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L-theanine, also known as N-ethyl-L-glutamine, is a major non-protein, water soluble  amino acid commonly found in green tea [2; 3], and has been the focus of much attention due its role in having positive effects in the brain [2; 4] and body. In green tea, L-theanine has been estimated to be between 1-2% of dry weight tea  which is translated as being around 10-30g/kg in green tea leaves – Table 1. In addition, L-theanine has been shown to have antioxidant properties , blood pressure lowering attributes; along with possessing neuroprotective effects .
Mechanism and interactions
Once consumed, L-theanine rapidly interacts with the intestinal tract, where it is absorbed, as well as being transported into the brain [10;8]. When taken orally, L-theanine takes only an hour to be detected in serum. Within 5 hours L-theanine reaches its maximum level, where it then lasts for 24 hours – having exited the kidneys, liver and brain [11 Other data has suggested that L- theanine, administered to rats, took only 30 minutes to reach the brain .
Suntheanine Vs L-theanine
Synthetic l-thanine, also known as Suntheanine, is made up of a ‘mixture’ of the two forms – D and L – of theanine . This commercially branded version of theanine is manufactured and sold as an herbal supplement . Considering that it is not naturally occurring L-theanine, suntheanine requires food-borne L-glutamine and ethylamine, along with the glutaminase enzyme for synthesis . Suntheanine (compared to L-theanine) has also been considered just as beneficial as L-theanine; and, its LD50 (toxic dose index) was found to be greater than 5,000mg/kg .
Caffeine and L-theanine
Caffeine (coffee) and L-theanine combinations have been reported to produce faster responses in memory and attention (figure 2.). Also, interactions of caffeine and L-theanine have reported that L-theanine protects against toxic caffeine doses, and stops the exciting effects felt from caffeine . In one study, 50mg of caffeine was used in combination with L-theanine (and also stand-alone) to compare effects on cognition and mood . Synergy between L-theanine and caffeine has been established: Another study, measuring the ratio of caffeine dosage (50mg) with L-theanine dosage (100mg) affecting cognitive function of attention showed an enhancement of attention over a 4-day period . L-theanine and caffeine were also concluded as significantly improving attention during a demanding exercise – this study used a moderate dose of 97mg (L-theanine) and 40mg (caffeine) . Overall, when combined L-theanine and caffeine improve cognitive performance and attention as opposed to their ‘stand-alone’ effects . A 20-person placebo-controlled study using a caffeine-L-theanine combination on cognitive and visual reaction time showed improvements cognition, with L-theanine and caffeine, in synergy, having an additive effect on attention .
Benefits and Effects
L-theanine has anti-tumour, anti-diabetes, anti-hypertension and anti-stress effects [19; 20]. Additionally, L-theanine prevents nerve cell damage and protects the liver from damage . Along with these benefits, theanine promotes relaxation, improves learning and concentration, improves the immune system and reduces blood pressure . Once consumed, theanine interacts and elicits its effects by passing across the blood brain barrier (BBB) where exerts it’s a range of positive neurophysiological and pharmacological effects . Also, L-theanine has been associated with an increased release and concentration of dopamine, along with blocking glutamate reuptake and glutamate receptors in the hippocampus [21; 22]. Remarkably, L-theanine has also been shown to have an antidepressant-like effect in a dose range between 1-20mg/kg over 10 days in mice. This effect might be mediated through the central nervous system .
L-theanine and major depressive disorder (MDD)
In a more recent study assessing the effect of L-theanine on patients with depression, L-theanine – in a 250mg/day dose administered over 8 weeks – showed a beneficial outcome in depressive symptoms: anxiety, sleep disturbance and cognitive impairment in all patients . Since 250mg of L-theanine is classed as a high dose, researchers concluded that this high L-theanine dose was highly tolerated . One major finding is that L-theanine has structural similarity to L-glutamate, and therefore mode of action is likely to follow the glutamatergic pathway .
L-theanine and ADHD
One study found that L-theanine in studying ADHD, given in a 400mg dose to 8-12-year-old boys, was effective in improving sleep quality . Researchers of this study suggested the importance of considering a 400mg, safe dose in treating childhood ADHD  – Figure 4.
L-theanine effects on sleep
L-theanine was found to improve sleep quality in patients suffering from schizophrenia . An investigation into ADHD-related sleep disorders found that L-theanine did not produce a significant change in total sleep time; however, it did significantly increase sleep efficiency along with a reduction in nocturnal activity . L-theanine promotes the generation of alpha waves in the brain, which creates a relaxed state without the feeling of drowsiness .
L-theanine and blood pressure
Animal work has found that L-theanine can reduce blood pressure in hypersensitive rats . This has largely been attributed to the way L-theanine interacts with the autonomic nervous syste, (ANS), where it carries out anti-stress activities . Regulation of blood pressure is dependent on the peripheral nervous system (PNS), and L-theanine alleviates high blood pressure through interacting with several peripheral nervous system pathways and blood vessels – thus, lowering the blood pressure and producing a calming effect .
L-theanine in Green tea
L-theanine, along with other constituents, is contained in black tea and green tea. L-Theanine contributes to the sweet taste of green tea . In a 250ml serving of green tea, it has been estimate that around 40mg of L-theanine is contained in this brew . L-theanine constitutes about 1-3% of the dry weight of green tea [31; 10; 11], and around 50% of the total amino acids in green tea leaves [10; 205]. A study seeking to quantify L-theanine in a standard cup of green tea found 7.9mg  to be contained to be contained in about 200mL of tea.
Typical doses of between 50-200mg daily is most commonly reported . Studies in rats have demonstrated that up to 4 g/kg per day – considered a high L-theanine dose – had a non-toxic outcome on food intake, body weight and morbidity . Other studies have reported that a high dose of 400mg daily L-theanine is safe, tolerable and effective . In addition, a 200-400mg dose of L-theanine reported a decrease in anxiety and stress in healthy participants . Interestingly, a study assessing the effect of L-theanine on tumour proliferation and growth in mice, found that a very high dose of between 12.5-25 times the recommended dietary allowance (RDA) of L-theanine decreased tumour growth by 36% .
Theanine is considered non-toxic for humans and animals . Regarding the safety of L-theanine, results of acute and toxicity have shown is safe even if a high dose is consumed . Toxicological descriptions have also reported the absence of negative side effects in animal studies investigating L-theanine . Currently, no indications have been made that a high dose of L-theanine causes any major side effects in humans , however L-theanine has been regarded as completely safe to consume as part of one’s diet .
Research has consistently used L-theanine and caffeine in low, moderate and high doses. In this manner, it has been shown that 100mg L-theanine stacked with 50mg caffeine has positive outcomes on attention . Stacking L-theanine with caffeine has shown to improve cognition and attention; and L-theanine and caffeine alone did not show such similar effects.
L-theanine is approved as generally regarded as safe (GRAS) by the Food and Drug Administration (FDA) . It has been documented that taking high doses of L-theanine is safe , with the FDA stating and recommending that the daily intake with a diet should be around 628mg per person . In addition, the FDA has suggested that the daily amount of L-theanine should not exceed 1200mg. Long-term use of L-theanine has yet to be adequately established. Overall, L-theanine, even when combined with caffeine has been approved as being safe for consumption.