Ingredient review —L-theanine
What is it?
Description
L-theanine (γ-glutamylethylamide) is the most abundant (50%) water-soluble non-protein amino acid found in Camellia sinensis (tea) leaves. (5)(6)(8)(11)(22)(23) L-theanine synthesis occurs in the roots of the tea plant and is then translocated to the leaves. (6)(24) It is responsible for the aroma and umami taste of tea. (22)
The researcher Sakato was the first to isolate and identify L-theanine in green tea leaves in 1949. (14)(22) In the early 1950s, he also isolated L-theanine from the inedible mushroom, Xerocomus badius. (5)(14)(22)
Historically, L-theanine has been used as a relaxing agent, primarily consumed as tea. (14) There is some controversy regarding the actual concentration of L-theanine in tea. The most recent study conducted in 2016 suggests that green tea has the highest amount (6.56 mg/g) of L-theanine followed by white tea (6.26 mg/g), oolong (6.09 mg/g), and black tea (5.23 mg/g). (4) Many animal trials have reported that L-theanine exerts neuroprotective effects, modulates the activity of neurotransmitters, focuses attention, and reduces psychological stress. (8)(11)(23) Studies are looking into understanding and quantifying the neural effects of this psychoactive component of tea.
Theanine has a glutamine core unit in its structure and occurs mainly as the L-(S) enantiomer, hence its name, L-theanine. (24)(25) L-theanine can be extracted from Camellia sinensis leaves and produced via chemical- and bio-syntheses. (24) Extraction from Camellia sinensis leaves does produce L-theanine with relatively high purity. However, this process comes with high production costs and lower overall yield. (24)
Chemical synthesis is a more convenient and cost-effective alternative to direct extraction of L-theanine from Camellia sinensis leaves. However, the synthetic product can be a racemic mixture of L- and D-enantiomers, raising safety and efficacy concerns. (24) The enzymatic synthesis of L-theanine is relatively complex. However, this method shows great promise for industrial-scale production, especially since the end product is theanine in its naturally occurring L-form. (24) Unfortunately, “no current technique offers an environmentally sustainable and economically viable method for commercial production of purified” L-theanine. (24)
Please note that this review focuses on L-theanine as an oral supplement only.
Main uses
Anxiolytic
Cognitive function
Insomnia
Stress and relaxation
Formulations
Form
Characteristics
Suntheanine®
Patented brand of L-theanine made by Taiyo
It is produced via chemical synthesis using L-glutamine, ethylamine, and glutaminase enzymes.
L-theanine
Currently no study has directly compared unbranded formulations of L-theanine to branded formulations such as Suntheanine®.
However, when compared to green tea, the kinetics of L-theanine uptake and metabolism are comparable. (20)
Slow and immediate release
There is a lack of research investigating the possible benefits or harms associated with slow- or immediate-release forms of Suntheanine® or L-theanine.
Dosing & administration
Anxiety
General outcomes from A-level evidence
stress & anxiety during acute stress in those with a “high propensity for anxiety and stress”
Note: There was insufficient evidence for reducing chronic stress and anxiety (25)
Dosing & administration
200-400 mg to individuals experiencing acute stress or anxiety in an acute single day trial
Outcomes
stress & anxiety during acute stress in those with a “high propensity for anxiety and stress”
Note: There was insufficient evidence for reducing chronic stress and anxiety (25)
Class of evidence
a
Dosing & administration
400 mg per day for eight weeks in patients with schizophrenia and schizoaffective disorder adjunct to ongoing antipsychotic treatment
Outcomes
Hamilton Anxiety Rating Scale (HARS) by 46%, Positive and Negative Syndrome Scale (PANSS) positive by 26%, & general psychopathology by 18% compared to placebo (17)
Class of evidence
b
Dosing & administration
200 mg (as Suntheanine®) before bed for four weeks to healthy individuals
Outcomes
state-trait anxiety intervention-trait score by 7% compared to placebo (8)
Class of evidence
c
Dosing & administration
200 mg (as Suntheanine ®) as a single administration to healthy individuals
Outcomes
state-trait anxiety intervention-trait score in response to an acute stressor compared to placebo (11)
Class of evidence
c
Blood pressure
General outcomes from A-level evidence
Has an antagonistic effect on caffeine when taken simultaneously by counteracting the arousing effects and lowering BP (6)
Dosing & administration
200 mg as a single administration to healthy individuals
Outcomes
L-theanine antagonized the BP-raising effects of caffeine. SBP and DBP were significantly lower in the solo-L-theanine group and L-theanine + caffeine group compared to the solo-caffeine group (18)
Class of evidence
c
Dosing & administration
200 mg (as Suntheanine®) as a single administration to healthy individuals
Outcomes
Compared to placebo, the high-response group (individuals that showed a greater than average change in BP in response to stress) had significantly lower SBP and DBP in response to psychological stress (26)
Class of evidence
c
Cognitive function
General outcomes from A-level evidence
Improves reaction time, long- and short-term memory, and suppression of distraction (6)
Dosing & administration
100.6 mg (as Suntheanine ®) per day for 12 weeks in individuals with self-assessed cognitive decline
Outcomes
reaction times and omission errors in the working memory task
correct answers in the working memory task (2)
Class of evidence
b
Dosing & administration
200 mg per day for four weeks to healthy individuals
Outcomes
cognitive function, verbal fluency (especially letter fluency), & executive function scores (8)
Class of evidence
c
Dosing & administration
200-400 mg as a single administration to healthy individuals
Outcomes
the % of prepulse inhibition (PPI) compared to placebo (16)
Class of evidence
c
Dosing & administration
200 mg (as Suntheanine ®) as a single administration to healthy individuals
Outcomes
Improved reaction time response
alpha band & attentional task score (about 39%) among the high anxiety propensity group
Note: The influence of L-theanine was maintained throughout the 60 min resulting in a slightly higher score (56.6%) (9)
Class of evidence
c
Dosing & administration
200 mg as a single administration to healthy individuals
Outcomes
Class of evidence
c
Dosing & administration
100 mg as a single administration to healthy individuals
Outcomes
omission errors by 36% and commission errors by 23% relative to placebo (7)
Class of evidence
c
Depression
General outcomes from A-level evidence
No data currently available.
Dosing & administration
200 mg per day for four weeks to healthy individuals
Outcomes
Self-rating depression scale score (SDS) was significantly ↓ compared to baseline score; however, the decrease was not significant when compared to placebo. (8)
Class of evidence
c
Insomnia
General outcomes from A-level evidence
time spent in restful sleep & fewer nocturnal activities in boys with ADHD (1)
Dosing & administration
200 mg (as Suntheanine®) twice per day (morning & afternoon) for six weeks in children (8-12 yoa) with ADHD
Outcomes
Class of evidence
b
Dosing & administration
450-900 mg per day for eight weeks in adults (18-75 yoa) with diagnosed generalized anxiety disorder
Outcomes
Greater sleep satisfaction compared to placebo (19)
Class of evidence
c
Dosing & administration
200 mg per day for four weeks in healthy adults (36-600 yoa)
Outcomes
Pittsburgh sleep quality index score by 14% compared to placebo, sleep latency by 25% compared to placebo, & daytime dysfunction by 35% compared to placebo (8)
Class of evidence
c
Stress & relaxation
General outcomes from A-level evidence
May help to reduce stress & anxiety during acute stress in those with a “high propensity for anxiety and stress”
Note: There was insufficient evidence for reducing chronic stress and anxiety (25)
Dosing & administration
200-400 mg per day to individuals experiencing acute stress or anxiety
Outcomes
May help to reduce stress & anxiety during acute stress in those with a “high propensity for anxiety and stress”
Note: There was insufficient evidence for reducing chronic stress and anxiety (25)
Class of evidence
a
Dosing & administration
200 mg (as Suntheanine®) as a single administration to healthy individuals
Outcomes
HR, LF/HF, s-IgA, & perception of stress in response to an acute stressor compared to placebo (11)
Class of evidence
c
Dosing & administration
200 mg twice per day (after breakfast and lunch) taken daily starting one week before the exam period and continued for ten days into the exam period. Administered to healthy university students.
Outcomes
pre-exam salivary alpha-amylase (sAA) & visual analogue scale (VAS) score compared to placebo
Note: No significant difference in post-exam sAA; however, the placebo group showed a tendency of higher levels compared to the theanine group (23)
Class of evidence
c
Dosing & administration
200 mg (as Suntheanine ®) as a single administration to healthy individuals
Outcomes
visual analogue mood scale (VAMS) score, especially in the tranquil-trouble dimension, by 40% compared to placebo and by 51% compared to Alprazolam in the relaxed experimental state (14)
Note: The tranquil-trouble dimension is one component of the VAMS. Subjects identify how tranquil or troubled they feel by placing a single mark along a 100 cm horizontal line that has either adjective at each end
Class of evidence
c
Adverse effects
Overall, L-theanine is generally well tolerated. No adverse effects were reported in an eight-week trial using 400 mg per day. (25) A four-week trial using 900 mg per day reported adverse effects both in the treatment and placebo groups, such as sleep disturbances, drowsiness, weakness/fatigue, irritability, trouble concentrating, and gastrointestinal discomfort. However, there was no significant difference between the groups. (19)
A 13-week dietary toxicity and toxicokinetic study in rats found no dose- or treatment-related adverse effects. They determined L-theanine’s no-observed-adverse-effect-level (NOAEL) was 4,000 mg/kg of body weight per day. (6)
In one study looking at treatments for ADHD-related sleep disorders in boys between the ages of 8 and 12, one participant developed a new facial tic. The adverse effect caused the participant to withdraw from the study. The authors wrote that the child had previously exhibited various tics. They determined that the event’s causality was unlikely. (1)(3)
Pharmacokinetics
Absorption
- L-theanine is absorbed in the small intestinal tract. It is then transported from the brush border of the GI tract into the bloodstream, potentially via both Na+-coupled co-transporters and the methionine carrier transport system. (6)(22)
- It is estimated that 72 to 74% of L-theanine is bioavailable. (6)
- A rodent study found that the intestinal tract absorbs L-enantiomer at a higher rate than D-enantiomer. (6)(22)
- Glutamine inhibits the absorption of L-theanine. Both have a similar structure and are competitors for the Na+-coupled co-transporter. The transporter has a greater affinity, possibly seven times greater, (12) for glutamine than L-theanine.(6)
Distribution
- Once absorbed, L-theanine is distributed to the peripheral tissues and organs (liver and kidney), but is mainly distributed to the brain. L-theanine crosses the blood-brain barrier via the amino acid L transport system. (6)(25)
- Studies indicate that it can take anywhere from ten to 24 minutes for L-theanine to reach the brain after ingestion. (24) Brain concentrations start to decrease around five hours after ingestion. (11)
- It is estimated that maximum plasma concentration is reached one to five hours after ingestion of L-theanine. Serum concentrations start to slowly decrease within 24 hours. (6)
Metabolism
- L-theanine can be hydrolyzed into glutamic acid and ethylamine in the blood, brain, kidneys, and liver. It is theorized that glutaminase and/or glutamyl transpeptidase are responsible for the metabolism of L-theanine. (6)
- It is thought that L-enantiomer is preferentially re-absorbed and metabolized by the kidneys, while D-enantiomer is more quickly metabolized. (6)(25)
Excretion
- L-theanine and its metabolites are eliminated in the urine. (6)(22)
- Approximately 2.4 to 3.1% of L-theanine is directly eliminated in the urine. (6)
- A small amount of L-theanine is retained in the erythrocytes. (6)
- The elimination half-life for L-theanine ranges from 58 to 74 minutes in humans when 100 mg of L-theanine is ingested. (6)
L-theanine is absorbed in the small intestinal tract and distributed to the peripheral tissues and organs (liver and kidney), but is mainly distributed to the brain. L-theanine and its metabolites are eliminated in the urine, however, a small amount is retained in the erythrocytes. (6)
References
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