Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia
Open accessAbstract
Anxiety disorders are highly prevalent in modern societies, and are ranked the sixth most important contributor of non-fatal negative health outcomes. L-theanine is an amino acid naturally found in green tea (Camellia sinensis) and some other plant extracts, and recent clinical studies have proposed promising adjuvant effects of L-theanine for the negative impact of anxiety and psychological stress on health. In this integrative narrative review, we aimed to appraise and further discuss the effects of L-theanine administration on anxiety disorders and psychological stress. Published data suggests that L-theanine administered at daily doses ranging from 200 to 400 mg for up to 8 weeks are safe and induce anxiolytic and anti-stress effects in acute and chronic conditions. L-theanine at doses lower and higher than these may also show promising therapeutic potential; however, a more thorough investigation through randomized double-blind placebo-controlled crossover clinical trials are necessary to elucidate its effects for longer periods, providing further insights for meta-analyses and the development of recommendation guidelines. Additionally, animal studies investigating a higher dosage, its combination with other pharmacological compounds and associated metabolic comorbidities are recommended, as cases of hepatotoxicity associated with the consumption of green tea extract have been reported.
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- Findingcitation
L-theanine administration also improved depression and psychopathological symptoms in several studies.
“Overall, several studies have shown that the administration of L-theanine improved anxiety and stress outcomes, alongside improvements in other manifestations such as depression and psychopathological symptoms (Table 1).”
Quote in the paperSubstantial claim - Findingcitation
Several studies found that L-theanine administration improved anxiety and stress outcomes.
“Overall, several studies have shown that the administration of L-theanine improved anxiety and stress outcomes, alongside improvements in other manifestations such as depression and psychopathological symptoms (Table 1).”
Quote in the paperSubstantial claim - Findingown data
Only three studies were found that investigated the effects of green tea intake on anxiety and stress parameters.
“However, we found only three studies [28,30,37] that have investigated the effects of green tea intake on parameters of anxiety and stress.”
Quote in the paperNot a substantial claim0 of 3 sources checked - Findingown data
No study was found that performed a specific intervention with epigallocatechin gallate.
“For instance, we did not find any study that performed an specific intervention with epigallocatechin gallate (EGCG), an important component of green tea that may possess relevant antioxidant properties upon diseases of the nervous system [75].”
Quote in the paperNot a substantial claim - Findingnone given
In comparison with placebo, L-theanine intake was linked to lower positive psychopathology scores on the PANSS 3-factor dimensional model.
“Compared with placebo, L-theanine intake was associated with reduction of anxiety measured by the HARS, and positive and general psychopathology scores measured by the PANSS 3-factor dimensional model.”
Quote in the paperSubstantial claim
- Findingnone given
In comparison with placebo, L-theanine intake was linked to lower anxiety scores on the HARS.
“Compared with placebo, L-theanine intake was associated with reduction of anxiety measured by the HARS, and positive and general psychopathology scores measured by the PANSS 3-factor dimensional model.”
Quote in the paperSubstantial claim - Findingnone given
Under the 5-dimension model of psychopathology, L-theanine caused significant decreases in PANSS activation factor scores relative to placebo.
“According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive and activation factor scores compared to placebo.”
Quote in the paperSubstantial claim - Findingnone given
No side effects or adverse reactions of L-theanine supplementation at 200 to 400 mg daily for up to eight weeks have been reported so far.
“To the best of our knowledge, no side effects or adverse reactions of L-theanine supplementation at daily doses of 200 to 400 mg for up to eight weeks have been reported so far.”
Quote in the paperSubstantial claim - Findingnone given
In comparison with placebo, L-theanine intake was linked to lower general psychopathology scores on the PANSS 3-factor dimensional model.
“Compared with placebo, L-theanine intake was associated with reduction of anxiety measured by the HARS, and positive and general psychopathology scores measured by the PANSS 3-factor dimensional model.”
Quote in the paperSubstantial claim - Findingnone given
Under the 5-dimension model of psychopathology, L-theanine caused significant decreases in PANSS positive factor scores relative to placebo.
“According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive and activation factor scores compared to placebo.”
Quote in the paperSubstantial claim - Findingcitation
A 200 mg dose of L-theanine reduced heart rate responses to an acute stress task compared with placebo.
“200 mg of L-theanine L-theanine intake decreased heart rate and salivary immunoglobulin A responses to acute stress task when compared to placebo.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Abdou et al., 2006 [31] source
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- Findingnone given
L-theanine counteracted caffeine's effect on blood pressure.
“antagonized the effect of caffeine on blood pressure”
Quote in the paperNot a substantial claim - Findingnone given
L-theanine showed some evidence of relaxing effects on the tranquil-troubled subscale of the VAMS.
“showed some evidence for relaxing effects on the tranquil-troubled subscale of the VAMS.”
Quote in the paperSubstantial claim - Findingnone given
Neither L-theanine nor alprazolam produced significant anxiolytic effects during the experimentally induced anxiety state.
“Neither L-theanine nor alprazalam had any significant anxiolytic effects during the experimentally induced anxiety state.”
Quote in the paperSubstantial claim - Findingcitation
A 200 mg dose of L-theanine reduced salivary immunoglobulin A responses to an acute stress task compared with placebo.
“200 mg of L-theanine L-theanine intake decreased heart rate and salivary immunoglobulin A responses to acute stress task when compared to placebo.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Abdou et al., 2006 [31] source
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- Premisecitation
Sarris et al observed no significant cognitive effects.
“No significant cognitive effects were observed either.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [36] source
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- Premisecitation
The same trial found that L-theanine significantly improved general psychopathological scores.
“Ritsner and colleagues found in a double-blind randomized placebocontrolled clinical trial recruiting 60 patients diagnosed with chronic schizophrenia and schizoaffective disorder that L-theanine supplementation for 8 weeks combined with the respective ongoing antipsychotic treatment was able to significantly reduce anxiety and significantly improve general psychopathological scores [25].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] source
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- Premisecitation
L-theanine has an inhibitory effect on glutamine transporters, believed to be another major central nervous system mechanism.
“Interestingly however, an inhibitory effect of L-theanine on glutamine transporters was also identified [50,52], and this is believed to be another major mechanism of action of L-theanine in the central nervous system.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
In participants with high trait anxiety, posterior resting alpha activity was significantly higher with L-theanine than with matched placebo.
“White and colleagues, employing the technique of magnetoencephalography, found that posterior resting alpha activity was significantly higher in the high trait anxiety group receiving L-theanine as compared to the matched placebo group [29].”
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- Premisecitation
Healthy individuals given 200 mg L-theanine improved on the tranquil-troubled subscale of the Visual Analogue Mood Scale.
“Healthy individuals supplemented with 200 mg of L- theanine showed improvement in the tranquil-troubled subscale of the Visual Analogue Mood Scale (VAMS) [26].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] source
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- Interpretationcitation
Taking 200 mg L-theanine at bedtime may improve sleep quality through anxiolysis rather than sedation.
“Overall, it is suggested that the intake of 200 mg of L-theanine at bedtime may improve sleep quality by anxiolysis rather than sedation, as the conventional pharmacological treatment for insomnia [40].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [40] source
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- Interpretationreasoning
Collectively, the findings support a multifaceted potential of L-theanine supplementation across a wide clinical spectrum from children and adolescents to adults.
“Collectively, the aforementioned findings support a multifaceted potential of L-theanine supplementation in a wide clinical spectrum, from children and adolescents to adult subjects (table 1).”
Quote in the paperSubstantial claim - Interpretationcitation
L-theanine may lower blood pressure indirectly by reducing stress manifestations, inhibiting cortical neural excitation, and attenuating sympathetic activity.
“L-theanine may have the potential to lower blood pressure, possibly indirectly via reduction of the manifestations associated with stress, inhibiting cortical neural excitation and consequently attenuating sympathetic activity [35].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] source
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- Study design and conductcitation
The anxiety and stress findings were obtained using validated psychometric tools including HARS, Tension Anxiety Scores, PSQI, and PANSS.
“Such findings were obtained through the employment of several validated psychometric tools, including the Hamilton Anxiety Rating Scale (HARS), Tension Anxiety Scores, Pittsburgh Sleep Quality Index (PSQI), Positive and Negative Syndrome Scale (PANSS) [24,25], and others.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
L-theanine is considered a promising adjunct therapeutic tool for children and adolescents with ADHD-related sleep disturbances.
“For instance, L-theanine is considered a promising adjunct therapeutic tool for children and adolescents with ADHD-related sleep disturbances [44,45], a complex and challenging medical condition in young psychiatric patients [46].”
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- cites [45] source
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- Premisecitation
Sarris et al found no improvement in Hamilton Anxiety Rating Scale anxiety scores after L-theanine 450 to 900 mg per day for eight weeks in a double-blind placebo-controlled trial.
“More recently however, in the opposite direction Sarris et al did not find improvements in anxiety scores based on HARS, nor in the severity of insomnia based on the Insomnia Severity Index, after L-theanine supplementation (450-900 mg/d) in an 8-week double-blind placebo-controlled trial [36].”
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- Premisecitation
In that subset, L-theanine supplementation improved the cortisol to dehydroepiandrosterone sulfate ratio.
“Another publication [32] from the same research group, analysing a subset of 40 participants from the clinical trial referred above, observed improvements in circulating levels of brain-derived neurotrophic factor and cortisol to dehydroepiandrosterone sulfate ratio after L-theanine supplementation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] source
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- Premisecitation
In individuals with major depressive disorder who received 250 mg L-theanine, verbal memory and executive function improved on the Brief Assessment of Cognition in Schizophrenia.
“Additionally, verbal memory and executive function were improved in individuals diagnosed with Major Depressive Disorder (MDD) supplemented with 250 mg of L-theanine and tested for the Brief Assessment of Cognition in Schizophrenia (BACS) [24].”
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- Premisecitation
In a subset of 40 participants from that trial, L-theanine supplementation improved circulating brain-derived neurotrophic factor levels.
“Another publication [32] from the same research group, analysing a subset of 40 participants from the clinical trial referred above, observed improvements in circulating levels of brain-derived neurotrophic factor and cortisol to dehydroepiandrosterone sulfate ratio after L-theanine supplementation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] source
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- Premisecitation
Two reviewed studies found decreased blood pressure in adults with high stress response after supplementation with 200 mg L-theanine.
“Two of the appraised studies have found decreased blood pressure in adults with high stress response after supplementation with 200 mg of L-theanine [33,35].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Improvements in anxiety symptoms were often accompanied by improvements in biomarkers including salivary alpha-amylase, cortisol, chromogranin A, and immunoglobulin A.
“An overall improvement in anxiety symptoms was often accompanied by improvements in biomarkers, including salivary α-amylase, cortisol, chromogranin A and immunoglobulin A [27][28][29][30].”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Sarris et al found no improvement in insomnia severity on the Insomnia Severity Index after L-theanine 450 to 900 mg per day for eight weeks.
“More recently however, in the opposite direction Sarris et al did not find improvements in anxiety scores based on HARS, nor in the severity of insomnia based on the Insomnia Severity Index, after L-theanine supplementation (450-900 mg/d) in an 8-week double-blind placebo-controlled trial [36].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [36] source
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- Premisecitation
Ota et al found that L-theanine modulated glutamate+glutamine concentrations in frontal and parietal brain regions, a possible mechanism for its therapeutic properties.
“Interestingly, employing 1 H magnetic resonance spectroscopy (MRS), the researchers found that L-theanine modulated glutamate+glutamine concentrations in the frontal and parietal regions of the brain, which could be a possible mechanism underlying its therapeutic properties [47].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [47] source
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- Premisecitation
In mice, an orally administered GABA/L-theanine mixture had a synergistic sleep-enhancing effect, decreasing sleep latency and improving NREM sleep compared with individual administration.
“In that sense, Kim and colleagues showed that there is a synergistic sleep enhancement effect of orally administered GABA/L-theanine mixture, whose combination has led to decreased sleep latency and improved NREM sleep in mice, when compared to their individual administration [43].”
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- Premisecitation
L-theanine appears to inhibit neuronal glutamine uptake, possibly by competing for the glutamine transporter ASCT2/SLC1A5.
“The exact mechanism is yet to be fully elucidated, but it appears that L-theanine inhibits the uptake of glutamine by neurons [54], possibly via competition for the glutamine transporter Alanine-Serine-Cysteine transporter 2 (ASCT2), also known as SLC1A5 [55].”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
In a double-blind randomized placebo-controlled trial of 60 patients with chronic schizophrenia and schizoaffective disorder, L-theanine for eight weeks combined with ongoing antipsychotic treatment significantly reduced anxiety.
“Ritsner and colleagues found in a double-blind randomized placebocontrolled clinical trial recruiting 60 patients diagnosed with chronic schizophrenia and schizoaffective disorder that L-theanine supplementation for 8 weeks combined with the respective ongoing antipsychotic treatment was able to significantly reduce anxiety and significantly improve general psychopathological scores [25].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] source
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- Premisecitation
Ota et al reported improved sleep quality in schizophrenia patients after 250 mg per day L-theanine for eight weeks.
“Moreover, Ota et al reported improved sleep quality in schizophrenia patients after 250 mg/day of L-theanine for 8 weeks [47].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [47] source
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- Premisecitation
Ota et al found that 250 mg per day L-theanine for eight weeks added to ongoing antipsychotic treatment ameliorated symptoms in schizophrenia.
“In addition to improvement in sleep quality, Ota and colleagues also observed that the daily administration of 250 mg/day of L-theanine for 8 weeks added to the patients' ongoing antipsychotic treatment was effective in ameliorating symptoms in schizophrenia.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [47] source
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- Premisecitation
L-theanine effects align with improvements in several sleep quality parameters including actigraphy-monitored sleep, obstructive sleep apnoea, sleep inventory questionnaire, dysfunctional arousal, autonomic nervous system assessment, and paediatric sleep questionnaire.
“Said effects line up with improvements seen in several sleep quality parameters, including sleep monitored by actigraphy, obstructive sleep apnoea, sleep inventory questionnaire, dysfunctional arousal, autonomic nervous system assessment, and paediatric sleep questionnaire [40].”
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- Premisecitation
The first observed mechanism of L-theanine was antagonistic binding to NMDA, AMPA, and kainate subtypes of ionotropic glutamate receptors.
“Putatively, the firstly observed mechanism of action of L-theanine was its antagonistic action by binding to NMDA, AMPA and kainate subtypes of ionotropic glutamate receptors [50,51].”
Quote in the paperNot a substantial claim0 of 2 sources checked - Study design and conductnone given
An important limitation of the available studies is their short intervention period, no longer than eight weeks.
“However, an important limitation of the studies so far available refer to their short intervention period, no longer than eight weeks.”
Quote in the paperSubstantial claim - Premisecitation
Animal studies found that L-theanine administration seems to increase brain GABA levels.
“Corroborating such findings, studies employing animal models have found that the administration of L-theanine seems to increase GABA levels in the brain [43,49].”
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- cites [49]
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- Interpretationnone given
L-theanine may raise GABA concentrations.
“Likewise, L-theanine may increase serotonin and GABA concentrations”
Quote in the paperSubstantial claim - Premisecitation
High-dose green tea extract caused experimentally induced toxicity in rats and dogs.
“Experimentally induced toxicity by high dose administration of green tea extract has been observed in rats [82] and dogs [83].”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Several studies identified health benefits associated with green tea consumption, including improvements in cognitive decline, depression, and psychological disturbances.
“Several studies have identified health benefits associated with the consumption of green tea, including improvements in cognitive decline, depression and psychological disturbances [72][73][74].”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisereasoning
This competition reduces glutamatergic activation.
“Antagonistic action of L-theanine versus glutamine at the ASCT2 transporter attenuates glutamatergic activation”
Quote in the paperSubstantial claim - Premisecitation
Schmidt et al showed that a milk whey-based drink containing green tea extract increased working memory by modulating connectivity between the right superior parietal lobe and the middle frontal gyrus.
“In another study from the same University and employing comparable design, Schmidt et al showed that 250 or 500 mL of milk whey-based drink containing 2.75 g/L of green tea extract increased working memory by modulating the connectivity between the right superior parietal lobe and the middle frontal gyrus [79].”
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- Interpretationcitation
The roles of serotonin, GABA, and dopamine in neurophysiology support the clinical observations in mood and behavior, such as stress, fear, and social interaction.
“The neurophysiological roles of the three neurotransmitters corroborate the clinical findings in behavior and mood, including stress, fear and social interactions[62][63][64].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [62][63][64]
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- Premisecitation
In Swiss albino mice, L-theanine administration enhanced the toxic effects of strychnine.
“Additionally, a study on Swiss albino mice found that L-theanine administration enhanced the toxic effects of strychnine [84].”
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- Premisecitation
In the same study, GABA and L-theanine reduced beta wave predominance, but not at a statistically significant level.
“In the same study [31], both GABA and L-theanine reduced the predominance of beta waves, but not at a statistically significant level.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] source
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- Premisecitation
In a double-blind randomized cross-over study, 100 mg L-theanine reduced error rate in 27 volunteers during two-hour Sustained Attention to Response Task sessions.
“Interestingly however, in a double-blind randomized cross-over study, the administration of 100 mg of L-theanine reduced error rate but did not influence alpha wave activity in 27 volunteers on two-hour sessions of the Sustained Attention to Response Task (SART) test [81].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [81] source
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- Premisenone given
L-theanine competes with glutamine at the ASCT2 transporter.
“Antagonistic action of L-theanine versus glutamine at the ASCT2 transporter attenuates glutamatergic activation”
Quote in the paperNot a substantial claim - Premisereasoning
This leads to a reduced depolarization pattern.
“triggering a decreased depolarization pattern”
Quote in the paperNot a substantial claim - Interpretationnone given
The green tea doses used in those studies probably contain low amounts of L-theanine.
“However, the doses of green tea employed probably contain low amounts of L-theanine.”
Quote in the paperNot a substantial claim - Premisecitation
Shen et al found in a rat model of depression that oral L-theanine improved depressive-like behaviours.
“More recently, Shen and colleagues [59] found in a rat model of depression that L-theanine oral administration not only improved depressive-like behaviours, it also increased dopamine and serotonin levels in the prefrontal cortex, nucleus accumbens and hippocampus, as compared to the control group.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [59] source
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- Premisecitation
L-theanine-treated rats showed increased neural activity on 18F-fluorodeoxyglucose positron emission tomography scanning.
“Additionally, the L-theanine-treated rats showed increased neural activity when submitted to 18 F-fluorodeoxyglucose positron emission tomography (PET) scanning [61].”
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- Premisecitation
Yokogoshi et al found higher serotonin levels in rat striatum, hippocampus, and hypothalamus after intragastric L-theanine compared with saline-treated controls.
“Prior to that, Yokogoshi and colleagues had found significantly higher levels of dopamine in rat striatum after intragastric administration of L-theanine, alongside higher levels of serotonin in striatum, hippocampus and hypothalamus, as compared to the saline-treated controls [60].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [60] source
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- Premisereasoning
The reduction in glutamatergic activation occurs through decreased presynaptic glutamate production.
“via reduced presynaptic production of glutamate”
Quote in the paperSubstantial claim - Premisecitation
In that study, 100 mg L-theanine did not influence alpha wave activity.
“Interestingly however, in a double-blind randomized cross-over study, the administration of 100 mg of L-theanine reduced error rate but did not influence alpha wave activity in 27 volunteers on two-hour sessions of the Sustained Attention to Response Task (SART) test [81].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [81] source
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- Premisecitation
Cases of liver injury associated with green tea consumption have been reported in the medical literature.
“Cases of liver injury associated with the consumption of green tea have been reported in the medical literature [85][86][87][88].”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationnone given
L-theanine may raise serotonin concentrations.
“Likewise, L-theanine may increase serotonin and GABA concentrations”
Quote in the paperSubstantial claim - Premisecitation
L-theanine significantly increased the generation of alpha waves.
“Furthermore, similarly to GABA administration, L-theanine was able to significantly increase the generation of alpha waves [31], which are more predominant in adults at rest with eyes closed, but also in relaxed conditions.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] source
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- Premisecitation
Yokogoshi et al found significantly higher dopamine levels in rat striatum after intragastric L-theanine compared with saline-treated controls.
“Prior to that, Yokogoshi and colleagues had found significantly higher levels of dopamine in rat striatum after intragastric administration of L-theanine, alongside higher levels of serotonin in striatum, hippocampus and hypothalamus, as compared to the saline-treated controls [60].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [60] source
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- Premisereasoning
As a result, binding to ionotropic NMDA, AMPA, and kainate receptors on postsynaptic neurons is suppressed.
“consequently suppressed binding to its ionotropic NMDA, AMPA and kainate postsynaptic receptors”
Quote in the paperSubstantial claim - Premisecitation
Yamada et al reported an up to two-fold increase in dopamine levels induced by L-theanine perfusion in rat striatal brain.
“Yamada and colleagues have reported an increase of up to two-fold in dopamine levels induced by L-theanine perfusion in rat striatal brain [51].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [51] source
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- Interpretationnone given
L-theanine appears to raise dopamine levels.
“L-theanine appears to increase dopamine levels.”
Quote in the paperSubstantial claim - Premisereasoning
The influx of depolarizing sodium and calcium currents is impeded.
“Influx of depolarizing Na + and Ca ++ currents is hindered”
Quote in the paperSubstantial claim - Premisecitation
In a double-blind study, green tea extract increased dorsolateral prefrontal cortex activation in a dose-dependent manner compared with placebo.
“The researchers found that the administration of green tea extract increased activation in the DLPFC in a dose dependant manner, compared with the placebo administration [78].”
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- Premisecitation
Ogawa et al found that repeated L-theanine administration induced an anxiolytic effect in Wistar Kyoto rats, an animal model of treatment-resistant depression.
“Ogawa et al in turn found in Wistar Kyoto rats, an animal model of treatment-resistant depression, that repeated administration of L-theanine induced an anxiolytic effect [61].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [61] source
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- Premisecitation
Shen et al found that oral L-theanine increased dopamine and serotonin levels in the prefrontal cortex, nucleus accumbens, and hippocampus compared with controls.
“More recently, Shen and colleagues [59] found in a rat model of depression that L-theanine oral administration not only improved depressive-like behaviours, it also increased dopamine and serotonin levels in the prefrontal cortex, nucleus accumbens and hippocampus, as compared to the control group.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [59] source
Not checked in the free run.
- Interpretationreasoning
The reductions in heart rate and salivary immunoglobulin A responses to the acute stress task were probably due to less sympathetic motor activation.
“These results were likely attributable to attenuation of sympathetic motor activation.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 6
- May combine two claims. 22
Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).
Findingnone givenL-theanine reduced overall reaction time.
“L-theanine slowed overall reaction time on the”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenCaffeine raised self-rated alertness and jitteriness.
“caffeine increased self-rated alertness and jitteriness”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataL-theanine did not significantly alter jitteriness, alertness, or other mood aspects.
“did not significantly affect jitteriness, alertness or other aspects of mood”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationGABA-mediated central nervous system inhibition may be associated with L-theanine's anxiolytic effects and may help sleep disturbances, particularly in individuals with major depressive disorder.
“Regarding its clinical features, inhibition of the central nervous system mediated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may be associated with the anxiolytic effects of L-theanine, and such association may be helpful for sleep disturbances, particularly in MDD individuals [24,31].”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationPreclinical studies suggest that L-theanine has antipsychotic-like and possibly antidepressant-like effects.
“Preclinical studies suggest that L-theanine has antipsychotic-like and possibly antidepressant-like effects.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationThe authors emphasized L-theanine's beneficial effects, safety, and good tolerance at daily doses of 400 mg.
“The authors emphasized in both studies the beneficial effects of L-theanine alongside its safety and good tolerance at daily doses of 400 mg [25,32].”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationL-theanine appears to stimulate hippocampal brain-derived neurotrophic factor, act agonistically on NMDA receptors, and modulate central monoaminergic neurotransmitter systems.
“At molecular level, L-theanine appears to stimulate brain-derived neurotrophic factor (BDNF) in the hippocampus whilst agonistically acting on NMDA receptors, having also a modulatory effect on central monoaminergic neurotransmitter systems [38,39].”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationHidese et al found that L-theanine administration reduced depressive symptoms and improved cognitive function in patients with major depressive disorder.
“As discussed earlier, Hidese and colleagues found that L-theanine administration reduced depressive symptoms and improved cognitive function in MDD patients [24].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] source
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Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataMost of the studies reviewed were double-blinded.
“Most of the studies appraised in our review recruited from 12 to 60 participants, were double-blinded and tested the effects of L-theanine in doses ranging from 15 to 400 mg [24][25][26][27]29,[31][32][33][34][35].”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationWakabayashi et al found that L-theanine increased hippocampal brain-derived neurotrophic factor and acted agonistically on NMDA receptors, suggesting it may be a partial antagonist/agonist rather than only a full antagonist of the glutamate system.
“So much so that Wakabayashi et al found that L-theanine increased BDNF in the hippocampus and yielded agonistic action upon NMDA receptors, suggesting that L-theanine may not be a full antagonist of the glutamate system only, possibly being a partial antagonist / agonist [38].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [38] source
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May combine two claims.
Study design and conductcitationHidese's study was open-labelled, so its interpretation requires caution.
“It is however worth noting that Hidese's study was open-labelled, thus caution may be necessary on its interpretation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] source
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May combine two claims.
InterpretationreasoningL-theanine taken daily at 200 to 400 mg for up to eight weeks is safe and produces anxiolytic and anti-stress effects in both acute and chronic conditions.
“Published data suggests that L-theanine administered at daily doses ranging from 200 to 400 mg for up to 8 weeks are safe and induce anxiolytic and anti-stress effects in acute and chronic conditions.”
- Also stated in: § 9. Conclusion · hedged
“L-theanine administration at daily doses of 200 to 400 mg appears to confer anxiolytic and stress-reducing effects.”
Quote in the paperSubstantial claim- Also stated in: § 9. Conclusion · hedged
May combine two claims.
PremisecitationL-theanine is a glutamate analogue that binds to glutamate receptors and hinders the neuroexcitatory effects of glutamatergic activation.
“Structurally, L-theanine is a glutamate analogue, hence binding to the same glutamate receptors and therefore hindering the neuroexcitatory effects triggered by glutamatergic activation [48,49].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [48] source
Not checked in the free run.
- cites [49]
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe potential benefits appear promising for several psychological and psychiatric manifestations, including anxiety and stress, sleep disturbances, hypertension, major depressive disorder, schizophrenia, and schizoaffective disorder.
“The potential benefits appear to be promising for several psychological and psychiatric manifestations, encompassing the management of anxiety and stress alongside conditions such as sleep disturbances and even hypertension, as well as MDD, schizophrenia and schizoaffective disorder.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn rats, L-theanine was detected in neural tissue after intragastric administration and was transported via a leucine-preferring transport system.
“Also in rats, two separate studies from the same research group [60,67], detected the presence of L-theanine in neural tissue after its intragastric administration, and that this transport occurred via a leucinepreferring transport system.”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationIn stressed mice, L-theanine restored prefrontal TNF-alpha, IL-6, noradrenaline, and 5-HT levels, restored plasma corticosterone, and improved memory and hippocampal apoptosis.
“A recent experimental study showed that C57BL/J male mice subjected to chronic restrain-induced stress showed restored levels of TNF-α, IL-6, noradrenaline and 5-HT in the prefrontal cortex, restored plasma corticosterone levels, alongside improved memory and hippocampal apoptosis after L-theanine administration [80].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [80] source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe risk of toxicity from green tea intake or L-theanine supplementation is small but should not be neglected.
“On those grounds, the risk of toxicity induced by green tea intake or L-theanine supplementation is small but should not be neglected.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationReported green tea liver injury cases occurred in individuals consuming high volumes for long periods, combining green tea with other plant extracts, multicomponent mixtures or drugs, or with a history of liver disease.
“Despite its low prevalence, as far as it is known, such cases were observed in individuals consuming high volumes of green tea for long periods, in individuals who combined green tea with other plant extracts, multicomponent mixtures or other drugs, and in individuals with history of liver disease.”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenThe effects of L-theanine administration seem proportional to the magnitude of anxiety and stress.
“The effects of L-theanine administration seem be proportional to the magnitude of anxiety and stress.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationIn rats, L-theanine concentrations in liver and serum began to decrease after one hour, brain levels peaked at five hours then decreased, and total clearance occurred after 24 hours.
“In liver and serum, L-theanine concentrations started to decrease after 1 hour of its administration, whereas in the brain it peaked at 5 hours, when it started to decrease [67], and total clearance observed after 24 hours [67].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [67] source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone givenL-theanine at doses lower and higher than 200 to 400 mg may also be a promising adjuvant in the broad clinical spectrum.
“L- theanine at doses lower and higher than those may also be a promising adjuvant in the broad clinical spectrum.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationL-theanine content in dry green tea extract is about 1 to 2%, with approximately 25 to 60 mg in a typical 200 mL cup of tea.
“L-theanine content in dry extract is circa 1 to 2%, with approximately 25 to 60 mg of L-theanine in a typical 200 mL cup of tea [69].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [69]
Not checked in the free run.
May combine two claims.
PremisecitationGreen tea, being unfermented, contains higher amounts of L-theanine than oolong or black tea, and the extent of fermentation lowers L-theanine concentrations.
“However, as green tea is unfermented, it contains higher amounts of L-theanine than oolong or black tea; the extent of fermentation is a factor for lower L-theanine concentrations [70,71].”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Interpretationnone givenAcute effects of L-theanine are observed a few hours after intake, and its chronic effects also appear positive.
“Acute effects of L-theanine are observed few hours after its intake, and its chronic effects also appear to be positive.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationUnno et al found in rats that the plasma concentration of orally administered L-theanine peaked at 30 minutes.
“Unno and colleagues found in rats that the plasma concentration of orally administered L-theanine peaked at 30 minutes [66].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [66] source
Not checked in the free run.
May combine two claims.
PremisecitationAt the intestinal brush-border membrane, L-theanine absorption is mediated by a common Na+-coupled co-transporter, with lower affinity than glutamine.
“At the intestinal brush-border membrane, similarly to glutamine, L-theanine absorption is mediated by a common Na + -coupled co-transporter; however, its affinity to L-theanine is lower than that of glutamine [65].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [65] source
Not checked in the free run.
May combine two claims.
PremisecitationOgawa et al found significantly decreased glutamate and increased methionine in cerebrospinal fluid after L-theanine, suggesting positive modulation of hippocampal activity coupled with anxiolytic action.
“The researchers found significantly decreased glutamate and increased methionine levels in the cerebrospinal fluid after L-theanine administration, suggesting a positive modulation in hippocampal activity coupled with the anxiolytic action.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [61] source
Not checked in the free run.
The paper relies on this without support.
Existing families of anxiolytic drugs have well-documented side effects including toxicity, tolerability problems, tolerance, addiction, and withdrawal.
“Each family and their respective drugs however are known for their well-documented side effects, including toxicity, tolerability, tolerance, addiction and withdrawal issues, not covered in the present study.”
The paper relies on this without support.
L-theanine's main mechanism for reducing anxiety and stress is through glutamatergic neurotransmission.
“It is believed that L-theanine mediation on glutamatergic neurotransmission is the main pathway by which this nonproteinaceous amino acid is able to attenuate anxiety disorders and mitigate the negative outcomes of exposure to acute and chronic stress.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Other reviews on the topics of L-theanine and cognition, mood and sleep cite consistent conclusions.
“it is important to note that there are also other reviews on these topics that cite consistent conclusions (42, 59–62).”
From Effects of L-theanine on cognition, mood and sleep: evidence from human trials (2026) · cites this paper as [61]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
A cited green-tea study is instead an L-theanine drug trial
MinorThe review counts reference 37 among studies of green tea intake, but the cited paper's title describes pregnenolone and L-theanine added to antipsychotic therapy, not green tea intake.
“However, we found only three studies [28,30,37] that have investigated the effects of green tea intake on parameters of anxiety and stress.”
“37. A. Kardashev, Y. Ratner, M.S. Ritsner, Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial, Clin Schizophr Relat Psychoses. 12 (2018) 31-41.”
The citation lists haven’t been fetched yet
References 89 · Cited by 49
- Authors
- Lopes Sakamoto, F., Metzker Pereira Ribeiro, R., Amador Bueno, A., & Oliveira Santos, H.
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 147
- Pages
- 104395
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W2968814059
- Semantic Scholar
- 66457d4e5e6682be09f896da965378a3bbea9cee
- Cited by
- 49
- References
- 89
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 12 · 2022: 8 · 2021: 5 · 2020: 5 · 2019: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Worcester Research and Publications (University of Worcester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- theanine, anxiety disorders, psychological stress, anxiolytic effects, anti-stress effects, schizophrenia, green tea, Camellia sinensis, amino acid supplementation, hepatotoxicity
- MeSH terms
- Sleep Aids, Pharmaceutical, Animals, Antihypertensive Agents, Anxiety, Blood Pressure, Major Depressive Disorder, Depressive Disorder, Major, Glutamates, Humans, Psychotropic Drugs, Schizophrenia, Stress, Psychological
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