotein amino acid and is soluble in water. Theanine can be found in some plants, such as green tea and some mushrooms. Under stress conditions, theanine is proposed to be a naturally effective additive in preventing reactive oxygen species, thus reducing oxidative stress. In addition, as an immune booster in animal bodies, L-theanine can be applied in the diet to help animals improve their performance, especially their immunity during stress conditions. The digestion of L-theanine improves γδ T cell growth and development. Thus, it is considered an essential compound in boosting the immune function. Moreover, the immune function of L-theanine is also shown in immune-related organs through increasing their weights. Theanine seems to be widely used in pigs, mice, and humans. However, the study of theanine in poultry species is scarce. Therefore, to fill the knowledge gap regarding the use of theanine in enhancing poultry immunity, this study aims to synthesize all information on the application of theanine in poultry, focusing on its immune-boosting role. 10.5455/OVJ.2022.v12.i2.13
l-theanine adjunct to sertraline for major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial. Journal of affective disorders BACKGROUND:Unsatisfactory responses to major depressive disorder (MDD) therapeutics available necessitated up-to-date treatment approaches. This study sought to investigate the efficacy and tolerability of adjunctive l-theanine, a green tea constituent with neuropsychotropic effects, for MDD. METHODS:Sixty MDD (DSM-5) patients were equally assigned to receive sertraline (100 mg/d) plus either l-theanine (200 mg/d) or matched placebo in a six-week randomized, parallel-group, double-blind, placebo-controlled study. The participants were assessed using the Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4, and 6. Changes in scores, early improvement, response and remission rates, and adverse events were compared between the groups. RESULTS:Twenty-five participants in each group, a total of 50 patients, completed the study. All baseline characteristics were similar between the groups. The general linear model repeated-measures analysis demonstrated a significant time-treatment interaction effect for HDRS during the trial (p-value = 0.014), indicating more remarkable symptom improvement in the l-theanine group. A greater reduction in HDRS scores was observed in the l-theanine group from baseline to weeks 2, 4, and 6 (p-values = 0.02, 0.03, and 0.01, respectively). All patients responded to sertraline plus l-theanine until week 6. l-theanine was superior to placebo regarding response to treatment and remission rates at week 6 (p-values = 0.05 and 0.02, respectively). The frequency of side effects was comparable between the groups. LIMITATIONS:The small sample size and short study period were the limitations. CONCLUSIONS:l-theanine adjunct to sertraline outperforms placebo in treating MDD in a safe manner. Further long-term, large-scale studies are recommended to confirm this evidence. 10.1016/j.jad.2023.04.029
Effect of a Combination of Magnesium, B Vitamins, Rhodiola, and Green Tea (L-Theanine) on Chronically Stressed Healthy Individuals-A Randomized, Placebo-Controlled Study. Nutrients The effect of a combination of magnesium, vitamins B6, B9, B12, rhodiola and green tea/L-theanine (Mg-Teadiola) on stress was evaluated in chronically stressed, otherwise healthy individuals. Effects on stress-related quality-of-life parameters (sleep and perception of pain) were also explored. Adults with stress for ≥1 month, scoring ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire, were randomized (1:1) to receive oral Mg-Teadiola (n = 49) or a placebo (n = 51), for 28 days, with a follow-up assessment on Day 56 (NCT04391452). The primary endpoint was the change in the DASS-42 stress score from baseline to Day 28 with Mg-Teadiola versus placebo. The DASS-42 stress scores significantly decreased from baseline to Day 28 with Mg-Teadiola versus placebo (effect size, 0.29; 95% CI [0.01, 0.57]; p = 0.04). Similar reductions were observed on Day 14 (p = 0.006) and Day 56 (p = 0.02). A significant reduction in sensitivity to cold pain (p = 0.01) and a trend for lower sensitivity to warm pain was observed (p = 0.06) on Day 28. Improvements in daytime dysfunction due to sleepiness (Pittsburgh Sleep Quality Index-7 component score) were reported on Day 28, and were significant on Day 56 (p < 0.001). Mg-Teadiola is effective in managing stress in otherwise healthy individuals. Its beneficial effects on sleep and pain perception need further investigation. 10.3390/nu14091863
L-Theanine alleviates MPTP-induced Parkinson's disease by targeting Wnt/β-catenin signaling mediated by the MAPK signaling pathway. International journal of biological macromolecules We evaluated the neuroprotective effect of L-theanine in Parkinson's disease and the underlying mechanism focusing on WNT/β-catenin signaling mediated by the MAPK pathway. We treated MPTP-induced SH-SY5Y cells with various concentrations of L-theanine (50, 100, 200, and 500 μg/mL), and we also treated Parkinson's model mice with L-theanine. L-theanine treatment effectively reduced the immunohistochemical hallmarks of Parkinson's disease, particularly Lewy bodies and α-synuclein, and increased the number of tyrosine hydroxylase-positive cells. L-theanine also improved the motor dysfunction in MPTP-induced Parkinson's disease model mice as measured by the rotarod test. The levels of several pro-inflammatory mediators that are overexpressed in Parkinson's disease, namely TNF-α, IL-6, COX-2, and MAC-1, were reduced following L-theanine treatment, and the levels of the pro-apoptotic proteins Bcl-2, caspase-3, p53, and PARP-1 were significantly reduced. L-theanine regulated the oxidative stress-related factors SOD-1, GST, and NOX-4 by targeting several proteins related to WNT/β-catenin signaling, i.e., β-catenin, WNT-3a, WNT-5a, TCF1/TCF7, and LEF1, via the MAPK pathway (p-JNK, p-ERK, and p-p38). Our results indicate that L-theanine is neuroprotective and has anti-inflammatory effects that could be beneficial for treating Parkinson's disease. 10.1016/j.ijbiomac.2022.12.030
Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT. Scientific reports 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. 10.1038/s41598-020-70037-7
l-Theanine: An astounding sui generis integrant in tea. Sharma Eshita,Joshi Robin,Gulati Ashu Food chemistry l-theanine (l-Th), a non-protein amino acid present in tea, is a valuable nutraceutical product with unique health benefits and used as an additive in food industry. l-Th enhances the umami taste but its use is limited due to its inadequate production. Different extraction approaches from tea shoots, chemical synthesis to microbial transformation have been tried to meet its demand. In vitro, in vivo as well as clinical studies have shown its positive effect in regulating CNS disorders. l-Th has become choice ingredient in CNS active products due to its anti-stress and neuroprotective role in dementias particularly in retrogression of Alzheimer's. l-Th biochemically modulates various anti-neoplastic agents by increasing their bioavailability in tumour cells. The review, is an effort to condense the recent research on l-Th highlighting its biological resource, plausible role in tea plant, production approaches, its physiological role on human health and future prospects. 10.1016/j.foodchem.2017.09.046
Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. White David J,de Klerk Suzanne,Woods William,Gondalia Shakuntla,Noonan Chris,Scholey Andrew B Nutrients L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an L-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18-40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of L-theanine. 10.3390/nu8010053
L-theanine: an astounding sui generis amino acid in poultry nutrition. Saeed Muhammad,Khan Muhammad Sajjad,Kamboh Asghar Ali,Alagawany Mahmoud,Khafaga Asmaa F,Noreldin Ahmed E,Qumar Muhammad,Safdar Muhammad,Hussain Mubashar,Abd El-Hack Mohamed E,Chao Sun Poultry science L-theanine (γ-Glutamylethylamide) is a nonprotein water soluble amino acid (AA) mostly found in leaves of Camellia sinensis (green tea). This is a key component of green tea and is considered as the most abundant form of total AAs in green tea (i.e., about 50%). L-theanine is an exclusive taste ingredient of tea producing an attractive flavor and aroma in tea. It has biological effects such as antioxidant, growth promoter, immune booster, anti-stresser, hepatoprotective, antitumor, antiaging, antimicrobial, anti-inflammatory, and antianxiety activities that are worth noticing. It could reduce the oxidative impairment by reducing the synthesis of reactive oxygen species, oxidative parameters, and lipid damage as well as increasing the activity of antioxidant enzymes. The oral ingestion of L-theanine enhanced γδ T-cell proliferation. Therefore, it is being considered an essential compound of green tea that has the ability to improve immune function. The L-theanine can be used as a potential treatment for hepatic injury and immune-related liver diseases via the downregulation of the inflammatory response through the initiation of nitric oxide synthesis and glutathione production which are likely to be critical for the control of hepatic diseases as well as for the improvement of immune function. In addition, it could be used as a best natural feed additive with a potent antistressor by decreasing the levels of corticosterone, dopamine, and noradrenaline. After systematically reviewing the literature, it is noticed that most studies were carried out on mice, pig, human, and butterfly; while dietary supplementation studies of L-theanine in animal and poultry especially among broilers are very limited because of less awareness of this AA. So, the aim of this review is to encourage the veterinarian and poultry researchers to conduct more research at the molecular level about this AA to expose its more beneficial effects and its mechanism of absorption for potential use of this unique green tea AA in poultry nutrition. 10.1016/j.psj.2020.07.016
L-theanine, a natural constituent in tea, and its effect on mental state. Nobre Anna C,Rao Anling,Owen Gail N Asia Pacific journal of clinical nutrition Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.
Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Hidese Shinsuke,Ogawa Shintaro,Ota Miho,Ishida Ikki,Yasukawa Zenta,Ozeki Makoto,Kunugi Hiroshi Nutrients This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age: 48.3 ± 11.9 years) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets were randomly and blindly assigned for four-week administration. For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration ( = 0.019, 0.006, and 0.013, respectively). The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all < 0.05). For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration ( = 0.001 and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency ( = 0.002), especially letter fluency ( = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments. 10.3390/nu11102362
L-Theanine reduces psychological and physiological stress responses. Kimura Kenta,Ozeki Makoto,Juneja Lekh Raj,Ohira Hideki Biological psychology L-Theanine is an amino acid contained in green tea leaves which is known to block the binding of L-glutamic acid to glutamate receptors in the brain. Because the characteristics of L-Theanine suggest that it may influence psychological and physiological states under stress, the present study examined these possible effects in a laboratory setting using a mental arithmetic task as an acute stressor. Twelve participants underwent four separate trials: one in which they took L-Theanine at the start of an experimental procedure, one in which they took L-Theanine midway, and two control trials in which they either took a placebo or nothing. The experimental sessions were performed by double-blind, and the order of them was counterbalanced. The results showed that L-Theanine intake resulted in a reduction in the heart rate (HR) and salivary immunoglobulin A (s-IgA) responses to an acute stress task relative to the placebo control condition. Moreover, analyses of heart rate variability indicated that the reductions in HR and s-IgA were likely attributable to an attenuation of sympathetic nervous activation. Thus, it was suggested that the oral intake of L-Theanine could cause anti-stress effects via the inhibition of cortical neuron excitation. 10.1016/j.biopsycho.2006.06.006
Effects of l-Theanine on Cognitive Function in Middle-Aged and Older Subjects: A Randomized Placebo-Controlled Study. Baba Yoshitake,Inagaki Shun,Nakagawa Sae,Kaneko Toshiyuki,Kobayashi Makoto,Takihara Takanobu Journal of medicinal food l-theanine (-glutamylethylamide), an amino acid in green tea, has been shown to affect brain functions by relieving stress disorders, improving mood, and maintaining normal sleep. However, the cognitive functions for which theanine is effective are unclear. This study aimed to clarify which cognitive functions are positively affected by intake of l-theanine. A double-blind, randomized, placebo-controlled study was conducted. The subjects were Japanese men and women aged 50-69 years. Mini Mental State Examination-Japanese version score was 24 or higher. Cognitrax was used as a test battery for cognitive function. Evaluations were performed before the intervention, after a single dose of l-theanine, and after 12 weeks of regular intake. The single dose of l-theanine reduced the reaction time to attention tasks (Stroop test, Part 1), and it increased the number of correct answers and decreased the number of omission errors in working memory tasks (4-Part continuous performance test, Part 4). In conclusion, our study indicated that l-theanine may contribute to improving attention, thus enhancing working memory and executive functions. Clinical Trial No.: UMIN000033812. 10.1089/jmf.2020.4803
L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial. Sarris Jerome,Byrne Gerard J,Cribb Lachlan,Oliver Georgina,Murphy Jenifer,Macdonald Patricia,Nazareth Sonia,Karamacoska Diana,Galea Samantha,Short Anika,Ee Carolyn,Birling Yoann,Menon Ranjit,Ng Chee H Journal of psychiatric research Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450-900 mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (p = 0.73) nor insomnia severity on the Insomnia Severity Index (ISI; p = 0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; p = 0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISI ≤ 14; p = 0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted. 10.1016/j.jpsychires.2018.12.014
A Novel Theanine Complex, Mg-L-Theanine Improves Sleep Quality Regulating Brain Electrochemical Activity. Frontiers in nutrition L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters. On the other hand, Mg, a natural NMDA antagonist and GABA agonist, has a critical role in sleep regulation. Using the caffeine-induced brain electrical activity model, here we investigated the potency of L-theanine and two novel Mg-L-theanine compounds with different magnesium concentrations on electrocorticography (ECoG) patterns, GABAergic and serotonergic receptor expressions, dopamine, serotonin, and melatonin levels. Furthermore, we evaluated the sleep latency and duration in the pentobarbital induced sleep model. We herein showed that L-theanine, particularly its various complexes with magnesium increases the expression of GABAergic, serotonergic, and glutamatergic receptors, which were associated with decreased ECoG frequency, increased amplitude, and enhanced delta wave powers. Besides increased dopamine, serotonin, and melatonin; decreased MDA and increased antioxidant enzyme levels were also observed particularly with Mg-complexes. Protein expression analyses also showed that Mg-L-theanine complexes decrease inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) levels significantly. In accordance with these results, Mg complexes improved the sleep latency and duration even after caffeine administration. As a result, our data indicate that Mg-L-theanine compounds potentiate the effect of L-theanine on sleep by boosting slow-brain waves, regulating brain electrical activity, and increasing neurotransmitter and GABA receptor levels. 10.3389/fnut.2022.874254
GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Kim Suhyeon,Jo Kyungae,Hong Ki-Bae,Han Sung Hee,Suh Hyung Joo Pharmaceutical biology CONTEXT:γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABA receptors favours sleep. l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits. OBJECTIVE:This study investigated the potential synergistic sleep enhancement effect of GABA/l-theanine mixture. MATERIALS AND METHODS:Pentobarbital-induced sleep test was applied to find proper concentration for sleep-promoting effect in ICR mice. Electroencephalogram (EEG) analysis was performed to investigate total sleeping time and sleep quality in normal SD rats and caffeine-induced awareness model. Real-time polymerase chain reaction (RT-PCR) was applied to investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture involved transcriptional processes. RESULTS:GABA/l-theanine mixture (100/20 mg/kg) showed a decrease in sleep latency (20.7 and 14.9%) and an increase in sleep duration (87.3 and 26.8%) compared to GABA or theanine alone. GABA/l-theanine mixture led to a significant increase in rapid eye movement (REM) (99.6%) and non-REM (NREM) (20.6%) compared to controls. The use of GABA/l-theanine mixture rather than GABA or l-theanine alone restored to normal levels sleep time and quality in the arousal animal model. The administration of GABA/l-theanine led to increased expression of GABA and the glutamate GluN1 receptor subunit. CONCLUSIONS:GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of GABA/l-theanine combination, which seems to affect sleep behaviour. 10.1080/13880209.2018.1557698
L-theanine, unique amino acid of tea, and its metabolism, health effects, and safety. Türközü Duygu,Şanlier Nevin Critical reviews in food science and nutrition Tea has been a very popular beverage around the world for centuries. The reason that it is delicious, enabling hydration, showing warming and relaxing effect can be mentioned why it is consumed so much in addition to its prominent health effects. Although the catechins and caffeine are the primary bioactive components that are related with the health effects of the tea, the health effects of theanine amino acid, which is a nonproteinic amino acid special to tea, has become prominent in recent years. It has been known that the theanine amino acid in tea has positive effects especially on relaxing, cognitive performance, emotional status, sleep quality, cancer, cardiovascular diseases, obesity, and common cold. The results of acute and chronic toxicity tests conducted on the safety of theanine express that L-theanine is reliable in general even if it is consumed too much with diet. However, it has not revealed a clear evidence-based result yet regarding theanine metabolism, health effects, and its safety. Within this frame, chemical structure of theanine, its biosynthesis, dietary sources, metabolism, health effects, and safety are discussed in present study. 10.1080/10408398.2015.1016141
The Cognitive-Enhancing Outcomes of Caffeine and L-theanine: A Systematic Review. Cureus Attention-deficit hyperactivity disorder (ADHD) affects multiple cognitive domains, including impaired attention, hyperactivity, and increased impulsivity. According to the CDC, 9.4% of children between 2 and 17 years old have been diagnosed with ADHD. Neurotransmitters such as noradrenaline and dopamine have been suggested as crucial players in the pathophysiology of ADHD and are often targets of modern medication. Adenosine receptors types A1 and A2a in the brain are inhibited by caffeine: a stimulant known to augment attention by increasing cholinergic and dopaminergic transmission. The cognitive function of attention is also enhanced by the amino acid: L-theanine. The mechanism of action is that it behaves like a glutamate reuptake inhibitor while also acting in the hippocampus as a competitive low-affinity glutamate receptor antagonist. It's also shown to have a neuroprotective effect by its action on the gamma aminobutyric acid (GABA)-A receptors. Our systematic review investigates the literature and clinical trials on the cognitive-enhancing effects of caffeine and L-theanine. 10.7759/cureus.20828
L-Theanine and Immunity: A Review. Molecules (Basel, Switzerland) L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with its sedative and calming activities, the immunomodulatory effects of L-theanine have received less attention. Clinical and epidemiological studies have shown that L-theanine reduces immunosuppression caused by strenuous exercise and prevents colds and influenza by improving immunity. Numerous cell and animal studies have proven that theanine plays an immunoregulatory role in inflammation, nerve damage, the intestinal tract, and tumors by regulating γδT lymphocyte function, glutathione (GSH) synthesis, and the secretion of cytokines and neurotransmitters. In addition, theanine can be used as an immunomodulator in animal production. This article reviews the research progress of L-theanine on immunoregulation and related mechanisms, as well as its application in poultry and animal husbandry. It is hoped that this work will be beneficial to future related research. 10.3390/molecules28093846