GABA

What is GABA?

Gamma-aminobutyric acid (GABA) is an amino acid that has been classified as a neurotransmitter. It is a calming neurotransmitter and the main inhibitory neurotransmitter in adults within the body which acts to block nerve impulses. It calms the firing nerves in the central nervous system (CNS).

GABA is made in brain cells from glutamate and in the nervous system. GABA is also produced in the insulin- producing β-cells of the pancreas in high amounts. It is also produced in the digestive system by gut probiotics.

The release of GABA occurs in the hippocampal region. Other neurotransmitter release in this region includes glutamate (GLU), acetylcholine (ACh), noradrenaline (NA) and serotonin (5-HT). [R]

In the developing brain GABA acts as the major excitatory neurotransmitter, once the brain matures it acts as an inhibitory neurotransmitter.

GABA receptors can be found in the brain. Approximately 40% of the synapses in the brain work with GABA.

GABA is considered a ‘zen’ neurotransmitter due to its calming relaxing effects.

GABA is the primary inhibitory neurotransmitter found in the brain.

Some of the functions of GABA includes producing calming effects which improves mood and produces anti-anxiety effects.

Health Benefits of GABA

Helps with relaxation and sleep

Glutamate which acts as an excitatory neurotransmitter is one of the precursors for GABA. GABA is inhibitory which has calming effects on the nervous system whilst glutamate is excitatory and fires up the CNS. GABA prevents neurons from firing up the nervous system.

GABA inhibits certain brain signals and decreases activity in the nervous system.

GABA slows down brain activity reducing the speed of thinking and has a sedative effect.

GABA is needed to balance the excitatory and inhibitory functions in the brain. It creates a relaxing calming effect when attaching to a GABA receptor (a protein in the brain) and is needed for sleep. The effect of this has shown to reduce anxiety, stress and fear levels. Low levels of GABA has shown to cause anxiety.

GABA supplement is best taken before going to bed for its sedative effects helping to sleep easily and longer.

Improves mood

GABA helps improve mood through its relaxation effects on the mind. Increased GABA levels reduces excitatory signals firing in the brain when GABA receptors are activated giving a calmer more relaxed state of mind.

Most mood disorders are due to an imbalance of neurotransmitters or excess excitatory firing of brain signals that can cause racing thoughts, panic and anxiety. GABA can mediate these effects.

Supports hormone health

GABA has many interactions with various hormones within the body. Progesterone which rises in the luteal phase of the menstrual cycle helps produce more GABA levels. The raised GABA levels will allow for more restful deep sleep which can increase energy levels.

Needed for muscles

GABA stimulates human growth hormone (HGH) which is needed for building muscles and muscle tone. GABA is involved in glucose metabolism which can prevent buildup of fat which can otherwise lead to obesity.

GABA helps regulate muscle contraction and involved in motor control.

Involved in vision

GABA is also involved in vision and has various effects over the retina, however limited studies exist in its direct role in vision and are mostly found in animal studies.

Needed for important brain functions

GABA is especially important for the developing brain in children as well as the adult mature developed brain.

High levels of GABA can improve focus which can help with many of the cognitive functions.

GABA transmission plays a role in neurogeneration. [R] [R]

Needed for development

GABA regulates the growth of embryonic and neural stem cells. [R]

However insufficient data exists whether GABA is safe to take during pregnancy. It may be safer to support natural bodily synthesis instead of raising GABA synthetically as the body will have a natural compensating and balancing mechanism. Many GABA raising drugs may also not be recommended during pregnancy.

Suppresses inflammation / immune system

GABA plays a role in the immune system and is needed for its function. It supports gut motility and controls inflammation. GABA immunomodulatory effects on T cells and macrophages with anti-inflammatory results being shown in some studies. [R] [R]

It is also involved in the regulation of appetite and metabolism.

Supports the endocrine system

GABA has a vital role in the endocrine system and plays a part in regulating appetite and metabolism. GABA can be found in high amounts in the pancreas with most of GABA concentrated within the pancreatic islet insulin producing B-cells of the pancreas and is produced in large amounts and released with insulin.

GABA is found in the tissues of many of the body’s organs involved in endocrine system which includes the pituitary, pancreas, adrenal glands, pineal, uterus, ovaries, placenta and testes.

GABA can assist with insulin release. Diabetes which is an endocrine disorder can impair this release. GABA is implicated in various disorders of the endocrine disorders such as diabetes mellitus, impaired adrenal glands and health problems in the reproductive organs (ovaries and testes).

Agonist / Synergist

Vitamins B1, B3, B6, B8, B12

Minerals Magnesium

Amino acids Essential amino acids, tryptophan, phenylalanine, taurine, glycine, glutamine, L-theanine (suntheanine)

Hormones Serotonin, melatonin, pregnenolone, progesterone, DHEA, growth hormone releasing hormone (GHRH)

Essential Oils Chamomile, Lavender, Lemon Balm, Valerian, Jasmine, Jatamansi, Bergamot

Brainwaves Theta

Herbs St. John’s Wort, kava, valerian root, passionflower, chamomile, ginseng, green tea, black tea, oolong tea

Medications GABApentin (GABA analogue), Pregabalin, Benzodiazepines, Hypnotics, Phenibut

Other Glucose, Butyric Acid (BTA), Lactobacillus and Bifodobacterium speices, Lactobacillus rhamnosus, CBD extracts

Bergamot may have protective effects against glutamate excitotoxicity

Bergamot can increase GABA levels [R]

GABA is made from glutamate

The enzyme glutamate decarboxylase which needs P5P (active form of vitamin B6) converts the main excitatory neurotransmitter glutamate into the main inhibitory neurotransmitter GABA

Glutamate is synthesized from the amino acid glutamine and also the precursor for GABA

The enzyme glutamic acid decarboxylase (GAD) converts glutamate into GABA

GAD needs pyridoxal 5′-phosphate (P5P) as cofactor

GABA counteracts the effects of glutamate possibly as glutamate begins to convert to GABA

B6 is needed for the synthesis of neurotransmitters which includes glutamate, GABA, serotonin and dopamine [R]

Probiotic foods include sauerkraut, kefir, miso, tempeh and yoghurt

GABA stimulates HGH (human growth hormone)

GABA synthesis will need adequate precursors (vitamins and minerals) for other neurotransmitters and hormones such as serotonin, melatonin and progesterone

Butyric acid (also known as butanoic acid or BTA) is a saturated short-chain fatty acid is a precursor for GABA synthesis and is made in the intestinal tract

Lactobacillus and Bifodobacterium species help produce GABA and need butyric acid

Lactobacillus rhamnosus

Natural extracts of CBD can help increase GABA levels

Glucose is the predominant GABA precursor

Glucose is metabolized to glutamate by the tricarboxylic acid cycle enzymes

Pyruvate and glutamine can also act as precursors [https://www.ncbi.nlm.nih.gov/books/NBK11084/]

Theta brainwaves have a frequency range of 3.5 to 7.5 hz. It is one of the fairly slower brainwaves and is associated with the subconscious state of mind. The functions of this brainwave involves vivid visualizations, dreams, inspiration, creativity, intuition and insights.

Theta is involved in learning, memory storage, emotions and sensations. Theta brainwaves can be found in children up to 13 years old in the waking state. In adults theta waves are uncommon in the waking state and occur more often in sleep. These waves are needed for healing and rejuvenation of the mind and body.

Theta brainwaves are present in deep meditation and sleep with withdrawn senses from the outer world. A state where dreams, creativity and insights are enhanced.

Examples of theta waves include deep relaxation, deep meditation (observable in experienced meditation practitioners), deep concentration, prayer, sleep, dreaming, daydreaming and autonomous tasks (brushing hair or teeth, walking).

Thiamine is needed for the synthesis of GABA and a deficiency of this vitamin can cause anxiety

Thiamine is needed for the synthesis of acetylcholine

Lithium reduces glutamate and dopamine and increases GABA. This is dependent on changes needed in neurotransmitter networks for achieving homeostasis

GABA supplement may be taken to increase GABA levels but it may not be as effective as synthesising in the brain due to difficulty in GABA being transported across the blood-brain barrier.

Phenibut is a chemical similar to GABA and prescribed as anti-anxiety medication which may be effective at calming nerves but may become addictive.

Pregnenolone acts as a GABA agonist by binding to the receptor GABA A [Rhttps://www.ncbi.nlm.nih.gov/pubmed/2177701] [Rhttps://pubmed.ncbi.nlm.nih.gov/3138576/]

BCAAs are needed for the production of excitatory neurotransmitter glutamate and inhibitory neurotransmitter gamma-aminobutyric acid (GABA) within the brain due to the role of these amino acids as nitrogen donors [R]

GABA enhances insulin secretion

Inositol (Vitamin B8) works with choline which when combined form lecithin, an essential component for cell membranes which protects cells from oxidation and protects the myelin sheath. This is important for regulating nerve transmissions

Many studies are showing potential benefits of inositol on mental health conditions such as anxiety, schizophrenia, Alzheimer’s disease, obsessive compulsive disorder (OCD) and attention deficit-hyperactivity disorder ADHD. Reports of inositol use reveal an increased levels of energy and improved memory, mental alertness and concentration. It has also shown to be helpful with treating anxiety.

Inositol can help regulate mood through its involvement in the manufacturing of GABA as well as other neurotransmitters serotonin, dopamine, norepinephrine, acetylcholine and the neurohormone melatonin derived from serotonin. These neurotransmitters require inositol for transmitting messages between the brain cells. A deficiency of inositol has been linked to various mental health problems which includes depression, anxiety and panic attacks where many of the neurotransmitters are out of balance.

Iodine along with selenium plays a very important role in the thyroid by supporting and maintaining its functions in the body. Iodine is needed for T4 and T3 production. In the brain these hormones are needed to activate neurotransmitters GABA and others such as dopamine, norepinepherine, serotonin and acetylcholine. Deficiency in iodine is linked to poor cognitive functions and intellectual disability.

GABA production needs T3 for its calming benefits when stressed. Deficiency in iodine can cause T3 levels to reduce which can impair GABA synthesis and cause anxiety. Iodine is also needed for serotonin production another neurotransmitter that reduces anxiety levels and increases feelings of mental wellbeing. Serotonin also acts as a cofactor for GABA [R]

Thyroid

Thyrotropin-releasing hormone (TRH) hormone increases GABA release [https://pubmed.ncbi.nlm.nih.gov/16990402/]

GABA in the hypothalamus inhibits the thyrotropin-releasing hormone (TRH) which is needed to stimulate thyroid stimulating hormone (TSH) release from the pituitary which stimulates thyroid hormone (TH) release from the thyroid gland. However this may be because GABA releases first after TRH and once GABA is released it regulates the thyroid system to prevent further release. GABA is usually high in the luteal phase of a woman’s monthly cycle and this may be an indicator that GABA release inhibition of TRH and therefore TSH is because the body does not require thyroid hormones as menstruation draws near in the end of the luteal phase where hormones significantly decrease. [R] [R]

Glutamine synthetase is the manganese-activated enzyme needed to convert glutamate to glutamine

Glutamate is an excitotoxic neurotransmitter if allowed to get too high. It is also a precursor to the inhibitory neurotransmitter, γ-aminobutyric acid (GABA)

Magnesium regulates the hormone melatonin needed for the sleep wake cycles. GABA works synergistically with melatonin and assists with deep restful sleep

Magnesium increases GABA levels. Magnesium binds to GABA receptors.

Animal studies have shown that magnesium intake can increase dopamine levels and can lower depressive symptoms

Magnesium inhibits the release of excitatory neurotransmitters and supports GABA synthesis

Magnesium acts as a voltage-gated antagonist at the glutamate, N-methyl-D- aspartate (NMDA) receptor.

Magnesium regulates neurotransmitter glutamate and GABA activity by modulating the activation of NMDA glutamate and GABAA receptors. This can have a calming and relaxing effect. Magnesium does this by binding to GABA receptors in the brain and has a calming effect on the brain and helps relax central nervous system and the muscles reducing excitation.

Vitamin B12 is a cofactor needed for the production of GABA and other neurotransmitters which includes dopamine, norepinephrine, and serotonin.

B12 deficiency also has an impact on mood, emotions and sleep which can contribute to psychiatric disorders.

B12 deficiency is linked to neurological conditions such as epilepsy, cognitive decline, Parkinson’s, Alzheimer’s and dementia.

Some parts of the brain needed for cognitive functions such as memory and learning are affected by folate deficiency. Additionally high homocysteine levels have been associated with neurological disorders which can also be an indicator for low levels of B12 and other deficiencies such as B6 and B9.

Deficiency of B12 can cause oxidative damage to brain cells leading to cognitive decline. In addition to B12 vitamin B9 is also needed to help the nerves function properly. [R] [R]

Many of the B-complex vitamins also play an important role in keeping the nervous system healthy and the brain functioning properly.

Vitamin B12 deficiency can cause high homocysteine which is also linked to neurodegenerative disorders and can cause damage to the myelin sheath of the neurotransmitters.

GABA supplements may increase GABA levels

Intense exercise increases glutamate and GABA

Specific strains of bacteria from the Lactobacillus and Bifidobacterium species produce GABA. Lactobacillus rhamnosus has shown to boost GABA function

The probiotic bacteria that produce GABA include Lactobacillus rhamnosus, Lactobacillus. delbrueckiisubsp. bulgaricus, Monascus purpureus and Streptococcus salivarius subsp. thermophiles.

Progesterone is a GABA agonist and fluctuating levels can affect health especially the female menstrual cycle. Low levels of progesterone may lead to symptoms of depression, anxiety, irritability and insomnia. These symptoms may get worse during the mid-luteal phase when progesterone levels should normally peak and is linked to conditions such premenstrual syndrome.

Serotonin can enhance GABA activity

5-HTP can convert to serotonin

Taurine amino acid is an agonist of GABAA receptors and counteracts excess glutamate levels [R]

Taurine amino acid protects brain from excess glutamate levels and calms GABA receptors

GABA inhibits dopamine and norepinephrine. GABA (both amino acid and neurotransmitter) metabolizes more easily if taken with inositol and niacinimide (B3)

GABA has antidepressant effects.

Many of the anti-convulsants prescribed to people with manic-depression act similar to GABA.

L-Taurine acts as both a neuroinhibitor and a neurotransmitter and counteracts the effects of dopamine and norepinephrine by inhibiting their release and reduces excitatory effects in the nervous system.

L-taurine is a non-essential amino acid as it can be synthesised in the body. Main function of taurine is to help get mineral ions (sodium, potassium, calcium and magnesium ions) in and out of cells which then normalizes cell membranes. The minerals calcium, sodium, potassium and magnesium are also important for those with manic depression. Taurine has shown to be helpful for seizures. People with mania are usually prescribed with anti-seizure medications.

Taurine is found to be depleted in people with manic-depression. [R]

Tyrosine was also found to be low in manic-depression along with taurine. [R]

Tyrosine needs various cofactor nutrients for the synthesis of dopamine and norepinephrine which includes the minerals iron, magnesium, copper, manganese, zinc and vitamins B9, B6 and C.

Tyrosine or phenylalanine should be taken in the morning as it is stimulating and taking it any later can interfere with sleep.

Formulas or cofactors that help synthesise inhibitory neurotransmitters such as GABA are better taken in the evening in order to help aid sleep. Taurine is a cofactor for GABA and is best taken at least an hour before bedtime to aid sleep.

Alcohol can increase the release of dopamine and stimulate GABA receptors but this is not the optimal or healthy method for overall health

Alcohol prevents communication between nerve cells through its interaction with glutamate and GABA receptors

Communication between the nerve cells are activated when glutamate binds to its receptor in the brain whereas communication between nerve cells are inhibited when GABA binds to its receptor in the brain. The net effect of this is slowing down the brain activity. Reduced activity in the brain can inhibit social anxiety and conscious self control. When nerve communication are significantly silenced motor skills are affected and is evident when a person is drunk who will find difficulty walking in a straight line. Slurred speech and slowed actions under the influence of alcohol are often the result of this inhibited communication between nerves.

GABAergic medications (GABA analogues) act as allosteric modulators (bind to a receptor to change that receptor's response to stimulus) of GABA receptors which increase the available amount of GABA. These medications induce relaxation and alleviate anxiety symptoms and have anti-convulsive effect.

An example of GABA analogue is the medication Gabapentin used to treat epilepsy and neurotic pain.

Other medications include Benzodiazepines, Barbiturates (GHB, Valium, Xanax), Baclofen (muscle relaxant) and Klonapin.

Antidepressants and hypertension medications interact with GABA

Amphetamines change the glutamate levels in the brain possibly causing a circulatory disturbance of the glutamine-glutamate-GABA circuit. A single dose of Amphetamine type stimulants (ATS) has shown to decrease levels of glutamine, glutamate, and GABA

This action of ATS is thought to be due to the excess stimulation of the glutamate system increasing the need for glutamate and subsequently insufficient GABA levels which needs glutamate for synthesis [R] [R]

Serotonin modulates GABA and glutamate

Serotonin increase GABA availability (SSRIs increase GABA)

GABAA receptors when activated increases the release of norepinephrine

Norepinephrine modulates synthesis of GABA in the central nervous system (CNS) [https://www.ncbi.nlm.gov/pmc/articles/PMC2430669/] [https://www.ncbi.nlm.gov/pubmed/14754790/] [https://www.ncbi.nlm.gov/pmc/articles/PMC3581018/]

When GABA levels increase the neurotransmitters, serotonin, endorphins, dopamine and endocannabinoids also increase

When GABA levels increase the hormone progesterone also increases

GABA may impact the stress hormone cortisol currently there are mixed studies and more research may be needed to understand its interactions

GABA counteracts the effects of norepinephrine and epinephrine (Adrenaline)

GABA has shown to reduce testosterone in rats with polycystic ovarian syndrome (PCOS) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603011/]

*DHEA which increases when serotonin increases, is found to be low in those with schizophrenia* People with schizophrenia have been found to have lower levels of GABA [R]

Animal studies have shown oxytocin increases phasic and tonic GABAergic transmission. [R]

Estrogen is linked to GABA activity with studies showing estrogen increasing both basal and stimulated extracellular GABA concentrations within the preoptic area. Studies have also shown that estrogen can modulate the actions of noradrenaline upon preoptic GABA neurones. [R]

Antagonists

Other Dairy (BCM Peptides), caffeine, nicotine, pregnenolone sulfate

Dairy can cause a mast cell or histamine response

Dairy contains the neuroactive peptide β-casomorphin-7 (BCM7) derived from casein which affects GABA levels. Goat milk may be an exception as β-casein in goat milk is mostly A2 type and does not produce BCM-7 [R]

Stimulants such as caffeine and nicotine should be avoided as they lower levels of GABA

Pregnenolone sulfate is an excitatory neurosteroid made from pregnenolone has antagonistic effects on GABA inhibiting the calming effects of GABA

GABA inhibits norepinephrine through activating the GABAB receptors which causes a decrease in norepinephrine levels

GABAB receptors decrease norepinephrine

Caffeine which is found in tea, coffee, and chocolate inhibits GABA release

Caffeine and any other stimulants that increase mental activity should be avoided especially before bed

Ginkgo compound is an antagonist of GABA(A) receptors [R]

GABA(A) antagonists may be possible targets for reducing morphine reward [R]

When GABA levels increase the neurotransmitters acetylcholine and glutamate decrease

Rubella virus (added in MMR vaccines) can interfere with the activity of GAD enzyme needed to convert glutamate into GABA which can cause a build-up of glutamate. Other factors interfering with this enzyme will also cause build-up of glutamate.

Food Sources of

Some foods that contain GABA include spinach, potato, sweet potato, kale, broccoli, seaweed, tomatoes beans, lentils, noni fruit, banana, berries, almonds, walnuts, brown rice and oats.

Eating fermented foods that are rich in probiotics can help to increase GABA levels.

Foods high in probiotics is important to take for healthy gut health which helps synthesise GABA. Most fermented foods contain healthy amounts of specific strains of bacteria that can promote a healthy digestive system. They include fermented pickles, sauerkraut, kimchi, miso, tempeh, kefir and yogurt.

Some herbs can also help increase GABA levels. Green tea contains l-theanine which can increase GABA levels.

Fish and shellfish is also a good source of GABA. There is a seafood seasoning which has high GABA content [R]. Some fermented fish products also contains GABA [R].

Sprouted whole grains are also a good source for GABA. GABA rice which is sprouted brown rice and sometimes parboiled before drying and then packaged also contains GABA. This type of rice is available in different varieties of rice grains.

It is also important to eat foods that contain cofactor nutrients which support GABA synthesis.

Butyric Acid (BTA) which is a precursor for GABA can be found in animal based fats such as butter, ghee and milk.

Recommended Daily Allowance

There are no set amounts of recommended neurotransmitters. Neurotransmitter synthesis depend on the nutrients obtained from the diet or supplementation. Brainwave frequencies and other practices such as meditation can also effect levels of neurotransmitters.

Neurotransmitters are made from protein and amino acids. They also need other cofactors such as vitamins and minerals for synthesis.

Dietary protein is therefore essential and getting adequate, sufficient supply of all nutrients in the correct balance is essential.

A healthy adult needs between 40 and 70 grams of daily protein intake. This can go up to as much as 90 grams for active and athletic people.

Diet and nutritional supplementation can be tweaked to meet the requirement of necessary nutrients and ensuring adequate levels of neurotransmitters.

Neurotransmitters operate at different times of the day and are largely dictated by light exposure. Serotonin and dopamine are produced mostly during daylight hours. During dark hours the serotonin converts to melatonin and more GABA is present.

Brainwaves also correspond with the different neurotransmitters. In the morning the brain has alpha waves which increase to beta waves throughout the day. Gamma waves may also facilitate the daylight hours and ideal for higher learning. The alpha and beta waves facilitate acetylcholine and dopamine.

Other factors such as the seasons and a woman’s monthly menstrual cycle can also determine the amount of specific neurotransmitters needed and at which point of the cycle. For example in the luteal phase GABA is the primary inhibitory neurotransmitter as this part of the phase we see a spike in the hormone progesterone which works synergistically with this calming neurotransmitter. Serotonin will also be present at this time as well as more conversion into melatonin to facilitate sleep.

In northern climates during winter with the lack of sunlight there is likely to be a lower production of serotonin or higher amounts of this may convert to melatonin possibly through daylight hours shortening. This may pick up slightly as spring emerges. Many people also find that spring makes them feel motivated.

Everyone is unique and a person’s life experience may dictate more of what neurotransmitter may be required on any given day. An example is a highly stressed person is very likely to be needing more serotonin and dopamine and possibly other neurotransmitters as the chronic stress quickly depletes all neurotransmitters and can lead to a state of depression.

Checking deficiency levels of neurotransmitters can help determine what may be needed along with using brainwave measuring device which uses electroencephalography (EEG) may help identify the neurotransmitters needed and balancing levels.

GABA Supplementation

Butyric acid and GABA are available as supplements. It is best to take GABA supplements before bed. Many of the cofactor nutrients are available as supplements. They can be found individually or in multi combined supplements.

There are various forms of magnesium supplements availabale such as magnesium taurate, magnesium glycinate and more. Magnesium glycinate might be the best form to take as it has many calming effects.

Supplementing with a combination of cofactors may help to synthesise GABA such as vitamin B6, magnesium and taurine. It is best to keep any combined formulas limited and to first check if there is any deficiency of the cofactor nutrients to determine which nutrients may be beneficial.

Deficiency Symptoms of GABA

GABA deficiency is quiet common.

When GABA becomes deficient there is more nerve transmissions taking place which can pave the way for some of the symptoms of anxiety.

Having sufficient GABA levels will make a person feel calm and content as it regulates the stimulating effects of norepinephrine, whereas very low levels will make a person feel overwhelmed and cause anxiety.

GABA calms down the nervous system which can reduce symptoms of anxiety.

Signs and symptoms of GABA deficiency include:

• Anxiety
• Stress
• Depression
• Memory problems
• Muscle pain
• Headaches
• Insomnia
• Difficulty sleeping
• Acting out dreams
• Heart palpitations
• Rapid or irregular heartbeat
• Muscle tension
• Muscle spasm
• Difficulty breathing
• Shortness of breath
• Cold, clammy hands and feet (feel sweaty)
• Easily scared (may be startled)
• Excessive worry*
• Out-of-body feelings
• Obsessive compulsive behaviour
• Expectations for negative outcomes*
• Feeling overwhelmed without any cause
• Racing thoughts (during attempts at relaxation)
• Difficulty concentrating
• Inability to focus on single tasks (easily distracted)
• Losing train of thought
• Tiring easily
• Fatigued without any exertion
• Mind feels empty
• Depersonalization
• Chronic pain
• Inflammation
• Alcoholism
• High blood pressure (Hypertension)

*Some of the feelings of stress, panic, overwhelm or anxiety associated with low GABA has no obvious explanation. The person will have these feelings as well as the physiological manifestations that come with it. GABA deficiency means the central nervous system will be firing too many neuronal signals which can lead to anxiety and the other symptoms associated with it.

*The excessive worrying will make the person dwell on situations that are not likely to occur

*Often the person with low GABA will have negative expectations from situations and people

Low GABA is linked to the following health conditions:

• Epilepsy
• Seizures
• Mood disorders
• Mal de Debarquement Syndrome (MdDS)
• Hypertension
• Diabetes
• Neurotic pain

GABA agonist medications which includes Pregabalin are used in the treatment of conditions related to chronic pain and neurotic pain such as fibromyalgia. [R]

One animal study has shown GABA and glycine triggers REM paralysis by switching off the activity of neurons that facilitate movement, speech and other actions which may be why people act out in dreams when GABA is significantly reduced. [R]

GABA levels raised artificially may trigger a depressive episode. [R] [R]

Causes of GABA deficiency include:

• Chronic stress
• Deficiency of cofactor nutrients
• Malnutrition
• Lack of exercise
• Impaired GABA synthesis*
• Glutamic acid decarboxylase (GAD) enzyme deficiency or interference

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*If glutamate is unable to properly convert into GABA this can cause high glutamate levels which can lead to health problems and have excitotoxic effects.

Vitamin B1 has been effectively used to reduce levels of anxiety and improve the body’s ability to deal with stressful conditions. Vitamin B1 or thiamine is often referred to as a “morale vitamin” as it has a positive effect on our mental attitude. Vitamin B1 is known to decreases feelings of fear and paranoia and may be helpful for those with mental health issues especially those who are very likely to be deficient. People who suffer from anxiety are usually fearful and worry constantly about minor issues. One study has shown these symptoms to be significantly reduced with Vitamin B1 supplementation [http://www.scirp.org/journal/PaperInformation.aspx?paperID=7555].

Studies on animals has shown low glutamate and GABA in the brains of thiamine deficient rats [https://pubmed.ncbi.nlm.nih.gov/2819010/]

Although GABA is a calming neurotransmitter it has shown to play a role in anger or aggression with some studies showing positive allosteric modulators of GABAA receptors increasing aggressive behaviour. Positive modulators of GABAA receptors include alcohol, benzodiazepines, and many neurosteroids but are dose dependent with higher doses showing to reduce aggressive behaviour to GABAs more sedative like effect inducing calmness and reducing aggression. [https://pubmed.ncbi.nlm.nih.gov/14609546/]

Chronic stress and smoking increases risk of cancer and suppresses cancer inhibiting GABA [https://jcmtjournal.com/article/view/2050]

Toxicity Symptoms of GABA

Too much GABA can reduce brain activity causing feelings of sleepiness throughout the day

Having too high GABA levels may be unlikely however certain medications can significantly raise GABA levels causing sleepiness as well as other symptoms.

Signs and symptoms of excess GABA includes:

• Excessive daytime sleepiness (hypersomnia)
• Reduced fear
• Low motivation*
• Unaware of emotions*
• Difficulty focusing
• Memory problems
• Low blood pressure
• Gastric problems
• Lack of appetite
• Constipation
• Nausea
• Drowsiness
• Dizziness
• Muscle weakness
• Fatigue
• Shortness of breath
• Shallow breathing
• Slurred speech
• Blurred vision

A person with excess GABA will not feel like doing anything and the excessive sleeping will not revitalize the senses and awareness. So although the person will be sleeping more it will not have the same effect of recharging the body in the same way having normal adequate amounts of GABA would. The person with high GABA will also have an inability or an awareness of emotions and may feel emotionally numb

Causes of toxicity:

Medications that raise levels too much. Some medications that act as a GABA agonist cause the side effect of feeling drunk.

Excessive supplementation of cofactor nutrients or substances may lead to excessive levels of GABA.

Alcohol has similar effects to GABA but does not directly raise GABA levels however it can overstimulate the GABA pathways causing desensitized GABA receptors. This can increase the chances of alcoholism and binge drinking or other alcohol use disorder.

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