Cognitive and Mental Health
The Vital Role of GABA for Mental Health and How to Optimize It Naturally
Gamma-aminobutyric acid is a neurotransmitter crucial in the nervous system as an inhibitory neurotransmitter affecting stress and anxiety.
Feel your best by balancing your GABA.
Are you experiencing chronic stress, anxiety, irritability, hyperactivity, impulsivity, attention deficit, depression, sleep deprivation, or muscle tension?
If your answer is yes to some of these points, this article may provide valuable insight into potential causes and practical tips to address these symptoms by optimizing a critical neurochemical.
Low GABA levels have been linked to chronic stress, anxiety, attention deficit, depression, sleep disorders, and muscle tension.
As a part of my writing objectives for 2023, I plan to carefully analyze and disseminate research on hormones and neurotransmitters to enhance readers' understanding of their impact on health and overall well-being.
I recently introduced dopamine, serotonin, and oxytocin. GABA is another critical neurotransmitter that significantly affects our stress and anxiety levels. Awareness of stress and anxiety is critical as they are the root cause of multiple physical and mental disorders.
Here’s an overview of GABA, its functions, factors that can impact its balance in the body, its interaction with hormones and other neurotransmitters, the effectiveness of supplementation, and strategies for optimizing it naturally.
What is GABA?
Gamma-aminobutyric acid (GABA) is a critical neurotransmitter for the proper function of the nervous system. It acts as a primary inhibitory neurotransmitter in the brain.
GABA is also a non-proteinogenic amino acid. It means that GABA is not used to synthesize proteins in the body. It serves as a precursor to other molecules.
Initially, GABA was discovered in plants in 1949. It was then identified in the mammalian brain, both in animals and humans.
As documented in this paper, researchers identified its crucial function for the central nervous system in the 1980s. New studies indicate that 60–75% of all synapses are GABAergic.
The brain creates GABA from the amino acid glutamate. This amino acid is also a neurotransmitter synthesized from other proteins. As the body can synthesize it, glutamate is not considered an essential amino acid.
An enzyme called “glutamate decarboxylase” helps convert glutamate into GABA with the assistance of a coenzyme called pyridoxal phosphate, which is an active form of Vitamin B6.
This process primarily happens in special brain cells called GABAergic neurons. The term GABAergic refers to neurons that use GABA as their primary neurotransmitter.
When it’s assembled, GABA is stored in tiny bubbles and is released into the space between cells when an electrical signal reaches the end of the cell.
GABA then attaches to receptors on nearby cells and slows their activity. You can learn more about the process from this resource.
As documented in this paper, “in addition to its role as a neurotransmitter, GABA also exists naturally in various foods, such as tea, tomato, soybean, germinated rice, and some fermented foods.”
As the brain creates GABA from the amino acid glutamate, it is necessary to get adequate and bioavailable protein in our diet. This synthesis occurs by utilizing glutamine, proline, aspartate, and alpha-ketoglutarate.
This paper informs that “GABA [from food or supplements] has long been thought to be unable to cross the blood–brain barrier (BBB), which raises questions about the mechanisms of action behind its health benefits. However, there are various accounts regarding GABA’s BBB permeability.”
“While some researchers argue that only small amounts of GABA cross the BBB, with the discovery of GABA-transporter systems in the brain, others believe that substantial amounts of GABA could cross the BBB.” You can check the cited studies in this publicly available review paper.
Critical Functions of the GABA in the Body
GABA plays multiple roles in the nervous system. It regulates the activity of neurons. It serves as the primary inhibitory neurotransmitter in the brain.
GABAergic neurons are found in numerous brain regions, including the cerebral cortex, hippocampus, and basal ganglia. I summarize the functions under five bullet points.
GABA has a calming effect on the central nervous system, which can help to reduce feelings of stress and anxiety and promote good sleep.
It creates an analgesic effect to reduce the perception of pain.
It has a calming effect on the cardiovascular system, which can help to regulate heart rate and blood pressure.
It plays a role in regulating muscle tone.
It is involved in the control of movement.
The most crucial aspect of GABA is regulating sleep and relaxation. Low GABA levels have been linked to insomnia and other sleep disorders, while naturally increasing GABA levels can promote relaxation and improve sleep quality.
Low levels of GABA may lead to increased anxiety and stress, as they may allow excitatory neurotransmitters to become overactive. Increasing GABA levels through supplementation may help to reduce anxiety and stress by inhibiting the activity of excitatory neurotransmitters.
Cognitive and Mental Health Implications of GABA
Balanced and optimized GABA levels are essential for regulating stress response and lowering anxiety. Imbalances are associated with chronic stress, anxiety, attention deficit, and depression.
This paper in Nature informs that “increasing evidence points to an association between major depressive disorders and diverse types of GABAergic deficits.”
The paper summarizes clinical and preclinical evidence supporting a central and causal role of GABAergic deficits in the etiology of depressive disorders.
Low levels of GABA have been linked to symptoms such as difficulties with attention, impulsivity, and hyperactivity. Therefore it is linked to ADHD.
For example, this paper concludes that “reduced GABA concentration in ADHD is concordant with recently reported deficits in short intracortical inhibition in ADHD and suggests a GABAergic deficit in ADHD.”
Factors that can adversely affect GABA balance
Several factors can affect GABA balance in the body. Lifestyle modifications to address these factors can balance and optimize GABA levels naturally. I summarize them under nine points.
1 — Chronic stress and sleep deprivation
2 — Excessive alcohol and caffeine consumption
3 — Poor diet leading to nutritional deficiencies such as vitamin B6 and zinc
4— Physical inactivity and sedentary lifestyle
5 — Environmental toxins, such as heavy metals, pesticides, air pollution, and cigarette smoke
6 — Some medications, such as benzodiazepines and antipsychotics
7— Hormonal imbalances, such as during menopause or pregnancy
8 — Genetics variations and aging
In addition, some illnesses and chronic pain interfere with the production and metabolism of GABA.
GABA’s Interaction with Hormones and Other Neurotransmitters
Several hormones and neurotransmitters can interact with GABA in the brain. Some of them can inhibit GABA production, and others can enhance its production and balance.
Hormones and neurotransmitters that increase GABA activity in the brain are thyroid hormones, estrogen, serotonin, oxytocin, acetylcholine, melatonin, and adenosine.
Hormones and neurotransmitters that decrease GABA activity in the brain are cortisol, dopamine, glutamate, norepinephrine, and histamine.
Does GABA supplementation work?
GABA supplements are available over the counter in some countries. Some preliminary and small-scale studies suggest that direct GABA supplements might relax the body and help reduce anxiety and promote sleep.
GABA supplements are usually produced via fermentation using microorganisms (bacteria or yeast). The microorganisms are fed a substrate, such as glucose or soybeans, producing GABA as a byproduct. The GABA is then purified and concentrated on creating the final supplement product.
This paper informs that “GABA’s stress-reducing and sleep-enhancing effects have been established. However, although several human clinical trials have been conducted, results regarding the role of natural and/or biosynthetic oral GABA intake on stress and sleep are mixed.”
The 2020 systemic review published in Frontier examining 14 studies' results shows that there is limited evidence for stress and very limited evidence for sleep benefits of oral GABA intake.
This 2015 paper titled “neurotransmitters as food supplements: the effects of GABA on brain and behavior” in Frontier informs that Pharma-GABA has been approved by the FDA as a food ingredient.
As informed in this 2021 review paper, “GABA is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data.”
The review informs that “clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for four days and in longer studies at intakes of 120 mg/d for 12 weeks.”
However, “some studies showed that GABA was associated with a transient and moderate drop in blood pressure. No studies were available on the effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA.”
As the literature indicates, although consumers claim that they experience benefits from using GABA products, it is still being determined whether these supplements confer benefits beyond a placebo effect.
Arguably, the most bioavailable form of GABA is considered to be Phenibut which affects brain chemistry noticeably. It is known as beta-phenyl-gamma-aminobutyric acid (beta-phenyl-GABA). Even though it is sold online, it is restricted in some countries.
For example, the sale, distribution, use, manufacture, and possession of Phenibut is prohibited except in certain circumstances, such as approved medical or scientific research. Phenibut is a Schedule 9 (prohibited) substance in Australia.
Although GABA supplements have been reported to be effective for some individuals in improving sleep and managing stress, I did not experience any benefits from a short-term trial of GABA supplementation. As a result, I discontinued its use.
I have found that supplementing lithium orate has been more effective for me in addressing sleep concerns and reducing my stress, as lithium increases GABA levels in cerebrospinal fluid.
As informed by the medical doctor and psychiatrist Flavio Guzman (CEO of the Psychopharmacology Institute), lithium inhibits excitatory neurotransmitters such as dopamine and glutamate and promotes GABA-mediated neurotransmission.
Summary
GABA, as a neurotransmitter, plays multiple roles in the nervous system, including serving as the primary inhibitory neurotransmitter in the brain. GABAergic neurons are found in various brain regions using it as the primary neurotransmitter.
GABA is involved in the regulation of multiple physical and mental functions, such as stress, sleep, anxiety, attention, focus, muscle tone, and movement. Low GABA levels have been linked to chronic stress, anxiety, attention deficit, depression, sleep disorders, and muscle tension.
Several factors can affect GABA balance in the body, including chronic stress, sleep deprivation, excessive alcohol, and caffeine consumption, poor diet leading to nutritional deficiencies, chronic pain, illness, physical inactivity, environmental toxins, some medications, hormonal imbalances, genetics, and aging.
Several hormones and neurotransmitters have the ability to interact with GABA in the brain, influencing its activity and potentially causing imbalances in GABA levels. These hormones and neurotransmitters may either enhance or inhibit GABA production and function.
For example, high serotonin, oxytocin, acetylcholine, melatonin, adenosine, and estrogen can increase GABA. And high levels of cortisol, dopamine, glutamate, norepinephrine, and histamine can decrease it.
Imbalances in neurotransmitter levels can have a detrimental effect on cognitive function and mental health, often manifesting as accumulated stress within the body that can lead to further complications.
Despite your healthy lifestyle habits, if you are experiencing the symptoms described in this article, you must seek the advice of qualified healthcare professionals, such as neurologists and psychiatrists, with a referral from your primary care physician.
Practical Tips to Balance GABA Naturally
Literature indicates several ways to optimize and naturally balance GABA levels in the body. Some strategies include exercise, diet, stress management techniques, improved sleep, and nutritional supplements. Based on my reviews, I summarize key points below.
Incorporate relaxation techniques such as yoga, deep breathing, progressive muscle relaxation, visualization, aromatherapy, or massage into your daily routine.
Practice good sleep hygiene for restorative sleep, maintain a consistent sleep schedule, and create a relaxing bedtime routine.
Get some natural light during the day, and avoid long periods of sitting or lying down in bed during the day.
Eat a healthy and balanced diet of whole foods with bioavailable proteins. Refrain from excessive sugary, salty, and oily products from junk food.
You may consider eating cheese, dairy cream, yogurt, fermented foods, and other food items recommended by dieticians or nutritionists.
Consider supplementing with vitamin B6, zinc, magnesium, and lithium orotate with the support of a family physician if you have a deficiency.
Try natural remedies such as herbs, melatonin, and GABA supplements with the support of a naturopathic doctor.
Take a spa or warm bath with Epsom salts.
Avoid caffeine, alcohol, smoking, large meals, and strenuous exercise close to bedtime.
Get your hormones and neurotransmitters checked if you have the symptoms mentioned in this article.
Thank you for reading my perspectives. I wish you a healthy and happy life.
You might also check other neurotransmitters such as glutamate, dopamine, serotonin, oxytocin, acetylcholine, norepinephrine, and histamine that I reviewed. Glutamate interacts with all of them directly or indirectly.
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