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The amino acid l-theanine (γ-N-ethylglutamine), occurs naturally in tea leaves and in the edible bay boletes mushroom Xerocomus badius. Green tea and black tea are made from the same plants. Black tea is manufactured through fermentation but green tea is not fermented. Green tea has been a mainstay of Chinese medicine for over 3 millenniums, and is used medicinally both in combination with other herbs and alone in the form of a concentrated liquid for enhancing stamina and concentration. The amount of l-theanine depends on where tea plants are grown, production methods and the time of harvesting. Different species of tea such as Camellia sinensivar have higher concentrations of l-theanine than the more familiar C. sinensis. A synthetic form of L-theanine (Suntheanine™) is also available.
L-theanine is widely used in Asian countries to treat a variety of medical and mental health problems and is rapidly gaining popularity in Western countries. Caffeine, the other major constituent of tea, increases brain levels of acetylcholine and dopamine resulting in improved attention, cognition and mood. Beneficial cognitive effects of caffeine take place more rapidly than those of l-theanine because it is absorbed more rapidly, reaching peak plasma levels after 30 minutes compared to peak plasma levels of l-theanine 50 minutes following consumption. In addition to l-theanine and caffeine, tea leaves contain other constituents that confer a variety of health benefits, including amino acids glutamine, arginine, serine and alanine, and the phenolic compounds epigallocatechin, epicatechin gallate, epicatechin and epigallocatechin-gallate (so-called ‘catechins’). Matcha is a special green tea preparation that contains higher levels of beneficial phytochemicals compared to regular green tea.
Animal and human studies support that L-theanine reduces subjective stress response, enhances cognitive performance, improves sleep quality, and has protective effects against chronic disease, cardiovascular disease, obesity, and the common cold. Different constituents of green tea including l-theanine, caffeine and catechins may help prevent metabolic syndrome and obesity. L-theanine reduces oxidative damage caused by reactive oxygen species (i.e. ‘free radicals’), increases glutathione concentration in the liver enhancing the capacity of liver enzymes such as superoxide dismutase to clear toxins from the blood. Research findings suggest that l-theanine has anti-aging benefits. Catechins from green tea may have beneficial antimicrobial and antiviral activities. In the gastrointestinal tract green tea has been shown to activate intracellular antioxidants and inhibit formation of procarcinogens.
L-theanine has been shown to improve learning, memory and cognitive function, and to enhance selective attention during mental tasks. Epidemiological studies support that regular consumption of tea made from the leaves of Camellia sinensis, is associated with decreased incidence of cognitive decline, improved mood and enhanced capacity to cope with stress. L-theanine is a promising augmentation therapy for schizophrenia, and may have beneficial effects on mood disorders, attention deficit hyperactivity disorder (ADHD) as well as panic disorder, obsessive compulsive disorder (OCD), and bipolar disorder.
Placebo-controlled studies have investigated the effects of L-theanine alone or in combination with caffeine on mood and cognitive performance, with the finding that cognitive functioning is enhanced in response to combined treatment but not in response to l-theanine alone. Two meta-analyses of human interventions on acute psychoactive effects of tea constituents on mood and cognitive performance found evidence that l-theanine improves self-reported relaxation, reduces subjective feelings of tension, and that caffeine improves performance on demanding cognitive tasks and enhances alertness and vigor.
Animal studies support that L-theanine rapidly crosses the blood brain barrier, increases brain levels of serotonin, GABA and dopamine, binds to glutamate and NMDA receptors, and may increase levels of brain-derived neurotrophic factor (BDNF). Long-term consumption of l-theanine (i.e. over 3 to 4 weeks) may have general neuroprotective benefits mediated by increased synthesis of brain-derived neurotrophic factor (BDNF) in the hippocampus an area of the brain that plays a central role in memory consolidation. All of these effects are believed to result in anxiety reduction.
As L-theanine is typically ingested together with caffeine and other bioactive constituents of tea, most studies have investigated the combined effects of l-theanine and caffeine on mood and cognition.
The anti-anxiety effects of L-theanine are mediated through different mechanisms including enhanced alpha brain wave activity, increased synthesis of GABA, and its role as a weak antagonist of AMPA glutamate receptors. General calming benefits of l-theanine are reflected in increased brain electrical activity in the alpha frequency range (8 to 13 Hz). Changes in brain electrical activity measured by electroencephalography (EEG) are dose-dependent, and are similar to beneficial EEG changes observed in meditation, including increased alpha waves in the occipital and parietal regions. Increased alpha activity has been shown to continue for 60 minutes following administration of a 200mg dose of l-theanine, and this effect was more marked in individuals with higher trait anxiety. Finally, ingestion of green tea with high l-theanine content has been found to decrease adrenal hypertrophy in mice exposed to chronic stress.
Individuals who drink green tea for stress or anxiety may experience greater calming effects than stimulating effects depending on the relative amounts of L-theanine and caffeine in the particular species of tea and how it is prepared. A general calming effect is usually noticed within 30 to 40 minutes after L-theanine is taken at a dose of 50 to 200mg, and typically lasts 8 to 10 hours. Moderate symptoms of anxiety often respond to a regimen of 200mg once or twice daily. More severe anxiety may require doses of 600mg to 800mg daily taken in increments of 100mg to 200mg spaced over the day. Unlike benzodiazepines and other prescription anti-anxiety medications, L-theanine does not cause drowsiness, slow reflexes or impair concentration, there is no risk of developing tolerance or dependence. There are no reports of serious adverse side effects or interactions between l-theanine and psychotropic drugs or other natural products.
Findings of studies on l-theanine for state anxiety are inconsistent. Differences in outcomes are probably related to different patient populations examined, and the fact that some studies investigated caffeine in combination with l-theanine. A placebo-controlled trial that compared l-theanine 200mg/day to the benzodiazepine alprazolam, found evidence for general anxiolytic effects but not for reduction in experimentally induced state anxiety. In contrast, two other studies reported significant reductions in measures of subjective stress such as decreases in heart rate and blood pressure, in response to the same dose of l-theanine. In a 4-week placebo-controlled trial (N=30) adults with no psychiatric illnesses randomized to l-theanine 200m/day experienced significantly greater reductions in state anxiety and improved sleep compared to the placebo group. In a small placebo-controlled trial 16 healthy adult volunteers were randomized to l-theanine 200mg/day vs alprazolam 1mg or a placebo while monitored during a relaxed and an experimentally induced acute anxiety condition. L-theanine had some relaxing effects during the baseline condition but neither alprazolam nor l-theanine had anxiolytic effects greater than placebo during the relaxed state or the experimentally induced anxiety state.
In a 10-week placebo-controlled study (N=46) adults with a DSM-5 diagnosis of Generalized Anxiety Disorder were randomized to receive l-theanine (450 to 900mg/day) vs placebo while continuing on their current medication. The adjunctive l-theanine group did not outperform the placebo group on measures of anxiety reduction or improved sleep quality. In a small placebo-controlled study (N=34) healthy adults aged 18-40 were administered an l-theanine drink vs placebo then subjected to a multitasking cognitive stressor. The l-theanine group reported significantly lower stress response compared to placebo one hour after ingesting the drink. Another study on a nutrient drink containing l-theanine 200mg, phosphatidylserine 1mg, chamomile 10mg, and glycerylphosphorylcholine 25mg, found significantly reduced subjective stress responses 1 hour following ingestion and significantly reduced serum cortisol levels 3 hours following ingestion.
A placebo-controlled study found that l-theanine 100mg twice daily significantly improved sleep quality in boys with ADHD suggesting that l-theanine may be an effective adjunctive therapy in ADHD. L-theanine does not cause drowsiness however taking l-theanine 200mg at bedtime may improve sleep quality by reducing anxiety.
Emerging findings support that l-theanine may have beneficial effects on symptoms of depressed mood and psychosis. In an 8-week open-label study (N=20) adults diagnosed with major depressive disorder treated with l-theanine 250mg/day reported improvements in mood, anxiety and sleep quality.
L-theanine may also have beneficial effects on anxiety related to psychosis. Findings of an 8-week placebo-controlled trial support that l-theanine augmentation in individuals with schizophrenia and schizoaffective disorder reduces anxiety levels. Beneficial effects of l-theanine augmentation in this population may be mediated by increases in cortisol and brain-derived neurotrophic factor (BDNF). A combination treatment containing the neurosteroid pregnenolone and the amino acid L-theanine may have beneficial effects on symptoms of psychosis. In an 8-week double-blind, placebo-controlled trial (N=40) adults with schizophrenia or schizoaffective disorder with suboptimal response to antipsychotics, were randomized to pregnenolone (50mg/day) plus l-theanine (400mg/day) vs placebo while continuing on their antipsychotic medication. At study end point the group receiving pregnenolone plus l-theanine had significantly fewer negative symptoms of psychosis such as blunted affect, anhedonia and paucity of speech, significantly reduced anxiety, and greater improvements in general functioning, compared to the placebo group.
Findings of animal studies suggest that l-theanine may help prevent cerebrovascular disease and mitigate the impact of cerebrovascular accidents (i.e. stroke). Neuroprotective effects of l-theanine following transient cerebral ischemia may be related to its action as an antagonist of AMPA glutamate receptors. Rats treated with l-theanine (0.3 to 1mg/kg) before being subjected to repeated episodes of experimentally induced cerebral ischemia showed significantly less impairment in spatial memory and significantly less neuronal cell death.
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By Dr. James Lake, M.D.
