As with most things in life, balance is key to an optimally functioning nervous system. GABA and glutamate are the primary calming and excitatory neurotransmitters in the central nervous system (respectively) and serve opposing functions. Despite their opposite roles, GABA and glutamate have many connections, including their existence in the same biological pathway (Figure 1).
Under normal physiological conditions, glutamate and GABA activity is in balance. However, under stressful conditions, such as inflammation or immune upregulation, glutamate activity increases. If the nervous system is functioning appropriately, GABA activity also increases to compensate for the excitation in an attempt to restore homeostasis.
Glutamate is the precursor to GABA, which means an increase in glutamate levels should cause a subsequent increase in GABA synthesis as well (Figure 2). This “allostatic mechanism” is the body’s attempt to restore homeostasis and balance excitatory and compensatory activity. Common symptoms of an imbalanced system in which glutamate levels are more elevated than GABA levels include anxiousness, overstimulation, sleep difficulties, and focus issues.
How do glutamate and GABA become out of balance though? There are a variety of factors that can prevent glutamate from converting to GABA. One of the most common is malnutrition or poor diet. Without an adequate amount of Vitamin B6 in their diet, or poor absorption of B6 in the GI tract, there may not be enough necessary cofactor for the glutamate decarboxylase enzyme to facilitate the conversion to GABA. Another possible contributor to inadequate conversion is gluten sensitivity. Gluten sensitivity creates gliadin antibodies which specifically inhibit the glutamate decarboxylase enzyme. Without the functional enzyme, GABA synthesis is compromised, which can lead to low GABA levels.
Regardless of the cause, imbalances between glutamate and GABA can lead to symptoms. For a healthy and optimally functioning nervous system, GABA and glutamate balance is essential. Even though GABA is the most calming neurotransmitter in the central nervous system, and glutamate the most excitatory, they are irreversibly linked as part of the same biochemical pathway and balance is key.