2. +
Overview
The Root of Relaxation
Cultivation
Mechanism of Action
3. +
The Root of Relaxation
Since ancient times, people have drunk green tea to induce
relaxation. The substance responsible for this effect is the
amino acid L-theanine(delta-glutamylethylamide), a significant
amino acid present in green tea (camellia sinensis).
L-theanine accounts for nearly half of the total amino acids
found in green tea and makes up from 1%–2% of the leaf dry
weight.
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Cultivation
L-theanine is made in the roots of the green tea plant.
It concentrates in the leaves, where sunlight converts it to
polyphenols.
Cultivating tea in the shade preserves L-theanine content.
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Mechanism of Action
L-theanine increases dopamine and serotonin production in the
brain, producing a sense of relaxation.
It balances and controls the excitement caused by caffeine also
found in the plant.
L-theanine us used therapeutically to reduce anxiety and has
been approved as a food additive in Japan since 1964.1,2
1. Juneja LR, Chu D-C, Okubo T, Nagato Y, Yokogoshi H. L-theanine—a unique amino acid of green tea and its
relaxation eff€ ect in humans. Trends in Food Science & Technology. 1999;10:199-204. Available here.
2. L-Theanine. Alternative Medicine Review. 2005;10(2):136-138. Available here.
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Human Studies
At least 6 different human clinical trials have
documented L-theanine’s effect on anxiety.
These data are augmented by a number of
animal studies that bring greater
understanding of pharmacokinetics and
mechanism of action.
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1998 Nippon NogeiKagakukaishi
Kobayashi et al reported L-theanine increases alpha-brain
wave activity, inducing a sense of relaxation.
Eight female college students, half rated as high anxiety and
half low anxiety, took 200 mg doses of L-theanine dissolved in
water.
The researchers concluded: ―These results indicate the
possibility for L-theanine to be applied to foods and beverages
as a new type of functional food ingredient for its relaxation
effect.‖3
3. Kobayashi K, Nagato Y, Aoi N, et al. Effects of L-theanine on the release of α-brain waves in human volunteers.
Nippon NōgeiKagakukaishi. 1998 (72)2:153-157.
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2004 Human Psychopharmacology
Lu et al reported on the effect of l-theanine on anticipatory
anxiety, comparing it to the prescription benzodiazepine anxiolytic drug
alprazolam.
Sixteen healthy volunteers took either alprazolam (1 mg), L-theanine (200
mg), or placebo in a double-blind, placebo-controlled repeated measures
design.
The acute effects of alprazolam and L-theanine were assessed under a
relaxed and experimentally induced anxiety condition.
L-theanine showed some effect on baseline anxiety but did not exert an
antianxiety effect when the subjects were performing anxiety-producing
tasks. Alprzolam had no significant effect either.4
4. Lu K, Gray MA, Oliver C, et al. The acute effects of L-theanineincomparison with alprazolam on anticipatory anxiety in humans.
Hum Psychopharmacol. 2004;19(7):457-465.
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2007 Biological Psychology
Kimura et al reported results of a double-blind trial that L-theanine
reduces psychological and physiological stress responses.
A series of mental arithmetic problems were used as a stressor on 12
participants who underwent 4 separate trials, taking L-theanine at the
start of the procedure and midway through, as well as 1 trial taking a
placebo and 1 taking nothing.
L-theanine reduced heart rate and salivary immunoglobulin response
because of a decrease in sympathetic nervous system activation.
Conclusion: ―L-theanine reduces psychological and physiological
stress responses.‖5
5. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses.
BiolPsychol. 2007;74(1):39-45.
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2011 Journal of Clinical Psychiatry
Ritsner et al examined the effect of L-theanine on 60 patients
with schizophrenia or schizoaffective disorder who participated
in an 8-week, double-blind, randomized, placebo-controlled
study taking 400 mg/d of L-theanine in addition to their regular
medications. Forty patients completed the study.
Compared with placebo, those taking L-theanine scored lower
on measures of anxiety (HARS scale) and improved on
measures of general psychopathology (PANSS 3-dimensional
model), suggesting it may be a useful addition to antipsychotic
medications.6
6. Ritsner MS, Miodownik C, Ratner Y, et al. L-theanine relieves positive, activation, and anxiety symptoms in patients with
schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin
Psychiatry. 2011 Jan;72(1):34-42.
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2011 Clinical Neuropharmacology
Miodownik C et al examined circulating levels of neurochemical
indicators and the beneficial clinical effects of L-theanine
augmentation.
Brain-derived neurotrophic factor (BDNF), DHEA, DHEA-
sulfate, cortisol, cholesterol, and insulin were monitored in the 40
who successfully completed the prior study.
Among L-theanine-treated patients, BDNF levels and cortisol-to-
DHEA-sulfate ratio were significantly associated with the beneficial
clinical effects of L-theanine supplementation, suggesting changes
in both chemical markers play a role.7
7. Miodownik C, Maayan R, Ratner Y, et al. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone
molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective
disorder patients. ClinNeuropharmacol. 2011 Jul-Aug;34(4):155-160.
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Animal Studies
At least 3 animal studies of interest on L-
theanine and anxiety have been published.
13. +
2009 American Association of
Nurse Anesthetists Journal
In 2009 Hesse et al divided 55 rats were into 5 groups: control
(saline), L-theanine (positive control), flumazenil (a known
benzodiazepine receptor antagonist) and L-theanine, and
midazolam and L-theanine.
L-theanine does not decrease anxiety by modulation of the
GABAA receptor. Combining L-theanine with midazolam
produced a synergistic or additive effect measured by
decreased anxiety and both fine and basic motor movements.8
8. Heese T, Jenkinson J, Love C, et al. Anxiolytic effects of L-theanine—a component of green tea—when combined with
midazolam, in the male Sprague-Dawley rat. AANA J. 2009;77(6):445-449.
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2012
Pharmacology, Biochemistry, and
Behavioret al tested L-theanine on monkeys addicted to
In 2012 Wise
opioids and found it reduced signs of withdrawal.
The authors ―suggest that L-theanine may be useful in the
pharmacotherapy of treating opioid withdrawal as well as
anxiety-associated behaviors … L-theanine attenuates
abstinence signs in morphine-dependent rhesus monkeys and
elicits anxiolytic-like activity in mice.‖9
9. Wise LE, Premaratne ID, Gamage TF, et al. l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys
and elicits anxiolytic-like activity in mice. PharmacolBiochemBehav. 2012;103(2):245-252.
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Safety Profile
Tea is the single most popular beverage in the world after water.
Significant toxicity is unlikely.
L-theanine was approved in Japan in 1964 for unlimited use in all
foods, including chocolates, soft drinks, and herb teas (except
infant foods) and has been granted GRAS (generally recognized
as safe) status by the US Food and Drug Administration (FDA).
In a 13-week rat toxicity study published in 2006, ―The no-
observed-adverse-effect-level (NOAEL) was 4,000 mg/kg
bw/day, the highest dose tested.‖ This would be equivalent to a
100-pound person taking 200 grams of l-theanine per day for a
year (1,000 times the typical dose).11
11. Borzelleca JF, Peters D, Hall W. A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats. Food ChemToxicol.
2006;44(7):1158-1166.
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Absorption
L-theanine crosses the blood-brain barrier, with effects
noticeable in 30 minutes and measurable up to 5 hours after
administration.12,13
12. Bryan J. Psychological effects of dietary components of tea: caffeine and L-theanine. Nutr Rev. 2008;66(2):82-90.
13. Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J ClinNutr.
2008;17(suppl 1):167-168.
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Contraindications
Information regarding safety and efficacy in pregnancy and
lactation is lacking.14
Little information adverse reactions from l-theanine is available.
One study using older participants reported more headaches in
those taking 1,000 mg per day.15,16
14. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-335.
15. Kell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB. The effects of L-theanine, caffeine and their combination
on cognition and mood. BiolPsychol. 2008;77(2):113-122.
16. Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB. The effects of L-theanine, caffeine and their
combination on cognition and mood. BiolPsychol. 2008;77(2):113-122.
