By Christopher Caracciolo, MD; Ted Wissink, MD; and Craig Schneider, MD
Dr. Caracciolo is a physician at Integrative Medicine Department, Maine Health, Falmouth.
Dr. Wissink is Associate Professor of Family Medicine, Tufts University School of Medicine; and Associate Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center, Portland.
Dr. Schneider is Associate Professor of Family Medicine, Tufts University School of Medicine; and Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center, Portland.
Summary Points
- Theanine is a major non-protein amino acid first isolated from green tea in the 1940s. L-theanine is the predominant isomer of theanine found naturally in tea.
- PubMed and Medline databases were used to review eight studies that met inclusion criteria assessing the effects of L-theanine on sleep in 417 patients.
- The data thus far published in the literature reveal an inconsistent and mild effect of L-theanine on various sleep-related parameters.
SYNOPSIS: This review of eight studies encompassing 417 patients assesses the effectiveness of L-theanine on sleep disorders. Results were inconsistent, but avenues of future study were identified.
Chronic stress, disordered sleep, and mood disturbances are extremely common and have the potential to negatively affect health in various ways. Supplements are a popular way of attempting to mitigate such symptoms and typically are available to consumers without a prescription. With that in mind, this article will review the clinical efficacy and safety of L-theanine, a supplement commonly used to support sleep and stress.
There is a major non-protein amino acid first isolated from green tea in the 1940s.1 L-theanine is the predominant isomer of theanine found naturally in tea. To explain the observed phenomenon that tea may have less stimulatory properties than other caffeinated beverages, such as coffee, it has been hypothesized that L-theanine attenuates the stimulatory properties of caffeine via anxiolytic properties. Most clinical research has evaluated L-theanine’s effectiveness in treating symptoms of stress and anxiety. In animal models, L-theanine has been proposed as a neuroprotective and cognitive-enhancing agent.2 L-theanine has been reported to act on the brain to modulate monoamine levels and glutamate and glycine transmissions in the central nervous system.3
In mice, L-theanine has shown anti-stress and antidepressant-like effects and has been shown to induce non-rapid eye movement sleep, with associated increases in gamma-aminobutyric acid signaling.4,5 In humans, different studies have examined acute effects of L-theanine on different mental states, and it has been hypothesized to have therapeutic effects in various mental conditions. This article will summarize these effects.
Results
PubMed and Medline databases were searched using the following search terms: “L-theanine” OR “theanine,” OR “tea” AND “sleep” OR “insomnia.” Inclusion criteria were: English language, intervention consisting of L-theanine as monotherapy or part of combination therapy, and either primary or secondary outcome measure including assessment of sleep quality. Reviewed studies are presented in Table 1.
Table 1. Summary of L-Theanine Studies |
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| Author/Year | Design | Results | Strengths and Limitations |
Evans (2023) |
RCT, crossover trial; n = 9; three days; tryptophan (1,000 mg), glycine (3,000 mg), magnesium (300 mg), tart cherry powder (220 mg), and L-theanine (200 mg) vs. placebo |
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Hidese (2017) |
Open-label cohort study; n = 20; eight weeks; individuals with MDD (active or in remission); eight weeks; L-theanine 250 mg, no placebo |
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Hidese (2019) |
RCT; n = 30; L-theanine (200 mg) crossover trial with two-week washout |
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|
Maloh (2022) |
Randomized, no control group; three groups (topical, combined, oral); n = 75; inner-calm; L-theanine, ashwagandha, saffron |
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|
Noah (2022) |
RCT; n = 100; four weeks; rhodiola, L-theanine (50 mg), vitamin B6, vitamin B12 combo |
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Sarris (2018) |
RCT; n = 46; eight weeks; patients with GAD; L-theanine (450 mg, uptitrated to 900 mg if no response) |
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Lyon (2011) |
RCT; n = 98; pediatric children with confirmed diagnosis of ADHD; L-theanine 200 mg twice daily |
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Thiagaraj (2022) |
RCT (crossover); n = 39; Malaysian adults; PSQI > 5; four-week interventions; combination s-casein/L-theanine (50 mg) |
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RCT: randomized, controlled trial; MDD: major depressive disorder; PSQI: Pittsburgh Sleep Quality Index; HAMD-21: Hamilton Depression Rating Scale; PO: orally; DASS-42: Depression Anxiety and Stress Scale; GAD: generalized anxiety disorder; ISI: Insomnia Severity Index; ADHD: attention-deficit/hyperactivity disorder; EEG: electroencephalogram |
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Eight studies met inclusion criteria, comprising a total of 417 patients. Study populations were heterogeneous, including healthy adults, adults with diagnoses of major depressive disorder and generalized anxiety disorder, as well as children diagnosed with attention-deficit/hyperactivity disorder. Doses of L-theanine ranged from 50 mg to 900 mg, with the most common dose being 200 mg to 250 mg in three of the eight studies. Four studies tested L-theanine monotherapy, and four studies employed L-theanine as part of a multi-supplement intervention.
The largest randomized, controlled trial (RCT) of L-theanine monotherapy to date randomized 93 children, mean age 9.3 years, to receive L-theanine 200 mg twice daily or placebo for six weeks.6 Both subjective (parental sleep questionnaires) and objective (wristwatch actinography) data were collected. At the end of the trial period, the treatment group had statistically significant improvements in actinography measures of sleep relative to the control group, including sleep efficiency (80% to 76%), and bouts of nocturnal activity (62 bouts vs. 56 bouts), as well as a non-significant reduction in minutes spent awake (76 vs. 59 minutes, P = 0.058). The precise definition of “bouts of nocturnal activity” was not defined in the study.
Subjective measurements of sleep using the parental sleep questionnaire were not specifically reported and were noted to be uncorrelated with actinography at baseline or at study end. An important limitation is that the baseline sleep data are not reported between the groups.
The next two largest and strongest RCTs of monotherapy demonstrated disparate results. The first study randomized 46 individuals with a diagnosis of generalized anxiety disorder on stable pharmacotherapy to L-theanine 450 mg or placebo for eight weeks. At four weeks, clinical non-responders had their doses of L-theanine increased to 900 mg.7 L-theanine did not outperform placebo with respect to the Insomnia Severity Index (ISI) score, or the Hamilton Anxiety scale.
In the second study, a randomized placebo-controlled crossover trial, 30 participants without psychiatric comorbidities received four weeks of L-theanine and four weeks of placebo separated by a two-week washout period. During L-theanine administration, the Pittsburgh Sleep Quality Index (PSQI) improved by a statistically significant 1.3 points, or 13% from baseline, whereas no change was noted in the placebo group. This difference was correlated with statistically significant improvements in sleep latency and daytime dysfunction.8
The final monotherapy study, an open-label cohort study of 20 patients with major depressive disorder, tested the effects of L-theanine 250 mg over an eight-week period.9 No difference in PSQI was noted during the study. However, in the 12 patients with major depression not in remission, a statistically significant improvement in PSQI of 1.1 points, or approximately 10%, was noted, possibly owing to more severe sleep dysfunction at baseline. An improvement in depressive symptoms, measured by the Hamilton Depression index of 3.5 points, or 30%, was noted.
The remaining four studies tested L-theanine as part of combined multiple supplement interventions. The largest trial randomized 100 participants to a combination product of L-theanine (50 mg), rhodiola, magnesium, and B vitamins or placebo for four weeks. The intervention group did not report improvement in PSQI relative to placebo.10 A 2022 randomized crossover study, where 39 healthy Malaysian adults received four weeks of both a combination intervention of L-theanine (50 mg) and s-casein as well as placebo, separated by a one-week washout period.11 The intervention group noted a 2.4-point, or 30%, improvement in PSQI from baseline, representing the largest benefit on sleep of any L-theanine-containing intervention in the literature.
A study of 16 individuals randomized to a one-week intervention of a combination product containing L-theanine (200 mg), tryptophan, glycine, magnesium, and tart cherry powder resulted in improved actinography parameters of sleep as well as decreased daytime sleepiness.12 A final uncontrolled three-arm study investigated the effects of topical, oral, and combined topical and oral L-theanine-containing products on various dermatologic, psychological, and sleep parameters. The 25 participants in the oral group, who received a supplement containing L-theanine, ashwagandha, and saffron, reported a statistically significant improvement in sleep as measured in the PSQI; however, the oral and topical group did not report significant improvement in sleep, possibly owing to a wide distribution and standard deviation of PSQI scores in this cohort.
L-theanine was safe and well tolerated in each of these studies, including a total of 417 patients, with doses of L-theanine ranging from 50 mg to 900 mg per day. All eight studies were partially funded by companies that manufacture L-theanine-containing supplements.
Commentary
The data thus far published in the literature reveal an inconsistent and mild effect of L-theanine on various sleep-related parameters. Definitive interpretation of the data is limited by the heterogeneity of patient populations, clinical endpoints, and L-theanine preparations used. Moreover, sample sizes generally were small, limiting the generalizability of the findings — only one of the eight studies included more than 50 participants. Five of eight trials measured sleep using the PSQI, which ranges in score from 0-21, with a higher score indicative of worsening sleep dysfunction. Among these five studies, three reported improvements in PSQI, with a difference of 1.5-2.5. The clinical significance of such an improvement in PSQI score is uncertain; this report interprets these data to suggest that the maximum benefit seen in the available literature is mild in various parameters of sleep.
L-theanine is well-tolerated in various doses ranging from 50 mg to 900 mg per day. The most commonly tested doses are 200 mg to 250 mg. Additionally, its safety profile in combination with other psychotropic medications is reassuring, both in the published literature as well as its well-established empiric history as an active ingredient in the diets of all who drink tea. This safety profile stands in contrast to many other pharmacologic options routinely used for the treatment of sleep disorders. The fact that all eight of the studies were funded by the supplement industry raises the risk of bias in the data.
Despite benefits for insomnia reported in several studies, the data do not confirm L-theanine to be a consistently effective treatment for insomnia. However, given its reassuring safety profile and some signals of benefit in the data, L-theanine can reasonably be considered both as monotherapy for insomnia, or more appropriately as part of an integrative treatment plan involving other modalities. A typical cup of black tea contains approximately 25 mg of L-theanine.13 However, it also contains caffeine and, therefore, may perpetuate sleep disturbances. Replacing coffee with tea to benefit sleep is a recommendation that is grounded in some of the evidence reported in the present review.
References
- Dodd FL, Kennedy DO, Riby LM, Haskell-Ramsay CF. 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) 2015;232:2563-2576.
- Nathan PJ, Lu K, Gray M, Oliver C. The neuropharmacology of L-theanine: A possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother 2006;621-630.
- Terashima T, Takido J, Yokogoshi H. Time-dependent changes of amino acids in the serum, liver, grain and urine of rats administered theanine. Biosci Biotechnol Biochem 1999;63:615-618.
- Unno K, Iguchi K, Tanida N, et al. Ingestion of theanine, an amino acid in tea, suppresses psychosocial stress in mice. Exp Physiol 2013;98:290-303.
- Dasdelen MF, Er S, Kaplan B, et al. A novel theanine complex, Mg-L-theanine improves sleep quality via regulating brain electrochemical activity. Front Nutr 2022;9:874254.
- Lyon MR, Kapoor MP, Juneja LR, 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. Altern Med Rev 2011;16:348-354.
- Sarris J, Byrne GJ, Cribb L, et al. L-theanine in the adjuvant treatment of generalized anxiety disorder: A double-blind, randomized, placebo-controlled trial. J Psychiatr Res 2019;110:31-37.
- 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;11:2362.
- 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 Neuropsychiatrica 2017;29:71-79.
- Noah L, Morel V, Bertin C, et al. Effect of a combination of magnesium, B-vitamins, rhodiola, and green tea (L-theanine) on chronically stressed healthy individuals — A randomized, placebo-controlled study. Nutrients 2022;14:1863.
- Thiagaraj K, Chee HP, Sit NW. Effect of alpha-s1-casein tryptic hydrolysate and L-theanine on poor sleep quality: A double blind, randomized placebo-controlled crossover trial. Nutrients 2022;14:652.
- Langan-Evans C, Hearris MA, Gallagher C, et al. Nutritional modulation of sleep latency, duration and efficiency: A randomized, repeated-measures, double-blind deception study. Med Sci Sports Exerc 2023;55:289-300.
- Keenan EK, Finnie MDA, Jones PS, et al. How much theanine in a cup of tea? Effects of tea type and method of preparation. Food Chem 2022;125:588-594.
This review of eight studies encompassing 417 patients assesses the effectiveness of L-theanine on sleep disorders. Results were inconsistent, but avenues of future study were identified.
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