Is Your Brain Making Enough GABA?
GABA (Gamma-AminoButyric Acid) is an inhibitory neurotransmitter that has a calming and relaxing effect in the brain. It acts like the brakes in a car, to where it slows down and/or stops brain activity on an as-needed basis to help us function better.
When we are low in GABA, our brain continues to hit the gas, overstimulating us with activity. Our gut microbiome plays an important role with GABA production and helps to convert glutamine and glutamic acid into GABA. A disordered microbiome is a major cause of low GABA production (1, 2).
GABA’s Activity in the Brain
GABA receptors are spread out throughout the brain and they are ligand-activated chloride channels that when activated, allow the negatively charged chloride ions across the cell membrane and into the cell where they reduce cellular activity. In addition, they help to shunt the positive charged potassium ions across the cell membrane and out of the cell in order to inhibit activity and take the nervous system away from threshold.
GABA is synthesized from the amino acid glutamate with the enzyme glutamate decarboxylase (GAD) and pyridoxal phosphate (which is the activated form of vitamin B6) as the key cofactor. This process converts glutamate, which is the principle excitatory neurotransmitter in the brain, to the principle inhibitory neurotransmitter GABA (3, 4).
In most regions of the brain, GABA is too large a molecule to cross the blood brain barrier (BBB) (5). However, there are certain areas that have a permeable barrier, such as the periventricular nucleus of the hypothalamus, which sits in the 3rd ventricle of the brain. GABA has been shown to influence brain activity through this region and help to modulate the amount of human growth hormone release (6).
GABA is also an important part of the synthesis of the sleep hormone melatonin. It has a key role in the conversion of serotonin into N-Acetylserotonin, which then converts to melatonin for inducing sleep (7). Melatonin also plays a huge role in the body’s immune function.
Symptoms of Low GABA Levels
People with low GABA will often see a worsening of these symptoms when they skip a meal or attempt to fast.
Factors Involved In Reducing GABA Levels
There are too many factors involved in reducing GABA levels to name. Here are some of the most common.
Chronic Stress and Adrenal Fatigue
Chronic stress will increase the levels of cortisol, norepinephrine and epinephrine in the brain and body. This also shunts the body into producing more excitatory glutamate and reduces GABA production (8).
Too much glutamate in the brain causes over-excitation of the brain cells. In addition, the increase in stress hormones ramps up cellular activity and causes excessive production of free radicals which damage brain cells and further reduce normal GABA production (9).
Overtime, when an individual is in a long-term, highly stressful condition, they rewire their brain cells and have a functional deficit in GABA production (10). This is where lifestyle intervention and GABA supplementation strategies done over a period of time, are so helpful in rewiring the brain to produce and use GABA effectively again.
Inadequate or Ineffective Sleep
Lack of quality sleep is a chronic stressor on the body and increases stress hormone production. This causes the same mechanisms as what was described right above. The question is, what came first, was it stress and low GABA and melatonin that caused the poor sleep or was it the poor sleep that caused chronic stress and low GABA and melatonin.
In either case, it is a true vicious cycle where several poor nights of sleep in a row can lead to a rewiring in the brain and a functional deficit in GABA production (11). This is another case where using lifestyle intervention and GABA supplementation strategies over a period of time is so extremely helpful for rewiring the brain to produce and use GABA effectively again.
Poor Blood Sugar Stability
Blood sugar dysregulation is a significant stressor in the brain and disrupts the Blood Brain barrier, which is designed to protect the brain from oxidative stress, infectious microbes, toxic debris and chronic inflammation.
Hypoglycemia or low blood sugar causes a partial starvation of the brain tissue, which increases stress hormones and opens up the BBB for more nutrients to cross over. This also allows more toxins and free radicals to effect brain tissue causing elevated stress hormones and glutamate release.
Additionally, high blood sugar causes insulin resistance in the brain and a functional starvation where there is enough glucose but we cannot get it into the brain to be used. In this case, it leads to opening the BBB and excessive oxidative damage to the brain with elevated stress hormones and glutamate release.
Gut Microbiome Dysbiosis
There is a growing body of research linking the gut microbiome to neurological health. Research has shown that breakdown of the intestinal lining along with low levels of good microbial inhabitants such as lactobacillus and Bifidobacterium are linked with lower GABA levels, increased brain excitability and neurological inflammation (12).
These microbes are essential for B6 absorbtion and activation, which is the critical cofactor in the conversion from the excitatory neurotransmitter glutamate into GABA. Without adequate activated B6, we end up with glutamate excitotoxicity and increased risk of anxiety, seizures, depression, dementia and Alzheimer’s (13, 14).
In an earlier section we discussed how the body converts glutamine to GABA using the glutamic acid decarboxylase enzyme and the activated form of vitamin B6. Some individuals have elevated antibodies (autoimmunity) to the GAD enzyme. This is especially common in individuals with epilepsy and other seizure disorders (15).
Other research has found this condition in individuals with cerebellar ataxia, stiff man syndrome, type I diabetes, drug-resistant epilepsy, balance problems and more (16). In these cases, following protocols to reduce inflammation and autoimmunity are especially helpful. In addition, these individuals may need large doses of supplemental GABA.
Low Zinc, Vitamin B6, Magnesium, Taurine & Glutamine
The amino acid L-glutamine is the most abundant amino acid in the body and it is the precursor to GABA production. Glutamine is first converted to glutamic acid or glutamate, which is key for a good attention span, brain energy, learning ability and memory.
This is important but we need an even percentage of the glutamic acid to then be converted into GABA or we risk over exciting our neuronal cells. The next step in converting glutamate to GABA is dependent upon the activated form of vitamin B6 (pyridoxal-5-phosphate P5P).
Additionally, the amino acid taurine increases the communication and productivity of P5P and promotes the production of GABA. There are studies that have shown that a deficiency of taurine can result in anxiety (17).
Zinc enhances the release of GABA by working to help activate P5P and stimulate the activity of GAD (18). Both B6 and zinc are also essential to the production and utilization of other neurotransmitters such as serotonin, dopamine, norepinephrine, epinephrine and histamine.
Magnesium is important for binding and activating GABA receptors. Without adequate magnesium, we are unable to effectively activate GABA receptors and utilize GABA effectively (19). Magnesium deficiency is extremely common with over 80% of women and 70% of men suffering with this and thus supplementation for most will dramatically impact GABA activity.
Testing For GABA Deficiency
The way that I and many functional health practitioners look at GABA levels is through symptom questionnaire’s and an organic acid test. If a client is demonstrating many of the symptoms listed above that are associated with low GABA than the organic acid test would be warranted.
The organic acid test is a urine test that will look at a biomarker of B6 called pyrodixic. Low levels can indicate that their isn’t enough B6 to successfully convert glutamate to GABA. We may also see very high or very low levels of homovanillic (HVA), which is a dopamine biomarker and vanillymandelic (VMA), a biomarker of adrenaline.
When these are very high it is a sign of heightened stress hormone production which would favor the production of glutamate over GABA. When these levels are very low, it may indicate an overwelmed hypothalamic-pituitary – adrenal axis. You can find the organic acid test here
Strategies to Raise GABA:
In order for the body to manufacture GABA, there needs to be an abundant amount of the amino acid L-glutamine present. Glutamine is then converted into another amino acid called glutamic acid and then into GABA.
This whole process depends upon the activity of zinc, vitamin B6 and taurine. If we are deficient in these nutrients we will not be able to produce adequate amounts of GABA.
- Adapt to Stress Better: Follow the 25 lifestyle strategies in this article to help adapt to stress better and heal any form of adrenal fatigue you may be suffering with.
- Anti-Inflammatory Diet: Be sure to follow the an anti-inflammatory nutrition plan using real and organic foods in order to provide the right nutrients to support healthy neurotransmitter function.
- Sleep Better: It is key for you to prioritize sleep if you are going to improve your GABA levels. Follow the strategies in this article to help you sleep better.
- Improve the Microbiome: Consume fermented foods, anti-microbial and carminitive herbs such as garlic, onions, oregano, basil, thyme, peppermint, ginger, etc. to help improve the overall constitution of the gut microbes.
- Take Epsom Salt Baths with Essential Oils: Epsom salt baths can provide magnesium into the blood stream that acts to relax the body. Adding in essential oils such as valerian, kava, chamomile, lavender, lemon balm and passionflower can be extremely supportive for healthy GABA levels.
- Deep Breathing: Taking time to focus on breathing can be very supportive for GABA levels. Try taking 3 minutes every hour and focus on doing deep breathing with a 5-10 second inhalation and a 5-10 second exhalation. Read this article for more info on breathing properly.
- Regular Exercise: Regular movement is good for all neurotransmitters. Individuals with low GABA should be doing low-intensity movement such as walking and doing lots of deep breathing. Practicing yoga can be extremely supportive of GABA levels.
Best Foods to Boost GABA Levels:
Healthy microbes such as lactobacillus strains produce GABA naturally as a byproduct of metabolizing the amino acids L-glutamine and glutamic acid. Fermented foods that are rich in these lactobacillus microbes are rich in GABA. They are truly the only dietary source of GABA. You may see other lists online, but those are foods that are richer in
- Grass-fed cow or goat kefir or yogurt
- Coconut Water Kefir
- Beet Kvass
- Coconut milk yogurt
- Pickled Ginger
- Miso, Natto or Tempeh
Supplements to Raise GABA Levels:
Magnesium: Supplemental magnesium helps to raise GABA levels. By far, the most effective form for this is called Magnesium L-threonate. I recommend doing 1-2 grams – 1-2 times daily.
B Complex: B6 deficiencies can cause low levels of GABA. I will typically recommend a full B complex supplement with activated forms of B vitamins to maintain.
Probiotics: In particular, supplementing with probiotics that contain a variety of lactobacillus and Bifidobacterium strains help to raise up GABA levels. I recommend taking 30-100 billion CFU’s daily.
GABA: Taking supplemental GABA can be very effective. It is thought to be too large to cross the blood brain barrier, however, most people with low GABA have a disrupted BBB and respond very well to supplemental GABA. I recommend doing 100-200 mg 1-2x daily.
L-Glutamine: Supplementing with L-glutamine can be very effective for supporting GABA levels. I recommend starting with 4-5 grams to see how your body is tolerating it and gradually going up to 10-12 grams for boosting GABA levels.
If you notice an increase in irritability, headaches or anxiety, you may be deficient in B6 and/or zinc. Try adding those in while reducing L-glutamine levels for a while and then try L-glutamine again.
Taurine: This is an amino acid precursor to GABA and has a similar structure but is smaller. In the brain, it helps to activate GABA receptors. I use 300-600mg, 1-2 times daily.
L-Theanine: is a naturally occurring, biologically active, free-form amino acid that provides relaxation support. L-theanine improves GABA production and induces a state of relaxation of the mind without inducing drowsiness. I recommend 50-100 mg, 1-2 times daily.
Valerian, Kava, Chamomile, Lavender, Lemon Balm & PassionFlower: These herbs help to improve GABA production and utilization in the brain. You can drink herbal teas with these or use the essential oils on your body, in an Epsom Salt bath and in a diffuser so you can breathe in these supportive compounds.
Dr Jockers Strategy:
I follow a number of the strategies, including healing the gut, balancing blood sugar and reducing stress. My main supplements I use to improve GABA levels are Brain Calm magnesium and Mood protect. Yes, you can take these both together without any problems.
Brain Calm Magnesium: This is a specific form of magnesium is the only form of magnesium proven in animal studies to cross the blood-brain barrier. Boosting the brain’s magnesium level is vital to healthy cognition, which includes long- and short-term memory, learning, stress management and sleep.
Normal Dosage: 1 scoop – 1x daily Advanced Dosage: 2 scoop – 2-3x daily
Mood Protect: Combination of herbs, nutrients and compounds that promote serotonin and GABA production to ease anxiety and improve overall mood and sleep. This product has clinical dosages of GABA, taurine, L-theanine and 5-HTP. This also contains small amounts of zinc, B6 and magnesium to improve natural GABA production.
Normal Dosage: Take 1 cap – 2 times daily (away from meals)
Advanced Dosage: Take 2 caps – 2 times daily (away from meals)
Sources For This Article Include:
- Galland L. The Gut Microbiome and the Brain. Journal of Medicinal Food. 2014;17(12):1261-1272.
- Evrensel A, Ceylan ME. The Gut-Brain Axis: The Missing Link in Depression. Clinical Psychopharmacology and Neuroscience. 2015;13(3):239-244.
- Petroff OA. GABA and glutamate in the human brain. Neuroscientist. 2002
- Dec;8(6):562-73. Review. PubMed PMID: 12467378
- Kuriyama K, Sze PY. Blood-brain barrier to H3-gamma-aminobutyric acid in normal and amino oxyacetic acid-treated animals. Neuropharmacology. 1971 Jan;10(1):103-8. PMID: 5569303
- Powers ME, Yarrow JF, McCoy SC, Borst SE. Growth hormone isoform responses to GABA ingestion at rest and after exercise. Med Sci Sports Exerc. PMID: 18091016
- Balemans MG, Mans D, Smith I, Van Benthem J. The influence of GABA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol in the pineal gland of the male Wistar rat. ReprodNutr Dev. PubMed PMID: 6844712
- Bremner JD. Traumatic stress: effects on the brain. Dialogues in Clinical Neuroscience. 2006;8(4):445-461.
- Alekseenko, A.V., Kolos, V.A., Waseem, T.V. Glutamate induces formation of free radicals in rat brain synaptosomes. BIOPHYSICS (2009) 54: 617.
- Liu ZP, Song C, Wang M, He Y, Xu XB, Pan HQ, Chen WB, Peng WJ, Pan BX. Chronic stress impairs GABAergic control of amygdala through suppressing the tonic GABAA receptor currents. Mol Brain. 2014 Apr 24;7:32. PMID: 24758222
- Winkelman JW, Buxton OM, Jensen JE, et al. Reduced Brain GABA in Primary Insomnia: Preliminary Data from 4T Proton Magnetic Resonance Spectroscopy (1H-MRS). Sleep. 2008;31(11):1499-1506.
- Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Frontiers in Cellular Neuroscience. 2015;9:392.
- Hill JM, Bhattacharjee S, Pogue AI, Lukiw WJ. The Gastrointestinal Tract Microbiome and Potential Link to Alzheimer’s Disease. Frontiers in Neurology. 2014;5:43.
- Burbaeva GSh, Boksha IS, Tereshkina EB, Savushkina OK, Prokhorova TA, Vorobyeva EA. Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer’s disease: phosphate-activated glutaminase and glutamic acid decarboxylase. Cerebellum. 2014 Oct;13(5):607-15.
- Stagg CJ, Lang B, Best JG, McKnight K, Cavey A, Johansen-Berg H, Vincent A, Palace J. Autoantibodies to glutamic acid decarboxylase in patients with epilepsy are associated with low cortical GABA levels. Epilepsia. 2010 Sep;51(9):1898-901.
- Vianello M, Tavolato B, Giometto B. Glutamic acid decarboxylase autoantibodies and neurological disorders. Neurol Sci. 2002 Oct;23(4):145-51. PMID: 12536283
- Kong WX, Chen SW, Li YL, Zhang YJ, Wang R, Min L, Mi X. Effects of taurine on rat behaviors in three anxiety models. Pharmacol Biochem Behav. Feb;83(2):271-6. Epub 2006 Mar 15. PubMed PMID: 16540157
- Ebadi M, Wilt S, Ramaley R, Swanson S, Mebus C. The role of zinc and zinc-binding proteins in regulation of glutamic acid decarboxylase in brain. Prog Clin Biol Res. 1984;144A:255-75. PubMed PMID: 6328536
- Möykkynen T, Uusi-Oukari M, Heikkilä J, Lovinger DM, Lüddens H, Korpi ER. Magnesium potentiation of the function of native and recombinant GABA(A) receptors. Neuroreport. 2001 Jul 20;12(10):2175-9. PMID: 11447329