Relaxing, and Focusing: GABA and Glutamate in the Human Brain

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As time passed, we started to learn about the importance of brain chemicals that affect our life, moods, and well-being. Knowing fundamental knowledge about balancing and optimizing brain chemicals is such an immense beauty inside.

In this article, we will cover the importance of balancing GABA and Glutamate for brain health.

Why is balancing GABA and Glutamate important for our brain? The brain’s most abundant free amino acid is glutamate, an intersection for many other metabolic pathways.

Increasing data indicate that abnormal glutamate signaling may contribute to the pathogenesis of attention-deficit hyperactivity disorder. Furthermore, a lack of glutamate may cause mild intellectual disability and modest physical and mental development delays. That’s why we need to balance.

Nevertheless, 30-40% of synapses contain the inhibitory neurotransmitter GABA. It reverses glutamate, the brain’s primary excitatory neurotransmitter.

Glutamate/GABA: The Neurotransmitters of Yin and Yang

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According to ancient Chinese philosophy, the inhibitory (yin) and excitatory (yang) live perfectly. Without realizing it, these ancient thinkers appear to have stumbled onto a primitive explanation of our two essential neurotransmitters hundreds of years before the scientific method was invented!

GABA is the most important inhibitory neurotransmitter in the brain, appearing in 30 to 40% of synapses. It helps counter-balance glutamate, the brain’s main excitatory neurotransmitter—the yang to GABA’s yin. It has been termed “nature’s Valium” for its relaxing impact.

GABA and glutamate are the most abundant neurotransmitters in the brain and are involved in controlling alertness, anxiety, muscular tension, and memory processes.

Glutamate

GABA’s precursor, glutamate, is used by more than half of all neurons and raises the brain’s overall level of excitement. Glutamate generally involves learning, memory, and synaptogenesis (forming new neural connections).

Excessive amounts can produce excitotoxicity, which harms nerve cells.

Dysfunction of the complex systems that govern glutamate release has been detected in Alzheimer’s disease and is a negative factor in ALS, a fast-progressing neurological illness that destroys the neurons that drive voluntary movement.

(One of the two primary types of medications used to treat dementia lowers glutamate-related excitotoxicity in the brain, and the only FDA-approved treatment for ALS is likewise a glutamate modulator.)

Mono-Sodium Glutamate (MSG)

MSG may be the most cognitively harmful food ingredient. MSG’s glutamate is an excitatory neurotransmitter that fires neurons. Too much MSG causes neurons to fire quickly for no reason. Excitotoxicity depletes mitochondrial energy, creates free radicals, and kills neurons.

Glutamate excitotoxicity is a cell death process caused by too much glutamate. There are research shows that the administration of NAC reduces glutamate levels.

However, we need a certain amount of glutamate because it’s the mind’s most abundant neurotransmitter and vital in learning and memory.

Anxious behavior seems to be increased by decreased glutamate activity, and glutamate levels inside the hippocampus, the brain region principally responsible for regulating emotions and memory, appear especially crucial.

The Reason You Have Mental Fatigue: Toxic Amount Of Glutamate

As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role of glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue.

Here are five reasons why too much MSG might be bad:

1. MSG’s glutamate is an excitatory neurotransmitter that fires neurons.
2. Too much MSG causes neurons to fire quickly for no reason.
3. Excitotoxicity depletes mitochondrial energy.
4. Excitotoxicity creates free radicals.
5. Excitotoxicity kills neurons.

According to research, too much glutamate leads to feeling as well, as the toxicity of excess glutamate may contribute to cognitive fatigue; the research in Current Biology discovered that Greater amounts of glutamate, a brain signaling molecule, were found in participants who worked on a cognitively challenging activity for more than six hours.

More information: Does The Brain Get Tired Of Thinking?

Because of the modern foods and lifestyle, we have tend to have “Glutamate excitotoxicity” than GABA

GABA: Calming Chemicals For Most People

GABA lowers the excitement in the brain, and you probably already know how it feels to change that. Anti-anxiety drugs make GABA work better and stop glutamate from doing its job.

The problem is that these drugs are tough to quit and have many side effects. For example, caffeine makes you feel more alert because it can increase glutamate activity and block GABA from being released. People think that problems with the GABA system cause anxiety, panic attacks, heart palpitations, and lack of sleep.

• If your neurons don’t have GABA, they can fire too often and easily. GABA regulates this action, and you need enough to be calm in stressful conditions.
• Anti-anxiety drugs often target GABA receptors in the brain and are very effective at lowering panic attacks, difficulty breathing, and other typically benign symptoms of low GABA levels. These medications, however, do not regulate the brain’s capabilities. Inducing GABA results in dependency, withdrawal, and perhaps increased anxiety.
• Do you know Anxiety disorders such as panic attacks and seizures are related to low GABA activity? Anxiety medications such as Valium enhance the effects of GABA in the brain.
• Also, Mice lacking GABAB1 or GABAB2 receptors are more anxious than the control group.
• Mutations in the ABAT gene cause GABA-transaminase deficiency, leading to some individuals’ low-level GABA. (source)

Why Should I Focus on Improving My GABA Level?

GABA can cross the blood-brain barrier in some people. It helps with relaxation and sleep. GABA also supports emotional and behavioral health by reducing excitability and promoting calmness. It can help fight nicotine addiction by aiding relaxation and reducing stress-related anxiety.

According to Graeme Mason, Ph.D., “GABA may be a helpful target for nicotine addiction therapy.”

However, GABA is the main neurotransmitter regulating sleep. Most sleep disorder drugs enhance GABAergic neuronal inhibition. In human studies, 5-HTP and GABA reduced sleep onset time, increased sleep duration, and improved sleep quality.

Body-Mind, Gut, and Vagus Nerve

The vagus nerve, which links your stomach and brain, is the principal information highway between the two organs. Your gut also communicates with your brain via the endocrine system in the stress pathway (the hypothalamus, pituitary, and adrenal axis)

Nevertheless, we also know that gut bacteria make and respond to other chemicals that the brain uses to create thoughts and sensations, such as melatonin, which regulates sleep; dopamine and norepinephrine, which are “stress hormones,” GABA, which are “relaxation chemicals.”, which clarifies why gut health is so essential for mental health.

The study examined how good gut bacteria may produce important brain chemicals, including BDNF, GABA, and Glutamate.

• The research showed that In a new perspective on such an experiment, mice’s microbiomes were colonized with Lactobacillus rhamnosus, which showed a marked increase in anti-anxiety GABA receptors in certain parts of the brain.
• Some microorganisms in the gut can release chemical messengers similar to those released by neurons, which communicate with the brain via the vagus nerve.

Simple techniques and strategies you can use to optimize your gut bacteria, such as dry fasting and consuming probiotics. Also, you can stimulate your vagus nerve with slow diaphragmatic breathing and cold exposure.

Related: What Are The Three Habits Weaken You And Your Brain?

Ketones For GABA

One benefit of ketones in the brain is that they appear to reduce glutamate levels (an excitatory neurotransmitter) while increasing GABA synthesis (an inhibitory neurotransmitter). And one mechanism of the ketogenic diet’s anti-epileptic impact is enhanced glutamate processing in the brain. (source)

Ketones also can cross the blood-brain barrier, which helps the brain works better. Ketones may also reduce brain inflammation. That may connect Alzheimer’s and Parkinson’s to brain inflammation. 

In multiple studies, ketones are both neurotherapeutic and neuroprotective.

Tips For Optimizing Glutamate/GABA 

To maintain the glutamatergic/GABAergic balance, include times of excitement and inhibition in your daily routine. High-intensity interval training improves balance by increasing GABA and glutamate levels in the brain.

Even one week after working out, increased resting glutamate levels correlate with improved performance.

Here are 5 things that can help GABA:

1. Take a synthetic form of GABA as a supplement.
2. Increase glutamate production by adding precursors like Glutamine, Taurine, and Theanine to your diet or supplement regimen.
3. Eat fermented foods like kimchi, tempeh, and fermented milk.
4. Consume foods that contain GABA or boost its production, like whole grains, fava beans, soy, lentils, nuts, fish, citrus, tomatoes, berries, spinach, broccoli, potatoes, and cocoa. 
5. If necessary and doctors advise, take medications targeting GABA, like barbiturates, anesthetics, benzodiazepines, antidepressants, and anti-seizure medications.

But the cheap and effective one is the Exercise.

Exercise helps depressive symptoms and prevents depression. Physical activity also decreases glutamate accumulation in the brain.

How Can You Optimize GABA Level?

Probiotics help the GI tract produce feel-good neurotransmitters like dopamine, GABA, and serotonin. They improve mood and reduce anxiety and stress. Gut health influences brain function, neurotransmitter production, behavior, pain management, and stress modulation.

Recent animal studies show that kefir consumption may increase GABA synthesis, reducing anxiety. Kefir also contains tryptophan, an amino acid that boosts serotonin.

Kefir also includes tryptophan, an amino acid that boosts serotonin. (source)

Thyroid hormones affect the production of GABA, dopamine, and serotonin. Iodine is essential for thyroid hormone function. Some people claim that iodine is a mild nootropic and protects from radiation.

In addition, L. rhamnosus (JB-1) increased GABAAα2 in the hippocampus. L. rhamnosus (JB-1) significantly reduced stress-induced corticosterone and anxiety- and depression-related behavior. (source)

Meditation, yoga, and deep breathing can increase GABA levels. Meditation improves gray matter, but it takes time. Like meditation, yoga increases gray matter and decreases the size of the amygdala, the brain’s fear center.

Hypothermic conditioning, like ice baths, cold showers, or cryotherapy, can balance the GABA/glutamatergic equilibrium. Cryotherapy involves entering a tank filled with freezing nitrogen gas for about three minutes.

Related: Why Gut Health is the Cornerstone For Brain Health?

The Way Of Optimizing Gut Bacteria Without Any Supplement

• Homemade bone broth: homemade bone broth is excellent for gut health. Why? Bone broth supports intestinal health because of the high amount of L-glutamine, fights inflammation, maintains joint health because of high collagen, helps weight loss, and improves sleep(thanks for Glycine) and cognitive function.
• Apple Cider Vinegar For Support Gut: ACV is naturally acidic, which helps improve digestion, such as proteins and minerals in the stomach. Yet, an acidic environment can help to protect against bad bacteria. Without enough acids, the bad bacteria can easy to pass intential layer. Candida is the most known because candida overgrowth in your gut has been linked to many health problems, such as yeast infections, f depression, headaches, and a strong desire for sugar. Apple cider vinegar is fermented with a beneficial yeast; it can be a prebiotic for healthy bacteria, helping good bacteria grow.
• Exercise And Gut Bacteria: Don’t be surprised to hear that exercise can alter the gut’s good bacteria. According to recent research, exercise may increase the quantity of beneficial microbial species, diversify the microflora, and boost the growth of gut flora. (source) The study discovered exercise boosts the support of the bacteria that make butyrate. Butyrate helps heal the gut lining and decrease inflammation, avoiding inflammatory bowel disease and diabetes. Exercise-induced gut microbiome changes may prevent obesity and enhance metabolic function.

Certain Lactobacillus strains have been shown to create short-chain fatty acids such as acetate, butyrate, and propionate, which are beneficial to health and aid in the formation of the gut barrier, making it less permeable to disease-causing microbes.

How Does Magnesium Affect The GABA System?

Bones and teeth contain 60-65% of the body’s magnesium. The rest is in organs, tissues, and fluids. The heart and brain cells have the most magnesium, making them vulnerable to deficiency. Magnesium deficiency can cause anxiety, depression, muscle weakness, fatigue, insomnia, anorexia, apathy, apprehension, poor memory, confusion, anger, nervousness, and rapid pulse.

Magnesium can affect the GABA system in several ways:

1. Magnesium binds to and stimulates GABA receptors in the brain.
2. This binding puts the brakes on brain activity, helping to calm the nervous system.
3. When GABA levels are low, magnesium can help increase them, reducing stress and anxiety.

Optimizing magnesium boosts gamma-aminobutyric acid (GABA) levels. Magnesium binds to and activates GABA receptors in the brain to slow down neural activity.

Taurine has been shown to boost GABA levels.

Taurine water soluble amino acids impact brain function, growth and development, neurotransmission, neuromodulation, antioxidant activity, and immunological function.

Taurine promotes neurogenesis, cell proliferation, and synapse synthesis in brain areas important for long-term memory and the hippocampus. Also, Taurine enhances and supports GABAergic neuron activity potentials and particularly targets the GABAA receptor. (source)

On the other hand, Caffeine has been shown to reduce inhibitory (GABAergic) action and alter GABA receptors. Hence, that’s why energy drinks combine taurine with caffeine to reduce to the negative side effects of energy drinks and the jittery effects.

Best Magnesium Form Relaxation

The new study showed that magnesium acetyl taurate could help increase the magnesium levels in brain tissue more efficiently than other magnesium forms.

Also, A study found magnesium acetyl taurate is far more effective in increasing brain tissue magnesium levels than magnesium malate, magnesium oxide, and magnesium glycinate forms which are directly linked to lower anxiety symptoms in animals. (source)

Magnesium acetyl taurate contains taurine. The combination made it easier for magnesium to pass the blood-brain barrier. For better, you can combine the B6 vitamin to promote Mg absorption and cellular uptake and helps cross the blood-brain barrier.

L-theanine and GABA

Theanine can cross the blood-brain barrier and blocks the binding of L-glutamic acid to glutamate receptors in the brain. That helps calm and stabilize one’s mood and nervous system.

L-theanine is an amino acid that can help with anxiety in several ways:

1. L-theanine can cross the blood-brain barrier and block the binding of L-glutamic acid to glutamate receptors in the brain.
2. L-theanine boosts GABA levels, helping to calm and stabilize mood and the nervous system.
3. L-theanine increases alpha brain wave activity, which is associated with relaxation.
4. L-theanine regulates neurotransmitter activity, reducing blood pressure and boosting neuron growth in the brain. 
5. L-theanine promotes learning, memory, concentration, and attention.

In summary, L-theanine can help with anxiety by blocking glutamate receptors, boosting GABA levels, increasing alpha brain wave activity, regulating neurotransmitter activity, and promoting cognitive function.

Besides L-Theanine, you can also use L-Glutamine supplements to support GABA production- research found that taking glutamine significantly increased GABA concentrations by 30% and enhanced the response evoked by NMDA alone (70%) to 120% over baseline. (source)

Balancing GABA and Glutamate

One way to maintain the delicate equilibrium of neurotransmitters is to limit your intake of processed foods containing added glutamate. One source is the flavor enhancer monosodium glutamate (MSG), often used in Chinese cuisine. Another is the noncaloric sweetener aspartame, which converts into glutamate precursors when consumed.

Also, when brain cells lack oxygen, glutamate, the brain’s primary excitatory neurotransmitter, doesn’t work efficiently with neuroreceptors. This can cause a toxic buildup of glutamate within brain cells, leading to neuron damage and death.

NAC helps regulate and normalize glutamate levels in the brain. Glutamate is necessary for normal brain activity, but excess glutamate depletes glutathione. NAC detoxes the brain and boosts glutathione levels.

Avoid alcohol because it desensitizes GABA receptors. Long-term alcohol use causes GABA receptor downregulation, leading to stress, anxiety, and drinking. Over time, alcohol tolerance may lead to addiction. Desensitized GABA receptors may explain why alcohol withdrawal causes anxiety.

Practically, Limit caffeine intake because it depletes GABA levels. Coffee drinkers may experience anxiety, irritability, panic attacks, and other symptoms of nervous tension.

How Does Stress Affect The GABA System?

When you’re stressed, your body secretes cortisol, a hormone that helps regulate your body’s stress response. Cortisol can affect the GABA system in several ways.

1. Stress can decrease levels of GABA in the brain.
2. Stress can affect the development of the nervous system and GABA activity. 
3. Low levels of GABA due to stress may play a role in brain function and mood disorders, including schizophrenia, autism, depression, and anxiety.

In summary, stress can decrease GABA levels and affect its activity in the nervous system, potentially leading to mental health disorders.

Neurotransmitter Balance is Disturbed By Iron Overload.

The majority of research has focused on iron-related liver injury. Unfortunately, iron overload can cause brain cells damages, and lower neurogenesis and BDNF provoke a neurotoxic effect.

People won’t be aware that iron buildup or iron overload in the brain is typically related to neurodegenerative illnesses such as Parkinson’s and Alzheimer’s, cellular damage after a hemorrhagic stroke, and even traumatic brain injury. (source)

• According to research, iron overload disrupts the balance of neurotransmitters. When iron is infused into the substantia nigra, it disrupts monoaminergic systems, notably the dopaminergic pathway, which results in Parkinson-like symptoms of motor impairment. (source)
• Iron overload may be more common and dangerous than iron deficiency anemia. There is no effective iron elimination pathway, so almost all adult males and postmenopausal women are at risk for iron excess. Some supplements may help.

In other words, these populations do not experience frequent blood loss. Some of the symptoms of iron overloads are:

• Fatigue (feeling tired a lot).
• General weakness
• Erectile Dysfunctions (iron toxicity may cause erectile dysfunction (impotence), lack of sex desire in males, and menstrual cycle absence in women.)
• Iron accumulation in the brain has been associated with Brain fog, neurodegenerative diseases, and psychosocial disorders. 

Balance Your Neurotransmitter With Getting Rid Of Excess Iron

Excess iron elimination and detoxification may benefit both men’s and women’s health by improving dopaminergic cells, neurotransmitter formations, sexuality, testosterone hormones, and cell health. Here are some pointers:

• Reduce heme iron intake and red meat will help overcome and prevent iron toxicity
• Exercise: Exercise can help you use excess iron for energy and mitochondrial energy, and the body and muscles utilize more iron while exercising and sweating.
• Milk Thistle: According to studies, milk thistle may reduce ferritin levels, improve liver health, and address other issues related to iron overload. Milk thistle polyphenols, such as silymarin and silybin, have been demonstrated to aid liver function and promote health. Milk thistle also helps to boost glutathione production, eliminating other heavy metal toxins.
• Donate blood: The best strategy for optimizing your iron level and helping others is donating blood. On average, you can give 20% of your iron in just one session of blood donation, which will help to overcome iron overloads.

If you have high levels of iron, it’s possible for blood vessels and develops heart disease since iron can cause oxidative stress. However, keeping an eye on your ferritin levels to ensure they aren’t much higher than 80 ng/ml would be the best approach for your health.

Quercetin Could Reduce Sleep Deprivation-Related Behavior

Optimizing the proper balance of GABA is crucial for sleep and anxiety-related behavior. GABA can disturb by oxidative stress and inflammation.

Again, Inflammation is the basis of many illnesses, including autoimmune disorders, heart disease, neurotransmitter balance, and cancer. Quercetin is an antioxidant and anti-inflammatory benefit since far better health benefits.

• In animal studies where the subjects didn’t get enough sleep, quercetin’s strong antioxidant properties are likely one reason why the mood-related behaviors of the animals were enhanced.
• According to the results of the research, quercetin minimized the negative effects of poor sleep on memory function, behavior like depression, and the death of brain cells in the prefrontal cortex.
• In a 2016 study, researchers show quercetin may lower mice’s manic-like behavior after 24 hours of paradoxical sleep deprivation.

Quercetin can function in several pathways to help reduce your risk of cancer and prevent mitochondrial damage. It’s a good option to consider short or long-term optimizing your Quercetin intake for managing overall inflammation body and protecting neurotransmitter balance as well as the prefrontal cortex.

Check Your Zinc Level For Mood, Depression, And Anxiety

Besides GABA, Anxiety, and depression may indicate a lack of zinc. Researchers found low zinc serum blood levels in depressed people, suggesting that zinc deficiency may cause depressive thoughts. Depression shrinks the hippocampus, responsible for emotional regulation, memory, and learning.

Zinc is important for treating depression and anxiety. It protects the hippocampus from inflammation caused by emotional and environmental stress. Zinc may also stimulate brain-derived neurotrophic factor (BDNF) synthesis, a critical metabolic agent that combats brain inflammation, anxiety, and depression.

Final Thoughts

Low GABA levels in the brain can cause anxious behavior. Like dopamine, GABA is an important brain chemical that helps calm and relax the mind, easing anxiety. People with GABA deficiency may crave alcohol and other addictive substances, but not everyone is the same.

You can optimize your GABA levels by meditating regularly and consuming fermented foods rich in Bifidobacterium.

I hope you enjoyed this article!