Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. Its principal role is in reducing neuronal excitability throughout the nervous system. This, in turn, induces a physiological state of relaxation, calm, balance, and sleep. The GABA shunt is a metabolic process with the dual roles of producing and conserving the supply of GABA. The GABA 
shunt interacts with the Krebs cycle, which is the primary energy-generating biochemical pathway in the mitochondria of our cells that releases stored energy as ATP.
The GABA Shunt
GABA is produced by neurons that are called GABAergic neurons. Once it is generated, GABA functions by acting on receptors in different cells. GABA(a) and GABA(c) receptors are chloride-gated ion channels which, when activated by GABA, allow the flow of chloride ions across cell membranes. Chloride ion flow and concentration affect the membrane potential of a cell and determine its excitability. An increase of chloride ions entering neurons through the GABA receptors can decrease its excitability, meaning the neuron won’t be as active. Decreasing neuron activity can help with conditions where the nervous system tends to be over excited, such as stress and anxious feelings.
So, it would seem that consuming GABA alone, which is available as a dietary supplement, would lead to nervous system inhibition and thus reduce stress or anxious feelings. However, this mechanism is not functional as GABA cannot cross the blood-brain barrier by itself – therefore, it cannot travel from the mouth, to the gut, to the blood, and ultimately to the brain to achieve the desired physiological effects.
Alternative Solutions
In place of GABA, there are several dietary ingredients that can cross the blood-brain barrier and directly act on GABA to then produce a state of relaxation. One of these is the amino acid L-theanine, found in green tea leaves. L-theanine has the ability to cross the blood-brain barrier. The exact mechanism by which L-theanine acts on GABA is not yet fully clear, however, studies in mice have shown that oral L-theanine increases GABA levels in the brain. Additionally, studies in rats have shown that oral L-theanine increases levels of dopamine in the brain – this is a separate mechanism by which L-theanine induces calmness and stress relief. Thus, there are clear mechanistic links between L-theanine and the physiological impact on stress, anxious feelings and sleep, with clinical effects having been demonstrated in a number of clinical studies on L-theanine (Suntheanine®).
In the botanical world, ashwagandha is the king of adaptogens. Adaptogens are natural substances (e.g. herbs and other plants) that help maintain homeostasis, or balance, through their calming effects – such as stress reduction and improved sleep function. Ashwagandha also acts on GABA by engaging GABAergic signaling. A high potency 35% withanolide glycoside ashwagandha extract (Shoden®) has been shown in rat studies to be an agonist to certain GABA receptors and thus directly inhibit these receptors, seeming to bypass the action of GABA itself.
Summary
The GABA shunt – GABA and its receptors – are a key component in the inhibition of the central nervous system, resulting in increased calmness, reduced stress, and improvements in sleep. L-theanine, as well as the withanolide glycoside components of ashwagandha, are able to cross the blood-brain barrier and directly or indirectly inhibit neurotransmitters, which in turn affect physiological stress.
More About the Ingredients
Suntheanine® L-theanine from NutriScience is the most completely studied form of L-theanine, made using a process that mimics the formation of L-theanine in green tea leaves. Many Suntheanine® studies have shown its effects on enhancing brain alpha-waves, reducing stress, and improving sleep. In combination with caffeine, Suntheanine® also reduces the side effects (e.g. jitteriness) of consuming caffeine.
Shoden® ashwagandha extract from NutriScience contains an industry-leading 35% withanolide glycosides, which can cross the blood-brain barrier and directly and indirectly affect the GABA receptors – this promotes calmness and relaxation. Shoden® has been clinically studied for anxiety, stress, sleep-related conditions, vitality, and increased testosterone in men.
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NutriScience Innovations develops and markets innovative ingredients for the dietary supplement and functional food markets. To learn more about Shoden® or Suntheanine®, please visit our website, or check out a short video on Suntheanine® below:
