L-Theanine

• How It Works

  L-theanine has not been shown to treat or prevent cancer.

  L-theanine is an amino acid found in green tea. An epidemiological study showed that the incidence of stroke was reduced in individuals who consumed green tea. However, it is unclear whether L-theanine contributed to this benefit.

  Laboratory and animal studies showed that L-theanine increases efficiency of chemotherapy drugs and also reduces their side effects. However, patients undergoing chemotherapy should discuss the use of L-theanine with their physicians because these effects are not based on clinical trials, and another component found in green tea called epigallocatechin-3-gallate (EGCG) reduces activity of the chemotherapy drug bortezomib.

• Purported Uses
  • Relaxant
    In patients with schizophrenia, two studies have shown that L-theanine alleviates anxiety, and improves sleep and other related symptoms when combined with antipsychotic treatment.
  • Cancer prevention
    There is no scientific evidence to substantiate this use.
  • Cancer treatment
    Laboratory and animal studies indicate that L-theanine has antitumor properties, but human data are lacking.
  • Stroke
    Results from a study done in Japan suggest that green tea consumption decreased the risk of stroke in individuals. However, it is unclear if L-theanine contributed to this benefit.
  • Attention deficit hyperactivity disorder (ADHD)
    A small study suggests L-theanine can improve sleep quality in boys with ADHD.
• Patient Warnings

  Although there are no reported side effects from taking L-theanine, consumption of large amounts of green tea can cause nausea, irritability, and GI upset because of its caffeine content.

• Side Effects

  Please see the monograph on green tea.

• Clinical Summary

  L-theanine is a water soluble amino acid found in green tea and in mushrooms. Purified L-theanine is available as an oral dietary supplement. It is consumed for its perceived antioxidant and relaxant effects ⁽¹²⁾. Several in vitro and animal studies have shown that L-theanine has lipid-lowering ⁽¹⁾, neuroprotective ^(2) (16), antiobesity ⁽³⁾, and antitumor ⁽¹⁾ properties. It can also affect the levels of some neurotransmitters ^(10) (11), prevent beta-amyloid-induced cognitive dysfunction ⁽¹³⁾, and was shown to extend longevity in C. elegans ⁽²⁰⁾.

  When combined with antipsychotic treatment, L-theanine alleviated anxiety and other related symptoms, and improved sleep in patients with schizophrenia ^(17) (21). In an open-label study of patients with major depressive disorder, L-theanine was safe and improved depressive symptoms, anxiety, sleep disturbance, and cognitive impairments ⁽²⁹⁾.

  Epidemiological data suggest its benefits with green tea for prevention of stroke ⁽⁴⁾, but it is unclear whether L-theanine contributed to this benefit. Small studies indicate that a combination of L-theanine and caffeine improves cognitive performance ^(14) (15), although behavior improvements observed with caffeine alone were lost with concomitant caffeine and L-theanine supplementation ⁽²²⁾. L-theanine may help improve sleep quality in boys with attention deficit hyperactivity disorder (ADHD) ⁽¹⁸⁾.

  Theanine derivatives are currently being studied in models of human and mouse cancers for their inhibitory effects ⁽²³⁾.

  L-theanine enhances the chemotherapeutic effects of doxorubicin ⁽⁵⁾ and idarubicin ⁽⁶⁾, and alleviates adverse effects from use of these agents both in vitro and in animal models ^(7) (24). However, patients undergoing chemotherapy should discuss the use of L-theanine with their physicians because these effects are not based on clinical trials, and epigallocatechin-3-gallate (EGCG) in green tea reduces activity of the chemotherapy drug bortezomib.

• Food Sources

  Green tea

• Purported Uses
  • Cancer prevention
  • Cancer treatment
  • Relaxation
  • Stroke
• Mechanism of Action

  As a non-protein amino acid, L-theanine crosses the blood-brain barrier, exerting various neurophysiological and pharmacological effects including: anxiolytic and calming effects, due to inhibitory neurotransmitters and selective serotonin and dopamine modulation; cognitive improvements perhaps through decreased NMDA-dependent CA1 long-term potentiation (LTP) and increased NMDA-independent CA1-LTP; and improved selective attention during mental tasks likely due to changes in alpha brain wave activity ⁽²⁵⁾. Neuroprotective effects are also thought to be due to its selective binding to glutamate receptors ⁽²⁾.

  In animal models, L-theanine appears to have a dose-dependent biphasic effect on NSAID-induced gastric ulcers, delaying healing at higher doses (40 mg/kg), but accelerating healing at lower doses (10 mg/kg) perhaps through the maintenance of glutathione levels thus protecting against oxidative damage ⁽²⁶⁾.

  In human studies, L-theanine attenuated effects of caffeine on oxygenated hemoglobin, cognition, and mood, suggesting both independent and interactive effects between the two compounds ⁽²²⁾. Other studies suggest that combining caffeine and theanine intake causes their individual effects to counteract each other ^(30) (31). L-theanine also stabilizes glutamatergic concentrations in the brain, which may explain its therapeutic effect in patients with schizophrenia ⁽²¹⁾.

  L-theanine was shown to increase the antitumor activity of chemotherapeutic drugs doxorubicin and idarubicin ^(5) (6). These agents normally bind the glutamate receptor and the complex is transported across the cell resulting in reduced concentrations, hence attenuating effects of these drugs. Consequent mechanistic studies revealed that L-theanine, a glutamate analogue, competes with glutamate to bind the glutamate receptor, resulting in suppression of chemotherapy efflux (extracellular transport), increasing their concentration ⁽²⁷⁾.

  Interestingly, L-theanine also reduces the adverse effects of doxorubicin. The proposed mechanism is based on the variance of glutamate receptors expressed in normal and tumor cells. Whereas theanine binds the glutamate receptor in tumor cells, it is metabolized to glutamate in normal cells. This increase in glutamate likely results in increased efflux of doxorubicin from the cells, thereby decreasing toxicity ⁽²⁸⁾.

  Animal models indicate the prevention of doxorubicin-induced acute hepatotoxicity occurs through suppression of intrinsic caspase-3-dependent apoptotic signaling ⁽²⁴⁾. L-theanine does not induce or inhibit cytochrome P450 enzymes ⁽⁹⁾.

  Some novel theanine derivatives were found to inhibit lung tumor growth by targeting EGFR/VEGFR-Akt/NF-kappaB pathways ⁽²³⁾.

• Warnings

  Although there are no reported side effects from taking L-theanine, consumption of large amount of green tea can cause nausea, irritability, and GI upset because of the caffeine content.

• Contraindications
  • Hypersensitivity to green tea
  • Pregnancy and lactation
  • Sedatives
• Adverse Reactions

  Please see monograph on Green Tea.

• Herb-Drug Interactions
  • Midazolam: L-theanine may have additive effects ⁽¹⁹⁾.
• References

  1. Zhang G, Miura Y, Yagasaki K. Effects of dietary powdered green tea and L-theanine on tumor growth and endogenous hyperlipidemia in hepatoma-bearing rats. Biosci Biotechnol Biochem. 2002; 66(4):711-6.

  2. Kakuda T. Neuroprotective effects of the green tea components L-theanine and catechins. Biol Pharm Bull. 2002; 25(12):1513-8.

  3. Zheng G, Sayama K, Okubo T, Juneja LR, Oguni I. Anti-obesity effects of three major components of green tea, catechins, caffeine and L-theanine, in mice. In Vivo. 2004;18(1):55-62.

  4. Sato Y, Nakatsuka H, Watanabe T, Hisamichi S, Shimizu H, Fujisaku S, et al. Possible contribution of green tea drinking habits to the prevention of stroke. Tohoku J Exp Med. 1989; 157(4):337-43.

  5. Sugiyama T, Sadzuka Y. Combination of L-theanine with doxorubicin inhibits hepatic metastasis of M5076 ovarian sarcoma. Clin Cancer Res. 1999; 5(2):413-6.

  6. Sadzuka Y, Sugiyama T, Sonobe T. Improvement of idarubicin induced antitumor activity and bone marrow suppression by L-theanine, a component of tea. Cancer Lett. 2000;158(2):119-24.

  7. Sugiyama T, Sadzuka Y. Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changing the glutathione level. Cancer Lett. 2004;212(2):177-84.

  8. Tsuge H, Sano S, Hayakawa T, Kakuda T, Unno T. Theanine, gamma-glutamylethylamide, is metabolized by renal phosphate-independent glutaminase. Biochim Biophys Acta. 2003;1620(1-3):47-53.

  9. Sadzuka Y, et al. Efficacy of theanine is connected with theanine metabolism by any enzyme, not only drug metabolizing enzymes. Food Chem Toxicol 2006; 44(2):286-92.

  10. Yokogoshi H, et al. Theanine-induced reduction of brain serotonin concentration in rats. Biosci Biotechnol Biochem 1998; 62(4): 816-17.

  11. Yokogoshi H, et al. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res 1998; 23(5): 667-73.

  12. Lu K, et al. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol Clin Exp 2004: 19: 457-65.

  13. Kim TI, Lee YK, Park SG, et al. l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways. Free Radic Biol Med. 2009 Dec 1;47(11):1601-10.

  14. Owen GN, Parnell H, De Bruin EA, Rycroft JA. The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci. 2008 Aug;11(4):193-8.

  15. Giesbrecht T, Rycroft JA, Rowson MJ, De Bruin EA. The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutr Neurosci. 2010 Dec;13(6):283-90.

  16. Di X, Yan J, Zhao Y, et al. L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway. Neuroscience. 2010 Jul 14;168(3):778-86.

  17. Ritsner MS, Miodownik C, Ratner Y, et al. 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. J Clin Psychiatry. 2011 Jan;72(1):34-42.

  18. Lyon MR, Kapoor MP, Juneja LR. 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. Altern Med Rev. 2011 Dec;16(4):348-54.

  19. Heese T, Jenkinson J, Love C, et al. Anxiolytic effects of L-theanine—a component of green tea—when combined with midazolam, in the male Sprague-Dawley rat. AANA J. 2009 Dec;77(6):445-9.

  20. Zarse K, Jabin S, Ristow M. L-Theanine extends lifespan of adult Caenorhabditis elegans. Eur J Nutr. 2012 Sep;51(6):765-8.

  21. Ota M, Wakabayashi C, Sato N, et al. Effect of l-theanine on glutamatergic function in patients with schizophrenia. Acta Neuropsychiatr. Apr 21 2015:1-6.

  22. Dodd FL, Kennedy DO, Riby LM, et al. A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood. Psychopharmacology (Berl). Mar 13 2015.

  23. Zhang G, Ye X, Ji D, et al. Inhibition of lung tumor growth by targeting EGFR/VEGFR-Akt/NF-kappaB pathways with novel theanine derivatives. Oncotarget. Sep 30 2014;5(18):8528-8543.

  24. Nagai K, Oda A, Konishi H. Theanine prevents doxorubicin-induced acute hepatotoxicity by reducing intrinsic apoptotic response. Food Chem Toxicol. Apr 2015;78:147-152.

  25. Lardner AL. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutr Neurosci. Jul 2014;17(4):145-155.

  26. Chatterjee S, Chatterjee A, Roy S, et al. L-Theanine healed NSAID-induced gastric ulcer by modulating pro/antioxidant balance in gastric ulcer margin. J Nat Med. Oct 2014;68(4):699-708.

  27. Sugiyama T, Sadzuka Y, Tanaka K, et al. Inhibition of glutamate transporter by theanine enhances the therapeutic efficacy of doxorubicin. Toxicol Lett. Apr 30 2001;121(2):89-96.

  28. Sugiyama T, Sadzuka Y. Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changing the glutathione level. Cancer Lett. Aug 30 2004;212(2):177-184.

  29. Hidese S, Ota M, Wakabayashi C, et al. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr. Apr 2017;29(2):72-79.

  30. Giles GE, Mahoney CR, Brunye TT, et al. Caffeine and theanine exert opposite effects on attention under emotional arousal. Can J Physiol Pharmacol. Jan 2017;95(1):93-100.

  31. Dodd FL, Kennedy DO, Riby LM, et al. A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood. Psychopharmacology (Berl). Jul 2015;232(14):2563-2576.