GABA: Managing Brain Stimulation, Anxiety, and Other Consequences

Monday, September 08, 2014
By: Linda J Dobberstein, DC, DACBN, DCBCN

Stimulation surrounds us everywhere and everyday. Our nervous system has to process and filter this stimulation 24/7. Oftentimes, we do not realize how massive the job is in managing stimulation until something goes wrong. This may manifest as a migraine headache, panic, anxiety, depression or feeling stressed out. Sometimes it is more serious, such as dealing with chronic neurological concerns such as fibromyalgia, PTSD, Reflex Sympathetic Dystrophy, dementias, concussions, traumatic brain injuries, Chronic Fatigue Syndrome, chronic pain, or some type of seizure disorder. Whatever the case, managing brain stimulation is vital to preventing and managing brain fatigue and neurological dysfunction.

Your central nervous system is managing thousands and thousands of signals every millisecond. It orchestrates every detail of life function with the vast majority of it under unconscious control. It observes how much light is in the environment to engage or relax our pupils so that our eyes can take in the information we are seeing. It monitors environmental temperature and keeps the body adjusted to that temperature. It monitors the pressure on the pelvis and low back when sitting or standing. It listens to the sounds of the environment, hears the hum of traffic or TV in the background. It also manages all of the internal communications with the endocrine and immune system. It vigilantly monitors every digestive, detoxification process, hormonal shift, and many other processes constantly. It does this all with the internal organs in an orchestrated clockwork process.

Add in the recovery process from recent yard work, the chronic IBS symptoms, or the recent dental procedure. Add in your work or homework, learning new tasks, performing basic tasks, or automatic daily behaviors. Uff dah! Then what about being on call 24/7? Smart phones, emails, MP3/4 players, iPods, daily traffic, parenting and more all get your brain’s attention. You get the picture. Command Central is busy! When the brain functions well, it is an absolutely astonishing organ. However, when it starts to be overworked or over-stimulated, consequences occur. The last two newsletters, Brain Fatigue 101 and Brain Fatigue: Fundamental Solutions, have discussed examples and scenarios regarding neurological fatigue. In this article, we delve into the major dynamic players that lead to excess neurological stimulation.

Neurotransmitters

In this vast brain relay information highway, there are some main players called neurotransmitters. They are the messenger molecules that communicate information throughout the brain and body. There are over 60 different molecules that are currently known as neurotransmitters. Some of the best known classical neurotransmitters are acetylcholine, serotonin, dopamine, norepinephrine, epinephrine, histamine, excitatory amino acids (aspartate and glutamate), inhibitory amino acids (GABA - gammaaminobutyric acid, glycine), adenosine, and ATP. There are also peptides such as substance P, beta endorphin, oxytocin, insulin, glucagon, and cholecystokinin and certain gases like nitric oxide that act as neurotransmitters. All of these compounds must intricately function together.

GABA

GABA is a critical neurotransmitter and is the primary inhibitory neurotransmitter functioning in the brain. Its purpose is to reduce nerve excitation or stimulation. It also sets the tone of muscles, i.e. too little GABA can lead to significant muscle stiffness or hypertonicity. GABA receptor sites compromises nearly 1/3 of all brain neurotransmitter receptor. This gives an idea of how vital GABA is to neurochemistry.

In recent years, researchers have found other exciting discoveries on GABA. They found that it is involved with immune system function and either activates or suppresses several immune system activities, including regulating cytokines. It is also found in a number of other tissues in the body other than the brain. This area of study most certainly will continue to develop, I suspect especially in the arena of autoimmune disorders and early life stress.

Lack of GABA can be felt in many different ways. Anxiety and panic disorders are common issues associated with lack of GABA. Having high levels of fear, a sense of something bad is going to happen/dooms day feeling is another manifestation. Often the symptoms increase when you are trying to relax, i.e. the mind goes on the gerbil wheel or rumination occurs. There may be problems with racing thoughts. There are often episodes of explosive behavior – temper tantrums or unstable mood in children or adults. There is poor organization to detail and problems with distraction. It can be hard to get to work or appointments on time, or trouble managing homework. There is inner tension or excitability that doesn’t allow relaxation or it’s hard to unwind. It can manifest with needing to fall asleep with the TV on, or needing to have a little “night cap.”

Glutamate and GABA

Glutamate is considered the main excitatory neurotransmitter and works in balance with GABA. It is essential to maintain wakefulness, alertness, memory and learning. Too much glutamate in the brain has been associated with several disorders including ALS, CFS/ME, Huntington’s Chorea, stroke, Alzheimer’s, Restless Leg Syndrome, MS, headaches, seizure disorders, PTSD, traumatic brain injuries, and many other concerns. The other classical neurotransmitters are generally stimulatory, but function may vary depending on the type of receptor site that receives the neurotransmitter. So in the course of a day’s work with the brain, it is absolutely vital to ensure that GABA stores are adequate to deal with the constant barrage of stimuli and to keep glutamate in balance.

GABA is synthesized in the brain. It normally does not cross the blood brain barrier when taken as a supplement or obtained in foods unless there is a leaky blood brain barrier. The inhibitory neurotransmitter GABA is made from the main excitatory neurotransmitter glutamate using an enzyme called GAD and B6 in a process called the GABA shunt pathway. The GABA shunt pathway is a by-product of the brain metabolizing glucose and making energy. The pathway does not always convert into GABA. It also continues making the excitatory neurotransmitter glutamate if the pathway is dysfunctional or too much stimulation is present. This can lead to trouble, i.e. any of the symptoms listed above or disorders like chronic migraine headaches, insomnia, PTSD, neuropathy pain syndromes, chronic pain disorders such as fibromyalgia, neurodegenerative disorders, etc. are concerns linked with this imbalance.

There are a number of things that can aggravate the GABA shunt pathway that are unrelated to excess external environmental stimuli that was discussed earlier. Lack of vitamin B6 is a significant factor for depletion of GABA, a build-up of glutamate and consequential brain overstimulation. Vitamin B6 is the vitamin that is essential for the GABA shunt pathway to turn glutamate into GABA. The end result is problems with anxiety, mood, sleep, focus, and energy, etc. Researchers identified this concern decades ago, but it continues be a common nutritional oversight. It is especially for problematic for women using birth control or HRT. These types of medications or high levels of estrogen deplete B6 in the body.

Besides lack of B6, the immune system can attack and destroy the GAD (glutamic acid decarboxylase) enzyme that is responsible for routing glutamate into GABA. This is often associated with autoimmune disorders such as Hashimoto’s, Celiac Disease or gluten intolerance, type 1 diabetes, and other neurological disorders with cognitive decline. This includes GAD destruction and GABA insufficiency associated with autism spectrum disorders.

Other GABA Implications

Proper formation and maturity of the GABA system in prenatal development requires a balance with thyroid and quality stress management. Researchers demonstrated that without adequate thyroid hormone, the development of GABA receptors and proper GABA signaling in the infant brain was compromised. Lack of adequate thyroid hormone in-utero severely affects brain development. Consequentially, it has an effect on fundamental neurotransmitter communications. Other studies have shown that being exposed to high levels of cortisol or stress in fetal development or early childhood cause altered brain metabolism or an imprinting of high stress brain circuitry. This means the child may start life with the brain semi-hard wired with a poor stress tolerance state. This can potentially lead to lifelong changes of altered production, function and levels of excess stimulatory and imbalanced neurotransmitters in the brainstem, cortex, and the limbic system – especially the hippocampus. The hippocampus is part of the limbic system that is involved with formation and consolidation of new memories, emotional responses, navigation and spatial orientation. Pregnant mothers with unborn children or young children absolutely need proper support and stimulation/stress management to prevent lifelong neurological consequences of early life stress.

Vitamin E deficiency (tocopherols and tocotrienols) has immense implications also with GABA and glutamate. Last week’s newsletter discussed the importance of oxygenation, blood sugar, and vitamin E for cellular respiration and making energy in the brain. Researchers demonstrated in animal studies that lack of vitamin E in fetal neurological development caused abnormal levels of glutamate and insufficient GABA function leading to faulty neurotransmitter signaling and increased stress responses. In essence, lack of vitamin E may lead to increased levels of stimulation during prenatal and perinatal brain development. As we learned last week, if the vitamin E deficiency continues, it can lead to brain fatigue and neurodegeneration. Without adequate vitamin E, nerves or axons actually become swollen and defective. This is considered diagnostic of vitamin E deficiency. Hopefully your next retinal eye exam does not show this pathology.

Concerns that cause stress and high amounts of stimulation to the brain must be dealt with. It is crucial. This includes anemia, poor oxygenation, toxin exposure (molds, pesticides, herbicides, etc.), food intolerances, autoimmune disorders, digestive problems and increased gut permeability, oxidative stress and inflammation, alcohol or other addictive substances, or being exposed to high levels of stress in prenatal development or early childhood will contribute to the imbalance of excess stimulation and impaired inhibition. The development of many autoimmune disorders and mood disorders often demonstrates a link with early life stress. The recent identification of GABA disturbances with immune system signaling and cytokines that occur systemically, as well as the in utero or in early life stress, may provide powerful tools in helping individuals with complex autoimmune disorders find explanations for why and how to manage their concerns.

Nutrition for GABA

There are a number of compounds that help improve GABA function and activity in the brain. Taurine, glycine, magnesium, lemon balm, B6, L-theanine, Noni, passion flower, and valerian root provide some of the best GABA supporting compounds. Taurine is a potent activator of GABA receptors in the limbic system. It acts as a natural internal regulator of nerve excitability.

Glycine is another major inhibitory neurotransmitter like GABA. The location of glycine is primarily found in the brainstem whereas GABA is in the limbic system and forebrain. Research published just days ago identified that glycine works with GABA together in the inner ear, i.e. the cochlear nucleus and regulates sound stimulus. A speculative clinical application may be that glycine and GABA may provide benefit for those with tinnitus or other auditory disorders.

Magnesium is a mineral that functions as a natural antagonist to excitatory stimulus and supports GABA activity. It is commonly used as a natural anti-stress nutrient and has been found highly beneficial for sleep and anxiety.

Lemon balm is commonly known for its anti-anxiety effects. It supports GABA levels and also helps to reduce excess cortisol levels.

L-theanine is a powerful nutrient that has been shown to reduce the effects of chronic stress related cognitive impairments and consequential oxidative damage. It is able to accomplish this by down-regulating excess cortisol and catecholamines. It is also considered a GABA supporting compound that promotes relaxation.

Noni is well recognized for its support with immune system function. It has been shown to protect the brain from cognitive decline associated with stress. Researchers have demonstrated that it can bind to GABA receptor sites as a helpful agonist. This action induces anti-anxiety and calming effects on the stress response.

Passion flower has a significant herbal medicine history. It is commonly used in treating various anxiety disorders, insomnia, nerve pain, seizure disorders, ADHD, cardiac arrhythmias and more. The mechanism of action for how this occurs is still under debate. Researchers have concluded that passion flower modulates the GABA system with receptor sites and GABA uptake.

Medical researchers and physicians have recognized the importance of GABA for many years in understanding neurological function with various mood concerns, hence the popularity of the benzodiazepine meds. Larger pieces of the puzzle are coming together in understanding neurological development, early life stress and how GABA molecular structure develops. In addition, the initial understanding of GABA functioning in tissues outside of the brain puts a spin on GABA like never before. Clearly we need to be mindful of stress input and output. As we have seen, this is especially critical for the unborn and children in neurodevelopment as well as adult life and stress management. Using nutritional support and behavioral changes to support GABA can make a profound difference in daily life. Try doing a GABA challenge with nutrients that support GABA formation. See if stress tolerance, sleep, behavioral disorders and mood improves. You might be pleasantly surprised!

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