L-theanine alleviates myocardial ischemia/reperfusion injury by suppressing oxidative stress and apoptosis through activation of the JAK2/STAT3 pathway in mice.

BACKGROUND: L-theanine is a unique non-protein amino acid in tea that is widely used as a safe food additive. We investigated the cardioprotective effects and mechanisms of L-theanine in myocardial ischemia-reperfusion injury (MIRI). METHODS: The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis. RESULTS: Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine. CONCLUSIONS: L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.

Pharmacokinetics of L-theanine and the effect on amino acid composition in mice administered with L-theanine.

L-theanine, an amino acid component of the tea leaves of Camellia sinensis, is sold in Japan as a supplement for good sleep. Although several studies in humans and mice have reported the effects of L-theanine on brain function, only a few reports have comprehensively clarified the disposition of theanine administered to mice and its effects on concentrations of other blood amino acids. In this study, we aimed to determine the changes in the blood levels of L-theanine administered to mice and amino acid composition of the serum. L-theanine were administered to four-week-old Std-ddY male mice orally or via tail vein injection. L-theanine and other amino acids in serum prepared from blood collected at different time points post-dose were labeled with phenylisothiocyanate and quantified. The serum concentration of orally administered L-theanine peaked 15 min after administration. The area under the curve for tail vein injection revealed the bioavailability of L- theanine to be approximately 70%. L-theanine administration did not affect any amino acid levels in the serum, but a significant increase in the peak area overlapping the Glycine (Gly) peak was observed 30 min after administration. L-theanine administered to mice was rapidly absorbed and eliminated, suggesting that taking L-theanine as a supplement is safe without affecting its own levels or serum levels of other amino acids. However, considering that Gly, similar to L-theanine, is used as a dietary supplement for its anxiolytic effects and to improve sleep, determining the effects of L-theanine administration on Gly is important and needs further research.

Effect of L-theanine on selective attention in a traffic-related reaction task in sleep-deprived young adults: a double-blind placebo-controlled, crossover study.

BACKGROUND: L-theanine is a non-protein-forming amino acid found in tea. Limited evidence suggests that it improves selective attention. Sleep deprivation impairs attention and psychomotor reactions, affecting automobile driving. We aimed to determine whether L-theanine improves neurobehavioral measures of visual attention in acutely sleep-deprived healthy adults in a traffic-scene-based attention task. METHODS: In a double-blind, placebo-controlled, counterbalanced, two-way crossover study, we compared the effects of a 200-mg dose of L-theanine with a placebo (150 ml of distilled water) on a computerised, traffic-scene-based visual recognition reaction task in 24 healthy volunteers (age 20-25 years; 13 males) sleep-deprived overnight. The participants made speeded button-presses to imminent accident scenes (i.e. hits), while ignoring safe scenes. They were tested pre-dose and 45 min post-dose, each treatment administered one week apart. RESULTS: Hit rates were more than 90% in all sessions, and were similar in two treatments, pre- vs post-dose. L-theanine significantly reduced false alarms (i.e. responses to safe scenes) (p = 0.014) and increased A' (i.e. target-distractor discriminability) (p = 0.009), whereas placebo did not (p > 0.05). L-theanine reduced hit reaction time by 38.65 ms (p = 0.007), and placebo by 19.08 ms (p = 0.016), however reaction time changes from baseline were not significantly different between treatments (p > 0.05). CONCLUSIONS: L-theanine in high doses appears to improve selective visual attention by concurrently improving information processing speed and target-distractor discriminability in acutely sleep-deprived individuals. This is consistent with previous functional neuroimaging findings, where L-theanine suppressed distractor-processing and default-mode-network activity in visual selective attention tasks.

Development of a SERS aptasensor for the determination of L-theanine using a noble metal nanoparticle-magnetic nanospheres composite.

An ultrasensitive surface-enhanced Raman spectroscopy (SERS) aptamer sensor (aptasensor) using a noble metal nanoparticle-magnetic nanospheres composite was developed for L-theanine detection. It makes use of Fe3O4@Au MNPs and Au@Ag NPs embedded with the Raman reporter 4-mercaptobenzoic acid (4MBA). Au@4MBA@Ag NPs modified by aptamer and Fe3O4@Au MNPs modified by cDNA created the aptasensor with the strongest Raman signal of 4MBA through the specific binding of the aptamer. With the preferred binding of L-theanine aptamer to L-theanine, Au@4MBA@Ag NPs were released from Fe3O4@Au MNPs, causing a linear decrease in SERS intensity to achieve the SERS detection of the L-theanine. The SERS peak of 4MBA at 1078 cm-1 was used for quantitative determination. SERS intensity showed a good log-linear relationship within the range 10-10 to 10-6 M of L-theanine. The aptasensor has a high selectivity for L-theanine compared with other twelve tested analytes. Hence, this aptasensor is a promising analytical tool for L-theanine detection. The developed method was applied to the analysis of real samples, demonstrating excellent performance. The comparison with the standard liquid chromatography mass spectrometry method showed an error within 20%.

The Response of Growth and Transcriptome Profiles of Tea Grey Blight Disease Pathogen Pestalotiopsis theae to the Variation of Exogenous L-Theanine.

Tea grey blight disease is one of the most destructive diseases that infects tea and is caused by the pathogen Pestalotiopsis theae (Sawada) Steyaert. L-theanine is a unique non-protein amino acid of the tea plant. Different concentrations of L-theanine exhibit significant inhibitory effects on the growth and sporulation ability of the pathogen causing tea grey blight disease. To understand the effect mechanism of L-theanine on P. theae, transcriptome profiling was performed on the pathogenic mycelium treated with three different concentrations of L-theanine: no L-theanine treatment (TH0), 20 mg/mL theanine treatment (TH2), and 40 mg/mL theanine treatment (TH4). The colony growths were significantly lower in the treatment with L-theanine than those without L-theanine. The strain cultured with a high concentration of L-theanine produced no spores or only a few spores. In total, 2344, 3263, and 1158 differentially expressed genes (DEGs) were detected by RNA-sequencing in the three comparisons, Th2 vs. Th0, Th4 vs. Th0, and Th4 vs. Th2, respectively. All DEGs were categorized into 24 distinct clusters. According to GO analysis, low concentrations of L-theanine primarily affected molecular functions, while high concentrations of L-theanine predominantly affected biological processes including external encapsulating structure organization, cell wall organization or biogenesis, and cellular amino acid metabolic process. Based on KEGG, the DEGs of Th2 vs. Th0 were primarily involved in pentose and glucuronate interconversions, histidine metabolism, and tryptophan metabolism. The DEGs of Th4 vs. Th0 were mainly involved in starch and sucrose metabolism, amino sugar, and nucleotide sugar metabolism. This study indicated that L-theanine has a significant impact on the growth and sporulation of the pathogen of tea grey blight disease and mainly affects amino acid metabolism, carbohydrate metabolism, and cellular structure-related biosynthesis processes of pathogenic fungi. This work provides insights into the direct control effect of L-theanine on pathogenic growth and also reveals the molecular mechanisms of inhibition of L-theanine to P. theae.

L-Theanine Prolongs the Lifespan by Activating Multiple Molecular Pathways in Ultraviolet C-Exposed Caenorhabditis elegans.

L-theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effects, regulation of the immune response, relaxing neural tension, and reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also upregulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provides a theoretical basis for the possibility that tea drinking may prevent mitochondrial-related diseases.

L-Theanine alleviates heat stress through modulation of gut microbiota and immunity.

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-1 ·d-1 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.

l-Theanine delays d-galactose-induced senescence by regulating the cell cycle and inhibiting apoptosis in rat intestinal cells.

BACKGROUND: Intestinal senescence is associated with several aging-related diseases. l-Theanine (LTA) has demonstrated strong potential as an antioxidant and antisenescence agent. This study investigated the regulatory effect of LTA on cellular senescence using an in vitro model of d-galactose (D-Gal)-induced senescence in the rat epithelial cell line, intestinal epithelioid cell-6 (IEC-6). RESULTS: Treatment of IEC-6 cells with 40 mg/mL D-Gal for 48 h resulted in the successful development of the senescent cell model. Compared with D-Gal alone, both LTA preventive and delayed intervention increased cell viability and the ratio of JC-1 monomers to aggregates, increased the antioxidant capacity, and decreased the advanced glycation end product (AGE) levels and the overall number of senescent cells. Preventive and delayed intervention with 1000 µM LTA alleviated the D-Gal-induced cell cycle arrest by regulating p38, p53, CDK4, and CDK6 expression at the mRNA and protein levels, and further induced CycD1 proteins. Moreover, LTA preventive intervention reduced apoptosis to a greater degree than delayed intervention by upregulating the expression of the receptors of AGEs, Bax, Bcl-2, and NF-κB at the mRNA and protein levels. CONCLUSION: Our findings indicate that LTA intervention could attenuate senescence in IEC-6 cells by regulating the cell cycle and inhibiting apoptosis. © 2023 Society of Chemical Industry.

Hepatoprotective effects and mechanisms of l-theanine and epigallocatechin gallate combined intervention in alcoholic fatty liver rats.

BACKGROUND: Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. RESULTS: The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. CONCLUSION: l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.

Comparison Between Efficacy of Oral Melatonin and Oral L-theanine in Improving Sleep in Cancer Patients Suffering From Insomnia: A Randomised Double-blinded Placebo-controlled Study.

Objectives: The primary objective was to compare the hypnotic efficacy of oral melatonin, oral L-theanine, and placebo in improving sleep in cancer patients with insomnia by the Athens Insomnia Scale (AIS). The secondary objective was to know the prevalence of insomnia in patients with cancer. Materials and Methods: A prospective, double-blinded, placebo-controlled study was conducted after obtaining Institutional Ethics Committee approval. One hundred and twenty patients were randomly assigned to either Group A (melatonin), Group B (L-theanine), or Group C (placebo). They were instructed to take the tablets for 14 consecutive days, two h (hours) before bedtime, and evaluated with AIS on the 1st day, 7th day, and 14th day. Results: There were seven dropouts: Two in Group A, two in Group B, and three in Group C. Significant differences in favour of melatonin treatment were found. There were statistically significant improvements in insomnia in cancer patients on melatonin intake compared to L-theanine. L-theanine had statistically significant improvements in insomnia in comparison to placebo. The mean ± standard deviation AIS on day one in Group A was 14.82 ± 1.29; on day seven was 10.92 ± 1.12; and on day 14 was 5.00 ± 0.70. Similarly, in Group B, the mean ± standard deviation AIS was 15.39 ± 1.03, 13.05 ± 1.06, and 9.55 ± 1.01, and in Group C, the mean AIS was 14.92 ± 1.40, 14.54 ± 1.35 and 13.05 ± 1.61 on the 1st, 7th and 10th day, respectively. There was an improvement in sleep from 1 to 7 days, 7 days to 14 days, and 1 day to 14 days in all the groups (P < 0.005). Conclusion: The hypnotic efficacy of oral melatonin 3 mg was better than oral L-theanine 200 mg in cancer patients having insomnia. Furthermore, L-theanine had a better hypnotic efficacy when compared to a placebo.

How does l-theanine treatment affect the levels of serum and hippocampal BDNF, insulin and adipocytokines in diabetic rats?

BACKGROUND: Diabetes Mellitus (DM), a metabolic disease characterized by the increased blood glucose level, insulin deficiency or ineffectiveness, may cause structural and functional disorders in the brain. l-Theanine (LTN) has the relaxing, psychoactive, antidepressant, anti-inflammatory and antinecrotic properties, and regulates the functions of hippocampus (HP) in brain. In the present study, the aim was to identify the effects LTN on the levels of BDNF, insulin and adipocytokines (TNF-α, leptin, adiponectin and resistin) in both HP and serum of diabetic rats. METHODS: 32 male Wistar rats were divided into four groups (n = 8/group): Control, LTN, DM and DM + LTN. Diabetes was induced by by nicotinamide/streptozotocin. 200 mg/kg/day LTN treatment was applied for 28 days. The serum and hippocampal levels of the parameters were determined by using commercial ELISA kits. Additionally, HP tissues examined histopathologically. RESULTS: LTN treatment significantly decreased leptin and adiponectin levels in HP tissues in diabetic rats (p < 0.05). Although it decreased the insulin level in both serum and HP, this was not statistically significant. No significant effect on other parameters was observed (p > 0.05). In histopathological analysis, although the damage was reduced by LTN in all sections of HP, this change was significant mainly in CA3 region (p < 0.05). CONCLUSION: It was concluded that LTN has the ability to reduce hippocampal degeneration and modulates adipocytokines in diabetic rats.

Caution may be required in using l-theanine in diabetes mellitus: A study on the rats.

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.

The protective effect of L-theanine addition to a cryoprotectant on the storage viability of lactic acid bacteria.

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.

Redesign of γ-glutamyl transpeptidase from Bacillus subtilis for high-level production of L-theanine by cavity topology engineering.

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-1 h-1 by whole-cell synthesis in a 5 L bioreactor, which was one of the highest concentrations reported so far at 92.4 g L-1. 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 -1 h-1 (92.4 g L-1) in a 5 L bioreactor.

Effects of L-theanine on intestinal morphology, barrier function, and MAPK signaling pathways in diquat-challenged piglets.

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 (p < 0.05). While for diquat-challenged piglets, L-theanine addition increased average daily gain, jejunum villus height, and interferon-γ level (p < 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 (p < 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.

L-theanine combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: A placebo-controlled, double-blind, randomized trial.

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 × $$ \times $$ 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.

L-Theanine and Immunity: A Review.

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.

L-Theanine regulates lipid metabolism by modulating gut microbiota and bile acid metabolism.

BACKGROUND: l-Theanine (LTA) is a biologically active ingredient in tea that shows great potential for regulating lipid metabolism. Bile acids (BA), an important end-product of cholesterol catabolism, participate in the regulation of lipid metabolism and gut microbiota. Here, we investigated the effect of LTA on lipid metabolism and the mechanism by which it regulates BA metabolism and gut microbiota. Male BALB/c mice were treated with LTA for 28 days. RESULTS: Daily LTA doses of 100 and 300 mg kg-1  d-1 altered the gut microbiota in mice, predominantly by decreasing Lactobacillus, Streptococcus, Bacteroides, Clostridium and Enterorhabdus microbes associated with bile-salt hydrolase (BSH) activity, thereby decreasing the activity of BSH and increasing the levels of ileum conjugated BA (such as glycocholic acid (GCA) and lithocholic acid), thereby inhibiting the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway. Inhibition of FXR-FGF15 signaling was accompanied by upregulation of cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and increased hepatic production of cholic acid, deoxycholic acid, GCA, glycine cholic acid and glycine ursodeoxycholic acid. Meanwhile, increasing hepatic unconjugated BA upregulated the mRNA and protein expression of liver 3-hydroxy-3-methylglutaryl-CoA reductase and downregulated the mRNA and protein expression of stearoyl-CoA desaturase-1, liver low-density lipoprotein receptor and type B scavenger receptor. Therefore, the serum levels of cholesterol and triglycerides decreased. CONCLUSION: Our findings indicate that LTA regulates lipid metabolism by modulating the gut microbiota and BA metabolism via the FXR-FGF15-CYP7A1 pathway. © 2022 Society of Chemical Industry.

Effects of dietary l-theanine supplementation on pork quality and muscle fiber type transformation in finishing pigs.

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*24 h 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.

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.

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.SIGNIFICANCE STATEMENT 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.