L-theanine: the calming neutraliser

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L-theanine has demonstrated promising anxiolytic, cognitive and sleep promoting benefits in humans, plus preliminary data suggest it may provide further benefits as a neuroprotective and chemotherapy adjuvant.

L-theanine, or gamma-glutamylethylamide, is synthesised from glutamic acid and ethylamide in tea roots. It is subsequently concentrated in the leaves, making up to 1-3% of the dry tea leaf weight. Small amounts of the amino acid can also be found in specific mushroom species.[1]

L-theanine’s actions on the brain are not fully understood, however consumption is shown to induce alpha brain wave activity in humans (as observed in an EEG). This change in brain function is associated with a state of mind described as alert, yet relaxed, making its effects beneficial for concentration during stressful situations, as well as supporting sleep without undesirable drowsiness during the day.[2,3]

L-theanine reaches peak plasma levels approximately 30 minutes after administration, and is able to cross the blood brain barrier.[1,3] It is structurally similar to glutamate and is thus able to interact with glutamate receptors (e.g. AMPA, NMDA) within the central nervous system (CNS). This receptor interaction inhibits the binding of glutamate in cortical neurons, possibly inhibiting excitation.[3]

Excessive glutamate release and resultant NMDA activation have each been noted as important considerations in depression, anxiety disorders and neurodegenerative conditions.[4] Imbalances within the glutamatergic system in specific areas of the brain have also been implicated in addictive[5] and obsessive compulsive disorders.[6] As a result, treatments which target these imbalances are being trialled to investigate the hypothesis that returning balance to this system, and suppressing excessive glutamate receptor activation, can be a useful means of improving mood and cognitive symptoms.

Doses as small as 50-200mg have achieved significant benefits for supporting stress relief,[7] relaxation,[3,8] and reduction of anxiety.[9]

Other supportive approaches which provide symptomatic relief via this mechanism include the minerals zinc and magnesium (NMDA agonists) and NAC (neuromodulatory, acting in the glutamatergic system).  

Addressing mitochondrial dysfunction, inflammation and oxidation, together with stress management practises, are all additional and valuable approaches to calming excessive glutamate release.

L-theanine may have potential here also. L-theanine itself is not an antioxidant, however via its ability to promote glutathione and preserve antioxidant status (e.g. preventing lipid peroxidation within tissues such as the CNS[10] and liver[11]), it exerts benefits in protecting specific tissues for toxicant- and oxidant-induced damage.

In addition to its protective benefits and structural similarity to glutamate, it is hypothesised that L-theanine may also regulate inhibitory neurotransmitters, including GABA and serotonin.[12,13]

More on alpha brain waves

L-theanine is demonstrated to increases alpha brain wave activity,[2] but what exactly does that mean? 

The human brain emits weak electrical impulses that can be measured on the surface of the head. These are referred to as brain waves, and are classified based on their frequency, and fall into four categories; alpha (α), beta (β), delta (δ), and theta (θ).[2] Each brain wave is related to individual mental states.

In human volunteers, alpha waves are generated on the occipital and parietal regions of the brain surface within 40 minutes of L-theanine consumption. Alpha waves are known to indicate an awake, alert and relaxed state, similar to what is achieved through meditation. However, L-theanine does not increase the levels of theta waves, which indicate light sleep or a drowsy state and therefore does not promote drowsiness. Beta waves are associated with a awake and excited state, while delta waves denote deep sound sleep.[2]

Sleep support

It is via a combination of its anxiolytic benefits that L-theanine is likely to be useful for promoting improved sleep (despite it not inducing drowsiness). 

Research investigating the amino acid’s benefit for sleep showed treatment to enhance sleep quality, reducing night waking and resulting in greater feelings of being well rested the following day. As a supplement it is safe, effective, non-addictive and without the side effects commonly associated with prescription sleep medications.[14] These benefits have been demonstrated in both children and adults.

Safety with anxiolytic medications

There is limited evidence surrounding the use of L-theanine in combination with anxiolytic medications. Preliminary animal studies investigating L-theanine in combination with both a benzodiazepine and a benzodiazepine receptor antagonist suggested that it is not via the GABA receptor that L-theanine works, and therefore its use in combination with these drugs is not believed to be of concern. The study did however suggest a synergistic effect of the two used in combination.[15]

Neuroprotection

Excessive activation of glutamate receptors (e.g. NMDA receptor) in the brain is associated with excitotoxicity, resultant neuronal damage and risk of neurodegenerative conditions. Many factors contribute to excessive glutamate release and NMDA activation. They include numerous psychological and physiologic stressors (e.g. chronic emotional stress, nutritional deficiencies (e.g. magnesium and zinc), inflammation, oxidative stress and local mitochondrial dysfunction). 

As a regulator of glutamate binding, L-theanine may exert neuroprotective properties by preventing this excitotoxicity. Furthermore, animal studies suggest L-theanine to be broader in its function as a neuroprotective agent. The amino acid is shown to provide benefits include preservation of antioxidant status within the CNS. 

For example, in animal studies, pre-treatment with L-theanine protected against aluminium-induced neurotoxicity in specific brain regions (cerebral cortex, hippocampus and cerebellum),[10] and attenuated toxin-induced neurological damage and suppression of nerve growth factors (e.g. BDNF) commonly seen in those susceptible to Parkinson’s disease.[16]

Broader protective benefits

Interestingly, L-theanine is also shown to promote glutathione in the liver and to protect hepatocytes against alcohol-induced toxicity.[11,17] In animal studies, L-theanine treatment preserved hepatocyte antioxidant capabilities and prevented local lipid peroxidation. 

Furthermore L-theanine was also shown to heal NSAID-induced gastric ulcer by modulating the pro- and antioxidant balance in the gastric ulcer margin. In this study a dose of 10mg/kg healed the gastric ulcer, however much higher doses of 40mg/kg aggravated the condition.[18]

Via its ability to support individuals during times of stress, L-theanine is shown to reduce the rise in blood pressure experienced by high-stress-response adults. In this group, doses of 200mg/day significantly changed both systolic and diastolic blood pressures when compared to placebo.[9]

Support for cancer patients

Preliminary evidence has suggested L-theanine may play a role in supporting cancer sufferers during treatment. Not only does its anxiolytic benefits provide support for wellbeing through what can be a significantly stressful period of time, but the amino acid’s ability to bind glutamate receptors may have a direct effect on tumour cells. It exerts these benefits by competitively inhibiting glutamate transport into tumour cells thereby decreasing intracellular glutathione levels and inhibiting the efflux of chemotherapeutic agents, resulting in their accumulation in tumour cells.

The hypothesis is that this function suppresses the tumour cells’ ability to protect themselves against therapy. L-theanine appears to have the opposite effect in healthy cells, assisting in the maintenance of intracellular glutathione levels, protecting these from oxidative stress.[19,20]

Furthermore, animal and in vitro research supports this, revealing L-theanine treatment to decreases tumour size, reduce metastases, reduce bone marrow suppression, and increases the efficacy of chemotherapeutic agents.[17,19] Human data is limited, and more research is warranted, however these potential additional benefits when utilising the supplement for management of anxiety is certainly positive.

REFERENCES

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belinda_reynolds's picture
Belinda Reynolds

Belinda is a dietitian and Senior Educator at one of Australia's leading nutraceutical companies. She graduated with an Honours Degree in Nutrition and Dietetics, and has been involved in the complementary medicine industry for over 15 years. Her key interests are immune modulation, the human microbiome and the impact they have on overall health.