A popular supplement for anxiety, l-theanine from green tea is often promoted as a miracle solution for mood and sleep.
This article examines the research and clinical trials on l-theanine, explaining how it works and the likely effects of supplementation.
What is l-theanine?
L-theanine is an amino acid with a similar chemical structure to glutamate, which is a neurotransmitter. It is found in green tea and mushrooms, and l-theanine is readily available as a supplement.
People often take l-theanine supplements for anxiety, and studies do back up this claim somewhat. But l-theanine is more than just a ‘chill pill’, as you will see from the research on inflammation and brain health.
In tea, l-theanine makes up about 1 -2% of the dry weight of the leaves. It is true for both black and green teas, with different tea varieties containing different amounts.[ref]
On average, a cup of tea contains about 25mg of l-theanine. Interestingly, l-theanine takes away some of the bitter taste of caffeine through binding to the taste receptors for umami, a savory taste.[ref]
In the brain, l-theanine binds to glutamate receptors. But l-theanine doesn’t have as strong an affinity to the receptor as glutamate, so it doesn’t replace it entirely. Instead, it somewhat inhibits glutamate reuptake and increases brain levels of GABA.[ref] GABA acts as an inhibitory neurotransmitter, putting the brakes on brain excitement.
Recent research also shows that l-theanine binds to cannabinoid receptor 1 (CB1). This competitive binding then inhibits the CB1 receptor.[ref]
Studies on l-theanine for anxiety:
L-theanine has been tested in clinical trials for anxiety. Let’s take a look at some of the results:
A 2006 cross-over trial found that l-theanine reduced heart rate and stress response molecules in response to acute stress tasks. The heart rate variability results showed that the reduction in heart rate was “attributable to an attenuation of sympathetic nervous activation.”[ref]
A randomized, placebo-controlled, cross-over, and double-blind trial looked at the effects of 200mg/d of l-theanine on adults with no mood issues. The results showed a decrease in depression and anxiety traits as well as better sleep. Cognitive function, executive function, and verbal fluency all improved.[ref]
On the other hand, an 8-week trial in people with Generalized Anxiety Disorder found that l-theanine did not reduce anxiety.[ref]
Researchers looked at different doses of l-theanine and measured the startle response. [ref] Doses of 200-400 mg did decrease the startle response, but at doses over 400 mg, there was no additional benefit.
A clinical trial looked at the anxiety reduction from 200 mg of l-theanine vs. alprazolam (benzodiazepine) or a placebo. The study results showed that l-theanine helped with relaxation during non-stress conditions, but neither then alprazolam nor l-theanine had acute anxiety-reducing effects during anticipatory anxiety.[ref] To me, the difference between anticipatory stress and a suddenly anxious situation is similar to dreading a final exam for a week vs. having a pop-quiz.
Studies on l-theanine for depression:
Surprisingly, there isn’t a lot of published research on l-theanine for depression. Anxiety and depression often go hand-in-hand, so I expected to find more research on the combination.
A clinical trial using 250mg/day of l-theanine in adults with major depressive disorder showed that anxiety traits improved. Sleep disturbances were helped by the l-theanine also.[ref]
Sleep studies with l-theanine:
It would make sense that something that can decrease anxiety would help people who have sleep problems due to constantly worrying about things all night. Plus, supplement sellers of l-theanine often promote its use for sleep. But, to be honest, the research on the topic is slim.
A randomized, double-blind, placebo-controlled trial using 100 mg of l-theanine 4x per day in boys with ADHD showed some improvements in sleep quality.[ref]
Additionally, the clinical trial mentioned above for stress-related symptoms also noted improved sleep quality scores in participants taking l-theanine.[ref]
Will it give you nightmares? An animal study showed that GABA plus l-theanine effectively decreased the time it took to fall asleep and the time spent sleeping. It also almost doubled the time spent in REM sleep.[ref] I mention this animal study because some people report that l-theanine causes vivid dreams for them, which may go along with changes in REM sleep.
Caffeine plus l-theanine: taking the edge off
One benefit of l-theanine is to take the edge off the caffeine jitters.
A clinical trial showed that combining l-theanine with caffeine eliminated the negative effects of caffeine in people who weren’t used to drinking it.[ref]
Another study found that moderate levels of l-theanine and caffeine improved accuracy and alertness in participants.[ref]
A double-blind, placebo-controlled study found that 100mg of l-theanine plus 50mg of caffeine increased vigilance and decreased errors during a sustained attention task. In other words, it increased the participants’ ability to focus.[ref]
Interestingly, caffeine jitters are something that happens based on genetic variants in the ADORA2A gene. Thus, if you naturally don’t feel anxious, then theanine may not have much of an impact as far as a combo with caffeine.
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Targeting inflammation and the immune system:
Animal studies show that l-theanine decreases TNF-alpha levels and increases the anti-inflammatory cytokine IL-10.[ref]
Psoriasis is a skin inflammatory disease that involves an increased immune cell response in the epidermis. Studies show that l-theanine reduces the overactive inflammatory response by inhibiting IL-23, an inflammatory cytokine. The animal study also indicates that l-theanine regulates other inflammatory pathways, including IL-17A and NF-κB.[ref]
T cells are one of the body’s first lines of defense against microbial pathogens. Supplementing with l-theanine has been shown to prime a specific subset of T cells, called gamma-delta T lymphocytes. It may be why supplementing with l-theanine decreases cold and flu symptoms.[ref]
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Animal studies show that l-theanine stimulates the growth of neural progenitor cells. Essentially, l-theanine inhibits glutamine uptake without affecting glutamic acid uptake. It stimulates an increase in SLCC38A1, which is the glutamine transporter. The overexpression of SLC38A1 facilitates the pathways required for neurogenesis.[ref]
Cell studies using neuronal cells show that the upregulation of SLC38A1 by l-theanine promotes the generation of new neurons.[ref]
Promoting neurogenesis may be why studies in older adults who drink green tea with high theanine concentration have less cognitive decline than typically seen in aging.[ref]
L-theanine in aging:
Animal studies show that l-theanine may help to delay neurodegenerative diseases. The research shows that l-theanine activates SIRT1 and inhibits nuclear factor-κB (NF-kB), both of which should be beneficial in aging through reducing the expression of inflammatory factors.[ref]
For any supplement pill or medication capsule to work in the body, it needs to be absorbed in the intestines, moved into the bloodstream, and taken up into cells. Along the way, many substances are broken down or metabolized by the liver or other enzymes so the body can eliminate them.
Absorption in the gut:
Both l-theanine in capsules and l-theanine in green tea are readily absorbed, with peak plasma values observed after 45 minutes.[ref]
The addition of piperine increases the absorption of l-theanine.[ref]
The half-life of l-theanine is about an hour to an hour and 15 minutes. Meaning l-theanine is absorbed and metabolized relatively quickly. It does cross the blood-brain barrier and is detectable in the brain about a half hour after oral administration.[ref]
Transport into the cell: A transporter protein is needed to move l-theanine into a cell. Research shows that the LAT1 transporter, which moves several amino acids into cells, including l-leucine, is utilized by l-theanine.[ref]
L-theanine’s uptake is inhibited by l-leucine, a branch chain amino acid found in many proteins, including milk. Thus, to increase your ability to absorb l-theanine, drink your green tea without milk and away from branch-chain amino acid protein drinks.
SLC7A5 gene: encodes the LAT1 transporter, which transports l-theanine into cells.[ref]
Studies don’t directly investigate the impact of the LAT1 variant on l-theanine, but the variant below does increase expression of the transporter and impacts levels of transport in other drugs.
Check your genetic data for rs4240803 (23andMe v4, v5):
The amount of l-theanine varies quite a bit by the type of tea.
L-theanine dosage for anxiety:
The average cup of tea is around 20 to 25mg of l-theanine. Someone drinking multiple cups of tea in a day could be getting 100+ mg of theanine.
Clinical trials above used doses in the range of 100 to 900 mg/day without negative effects. There doesn’t seem to be evidence, though, that the higher doses are more effective. Some trials split the dosage into several 100 mg capsules over the course of the day. It makes sense when you look at the short half-life of l-theanine.
Tea is one of the most popular beverages consumed worldwide, and l-theanine is a beneficial component.
The clinical trials on l-theanine show that there may be mild benefits for anxiety for some people. More interesting, and perhaps related to decreasing anxiety, are the benefits for reducing and modulating the immune response. Overall, theanine is generally regarded as safe and seems to have few safety concerns.
Is Anxiety Genetic?
This article covers genetic variants related to anxiety disorders. Genetic variants combine with environmental factors (nutrition, sleep, relationships, etc) when it comes to anxiety. There is not a single “anxiety gene”. Instead, there are many genes that can be involved – and many genetic pathways to target for solutions.
Boros, Klára, et al. “Theanine and Caffeine Content of Infusions Prepared from Commercial Tea Samples.” Pharmacognosy Magazine, vol. 12, no. 45, 2016, pp. 75–79. PubMed Central, https://doi.org/10.4103/0973-1296.176061.
—. “Theanine and Caffeine Content of Infusions Prepared from Commercial Tea Samples.” Pharmacognosy Magazine, vol. 12, no. 45, 2016, pp. 75–79. PubMed Central, https://doi.org/10.4103/0973-1296.176061.
Childs, Emma, et al. “Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety.” Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 33, no. 12, Nov. 2008, pp. 2791–800. PubMed Central, https://doi.org/10.1038/npp.2008.17.
—. “Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety.” Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 33, no. 12, Nov. 2008, pp. 2791–800. PubMed Central, https://doi.org/10.1038/npp.2008.17.
Cho, Yu Kyoung, et al. “Associations of High-Dose Melphalan Pharmacokinetics and Outcomes in the Setting of a Randomized Cryotherapy Trial.” Clinical Pharmacology and Therapeutics, vol. 102, no. 3, Sept. 2017, p. 511. www.ncbi.nlm.nih.gov, https://doi.org/10.1002/cpt.644.
Dodd, F. L., 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, vol. 232, no. 14, July 2015, pp. 2563–76. PubMed, https://doi.org/10.1007/s00213-015-3895-0.
Foxe, John J., et al. “Assessing the Effects of Caffeine and Theanine on the Maintenance of Vigilance during a Sustained Attention Task.” Neuropharmacology, vol. 62, no. 7, June 2012, pp. 2320–27. PubMed, https://doi.org/10.1016/j.neuropharm.2012.01.020.
Giesbrecht, T., et al. “The Combination of L-Theanine and Caffeine Improves Cognitive Performance and Increases Subjective Alertness.” Nutritional Neuroscience, vol. 13, no. 6, Dec. 2010, pp. 283–90. PubMed, https://doi.org/10.1179/147683010X12611460764840.
Hidese, Shinsuke, Miho Ota, et al. “Effects of Chronic L-Theanine Administration in Patients with Major Depressive Disorder: An Open-Label Study.” Acta Neuropsychiatrica, vol. 29, no. 2, Apr. 2017, pp. 72–79. PubMed, https://doi.org/10.1017/neu.2016.33.
Hidese, Shinsuke, Shintaro Ogawa, et al. “Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial.” Nutrients, vol. 11, no. 10, Oct. 2019, p. E2362. PubMed, https://doi.org/10.3390/nu11102362.
—. “Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial.” Nutrients, vol. 11, no. 10, Oct. 2019, p. 2362. PubMed Central, https://doi.org/10.3390/nu11102362.
Hohoff, Christa, et al. “Association of Adenosine Receptor Gene Polymorphisms and in Vivo Adenosine A1 Receptor Binding in the Human Brain.” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, vol. 39, no. 13, Dec. 2014, pp. 2989–99. PubMed, https://doi.org/10.1038/npp.2014.150.
Kakuda, Takami. “Neuroprotective Effects of Theanine and Its Preventive Effects on Cognitive Dysfunction.” Pharmacological Research, vol. 64, no. 2, Aug. 2011, pp. 162–68. PubMed, https://doi.org/10.1016/j.phrs.2011.03.010.
Kim, Suhyeon, et al. “GABA and L-Theanine Mixture Decreases Sleep Latency and Improves NREM Sleep.” Pharmaceutical Biology, vol. 57, no. 1, Feb. 2019, pp. 65–73. PubMed Central, https://doi.org/10.1080/13880209.2018.1557698.
Kimura, Kenta, et al. “L-Theanine Reduces Psychological and Physiological Stress Responses.” Biological Psychology, vol. 74, no. 1, Jan. 2007, pp. 39–45. PubMed, https://doi.org/10.1016/j.biopsycho.2006.06.006.
Liu, An, et al. “L-Theanine Regulates Glutamine Metabolism and Immune Function by Binding to Cannabinoid Receptor 1.” Food & Function, vol. 12, no. 13, July 2021, pp. 5755–69. PubMed, https://doi.org/10.1039/d1fo00505g.
—. “L-Theanine Regulates Glutamine Metabolism and Immune Function by Binding to Cannabinoid Receptor 1.” Food & Function, vol. 12, no. 13, July 2021, pp. 5755–69. PubMed, https://doi.org/10.1039/d1fo00505g.
Lyon, Michael R., et al. “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, vol. 16, no. 4, Dec. 2011, pp. 348–54.
Narukawa, Masataka, et al. “L-Theanine Elicits Umami Taste via the T1R1 + T1R3 Umami Taste Receptor.” Amino Acids, vol. 46, no. 6, June 2014, pp. 1583–87. PubMed, https://doi.org/10.1007/s00726-014-1713-3.
Ota, Miho, et al. “Effect of L-Theanine on Sensorimotor Gating in Healthy Human Subjects.” Psychiatry and Clinical Neurosciences, vol. 68, no. 5, 2014, pp. 337–43. Wiley Online Library, https://doi.org/10.1111/pcn.12134.
—. “Effect of L-Theanine on Sensorimotor Gating in Healthy Human Subjects.” Psychiatry and Clinical Neurosciences, vol. 68, no. 5, 2014, pp. 337–43. Wiley Online Library, https://doi.org/10.1111/pcn.12134.
Poi, Ming J., et al. “A Single Nucleotide Polymorphism in SLC7A5 Was Associated With Clinical Response in Multiple Myeloma Patients.” Anticancer Research, vol. 39, no. 1, Jan. 2019, pp. 67–72. PubMed, https://doi.org/10.21873/anticanres.13080.
Renda, Giulia, et al. “Genetic Determinants of Cognitive Responses to Caffeine Drinking Identified from a Double-Blind, Randomized, Controlled Trial.” European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, vol. 25, no. 6, June 2015, pp. 798–807. PubMed, https://doi.org/10.1016/j.euroneuro.2015.03.001.
—. “Genetic Determinants of Cognitive Responses to Caffeine Drinking Identified from a Double-Blind, Randomized, Controlled Trial.” European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, vol. 25, no. 6, June 2015, pp. 798–807. PubMed, https://doi.org/10.1016/j.euroneuro.2015.03.001.
Sarris, Jerome, et al. “L-Theanine in the Adjunctive Treatment of Generalized Anxiety Disorder: A Double-Blind, Randomised, Placebo-Controlled Trial.” Journal of Psychiatric Research, vol. 110, Mar. 2019, pp. 31–37. PubMed, https://doi.org/10.1016/j.jpsychires.2018.12.014.
Sato, Yuki, et al. “An Imaging Approach for Determining the Mechanism of Enhancement of Intestinal Absorption of an L-Theanine Supplement.” PLoS ONE, vol. 16, no. 6, 2021. www.ncbi.nlm.nih.gov, https://doi.org/10.1371/journal.pone.0253066.
Scheid, Lisa, et al. “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, vol. 142, no. 12, Dec. 2012, pp. 2091–96. PubMed, https://doi.org/10.3945/jn.112.166371.
UQ ESpace. https://espace.library.uq.edu.au/view/UQ:284103. Accessed 6 Oct. 2021.
White, David J., et al. “Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial.” Nutrients, vol. 8, no. 1, Jan. 2016, p. 53. PubMed Central, https://doi.org/10.3390/nu8010053.
Xu, Yaohan, et al. “L-Theanine Alleviates IMQ-Induced Psoriasis Like Skin Inflammation by Downregulating the Production of IL-23 and Chemokines.” Frontiers in Pharmacology, vol. 12, 2021. www.ncbi.nlm.nih.gov, https://doi.org/10.3389/fphar.2021.719842.
Yamamoto, Sachiko, et al. “The Involvement of L-Type Amino Acid Transporters in Theanine Transport.” Bioscience, Biotechnology, and Biochemistry, vol. 76, no. 12, 2012, pp. 2230–35. PubMed, https://doi.org/10.1271/bbb.120519.
Yoneda, Yukio, Koichi Kawada, et al. “Selective Upregulation by Theanine of Slc38a1 Expression in Neural Stem Cell for Brain Wellness.” Molecules (Basel, Switzerland), vol. 25, no. 2, Jan. 2020, p. E347. PubMed, https://doi.org/10.3390/molecules25020347.
Yoneda, Yukio, Nobuyuki Kuramoto, et al. “The Role of Glutamine in Neurogenesis Promoted by the Green Tea Amino Acid Theanine in Neural Progenitor Cells for Brain Health.” Neurochemistry International, vol. 129, Oct. 2019, p. 104505. PubMed, https://doi.org/10.1016/j.neuint.2019.104505.
Zeng, Li, et al. “L-Theanine Ameliorates d-Galactose-Induced Brain Damage in Rats via Inhibiting AGE Formation and Regulating Sirtuin1 and BDNF Signaling Pathways.” Oxidative Medicine and Cellular Longevity, vol. 2021, July 2021, p. 8850112. PubMed Central, https://doi.org/10.1155/2021/8850112.
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Author Information: Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.