<h2> Key Points</h2><ul><li>L-theanine is a calming amino acid that promotes relaxing alpha waves in the brain.</li><li>Primary clinical applications include stress, anxiety, insomnia, and cognitive function.</li><li>Dosage range of 200-400 mg/day induces relaxation and relieves nervous tension.</li><li>Oral administration results in an increased secretion of neurotransmitters, such as dopamine and serotonin, after 30 minutes and the generation of alpha waves in the brain within 40 minutes. </li><li>Supplemental L-theanine is well-tolerated and has a good safety profile.</li></ul><h2> Overview</h2> L-theanine is a non-protein forming and water-soluble amino acid.1,2 In nature, L-theanine is found almost exclusively in the tea plant (Camellia sinensis).1,2 It makes up 1–2.5% of the dry weight of fresh tea leaves and is the major compound providing the umami taste of tea.1 Yellow tea and green tea contain the highest amount of L-theanine, however, L-theanine is also found in considerable quantities in white, oolong, and black tea.2 Non-protein amino acids Amino acids can be proteinogenic (used to form proteins) or non-proteinogenic (perform a range of other important biological roles in the body).3 Why supplement? Due to the degree of variation of L-theanine content in tea, supplementation is often required for consistent therapeutic outcomes.2 <img src="https://images.contentstack.io/v3/assets/blt948bd74310fc0ad0/blte2e7a0e563ac14c7/6a82a0e35751aa2de37e3774/Technical-Explainer-L-Theanine-Coffee.jpg" alt="Technical-Explainer-L-Theanine-Coffee.jpg" class="embedded-asset" /><h2> Actions and benefits</h2>L-theanine induces relaxation and relieves nervous tension via the following mechanisms:<ul><li>Stimulates the production of alpha brain waves, which: <ul><li>Support the transition to sleep</li><li>Are associated with light meditative states4</li></ul> </li><li>Modulates neurotransmitter activity to: <ul><li>Reduce glutamate release</li><li>Increase the release of gamma-aminobutyric acid (GABA), glycine, serotonin, and dopamine1</li></ul> </li><li>Enhances neurogenesis1</li><li>Inhibits the excitatory effects of caffeine1</li></ul>Evidence also indicates that L-theanine has many other health benefits, exerting antioxidant, anti-inflammatory, neuroprotective, metabolic regulatory, cardiovascular protective, and immunomodulatory effects.<h2> Alpha brain waves for a relaxed mind</h2> Brain waves are oscillating electrical voltages in the brain that result from groups of neurons firing in a synchronised pattern.5 They are measured by frequency, cycles per second, or hertz (Hz), and are correlated with very fast to slow brain activity. The human brain has five types of brain waves: gamma, beta, alpha, theta and delta (See Figure 1).4 <ul><li>Gamma and beta waves are produced when alert and focused.</li><li>Alpha waves fall in the middle of the brain wave spectrum and are associated with feelings of calm and relaxation.</li><li>Theta and delta waves are produced during sleep and deep relaxation.4</li></ul> By enhancing the production of alpha waves, L-theanine has a significant effect on the nervous system. Increases in alpha power reduce cortisol levels, relaxing the mind and decreasing stress.6 Alpha brain waves also stimulate parasympathetic nervous system activity and decrease sympathetic nervous system responses, reducing anxiety.1 This can help to promote sleep onset by calming the body and facilitating the transition to a theta-dominant state. Alpha brain waves are also found to be the optimal state for learning and can boost creativity.4 <img src="https://images.contentstack.io/v3/assets/blt948bd74310fc0ad0/blt0283e45a07f254dc/6a82a1060da67360dc57d100/Technical-Explainer-L-Theanine-Brain-Waves.jpg" alt="Technical-Explainer-L-Theanine-Brain-Waves.jpg" class="embedded-asset" />Figure 1. Alpha brain waves are associated with a relaxed mind and are typically present during light meditation.4 Alpha brain waves dominate when the mind is in a wakeful state, however with increased inhibition of sensory inputs, as seen when in a state of relaxation. They hold the middle ground of the brain wave spectrum, representing a bridge between relaxed conscious awareness and the transition to sleep. 4The effect of L-theanine on neurotransmitters A delicate balance between neurotransmitters is essential for a healthy stress response, quality sleep, and optimal neurological function. The main neurotransmitters in the brain responsible for maintaining this balance between inhibition and excitation of the nervous system are glutamate and GABA.7,8 Glutamate is the major excitatory neurotransmitter of the central nervous system and is responsible for promoting neural activity.7 GABA is the major inhibitory neurotransmitter and is responsible for preventing over-excitation.1,8 When glutamate overactivity is suppressed and the inhibitory effects of GABA are enhanced, nervous system excitation is reduced, resulting in a more relaxed mental state.1,7,8 <img src="https://images.contentstack.io/v3/assets/blt948bd74310fc0ad0/bltc0e3794d79e39c1f/6a82a122288839a8da07f67f/Technical-Explainer-L-Theanine-Structure.jpg" alt="Technical-Explainer-L-Theanine-Structure.jpg" class="embedded-asset" />Figure 2. Chemical structure of L-theanine, L-glutamate and L-glutamine.1 L-theanine increases the release of GABA. It also suppresses glutamine (a precursor to glutamate) transporters to inhibit the incorporation of extracellular glutamine into the neuron. L-theanine also competes for glutamate receptors, such as N-methyl-D-aspartate (NMDA) and amino-3-hydroxy-5- methyl-4-isoxazole propionic acid (AMPA), thereby reducing glutamine’s excitatory actions (See Figure 3).1Additionally, L-theanine increases the release of glycine, serotonin, and dopamine, further supporting its relaxing effects.1Glycine is a neurotransmitter that has a balancing neurological effect on the brain. Research has found it may help with sleep latency (the time it takes to fall asleep) and sleep quality by lowering core body temperature and modulating circadian rhythms.9,10<img src="https://images.contentstack.io/v3/assets/blt948bd74310fc0ad0/blt83df630a2c42ba30/6a82a13dc5d6fd427f95a211/Technical-Explainer-L-Theanine-Glutamine.jpg" alt="Technical-Explainer-L-Theanine-Glutamine.jpg" class="embedded-asset" />Figure 3. Glutamine (Gln), glutamate (Glu), and L-theanine activity at the synapse.1<h2> Absorption and bioavailability </h2>L-theanine is absorbed by sodium-coupled cotransporters in the intestinal brush-border membrane and distributed to various organs.1,11 It can cross the BBB, with an increase in brain-theanine levels seen after 30 minutes of ingestion.1Why L-theanine?With the exception of glycine, natural amino acids are found in two forms, L (left) and D (right) enantiomers (mirror-image versions of molecules).12 L-theanine is more commonly found in natural foods and is much more bioavailable than D-theanine.13<img src="https://images.contentstack.io/v3/assets/blt948bd74310fc0ad0/blt7dc99c4a78eafa73/6a82a15d0f118a58b42d9b93/Technical-Explainer-L-Theanine-Oral-Administration.jpg" alt="Technical-Explainer-L-Theanine-Oral-Administration.jpg" class="embedded-asset" /><h2> Interactions and safety </h2>Safety L-theanine supplementation is generally well tolerated in humans.7AlphaWave® L-theanine at 400 mg/day is considered safe and well tolerated.14Pregnancy and breastfeedingThe safety of L-theanine has not been examined in pregnant or lactating women; hence, it is not recommended for use in these populations.16Anti-hypertensive medicationsAs L-theanine may decrease blood pressure, a theoretical concern exists.SedativesAs L-theanine may compete with glutamate and increase GABA levels, a theoretical concern exists.There is no evidence from human studies to support clinical recommendations, however, patient monitoring is recommended.<h2> Prescribing guide </h2>Clinical evidence-based dosage guide for the prescribing of L-theanine supplements<table><tbody><tr><th>Condition</th><th>Level of Evidence</th><th>Dosage and Duration</th></tr><tr><td>Alpha brain wave enhancements</td><td>B</td><td>200 mg AlphaWave® prior to acute stressful mental challenge7</td></tr><tr><td>Anxiety</td><td>A/B</td><td>200–400 mg/day acutely and up to 8 weeks17
 200 mg/day before bed each night for four weeks18</td></tr><tr><td>Cognitive function</td><td>B</td><td>100 mg prior to mental task, and after taking for 12 weeks19
 200 mg/day before bed each night for four weeks18
 200 mg AlphaWave® twice daily for 28 days14</td></tr><tr><td>Major depressive disorder (depression symptoms, anxiety, sleep disturbance and cognitive impairments)</td><td>C</td><td>250 mg/day for eight weeks, alongside regular medication20</td></tr><tr><td>Immunity and inflammation</td><td>C</td><td>150 mg/day for six weeks21</td></tr><tr><td>Sleep quality, latency and depth</td><td>B</td><td>200 mg/day before bed each night for four weeks18
 200 mg AlphaWave® twice daily for 28 days14</td></tr><tr><td>Stress (including salivary cortisol decreases)</td><td>A/B</td><td>200 mg/day before bed each night for four weeks18
 200–400 mg/day acutely and up to 8 weeks17
 200 mg AlphaWave® prior to acute stressful mental challenge7
 200 mg AlphaWave® twice daily for 28 days14</td></tr><tr><td>Working memory</td><td>B</td><td>100 mg prior to mental task, and after taking for 12 weeks19</td></tr></tbody></table>Evidence levelsA: Meta-analysis and/or systematic review B: High quality clinical trial C: Good quality clinical trial <h2> References</h2><ol><li>Wang L, Brennan M, Li S, et al. How does the tea L-theanine buffer stress and anxiety. Food Sci. Hum. Wellness. 2022;11(3):467–75.</li><li>Li MY, Liu HY, Wu DT, et al. L-theanine: a unique functional amino acid in tea (Camellia sinensis L.) with multiple health benefits and food applications. Front Nutr. 2022;9:853846.</li><li>Ding Y, Ting JP, Liu J, et al. Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics. Amino Acids. 2020;52(9):1207–26.</li><li>Srimaharaj W, Chaisricharoen R, Chaising S, et al. Classification of human brain attention focused on meditation, effected by L-theanine acid in Oolong tea. In: 2018 International Conference on Digital Arts, Media and Technology (ICDAMT). 2018, p. 262–6. Viewed 20 November 2024. https://ieeexplore.ieee.org/document/8376536</li><li>Jee S. Brain oscillations and their implications for neurorehabilitation. Brain Neurorehabil. 2021;14(1):e7</li><li>Evans M, McDonald AC, Xiong L, et al. A randomized, triple-blind, placebo-controlled, crossover study to investigate the efficacy of a single dose of AlphaWave® L-theanine on stress in a healthy adult population. Neurol Ther. 2021;10(2):1061–78.</li><li>Köles L, Kató E, Hanuska A, et al. Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems. Purinergic Signal. 2016;12(1):1–24.</li><li>Allen MJ, Sabir S, Sharma S. GABA receptor. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. Viewed 20 November 2024 , https://www.ncbi.nlm.nih.gov/books/NBK526124/</li><li>Kawai N, Sakai N, Okuro M, et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015;40(6):1405–16.</li><li>Gratwicke M, Miles KH, Pyne DB. Nutritional interventions to improve sleep in team-sport athletes: a narrative review. Nutrients. 2021;13(5):1586.</li><li>Chen S, Kang J, Zhu H, et al. L-theanine and immunity: a review. Molecules. 2023;28(9):3846.</li><li>Abdulbagi M, Wang L, Siddig O, et al. D-amino acids and D-amino acid-containing peptides: potential disease biomarkers and therapeutic targets? Biomolecules. 2021;11(11):1716.</li><li>Adhikary R, Mandal V. l-theanine: A potential multifaceted natural bioactive amide as health supplement. Asian Pacific Journal of Tropical Biomedicine. 2017;7(9):842–8.</li><li>Moulin M, Crowley DC, Xiong L, et al. Safety and efficacy of AlphaWave® L-theanine supplementation for 28 days in healthy adults with moderate stress: a randomized, double-blind, placebo-controlled trial. Neurol Ther. 2024;13(4):1135–53.</li><li>Ethical Naturals. AlphaWave® – L-Theanine. Viewed 18 January 2024, https://ethicalnaturals.com/products-manufacturing-services/alphawave-l-theanine/</li><li>Theanine. NatMed 2024. Viewed 20 November 2024, https://naturalmedicines.therapeuticresearch. com</li><li>Williams JL, Everett JM, D’Cunha NM, et al. The effects of green tea amino acid L-theanine consumption on the ability to manage stress and anxiety levels: a systematic review. Plant Foods Hum Nutr. 2020;75(1):12–23.</li><li>Hidese S, Ogawa S, Ota M, et al. Effects of L-theanine administration on stress-related symptoms and cognitive functions in healthy adults: a randomized controlled trial. Nutrients. 2019;11(10):2362.</li><li>Baba Y, Inagaki S, Nakagawa S, et al. Effects of l-theanine on cognitive function in middle-aged and older subjects: a randomized placebo-controlled study. J Med Food. 2021;24(4):333–41.</li><li>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. 2017;29(2):72–9. 21 Juszkiewicz A, Glapa A, Basta P, et al. The effect of L-theanine supplementation on the immune system of athletes exposed to strenuous physical exercise. J Int Soc Sports Nutr. 2019;16(1):7. .</li></ol>

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