Common Name(s): Gamma-ethylamino-L-glutamic acid, Gamma-glutamylethylamide, L-theanine, N-ethyl-L-glutamine, Suntheanine
Medically reviewed by Drugs.com. Last updated on Feb 20, 2023.
Note: This monograph specifically discusses L-theanine, a chemical constituent of the tea plant (Camellia sinensis). For more information regarding clinical uses, interactions, adverse reactions, and toxicology associated with C. sinensis, see the Green Tea monograph.
Very limited clinical data support the adjunctive use of L-theanine to improve certain mood outcomes in patients with schizophrenia as well as some sleep problems in patients with major depressive disorder, schizophrenia, or generalized anxiety disorder (GAD). Sufficient clinical trial data are lacking to recommend use of L-theanine for any indication.
Robust, unequivocal data are currently unavailable to support dosing for any clinical use.
Cardiovascular: Supplementation with 50 mg or 200 mg of L-theanine has been used in healthy adults to attenuate acute caffeine-induced cerebral hemodynamics or behaviors and stress-induced increases in heart rate or blood pressure, respectively.
Schizophrenia: Adjunctive L-theanine 250 mg/day or 400 mg/day for 8 weeks (ie, in addition to current antipsychotic medication) has been studied for use in improving Positive and Negative Syndrome Scale (PANSS) positive and general psychopathology scores in patients with schizophrenia.
Sleep disorders: Adjunctive use of L-theanine 250 mg/day or 450 mg/day (225 mg twice daily) for 8 weeks (ie, in addition to current antipsychotic medication) has been studied for improvement of some sleep measures in patients with major depressive disorder, schizophrenia, or GAD.
None well established.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
None well documented.
Few adverse reactions have been reported; those recorded in human pharmacokinetic studies evaluating tea extracts include headache, dizziness, and GI symptoms. HDL-C was decreased significantly in adults with major depressive disorder administered adjunctive L-theanine.
L-theanine is sold in the United States as a dietary supplement and has been granted generally recognized as safe (GRAS) status by the US Food and Drug Administration (FDA).
L-theanine is derived from the leaves of C. sinensis (tea) and 2 other Camellia species (Camellia japonica and Camellia sasanqua). C. sinensis is native to eastern Asia and is a member of the Theaceae family. The evergreen shrub or tree grows to more than 9 m in height and is pruned from 60 cm to 1.5 m for cultivation. Its dark green, serrated-edged leaves are alternate and oval, while its white and fragrant blossoms appear singly or in clusters.(Green tea 2000, L-theanine 2005, USDA 2021)
The chemical has also been isolated from the edible mushroom Boletus badius, although information is limited to a single 1960 publication.(Casimir 1960) The mushroom is commonly found in late summer and autumn in the United States. It is reddish brown to dark brick/brown in color with a stem 4 to 12 cm in height. The flesh is white to yellow in color and becomes a light blue-green color when cut or bruised.
Second only to water, tea is the most widely consumed beverage in the world. L-theanine was discovered as a constituent of green tea in 1949 and was approved in Japan in 1964 for unlimited use in all foods (including chocolates, soft drinks, and herb teas), except infant foods. It also provides a unique umami (brothy or savory) taste and flavor to green tea infusion.(Juneja 1999, L-theanine 2005)
L-theanine (L-gamma-glutamylethylamide or N-ethyl-L-glutamine) constitutes 1% to 2% of the dry weight of tea leaves. It comprises approximately 50% of the total amino acids in green tea leaves and exists only in the free (nonprotein) form. Structurally, it is similar to glutamate and gamma-aminobutyric acid (GABA). An enzymatic method for manufacturing synthetic L-theanine (Suntheanine) has been developed.(Altinkaynak 2018, Bryan 2008, Juneja 1999, L-theanine 2005, Ota 2014)
Uses and Pharmacology
The uses described in the following sections focus on L-theanine specifically. See the Green Tea monograph for further information regarding potential uses of L-theanine when consumed as a component of tea.
In rats with doxorubicin-induced nephrotoxicity, supplementation of L-theanine for 5 days improved renal function test parameters (ie, blood urea nitrogen, creatinine) compared with rats not receiving supplementation (doxorubicin only group), with no differences observed between L-theanine and control (saline). Renal histopathology as well as plasma and renal antioxidant measures (ie, malondialdehyde, glutathione) supported these results. Anti-inflammatory activity of L-theanine was also noted via reductions in nuclear factor kappa B (NF-KB) concentrations in the doxorubicin-theanine group compared with the doxorubicin only group.(Altinkaynak 2018) Similarly, haloperidol-induced increases in lipid peroxidation and decreases in antioxidant enzymes were completely reversed in rats given 300 mg/kg of L-theanine for 35 days. A 100 mg/kg dose also completely inhibited changes in lipid peroxidation. No differences were seen between L-theanine at these doses and controls.(Chen 2018)
In a small pilot study in male competitive athletes (N=20), 2 L-theanine 150 mg capsules per day for 6 weeks resulted in higher 24-hour postrecovery total antioxidant capacity than 1-minute postexercise levels compared to placebo.(Juszkiewica 2019)
Limited studies have evaluated the effects of L-theanine supplementation in the prevention of cancer; the vast majority of studies have been conducted with green tea.
A dose-dependent hypotensive effect was demonstrated in spontaneously hypertensive, but not normotensive, rats injected with L-theanine. The effect may have been related to reductions in central levels of dopamine and serotonin.(L-theanine 2005)
In healthy volunteers, synthetic L-theanine 200 mg muted the increase in heart rate response to an acute stress test(Kimura 2007); it has also been suggested that L-theanine antagonizes the hypertensive effect of caffeine.(Rogers 2008) Hemodynamically in a small crossover study conducted in 24 healthy young adults, the addition of L-theanine 50 mg to caffeine 75 mg attenuated the decrease in cerebral blood flow and the increase in blood pressure that accompany caffeine consumption.(Dodd 2015) Similarly in another small crossover study in 16 young healthy adults, administration of L-theanine 200 mg attenuated systolic and diastolic blood pressure increases during acute psychological stress tests but not physical stress tests among the group of high-stress-response adults.(Yoto 2012) In contrast, in healthy males enrolled in a small double-blind, randomized, controlled crossover trial (N=18), the addition of L-theanine 200 mg to a food product resulted in no acute differences in blood pressure or heart rate variability over 90 minutes compared with placebo.(Williams 2020)
Although the pharmacological effects of L-theanine are uncertain, several researchers have proposed a number of mechanisms by which it may act on the CNS. These include inhibiting glutamate receptors, increasing the concentration of GABA, increasing dopamine and serotonin in specific brain regions, inhibiting glutamate-induced effects including apoptosis and amyloid beta toxicity, hippocampal neurogenesis and enhanced memory, and neuroprotective blockage of multiple glutamate receptor subtypes in the hippocampus, mechanisms suggestive of a potential role in Parkinson and Alzheimer diseases.(Bryan 2008, Cho 2008, Di 2010, Lu 2004, Mancini 2017, Takeda 2011)
Cognitive function, attention, and mood
In a rat model of adolescent tetrahydrocannabinol (THC) exposure, L-theanine demonstrated neuroprotective effects; rats pretreated with L-theanine did not develop the cognitive and affective abnormalities associated with adolescent THC exposure. L-theanine also prevented the downregulation of prefrontal cortex signalling pathways associated with increased psychiatric disease risk. Though the novel findings of this report suggest a neuroprotective role of L-theanine against effects of THC exposure, future studies are required to further explore these possibilities.(De Felice 2020)
In a small crossover trial conducted in 30 Japanese adults with stress-related symptoms and no psychiatric disorder, no significant difference in cognitive function scores was observed with administration of L-theanine 200 mg/day for 4 weeks compared with placebo treatment. However, during L-theanine treatment, letter fluency improved significantly (P=0.001), particularly in subjects in the lower half of baseline scores (P=0.002). In contrast, Trail Making Test A and B scores improved significantly during placebo treatment (P=0.042 and P=0.038, respectively).(Hidese 2019)
A meta-analysis of 11 randomized clinical trials assessed the acute effects of the tea constituents L-theanine and (-)-epigallocatechin gallate (alone or in combination with caffeine) on cognitive function and mood in healthy adults. Data were sufficient to conduct 1 meta-analysis (3 studies; N=78) for L-theanine alone on anxiety but not for other mood, attention, or cognition measures. L-theanine 200 mg did not produce an effect on anxiety at 40 to 70 minutes postdose. Moderator analyses found no effect of L-theanine alone for alertness, calmness, contentedness, or attentional switch measures.(Camfield 2014) A subsequent small, double-blind, crossover study conducted in 24 healthy young adults used lower single doses of L-theanine (50 mg) and caffeine (75 mg), alone and in combination; these doses were more reflective of those in 1 or 2 cups of tea. The authors observed significantly fewer errors with L-theanine compared with the combination (P<0.05) when testing for reaction time to congruent and incongruent stimuli (Stroop test). However, no other significant differences in cognitive or mood assessments were found with L-theanine. Hemodynamically in this study, the addition of L-theanine attenuated the decrease in cerebral blood flow and the increase in blood pressure that was evident following caffeine administration.(Dodd 2015) A nonlinear dose response was found between L-theanine administration and inhibition of the startle response in a study of 14 healthy Japanese participants. Inhibition was observed with 200 mg and 400 mg doses through mechanisms that appeared to be similar to nicotine.(Mancini 2017, Ota 2014)
Effects of high doses of L-theanine alone as well as in contrast to and in combination with caffeine on attention have been described in small placebo-controlled studies in healthy young adults (N range, 9 to 36). L-theanine doses studied were predominantly 200 mg (equivalent to the amount in approximately 8 cups of tea and also what is available in most commercial supplements), but doses of 100 and 400 mg were also described in a dose-finding study. Caffeine was dosed at 160 mg or 200 mg (equivalent to 8 cups of tea or 1 cup of coffee, respectively). The studies, conducted predominantly by 1 group of researchers, reported improvements with L-theanine in certain neurophysiological attention measures (ie, recognition visual reaction time, auditory event–related potentials). These were equally improved by caffeine, with an additive improvement seen with the combination of L-theanine and caffeine, suggesting effects on stimulus discrimination and response inhibition to distractors in later stage attention processing.(Dassasnayake 2020, Giles 2017, Kahathuduwa 2017, Kahathuduwa 2018) These results were supported by brain scans that documented increased activity with L-theanine in several regions associated with responsiveness to distractor stimuli.(Kahathuduwa 2018) In contrast, executive functioning was decreased by L-theanine compared with placebo. Salivary cortisol was lower 2 hours after L-theanine intake compared with caffeine intake.(Giles 2017) Other groups have reported equivocal results, including differences in reaction times observed only with a 400 mg dose of L-theanine.(Dassanayake 2020)
A small, open-label study conducted in 20 adults (16 females) with major depressive disorder reported improvements in symptoms and cognitive function with L-theanine. L-theanine 250 mg/day for 8 weeks (administered alone or as an adjunct to antidepressant medication) reduced total depression scores (21-item version of Hamilton Rating Scale for Depression [HAMD21]; P=0.007) and 4 subscale scores (core [P=0.018], psychic anxiety [P=0.012], somatic anxiety [P=0.023], delusion [P=0.024]) compared to baseline. Subgroup analysis revealed significance was retained in patients who were unremitted at baseline but not in remitted patients. Changes in sleep scores were not statistically significant from baseline overall but were significantly improved in the unremitted subgroup (P=0.03). Anxiety trait indices improved overall (P=0.012) but not when assessed in either subgroup. Cognitive improvements were documented for response latency (P=0.001), error rate (P=0.036), verbal memory (P=0.005), and executive function (P=0.016). A decrease in mean HDL of 4.4 mg/dL (P=0.011) was the only significant change in laboratory parameters; no notable adverse events were observed.(Hidese 2017)
In an 8-week, randomized, placebo-controlled study in patients with schizophrenia and schizoaffective disorder (N=40), adjunctive L-theanine 400 mg/day (ie, in addition to current antipsychotic medication) produced reductions compared with placebo for PANSS positive and general psychopathology subscale scores. PANSS negative subscale and negative factor scores were not different. Hamilton Anxiety Rating Scale scores for anxious mood, tension, concentration, muscular complaints, and sensory somatic complaints were also improved with L-theanine compared with placebo.(Ritsner 2011) Similarly, in a small open-label Japanese study (N=39; 17 patients with schizophrenia, 22 healthy subjects), L-theanine 250 mg/day added to ongoing antipsychotic medication for 8 weeks significantly improved PANSS (P=0.03) and sleep quality (P=0.008) total scores compared with baseline in those with schizophrenia. Additionally, brain scans revealed that L-theanine significantly affected concentrations of glutamate/glutamine in the frontal and inferior parietal regions; this effect was negatively associated with baseline values.(Ota 2015)
L-theanine 400 mg/day was evaluated for effects on objective sleep quality in pediatric males with attention-deficit/hyperactivity disorder (ADHD) (N=93; age range, 8 to 12 years) in a 6-week, randomized, placebo-controlled study. Data from Pediatric Sleep Questionnaires completed by parents showed a benefit with L-theanine compared with placebo for sleep efficiency, awakenings after sleep onset, and reduction in bouts of nocturnal activity. No difference between groups was seen for sleep latency or total sleep time. According to a 2013 systematic review, this was the only robust study identified between 1983 and 2013 that evaluated use of L-theanine for reducing sleep disturbances in patients with ADHD.(Barrett 2013, Lyon 2011)
Adjunctive administration of L-theanine 250 mg/day for 8 weeks significantly improved sleep scores in a study of symptomatic adults with major depressive disorder (P=0.03 vs baseline)(Hidese 2017) and total sleep quality scores in a study of adults with schizophrenia (P=0.008 vs baseline).(Ota 2015) In a double-blind, randomized, placebo-controlled trial, adults with GAD (N=46) with nonclinical levels of insomnia symptoms experienced significant reductions in insomnia scores with adjunctive use of L-theanine 450 mg/day for 8 weeks (P=0.007 vs placebo).(Sarris 2019)
Stress and anxiety
L-theanine crosses the blood-brain barrier, and most research has focused on its relaxing effect. A wakeful relaxation effect of L-theanine alone is apparent in most published data. The effect is weak in comparison with benzodiazepines and may differ based on consumption of L-theanine in the relaxed state versus an already anxious state.(Bryan 2008, Gomez-Ramirez 2009, Lu 2004, Owen 2008) Enhancements in brain resting alpha oscillatory activity have been reported with L-theanine in participants with high-anxiety traits.(Williams 2020)
Studies have evaluated the effect of L-theanine, alone or in combination with caffeine, in concentrations naturally found in tea. These studies predominantly use self-reporting measures of stress and electroencephalographic recordings of brain activity. However, study data are inconsistent in methodology and outcome measures, making comparisons difficult.(Dimpfel 2007, Dimpfel 2007, Dimpfel 2007, Einöther 2010, Foxe 2012, Giesbrecht 2010, Gomez-Ramirez 2009, Haskell 2008, Juneja 1999, Kelly 2008, Kimura 2007, Kobayashi 1998, Lu 2004, Nobre 2008, Rogers 2008, Williams 2020)
In a small crossover trial in 30 healthy Japanese adults with stress-related symptoms and no psychiatric disorder, L-theanine 200 mg/day for 4 weeks produced a significant improvement in stress-related depression, anxiety, and sleep symptom scores (P=0.019, P=0.006, and P=0.013, respectively). Between-treatment comparisons yielded a statistically significant improvement in 3 of the sleep subscores: latency (P=0.049), sleep disturbance (P=0.046), and use of sleep medication (P=0.047). No adverse events were observed.(Hidese 2019) In a systematic review of randomized controlled trials evaluating effects of L-theanine on anxiety and stress outcomes, an improvement in blood pressure in high-anxiety students was reported with administration of L-theanine 200 mg (P=0.0016 vs placebo).(Williams 2020)
In a phase 2 pilot study that enrolled 46 patients with GAD, adjunctive use of L-theanine (225 mg twice daily for 8 weeks) provided an improvement in insomnia scores (P=0.007) but not in anxiety scores compared with placebo. Reductions in insomnia scores were independent of changes in anxiety severity and occurred only in GAD patients without a diagnosis of clinical insomnia, but were correlated to baseline anxiety severity scores. Doubling the dose of L-theanine did not affect results. Similarly, caffeine intake did not appear to interact with any of the L-theanine outcomes. Adverse events were similar between groups.(Sarris 2019)
Significant dose-dependent reductions in haloperidol-induced orofacial dyskinesia symptoms were observed in rats administered oral L-theanine 30, 100, or 300 mg/kg for 35 days (P<0.001). Reductions ranged from 35.7% to 75.85% in vacuous chewing motion, 49.38% to 84.57% in tongue protrusion, and 48.2% to 77.8% in facial twitching. However, these outcomes were still significantly more pronounced compared with controls.(Chen 2018)
Immune system function
A limited number of studies suggest L-theanine may enhance the action of immune system components.
Animal and in vitro data
Animal and in vitro data have shown a reduction in histamine and proinflammatory cytokine release from mast cells.(Kim 2012) A reduction in NF-KB concentrations was observed in rats treated with doxorubicin plus L-theanine compared with a doxorubicin only group. The apoptotic index was also lower with L-theanine.(Altinkaynak 2018) Similarly, in a rat model of knee osteoarthritis, L-theanine reduced inflammatory and catabolic mediators as well as COX-2, inducible nitric oxide synthase, and NF-KB in chondrocytes. In vivo, cartilage degradation, proteoglycan expression, and osteoarthritic lesions were improved with L-theanine 200 mg/kg, with scores similar to the positive control (celecoxib).(Bai 2020)
A review of results from in vitro studies, a pilot study, and a small clinical trial suggests enhancement of gamma delta T lymphocytes may play a role in the observed decrease in cold and influenza symptoms with dietary L-theanine.(Bukowski 2008)
In contrast to placebo, 24-hour postrecovery interleukin 10 (IL-10) levels were lower than baseline and 1-minute postexercise levels in male competitive athletes who received L-theanine 150 mg supplementation for 6 weeks in a small, double-blind, placebo-controlled trial (N=20). Similarly, supplementation also increased the 24-hour postrecovery ratio of T-cells to natural killer cells compared with 1-minute postexercise levels. In contrast, L-theanine yielded no effect on the Th1/Th2 balance or the exercise-induced increase in levels of cytotoxic cells (ie, interferon-gamma, natural killer, T-delta/gamma, cytotoxic T lymphocytes). Neither IL-2 nor IL-4 were modulated by exercise or supplementation. No adverse events were reported.(Juszkiewicz 2019)
In vitro data
While certain constituents of a green tea extract, such as (-)-epigallocatechin gallate, attenuated the ethanol cytotoxicity in HepG2 cells treated with ethanol, L-theanine showed no hepatoprotective effect.(Lee 2008)
Note: 200 mg of L-theanine is approximately the amount found in 8 cups of tea.(Kahathuduwa 2018)
Robust, unequivocal data are currently unavailable to support dosing for any clinical use.
Supplementation with 50 mg or 200 mg of L-theanine has been used in healthy adults to attenuate acute caffeine-induced cerebral hemodynamics or behaviors and stress-induced increases in heart rate or blood pressure, respectively.(Dodd 2015, Kimura 2007, Rogers 2008, Yoto 2012)
Adjunctive L-theanine 250 mg/day or 400 mg/day for 8 weeks (ie, in addition to current antipsychotic medication) has been studied for use in improving PANSS positive and general psychopathology scores in patients with schizophrenia.(Ota 2015, Ritsner 2011)
Adjunctive use of L-theanine 250 mg/day or 450 mg/day (225 mg twice daily) for 8 weeks (ie, in addition to current antipsychotic medication) has been studied for improvement of some sleep measures in patients with major depressive disorder, schizophrenia, or GAD.(Hidese 2017, Ota 2015, Sarris 2019)
L-theanine is the precursor to ethylamine and glutamic acid; its plasma and urinary pharmacokinetics in humans have been observed to be similar when taken via oral capsules or consumed in green tea.(Scheid 2012) Peak plasma concentrations occur at 32 and 50 minutes after oral administration, with a half-life range of 58 to 74 minutes. It crosses the blood-brain barrier, with effects on brain activity apparent within 30 minutes and measurable up to 5 hours after administration(Bryan 2008, Dimpfel 2007b, Nobre 2008, Ota 2014, Yoto 2012).
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.(Ernst 2002)
Clinical data are limited. L-theanine counteracted the stimulatory effect of caffeine in rats, although at smaller doses, excitatory effects were observed.(L-theanine 2005) In human trials, L-theanine mitigated the stimulatory effects of caffeine on smooth muscle.(Dodd 2015)
Information regarding adverse reactions to L-theanine alone (versus combined with caffeine, as in tea) is lacking. Clinical trials used small numbers of participants and reported poorly on adverse events. One study among elderly participants recorded a higher number of reported headaches among those receiving 4 doses of L-theanine 250 mg.(Haskell 2008)
A decrease in mean HDL of 4.4 mg/dL (P=0.011) has been observed in adults with major depressive disorder who received adjunctive L-theanine 250 mg/day for 8 weeks.(Hidese 2017)
L-theanine is sold in the United States as a dietary supplement and has been granted FDA GRAS status at doses up to 250 mg per serving.(Kraska 2020)
The median lethal dose (LD50) of L-theanine is suggested to be 5 g/kg. Mutagenicity and acute and subacute toxicity tests have failed to show toxicity of synthetic L-theanine.(Juneja 1999)
A toxicity study in rats showed no effect on behavior, morbidity, mortality, body weight, hematology, or urinalysis. An increased incidence of renal tubule adenomas in a small number of female rats given high dosages (400 mg/kg body weight per day) was attributed to genetic predisposition.(Borzelleca 2006)
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