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Information, effects, deficiency, dosage, side effects
The gamma-aminobutyric acid (GABA) is one of the most common inhibitory (inhibitory) neurotransmitters in the brain. Many people value nutritional supplements with the active ingredient for their relaxing effects, but in fact GABA also plays a crucial role in regulating many aspects in the body, such as mood, concentration, pain, sleep, and much more.
The abbreviation GABA stands for Gamma-Aminobutyric Acid. In German-speaking countries, it is also known asgamma-aminobutyric acid. It belongs to the non-proteinogenic amino acids. That is, it is not used for the synthesis of proteins.
GABA is a widely used neurotransmitter that affects many aspects of health, especially emotional stability. It regulates and limits neuroelectric activity. Without GABA, electrical impulses in the brain could get out of control and lead to seizures.
As an inhibitory neurotransmitter, GABA is particularly active in the brain. In mammals and thus also in humans, 25-50% of all synapses contain GABA receptors. This means that their transmission of stimuli can be inhibited by GABA.
Researchers have found that GABA is not only found in the brain, but also in the entire gastrointestinal tract. The neurotransmitter is represented both in the enteral nerves and in the endocrine cells. This suggests that GABA affects the digestive system both as a neurotransmitter and as an endocrine mediator.
GABA is synthesised in presynaptic neurons and stored in synaptic vesicles. The rate of GABA synthesis is determined by the enzyme L-glutamic acid decarboxylase (GAD).
GABA was first synthesised in the year 1883. At that time it was only known as a metabolite of plants and microorganisms. It was not until 1950 that researchers discovered the amino acid in the mammalian brain. However, the actual meaning and function as an inhibitory neurotransmitter could only be explained 16 years later.
In order for neurons to be able to send signals through the body, they must be able to communicate with one another in order to enable stimulus transmission. However, since the neurons are not directly connected to each other, communication takes place via the neurotransmitters.
There is a gap at the end of each neuron called the synapse. In order to communicate with the next cell, the signal has to cross this small space. This process is called neurotransmission. In most cases, a neurotransmitter is released from the so-called axon terminal after an action potential has reached the synapse.
When an electrical signal reaches the synapse, it releases small vesicles. These contain the neurotransmitters. They pour them out into the gap between the synapses, where the neurotransmitters then move to the neighboring cells.
These cells contain receptors to which the neurotransmitters bind and can trigger changes in the cells. The neurotransmitters and receptors work according to the key-lock principle. In the case of GABA, this means that it can only bind to one GABA receptor.
If the neurotransmitter binds to the transmembrane receptor, it can either put it into an excited state or inhibit it. This is done by changing the electrical charge in the postsynaptic neuron through negatively charged chloride ions or positively charged potassium ions.
Through hyper-polarisation, GABA ensures that no further action potentials are fired in the neurons. The permeability of the membrane for chloride or potassium ions is changed. This is done by opening the corresponding channels so that chloride diffuses in or potassium out.
Every movement of ions ultimately causes the membrane potential to decrease so much that an action potential is no longer continued. Because it is too difficult for the membrane to increase its potential voltage so far and to exceed the threshold for the action potential. This stops the signal transmission.
Blood vessels transport nutrients and oxygen in the body and supply the cells with vital substances. However, the brain as a sensitive organ with a sensitive chemical balance has been equipped by nature with special blood vessels, which are referred to as the blood-brain barrier.
These blood vessels are semi-permeable and regulate the movement of ions, molecules and foreign substances. They allow the brain to work in a safe and controlled environment and protect it from toxins and pathogens.
To date, researchers are not sure whether GABA can cross the blood-brain barrier. A research group from Germany and the Netherlands has summarised and critically evaluated the results of various studies from the past decades on this topic.
Initial animal studies in the 1950s indicated that GABA does not cross the blood-brain barrier. This result has since been confirmed by several research groups. However, a number of studies have also reported that GABA can overcome this barrier, albeit in low concentrations.
One possible reason for these contradicting results lies in the chemical compound used. The differences can also be attributed to whether GABA was administered orally or by injection.
In the past, human examinations have failed due to the lack of technology and the imaging method used to display the GABA level in the brain. With the new methods of magnetic resonance spectroscopy (MRS), however, this could change in the near future.
In 2001, a study identified a GABA transporter in mice. This would mean that GABA would be able to cross the blood-brain barrier through these transporters. So far, however, researchers have not been able to determine whether this GABA transporter also exists in humans.
Several placebo-controlled studies have shown that taking GABA orally has a positive effect on humans. These results are consistent with reviews from consumers who take GABA as a dietary supplement. More on this in the following sections.
However, it is not entirely clear whether the supplementation of GABA is able to cross the blood-brain barrier in humans. The positive effect could also be explained indirectly via the enteric nervous system. The connection between the oral administration of GABA, the vagus nerve and the GABA level in the brain has not yet been exactly established and must be supported by further research results.
As already mentioned, GABA has an inhibitory effect. At first glance, the term seems to have a negative effect, but it is important for the body and especially the brain to switch off as well. Because a permanent state of excitement strains the nerve cells. If the chemistry of the brain gets into an imbalance, this has serious consequences.
Typical symptoms that indicate GABA deficiency are:
Researchers also see a correlation between various neurological diseases and low GABA levels in the brain. They found decreased GABA levels in the thalamus of patients with schizophrenia and Huntington's disease.
GABA is usually produced by the body itself. However, the body's own production can be supported by certain foods, since the body needs building blocks to produce the amino acid.
This includes:
A Korean research group has determined the content of gamma-aminobutyric acid in various foods in dry weight (TW). The following foods achieved the highest values in descending order:
The researchers noticed that the GABA content in germs and sprouts, as can be seen from the examples of rice, beans or barley, is higher than in other components of the plant. The researchers justify this with the fact that GABA is produced from glutamate by enzymatic processes. The activity of the glutamate decarboxylase (GAD) responsible for this process is particularly high during germination.
Various studies from Asia have also dealt with the GABA concentration in fermented foods. According to these studies, various Lactobacillus strains are able to produce GABA as a by-product of their metabolism. [7]
The central nervous system (CNS) consists of the brain and spinal cord. It is responsible for many important bodily functions, such as:
Since, as already mentioned, GABA is the most common neurotransmitter in the body, it also significantly influences many of the functions mentioned above. But gamma-aminobutyric acid does not only play an important role in the mature brain. Researchers found that it was also of crucial importance during the development of the CNS.
Neurotransmitters are the chemical messengers that neurons use to communicate with each other and with other types of cells. Every neurotransmitter behaves differently. The main function of GABA as the main inhibitor neurotransmitter of the brain is to prevent over-stimulation.
As with most things in life, balance is the key to an optimally functioning nervous system. GABA and glutamate are the primary calming and arousing neurotransmitters in the central nervous system and serve opposite functions. Despite their opposite roles, GABA and glutamate have many compounds, including their existence in the same biological way.
Under normal physiological conditions, glutamate and GABA activities are balanced. However, glutamate activity increases under stressful conditions such as inflammation or increased immune activity. If the nervous system is working properly, GABA activity will also increase to compensate for the arousal and restore balance.
Glutamate is the precursor to GABA, which means that an increase in glutamate levels should also cause a subsequent increase in GABA synthesis. This 'allostatic mechanism' is the body's attempt to restore homeostasis. Common symptoms of an unbalanced system in which the glutamate level is higher than the GABA level include anxiety, overstimulation, sleep and concentration problems.
Insomnia can have many different causes and is estimated to affect 30% of adults worldwide. The technical term insomnia includes many different complaints, such as difficulty falling asleep. However, problems such as restless sleep, frequent waking up at night or waking up too early also count as complaints.
GABA has a calming, sedative effect and can help to facilitate falling asleep in a natural way. This is achieved by reducing the excitability of the nerves. A 2015 study found that taking GABA helped participants fall asleep faster. The subjects were able to fall asleep about 5 minutes faster on average.
Another study from 2008 looked at the relationship between insomnia and the GABA level. Researchers discovered that GABA levels in the brain were significantly reduced in people with insomnia. Compared to people without sleep disorders, the values were 30% lower.
In addition to taking GABA, maintaining a sleep ritual and good sleep hygiene can promote good and restful sleep.
Every day our bodies are exposed to a wide variety of stimuli. Dates and obligations can become a burden. The exciting neurotransmitters flood the brain with stress hormones.
Researchers at the University of Bern determined the concentration of GABA levels in the prefrontal cortex of 10 healthy volunteers in a relaxed state and in an acute stressful situation. The stress was triggered by slight electric shocks on the right foot. The intensity was so high that the stimulus was unpleasant but not painful.
The measurements showed that the GABA concentration decreased on average by 18% compared to the neutral state without stress. The molecular mechanism and the functional significance of this reduced inhibitory effect in acute psychological stress have not yet been clearly clarified and must be investigated further.
Exercise is known to have a positive impact on mood and can help with stress. Researchers have therefore dealt with the question of how the GABA concentration in the brain changes during two different sports activities and what effect this has on mood.
A total of 34 subjects without previous psychological or medical illnesses were divided into two groups. One group completed a 60-minute yoga session three times a week. The other group took walks at the appropriate time.
Every 4 weeks, surveys were carried out on the mood of the test subjects, in addition to the magnetic resonance scans of the brain. The study found that there was a correlation between good mood and elevated GABA levels in the subjects' thalamus. This effect was more pronounced in the yoga group.
As the most common inhibitory neurotransmitter, GABA is responsible for reducing the excitability of synapses. This excitement is usually expressed by those affected by emotions such as fear, inner restlessness or tension. In a real dangerous situation, this state of excitement makes sense, because it puts the body on alert and improves the reflexes in order to be able to react more quickly.
Persistent and irrational fears often lead to panic attacks and strain the body and the psyche. These diseases are summarised under the collective term anxiety disorders. GABA and GABA-analogue active ingredients have long proven themselves as natural remedies because of their calming effects.
Various studies in the past have shown that reduced GABA levels and certain panic or anxiety disorders may be related.
The various studies found, among other things, reduced GABA values in the prefrontal cortex and in the occipital lobe. The prefrontal cortex is responsible for emotional evaluation and planning and is considered the planning center and problem solver for the brain. The occipital lobe, on the other hand, analyses the incoming stimuli from the eyes and is therefore responsible for the ability to see.
A 2006 study looked at the effects of oral GABA in people who are afraid of heights. The participants had to cross a suspension bridge as a trigger for fear. Just one hour after the dose, the group receiving GABA showed higher alpha waves and reduced beta waves, an indication that they were more relaxed.
Inflammation is a natural and sometimes necessary reaction of the body that is triggered by illness or injury, among other things. The immune system thus protects the body from foreign substances and potential pathogens. However, if the inflammation becomes chronic, it can lead to serious diseases such as cancer, heart disease and arthritis.
Some research suggests that GABA can not only inhibit the occurrence of inflammation, but also relieve the symptoms of the resulting diseases. For example, an animal study showed that mice supplemented with GABA showed a lower risk of developing rheumatoid arthritis. The symptoms of animals that were already ill could be reduced in this way. Another work in the Journal of Neuroinflammation suggested that GABA could reduce the activity of a signaling pathway that triggers joint inflammation.
The current state of research is limited to animal and in vitro studies. Further research in this area is important in order to shed light on the mechanisms in the human body.
GABA is synthesised by the enzyme GAD from the amino acid glutamate in nerve cells, but also in insulin-producing beta cells in the pancreas. GAD has 2 forms, GAD65 and GAD67. Type 1 diabetes destroys beta cells, while type 2 diabetes is associated with impaired beta cell function and insulin resistance.
Patients with type 1 diabetes often have antibodies to GAD65. However, until recently there was no proven link between GABA and type 2 diabetes. Researchers have now been able to show that GABA is important for the maintenance and possibly also for the production of new beta cells.
The two recent studies reinforce the assumption that GABA plays a crucial role in both types of diabetes. The scientists used the GABA-A receptors as a biological sensor for GABA and were able to determine the effective physiological GABA concentrations in human pancreatic islets. They also showed that the ion channels in type 2 diabetes are more sensitive to GABA and this regulates insulin secretion.
The scientists further isolated immune cells from human blood and examined the effects that GABA had on these cells. The results show that GABA inhibits the cells and reduces the secretion of inflammatory molecules. The anti-inflammatory effects of GABA can be vital in the pancreatic islands, since the formation of toxic white blood cells can be inhibited as long as GABA is present.
This ensures the survival of the insulin-secreting beta cells. If the number of beta cells decreases, as is the case with type 1 diabetes, GABA is consequently also reduced, and thus the protective shielding of the beta cells. However, if the inflammatory molecules increase, this can weaken the remaining beta cells and even kill them.
In additional studies, the scientists would now like to concentrate on elucidating the GABA signaling mechanisms in the immune cells and in human beta cells. You will also investigate to what extent the effects of GABA can be influenced by medication.
Depression is one of the most common mental health problems in industrialised countries. Studies have shown that people who suffer from depression usually have a lower concentration of GABA in the brain. Therefore, researchers assume that this neurotransmitter plays a factor in depression in a direct or indirect form.
Conversely, studies have shown that GABA levels can increase after treatment for depression. A study by the Department of Psychiatry at the Yale University School of Medicine showed that patients who underwent electro-seizure therapy to treat their depression subsequently increased GABA levels. The GABA concentration in the occipital cortex increased.
The premenstrual syndrome or PMS, which occurs in connection with the female cycle, is characterised by various symptoms. These include:
A study compared the GABA concentration in the occipital cortex of women with PMS and women without symptoms during the menstrual cycle. It was shown that the GABA level can be disturbed by menstruation and decrease over the menstrual cycle.
Researchers also suspect that GABA could be an analgesic in the future. They assume that the inhibitory effect on the ion channels is responsible for the pain-relieving effect. However, further studies are needed to confirm this theory.
The human growth hormone is produced in the pituitary gland and has various effects on the organism. It can increase muscle strength, reduce the risk of heart disease, and strengthen bones. If there is a deficiency, this can trigger serious symptoms, for example:
In a placebo-controlled study, researchers showed that taking GABA as a dietary supplement can lead to an increased release of growth hormones. For this purpose, 11 subjects received 3g of GABA or a placebo, followed by a rest phase or a unit of strength training. It was shown that taking GABA increased growth hormones by up to 400% as compared to the placebo group.
To master everyday life, it is sometimes useful to master multi-tasking. This performance is made possible by working memory. A 2016 study showed that GABA concentration in certain regions of the brain allows a prediction of a person's working memory capacity.
In the study, 23 healthy participants aged 19 to 32 were subjected to a number of tasks to determine working memory.
Using a special magnetic resonance spectroscopy method, the researchers measured the GABA level in the dorsolateral prefrontal cortex. People with a better working memory had higher GABA values.
Attention deficit hyperactivity disorder, commonly known as ADHD, is a condition that affects both children and adults and can cause symptoms such as restricted attention, impulsivity, and hyperactivity. A 2012 study by the Johns Hopkins University School of Medicine compared the levels of GABA in children with and without ADHD and found that children with ADHD had a lower concentration in the brain.
Another study examined the in vivo concentration of GABA levels in adolescents. It was shown that lower GABA levels were associated with more impulsivity and less inhibition. Researchers suspect that a GABA deficiency is a cause of impulsive and irrational behaviour in children during puberty.
Science has developed several GABA-like drugs, also called derivatives or analogues, that work like GABA in the brain and cross the blood-brain barrier. Some of these analogs require a prescription.
One of the most commonly prescribed GABA derivatives is gabapentin. Studies have shown that taking gabapentin can increase GABA levels in the brain. How exactly this mechanism works is not known. The drug is usually prescribed for the treatment of epilepsy.
GHB, which stands for gamma-hydroxybutyrate or -hydroxybutyric acid, is another prescription GABA analogue. GHB is a precursor to gamma-aminobutyric acid. It is used in medicine to treat narcolepsy. Other possible uses in the past were as an anesthetic or to treat alcohol addiction.
Another known GABA derivative that crosses the blood-brain barrier is phenibut, also known as beta-phenyl-gamma-aminobutyric acid. This substance is structurally similar to GABA, but has an additional carbon ring. This addition is sufficient to be able to cross the blood-brain barrier.
Once Phenibut has overcome the barrier, it works on the same receptors as GABA and produces a similar effect. The drug is widely used in Russia to relieve tension and anxiety. It is also used to treat psychosomatic or neurotic sleep disorders. It is also used to treat depression, exhaustion, post-traumatic stress, stuttering, and balance disorders.
GABA is available in capsule, drink and powder form. Which variant is better is often a question of personal preference. The main differences are in applicability and cost.
The classic variant is GABA capsules. They are available as tablets, capsules, or gel capsules. Depending on the product and area of use, they can contain between 100 mg and up to 750 mg GABA per tablet.
GABA is also available in the form of sticks or in powder form. This form is suitable for people who want to do without capsule fillers or who have to do without intolerance. Another advantage of the sticks is that they can be conveniently stored in your pocket and can also be taken on the go if necessary, as they do not have to be taken with water.
The GABA tea or Gabaron was developed by Japanese scientists. In recent decades, Japanese scientists have shown great interest in developing foods with an increased GABA concentration. This resulted in soy milk or yoghurt enriched with GABA.
All products are based on the fermentation process. Japanese researchers used oolong, black and green tea to make GABA tea. The tea leaves were exposed to nitrogen or carbon dioxide gas for 6 hours.
The green tea leaves, which were exposed to the nitrogen gas, developed a GABA concentration of over 150 mg per 100 g of tea leaves. The treatment had no effect on the aroma of the tea.
The right dosage depends on many different factors. Taking GABA as a dietary supplement cannot replace a medication prescribed by a doctor.
Since everyone has their own individual brain chemistry, recommendations should only be used as guidelines. It is therefore advisable to start with smaller amounts and carefully approach the optimal dosage.
GABA has a calming effect and, as already mentioned, is often used for sleep disorders. For this application, it should ideally be taken shortly before going to bed. If symptoms of fatigue generally appear, the intake can also be postponed to the evening for other symptoms in order to stay active during the day.
In case of anxiety and panic attacks, the dose can be divided into several doses throughout the day. The following also applies here: the inhibitory function means that the effect on the body should be closely monitored in the first few days and, when in doubt, driving and operating heavy machinery should be avoided.
The effects of GABA can be influenced by various other nutritional supplements and active ingredients. A combination is therefore recommended to increase the positive effect.
According to the current state of science, niacin, also known as vitamin B3 or niacinamide, has a structural similarity to benzodiazepines. This is a group of drugs that increases the effects of GABA in the brain.
Taurine is one of the richest amino acids in the human brain, but neuroscientists are still not sure how it is used by brain cells. A team of researchers at Weill Cornell Medical College in New York has uncovered a major site of action for the molecule, which will bring them closer to the answer to this question in the future.
The researchers exposed thin layers of thalamic tissue from the brains of mice to concentrations of taurine that are very similar to those in the human brain. They found that taurine was active on the GABA receptors in the thalamus. This indicates that both may be using the same receptor.
The passion flower has a long tradition in herbal medicine. It is widely used in the treatment of various anxiety disorders, insomnia, nerve pain, seizures, ADHD, cardiac arrhythmia, and more. The mechanism behind this is still under discussion. Researchers have concluded that passionflower extract modulates the GABA system with receptor sites.
Magnesium is an essential mineral and magnesium deficiency is one of the most common deficiency symptoms in industrialised countries. Researchers believe that magnesium helps potentiate the activity of GABA receptors in the brain. However, the study showed that activity appears to be dose dependent.
A Canadian study from 2009 showed that lemon balm active ingredients, Melissa officinalis, can inhibit GABA transaminase, a GABA-degrading enzyme. Rosemary acid, ursolic acid, and oleanolic acid were identified as active ingredients. The researchers suspect that rosemic acid is the main active ingredient due to the high proportion in the dry matter.
These results are in line with experience in the use of traditional medicine. It is believed that lemon balm could be a possible alternative to treating a variety of diseases, particularly anxiety and some other CNS disorders. However, further studies are needed to confirm these assumptions.
Valerian is a popular natural remedy for sleep disorders and is often used as a sedative. Valerian root studies have shown that it increases the release of GABA from the cranial nerve endings and prevents it from being transported back to the nerve cells.
In the body, the neurotransmitter GABA is synthesised from the neurotransmitter glutamate and the essential vitamin B6 (pyridoxine) as a co-factor. If the body does not have enough B6 available, this can lead to reduced GABA synthesis. And it also builds up glutamate, which in some cases contributes to anxiety, chronic pain disorders, and neurodegenerative diseases.
L-theanine is an amino acid found in black and green teas. Studies have shown that it increases the levels of GABA and two other important neurotransmitters, serotonin and dopamine.
L-theanine is considered an adaptogen, a substance that reduces psychological and physiological stress reactions. The results showed that theanine led to a decrease in heart rate during an acute stressful situation. This effect was attributed to the weakening of sympathetic activation.
Kava is a plant that is native to the Pacific Islands. It is also known as Piper methysticum or intoxicant. The plant is traditionally used in her home country as a ceremonial and relaxing tea.
In-depth studies have shown that the herbal remedy is effective in reducing stress. The effect is partly due to the increase in GABA levels. It has also been shown to be just as effective for anxiety and generalised anxiety disorder.
Probiotic supplements that have a positive effect on the psyche are known as psychobiotics. The neurotransmitters synthesised by the microorganisms, such as GABA, explain this effect. In fact, there seems to be bacteria in the human gut that create GABA.
Research has identified a total of 29 bacterial strains that produce GABA. Most of them belong to the Lactobacillus strain and some are also found in the human intestine. A probiotic diet is therefore useful to support the activity of these bacteria.
Laboratory experiments on mice have shown that Lactobacillus facilitates direct communication between the intestine and brain via the vagus nerve in order to reduce stress and anxiety. Lactobaciullus brevis and Bifidobacterium dentium have proven to be particularly potent GABA producers.
Overdose of GABA is rare and can lead to various symptoms. Doctors speak of a paradox effect: if the dose is too high, GABA can have the opposite effect and trigger anxiety, inner restlessness and insomnia.
Skin reactions may occur, such as a slight tingling sensation, reddening of the skin or slight numbness in the extremities. However, these symptoms usually resolve quickly when the dosage is adjusted.
People who are already taking GABA-analog drugs or prescription psychotropic drugs should speak to a doctor or pharmacist before taking GABA as a dietary supplement and seek detailed advice. Since both active substances influence brain chemistry and the activity of the nervous system, possible overdoses or undesirable interactions cannot be excluded.
Taking GABA as a dietary supplement is generally considered safe if the recommended dosage is followed. If unusual health problems or side effects occur while taking GABA as a dietary supplement, a doctor should be consulted for further evaluation. Since there is still no well-founded information on the effects of GABA during pregnancy and breastfeeding, it should be avoided for safety reasons.
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