Caffeine, a naturally occurring psychoactive drug, has been a part of people’s routines for a long time. Its effects on the Central Nervous System lead to higher levels of vigilance, attention and performance, reducing sedation and fatigue. However, the mechanisms of action of caffeine can lead to negative side effects such as headaches, jitters and increased blood pressure. L-theanine is an amino acid analogue present in small amounts in tea leaves. This molecule regulates neurotransmitters, enhancing neurological health and leading to a more relaxed state, reducing one’s perception of stress and anxiety. The synergetic action of caffeine and L-theanine makes the combination of these compounds a great solution for the increasing demands of daily life. L-theanine enhances caffeine’s cognitive benefits while eliminating the previously mentioned adverse effects, resulting in a calm and focused state.
Caffeine is the most vastly used psychoactive drug in the world [1, 2]. Chemically, it’s a methylxanthine related to the nucleobases in our own DNA, and it’s a naturally occurring molecule in coffee plants, mate herb leaves, guarana berries, among others [2-4].
The mechanisms of action of caffeine are mainly related to the Central Nervous System (CNS), which then greatly influences blood flow, metabolism, cerebral electrical activity and many others [5-7]. Caffeine’s interaction with Adenosine receptors in neurons prevents Adenosine itself from binding to them, reducing post-prandial drowsiness and conferring caffeine its stimulant effects through the release of neurotransmitters such as acetylcholine [8, 9]. Since caffeine is soluble both in water and fats, it penetrates the blood-brain barrier and exerts its effects directly in brain neurons [10, 11]. Caffeine is also involved in the mobilization of intracellular calcium [12, 13] and inhibition of phosphodiesterase activity , which leads to the accumulation of cyclic Adenosine Monophosphate (cAMP), increasing respiratory rate and vasoconstriction (fight or flight response). Other mechanisms of action are related to caffeine’s interaction with benzodiazepine binding sites and neurotransmitters themselves .
All these biochemical effects are translated into physiological responses that are felt after caffeine consumption. Studies report effects such as increase in vigilance, alertness, attention, performance and visual perception, as well as decreased reaction time, sedation and fatigue [16-18]. In cases of hypotension or some postnatal problems, it can be used as treatment [19, 20]. Reported but not confirmed effects include increased stamina, memory and protection against problems such as kidney stones and liver fibrosis.
However, the overall effects of caffeine intake are dictated by the caffeine source, dose and the person’s own system (metabolism, hormone levels, illnesses, age and others) [21, 22].
In some cases, caffeine is responsible for several detrimental effects [23-25]. There have been reports of caffeine-induced headaches (while others report headache relief due to the substance)  and jitters (which are worsened in cases of anxiety or sleep disorder, among others) . Caffeine also induces an increase in stomach acidity (lowering of the pH) [28, 29], which can be dangerous for people with ulcers or gastric reflux. Effects such as rapid or erratic heart rhythm and hypertension have also been reported . The changes in calcium storage and uptake caused by caffeine can worsen or influence osteoporosis in people with previous bone density-related problems . For some people, caffeine withdrawal is also related with all sorts of adverse reactions such as nausea and vomiting, convulsions and increased thirst.
L-Theanine is an amino acid analogue (similar chemical structure to L-glutamate and L-theanine, which are naturally occurring in humans) [32, 33]. The ‘L’ indicator refers to the enantiomeric form of the compound, theanine, which is related to the spatial orientation of the atoms around a specific (chiral) carbon atom. L-theanine is naturally occurring in tea leaves from the Camellia sinensis plant, being present in black, green and white tea [34, 35]. It’s important to point out that L-theanine is only naturally present in very small doses that don’t exert significant effects, as opposed to caffeine, which is easily found in larger doses. To experience the effects of L-theanine, very large amounts of tea must be consumed (which are accompanied by several unfavourable side effects) or supplements must be taken.
After ingestion, L-theanine is absorbed in the small intestine and it enters the bloodstream, from where it’s able to cross the blood-brain barrier since it’s also water and fat soluble . L-theanine’s effect can be described in general terms as upregulation of inhibitory neurotransmitters (such as GABA and glycine) and inhibition of excitatory neurotransmitters, which means it has a regulatory role in brain function, modulating excitatory brain responses [37, 38]. Since it’s similar to glutamate, it can bind to the same receptors and transporters, inhibiting the damaging effects that excess glutamate can have on the neurological system, thus acting as a neuroprotectant [39, 40]. L-theanine also promotes the production of Nitric Oxide (NO) by endothelial cells, which in turn leads to vasodilation. This molecule is also reportedly associated with increased alpha-wave brain oscillations , which are indicative of a relaxed but attentive state.
The overall physiological effects of L-theanine include relaxation without sedation, reduction of blood pressure and of one’s perception of stress and anxiety [42, 43]. Besides being used as treatment for high blood pressure, there are extensive reports on the beneficial effects of L-theanine coupling with medication or other supplements.
Caffeine’s not perfect and L-theanine can’t provide the required boost for a stressful and demanding life, but together their properties become much more interesting. The mechanisms of synergistic interaction between these two compounds been studied and verified.
On a cognitive level, L-theanine enhances the effects of caffeine on speed and accuracy of information processing, reduction of mental fatigue and tiredness, performance on complex tasks such as sentence verification, word recognition, speed and accuracy of sustained attention [44, 45]. L-theanine exerts slow and constant effects, modulating the spikes in performance that caffeine brings about, working in combination with it to improve task switching and the ability to ignore distraction [46, 47].
Negative effects resulting from caffeine such as headaches, jitters, blood pressure and heart rhythm increase can be counteracted by the addition of L-theanine [48, 49].
Psychologically, the combination of these two components is more reflective of the cognitive performance required in stressful, everyday occupations than the simple speed of perception and speed of reaction tasks that’s obtained using only caffeine.Fundamentally, the synergetic action of caffeine and L-theanine enhances all the cognitive and alertness benefits of caffeine while contributing to a calmer and more focused mental state, as well as promoting long-term improvement of neurological health.
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