theanine theanine theanine /ˈθiːəniːn/, also known as l-γ-glutamylethylamide and n5-ethyl-l-glutamine, is an amino acid analogue of the proteinogenic amino acids l-glutamate and l-glutamine and is found primarily in particular plant and fungal species. it was discovered as a constituent of green tea in 1949; in 1950, it was isolated from gyokuro leaves. theanine provides a unique brothy or savory (umami) flavor to green tea infusions. not to be confused with threonine, a distinct amino acid, or theine, an archaic synonym of caffeine. theaninel-theanineclinical dataother namesγ-l-glutamylethylamidedependenceliabilitynoneroutes ofadministrationoralatc codenonelegal statuslegal status us: otc un: unscheduled pharmacokinetic dataonset of actionabout 1 hourelimination half-lifecapsule ~1.2 hours green tea ~0.8 hoursidentifiers iupac name (2s)-2-ammonio-5-(ethylamino)-5-oxopentanoate or n-ethyl-l-glutamine cas number3081-61-6 ypubchem cid439378drugbankdb12444chemspider388498 yunii8021pr16qokeggc01047chebichebi:17394 ychemblchembl3039113comptox dashboard (epa)dtxsid80184817 echa infocard100.019.436 chemical and physical dataformulac7h14n2o3molar mass174.200 g·mol−13d model (jsmol)interactive imageinteractive imagemelting point174.20 °c (345.56 °f) boiling point215 °c (419 °f) smiles ccnc(=o)cc(n)c(=o)occnc(=o)ccc(n)c(o)=o inchi inchi=1s/c7h14n2o3/c1-2-9-6(10)4-3-5(8)7(11)12/h5h,2-4,8h2,1h3,(h,9,10)(h,11,12) ykey:datagrpvkzewha-uhfffaoysa-n y the name theanine without a prefix generally implies the enantiomer, l-theanine, which is the form found in tea leaves and as a dietary supplement ingredient. most studies have used l-theanine. the opposite enantiomer, d-theanine, has been studied less. the regulatory status of theanine varies by country. in japan, l-theanine has been approved for use in all foods, with some restrictions in the case of infant foods. in the united states, the food and drug administration (fda) considers it to be generally recognized as safe (gras) and allows its use as an ingredient in dietary supplements or foods up to a maximum of 250 mg per serving. the german federal institute for risk assessment, an agency of their federal ministry of food and agriculture, objects to the addition of l-theanine to beverages. in 2011, the european food safety authority concluded that a cause and effect relationship had not been established between consumption of l-theanine and improved cognitive function, alleviation of psychological stress, maintenance of normal sleep, or reduction of menstrual discomfort. therefore, health claims for l-theanine are not recognized in the european union. structure and properties the chemical name n5-ethyl-l-glutamine and other synonyms (see box) for theanine reflect its chemical structure. the name theanine, without prefix, is generally understood to imply the l- (s-) enantiomer, derived from the related proteinogenic l-amino acid glutamic acid. theanine is an analog of this amino acid, and its primary amide, l-glutamine (also a proteinogenic amino acid). theanine is a derivative of glutamine that is ethylated on the amide nitrogen (as the name n5-ethyl-l-glutamine describes), or alternatively, to the amide formed from ethylamine and l-glutamic acid at its γ- (5-) side chain carboxylic acid group (as the name γ-l-glutamylethylamide describes). relative to theanine, the opposite (d-, r-) enantiomer is largely absent from the literature, except implicitly. while natural extracts that are not harshly treated are presumed to contain only the biosynthetic l- enantiomeric form, mishandled isolates and racemic chemical preparations of theanines necessarily contain both theanine and its d-enantiomer (and from racemic syntheses, in equal proportion), and studies have suggested that the d-isomer may actually predominate in some commercial supplement preparations. amino acid racemization in aqueous media is a well-established chemical process promoted by elevated temperature and non-neutral ph values; prolonged heating of camellia extracts—possible for oversteeped teas and in undisclosed commercial preparative processes—has been reported to result in increasing racemization of theanine to give increasing proportions of the nonnatural d-theanine, up to equal proportions of each enantiomer. discovery and distribution theanine is found primarily in plant and fungal species. it was discovered as a constituent of tea (camellia sinensis) in 1949, and in 1950 a laboratory in kyoto successfully isolated it from gyokuro leaf, which has high theanine content. theanine is substantially present in black, green, and white teas from camellia sinensis in quantities of about 1% of the dry weight. deliberately shading tea plants from direct sunlight, as is done for matcha and gyokuro green tea, increases l-theanine content. the l-enantiomer is the form found in freshly prepared teas and some human dietary supplements. digestion and metabolism as a structural analog of glutamate and glutamine, the theanine in preparations (teas, pure supplements, etc.) is absorbed in the small intestine after oral ingestion; its hydrolysis to l-glutamate and ethylamine occur both in the intestine and liver, so theanine can be considered to function as a donor that supplies glutamate to the body. glutamate can be metabolized to glutamine in astrocytes, a process catalysed by glutamine synthetase and can also be decarboxylated to gaba by glutamate decarboxylase, thus theanine can supply the neurotransmitter pools of amino acids. it can also cross the blood–brain barrier intact, and register pharmacological effects directly. pharmacology in vitro theanine is structurally similar to the excitatory neurotransmitter glutamate, and in accordance, binds to glutamate receptors in vitro, though with much lower affinity in comparison. specifically, it binds to ionotropic glutamate receptors in the micromolar range, including the ampa and kainate receptors and, to a lesser extent, the nmda receptor. it acts as an antagonist of the former two sites, and a partial co-agonist of the nmda receptors. in vitro, theanine also binds to group i mglurs. in addition, it inhibits glutamine transporters and glutamate transporters, and thus blocks the reuptake of glutamine and glutamate. theanine may elicit umami taste, a consequence potentially associated with binding to and activation of the t1r1 + t1r3 heterodimer or umami (savory) taste receptor. in vivo in laboratory studies, theanine increases serotonin, dopamine and glycine levels in various areas of the brain, as well as bdnf and ngf levels in certain brain areas. assessment of potential effects in 2003, the german federal institute for risk assessment (bundesinstitut für risikobewertung, bfr) objected to the addition of isolated theanine to beverages. the institute stated the amount of theanine consumed by regular drinkers of tea or coffee is virtually impossible to determine. while it was estimated the quantity of green tea consumed by the average japanese tea drinker per day contains about 20 mg of the substance, there are no studies measuring the amount of theanine being extracted by typical preparation methods, or the percentage lost by discarding the first infusion. therefore, with the japanese being exposed to possibly much less than 20 mg per day, and europeans presumably even less, it was the opinion of the bfr that pharmacological reactions to drinks typically containing 50 mg of theanine per 500 milliliters could not be excluded—reactions such as impairment of psychomotor skills and amplification of the sedating effects of alcohol and hypnotics. the 2007 gras notice in the united states for theanine stated that it is safe for use in foods or supplements in amounts up to 250 mg. in 2011, the european food safety authority provided a scientific opinion that there was insufficient evidence for l-theanine to affect cognitive functions, psychological stress, normal sleep or menstrual discomfort. research on supplement use a 2020 systematic review concluded that l-theanine supplementation between 200 and 400 mg per day may help reduce stress and anxiety in people with acute stress, but there was insufficient evidence for treatment of chronic stress. the combination of theanine and caffeine has been shown to promote faster simple reaction time, task switching, sustained attention, faster numeric working memory reaction time and improved sentence verification accuracy.