L-Theanine Benefits (Scientific Research)

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L-Theanine is considered an amino acid analogue of both L-glutamate and L-glutamine, and is commonly derived from various species of plants. L-theanine is perhaps best known for being present within green tea, and was scientifically noted as an element of green tea just before the year 1950. In addition to being present in green tea, it is also common in black teas and white teas brewed with the Camellia sinensis plant.

A majority of references to “theanine” are to the specific L-enantiomer or the levorotatory (left-handed) stereoisomer of theanine. While there is a D-theanine referring to the dextrorotatory enantiomer (right-handed), the D-enantiomer isn’t as well understood. The FDA (Food and Drug Administration) recognizes L-theanine as a “GRAS” (Generally Recognized As Safe) substance, which has lead many people to use it strategically as a dietary supplement.

Many people supplement with L-theanine to enhance cognitive function, especially in synergy with caffeine. The combination of both L-theanine and caffeine has been shown to improve IQ scores. Others have found the supplement beneficial for stress reduction, decreasing generalized anxiety, and reducing the severity of insomnia.

L-Theanine Mechanism of Action

Regardless of the source of L-theanine, it is apparent that the substance crosses the blood-brain barrier, altering various aspects of cortical function. The structure of L-theanine is considered similar in structure to glutamate, an excitatory neurotransmitter. As a result of the structural similarity, L-theanine is capable of binding to glutamate receptors to a minor extent.

L-theanine specifically binds to AMPA receptors, kainate receptors, as well as NMDA receptors to a minor extent; these are considered “ionotropic” glutamate receptors. At the AMPA and kainate receptors, L-theanine acts as an antagonist, while at the NMDA receptor it acts as an agonist. All of these receptors are known to aid in synaptic plasticity, hence L-theanine may be modulating synaptic strength and transmission.

It has also been discovered that L-theanine binds to Metabotropic Glutamate Receptors, specifically “Group I.” This means that L-theanine is affecting the release of glutamate and likely influencing voltage-dependent calcium channels. It notably blocks transporters of both glutamate and glutamine, inhibiting reuptake of these neurotransmitters; leading to increased extracellular levels.

Further effects on the umami taste receptor as a result of binding to the T1R1 + T1R3 heterodimer, leading to increased activation. Moreover, the ingestion of L-theanine increases levels of various neurotransmitters including: GABA, dopamine, serotonin, and glycine – in addition to levels of BDNF and NGF. In addition to a its effect on neurochemistry, L-theanine alters neuroelectrical activity, promoting increases in alpha brain waves.

Source: https://www.ncbi.nlm.nih.gov/pubmed/17182482

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L-Theanine Benefits (Scientific Research)

Most people think of L-theanine as a non-essential amino acid that promotes relaxation without sedation and/or grogginess. In other words, it elicits a minor anxiolytic effect to the extent that stress is reduced and concentration improves. There are many benefits associated with L-theanine supplementation including: anxiety reduction, cognitive enhancement, sleep quality improvement, and increased subjective well-being.

Anti-Aging: There is preliminary evidence to suggest that L-theanine supplementation may elicit an anti-aging effect. This evidence is based off of a study published in 2012 that analyzed the effect of L-theanine in Caenorhabditis elegans roundworms. The study involved placing L-theanine on agar plates and C. elegans processing the L-theanine.

Researchers noted that L-theanine increased the lifespan of C. elegans at various concentrations. Authors suggest that L-theanine may extend lifespan in mammals, and potentially humans. Drinking green tea has been suggested to extend lifespan in humans, providing an anti-aging effect. Perhaps the L-theanine content within green tea contributes to significant anti-aging properties.

Source: http://www.ncbi.nlm.nih.gov/pubmed/22422488

Anticancer: There is reason to believe that L-theanine may serve as an anticancer and antitumor agent. It has been studied in mice and noted to increase the proliferation of healthy T cells (e.g. gamma delta T cells), suppress tumor growth, and enhance the efficacy of anticancer drugs. Moreover, it appears to mitigate various adverse physiological adverse reactions induced by anticancer drugs.

2014: A study published in 2014 documented the effects of theanine-derivatives for the treatment of lung cancer. Researchers synthesized the following 4 derivatives: methyl coumarin-3-carboxylyl L-theanine (TMC), ethyl coumarin-3-carboxylyl L-theanine (TEC), ethyl 6-fluorocoumarin- 3-carboxylyl L-theanine (TFC), and ethyl 6-nitrocoumarin-3-carboxylyl L-theanine (TNC). Results demonstrate that these theanine-derivatives significantly inhibit cancerous cell migration and growth.

Moreover, these derivatives appear to elicit synergistic effects when co-administered with certain anticancer drugs. Due to the fact that these agents were considered effective and non-toxic in mice, they warrant investigation in humans as a potential adjunct therapy.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25138052

2009: A study published in 2009 analyzed the effect of L-theanine on human lung cancer and leukemia cells. It was determined that L-theanine was able to suppress growth of lung cancer and leukemia cell lines. It appeared as though the suppression was influenced by factors of L-theanine dosing as well as timing of administration.

In addition, authors reported that L-theanine enhanced the anticancer effects of various anticancer agents. Results note that L-theanine may have major therapeutic potential for the treatment of lung cancer and leukemia. It should be hypothesized that L-theanine may serve as a clinically beneficial adjunct therapy.

Source: http://www.ncbi.nlm.nih.gov/pubmed/19760127

2008: A report published in 2008 indicated that L-theanine enhances activation of gamma delta T cells. Gamma delta T cells are known to inhibit tumor growth and serve as protective agents within the body. This provides evidence suggesting that among individuals with tumors, administration of L-theanine may provide substantial benefit.

L-theanine may decrease the growth of tumors and spread of malignant cells. While L-theanine hasn’t been fully explored as an adjunct treatment for tumors in humans, it warrants investigation.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18156395

2008: L-theanine supplementation is known to enhance the function of gamma delta T lymphocytes, a specific type of “T cell.” These specific T cells are considered a first-line of protection against tumor cells. Specifically, when an individual ingests L-theanine they increase their levels of alkylamines – which serve to activate the gamma delta T lymphocytes.

As a result of L-theanine supplementation, tumor cells become less likely to propagate. When catechins (which are present in green tea) are combined with L-theanine, the two are thought to produce a synergistic effect. This research implies that L-theanine could halt the growth of (potentially cancerous) tumors.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18254876

2004: Many anticancer agents tend to produce adverse reactions and side effects. Since L-theanine has been discovered to enhance the efficacy of various anticancer agents, researchers investigated whether it may also minimize unwanted physiological effects of anticancer drugs. A study published in 2004 analyzed how L-theanine administration in mice affected glutamate and glutathione levels during treatment with doxorubicin.

L-theanine appeared to reduce a variety of adverse reactions from doxorubicin. Specifically, it was noted to increase glutamate concentrations within the body (liver and heart), without affecting concentrations in tumors. Further, it was noted that L-theanine attenuated glutathione reductions from doxorubicin administration while mitigating oxidative damage.

Source: http://www.ncbi.nlm.nih.gov/pubmed/15279898

1999: A study published in 1999 indicated that L-theanine derived from green tea may bolster the antitumor effects of doxorubicin. Researchers set up a study administering L-theanine along with doxorubicin to fight hepatic metastasis of M5076 ovarian sarcoma. Results indicated that the tumor was significantly altered with the combination of L-theanine and doxorubicin.

It was noted that liver weight increases were suppressed and hepatic metastasis was blocked. L-theanine was discovered to enhance efficacy of doxorubicin’s antitumor effect as well as its ability to suppress metastasis. Preliminary research incorporating L-theanine as an adjunct therapy for cancer is promising.

Source: http://www.ncbi.nlm.nih.gov/pubmed/10037191

Anxiety treatment: L-theanine is commonly used as an anxiolytic supplement. It is believed to decrease anxiety by acting on various neurotransmitters, most notably GABA and simultaneously increasing alpha waves. Increasing concentrations of GABA are beneficial among those who are stressed, and alpha waves tend to be abnormally low among individuals with heightened anxiety.

2012: A study published in 2012 documented the effect of L-theanine or caffeine on mental task performance and physiology when exposed to various physical and psychological stressors. A total of 14 participants engaged in the study during which they received either L-theanine and a placebo, caffeine and a placebo, or a standalone placebo. Results from the study demonstrated that L-theanine significantly decreased elevations in blood pressure, and notably decreased “Tension Anxiety” scores as measured by the Profile of Mood States.

The authors of the study suggest that L-theanine is capable of decreasing anxiety and simultaneously inhibits blood pressure spikes stemming from acute stress. While this was a relatively small-scale study, it provides preliminary evidence that L-theanine may provide therapeutic benefit for individuals with anxiety and may mitigate certain physiological responses to acute stress.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23107346

2011: In a study published in 2011, researchers sought to determine the effect of L-theanine on both attention and reaction time. They recruited a total of 18 participants, all of whom were considered healthy University students. Researchers measured levels of anxiety with the Manifest Anxiety Scale (MAS), and proceeded to divide the participants into 2 groups: a high-anxiety group and a minimal anxiety group.

Both groups were administered L-theanine (200 mg) and a placebo in this double-blind study. An estimated 15 minutes to 60 minutes post-administration of the L-theanine and placebo, participants completed a visual attention task and audio response test. Secondary measures included: State-Trait Anxiety Inventory (STAI), EEG alpha wave activity, and heart rate.

Results from the study suggested increased alpha waves, decreased heart rate, and performance enhancement among individuals with high-anxiety that were administered 200 mg L-theanine. Individuals with minimal anxiety levels didn’t experience noticeable improvement in these measures. This suggests that L-theanine may be a beneficial supplement for individuals with anxiety, possibly normalizing certain aspects of neuroelectrical activity and/or neurotransmission.

Source: http://www.sciencedirect.com/science/article/pii/S1756464611000351

2009: Rodent studies have also demonstrated anxiolytic effects upon administration of L-theanine. It was long suspected that interactions with the GABA-A receptor was a primary cause of these anxiolytic effects. To get a better understanding of how L-theanine affects rodents, researchers attained 55 rats and divided them into the following groups: saline, L-theanine, Flumazenil + L-theanine, or Midazolam + L-theanine.

Researchers assessed behavioral anxiety with the “elevated plus-maze,” and determined the total time spent in the open arm portion of the maze compared to total time in the maze. Evidence suggested that L-theanine does not elicit anxiolytic effects via interaction with the GABA-A receptor, but it does enhance the efficacy of a benzodazepine (Midazolam). Authors conclude that L-theanine may provide synergistic benefit for the treatment of anxiety when used with a benzodiazepine.

Source: http://www.ncbi.nlm.nih.gov/pubmed/20108732

2004: A study published in 2004 investigated the effects of L-theanine as an anxiolytic agent compared to Xanax (Alprazolam) (a sedative hypnotic drug) on behavioral measures of anxiety. The study was considered double-blind, placebo-controlled, and involved a total of 16 participants. The participants were assigned to receive either: Xanax (1 mg), L-theanine (200 mg), or a placebo.

The effects of the agents (L-theanine, Xanax, placebo) were analyzed in a “relaxed” condition and in an “anxiety” condition induced by researchers. Anxiety was measured with subjective self-reports including the BAI, VAMS, and STAI state anxiety scales. Measurements were collected prior to administration of the substances as well as following administration.

Administration of L-theanine appears to enhance relaxation during the “relaxation” condition based on scores of the VAMS, whereas Xanax was not noted to produce an increase. While neither substance produced clinically significant anxiolytic effects – L-theanine may produce relaxation effects during rest. L-theanine may not be a viable treatment for anxiety disorders, but it may function as an effective adjunct.

Moreover, it should be suggested that since benzodiazepines are linked to dementia (and are dangerous psychiatric drugs), L-theanine may be a favorable anxiolytic intervention for certain people (i.e. a Xanax alternative). That said, further larger-scale trials need to be conducted to elucidate any anxiolytic properties associated with L-theanine.

Source: http://www.ncbi.nlm.nih.gov/pubmed/15378679

2003: A study was published in 2003 investigating the effect of L-theanine administration on brain waves. Researchers specifically analyzed the effect of L-theanine on the production of alpha brain waves within the cortex. Alpha brain waves are associated with reductions in anxiety, increases in relaxation, and tend to promote calm states of consciousness.

Individuals with high anxiety generally record significant “alpha blocking” on an EEG (electroencephalograph). Alpha blocking means that the brain isn’t capable of producing sufficient alpha waves to help the individual relax. Those without adequate alpha activity tend to have an overabundance of beta waves and/or theta waves, causing heightened stress, poor focus, and reduced cognitive function.

Researchers in this study recruited 20 young adult males (18 to 30 years of age) in good physical and mental health. Following administration of L-theanine, researchers noted significant increases in alpha wave activity in the occipital regions of the brain compared to those who had been given a placebo. Authors of the study suggest that L-theanine supplementation promote alpha waves and yield an anxiolytic effect, perhaps in part due to neuroelectrical effects.

Source: http://www.koreamed.org/SearchBasic.php?RID=0124KJN/2003.36.9.918&DT=1

Blood pressure: There is modest evidence to suggest that L-theanine may reduce blood pressure. It seems to counteract stress-induced hypertension as well as caffeine-induced hypertension. While the mechanisms of blood pressure reduction associated with L-theanine aren’t well known, this effect may result from regulation of excitatory neural activity, increases in alpha waves, and other alterations in neurotransmission.

2012: A study published in 2012 sought to determine the effect of L-theanine on cognitive function when exposed to stress. One of the secondary measures recorded in the study was blood pressure. Researchers administered L-theanine + placebo, caffeine + placebo, or a placebo to 14 participants and documented the results.

Results suggested that high-stress individuals taking L-theanine had significantly lower blood pressure than other high-stress individuals when exposed to a stressor. Authors note that L-theanine’s blood pressure lowering effect may be associated with its anxiolytic effect. Its ability to lower blood pressure may be related to modulation of neural excitation and various physiological biomarkers.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23107346

2008: A study published in 2008 documented the effects of caffeine and theanine in a double-blind, placebo-controlled, randomized trial. A total of 48 adults were given either: theanine (200 mg), caffeine (250 mg), a combination of both, or neither. One of the secondary assessments in the study was blood pressure, which was recorded before supplementation and 40 minutes after.

Results indicated that theanine administration offset caffeine-induced hypertension in the combined treatment. This suggests that theanine may be an effective intervention for individuals dealing with caffeine-induced hypertension. Due to the fact that this was a relatively small study, follow up research is warranted.

Source: http://www.ncbi.nlm.nih.gov/pubmed/17891480

Brain waves: Many people with neurological conditions and/or high stress have abnormal brain waves (neuroelectrical activity) as evidenced by EEG (electroencephalograph) readings. While brain wave science is imperfect in that we cannot assume that everyone’s electrical activity should be the exact same, certain conditions may be exacerbated by excessive amounts of certain brain waves. For example, most individuals with high anxiety and stress tend to produce excessive amounts of beta waves with minimal amounts of alpha waves.

Beta waves are associated with concentration and external focus, but when they accumulate in excess or are present in regions of the brain not suited for beta activity, they can be problematic. A 2008 study investigated the effect of L-theanine consumption on brain wave (neuroelectrical) activity. For the study, researchers recruited 35 healthy participants and divided them into 2 groups: one received L-theanine (50 mg) and the other received a placebo.

EEG activity was measured in the participants prior to administration of L-theanine (or placebo), as well as at post-administration intervals of 45, 60, 75, 90, and 105 minutes. Researchers noted that L-theanine significantly increased alpha waves compared to the placebo. While no brain wave is utopian, many people dealing with excess stress and/or anxiety may benefit from enhancement of the alpha band via L-theanine.

It is unknown as to how long the alpha increase is sustained following L-theanine administration as well as if the effect is adaptogenic or restorative of homeostatic brain waves following a stressful event. In any case, enhancement of alpha activity may improve cognitive function, promote relaxation, and normalize certain aspects of abnormal neuroelectrical activity – particularly among those with “alpha blocking.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/18296328

Cognitive enhancement: While L-theanine doesn’t appear to significantly enhance cognitive function as a standalone supplement, there is ample evidence to suggest that L-theanine provides synergistic cognitive enhancement when co-administered with caffeine. Many studies listed below have employed an administration ratio of approximately 2:1 (L-theanine to caffeine). If your goal is to enhance cognitive function with L-theanine, the science suggests you’re best suited supplementing it with caffeine.

2014: A meta-analysis published in 2014 analyzed the effect of L-theanine administered alone and/or with caffeine for its effect on cognitive function and mood. The meta-analysis incorporated results from 11 studies with randomized, placebo-controlled designs. Assessments in these studies measured: the Bond-Lader scale (alertness, calmness, contentedness), State-Trait Anxiety Inventory (anxiety), and various cognitive measures (attention switching, intersensory attention, and visual information processing).

Results indicated that L-theanine with caffeine provided the most cognitive enhancement. This was based primarily on significant improvements in measures of alertness and attentional switching accuracy; suggesting increases in cognitive flexibility. This meta-analysis provides evidence to suggest substantial cognitive enhancement effects can be attained from L-theanine when administered in conjunction with caffeine.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24946991

2013: Researchers analyzed the effect of L-theanine administration on cognitive function among mice that were exposed to CRS (chronic restraint stress). The stress was induced by restraining the mice in polypropylene tubes for 8 hours per day for 21 straight days. L-theanine was administered prior to the stress at 2 mg/kg and 4 mg/kg.

The mice’s cognitive function was assessed with a Morris water maze. Results demonstrated that mice exposed to CRS (chronic restraint stress) exhibited cognitive deficits and altered levels of neurotransmitters. L-theanine administration reversed cognitive deficits as a result of the restraint stress, plus reversed oxidative damage and restored normative neurotransmission.

This suggests that L-theanine clearly prevents cognitive dysfunction as a result of excess stress in mice. It should be hypothesized that similar outcomes may be evident for humans. Further research is necessary to understand L-theanine’s ability to protect and/or restore cognition under stress.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23395732

2010: A study published in 2010 analyzed the combination of L-theanine with caffeine. The researchers specifically assessed measures of cognitive function, alertness, blood pressure, and heart rate in a sample of 44 young-adult participants. The participants were divided into two groups, one of which received L-theanine (97 mg) + caffeine (40 mg), and the other of which received a placebo.

Measures of cognitive function, self-reported mood, blood pressure, and heart rate were measured prior to administration of L-theanine + caffeine OR the placebo. In addition, these measures were assessed at intervals of 20 minutes and 70 minutes post-administration. Results suggested that the combination of L-theanine + caffeine enhanced accuracy of “task switching” tests and alertness.

On measures of other aspects of cognition, there wasn’t a significant difference between L-theanine + caffeine and the placebo. That said, improved task switching is significant in that it is indicative of cognitive flexibility. Authors imply that using L-theanine with caffeine can promote sustained mental alertness and improve select measures of cognitive function.

Source: http://www.ncbi.nlm.nih.gov/pubmed/21040626

2008: Evidence from a study published in 2008 highlights the cognitive enhancing effect of L-theanine when used in conjunction with caffeine. Researchers measured aspects of cognitive function such as word recognition, speed of visual information processing, attention switching, mood, etc. They recruited 27 participants for the study, and measures were recorded at baseline, plus following administration (once at 60 minutes, and again at 90 minutes).

It was noted that L-theanine plus caffeine improved speed and accuracy of performance during an “attention-switching” task at 60 minutes. In addition, results suggested that susceptibility to distraction significantly decreased at intervals of 60 minutes and 90 minutes post-administration. Authors highlight the synergistic effect of L-theanine and caffeine, documenting that the supplemental tandem significantly enhances performance when faced with cognitively demanding tasks.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18681988

2008: Another study published in 2008 analyzed the effects of L-theanine and caffeine on cognitive function and mood. Researchers set up a double-blind, placebo-controlled, randomized design to assess how L-theanine and caffeine affect cognitive function and mood. This particular trial was unique in that it sought to determine the isolated effects of L-theanine (250 mg) and caffeine (150 mg) in addition to the synergistic effects.

L-theanine in isolation actually reduced accuracy of certain measures of cognitive function (e.g. serial subtractions). Caffeine in isolation sped up reaction time, increased accuracy on visual information processing, and decreased fatigue. That said, the combination of L-theanine + caffeine elicited significantly more benefit than either substance in isolation.

Benefits of the combination included: expedited visual information processing, reduced mental fatigue, faster reaction times, quicker working memory function, increased accuracy on a “sentence verification” task, plus a faster reaction time on a “delayed word recognition” task.” While L-theanine may not provide substantial cognitive enhancement as a standalone supplement, co-administration of L-theanine with caffeine provides greater cognitive enhancement than standalone caffeine and may help you increase your IQ score.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18006208

2006: Research published in 2006 implied that L-theanine may enhance cognitive function and provide neuroprotective benefit. Based on some animal research, it has been discovered, that L-theanine alters levels of GABA, dopamine, and serotonin, while simultaneously affecting AMPA, kainate, and NMDA receptors. In animal research, L-theanine has been shown to alter behavior to promote enhancement of learning ability and memory function.

The complex mechanism of L-theanine may contribute to this nootropic-esque effect. While significantly more research is necessary to understand the potential cognitive benefits associated with L-theanine administration in humans, many believe that supplementation could be conducive to certain aspects of cognitive function.

Source: http://www.ncbi.nlm.nih.gov/pubmed/17182482

Neuroprotective effects: L-theanine has long been speculated to act as a neuroprotective agent, and there’s plenty of research to support this speculation. While the degree to which it elicits neuroprotective effects isn’t well-known, most research suggests that it is likely to provide benefit. There is significant evidence that L-theanine is neuroprotective in animals, possibly via its antagonist action on Metabotropic Glutamate Receptors.

2014: A rodent study involving L-theanine administration to rats demonstrated neuroprotective effect upon administration of 100 mg/kg and 200 mg/kg doses. For the study, researchers administered either L-theanine orally (100 mg/kg or 200 mg/kg) prior to utilizing the substance (3-NP) to induce Huntington’s-like symptoms. The L-theanine was administered once per day approximately 1 hour before the 3-NP treatments.

Measures of the following were recorded: Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) levels, mitochondrial enzyme complex, and Succinate dehydrogenase (SDH). Results indicated that L-theanine reduced oxidative stress from (3-NP), decreased neuronal damage, and restored SOD, GSH, CAT, and SDH biomarkers. Authors highlight the apparent neuroprotective effect against (3-NP) neurotoxicity.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24325390

2013: Researchers investigated the neuroprotective effect of L-theanine when administered to rats following a stroke. In rat models of stroke, researchers administered L-theanine at doses of 1 mg/kg and 4 mg/kg. The L-theanine was administered at various intervals following the stroke (3 hours, 12 hours, and 24 hours).

It was noted that L-theanine administered 3 hours and 12 hours following the stroke resulted in significantly less dead tissue (resulting from lack of blood supply). In other words, L-theanine lessened the brain damage, suggesting neuroprotective effects. Authors note that L-theanine provides neuroprotective benefit for rat models of brain injury, likely due its effect on glutamate receptors.

It is unknown as to whether this would have similar effects in humans. While there are often similarities between human and rodent trials, there are often differences. It should be hypothesized that L-theanine could provide benefit to human stroke victims when administered within 12 hours of the stroke.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23097345

2011: A study published in 2011 noted that L-theanine crosses the blood-brain barrier and provides cerebroprotective effects, preventing brain cell death following a transient ischemic attack. Authors note that the protective effect is a direct result of L-theanine’s antagonist effect on the AMPA and kainate receptors. As a result of the cerebroprotective effect of L-theanine, researchers sought to determine whether it may provide benefit to elderly individuals with cognitive deficits.

It was reported that elderly individuals who consumed green tea (with 47.5 mg L-theanine) demonstrated significantly less cognitive decline than a placebo group. Authors suggest that L-theanine administration could improve cognitive function among elderly individuals. This improvement in cognitive function may be related to neuroprotective mechanisms.

Source: http://www.ncbi.nlm.nih.gov/pubmed/21477654

2008: A study published in 2008 documented various neuroprotective effects of L-theanine. Researchers noted that L-theanine can elicit an anti-ischemic effect, possibly preventing strokes in certain individuals. For this study, researchers administered L-theanine to cultured human doapminergic cell line SH-SY5Y to determine whether it could provide protection against neurotoxicity as a result of Parkinson’s-inducing neurotoxins (Rotenone and Dieldrin).

Results suggested that 500 microM of L-theanine decreased cellular death and DNA fragmentation as a result of the neurotoxins. In addition, L-theanine administration prevented reduction of GDNF and BDNF levels, both important neurotrophins. This research suggests that L-theanine may prove clinically therapeutic for the prevention of Parkinson’s disease.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18452993

2006: A report published in 2006 noted that L-theanine acts as a neuroprotective agent among animals. They hypothesize that the neuroprotective effect may result from L-theanine’s effect as a Metabotropic Glutamate Receptor (Group I) antagonist. Despite the fact that L-theanine displays a notable neuroprotective effect in animal studies, it is unclear whether these effects are apparent in humans.

Source: http://www.ncbi.nlm.nih.gov/pubmed/17182482

Neurotransmitter levels: L-theanine may alter concentrations of neurotransmitters, promoting healthy brain function, especially following exposure to stress. Most reports suggest that L-theanine affects GABA, while eliciting secondary effects on norepinephrine and serotonin. Some reports suggest that L-theanine can increase cerebral concentrations of GABA by nearly 20%.

A report published in 1998 indicated that brain tryptophan (a precursor to 5-HT) significantly increased, but serotonin levels actually decreased as did 5HIAA. The researchers believed that L-theanine enhanced breakdown of serotonin while simultaneously decreasing synthesis. Older rodent studies suggest that norepinephrine levels are also decreased with L-theanine, but this effect can be reversed with caffeine.

For certain individuals, L-theanine may elicit favorable alterations in the levels of neurotransmitters, particularly GABA. If you buy into the theory that too much serotonin causes social anxiety, perhaps administration of L-theanine could help; reducing both serotonin, increasing GABAergic activity, and decreasing norepinephrine.

Source: http://www.ncbi.nlm.nih.gov/pubmed/4397636

Source: http://www.ncbi.nlm.nih.gov/pubmed/9614715

Source: http://www.ncbi.nlm.nih.gov/pubmed/3769108

Obesity: There isn’t significant research that has studied L-theanine as an anti-obesogenic agent. Some believe that L-theanine may help reverse certain symptoms of obesity due to the fact that it alters food intake, reduces body weight, and fat accumulation in rats. It is unclear as to whether L-theanine offers similar benefit in humans, therefore further research is warranted to decipher any anti-obesogenic mechanisms of this supplement.

2008: In 2008, a report was published that documented the effect of L-theanine administration on rat feeding. It was determined that oral administration of L-theanine suppressed the food intake of rats. Specifically, L-theanine appears to alter insulin concentrations (reducing them) and corticosterone concentrations (increasing them).

Authors suggested that L-theanine notably altered hormone levels of the rats, thereby yielding an appetite suppressant effect. This finding necessitates further investigation, particularly in human trials; it remains unknown as to whether similar effects would occur in humans.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18460793

2004: A study in 2004 determined the anti-obesogenic effects of catechins, caffeine, and L-theanine (all within the contents of green tea). They tested the effects of these three substances in mice that were fed diets of 2% green tea powder – containing varying amounts of each over a 16 week period. Results indicated that L-theanine and caffeine were responsible for reductions in body weight and body fat.

Evidence suggests that all three of the substances: catechins, caffeine, and L-theanine work in synergy to prevent obesity. While this study was conducted on mice, it should be hypothesized that similar results may occur in humans.

Source: http://www.ncbi.nlm.nih.gov/pubmed/15011752

PTSD: A study published in 2014 indicated that L-theanine may provide benefit for those suffering from PTSD. To test this hypothesis, researchers administered L-theanine to a group of rats and noted gene expression changes in specific regions within the brain, including the amygdala and hippocampus. It appeared as though L-theanine administration modulated the expression of 17 genes, of which 5 were in the amygdala and 3 in the hippocampus.

While it wasn’t clear whether these changes in expression proved to be therapeutic, there were notable changes. It could be hypothesized that L-theanine administration may therapeutically modulate specific PTSD-induced abnormalities in the amygdala and the hippocampus. Further research is necessary to understand the expressional changes in the aforementioned regions.

It is possible that L-theanine may provide benefit as an adjunct treatment for the anxiety and/or stress associated with PTSD. Furthermore, it may be used to restore neural homeostasis among individuals attempting to overcome PTSD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25165739

Schizophrenia: There is preliminary evidence suggesting that L-theanine can reduce certain symptoms of schizophrenia. While it may not provide relief when used as a standalone agent, it appears to provide additional benefit when administered as an adjunct to an antipsychotic drug. Specifically, L-theanine is capable of decreasing anxiety levels and reducing the prevalence of positive symptoms such as hallucinations and delusions.

2015: Individuals diagnosed with schizophrenia have been suggested to have abnormal neurotransmission associated with glutamate. Since L-theanine influences glutamate neurotransmission, some studies suggest that administration could alleviate and/or reduce certain symptoms of schizophrenia. In 2015, researchers published a study analyzing the effect of L-theanine among patients diagnosed with “chronic schizophrenia.”

They specifically looked at various measures including glutamate and glutamine levels. A total of 17 participants engaged in the study and received L-theanine (250 mg/day) as an adjunct to antipsychotic treatment for a period of 8 weeks. Measures were recorded with the PANNS (Positive and Negative Syndrome Scale) and the Pittsburgh Sleep Quality Index.

Results indicated that positive symptoms of schizophrenia were reduced and sleep quality improved following administration of L-theanine. That said, there were no significant changes in levels of glutamate nor glutamine following 8 weeks of treatment. Authors suggest that the L-theanine aids in stabilization of glutamate, thereby reducing certain symptoms (e.g. hallucinations and delusions) and improving sleep quality.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25896423

2011: Due to the fact that L-theanine is capable of enhancing cognitive function, decreasing stress, and reducing anxiety – researchers decided to investigate supplementation among individuals with schizophrenia. A study published in 2011 determined both the therapeutic efficacy and safety of L-theanine administration as an adjunct to an antipsychotic medication. All 60 participants in the study had been diagnosed with either schizophrenia and/or schizoaffective disorder based on DSM-IV criteria.

The study lasted for 8-weeks and was considered double-blind, placebo-controlled, and randomized. Individuals received either a placebo or L-theanine (400 mg) as an adjunct to their antipsychotic medication. Measures prior to treatment were recorded with the PANNS (Positive and Negative Syndrome Scale), HARS (Hamilton Anxiety Rating Scale), and CANTAB (Cambridge Neuropsychological Test Automated Battery.

Results suggested that individuals receiving the L-theanine as an adjunct had significantly less anxiety as evidenced by HARS scores, and fewer positive symptoms as recorded by the PANNS. Furthermore, L-theanine was considered safe and well-tolerated over the 8-week term. Results suggest that L-theanine may improve treatment outcomes among those diagnosed with schizophrenia.

It is logical to also suspect that L-theanine may improve various cognitive symptoms of schizophrenia. While this study is not considered long-term nor large-scale, it provides evidence that L-theanine may prove therapeutic among those with schizophrenia when administered as an adjunct treatment. Some may consider it to be among favorable natural remedies for schizophrenia, especially when used in conjunction with other substances.

Source: http://www.ncbi.nlm.nih.gov/pubmed/21208586

Seizures: There is a well-established link between GABAergic activity and seizures. In a study published in 2013, researchers attempted to determine the effect of L-theanine on mice models with limbic seizures and generalized seizures. The researchers also noted the impact of L-theanine on glutamate and GABA concentrations via microdialysis.

Results demonstrated that L-theanine significantly decreased occurrences of limbic seizures, but actually increased susceptibility to generalized seizures. An increase in generalized seizures was associated with heightened levels of GABA in the prefrontal region. It is unknown as to whether findings would be similar in other animal models or humans, but a decrease in limbic seizures could offer therapeutic benefit in certain individuals.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23324588

Sleep enhancement: There is increasing evidence to suggest that L-theanine can enhance sleep quality and efficiency. L-theanine promotes sleep via a subtle anxiolytic effect, altering levels of neurotransmitters and enhancing alpha brain waves. In addition, supplementation does not promote drowsiness, cause dependence, or lead to adverse reactions – making it favorable over pharmaceutical options.

2015: It is well-established that most “sleeping pills” are problematic in regards to side effects and dependence. A person who takes a sleeping pill at night is at increased risk of “next-day” motor vehicle accidents and/or related accidents associated with operating heavy machinery. In addition it appears as though most sleeping pills are dangerous to long-term brain health; some cause permanent memory impairment.

For this reason, many have turned to herbal sleep aids like L-theanine. A study published in 2015 investigated the effect of L-theanine on sleep. It appears as though taking L-theanine (200 mg) prior to bed may enhance sleep quality via a non-sedating anxiolytic effect. In other words, it reduces anxiety, promotes alpha brain waves, and allows people that are stressed to sleep.

Moreover, a notable advantage of L-theanine over traditional sleeping pills is that it doesn’t cause drowsiness. Researchers noted that doses up to 2000 mg per day produced no significant adverse effects. This publication provides substantial evidence that L-theanine is an effective supplement for enhancing sleep.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25759004

2015: Another study investigated the effects of L-theanine among individuals diagnosed with schizophrenia. In this study, the L-theanine was administered for 8 weeks along with an antipsychotic medication. Researchers recruited 17 participants and documented sleep quality with the Pittsburgh Sleep Quality index.

Results suggested significant improvement in sleep quality over the 8 weeks as a result of L-theanine supplementation. Authors suggested that sleep quality may have improved as a result of glutamatergic modulation. While this study was conducted strictly among individuals with schizophrenia, sleep quality improvements from L-theanine may also be apparent among those with normative mental health.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25896423

2013: A study published in 2013 sought to review evidence on using sleep medications among individuals with ADHD. Those with ADHD often take stimulant medications which promote insomnia and reduced sleep quality. Researchers found 5 articles that fit the inclusion criteria for their review.

Evidence from their report suggested that Ambien (Zolpidem) and L-theanine each were ineffective for reducing sleep latency and increasing total sleep time. However, L-theanine significantly improved sleep efficiency without substantial side effects. Ambien produced significant side effects and wasn’t well-tolerated.

The results indicate that L-theanine may be a beneficial supplement for individuals with ADHD who are unable to get quality sleep. It should be noted that melatonin improved sleep latency, sleep time, and efficiency. Perhaps the combination of L-theanine and melatonin could provide synergistic benefit.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24261659

2012: A study published in 2012 determined the effect of L-theanine administration on excitatory responses following caffeine consumption in rats. Specifically, researchers wanted to determine whether L-theanine could alter caffeine-induced sleep abnormalities in the rats. The rats were set to receive either: saline and saline (control), caffeine and saline, or caffeine followed by L-theanine.

Researchers recorded degrees of wakefulness, transitions to slow-wave sleep, slow-wave sleep, and rapid-eye movement (REM) activity) sleep. Caffeine was noted to increase wakefulness and decrease slow-wave sleep and rapid-eye movement sleep. L-theanine administration was able to offset caffeine-induced slow-wave sleep decreases.

Authors suggest that L-theanine can reverse caffeine-induced slow-wave sleep abnormalities. It remains unclear as to whether similar effects would be noted among humans. The basis for a future study could be to determine whether L-theanine yields this same effect and/or perhaps additional sleep benefits that aren’t observed among rats.

Source: http://www.ncbi.nlm.nih.gov/pubmed/22285321

2011: A study published in 2011 analyzed the efficacy of L-theanine as a sleep aid, primarily for increasing quality, among 98 children (8 to 12 years of age) diagnosed with ADHD. All children were males, and the study was considered double-blind, placebo-controlled, and randomized. The children received either a placebo or tablets with 400 mg L-theanine.

The study lasted 6 weeks, and participants were evaluated with a Pediatric Sleep Questionnaire (PSQ) as well as with an actigraph administered via the wrist. Results suggested that L-theanine significantly increased sleep percentage and sleep efficiency compared to those receiving a placebo. Authors noted that administration of 400 mg L-theanine was effective for improving certain aspects of sleep quality.

That said, it is unknown whether these results would be similar in a more diverse sample; all of the participants were children, boys, and had ADHD. It is possible that L-theanine may enhance sleep quality in general populations.

Source: http://www.ncbi.nlm.nih.gov/pubmed/22214254

Stress reduction: There is modest evidence to suggest that L-theanine may reduce stress and help combat stress via anxiolytic effects. There are numerous studies documenting L-theanine’s ability to reduce anxiety and mitigate stress-induced cognitive deficits. L-theanine administration may reverse stress-induced cognitive dysfunction in humans.

2007: Researchers have long known that L-theanine inhibits binding of L-glutamic acid to glutamate receptors in the brain. A study published in 2007 investigated the administration of L-theanine on psychological and physiological states under stress. For the study, researchers induced stress with a mental arithmetic task; this served as an “acute stressor.”

A total of 12 participants were exposed to 4 trials: the first involved L-theanine supplementation prior to the experiment, the second involved L-theanine supplementation halfway through the experiment, while the remaining two served as controls and involved a placebo or nothing. Results from the study suggested that L-theanine reduced heart rate and salivary immunoglobulin A responses to stress compared to a control. Authors noted that L-theanine administration modulated activation of the sympathetic nervous system.

They specifically suggested that L-theanine may reduce stress by inhibiting excitatory neural activity. Although this was a small-scale study, it confirms previous findings that have suggested anti-stress effects associated with L-theanine.

Source: http://www.ncbi.nlm.nih.gov/pubmed/16930802

What are the most prominent benefits of L-theanine supplementation?

Perhaps the most notable benefit derived from L-theanine supplementation is cognitive enhancement. While L-theanine doesn’t appear to enhance cognition as a standalone agent, there is robust evidence indicating that when administered with caffeine, cognitive measures improve to a greater extent than isolated caffeine administration. Therefore it appears to be a potent, synergistic cognitive enhancer when consumed with caffeine.

There is also substantial evidence to suggest that L-theanine acts as an anxiolytic, and can mitigate cognitive impairment associated with acute stress. Among individuals without sufficient alpha brain waves, L-theanine appears to increase their levels – perhaps normalizing them. Some evidence even suggests that L-theanine may enhance the anxiolytic efficacy of a benzodiazepine agent.

In addition, L-theanine appears to improve certain measures of sleep quality and efficiency, plus yields anticancer and antitumor effects. There is mounting evidence to suggest that L-theanine (and various derivatives) may decrease susceptibility to cancer, tumors, and enhance efficacy of anticancer drugs. L-theanine appears to be a very safe supplement and conducive to optimal neurophysiological health without any known adverse reactions or drawbacks.

Are there any drawbacks associated with L-theanine supplementation?

The scientific literature on L-theanine does not suggest any significant side effects nor adverse reactions. In addition, there don’t appear to be any substantial drawbacks associated with taking L-theanine. Some studies have gone as far as to document the effects of L-theanine administration up to 2000 mg per day – and failed to find any drawbacks.

Therefore even at supratherapeutic doses, no substantial adverse reactions have been noted. The drug may slightly decrease certain measures of cognitive function when administered at high doses as a standalone (i.e. without caffeine). That said, L-theanine should be considered a safe supplement – and is recognized as such by the FDA with “GRAS” (Generally Recognized As Safe) status.

Note: Certain drawbacks may be subject to individual variation and/or subjectivity.

Limitations associated with L-theanine research…

While most research with L-theanine isn’t problematic, there are some limitations to consider. These limitations in the research include: lack of human studies, small numbers of participants, dosage variation, and variations in the type of L-theanine administered.

Dosage variation: The dosage of L-theanine used in research has been largely subject to variation based on the particular study. Researchers should attempt to come up with a dosing criteria for humans based on the particular condition being targeted. In other words, determine the dosage at which L-theanine elicits the greatest therapeutic effect (based on the condition).

Evaluation criteria: When evaluating L-theanine, primary measures should be kept consistent based on the condition. For example, if L-theanine is being investigated as a cognitive enhancer, primary cognitive assessments should be selected in conjunction with past-research as should secondary measures. By maintaining a consistent evaluation criteria, past evidence can be better understood (possibly strengthened or debunked).

Participants: There is an need for increased participant diversity in L-theanine research. Specifically, researchers should focus on incorporating individuals of various ages and sexes in their trials. While it is important to understand L-theanine’s effect in specific subsets of the population such as young adults or individuals with ADHD – diversification of samples in larger scale studies is necessary.

Small-scale studies: A majority of L-theanine studies are small-scale, meaning they do not contain a significant number of participants. Ideally, researchers would recruit hundreds or thousands of participants and set up a double-blind, placebo-controlled, randomized study. Results from small-scale studies need to be confirmed by larger-scale trials due to the fact that small samples may skew trial outcomes.

Short-term trials: Many of the trials associated with L-theanine document immediate benefits following administration, but fail to account for long-term effects. It is unknown as to whether many L-theanine benefits can be maintained when the supplement is administered on a daily basis over an extended period of time. In addition, it is unknown as to whether any potential side effects could emerge over a long-term compared to a shorter-term of supplementation.

Study designs: Idealistically, study designs should be double-blind, placebo-controlled, and randomized. In a large sample, this design gives more scientific credibility to the findings. Much of the current research may not incorporate this type of a design and/or lacks sufficient numbers of participants – potentially skewing the data.

Type of L-theanine: Some individuals believe that the specific brand of L-theanine used in research should be considered. For example, certain studies used the brand name “Suntheanine” instead of standard L-theanine. The purpose of this is to ensure a higher percentage of the levorotatory enantiomer in comparison to the dextrorotatory enantiomer. Brands will vary in L-theanine content and possibly contain other herbal extracts based on their sourcing. The L-theanine quality could influence results of scientific research.

Further research of L-theanine is warranted

There is a significant need for more research involving L-theanine. A variety of studies have noted preliminary benefits of L-theanine in mice and rats, but it is unknown whether these benefits would be similar among humans. In addition, many of the human studies conducted with L-theanine have been small-scale (including a small number of participants). Moreover, much of the research lacks diversity and fails to document specific extraction and/or manufacturers of the L-theanine utilized.

Preclinical evidence suggests significant potential benefit from L-theanine, but follow-up studies are necessary to confirm these benefits. In addition, new avenues of investigation such as stroke rehabilitation or neurodegenerative disease treatment should be considered. L-theanine appears to be safe, well-tolerated, and holds significant potential as an adjunct therapy in a variety of health conditions.

Have you noticed any L-theanine benefits?

If you’ve supplemented with L-theanine, leave a comment below mentioning the specific benefits you’ve noticed. To help others get a better understanding of your situation, share the dosage of L-theanine you consume and specific brand that you take. In addition, mention the frequency by which you use L-theanine and whether you take it as part of a “stack” (e.g. L-theanine plus caffeine) or as a standalone supplement.

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