The neuropharmacology of L-theanine(N-ethyl-L-glutamine): A possible neuroprotective and cognitive enhancing agent

Behavioural Neuroscience Laboratory, Department of Physiology, Monash Center for Brain and Behaviour, Monash University, Australia.
Journal of Herbal Pharmacotherapy 02/2006; 6(2):21-30. DOI: 10.1080/J157v06n02_02
Source: PubMed


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.

    • ". Also, animal studies report that theanine, a form of amino acid which is abundant in green tea increases brain dopamine [30] and serotonin [31], resulting in improved cognitive capacity and attention [32]. Interaction between caffeine and theanine may also be possible. "
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    ABSTRACT: Background and Purpose: We examined the association between green tea consumption and mortality due to all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries and other causes of death in a large-scale population-based cohort study in Japan. Methods We studied 90,914 Japanese (aged between 40 and 69 years) recruited between 1990 and 1994. After 18.7 years of follow-up, 12,874 deaths were reported. The association between green tea consumption and risk of all causes and major causes of mortality was assessed using the Cox proportional hazards regression model with adjustment for potential confounders. Results Hazard ratios for all-cause mortality among men who consumed green tea compared with those who drank less than 1 cup per day were 0.96 (0.89 to 1.03) for 1 to 2 cups per day, 0.88 (0.82 to 0.95) for 3 to 4 cups per day, and 0.87 (0.81 to 0.94) for more than 5 cups per day (p for trend <0.001). Corresponding hazard ratios for women were 0.90 (0.81 to 1.00), 0.87 (0.79 to 0.96), and 0.83 (0.75 to 0.91) (p for trend <0.001). Green tea was inversely associated with mortality from heart disease in both men and women, and mortality from cerebrovascular disease and respiratory disease in men. No association was found between green tea and total cancer mortality. Conclusion This prospective study suggests that the consumption of green tea may reduce the risk of all-cause mortality and the three leading causes of death in Japan.
    No preview · Article · Mar 2015 · Annals of Epidemiology
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    • "). Remarkably, EGCG decreases Aβ levels and plaques in mice, reduced Aβ mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice (Lee et al. 2009; Rezai-Zadeh et al. 2005, 2008), as well as prevents Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca 2+ influx and ROS production (He et al. 2011). In addition to tea catechins, theanine, which is an amino acid uniquely found in tea leaf, may also possess neuroprotective effect (Nathan et al. 2006), probably by its antagonistic effect on ionotropic glutamate receptor subtypes, such as NMDARs (Kakuda 2011). Moreover , the beneficial effects of caffeine on stress-induced memory disturbance are mimicked by antagonists of adenosine A2a receptors, likely mediated by its ability to control glutamatergic transmission, especially NMDAR-dependent plasticity (Cunha and Agostinho 2010). "
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    ABSTRACT: It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown. This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance. Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5 g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling. Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance. Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia.
    Full-text · Article · Mar 2014 · Psychopharmacology
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    • "L-Theanine was originally found in green tea and has historically been recognized as a relaxing agent (de Mejia et al. 2009; Nathan et al. 2006). Besides its similar chemical structure to glutamate, L-theanine shows micromolar affinities for kainate, α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA), and N-methyl D-aspartate (NMDA) glutamate receptors (Kakuda et al. 2002). "
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    ABSTRACT: 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. 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. 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. 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.
    Full-text · Article · Dec 2013 · Psychiatry and Clinical Neurosciences
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