When I researched at the best ways to improve GABA levels, I also evaluated how these supplements would help correct symptoms of GABA deficiency particularly anxiety, stress and depression, sleeping problems, muscle spasticity and seizures. To review prescription drugs that raise GABA click here and for a detailed list of GABA deficiency symptoms, read my other article .
How To Increase GABA Naturally
1.Natural GABA Supplements : GABA and Phenibut
GABA
The first GABA natural supplement to think of would be to take straight GABA, right? Here is the old theory: GABA supplements would not cross the blood brain barrier (BBB) and therefore won’t reach the brain /provide any benefits. However, other studies showed that GABA supplement can cross the BBB [1]. Another theory: some doctors claim that increased BBB permeability is the only reason why GABA supplements work, and use GABA supplements as a “test” to evaluate BBB integrity. If you feel better means it is always bad because your BBB has increased permeability.
In my opinion, GABA supplement will have a hard time to reach the brain because GABA is a large molecule. If you take GABA supplement and experience symptoms improvement (less anxious, more calm, better sleep, etc), it is most likely due to the fact that the supplement improves GABA levels in the gut and other tissues (and brain effects are seen due to the fact the brain and gut are connected).
Another possibility is that your BBB permeability is increased (aka leaky brain), thus allowing the large molecule of GABA to reach the brain — but I consider this a second option.
Thirdly, your BBB may have normal permeability. Research shows that certain areas of the brain have naturally (not pathologically) a permeable barrier (ie. periventricular nucleus of the hypothalamus), thus GABA could reach the brain through these areas [2].
My conclusion : GABA can sometimes help restore GABA levels in the brain, thus you may or may not experience its relaxing, calming, anti anxiety effects or better sleep.
Even if GABA does not reach the brain, you can still get other benefits from taking the supplement: GABA receptors are found in many body’s tissue- for example gut, muscles and pancreas. Supplementing with GABA appears to help prevent obesity, manage diabetes [3],[4] ,may reduce inflammation/autoimmunity (animal models) [5] ,decrease body fat and increase lean muscle growth, stabilize the blood pressure and relief pain and PMS symptoms [6].
Could GABA supplement have anti-aging and anti wrinkle qualities ? There is some research showing that GABA promotes the production of skin collagen and elastin [7]. I see another reason why GABA would improve skin appearance: is a muscle relaxant, this alone would help to manage wrinkles. The anti aging effects could also derive from boosting the human growth hormone (HGH), as some studies suggest (although increasing HGH would imply that GABA reaches the brain). Since GABA penetrates poorly the skin [8] . A GABA supplement taken orally would likely benefit more for anti wrinkle anti aging purposes.
Phenibut
Phenibut(beta-phenyl-GABA) is another natural GABA supplement, the GABA ‘s close relative. It discovered few decades ago by Russian scientists. . Unlike GABA, phenibut can easily cross the BBB, and appears to work more on GABA-B receptors (like baclofen), but also on GABA-A. Just like GABA, it has anti-anxiety, anti-stress effects and promotes sleep. It also works as a smart drug (nootropic) as improves cognitive function [9]. I see more risk than benefits from taking it. Side effects include dependence, tolerance, withdrawal -and can be quite severe [10]. Risk of overdose /intoxication can occur (symptoms include confusion, altered mental state, low body temperature requiring urgent medical treatment) [11],[12],[13].
2.Natural GABA supplements: Amino Acids
L lysine and L arginine combo
Imbalance of neurotransmitters (GABA, serotonin, dopamine and norepinephrine) correlates with anxiety. Besides using the tyrosine and tryptophan to balance dopamine, norepinephrine and serotonin, another two amino acids influence the neurotransmitters involved in stress and anxiety: L-lysine and L-arginine. This combination had been researched in randomized clinical trials as well. L-lysine plus L-arginine combo helps balance cortisol levels triggered by stress in both healthy individuals and those with high trait anxiety [14]. Note : the ratio lysine/arginine to raise GABA can increase the risk of herpes reactivation; may not be a good choice for those who have recurrent herpes infection (to prevent herpes reinfections, you a different ratio lysine/arginine; lysine should be taken in supplement form, and excess arginine should be avoided)
L-Glutamine
The precursors of GABA are glucose (the predominant precursor) [3] , as well as pyruvate and the amino acid glutamine. Let s look at glutamine –> GABA conversion:
Glutamine → Glutamate → GABA
↑ ↓
Citric Acid Cycle ← Succinate semialdehyde (SA)
L-glutamine is a precursor of GABA, and an amino acid (now labeled conditionally essential amino acid). It is very abundant in the body, especially in the muscles. It can be as powerful as a drug, especially when used in critical illness, cancer and heart injury (it is used i.v.) . It can reduce inflammation, improve gut barrier function, immune cell function and reduce mortality in cases of critical ill patients. It has an excellent safety profile, too [15],[18]. There is some evidence that glutamine can raise GABA levels (animal studies) [19]. L- glutamine promotes brain health and gut health. In the brain, glutamine is a precursor of the neurotransmitters GABA, glutamate and aspartate [20]. It is also essential in the gut- being the most important amino acid to improve intestinal permeability (aka leaky gut, which is associated with MS and other autoimmune diseases). It promotes gut repair [21] and symptom improvement in IBS [22] and IBD [23]. It can help decrease cardiovascular risk factors [24], reduce body fat and muscle wasting [25] and improve muscle growth in athletes. L glutamine in free form should be taken with foods. Alanyl l glutamine form is better absorbed in your body and can be taken with or without food.
Why glutamine may not be the best GABA natural supplement for managing MS: Both glutamine and glutamate levels decrease as MS progresses, and therefore could be used as marker of MS progression [26]. Glutamine and lactate levels are also lower in the cerebrospinal fluid in those with MS compared with healthy controls [27]. Yet, another study shows higher levels of glutamine and glutamate in white matter of the brain in individuals with MS [28].
Here is the problem: Glutamine is the precursor for both glutamate and GABA. The link between GABA and multiple sclerosis? Generally speaking, MS is associated with excess glutamate and GABA deficiency. The main enzyme that converts glutamine to glutamate also is increased in MS. Therefore, supplementing with glutamine has the potential to further increase glutamate (and aggravate MS) rather than convert to GABA. Taking glutamine without vitamin B6 (co factor for the conversion glutamate to GABA) can also increase the risk of too glutamate excess if you supplement with glutamine. Although glutamine shows many health benefits, I would use glutamine in small doses and always combined with other amino acids. I do not recommend l glutamine single — high doses supplement for MS. GABA levels can be effectively increased in the brain with supplements that influence directly GABA and GABA receptors.
L theanine
L theanine is the close relative of glutamine (formula: N-ethyl-L-glutamine) and is found in green tea and black tea.L theanine can also increase GABA (as well as serotonin and dopamine) levels in the brain. Studies found l theanine beneficial for managing anxiety, improve mental function, protect the brain against degeneration, has anti-oxidant and anti-inflammatory qualities, and promotes better sleep [29].
L theanine as a natural GABA supplement for MS? Maybe not a good idea. The amounts of l theanine in tea are safe. However, I would not recommend l theanine in supplement form- because I see the same problem as with glutamine. L theanine would require conversion to glutamate and then GABA, and it could potentially lead to increased glutamate levels. In addition, it seems that is also stimulating the immune system, specifically TH1 cells (which are often high in MS) [30],[31].
Taurine
Taurine is an amino acid made in the body from another two amino acids cysteine and methionine. It is also available in supplement form. It seems to work similar with GABA neurotransmitter. It seems to increase the function of GABA receptors in the brain that can help improve GABA levels and manage symptoms of GABA deficiency [32]. Taurine may help reduce seizure frequency [33] and have anti-anxiety/anti-depressant effects [34].
Taurine for MS : Taurine combined with another drug can help repair damaged cells in multiple sclerosis, according to a new study [35]. More details about the many benefits of taurine here.
3.Natural GABA Supplements: Vitamins and Minerals
Magnesium & Vitamin B6
I covered many benefits of magnesium in this article. Magnesiu can help manage different symptoms of GABA deficiency including anxiety, insomnia, spasticity and seizures. Its anti-anxiety effects had been researched in three human trials (alone or in combination), all showing positive effects [36]. Magnesium can be effective to treat muscle spasms and cramps (spasticity). In the iv form is used in hospitals to treat severe muscle rigidity and cramps [37]. Seizures are associated with magnesium deficiency [38] and correcting this deficiency can prevent and treat seizures. (quick note: acid blockers PPIs can cause significant magnesium deficiency [39]).
Vitamin B6 is an important factor in the GABA metabolism, and has many other benefits- supports healthy brain function, prevents heart diseases and high blood pressure, is involved in the metabolism of fats, sugars and proteins and regulates sleep.
Selenium
Selenium is a vital mineral for the brain, being involved in motor skills, coordination, memory and cognition. Selenium also has a significant impact on neurotransmitters especially GABA, dopamine and acetylcholine [16]. Selenium has antioxidant and anti inflammatory qualities. Supplementation with selenium can help protect substantia nigra (which contains dopa producing neurons) against damage and degeneration and improve dopamine pathways [17]. Seizures had been linked with selenium deficiency and had been found helpful to reduce the frequency of seizures [40],[41]. It also has anti-anxiety and anti depressant effects [42].
Vitamin C
Vitamin C protects the brain/ prevents the damage from excess glutamate while modulating the GABA receptors and supporting the conversion of GABA. Vitamin C is also important for healthy levels of other neurotransmitters -like dopamine and acethylcholine. It protects the integrity of blood brain barrier and can effectively fight inflammation and neurodegeneration. [83].
4.Natural GABA Supplements- Herbs
Valerian Root
Valerian root (Valeriana officinalis)offers a great, safer alternative to benzodiazepines, the prescription drugs used to raise brain GABA. It stimulates GABA-A receptors, appears to be as effective as the anti-anxiety drug oxazepam [43]. It has an excellent safety profile. Besides helping relieve anxiety and stress, valerian root helps treat insomnia, and promote deep, restful sleep. Unlike classical sedatives, valerian extract does not impair your ability to drive or use machines, does not cause tolerance, dependence or withdrawal effects for most people. However, it takes about two weeks to experience better sleep [44].
Possible herb- drug interactions: benzodiazepines, barbiturates, tricyclic antidepressants, alcohol, statin drugs [45]. An extensive review of studies found them safe when used with anti-cancer drugs (the interaction valerian-anticancer drugs was debated in the past) [46].
Passionflower
Passionflower (Passiflora incarnata Linn) works as well as oxazepam (benzodiazepine drug) for managing anxiety, according to a double-blind, placebo-controlled study [47]. It modulates the GABA system including affinity to GABA-A and GABA-B receptors, and influences GABA uptake. This supplement is also used for generalized anxiety disorder (GAD), managing opiate withdrawal, insomnia, neuralgia, convulsion, asthma, ADHD, palpitations, cardiac rhythm abnormalities, hypertension, sexual dysfunction and menopause [48]. Passion has milder anti-anxiety effects than valerian or kava, thus is usually combined with lemon balm. It has an excellent safety profile. Side effects are rare and include mild dizziness and drowsiness. Possible drug interactions : benzodiazepines, barbiturates, MAO inhibitors and blood thinners [49].
St John’s Wort
St John’s wort (Hypericum perforatum) is considered a supplement in many countries, while in Germany is a prescription drug approved to treat anxiety, depression and sleep disorders. It works not only on GABAA, GABAB and glutamine receptors, but also influences MAO A and B activity, serotonin, dopamine and noradrenaline (I also mentioned this herb in my article about how to deal with serotonin deficiency). There are several randomized controlled trials exploring the benefits of this herb. Some of these studies found it beneficial for treating depression (effects comparable with SSRI drugs) and anxiety [50]. Other uses: menopause (especially when combined with black cohosh), PMS, OCD, eczema (applied topically). It may take 3-6 weeks to see the antianxiety effects. Possible drug interactions: antidepressant drugs, some cough medication, antihistamines, digoxin and immunosuppressants [51].
Kava Kava
Kava Kava(Piper methysticum) is by far, one of the most researched anti anxiety herbs (10 randomized controlled studies) Some of these studies found similar anti-anxiety effects when compared with benzodiazepines. Unlike benzodiazepines, Kava did not cause cognitive dysfunction. There were some concerns in the past when Kava was linked with potentially serious side effects like liver failure, hepatitis and cirrhosis- but a recent review of over four hundred clinical trials show no reported liver problems (even when high doses of kava were used) The conclusion: liver toxicity is indeed a rare side effect. Possible drugs interactions: benzodiazepines, some anti seizure drugs, levodopa, diuretics, drugs metabolized by liver [52],[53]. It appears that those cases of liver toxicity were associated with kava taken along with drugs. Even with this documented risk of liver problems, kava kava is much safer (and as effective) compared with prescription anxiety drugs, according to researchers [54].
Rhodiola
Rhodiola (Rhodiola rosea) is an adaptogen, helping you cope with physical and emotional stress. Its mechanism of action is complex, and involves activating GABA receptors in the brain. It contains over 40 active ingredients which help ameliorate symptoms of stress, anxiety, depression, fatigue, insomnia; it modulates the immune system and promotes brain and heart health. It may also help alleviate pain.It has antioxidant and anti inflammatory qualities (stimulates Nrf2 pathway) [55],[56],[57],[58],[59].
Medical Marijuana
Cannabis (Cannabis sativa,Cannabisindica) based supplements had been extensively researched in scientific studies in both animal models and humans. Cannabis can help improve not only GABA, but also dopamine, norepinephrine and serotonin levels as well, having antidepressant and anti anxiety effects. Cannabis modulates the immune system and promotes neuroprotection. For insomnia and other sleeping problems, CBD may be more helpful than THC. Cannabis based supplements and drugs are effective for muscle spasticity and tremors, neuropathic pain, bladder problems associated with MS [60],[61]. Medical marijuana has shown positive effects on only for treating MS, but many other conditions: from severe pains, to mood disorders, degenerative conditions like Parkinson’s disease, post-traumatic stress disorder, seizures, glaucoma, nausea. Some individuals with IBS, fibromyalgia and Crohn’s disease respond well to this herb too [63]. The response to cannabis will vary significantly from one person to another as there are genetic and environmental factors to take into consideration, in addition to different marijuana products (which have different ratio THC to CBD) [64].For this reason, it really is important to seek professional advice and get the right formula for your condition.
Side effects will also vary from one formulation to another- the THC from marijuana is responsible for getting “high”. It can also cause dependence, withdrawal symptoms, dizziness, dry mouth, nausea, vomiting, dry eyes, changes in blood pressure. As a general rule, medical marijuana is much safer than the synthetic marijuana (created in the lab). The synthetic marijuana use had been linked with serious side effects such as stroke, brain damage, heart and kidney complications and psychosis.
5.Natural GABA Supplements: Probiotics
Probiotics
The gut microbiome is essential in GABA production and further helps convert glutamine and GABA. To no surprise, an impaired gut microbiome is a major cause of GABA deficiency [65],[66].
Some strains of probiotics have the ability to produce GABA. Specifically, bacteria from the strains Lactobacillus and Bifidobacterium were effective at increasing GABA levels in the gut (enteric nervous system, which has many receptors for GABA). Since the gut and the brain are connected via vagus nerve, improved levels of gut GABA can also have a positive impact on brain health [67].
6.Other Ways To Increase GABA
Diet : Since GABA production starts with glucose, a healthy metabolism of sugar is crucial for healthy GABA levels. Unhealthy glucose levels from high sugar high fat (Western type) diets will create GABA deficiency. On the other hand, a low carb diet can help improve abnormal sugar levels (ie insulin resistance/diabetes and or hypoglycemia) and manage GABA deficiency as well [68]. Ketogenic diet (which is very low carb) may even a better option. Something great happens when your brain runs on ketone bodies, rather than sugar. The metabolism of certain brain cells (astrocytes) is more active leading to a more efficient conversion of glutamate to GABA and more efficient removal of glutamate [69],[70]. Caloric restriction and fasting could also be very helpful [71].
Deep breathing, Meditation, Yoga -can all effectively increase GABA in the brain [72],[73],[74],[75],[76]. (my note: while these studies focused on brain GABA, it is likely to increase GABA in the gut, muscles and other organs/tissues as well).
Exercise: working out regularly can also help you maintain healthy GABA levels, although yoga seem to work even better. A 12-week yoga program showed decreased anxiety and increased GABA levels is a specific part of the brain (thalamus) better compared with walking. Exercise improves not only GABA levels, but dopamine, norepinephrine, serotonin levels as well [77] . Exercise can also help you sleep better, improve mood and decrease muscle spasticity.
Vagal nerve stimulation: Vagus nerve connects the gut with the brain. Stimulation of vagus nerve had been found to positively influence GABA levels as well as other neurotransmitters [78]. Vagus nerve can be stimulated in various ways. Deep breathing, yoga, meditation all stimulate vagus nerve [79]. Special devices, massage therapy, cold therapy or even simple actions like gargling, chewing gum can activate vagus nerve.
PEMF (Pulsed electromagnetic field): I mentioned rTMS therapy in my other article, as a conventional treatment for depression and anxiety (which also raises GABA levels in the brain). rTMS uses similar electromagnetic fields with Pulsed electromagnetic field (PEMF) devices. PEMF devices come in different forms and intensities. They increase GABA levels in the brain while reducing glutamate toxicity [80],[81].
My favorite ways to raise GABA naturally and treat symptoms of GABA deficiency
When trying to boost GABA levels in the brain, it’s very important to look how that supplement influences other neurotransmitters (ie serotonin, dopa, norepi deficiencies, glutamate excess). Other factors such as inflammation, autoimmunity, infections, impaired sugar metabolism (in the brain) should also be considered.
-Deep breathing/yoga /meditation
-Low carb (gluten free/dairy and low lectin) diet alternating with keto diet and fasting
-Exercise (for its many health benefits, not just correcting GABA deficiency)
-Supplements: magnesium with B6, selenium, taurine, probiotics.
-L glutamine not as a single supplement; only in small doses and in combination with other amino acids- for example l glutamine is found collagen powder, gelatin, AI paleo protein powders, hemp protein powder, bone broth powders (bone broth powder should not be used in case of excess histamine, histamine intolerance, MCAS/MCAD)
-PEMF
-Herbs- only when needed, as an alternative to benzodiazepines (to improve sleep and anxiety): valerian root, lemon balm + passion flower or St John wort. Medical Marijuana for muscle spasticity, as an alternative to baclofen. Herbs should not be used in combination with benzodiazepines (too many drug-herb interactions).
-Massage therapy and TENS devices can also help with muscle spasticity [82].
-For seizures, the prescription drug levetiracetam (Keppra) seems to be the safest, and is also very effective- along with ketogenic diet, taurine, magnesium and B6.
