L-theanine, unique amino acid of tea, and its metabolism, health effects, and safety

References

• Alcázar, A., Ballesteros, O., Jurado, J. M., Pablos, F., Martín, M. J., Vilches, J. L. and Navalón, A. (2007). Differentiation of green, white, black, Oolong, and Pu-erh teas according to their free amino acids content. J. Agric. Food Chem. 55(15):5960–5965.
   PubMed Web of Science ®Google Scholar
• Anonymous. (2013). World Tea News Market Reports: Increasing Value for the World's Most Consumed Beverage. Issue: 4.
   Google Scholar
• Borzelleca, J., Peters, D. and Hall, W. (2006). A 13-week dietary toxicity and toxicokinetic study with L-theanine in rats. Food Chem. Toxicol. 44(7):1158–1166.
   PubMed Web of Science ®Google Scholar
• Bryan, J. (2008). Psychological effects of dietary components of tea: Caffeine and L-theanine. Nutr. Rev. 66(2):82–90.
   PubMed Web of Science ®Google Scholar
• Bukowski, J. F. and Percival, S. S. (2008). L-theanine intervention enhances human γδT lymphocyte function. Nutr. Rev. 66(2):96–102.
   PubMed Web of Science ®Google Scholar
• Camfield, D. A., Stough, C., Farrimond, J. and Scholey, A. B. (2014). Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: A systematic review and metaanalysis. Nutr. Rev. 72(8):507–522.
   PubMed Web of Science ®Google Scholar
• Chu, D. C. (1997). Green tea: Its cultivation, processing of the leaves for drinking materials, and kinds of green tea. In: Chemistry and Applications of Green Tea, pp. 1–11. Yamamoto, T., Lekh, J. R., Chu, D. C. and Kim, M., Eds., CRC Press, Boca Raton.
   Google Scholar
• da Silva Pinto, M. (2013). Tea: A new perspective on health benefits. Food Res. Int. 53(2):558–567.
   Web of Science ®Google Scholar
• Deng, W. W., Ogita, S. and Ashihara, H. (2008). Biosynthesis of theanine (γ-ethylamino-l-glutamic acid) in seedlings of Camellia sinensis. Phytochem. Lett. 1(2):115–119.
   Web of Science ®Google Scholar
• Desai, M. J., Gill, M. S., Hsu, W. H. and Armstrong, D. W. (2005). Pharmacokinetics of theanine enantiomers in rats. Chirality. 17(3):154–162.
   PubMed Web of Science ®Google Scholar
• Ekborg-Ott, K. H., Taylor, A. and Armstrong, D. W. (1997). Varietal differences in the total and enantiomeric composition of theanine in tea. J. Agric. Food Chem. 45(2):353–363.
   Web of Science ®Google Scholar
• European Food Safety Authority (EFSA). (2011). Panel on Dietetic Products, Nutrition and Allergies (NDA): Scientific opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004), and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J. 9(6):223–228.
   Google Scholar
• Food and Drug Administration (FDA) CFSAN/Office of Food Additive Safety. Agency Response Letter GRAS Notice No. GRN 000209. GRAS Notice Inventory of L-Theanine, 2006.
   Google Scholar
• Fraser, M. L., Mok, G. S. and Lee, A. H. (2007). Green tea and stroke prevention: Emerging evidence. Complement. Ther. Med. 15(1):46–53.
   PubMed Web of Science ®Google Scholar
• Friedman, M., Mackey, B. E., Kim, H. J., Lee, I. S., Lee, K. R., Lee, S. U., Kozukue, E. and Kozukue, N. (2007). Structure-activity relationships of tea compounds against human cancer cells. J. Agric. Food Chem. 55(2):243–253.
   PubMed Web of Science ®Google Scholar
• Fujii, S. and Inai, K. (2008). Tumorigenicity study of L-theanine administrated orally to mice. Food Chem. 110(3):643–646.
   Web of Science ®Google Scholar
• Gomez-Ramirez, M., Higgins, B. A., Rycroft, J. A., Owen, G. N., Mahoney, J., Shpaner, M. and Foxe, J. J. (2007). The deployment of intersensory selective attention: A high-density electrical mapping study of the effects of theanine. Clin. Neuropharmacol. 30(1):25–38.
   PubMed Web of Science ®Google Scholar
• Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A. and Scholey, A. B. (2008). The effects of L-theanine, caffeine, and their combination on cognition and mood. Biol. Psychol. 77(2):113–122.
   PubMed Web of Science ®Google Scholar
• Hilal, Y. and Engelhardt, U. (2007). Characterization of white tea: Comparison to green and black tea. J. Verbr. Lebensm. 2(4):414–421.
   Google Scholar
• Jain, A., Manghani, C., Kohli, S., Nigam, D. and Rani, V. (2013). Tea and human health: The dark shadows. Toxicol. Lett. 220(1):82–87.
   PubMed Web of Science ®Google Scholar
• Jang, H. S., Jung, J. Y., Jang, I. S., Jang, K. H., Kim, S. H., Ha, J. H., Suk, K. and Lee, M. G. (2012). L-theanine partially counteracts caffeine-induced sleep disturbances in rats. Pharmacol. Biochem. Behav. 101(2):217–221.
   PubMed Web of Science ®Google Scholar
• Juneja, L. R., Chu, D. C., Okubo, T., Nagato, Y. and Yokogoshi, H. (1999). L-theanine: A unique amino acid of green tea and its relaxation effect in humans. Trend Food Sci. Technol. 10(12):425.
   Web of Science ®Google Scholar
• Kakuda, T. (2011). Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol. Res. 64(2):162–168.
   PubMed Web of Science ®Google Scholar
• Keenan, E. K., Finnie, M. D. A., Jones, P. S., Rogers, P. J. and Priestley, C. M. (2011). How much theanine in a cup of tea? Effects of tea type and method of preparation. Food Chem. 125(2):588–594.
   Web of Science ®Google Scholar
• Kelly, S. P., Gomez-Ramirez, M., Montesi, J. L. and Foxe, J. J. (2008). L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance. J. Nutr. 138(8):1572–1577.
   PubMed Web of Science ®Google Scholar
• Kim, T. I., Lee, Y. K., Park, S. G., Choi, I. S., Ban, J. O., Park, H. K., Nam, S. Y., Yun, Y. W., Han, S. B., Oh, K. W. and Hong, J. T. (2009). L-theanine, an amino acid in green tea, attenuates β-amyloid-induced cognitive dysfunction and neurotoxicity: Reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-κB pathways. Free Radic. Biol. Med. 47(11):1601–1610.
   PubMed Web of Science ®Google Scholar
• Kimura, K., Ozeki, M., Juneja, L. R. and Ohira, H. (2007). L-theanine reduces psychological and physiological stress responses. Biol. Psychol. 74(1):39–45.
   PubMed Web of Science ®Google Scholar
• Kobayashi, K., Nagato, Y., Aoi, N., Juneja, L., Kim, M., Yamamoto, T. and Sugimoto, S. (1998). Effects of L-theanine on the release of alpha-brain waves in human volunteers. Nippon Nogeik. Kaishi 72(2):153–157.
   Google Scholar
• Kobayashi, M. and Ikeda, I. (2014). Chapter 48: Modulation of intestinal cholesterol absorption by dietary tea polyphenols. In: Polyphenols in Human Health and Disease, pp. 625–638. Watson, R. R., Preedy, V. R. and Zibadi, S., Eds., Academic Press, San Diego.
   Google Scholar
• Kurihara, S., Hiraoka, T., Akutsu, M., Sukegawa, E., Bannai, M. and Shibahara, S. (2010). Effects of L-cystine and L-theanine supplementation on the common cold: A randomized, double-blind, and placebo-controlled trial. J. Amino Acids 2010:1–7.
   Google Scholar
• Kurihara, S., Shibahara, S., Arisaka, H. and Akiyama, Y. (2007). Enhancement of antigen-specific immunoglobulin G production in mice by coadministration of L-cystine and L-theanine. J. Vet. Med. Sci. 69(12):1263–1270.
   PubMed Web of Science ®Google Scholar
• Lin, Y. S., Tsai, Y. J., Tsay, J. S. and Lin, J. K. (2003). Factors affecting the levels of tea polyphenols and caffeine in tea leaves. J. Agric. Food Chem. 51(7):1864–1873.
   PubMed Web of Science ®Google Scholar
• Liu, Q., Duan, H., Luan, J., Yagasaki, K. and Zhang, G. (2009). Effects of theanine on growth of human lung cancer and leukemia cells as well as migration and invasion of human lung cancer cells. Cytotechnology. 59(3):211–217.
   PubMed Web of Science ®Google Scholar
• Lu, K., Gray, M. A., Oliver, C., Liley, D. T., Harrison, B. J., Bartholomeusz, C. F., Phan, K. L. and Nathan, P. J. (2004). The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Human Psychopharmacol. 19(7):457–465.
   PubMed Web of Science ®Google Scholar
• Lyon, M. R., Kapoor, M. P. and Juneja, L. R. (2011). The effects of L-theanine (Suntheanine(R)) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): A randomized, double-blind, placebo-controlled clinical trial. Altern. Med. Rev. 16(4):348–354.
   PubMed Web of Science ®Google Scholar
• Matsumoto, K., Yamada, H., Takuma, N., Niino, H. and Sagesaka, Y. M. (2011). Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: A randomized controlled trial. BMC Complement. Altern. Med. 11(1):15.
   PubMed Web of Science ®Google Scholar
• Nagai, K. and Konishi, H. (2013). Protection of theanine against doxorubicin-induced acute cardiac toxicity. Biomed. Prev. Nutr. 3(2):197–199.
   Google Scholar
• Nantz, M. P., Rowe, C. A., Bukowski, J. F. and Percival, S. S. (2009). Standardized capsule of Camellia sinensis lowers cardiovascular risk factors in a randomized, double-blind, placebo-controlled study. Nutrition (Burbank, Los Angeles County, Calif). 25(2):147–154.
   PubMed Web of Science ®Google Scholar
• Narukawa, M., Toda, Y., Nakagita, T., Hayashi, Y. and Misaka, T. (2014). L-theanine elicits umami taste via the T1R1 + T1R3 umami taste receptor. Amino Acids 46(6):1583–1587.
   PubMed Web of Science ®Google Scholar
• Sakato, Y. (1949). The chemical constituents of tea: III. A new amide theanine. Nippon Nogeik. Kaishi 23:262–267.
   Google Scholar
• Sayama, K., Lin, S., Zheng, G. and Oguni, I. (1999). Effects of green tea on growth, food utilization, and lipid metabolism in mice. In Vivo (Athens, Greece). 14(4):481–484.
   Web of Science ®Google Scholar
• Siamwala, J. H., Dias, P. M., Majumder, S., Joshi, M. K., Sinkar, V. P., Banerjee, G. and Chatterjee, S. (2013). L-theanine promotes nitric oxide production in endothelial cells through eNOS phosphorylation. J. Nutr. Biochem. 24(3):595–605.
   PubMed Web of Science ®Google Scholar
• Song, C. H., Jung, J. H., Oh, J. S. and Kim, K. S. (2003). Effects of theanine on the release of brain alpha wave in adult males. Korean J. Nutr. 36(9):918–923.
   Google Scholar
• Sugiyama, T. and Sadzuka, Y. (2004). Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changing the glutathione level. Cancer Lett. 212(2):177–184.
   PubMed Web of Science ®Google Scholar
• The Republic of Turkey Ministry of Health and Hacettepe University Nutrition and Dietetics Department. Turkey Nutrition and Health Survey 2010. Nutrition Situation and Behaviors Evaluation Result Report. Directorate General for Health Surveys Publication No: SB-SAG-2014/0, ISBN : 978–975–590–483–2.
   Google Scholar
• Unno, T., Suzuki, Y., Kakuda, T., Hayakawa, T. and Tsuge, H. (1999). Metabolism of theanine, γ-glutamylethylamide, in rats. J. Agric. Food Chem. 47(4):1593–1596.
   PubMed Web of Science ®Google Scholar
• van der Pijl, P. C., Chen, L. and Mulder, T. P. J. (2010). Human disposition of L-theanine in tea or aqueous solution. J. Funct. Foods 2(4):239–244.
   Web of Science ®Google Scholar
• Vuong, Q. V., Bowyer, M. C. and Roach, P. D. (2011). L-theanine: Properties, synthesis, and isolation from tea. J. Sci. Food Agric. 91(11):1931–1939.
   PubMed Web of Science ®Google Scholar
• Vuong, Q. V. (2014). Epidemiological evidence linking tea consumption to human health: A review. Crit. Rev. Food Sci. Nutr. 54(4):523–536.
   PubMed Web of Science ®Google Scholar
• Yamada, T., Nishimura, Y., Sakurai, T., Terashima, T., Okubo, T., Juneja, L. R. and Yokogoshi, H. (2008). Administration of theanine, a unique amino acid in tea leaves, changed feeding-relating components in serum and feeding behavior in rats. Biosci. Biotechnol. Biochem. 72(5):1352–1355.
   PubMed Web of Science ®Google Scholar
• Yamada, T., Terashima, T., Wada, K., Ueda, S., Ito, M., Okubo, T., Juneja, L. R. and Yokogoshi, H. (2007). Theanine, r-glutamylethylamide, increases neurotransmission concentrations and neurotrophin mRNA levels in the brain during lactation. Life Sci. 81(16):1247–1255.
   PubMed Web of Science ®Google Scholar
• Ying, Y., Ho, J. W., Chen, Z. Y. and Wang, J. (2005). Analysis of theanine in tea leaves by HPLC with fluorescence detection. J. Liq. Chromatogr. R. T. 28(5):727–737.
   Web of Science ®Google Scholar
• Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T. and Takeuchi, N. (1995). Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci. Biotechnol. Biochem. 59(4):615–618.
   PubMed Web of Science ®Google Scholar
• Yokozawa, T. and Dong, E. (1997). Influence of green tea and its three major components upon low-density lipoprotein oxidation. Exp. Toxicol. Pathol. 49(5):329–335.
   PubMed Web of Science ®Google Scholar
• Yokozawa, T., Oura, H., Nakagawa, H., Sakanaka, S. and Kim, M. (1995). Effects of a component of green tea on the proliferation of vascular smooth muscle cells. Biosci. Biotechnol. Biochem. 59(11):2134–2136.
   PubMed Web of Science ®Google Scholar
• Yoto, A., Motoki, M., Murao, S. and Yokogoshi, H. (2012). Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J. Physiol. Anthropol. 31:28.
   PubMed Web of Science ®Google Scholar
• Zhang, L., Zhang, Z. Z., Lu, Y. N., Zhang, J. S. and Preedy, V. R. (2013). Chapter 35: L-theanine from green tea: Transport and effects on health. In: Tea in Health and Disease Prevention, pp. 425–435. Preedy, V. R., Ed., Academic Press, USA.
   Google Scholar
• Zhao, M., Ma, Y., Wei, Z. Z., Yuan, W. X., Li, Y. L., Zhang, C. H., Xue, X. T. and Zhou, H. J. (2011). Determination and comparison of gamma-aminobutyric acid (GABA) content in pu-erh and other types of Chinese tea. J. Agric. Food Chem. 59(8):3641–3648.
   PubMed Web of Science ®Google Scholar
• Zheng, G., Sayama, K., Okubo, T., Juneja, L. and Ogunı, I. (2004). Antiobesity effects of three major components of green tea, catechins, caffeine, and theanine, in mice. In Vivo 18(1):55–62.
   PubMed Web of Science ®Google Scholar