Theanine

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Not to be confused with threonine, a distinct amino acid, or theine, an archaic synonym of caffeine.
Theanine
Stereo, skeletal formula of theanine (S)
Identifiers
CAS number 3081-61-6 S YesY
PubChem 228398, 9964226 R, 439378 S
ChemSpider 198778 YesY, 8139819 R YesY, 388498 S YesY
UNII 8021PR16QO YesY
EC number 3081-61-6
MeSH theanine
ChEBI CHEBI:17394 YesY
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C7H14N2O3
Molar mass 174.20 g mol−1
Related compounds
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)
Infobox references

Theanine /ˈθənn/ is an amino acid analog of the proteinogenic amino acids L-glutamic acid and L-glutamine and is found primarily in particular plant and fungal species. It is also known as N5-ethyl-L-glutamine, and by a variety of other synonyms (see box). 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.[not verified in body] It is substantially present in black, green, and white teas prepared from Camellia sinensis,[not verified in body] and has also been isolated from Amazonian guayusa (a caffeine-producing holly),[not verified in body] and from the basidiomycete mushroom Boletus badius. 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 analog of glutamate and glutamine, the theanine in common preparations (teas, enantiopure 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.

Theanine has been approved for use in all foods, including herb teas, soft drinks, desserts, etc. with some restrictions applying to infant foods.[citation needed] 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[edit]

All except the common name of theanine reflect its actual chemical structure; for instance, it is also known as N5-ethyl-L-glutamine,[1] 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,[1] 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.[3][4] (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.[4])

Discovery and distribution[edit]

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[which?] successfully isolated it from gyokuro leaf, which has high theanine content.[citation needed] In actuality, theanine is substantially present in black, green, and white teas in varying quantities, when prepared from this plant.[citation needed] It has also been isolated from Amazonian guayusa (a caffeine-producing holly),[citation needed] and from the basidiomycete mushroom Boletus badius.[5][non-primary source needed] The L-enantiomer[1] is the form found in freshly prepared teas, and some but not all human dietary supplements.[4]

Digestion and metabolism[edit]

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.[6] It can also cross the blood–brain barrier intact, and register pharmacological effects directly.[7]

Pharmacological effects[edit]

Able to cross the blood–brain barrier, theanine has reported psychoactive properties.[8] Theanine has been studied for its potential ability to reduce mental and physical stress,[9] improve cognition,[10] and boost mood and cognitive performance in a synergistic manner with caffeine.[11][12][13][14][15][16]

Theanine is reported to promote alpha wave production in the brain.[8] 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.[17] 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.[18] It is structurally similar to the excitatory neurotransmitter glutamate, however has only weak affinity for the glutamate receptors on postsynaptic cells.[19] While it only has a low affinity for the ionotropic glutamate receptors - AMPA, kainate, and NMDA receptors - it does however increase brain dopamine levels.[20] 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.[7][21] It has also been found that injecting spontaneously hypertensive mice with theanine significantly lowered levels of 5-hydroxyindoles in the brain.[22] Researchers also speculate it may inhibit glutamate excitotoxicity thereby increasing glutamate.[20]

Studies on test rats have shown even repeated, extremely high doses of theanine cause little to no harmful psychological or physical effects.[23] Theanine showed neuroprotective effects in one rat study.[24]

A placebo-controlled trial has shown adding theanine to ongoing antipsychotic medication is helpful in reducing some symptoms of schizophrenia.[25][26]

Several beverage manufacturers are selling drinks containing theanine and are marketing them as drinks to help people focus and concentrate,[17] while other manufacturers claim relaxing and tranquillizing properties.[25]

Supplement use[edit]

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.[25]

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.[23] 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.[9][27][28][bare URL][29]

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.[11][13][30][31]

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.[32] L-Theanine may contain mast cell-stabilizing properties in an animal model.[33]

Theanine has been reported to raise levels of brain serotonin, dopamine, and GABA, with possible improvement in to specific memory and learning tasks.[34][bare URL]

See also[edit]

Notes and References[edit]

  1. ^ a b c d e f Royal Society of Chemistry (2014) Chemspider: Theanine, see [1], accessed 17 August 2014.
  2. ^ 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.
  3. ^ 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 [2], accessed 17 August 2014.
  4. ^ a b c 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 [3], accessed 17 August 2014.
  5. ^ Casimir, J.; Jadot, J.; Renard, M. (1960). "Séparation et caractérisation de la N-éthyl-γ-glutamine à partir de Xerocomus badius" [Separation and characterization of N-ethyl-γ-glutamine from Xerocomus badius]. Biochimica et Biophysica Acta (in French) 39 (3): 462–8. doi:10.1016/0006-3002(60)90199-2. PMID 13808157. 
  6. ^ S. Kurihara, T. Shibakusa & K.A.K. Tanaka (2013) Cystine and theanine: amino acids as oral immunomodulative nutrients, Springerplus 2:635, DOI 10.1186/2193-1801-2-635, PMID 24312747, see [4], accessed 17 August 2014.
  7. ^ a b Yokogoshi, Hidehiko; Kobayashi, Miki; Mochizuki, Mikiko; Terashima, Takehiko (1998). "Effect of theanine, γ-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats". Neurochemical Research 23 (5): 667–73. doi:10.1023/A:1022490806093. PMID 9566605. 
  8. ^ a b 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. 
  9. ^ a b Kimura, Kenta; Ozeki, Makoto; Juneja, Lekh Raj; Ohira, Hideki (2007). "L-Theanine reduces psychological and physiological stress responses". Biological Psychology 74 (1): 39–45. doi:10.1016/j.biopsycho.2006.06.006. PMID 16930802. 
  10. ^ 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. 
  11. ^ a b 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. 
  12. ^ Raloff, Janet (September 29, 2007). "Distracted? Tea might help your focus". Science News 172 (13): 206. doi:10.1002/scin.2007.5591721319. "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." 
  13. ^ a b 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ Kelly, Simon P.; Gomez-Ramirez, Manuel; Montesi, Jennifer L.; Foxe, John J. (2008). "L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance". The Journal of Nutrition 138 (8): 1572S–1577S. PMID 18641209. 
  17. ^ a b Roan, Shari (May 17, 2009). "L-theanine: New drinks promise focus, but more research attention needed". Chicago Tribune. 
  18. ^ Nobre, AC; Rao, A; Owen, GN (2008). "L-theanine, a natural constituent in tea, and its effect on mental state". Asia Pacific journal of clinical nutrition. 17 Suppl 1: 167–8. PMID 18296328. 
  19. ^ Kakuda, Takami; Nozawa, Ayumu; Sugimoto, Akio; Niino, Hitoshi (2002). "Inhibition by Theanine of Binding of [3H]AMPA, [3H]Kainate, and [3H]MDL 105,519 to Glutamate Receptors". Bioscience, Biotechnology, and Biochemistry 66 (12): 2683–6. doi:10.1271/bbb.66.2683. PMID 12596867. 
  20. ^ a b Nathan, Pradeep; Lu, Kristy; Gray, M.; Oliver, C. (2006). "The Neuropharmacology of L-Theanine(N-Ethyl-L-Glutamine)". Journal of Herbal Pharmacotherapy 6 (2): 21–30. doi:10.1300/J157v06n02_02. PMID 17182482. 
  21. ^ 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. 
  22. ^ Yokogoshi, Hidehiko; Kato, Yukiko; Sagesaka, Yuko M.; Takihara-Matsuura, Takanobu; Kakuda, Takami; Takeuchi, Naokazu (1995). "Reduction Effect of Theanine on Blood Pressure and Brain 5-Hydroxyindoles in Spontaneously Hypertensive Rats". Bioscience, Biotechnology, and Biochemistry 59 (4): 615–8. doi:10.1271/bbb.59.615. PMID 7539642. 
  23. ^ a b Borzelleca, J.F.; Peters, D.; Hall, W. (2006). "A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats". Food and Chemical Toxicology 44 (7): 1158–66. doi:10.1016/j.fct.2006.03.014. PMID 16759779. 
  24. ^ 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. 
  25. ^ a b c Ritsner, Michael S.; Miodownik, Chanoch; Ratner, Yael; Shleifer, Tatyana; Mar, Maria; Pintov, Leonid; Lerner, Vladimir (2011). "L-Theanine Relieves Positive, Activation, and Anxiety Symptoms in Patients with Schizophrenia and Schizoaffective Disorder". The Journal of Clinical Psychiatry 72 (1): 34–42. doi:10.4088/JCP.09m05324gre. PMID 21208586. 
  26. ^ Di, X.; Yan, J.; Zhao, Y.; Chang, Y.; Zhao, B. (2012). "L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway". Science China Life Sciences 55 (12): 1064–1074. doi:10.1007/s11427-012-4401-0. PMID 23233221.  edit
  27. ^ Lyon, Michael R.; Kapoor, Mahendra P.; Juneja, Lekh R. (2011). "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". Alternative Medicine Review 16 (4): 348–54. PMID 22214254. 
  28. ^ "L-Theanine". 
  29. ^ Kobayashi, Kanari; Nagato, Yukiko; Aoi, Nobuyuki; Juneja, Lekh Raj; Kim, Mujo; Yamamoto, Takehiko; Sugimoto, Sukeo (1998). "L-テアニンのヒトの脳波に及ぼす影響" [Effects of L-Theanine on the Release of α-Brain Waves in Human Volunteers]. Journal of the Agricultural Chemical Society of Japan (in Japanese) 72 (2): 153–7. doi:10.1271/nogeikagaku1924.72.153. 
  30. ^ Bryan, Janet (2008). "Psychological effects of dietary components of tea: Caffeine and L-theanine". Nutrition Reviews 66 (2): 82–90. doi:10.1111/j.1753-4887.2007.00011.x. PMID 18254874. 
  31. ^ Kelly, Simon P.; Gomez-Ramirez, Manuel; Montesi, Jennifer L.; Foxe, John J. (2008). "L-Theanine and Caffeine in Combination Affect Human Cognition as Evidenced by Oscillatory alpha-Band Activity and Attention Task Performance". The Journal of Nutrition 138 (8): 1572S–1577S. PMID 18641209. 
  32. ^ Kamath, Arati B.; Wang, Lisheng; Das, Hiranmoy; Li, Lin; Reinhold, Vernon N.; Bukowski, Jack F. (2003). "Antigens in tea-beverage prime human Vγ2Vδ2 T cells in vitro and in vivo for memory and nonmemory antibacterial cytokine responses". Proceedings of the National Academy of Sciences 100 (10): 6009–14. Bibcode:2003PNAS..100.6009K. doi:10.1073/pnas.1035603100. JSTOR 3147533. PMC 156317. PMID 12719524. 
  33. ^ Kim, N. H.; Jeong, H. J.; Kim, H. M. (2011). "Theanine is a candidate amino acid for pharmacological stabilization of mast cells". Amino Acids 42 (5): 1609–18. doi:10.1007/s00726-011-0847-9. PMID 21344174. 
  34. ^ http://www.ncbi.nlm.nih.gov/pubmed/17182482

Further reading[edit]

Y. Orihara & T. Furuya (1990) "Production of theanine and other γ-glutamyl derivatives by Camellia sinensis cultured cells," Plant Cell Reports 9(2):65–68, DOI 10.1007/BF00231550, PMID 24226431.

E.K. Keenan, M.D.A. Finnie, P.S. Jones, P.J. Rogers, C.M. Priestley (2011) How much theanine in a cup of tea? Effects of tea type and method of preparation, Food Chemistry 125(2):588–594, DOI 10.1016/j.foodchem.2010.08.071.