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What is GABA? GABA is Gamma-aminobutyric acid, a neurotransmitter and the cornerstone of the inhibitory (calming) system in the body; controlling the action of epinephrine, norepinephrine, and dopamine.
Inhibitory neurotransmitters and their receptors reduce excitability in the brains neurons and increase the likelihood that an incoming signal will be terminated. For optimal functioning, the brain must balance the excitatory and inhibitory influences: Excessive excitation can lead to seizures, insomnia, anxiety, and many other clinical conditions, whereas excessive inhibition of neurons can result in incoordination, sedation, and anesthesia.
GABA is the primary inhibitory neurotransmitter in the brain and therefore filters out irrelevant messages (static) by terminating signals from the excitatory neurotransmitters: glutamate, and its positive modulators epinephrine, norepinephrine, and PEA. GABA can be viewed as the “braking system” in the realm of neurotransmitters.
In situations where there is high excitatory neurotransmitter activity, the brain typically responds with an increase in the inhibitory GABA activity as well. In essence this slows down neurotransmission by pressing on the GABA “brakes.” Under normal conditions, normal levels of GABA are sufficient to maintain control of the excitatory stimuli. If, however, GABA function is impaired (worn brakes) then higher levels (pressing harder on the pedal) of GABA are required.
GABA’s high concentration in the hypothalamus suggests it plays a significant role in hypothalamic-pituitary function. The hypothalamus is a region of the posterior section of the brain that is the regulating center for visceral (instinctive) functions such as sleep cycles, body temperature and the activity of the pituitary gland.
The pituitary gland is the master endocrine gland affecting all hormone functions of the body.
A recent study indicates that GABA also enhances alpha wave production in the brain to promote relaxation and moderate occasional stress. In the same study, it supported healthy IgA levels, suggesting that it may support immune health during occasional stress. Pyridoxal 5’phosphate is an important cofactor involved in the natural synthesis of GABA, providing synergistic support.
Low GABA levels have been found in the brains of patients with multiple sclerosis, action tremors, tardive dyskinesia, & other disorders of movement.
GABA receptor function may be reduced because of a genetic polymorphism in the GABA receptor that reduces the efficiency of GABA neurotransmission, the presence of GABA receptor inhibitors, or low serotonin levels. Serotonin is a positive regulator of GABA-GABA receptor interaction.
An inadequate GABA response may lead to an extended state of excitement and electrical stimulation in the brain.
GABA deficiency can be linked to anxiety disorders such as panic attacks, seizure disorders like epilepsy, and numerous other conditions including addiction, headaches, Parkinson’s Syndrome, and cognitive impairment. GABA’s role is that of the primary inhibitory neurotransmitter and functions by down-regulating neurotransmission.
GABA is formed through the activity of the enzyme glutamic acid decarboxylase (GAD). GAD catalyzes the formation of GABA from glutamic acid. The synthesis of GABA is linked to the Kreb’s cycle. GAD requires vitamin B6 (pyridoxal phosphate) as a cofactor, which can be used to regulate the levels of GABA. Vitamin B6 is a key GABA vitamin.
GABA can be metabolized by a transamination reaction with a-ketoglutarate, catalyzed by GABA-transaminase. Compounds such as the competitive GAD inhibitor allylglycine, inhibit GABA formation and cause convulsions due to the lack of GABA activity.
The importance of GABA is underscored by the frequency in which it is a pharmaceutical target and how many commonly used drugs affect its function, e.g. Xanax, Klonapin, Valium, Neurontin.
The GABA receptor is a relatively large molecule and has binding sites not only for GABA but also for many modulatory compounds. Many of these modulatory compounds are useful therapeutic agents. Positive GABA modulators, like the benzodiazepines, do not cause the ion channel to open and an influx of chloride ions to occur on their own. They only enhance the activity of naturally occurring GABA by potentiating its function and therefore have vastly reduced potential for overdose or side effects than receptor agonist compounds, like barbiturates. While much safer than barbiturates benzodiazepine use frequently leads to dependence and withdrawal syndrome effects. This limits their utility for mild/moderate symptoms as well as for long-term therapy.
While drugs alter or potentiate the GABA receptor, they do not add any GABA to the system. Drugs rely on a sufficient supply of endogenous GABA in the brain to function properly. However, due to factors like diet, stress, and genetics, a healthy supply of GABA may not be available.
Gamma-aminobutyric acid (GABA) is a non-essential amino acid formed from glutamic acid with the help of vitamin B6. GABA (gamma-aminobutyric acid) is found in almost every region of brain, and is formed through the activity of the enzyme glutamic acid decarboxylase (GAD). GAD catalyzes the formation of GABA from glutamic acid. GAD requires vitamin B6 (pyridoxal phosphate) as a cofactor, which can be used to regulate the levels of GABA.
GABA has little to no side effects. Some sleepiness has been reported.
A second approach to enhancing the GABA system includes supplementing with GABAs precursors and potentiators. These include the amino acids listed below. These amino acids freely cross the blood brain barrier and are a safe, effective option for patients using or considering prescription medications or large doses of GABA.
Phenibut better known as Beta-phenyl-gamma-aminobutyric acid is derived from the neurotransmitter GABA and is capable of crossing the blood brain barrier. Phenibut is cited as a nootropic (that is, “smart drug”) for its ability to improve neurological functions. Check out Kavinace, a GABA supplement that contains Phenibut.
Taurine is an amino acid that is present at significant levels in the CNS and is positive modulator of GABA that does not have any adverse side-effects. Taurine also potentiates glycine – the inhibitory neurotransmitter in the spinal cord.
The role of taurine as an inhibitory amino acid has been confirmed in many studies. Not surprisingly, brain tissue and cardiac tissue, which are susceptible to high levels of neurotransmitter stimulation, maintain high levels of taurine. Taurine has been shown to prevent the neuronal damage that can occur when there is an exposure to increased levels of the excitatory neurotransmitter glutamate. Over stimulation by excitatory neurotransmitters is the primary cause of neuron death in ischemic stroke. Taurine has been found to significantly reduce neuron death caused by over stimulation.
The calming effects of taurine have been well studied. Other studies of taurine have found that it can reduce epileptic seizures and that low taurine levels are associated with anxiety.
Glutamine is an amino acid and a common precursor for the biosynthesis of GABA and glutamate. Significant quantities of glutamine are normally present in the brain to support the complex process of GABA synthesis. Those with high Glutamate levels should not supplement with Glutamine.
Serotonin is a neurotransmitter, or more correctly a neuromodulator, that is widely distributed throughout the brain and generally enhances GABA and therefore has inhibitory activity. Therefore, as a precursor to serotonin, 5-HTP can further increase the activity of GABA. Low serotonin levels are frequently an underlying component of many clinical conditions that are also related to GABA function, e.g. insomnia, depression, & anxiety.
Neurotransmitter tests show that GABA needs serotonin to function properly. Normally, GABA increases and acts through a negative feedback mechanism to reduce elevated excitatory neurotransmitters. However, this feedback mechanism requires the neuromodulating effects of serotonin. This is evident in patients with symptoms related to low GABA who have adequate GABA levels but low serotonin.
Theanine is another amino acid that affects GABA. Initial interest in theanine arose due to the seemingly paradoxical calming effect of a caffeine containing drink. Theanine is a naturally occurring amino acid present at significant levels in green tea leaves and is the component responsible for this reaction.
Theanine has been found to alter glutamate transport and actually increase GABA levels. Further studies reveal that theanine reduces hypertension in models of hypertension, increases the effectiveness of some chemotherapy compounds, reduces the stimulatory effect of caffeine, and calms patients.
Add GABA to your diet. Fish (especially mackerel), wheat and bran are sources of GABA Gamma Amino.
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