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L-theanine, also known as L-γ-glutamylethylamide and N⁵-ethyl-L-glutamine is a non-protein amino acid that’s naturally occurring in some plants and fungus. Theanine is the name given to L-theanine when it is used as a food supplement, which is permitted in many international locations. Most famously L-theanine was found to be an active ingredient in green tea back in 1949. Multiple lab studies on L-theanine have found it to improve cognitive function, alleviate psychological stress, maintain normal sleep patterns, and provide comfort during menses.
Multiple animal studies have shown that L-theanine stimulates the production of serotonin, dopamine and GABA, which have neuroprotective effects on the brain and enhance cognition. L-theanine also blocks the activity of glutamate, thus it is “glutamatergic”. Glutamate and GABA have a complex interwoven bidirectional relationship; an optimal balance of both factors brings about enhanced cognitive abilities.
Glutamate is the brain and central nervous system’s excitatory neurotransmitter (alongside aspartate), responsible for getting your brain fired up and ready for action. In pre- and post-natal development, glutamate is required for healthy brain development and, in maturity, it plays a pivotal role in learning. Conversely, elevated levels of glutamate can cause pain amplification, anxiety, neurological inflammation and premature cellular death.
Glutamate is effectively blocked when L-theanine binds to the AMPA, kainate and NMDA receptor ligands in the brain indicating that long-term glutamate excitotoxicity could be fended off by effective L-theanine supplementation. Glutamate can be derived from blood glucose, suggesting reducing sugar in your diet may also help lower glutamate serum levels.
Gamma-Aminobutyric Acid (GABA) is the body’s primary inhibitory neurotransmitter that is responsible for the proliferation of both embryonic cells and stem cells. GABA’s chief role is the reduction of excitability in the central nervous system. GABA counteracts glutamate and promotes restful sleep and also aids in the regeneration of muscle tissue. Interestingly, in speech, GABA is the “pause” between the words, uncovering a possible link between the stringing of sentences or excessive talkativeness in patients with anxiety and bipolar disorder and low levels of GABA.
When exposed to stressful stimulus, blood pressure rises and glutamate receptors are activated. If blood pressure rises too much then the brain’s blood vessels get damaged and this can result in a stroke. L-theanine has been shown to modulate extreme spikes in blood pressure, promoting associated vascular health throughout the body.
Other long-term neurodegenerative disorders are being studied to assess the viability of L-theanine as a possible glutamatergic. In one animal study, L-theanine significantly altered gene expression in the brain’s amygdala region, the area responsible for the fear and stress response, promoting relaxation in rats.
A strong or prolonged stress response has negative effects on cognition. This, in turn, can lead to oxidative stress, inflammation and weakened blood vessels. A promising animal study showed that animals treated with L-theanine, before the stress stimulus was applied, lowered the stress hormones and preserved cognition in the brain.
Chronic restraint stress (CRS) results in increased glucocorticoid levels and altered brain-derived neurotrophic factor (BDNF) function. This immobilized stress has catastrophic effects on cognitive abilities. L-theanine offered cognitive protection in rats subjected to CRS for 8 hours per day.
A further animal study exposed neuroprotective activity in rats induced with Huntington's disease (HD)-like symptoms by induction of 3-nitropropionic acid (3-NP). When exposed to 3-NP, rats experienced many degenerative effects such as a reduction in body weight, oxidative defences and decreased locomotor activity. Use of L-theanine resulted in an improvement in behaviour, as well as increased biochemical and mitochondrial enzyme activities.
L-theanine has also been found to offer neuroprotection from toxic compounds such as aluminium. In one study, aluminium was found to produce histopathological changes in the rat brain. When the subjects ingested L-theanine, the researchers found protection against neurodegenerative effects and concluded, “The present study clearly indicates the potential of L-theanine in counteracting the damage inflicted by aluminium on rat brain regions.”
A healthy balance between GABA and glutamate is essential to maintain homeostasis throughout the body. Glutamate is the accelerator, allowing you to go places and GABA works like the brakes, allowing you to regulate your speed and rest. Excess glutamate can be converted into GABA with the help of the enzyme glutamic acid decarboxylase (GAD) that is produced in the pancreas.
However, there are reasons that the body will not be able to perform this essential metabolic reaction, for example, Candida overgrowth or gut dysbiosis. Other reasons that the body cannot convert excess glutamate into GABA are lead toxicity and B vitamin deficiency.
In summary, L-theanine can target the glutamate receptors, which not only inhibits glutamate from binding to those receptors, but also triggers the production of GABA, offering a viable pathway to balance the GABA-glutamate balance.
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