Scientific Name(s): Boletus badius., Camellia sinensis., Gamma-ethylamino-L-glutamic acid.
Common Name(s): L-theanine, Suntheanine
L-theanine has been used for a variety of conditions including anxiety, cognitive impairment, to improve mental alertness, and boost immune function; however, limited clinical information is available to support these claims.
Studies reporting an anxiolytic effect used single doses of theanine 200 to 250 mg. Short-term studies conducted for psychiatric disorders examined doses ranging from 240 to 400 mg per day in divided doses. Single-dose studies evaluating effects on cognitive performance and mental alertness combined caffeine with L-theanine doses of 97 to 100 mg.
None well established.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
None well documented.
Few adverse reactions have been reported. Adverse reactions recorded in human pharmacokinetic studies using tea extracts include headache, dizziness, and GI symptoms.
Theanine is sold in the United States as a dietary supplement and has been granted GRAS (generally recognized as safe) status by the Food and Drug Administration (FDA).
Theanine is derived from the leaves of Camellia sinensis (tea) and 2 other Camellia species (Camellia japonica and Camellia sasanqua). C. sinensis is native to eastern Asia and is a member of the Theaceae family. This evergreen shrub or tree grows to over 9 m in height and is pruned from 60 cm to 1.5 m for cultivation. Its dark green, serrated-edged leaves are alternate and oval, while its white and fragrant blossoms appear singly or in clusters.1, 2
The chemical has also been isolated from the edible mushroom Boletus badius, although information is limited to a single 1960 publication.3 The mushroom is commonly found in late summer and autumn in the United States, and is reddish brown to dark brick/brown in color with a 4 to 12 cm tall stem. The flesh is white to yellow in color, and becomes a light blue/green color when cut or bruised.
Second only to water, tea is the most widely consumed beverage in the world. L-theanine was discovered as a constituent of green tea in 1949 and was approved in Japan in 1964 for unlimited use in all foods, including chocolates, soft drinks, and herb teas, except infant foods. It also provides a unique umami (brothy or savory) taste and flavor to green tea infusion.2, 4
L-theanine (or L-gamma-glutamylethylamide) was discovered in 1949 and constitutes 1% to 2% of the dry weight of tea leaves. It exists only in the free (nonprotein) form. An enzymatic method for manufacturing synthetic L-theanine (Suntheanine) has been developed.2, 4, 5
Uses and Pharmacology
Limited studies evaluate the effects of L-theanine in the prevention of cancer. A Cochrane meta-analysis of the effects of green tea in cancer has found insufficient and conflicting evidence to support a preventative role.6 The observed anticancer effects are largely attributed to the catechins found in tea6 while action on tumors may be due to an enhanced immune response.7
A dose-dependent hypotensive effect was demonstrated in spontaneously hypertensive rats, but not in normotensive ones. The effect may have been related to reduction in central levels of dopamine and serotonin.2 In healthy volunteers, synthetic theanine 200 mg muted the increase in heart rate response to an acute stress test8 while theanine has been observed to antagonize the hypertensive effect of caffeine.9 L-theanine exerts a weak (compared with green tea) antioxidant action as measured by the inhibition of LDL oxidation.2, 10
Although the pharmacological effects of theanine are uncertain, several researchers have proposed a number of mechanisms by which it may act on the CNS. These include the inhibition of glutamate receptors, increasing the concentration of gamma-aminobutyric acid (GABA), increasing dopamine and serotonin in specific brain regions, inhibition of glutamate-induced effects including apoptosis and amyloid beta toxicity, hippocampal neurogenesis and enhanced memory, and neuroprotective blockage of multiple glutamate receptor subtypes in the hippocampus, suggesting a potential role in Parkinson and Alzheimer diseases.5, 11, 12, 32, 33
A proprietary product with daily doses of green tea extract 1,440 mg and L-theanine 240 mg was evaluated in a randomized, double-blind, placebo-controlled 16-week trial in adults (n = 46) with mild cognitive impairment. Between group comparisons for improvement in memory at week 16 were not significantly different. The green tea/L-theanine group results were significantly better than placebo when stratified according to baseline memory scores. Attention was improved compared with baseline for green tea/L-theanine.34 A meta-analysis of 11 randomized clinical trials assessed the acute effects of L-theanine and (-)–epigallocatechin gallate (alone or in combination with caffeine) on cognitive function and mood in healthy adults. During the 1st and 2nd hours postdose, mood ratings favored tea constituents (P < 0.01) via random effects model. Additionally, alertness and attentional switching accuracy were improved in the first 2 hours, especially with the combination of caffeine and L-theanine.42
L-theanine 400 mg/day was evaluated for schizophrenia and schizoaffective disorder in an 8-week, randomized, placebo-controlled study (n = 40) in patients who continued to receive antipsychotic medications. L-theanine produced significant reductions compared with placebo for Positive and Negative Syndrome Scale (PANSS) positive and general psychopathology subscale scores. PANSS negative subscale and negative factor scores were not significantly different. Hanson Anxiety Scale scores for anxious mood, tension, concentration, muscular complaints, and sensory somatic complaints were also significantly improved with L-theanine compared with placebo.35
L-theanine 400 mg/day was evaluated for objective sleep quality in pediatric males (n = 93; range, 8 to 12 years of age) with attention deficit hyperactivity disorder in a 6-week, randomized, placebo-controlled study. Data from Pediatric Sleep Questionnaires completed by parents showed a significant benefit for L-theanine compared with placebo for sleep efficiency, awakenings after sleep onset, and reduction in bouts of nocturnal activity. No significant difference between groups was seen for sleep latency or total sleep time.36
L-theanine is able to cross the blood-brain barrier, and most research has focused on its relaxing effect. Studies have evaluated the effect of L-theanine alone or in combination with caffeine in concentrations naturally found in tea, and use self-reporting measures of stress and electroencephalographic recordings of brain activity. However, study data are inconsistent in methodology and outcome measures, making comparisons difficult.4, 8, 9, 11, 13, 14, 15, 16, 17, 18, 19, 20, 37, 38, 39
An effect of wakeful relaxation of theanine alone is apparent in most published data. The effect is weak in comparison with benzodiazepines, and may differ with consumption of theanine in the relaxed state versus an already anxious state. Some studies suggest a positive contribution to cognitive performance.5, 11, 17, 21
Immune system function
A limited number of studies conducted primarily by 2 groups of researchers suggest L-theanine may enhance the action of immune system components.
Results of in vitro studies, a pilot study, and a small clinical trial suggest that the enhancement of gamma delta T lymphocytes may play a role in the observed decrease in cold and influenza symptoms. A combination preparation was used in the clinical trial.7, 22, 23 Animal and in vitro data from another study showed a reduction in histamine and pro-inflammatory cytokine release from mast cells.40
Other researchers have evaluated the combined effect of L-cystine and L-theanine on the immunologic response to vaccinations in the elderly and health care workers and to exercise in athletes, as well as in rats, and suggest an enhanced immunologic response.8, 24, 25, 26, 41
L-theanine showed no hepatoprotective effect in an in vitro study.27
L-theanine crosses the blood-brain barrier, with effects evident within 30 minutes and measurable up to 5 hours after administration.5, 15, 19 The chemical is metabolized in the kidneys to glutamic acid and ethylamine.28 Data supporting a clinical role for theanine are weak. Studies reporting an anxiolytic effect used single doses of theanine 200 to 250 mg.8, 9, 16, 17, 20 Single-dose studies for cognitive and vigilance effects used 97 to 100 mg.37, 38, 39 Short-term studies ranging in duration from 6 to 16 weeks used a twice daily dosing schedule with individual L-theanine doses ranging from 120 to 200 mg.34, 35, 36 No dosage of L-theanine is suggested for enhanced immune system functioning. A study of benefit for influenza infection prophylaxis used L-theanine 210 mg per day.41
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.29
Clinical data are limited. L-theanine counteracted the stimulatory effect of caffeine in rats, although at smaller doses excitatory effects were observed.2
Information regarding adverse reactions to theanine alone (versus combined with caffeine, as in tea) is lacking. Clinical trials used small numbers of participants and reported poorly on adverse events. One study among elderly participants recorded a higher number of reported headaches among those receiving 4 doses of theanine 250 mg.16
There are no reports of clinical toxicity from daily tea consumption. Adverse reactions recorded in human pharmacokinetic studies using tea extracts include headache, dizziness, and GI symptoms.6
Theanine is sold in the United States as a dietary supplement and has been granted GRAS status in doses up to 250 mg per serving by the FDA.30
The median lethal dose (LD50) of L-theanine is suggested to be 5 g/kg. Mutagenicity and acute and subacute toxicity tests have failed to show toxicity of synthetic L-theanine.4
A toxicological study in rats showed no effect on behavior, morbidity, mortality, body weight, hematology, or urinalysis. An increased incidence of renal tubule adenomas in a small number of female rats given high dosages (400 mg/kg body weight per day) was attributed to genetic predisposition.31
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