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Focus on GABA

Artistic rendering of the brain with the central nervous system outlined in blue.
Dr. Ilene Ruhoy
Medical Director, Neurologist

GABA (gamma-aminobutyric acid) is an important neurotransmitter in the central nervous system. It is the major inhibitory neurotransmitter and has been implicated in a multitude of health challenges including anxiety disorders, insomnia, depression, psychiatric disorders, epilepsy, and movement disorders. The receptors for GABA are distributed diffusely throughout different regions of the brain such as the cortex and the basal ganglia. The cortex is the layer of the brain associated with seizure activity, which is why so many anti-seizure medications work to increase the ratio of the inhibitory action of GABA over the excitatory action of another important neurotransmitter called glutamate. But the cortex also works in conjunction with other areas of our brain to control how we think, move, feel, perceive, learn, and behave. The basal ganglia region of the brain is associated with movement and GABA is one of its major neurotransmitters to send signals to the cortex and other areas to initiate and suppress movements of the muscle groups of our bodies. When there are appropriate levels of GABA, there is a muscle relaxant effect and not only do we feel less tense but we can move more smoothly and have more control over the way we move.

GABA plays a critical role in the development of the cells of the central nervous system, known as neurons. The presence of GABA allows cells to differentiate into appropriate numbers of neurons during brain formation and continued maturation. When the GABA molecule interacts with its two receptors, GABA-A and GABA-B, a certain change in conformation of the receptor occurs and sends signals within the cells that further results in the release of peptides and chemokines that can quell hyperexcitability of the neurons. Hyperexcitability of the neurons, depending on the area of the brain involved, can manifest as seizures, headaches, muscle cramping, anxiety, insomnia, tics, or psychiatric disorders. There are many reasons for heightened activity of the neurons but an important physiologic cause is either because of decreased GABA activity or increased glutamate activity. Balancing of these neurotransmitters is important for health and well-being. Indeed, low GABA activity has been correlated to anxiety, depression, focus and attention difficulties. Anti-seizure medications, due to their effects on GABA levels, have mood stabilizer properties and can be therapeutic for those suffering from mood disorders.

GABA receptors are also found in the hypothalamus, which contains unique anatomy that controls our circadian rhythms, or our sleep-wake cycles. Many sleep medications and even some botanical sleep aids work to increase activity of GABA. An important mineral is magnesium, which is a GABA agonist, meaning it adheres to the GABA receptors and activates the receptor as GABA would. It not only stimulates the GABA receptors to simulate the function of GABA, but magnesium also has properties that function to stabilize cellular membranes. Daily supplementation with magnesium can help treat headaches, concussion, anxiety, and insomnia. Foods that are rich in magnesium should be included in our daily diet. These foods include a variety of nuts, seeds, and beans, as well as bananas, spinach, broccoli, edamame, and quinoa.

GABA is ultimately a product of glucose metabolism with glutamate serving as its precursor for synthesis. GABA’s production is dependent on the health of the brain’s ability to form and degrade glutamate. Synthesis of GABA is dependent upon the enzyme glutamic acid decarboxylase (GAD), which helps make GABA from glutamate and requires pyridoxine as a co-factor in order to function efficiently. Pyridoxine is also known as vitamin B6. Vitamin B6 is a water soluble vitamin that increases the synthesis in GABA. This important vitamin can be found in spinach, bananas, potatoes, rice, raisins, and chickpeas and more.

Excessive levels of GABAergic activity can cause sedation and lethargy. To maintain control of concentration and balance of GABA levels, this neurochemical is metabolized with the help of a mitochondrial enzyme known as GABA transaminase (GABA-T). This enzyme works well in the presence of vitamin E. Vitamin E is a fat soluble nutrient that can be found in several different types of nuts and seeds, spinach, and vegetable oils. Considering the vital role of the mitochondria to produce energy for the cell and, by extension, the organ within which the cell resides, it makes sense the mitochondria would have a hand in helping the body maintain a balance of neurotransmitters that may make us sedated and lethargic. The mitochondria are interested in keeping a healthy energy balance. The brain is a very metabolically active organ and therefore contains many, many mitochondria so mitochondrial health is important.

This neurotransmitter is integral to how our brain functions and how our bodies feel. Supplementation with GABA formulations have not been shown to be highly effective in replenishing significantly low levels of GABA due to poor absorption and assimilation, though consistent supplementation may help some people over time. Supplementation of the vitamins necessary for GABA synthesis and metabolism, such as magnesium, vitamin B6, and vitamin E, are likely more useful. While there are many medications available today that have strong effects on GABA levels and activity such as benzodiazepines, anticonvulsants, neuropathic pain medications, anesthetics, sleep medications, and barbiturates, these medications have side effects and long-term consequences. When necessary for control of severe depression, epilepsy, chronic pain, or movement disorders, they can be very useful.

Whole food sources of vitamins that support GABA function as well as foods that contain compounds that boost mitochondrial health is the healthiest way we can support our brain GABA function. Mitochondrial support vitamins and compounds include CoQ10, ribose, arginine, and vitamin C, among others. Spinach, broccoli, and cauliflower contain CoQ10, pumpkin seeds and peanuts contain arginine, mushrooms contain ribose, citrus fruits, bell peppers, and Brussel sprouts contain vitamin C.

Further plant-based support comes in the form of medicinal botanicals. Many herbs have demonstrated GABAergic activity by behaving as GABA receptor agonists. These botanicals include skullcap, valerian, passionflower, ashwagandha, and lemon balm and are commonly recommended for insomnia and anxiety but are also thought to be helpful as adjunct therapy for seizure or movement disorders. Many of these botanicals also serve as adaptogens and can help the body modulate its response to stressors which can lead to a low balance of GABA compared to the stress hormone neurochemicals. These herbs are important for stress management.

Additional ways of improving GABAergic activity include movement, deep breathing exercises, and meditation. Exercise such as yoga, Pilates, running, or walking and daily meditation with focused deep breathing can help us feel relaxed. These modalities serve to decrease tone and tension in the central nervous by way of increasing GABA, decreasing glutamate as well as improving serotonin, epinephrine, and dopamine levels, other essential neurotransmitters for brain and body health. A key point to understand is the interplay of different neurotransmitters in brain health, which is why some of the medications used to increase GABA function will commonly have side effects of irritability and other concerns due to change in transmitter ratios and balance.

Movement, deep breathing exercises, and mediation can have fairly immediate effects of GABA levels but may be transient while nutritional and botanical approaches may take a while to naturally increase GABA but these are more sustainable. Consuming foods with the necessary vitamins, nutrients, and compounds to enhance GABAergic activity will help maintain a more natural, homeostatic static of neurotransmitter balance and will allow for better tolerance and adaptability to stressors, whether they be internal or external. These are examples of how we can support GABA and overall neurotransmitter function in a natural and healthy way. Much of what we eat and how we live creates inflammation. When the inflammatory fires are stoked within our body, physiologic energy has to then be diverted to combat the inflammation. Therefore, energy and resources are depleted and not available for brain function, which requires many different biochemical reactions to synthesize, utilize, and degrade neurotransmitters. Often times, we just succumb to poor sleep, depressed mood, anxiousness, pain, tension, and agitation and seek to either self-medicate or take pharmaceuticals to help us get through the day.

Many of these symptoms can be at least minimized by certain lifestyle choices we make. These choices are important in an effort to avoid chronic use of medication, minimize dosages of medications needed, or to avoid the need for medication all together. GABA is a chief inhibitory chemical in the brain and when levels are too low it can alter our perception of our world. With appropriate nutrition and botanicals, and other modalities to improve GABA, we can be more relaxed, sleep better, feel happier, and have more energy. These healthy choices will also have ancillary effects of reducing our risk of disease.

Photo © Geralt, available under Creative Commons CCO.