Ingredient review

L-theanine

Description

What is it?

L-theanine (γ-glutamylethylamide) is the most abundant (50%) water-soluble non-protein amino acid found in Camellia sinensis (tea) leaves. (5)(6)(8)(11)(22)(23) L-theanine synthesis occurs in the roots of the tea plant and is then translocated to the leaves. (6)(24) It is responsible for the aroma and umami taste of tea. (22

The researcher Sakato was the first to isolate and identify L-theanine in green tea leaves in 1949. (14)(22) In the early 1950s, he also isolated L-theanine from the inedible mushroom, Xerocomus badius. (5)(14)(22)

Historically, L-theanine has been used as a relaxing agent, primarily consumed as tea. (14) There is some controversy regarding the actual concentration of L-theanine in tea. The most recent study conducted in 2016 suggests that green tea has the highest amount (6.56 mg/g) of L-theanine followed by white tea (6.26 mg/g), oolong (6.09 mg/g), and black tea (5.23 mg/g). (4) Many animal trials have reported that L-theanine exerts neuroprotective effects, modulates the activity of neurotransmitters, focuses attention, and reduces psychological stress. (8)(11)(23) Studies are looking into understanding and quantifying the neural effects of this psychoactive component of tea.

Theanine has a glutamine core unit in its structure and occurs mainly as the L-(S) enantiomer, hence its name, L-theanine. (24)(25) L-theanine can be extracted from Camellia sinensis leaves and produced via chemical- and bio-syntheses. (24) Extraction from Camellia sinensis leaves does produce L-theanine with relatively high purity. However, this process comes with high production costs and lower overall yield. (24

Chemical synthesis is a more convenient and cost-effective alternative to direct extraction of L-theanine from Camellia sinensis leaves. However, the synthetic product can be a racemic mixture of L- and D-enantiomers, raising safety and efficacy concerns. (24) The enzymatic synthesis of L-theanine is relatively complex. However, this method shows great promise for industrial-scale production, especially since the end product is theanine in its naturally occurring L-form. (24) Unfortunately, “no current technique offers an environmentally sustainable and economically viable method for commercial production of purified” L-theanine. (24

Please note that this review focuses on L-theanine as an oral supplement only. 

 

Main uses

Anxiolytic
Cognitive function
Insomnia
Stress and relaxation

Formulations

Form
Characteristics
Suntheanine®
Patented brand of L-theanine made by Taiyo
It is produced via chemical synthesis using L-glutamine, ethylamine, and glutaminase enzymes.
Chemical synthesis results in a racemic mixture product of D- and L-theanine. (22) However, a 2004 study found that Suntheanine® contained no substantial amount of D-theanine compared to five other commercially available theanine products. (5)
L-theanine
Currently no study has directly compared unbranded formulations of L-theanine to branded formulations such as Suntheanine®.
However, when compared to green tea, the kinetics of L-theanine uptake and metabolism are comparable. (20)
Slow and immediate release
There is a lack of research investigating the possible benefits or harms associated with slow- or immediate-release forms of Suntheanine® or L-theanine.

Dosing & administration

Adverse effects

Overall, L-theanine is generally well tolerated. No adverse effects were reported in an eight-week trial using 400 mg per day. (25) A four-week trial using 900 mg per day reported adverse effects both in the treatment and placebo groups, such as sleep disturbances, drowsiness, weakness/fatigue, irritability, trouble concentrating, and gastrointestinal discomfort. However, there was no significant difference between the groups. (19)

A 13-week dietary toxicity and toxicokinetic study in rats found no dose- or treatment-related adverse effects. They determined L-theanine’s no-observed-adverse-effect-level (NOAEL) was 4,000 mg/kg of body weight per day. (6)

In one study looking at treatments for ADHD-related sleep disorders in boys between the ages of 8 and 12, one participant developed a new facial tic. The adverse effect caused the participant to withdraw from the study. The authors wrote that the child had previously exhibited various tics. They determined that the event’s causality was unlikely. (1)(3)

Pharmacokinetics

Absorption

  • L-theanine is absorbed in the small intestinal tract. It is then transported from the brush border of the GI tract into the bloodstream, potentially via both Na+-coupled co-transporters and the methionine carrier transport system. (6)(22
  • It is estimated that 72 to 74% of L-theanine is bioavailable. (6
  • A rodent study found that the intestinal tract absorbs L-enantiomer at a higher rate than D-enantiomer. (6)(22)
  • Glutamine inhibits the absorption of L-theanine. Both have a similar structure and are competitors for the Na+-coupled co-transporter. The transporter has a greater affinity, possibly seven times greater, (12) for glutamine than L-theanine.(6)

Distribution

  • Once absorbed, L-theanine is distributed to the peripheral tissues and organs (liver and kidney), but is mainly distributed to the brain. L-theanine crosses the blood-brain barrier via the amino acid L transport system. (6)(25
  • Studies indicate that it can take anywhere from ten to 24 minutes for L-theanine to reach the brain after ingestion. (24) Brain concentrations start to decrease around five hours after ingestion. (11)
  • It is estimated that maximum plasma concentration is reached one to five hours after ingestion of L-theanine. Serum concentrations start to slowly decrease within 24 hours. (6)

Metabolism

  • L-theanine can be hydrolyzed into glutamic acid and ethylamine in the blood, brain, kidneys, and liver. It is theorized that glutaminase and/or glutamyl transpeptidase are responsible for the metabolism of L-theanine. (6)
  • It is thought that L-enantiomer is preferentially re-absorbed and metabolized by the kidneys, while D-enantiomer is more quickly metabolized. (6)(25)

Excretion

  • L-theanine and its metabolites are eliminated in the urine. (6)(22)
  • Approximately 2.4 to 3.1% of L-theanine is directly eliminated in the urine. (6
  • A small amount of L-theanine is retained in the erythrocytes. (6
  • The elimination half-life for L-theanine ranges from 58 to 74 minutes in humans when 100 mg of L-theanine is ingested. (6

L-theanine is absorbed in the small intestinal tract and distributed to the peripheral tissues and organs (liver and kidney), but is mainly distributed to the brain. L-theanine and its metabolites are eliminated in the urine, however, a small amount is retained in the erythrocytes. (6)

References

  1. Anand, S., Tong, H., Besag, F. M. C., Chan, E. W., Cortese, S., & Wong, I. C. K. (2017). Safety, tolerability and efficacy of drugs for treating behavioural insomnia in children with attention-deficit/hyperactivity disorder: A systematic review with methodological quality assessment. Paediatric Drugs, 19(3), 235–250. https://doi.org/10.1007/s40272-017-0224-6 
  2. Baba, Y., Inagaki, S., Nakagawa, S., Kaneko, T., Kobayashi, M., & Takihara, T. (2021). Effects of l-theanine on cognitive function in middle-aged and older subjects: A randomized placebo-controlled study. Journal of Medicinal Food, 24(4), 333–341. https://doi.org/10.1089/jmf.2020.4803 
  3. Barrett, J. R., Tracy, D. K., & Giaroli, G. (2013). To sleep or not to sleep: A systematic review of the literature of pharmacological treatments of insomnia in children and adolescents with attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology, 23(10), 640–647. https://doi.org/10.1089/cap.2013.0059 
  4. Boros, K., Jedlinszki, N., & Csupor, D. (2016). Theanine and caffeine content of infusions prepared from commercial tea samples. Pharmacognosy Magazine, 12(45), 75–79. https://doi.org/10.4103/0973-1296.176061 
  5. Desai, M. J., Gill, M. S., Hsu, W. H., & Armstrong, D. W. (2005). Pharmacokinetics of theanine enantiomers in rats. Chirality, 17(3), 154–162. https://doi.org/10.1002/chir.20144 
  6. Dietz, C., & Dekker, M. (2017). Effect of green tea phytochemicals on mood and cognition. Current Pharmaceutical Design, 23(19), 2876–2905. https://doi.org/10.2174/1381612823666170105151800 
  7. Foxe, J. J., Morie, K. P., Laud, P. J., Rowson, M. J., de Bruin, E. A., & Kelly, S. P. (2012). Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology, 62(7), 2320–2327. https://doi.org/10.1016/j.neuropharm.2012.01.020 
  8. Hidese, S., Ogawa, S., Ota, M., Ishida, I., Yasukawa, Z., Ozeki, M., & Kunugi, H. (2019). Effects of l-theanine administration on stress-related symptoms and cognitive functions in healthy adults: A randomized controlled trial. Nutrients, 11(10). https://doi.org/10.3390/nu11102362 
  9. Higashiyama, A., Htay, H. H., Ozeki, M., Juneja, L. R., & Kapoor, M. P. (2011). Effects of l-theanine on attention and reaction time response. Journal of Functional Foods, 3(3), 171–178. https://doi.org/10.1016/j.jff.2011.03.009 
  10. Kahathuduwa, C. N., Dassanayake, T. L., Amarakoon, A. M. T., & Weerasinghe, V. S. (2017). Acute effects of theanine, caffeine and theanine-caffeine combination on attention. Nutritional Neuroscience, 20(6), 369–377. https://doi.org/10.1080/1028415X.2016.1144845 
  11. Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39–45. https://doi.org/10.1016/j.biopsycho.2006.06.006 
  12. Kitaoka, S., Hayashi, H., Yokogoshi, H., & Suzuki, Y. (1996). Transmural potential changes associated with the in vitro absorption of theanine in the guinea pig intestine. Bioscience, Biotechnology, and Biochemistry, 60(11), 1768–1771. https://doi.org/10.1271/bbb.60.1768 
  13. Konofal, E., Lecendreux, M., Bouvard, M. P., & Mouren-Simeoni, M. C. (2001). High levels of nocturnal activity in children with attention-deficit hyperactivity disorder: A video analysis. Psychiatry and Clinical Neurosciences, 55(2), 97–103. https://doi.org/10.1046/j.1440-1819.2001.00808.x 
  14. Lu, K., Gray, M. A., Oliver, C., Liley, D. T., Harrison, B. J., Bartholomeusz, C. F., Phan, K. L., & Nathan, P. J. (2004). The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Human Psychopharmacology, 19(7), 457–465. https://doi.org/10.1002/hup.611 
  15. Lyon, M. R., Kapoor, M. P., & Juneja, L. 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: A Journal of Clinical Therapeutic, 16(4), 348–354. https://www.ncbi.nlm.nih.gov/pubmed/22214254 
  16. Ota, M., Wakabayashi, C., Matsuo, J., Kinoshita, Y., Hori, H., Hattori, K., Sasayama, D., Teraishi, T., Obu, S., Ozawa, H., & Kunugi, H. (2014). Effect of l-theanine on sensorimotor gating in healthy human subjects. Psychiatry and Clinical Neurosciences, 68(5), 337–343. https://doi.org/10.1111/pcn.12134 
  17. Ritsner, M. S., Miodownik, C., Ratner, Y., Shleifer, T., Mar, M., Pintov, L., & Lerner, V. (2011). L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: An 8-week, randomized, double-blind, placebo-controlled, 2-center study. The Journal of Clinical Psychiatry, 72(1), 34–42. https://doi.org/10.4088/JCP.09m05324gre 
  18. Rogers, P. J., Smith, J. E., Heatherley, S. V., & Pleydell-Pearce, C. W. (2008). Time for tea: Mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology, 195, 569–577. https://doi.org/10.1007/s00213-007-0938-1 
  19. Sarris, J., Byrne, G. J., Cribb, L., Oliver, G., Murphy, J., Macdonald, P., Nazareth, S., Karamacoska, D., Galea, S., Short, A., Ee, C., Birling, Y., Menon, R., & Ng, C. H. (2019). L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial. Journal of Psychiatric Research, 110, 31–37. https://doi.org/10.1016/j.jpsychires.2018.12.014 
  20. Scheid, L., Ellinger, S., Alteheld, B., Herholz, H., Ellinger, J., Henn, T., Helfrich, H.-P., & Stehle, P. (2012). Kinetics of l-theanine uptake and metabolism in healthy participants are comparable after ingestion of l-theanine via capsules and green tea. The Journal of Nutrition, 142(12), 2091–2096. https://doi.org/10.3945/jn.112.166371 
  21. Sur, S., & Sinha, V. K. (2009). Event-related potential: An overview. Industrial Psychiatry Journal, 18(1), 70–73. https://doi.org/10.4103/0972-6748.57865 
  22. Türközü, D., & Şanlier, N. (2017). L-theanine, unique amino acid of tea, and its metabolism, health effects, and safety. Critical Reviews in Food Science and Nutrition, 57(8), 1681–1687. https://doi.org/10.1080/10408398.2015.1016141 
  23. Unno, K., Tanida, N., Ishii, N., Yamamoto, H., Iguchi, K., Hoshino, M., Takeda, A., Ozawa, H., Ohkubo, T., Juneja, L. R., & Yamada, H. (2013). Anti-stress effect of theanine on students during pharmacy practice: Positive correlation among salivary α-amylase activity, trait anxiety and subjective stress. Pharmacology, Biochemistry, and Behavior, 111, 128–135. https://doi.org/10.1016/j.pbb.2013.09.004 
  24. Williams, J., Kellett, J., Roach, P. D., McKune, A., Mellor, D., Thomas, J., & Naumovski, N. (2016). L-theanine as a functional food additive: Its role in disease prevention and health promotion. Beverages, 2(2), 13. https://doi.org/10.3390/beverages2020013 
  25. Williams, J. L., Everett, J. M., D’Cunha, N. M., Sergi, D., Georgousopoulou, E. N., Keegan, R. J., McKune, A. J., Mellor, D. D., Anstice, N., & Naumovski, N. (2020). The effects of green tea amino acid l-theanine consumption on the ability to manage stress and anxiety levels: A systematic review. Plant Foods for Human Nutrition , 75(1), 12–23. https://doi.org/10.1007/s11130-019-00771-5
  26. Yoto, A., Motoki, M., Murao, S., & Yokogoshi, H. (2012). Effects of l-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. Journal of Physiological Anthropology, 31, 28. https://doi.org/10.1186/1880-6805-31-28