L-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 and in 1950 was isolated from gyokuro leaves. Theanine provides a unique brothy or savory (umami) flavor to green tea infusions. 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 and in 1950 was isolated from gyokuro leaves. Theanine provides a unique brothy or savory (umami) flavor to green tea infusions. 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, including herb teas, soft drinks, desserts, etc. Restrictions apply to infant foods. In the United States, the Food and Drug Administration (FDA) considers it to be generally recognized as safe (GRAS) and allows its sale as a dietary supplement. 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. The European Food Safety Authority EFSA advised negatively on the use of L-theanine for improving cognitive function, alleviation of psychological stress, maintenance of normal sleep, and reduction of menstrual discomfort. Therefore, health claims for L-theanine are not recognized in the European Union. 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. 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, but not all, human dietary supplements. 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. It can also cross the blood–brain barrier intact, and register pharmacological effects directly. Theanine is structurally similar to the excitatory neurotransmitter glutamate, and in accordance, binds to glutamate receptors, 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 as an agonist of the latter site. 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. Lastly, theanine elicits umami taste, and this effect has been found to be a consequence of the fact that it directly binds to and activates the T1R1 + T1R3 heterodimer or umami (savory) taste receptor. Theanine increases serotonin, dopamine, GABA, and glycine levels in various areas of the brain, as well as BDNF and NGF levels in certain brain areas. However, its effect on serotonin is still a matter of debate in the scientific community, with studies showing increases and decreases in brain serotonin levels using similar experimental protocols. It has also been found that injecting spontaneously hypertensive mice with theanine significantly lowered levels of 5-hydroxyindoles in the brain. Researchers also speculate that it may inhibit glutamate excitotoxicity.