GABA (gamma amino butyric acid) is considered the main inhibitory neurotransmitter in the central nervous system. It regulates neuronal excitability and muscle tone.1
GABA is synthesized from glutamate (using vitamin B6 as a cofactor). GABA is Interestingly, while glutamate is the brain’s main excitatory neurotransmitter,2 GABA “puts the brakes” on in the brain, helping to control overstimulation.
gamma-Aminobutyric acid (γ-Aminobutyric acid) /ˈɡæmə əˈmiːnoʊbjuːˈtɪrᵻk ˈæsᵻd/ (also called GABA /ˈɡæbə/ for short) is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone.
Although in chemical terms it is an amino acid, GABA is rarely referred to as such in the scientific or medical communities, because the term “amino acid,” used without a qualifier, by convention refers to the alpha amino acids, which GABA is not, nor is it considered to be incorporated into proteins.
NEUROTRANSMITTER REVIEW
The nervous system is made up of individual nerve cells called neurons. They serve as the body’s wiring. Nerve signals are transmitted through the length of a neuron as an electrical impulse. When a nerve impulse reaches the end of the neuron it can jump over to the next cell using chemical messengers called neurotransmitters.
In the central nervous system, which consists of the brain and the spinal cord, neurotransmitters pass from neuron to neuron. In the peripheral nervous system, which is made up of the nerves that run from the central nervous system to the rest of the body, the chemical signals pass between a neuron and an adjacent muscle or gland cell.
Glutamate and GABA are the most abundant neurotransmitters in the central nervous system, and especially in the cerebral cortex, which is where thinking occurs and sensations are interpreted.
Tiny sacs filled with neurotransmitters are stored at the end of each neuron. When a nerve impulse reaches the cell’s end it triggers these sacs to dump the neurotransmitters into the gaps that separate one nerve cell from another. These spaces are called synapses. The neurotransmitters float across the synapse. When they reach the neighboring neuron, the neurotransmitters click into specialized receptor sites much as a key fits into a lock. When enough neurotransmitters attach to the receptors, the neuron “fires,” sending an electrical impulse down its length.
GABA’S ROLE IN THE BRAIN
GABA is made in brain cells from glutamate, and functions as an inhibitory neurotransmitter – meaning that it blocks nerve impulses. Glutamate acts as an excitatory neurotransmitter and when bound to adjacent cells encourages them to “fire” and send a nerve impulse. GABA does the opposite and tells the adjoining cells not to “fire”, not to send an impulse.
Without GABA, nerve cells fire too often and too easily. Anxiety disorders such as panic attacks, seizure disorders, and numerous other conditions including addiction, headaches, Parkinson’s syndrome, and cognitive impairment are all related to low GABA activity. GABA hinders the transmission of nerve impulses from one neuron to another. It has a calming or quieting influence. A good example to help understand this effect is caffeine. Caffeine inhibits GABA release. The less GABA, the more nerve transmissions occur. Think what too much coffee feels like: that is the sensation of glutamate without enough GABA.
The reason caffeine does this is that other molecules can bind to the neuron near the GABA binding site and influence GABA’s effect. This is how tranquilizing drugs such as Benzodiazepines and barbiturates work. They increase or imitate GABA’s effect, inhibiting nerve transmission.
Research on GABA
In the half century since GABA was identified as a neurotransmitter there has been an enormous amount of research published directed toward its role in both animals and humans. Most of this has focused on the mechanics of GABA action and the drugs and chemicals which affect its action along with GABA’s role in various disease states. A search on the term GABA on PubMed today ( October 7, 2004 ) brings up a list of 43,859 published papers. Only a handful of these papers focus on using GABA orally as a nutritional supplement. Some nutritional writers suggest a conspiracy on the part of the drug industry to suppress GABA research so as to promote their drugs such as Valium. [1] A more likely explanation rests in the fact that the common belief among scientists is that GABA will not cross the blood brain barrier. If GABA does not reach the brain, it will have no effect. Although I have found no direct published evidence proving that oral GABA changes brain levels of GABA, some scientists assume that with large enough doses some may cross over. [2] This amount may vary from person to person, their nutritional status, physical conditioning and activity level.
This lack of research caught me by surprise. With most nutritional and herbal supplements these days there is ample research to argue in support of their therapeutic use. This is an unusual situation in modern nutritional medicine. Few of the websites which sell GABA list references for the scientifically proven benefits attributed to its use. This is unsatisfactory and discredits the bona fide claims made for other products. Instead of garnering uses directly from clinical research, we are left to look elsewhere.
Possible Uses of GABA:
The best information I have on clinical use comes from the writing of Eric Braverman and Carl Pfeiffer. [3] Their 1987 book on the clinical use of amino acids is a classic treatise for the practice of nutritional medicine.
Anxiety:
If oral GABA reaches the brain in any significant amount it should act as a tranquilizer. GABA as a neurotransmitter, blocks nerve impulses and slows neuronal transmission. It should make you feel the opposite of a double espresso.
Braverman and Pfeiffer write an anecdotal account of the successful treatment of a forty year old woman suffering from anxiety with 800 mg of GABA a day. They also gave her an undisclosed amount of inositol which we now know is an effective anxiolytic used in treating obsessive compulsive disorder. Was it the GABA or the inositol that helped this patient? Perhaps the combination.
Though this anecdote is inconclusive, using GABA to treat anxiety is the most common and reasonable use.
Will the brain adapt to supplemental GABA? There are no answers to this as no one has proven GABA reaches the brain. Looking at the brain’s capacity to change GABA receptor response and its tendency to build up tolerance to drugs which modify GABA, it is possible that a tolerance to oral GABA might develop and withdrawal symptoms might occur. None are reported in the literature to my knowledge.