Neurobiological effects of theanine and its possible use in neurology and psychiatry

Close metadata

Recommended articles:

The regulatory role of gut microbiota in inflammation in depression and anxiety. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(11):33-39

Behavioral phenomena of depression in adolescence. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(11-2):9-13

Experience of clinical use of fluvoxamine for the treatment of comorbid depression in childhood and adolescence. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(11-2):14-21

Anxiety-depressive symptoms in the structure of eating disorders in adolescents. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(11-2):22-29

Psychosocial pathomorphosis of depressions. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(11-2):30-37

Effectiveness, safety and adherence to therapy with Elicea Q-Tab in real clinical practice. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(11-2):46-54

Features of inflammatory reactions in patients with juvenile depression with a clinically high risk of psychosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(11-2):55-61

Risk factors of chronic postoperative pain in cardiac surgery: mental characteristics and central sensitization. Russian Journal of Pain. 2023;(4):32-38

Correlation of sarcopenia and depression: common risk factors and pathogenetic mechanisms. Russian Journal of Preventive Medicine. 2023;(11):57-63

Depression as a predictor of high arterial stiffness in patients with low/moderate risk of cardiovascular complications. Russian Cardiology Bulletin. 2023;(4):49-55

Theanine is an analog of glutamate and the major aminoacid in green tea. It has received growing attention in recent years because of its beneficial effects on the central nervous system. Theanine was shown to increase levels of brain-derived neurotrophic factor and to stimulate neurogenesis. Anti-stress and calming effects of theanine are the most apparent and well-studied. A number of studies showed neuroprotective effects of theanine after an ischemic cerebral injury or the exposure to toxic chemicals. It also improved cognitive function including attention, memory and learning. Recent studies demonstrated a promising role of theanine in augmentation therapy for major depressive disorder and schizophrenia. Theoretical grounds for using theanine in treatment of bipolar disorder, anxiety disorder and some neurodegenerative disorders are discussed.

Keywords:

theanine

brain wave activity

neurodegenerative diseases

memory

learning

depression

schizophrenia

Authors:

Katasonov A.B.

List of references:

Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. Effect of theanine, γ-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. 1998;23(5):667-673.
Kimura R, Murata T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system. I. Central depressant effect of theanine. Chem Pharm Bull (Tokyo). 1971;19(6):1257-1261. https://doi.org/10.1248/cpb.19.1257
Unno T, Suzuki Y, Kakuda T, Hayakawa T, Tsuge H. Metabolism of theanine, gamma-glutamylethylamide, in rats. J Agric Food Chem. 1999;47(4):1593-1596. https://doi.org/10.1021/jf981113t
Tsuge H, Sano S, Hayakawa T, Kakuda T, Unno T. Theanine, gamma-glutamylethylamide, is metabolized by renal phosphate-independent glutaminase. Biochim Biophys Acta. 2003;17:1620(1-3):47-53. https://doi.org/10.1016/s0304-4165(02)00504-4
Ma QP, Huang C, Cui QY, Yang DJ, Sun K, Chen X, Li XH. Meta-Analysis of the Association between Tea Intake and the Risk of Cognitive Disorders. PLoS One. 2016;11(11):0165861. https://doi.org/10.1371/journal.pone.0165861
Finger A, Kuhr S, Engelhardt UH. Chromatography of tea constituents. J Chromatogr. 1992;624(1-2):293-315. https://doi.org/10.1016/0021-9673(92)85685-M
Borzelleca JF, Peters D, Hall W. A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats. Food Chem Toxicol. 2006;44(7):1158-1166. https://doi.org/10.1016/j.fct.2006.03.014
Türközü D, Şanlier N. L-theanine, unique amino acid of tea, and its metabolism, health effects, and safety. Crit Rev Food Sci Nutr. 2017;57(8):1681-1687. https://doi.org/10.1080/10408398.2015.1016141
Eschenauer G, Sweet BV. Pharmacology and therapeutic uses of theanine. Am J Health Syst Pharm. 2006;63(1):26, 28-30. https://doi.org/10.2146/ajhp050148
Gomez-Ramirez M, Higgins BA, Rycroft JA, Owen GN, Mahoney J, Shpaner M, Foxe JJ. The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine. Clin Neuropharmacol. 2007;30(1):25-38. https://doi.org/10.1097/01.WNF.0000240940,13876.17
Owen GN, Parnell H, De Bruin EA, Rycroft JA. The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci. 2008;11(4):193-198. https://doi.org/10.1179/147683008X301513
Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17(suppl 1):167-168.
Kakuda T, Nozawa A, Unno T, Okamura N, Okai O. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem. 2000;64(2):287-293. https://doi.org/10.1271/bbb.64.287
Gomez-Ramirez M, Kelly SP, Montesi JL, Foxe JJ. The effects of L-theanine on alpha-band oscillatory brain activity during a visuo-spatial attention task. Brain Topogr. 2009;22(1):44-51. https://doi.org/10.1007/s10548-008-0068-z
Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-208. https://doi.org/10.1002/biof.5520260305
Yoto A, Murao S, Motoki M, Yokoyama Y, Horie N, Takeshima K, Masuda K, Kim M, Yokogoshi H. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids. 2012;43(3):1331-1337. https://doi.org/10.1007/s00726-011-1206-6
Lyon MR, Kapoor MP, Juneja LR. 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. Altern Med Rev. 2011;16(4):348-354.
Yamada T, Terashima T, Okubo T, Juneja LR, Yokogoshi H. Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutr Neurosci. 2005;8(4):219-226. https://doi.org/10.1080/10284150500170799
Schallier A, Vermoesen K, Loyens E, Van Liefferinge J, Michotte Y, Smolders I, Massie A. L-Theanine intake increases threshold for limbic seizures but decreases threshold for generalized seizures. Nutr Neurosci. 2013;16(2):78-82. https://doi.org/10.1179/1476830512Y.0000000033
Kakuda T, Hinoi E, Abe A, Nozawa A, Ogura M, Yoneda Y. Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain. J Neurosci Res. 2008;86(8):1846-1856. https://doi.org/10.1002/jnr.21637
Kakuda T, Nozawa A, Sugimoto A, Niino H. Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem. 2002;66(12):2683-2686. https://doi.org/10.1271/bbb.66.2683
Sebih F, Rousset M, Bellahouel S, Rolland M, de Jesus Ferreira MC, Guiramand J, Cohen-Solal C, Barbanel G, Cens T, Abouazza M, Tassou A, Gratuze M, Meusnier C, Charnet P, Vignes M, Rolland V. Characterization of l-Theanine Excitatory Actions on Hippocampal Neurons: Toward the Generation of Novel N-Methyl-d-aspartate Receptor Modulators Based on Its Backbone. ACS Chem Neurosci. 2017;8(8):1724-1734. https://doi.org/10.1021/acschemneuro.7b00036
Shen H, Shen X, Wang R, Wu M. Effects of theanine on cerebral ischemia-reperfusion injury in rats. Wei Sheng Yan Jiu. 2011;40(6):684-687.
Yokogoshi H, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines, striatal dopamine release and some kinds of behavior in rats. Nutrition. 2000;16(9):776-777. https://doi.org/10.1016/S0899-9007(00)00384-1
Yamada T, Terashima T, Honma H, Nagata S, Okubo T, Juneja LR, Yokogoshi H. Effects of theanine, a unique amino acid in tea leaves, on memory in a rat behavioral test. Biosci Biotechnol Biochem. 2008;72(5):1356-1359. https://doi.org/10.1271/bbb.70669
Walton HS, Dodd PR. Glutamate-glutamine cycling in Alzheimer’s disease. Neurochem Int. 2007;50(7-8):1052-1066. https://doi.org/10.1016/j.neuint.2006.10.007
Egashira N, Hayakawa K, Mishima K, Kimura H, Iwasaki K, Fujiwara M. Neuroprotective effect of gamma-glutamylethylamide (theanine) on cerebral infarction in mice. Neurosci Lett. 2004;363(1):58-61. https://doi.org/10.1016/j.neulet.2004.03.046
Egashira N, Hayakawa K, Osajima M, Mishima K, Iwasaki K, Oishi R, Fujiwara M. Involvement of GABA(A) receptors in the neuroprotective effect of theanine on focal cerebral ischemia in mice. J Pharmacol Sci. 2007;105(2):211-214. https://doi.org/10.1254/jphs.scz070901
Kakuda T. Neuroprotective effects of the green tea components theanine and catechins. Biol Pharm Bull. 2002;25(12):1513-1518. https://doi.org/10.1248/bpb.25.1513
Nagasawa K, Aoki H, Yasuda E, Nagai K, Shimohama S, Fujimoto S. Possible involvement of group I mGluRs in neuroprotective effect of theanine. Biochem Biophys Res Commun. 2004;320(1):116-122. https://doi.org/10.1016/j.bbrc.2004.05.143
Zukhurova M, Prosvirnina M, Daineko A, Simanenkova A, Petrishchev N, Sonin D, Galagudza M, Shamtsyan M, Juneja LR, Vlasov T. L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion. Phytother Res. 2013;27(9):1282-1287. https://doi.org/10.1002/ptr.4868
Kim TI, Lee YK, Park SG, Choi IS, Ban JO, Park HK, Nam SY, Yun YW, Han SB, Oh KW, Hong JT. 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. Free Radic Biol Med. 2009;47(11):1601-1610. https://doi.org/10.1016/j.freeradbiomed.2009.09.008
Di X, Yan J, Zhao Y, Zhang J, Shi Z, Chang Y, Zhao B. L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway. Neuroscience. 2010;168(3):778-786. https://doi.org/10.1016/j.neuroscience.2010.04.019
Wu Z, Zhu Y, Cao X, Sun S, Zhao B. Mitochondrial toxic effects of Aβ through mitofusins in the early pathogenesis of Alzheimer’s disease. Mol Neurobiol. 2014;50(3):986-996. https://doi.org/10.1007/s12035-014-8675-z
Asanuma M, Miyazaki I, Ogawa N. Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease. Neurotox Res. 2003;5(3):165-176. https://doi.org/10.1007/BF03033137
Takeshima M, Miyazaki I, Murakami S, Kita T, Asanuma M. l-Theanine protects against excess dopamine-induced neurotoxicity in the presence of astrocytes. J Clin Biochem Nutr. 2016;59(2):93-99. https://doi.org/10.3164/jcbn.16-15
Ben P, Zhang Z, Xuan C, Sun S, Shen L, Gao Y, Cao X, Zhou Y, Lan L, Yin Z, Luo L. Protective Effect of L-Theanine on Cadmium-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondria-Mediated Pathway. Neurochem Res. 2015;40(8):1661-1670. https://doi.org/10.1007/s11064-015-1648-4
Ben P, Zhang Z, Zhu Y, Xiong A, Gao Y, Mu J, Yin Z, Luo L. l-Theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Neurotoxicology. 2016;57:95-103. https://doi.org/10.1016/j.neuro.2016.09.010
Sumathi T, Shobana C, Thangarajeswari M, Usha R. Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain — histopathological, and biochemical approach. Drug Chem Toxicol. 2015;38(1):22-31. https://doi.org/10.3109/01480545.2014.900068
Cho HS, Kim S, Lee SY, Park JA, Kim SJ, Chun HS. Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell death. Neurotoxicology. 2008;29(4):656-662. https://doi.org/10.1016/j.neuro.2008.03.004
Takeda A, Sakamoto K, Tamano H, Fukura K, Inui N, Suh SW, Won SJ, Yokogoshi H. Facilitated neurogenesis in the developing hippocampus after intake of theanine, an amino acid in tea leaves, and object recognition memory. Cell Mol Neurobiol. 2011;31(7):1079-1088. https://doi.org/10.1007/s10571-011-9707-0
Wakabayashi C, Numakawa T, Ninomiya M, Chiba S, Kunugi H. Behavioral and molecular evidence for psychotropic effects in L-theanine. Psychopharmacology (Berl). 2012;219(4):1099-1109. https://doi.org/10.1007/s00213-011-2440-z
Tian X, Sun L, Gou L, Ling X, Feng Y, Wang L, Yin X, Liu Y. Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain Res. 2013;1503:24-32. https://doi.org/10.1016/j.brainres.2013.01.048
White DJ, de Klerk S, Woods W, Gondalia S, Noonan C, Scholey AB. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. Nutrients. 2016;19:8(1):53. https://doi.org/10.3390/nu8010053
Takeda A, Tamano H, Suzuki M, Sakamoto K, Oku N, Yokogoshi H. Unique induction of CA1 LTP components after intake of theanine, an amino acid in tea leaves and its effect on stress response. Cell Mol Neurobiol. 2012;32(1):41-48. https://doi.org/10.1007/s10571-011-9732-z
Yamin G. NMDA receptor-dependent signaling pathways that underlie amyloid beta-protein disruption of LTP in the hippocampus. J Neurosci Res. 2009;87(8):1729-1736. https://doi.org/10.1002/jnr.21998
Song J, Xu H, Liu F, Feng L. Tea and cognitive health in late life: current evidence and future directions. J Nutr Health Aging. 2011;16(1):31-34. https://doi.org/10.1007/s12603-011-0139-9
Park SK, Jung IC, Lee WK, Lee YS, Park HK, Go HJ, Kim K, Lim NK, Hong JT, Ly SY, Rho SS. A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. J Med Food. 2011;14(4):334-343. https://doi.org/10.1089/jmf.2009.1374
Kakuda T. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol Res. 2011;64(2):162-168. https://doi.org/10.1016/j.phrs.2011.03.010
Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders Pharmacol Rev. 2012;64(2):238-258. https://doi.org/10.1124/pr.111.005108
Singal A, Tirkey N, Muragundla A, Chopra K. Green tea [Camellia sinensis (L.) O. Kuntze] extract reverses the despair behaviour in reserpinised and diabetic mice. Indian J Exp Biol. 2006;44(11):913-917.
Di Lorenzo A, Nabavi SF, Sureda A, Moghaddam AH, Khanjani S, Arcidiaco P, Nabavi SM, Daglia M. Antidepressive-like effects and antioxidant activity of green tea and GABA green tea in a mouse model of post-stroke depression. Mol Nutr Food Res. 2016;60(3):566-579. https://doi.org/10.1002/mnfr.201500567
Yin C, Gou L, Liu Y, Yin X, Zhang L, Jia G, Zhuang X. Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice. Phytother Res. 2011;25(11):1636-1639. https://doi.org/10.1002/ptr.3456
Unno K, Fujitani K, Takamori N, Takabayashi F, Maeda K, Miyazaki H, Tanida N, Iguchi K, Shimoi K, Hoshino M. Theanine intake improves the shortened lifespan, cognitive dysfunction and behavioural depression that are induced by chronic psychosocial stress in mice. Free Radic Res. 2011;45(8):966-974. https://doi.org/10.3109/10715762.2011.566869
Dimpfel W, Kler A, Kriesl E, Lehnfeld R. Theogallin and L-theanine as active ingredients in decaffeinated green tea extract: I. electrophysiological characterization in the rat hippocampus in-vitro. J Pharm Pharmacol. 2007;59(8):1131-1136. https://doi.org/10.1211/jpp.59.8.0011
Hidese S, Ota M, Wakabayashi C, Noda T, Ozawa H, Okubo T, Kunugi H. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr. 2017;29(2):72-79. https://doi.org/10.1017/neu.2016.33
Shim SS, Hammonds MD, Kee BS. Potentiation of the NMDA receptor in the treatment of schizophrenia: focused on the glycine site. Eur Arch Psychiatry Clin Neurosci. 2008;258(1):16-27. https://doi.org/10.1007/s00406-007-0757-8
Ritsner MS, Miodownik C, Ratner Y, Shleifer T, Mar M, Pintov L, Lerner V. 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. J Clin Psychiatry. 2011;72(1):34-42. https://doi.org/10.4088/JCP.09m05324gre
Miodownik C, Maayan R, Ratner Y, Lerner V, Pintov L, Mar M, Weizman A, Ritsner MS. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients. Clin Neuropharmacol. 2011;34(4):155-160. https://doi.org/10.1097/WNF.0b013e318220d8c6
Ota M, Wakabayashi C, Sato N, Hori H, Hattori K, Teraishi T, Ozawa H, Okubo T, Kunugi H. Effect of L-theanine on glutamatergic function in patients with schizophrenia. Acta Neuropsychiatr. 2015;27(5):291-296. https://doi.org/10.1017/neu.2015.22
Kardashev A, Ratner Y, Ritsner MS. Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Clin Schizophr Relat Psychoses. 2018;12(1):31-41. https://doi.org/10.3371/CSRP.KARA.070415
Martinowich K, Manji H, Lu B. New insights into BDNF function in depression and anxiety. Nat Neurosci. 2007;10(9):1089-1093. https://doi.org/10.1038/nn197
Kim J, Lee S, Kang S, Kim SH, Kim JC, Yang M, Moon C. Brain-derived neurotropic factor and GABAergic transmission in neurodegeneration and neuroregeneration. Neural Regen Res. 2017;12(10):1733-1741. https://doi.org/10.4103/1673-5374.217353

Close metadata