|PubChem||, R, S|
|ChemSpider||, R , S|
|Jmol-3D images||Image 1
|Molar mass||174.20 g mol−1|
|Related amino acids|
|Related compounds||γ-L-glutamylmethylamide, bacterial biosynthetic intermediate|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
Theanine //, also known as L-γ-glutamylethylamide and N5-ethyl-L-glutamine (see box for more synonyms), is an amino acid analogue of the proteinogenic amino acids L-L-glutamate and L-glutamine and is found primarily in particular plant and fungal species. It was discovered as a constituent of a green tea in 1949; in 1950 it was isolated from gyokuro leaves, which have high theanine content. Appearance of the name "theanine" without a prefix can be understood to imply the L-enantiomer; this is the form found in fresh teas and in some, but not all human dietary supplements; the opposite D-enantiomer has far less studied pharmacologic properties, but is present in racemic chemical preparations, and substantially in some studied theanine supplements.
As an an analogue of glutamate and glutamine, the theanine in common preparations (teas, enantiomer supplements, etc.) is absorbed in the small intestine after oral ingestion; its hydrolysis is to L-glutamate and ethylamine and occurs both in the intestine and liver. It can also cross the blood–brain barrier intact, and register pharmacological effects directly.
In Japan, L-Theanine has been approved for use in all foods, including herb teas, soft drinks, desserts, etc. with some restrictions applying to infant foods. It provides a unique brothy or savory (umami) flavor to green tea infusions. It is generally recognized as safe (GRAS) as an ingredient by the Food and Drug Administration (FDA), and is sold as a dietary supplement in the US. However, the German Federal Institute for Risk Assessment, an agency of their Federal Ministry of Food and Agriculture, has objected to the addition of isolated theanine to beverages.
Structure and properties
All except the common name of theanine reflect its actual chemical structure; for instance, it is also known as N5-ethyl-L-glutamine, and by a variety of other synonyms (see box). The name theanine, without prefix, is generally understood to imply the L- (S-) enantiomer, derived from the related proteinogenic L-amino acid glutamic acid. Hence, theanine is an analog of this amino acid (and its amide relative, glutamine). Simply put, it is equivalent to the amino acid L-glutamine when ethylated on the amide nitrogen (as the name N5-ethyl-L-glutamine describes), alternatively, to the ethyl 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 inexplicitly. 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 natural 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.)
Discovery and distribution
Theanine is found primarily in plant and fungal species; it was discovered as a constituent of green tea prepared from Camellia sinensis in 1949; in 1950, a laboratory in Kyoto successfully isolated it from gyokuro leaf, which has high theanine content. In actuality, theanine is substantially present in black, green, and white teas from Camellia sinensis in quantities of about 1% of the dry weight. The L-enantiomer is the form found in freshly prepared teas, and some but not all human dietary supplements.
Digestion and metabolism
As an 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.
||This section needs more medical references for verification or relies too heavily on primary sources. (August 2014)|
||The neutrality of this section is disputed. (August 2014)|
Able to cross the blood–brain barrier, theanine has reported psychoactive properties. Theanine has been studied for its potential ability to reduce mental and physical stress, improve cognition, and boost mood and cognitive performance in a synergistic manner with caffeine.
A Natural Standard monograph that reviews current research on theanine reports that it is likely safe in doses of 200–250 mg up to a maximum daily dose of 1,200 mg. Theanine is used to help with anxiety, blood pressure control, mood, and cognition. Natural Standard rates the evidence to support the usage for anxiety, blood pressure control, and mood as “unclear or conflicting scientific evidence” and the evidence for cognition as “fair negative scientific evidence.” Many of the studies of theanine were done in combination with caffeine as found in tea. While the studies found that the combination had some effect on mood, the studies found that theanine alone had little effect. More sufficiently designed studies in humans are warranted to further our understanding of the effects of theanine.
Theanine is reported to promote alpha wave production in the brain. Early studies of theanine involved much larger doses than those found in an everyday cup of tea. Researchers wonder whether drinking tea might have the same effects found in those studies. However, one recent study funded by Unilever found that smaller doses typical of those found in a cup of tea did induce changes in alpha waves as shown by EEG.
Studies on test rats have shown even repeated, extremely high doses of theanine cause little to no harmful psychological or physical effects. Theanine showed neuroprotective effects in one rat study.
Several beverage manufacturers are selling drinks containing theanine and are marketing them as drinks to help people focus and concentrate, while other manufacturers claim relaxing and tranquillizing properties.
||This section needs more medical references for verification or relies too heavily on primary sources. (August 2014)|
||The neutrality of this section is disputed. (August 2014)|
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.
In 2006, a study found no consistent, statistically significant treatment-related adverse effects on behavior, morbidity, mortality, body weight, food consumption and efficiency, clinical chemistry, hematology, or urinalysis in rats fed high doses of theanine for 13 weeks. Large studies in humans have not been undertaken, however several smaller-scale studies (less than 100 participants) have shown increased alpha wave generation and lowered anxiety, along with benefits to sleep quality in patients with ADHD.[bare URL]
The combination of theanine and caffeine has been shown to promote faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy.
Theanine may help the body's immune response to infection by boosting the disease-fighting capacity of gamma delta T cells. The study, published in 2003, included a four-week trial with 11 coffee drinkers and 10 tea drinkers, who consumed 600 milliliters of coffee or black tea daily. Blood sample analysis found the production of antibacterial proteins was up to five times higher in the tea drinkers, an indicator of a stronger immune response. L-Theanine may contain mast cell-stabilizing properties in an animal model.
Notes and References
- Royal Society of Chemistry (2014) Chemspider: Theanine, see , accessed 17 August 2014.
- Note rotation (flip) of molecules orientation between the image appearing and the citation, such that amino group points upward here, and so projects in front of the page.
- SAKATO Y. J. Agri. Chem. Soc. 1949, 23, 262-7
- MASON R. Altern. & Complementary Ther. 2001, 7, 91-5
- Q.V. Vuong, M.C. Bowyer & P.D. Roach (2011) J Sci Food Agric. L-Theanine: properties, synthesis and isolation from tea, 91(11):1931-1939, DOI 10.1002/jsfa.4373, see , accessed 17 August 2014.
- See also, e.g., M.J. Desai & D.W. Armstrong (2004) Analysis of derivatized and underivatized theanine enantiomers by high-performance liquid chromatography/atmospheric pressure ionization-mass spectrometry, Rapid Commun Mass Spectrom. 18(3):251-256, and references therein, see , accessed 17 August 2014.
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- Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T (1998). "Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats". Neurochem. Res. 23 (5): 667–73. PMID 9566605.
- Yokogoshi, Hidehiko; Mochizuki, Mikiko; Saitoh, Kotomi (1998). "Theanine-induced Reduction of Brain Serotonin Concentration in Rats". Bioscience, Biotechnology, and Biochemistry 62 (4): 816–7. doi:10.1271/bbb.62.816. PMID 9614715.
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- Gomez-Ramirez, Manuel; Higgins, Beth A.; Rycroft, Jane A.; Owen, Gail N.; Mahoney, Jeannette; Shpaner, Marina; Foxe, John J. (2007). "The Deployment of Intersensory Selective Attention". Clinical Neuropharmacology 30 (1): 25–38. doi:10.1097/01.WNF.0000240940.13876.17. PMID 17272967.
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- Park, Sang-Ki; Jung, In-Chul; Lee, Won Kyung; Lee, Young Sun; Park, Hyoung Kook; Go, Hyo Jin; Kim, Kiseong; Lim, Nam Kyoo et al. (2011). "A Combination of Green Tea Extract andl-Theanine Improves Memory and Attention in Subjects with Mild Cognitive Impairment: A Double-Blind Placebo-Controlled Study". Journal of Medicinal Food 14 (4): 334–43. doi:10.1089/jmf.2009.1374. PMID 21303262.
- Haskell, Crystal F.; Kennedy, David O.; Milne, Anthea L.; Wesnes, Keith A.; Scholey, Andrew B. (2008). "The effects of l-theanine, caffeine and their combination on cognition and mood". Biological Psychology 77 (2): 113–22. doi:10.1016/j.biopsycho.2007.09.008. PMID 18006208.
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John J. Foxe of the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, N.Y., and his colleagues recruited 16 people for tests of attentiveness on four days. Before testing, each individual drank a glass of water. On 3 days, the drink was spiked with 100 milligrams of theanine, 60 mg of caffeine, or both. The theanine dose was equivalent to that in 4 to 5 cups of tea, and the caffeine translated to about 2.5 cups of tea. In the difficult tests, participants watched a computer screen and pressed a button when a designated shape appeared on the side of a busy visual field to which an arrow had previously pointed. Participants' accuracy differed little between days when they got water alone or with only one additive. Accuracy improved dramatically, however, on the day that they got the theanine-caffeine combination. The attention benefit lasted throughout the 3 hours of testing.
- Owen, Gail N.; Parnell, Holly; De Bruin, Eveline A.; Rycroft, Jane A. (2008). "The combined effects of L-theanine and caffeine on cognitive performance and mood". Nutritional Neuroscience 11 (4): 193–8. doi:10.1179/147683008X301513. PMID 18681988.
- Einöther, Suzanne J.L.; Martens, Vanessa E.G.; Rycroft, Jane A.; De Bruin, Eveline A. (2010). "L-Theanine and caffeine improve task switching but not intersensory attention or subjective alertness". Appetite 54 (2): 406–9. doi:10.1016/j.appet.2010.01.003. PMID 20079786.
- Giesbrecht, T.; Rycroft, J.A.; Rowson, M.J.; De Bruin, E.A. (2010). "The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness". Nutritional Neuroscience 13 (6): 283–90. doi:10.1179/147683010X12611460764840. PMID 21040626.
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- "Theanine Monograph". Natural Standard. Retrieved 30 October 2014.
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- Egashira, Nobuaki; Ishigami, Noriko; Pu, Fengling; Mishima, Kenichi; Iwasaki, Katsunori; Orito, Kensuke; Oishi, Ryozo; Fujiwara, Michihiro (2008). "Theanine prevents memory impairment induced by repeated cerebral ischemia in rats". Phytotherapy Research 22 (1): 65–8. doi:10.1002/ptr.2261. PMID 17705146.
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