straight gaba
GABA: Gamma-Amino Butyric Acid
INTRODUCTION:
Gamma-Amino Butyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. It inhibits nerve transmission in the brain, calming nervous activity. As a supplement it is sold and promoted for these neurotransmitter effects as a natural tranquilizer. It is also touted as increasing Human Growth Hormone levels and is popular among body builders. The published research supporting any of these promotional claims is weak. Current medical opinion says that GABA taken as a supplement does not reach the brain and has no effect or benefit aside from being a benign placebo.
Many websites claim that the neurotransmitter GABA was discovered in Berlin in 1863, which is an outlandish claim. The concept of neurotransmitters had yet to be conceived of. It is more likely that GABA was isolated and identified as an amino acid in 1863. It was 87 years later, in 1950, that Eugene Roberts and J. Awapara discovered that GABA acted as an inhibitory neurotransmitter.
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.
HUMAN GROWTH HORMONE
There is evidence that getting extra GABA into the brain increases Human Growth Hormone. Injections of GABA directly into the brain increase Growth Hormone in rats. Baclofin, a drug analog of GABA that does reach the brain, increases HGH [14] so it makes sense that GABA would do the same.
Several studies support the notion that taking oral GABA increases Human Growth Hormone (HGH). Two of the studies were published almost 25 years ago. They used a small number of test subjects. Yet they produced significant increases, HGH levels increased 500%. [15] [16] No studies replicated this effect for years bringing the initial results into question. In May of 2003, a new study confirmed the results of the early studies. The new study measured GABA and HGH in body builders. Three grams doses of GABA increased HGH levels, but only if taken just before exercise. Without exercise, the GABA had no effect on HGH. [17] We should clarify the term exercise, test subjects were body builders; we are talking about a strenuous workout. If GABA can raise HGH levels, some of it may cross the blood brain barrier, perhaps only after exhausting exercise.
The HGH studies raise some concerns. Oral GABA also affects the pancreas increasing insulin production. [18] Of course with all the concern about Syndrome X and hyperinsulinemia, making more insulin might not desirable. Yet a diabetic might find the insulin stimulating effect contributes to better blood sugar control. Besides increasing insulin and HGH, oral GABA increases prolactin, a finding not emphasized in the promotional literature. Prolactin is the hormone that stimulates the breasts to produce milk. Although body builders want to build up their chest size, they probably don't want to do it this way. Although there is no research on taking GABA during pregnancy or nursing, pregnant or nursing mothers should not take this information to suggest that GABA might increase their milk supply. It might, but it also might stimulate early breast development and lactation in their infants.
There are other amino acids besides GABA that increase HGH. [19] Whether they are more effective is unknown.
Suggested Dosages:
I would consider suggesting GABA to patients who are over anxious or who complain of insomnia due to “too many thoughts which I can't shut off.” Again I like the coffee analogy: If they look or feel like they drank too much coffee, GABA may help.
Research no longer supports using GABA for depression, bipolar disease or PMS: if it looks like they need a cup of coffee, don't use GABA
For increasing Human Growth Hormone production the studies used between 3 and 18 grams. Keep in mind that at these doses expect tingling.
CAUTIONS
GABA may cause sleepiness, that is if it works: Do not operate or drive heavy machinery while taking GABA, at least until you know what effect it has on you. Do not take GABA if you have been diagnosed with bipolar or unipolar depressive disorders. If taking doses greater than 3-4 grams do not be surprised if you experience a flushed tingling sensation; this appears to be a common experience. Caution should also be taken in combining GABA with any drug which affects GABA pathways in the brain. These drugs include but are not limited to barbiturates, benzodiazepines, and alcohol. GABA has not been tested in pregnant or breast-feeding women, children, or people with liver or kidney disease.
GHB
Gamma-hydroxybutyric acid (GHB) has a similar name but is a different chemical. It is made within the brain from GABA. GHB has been researched for treating alcohol, opiate and other drug dependencies and for treating withdrawal symptoms. [21] [22] [23] [24] GHB unfortunately can also be abused [25] and employed as a ‘date rape drug'. [26] It has gone from a promising new treatment for addictions to an addictive and dangerous drug in its own right. [27] Instead of touting potential benefits recent articles focus on how to treat overdoses [28] and the withdrawal syndrome associated with GHB. [29] Don't mix these two names up.
Other ways to skin the cat: other ways to increase GABA effect
Another approach is to look at substances which change GABA action in the brain. There seems to be more and better clinical research on the use of many of these substances in humans than there is on GABA. There are numerous natural substances which affect GABA. In fact understanding GABA helps explain the action of many commonly used herbs, vitamins and minerals.
Valerian root has a long history of use as a tranquilizer and works by increasing the effect of GABA on its receptors [30] American Ginseng also acts on the GABA receptors. [31] So does Kava Kava. [32]
All sorts of other unexpected things change GABA activity; the chemicals formed by aging whiskey in oak barrels increase GABA effect. Aging really does make whiskey mellower literally based on what it does to brain neurotransmitters. [33] These chemicals are released from the alcohol as a fragrance and appear to reach the brain by inhalation. [34] The fragrance of Oolong tea has a similar effect, increasing GABA action. [35] Extracts of green tea, black tea and oolong tea elicit a GABA response in test models. [36] Epigallocatechin gallate extracts from tea had the opposite effect, inhibiting the GABA response. Coffee extracts also inhibit GABA response. [37] Magnesium binds to GABA sites and increases effect. [38] Taurine protects against glutamate overstimulation. [39] [40] Its inhibitory effect may act as anxiolytic. [41]
Serotonin is another neurotransmitter and it enhances GABA. Therefore, as precursors to serotonin, Tryptophan and 5-HTP increase GABA action.
Theanine is an amino acid found in large amounts in tea. It is why a cup of tea can be calming despite the fact it contains caffeine. Theanine may increase glutamate transport [42] and increase GABA levels.
The vitamin B6 derivative pyridoxal phosphate is a cofactor in the synthesis of GABA. Some people have trouble converting Vitamin B-6 to pyridoxal phosphate and for those people taking this active B-6 may increase GABA levels.
While these other supplements alter or potentiate the GABA receptor, they do not add any GABA to the system. Many companies add one or more of these other materials to capsules containing GABA. The idea may be to amplify the effect of any GABA that crosses the Blood Brain Barrier into the brain. These other ingredients may work independently and be the active ingredient in the product.
At this point GABA is more interesting for the understanding it provides of the mechanics of the mind than it is as a nutritional supplement. Although small amounts of orally taken GABA may reach the brain and have a tranquilizing effect in certain individuals, there are many other alternatives which have both a longer history of safe use and better research support for their use. There are unanswered questions about the safety of the long term high doses promoted by some supplement companies. Although I can say as others do that there is no evidence of harm from oral doses, there are no long term clinical trials published.
Try GABA if you want. If it provides a suitable tranquilizing effect, you are probably safe to use it for short term, low dose intervention.
