GABA, or “gamma aminobutyric acid,” produced in the central nervous system, is the body’s natural muscle relaxant, tranquilizer, and nerve calmer. GABA, a brain chemical (neurotransmitter), also available as a supplement, works by limiting the nerve cell activity in areas of the brain associated with anxiety. Some anxiety disorders have increased cell activity in these areas. GABA functions as a calming neurotransmitter in your brain inhibiting nerve impulses related to stress and anxiety.
Current anti-anxiety medications include benzodiazepines. Benzodiazepines are widely prescribed, with four of them, alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium) and lorazepam (Ativan), listed among the top 100 most commonly prescribed medications.(1) These prescription medications target GABA receptors in the brain, and limit the nerve cell activity in areas of the brain associated with anxiety. However, the down side is that chronic reliance on benzodiazepines can be addicting. Antidepressants such as Prozac (SSRIs) are also prescribed for anxiety. While antidepressants are not associated with physical dependence, their side effects are numerous including depletion of the very neurotransmitters that they affect.
If you’re one of the millions who suffers from anxiety or panic disorders, consider amino acids as an alternative to prescriptions. GABA as a supplement, is available as an amino acid and has few side effects, especially when stacked up against prescription medications. Clinically, GABA has been used in the treatment of anxiety, depression, panic disorders, substance abuse recovery, manic-depressive (bipolar) disorder, seizures, and premenstrual mood disorder. In a healthy, well-nourished person, the brain produces sufficient amounts of GABA. However, amino acid deficiencies are not uncommon due to protein deficient diets, and from protein maldigestion. Amino acids are metabolized from dietary protein. Several lab assessments that I utilize consistently reveal that many individuals do not break down, (metabolize) their protein well, resulting in B12 and mineral deficiencies, and a delpleted availability of protein and amino acid substrates for neurotransmitter metabolism. A good balanced diet should include half your body weight in grams of protein each day-i.e. if you weigh 120 lbs., then your minimum protein intake should be 60 grams of protein daily. Active individuals and athletes require more. Additionally, B vitamins are important cofactors to amino acid metabolism-especially B6. B12 and B3 (niacinamide) are also integral in a number of enzyme reactions to help convert glutamine, an amino acid, to GABA. In one study Nicotinamide, a form of vitamin B3, also referred to as Niacinamide, produced an anti-anxiety effect equivalent to a benzodiazepine. Like benzodiazepines, niacinamide appears to stimulate GABA receptors without binding to receptor sites. GABA deficiencies are strongly correlated with states of anxiety, and attempting to rectify a possible chemical imbalance within the brain by using GABA may be very useful.
Most of the research on GABA has focused on how drugs enhance GABA activity in the brain. There is a dearth of research on GABA supplementation and it’s impact on mood disorders or any of the other conditions noted above. However, a recent study at the Yale University School of Medicine demonstrated a relationship between GABA levels and panic disorder. Overall, the tests showed a 22% reduction in GABA levels in the participants with panic disorder compared with those without panic disorder. According to the researchers, there was previously “no direct assessment” of GABA levels in people with panic disorder.(2) Similarly, another recent study, demonstrated the benefits of GABA administration for anxiety reduction, as a natural relaxant, and for immune enhancement and protection under stressful conditions.(3)
Another effective method for managing anxiety and panic disorders is exercise and walking. Acupuncture, meditation and movement meditation exercises like yoga can be very beneficial as well. Researchers at Boston University School of Medicine (BUSM) and McLean Hospital have found that practicing yoga may elevate brain GABA levels.(4) The findings, which appear in the May issue of the Journal of Alternative and Complementary Medicine, suggest that the practice of yoga be explored as a possible treatment for anxiety and depression, disorders associated with low GABA levels.
Another useful nutrient for anxiety relief is glycine. Like GABA, glycine, exerts inhibitory effects in certain areas of the brain which results in significant anxiety relief. Glycine is an amino acid and a neurotransmitter as is GABA. In one study on the biochemical effects of glycine on anxiety responses it was noted that benzodiazepines “may exert their anti-anxiety, anticonvulsant and muscle-relaxant effects by mimicking the effects of the neurotransmitter glycine at its central nervous system receptor sites”.(5)
Many anxiety disorders are exacerbated by stress, and regular exercise and meditation disciplines are important methods for ameliorating stress responses and the anxiety that accompanies it. Along with such techniques, evaluation by an experienced practitioner, or an alternative mental healthcare professional can shed insights into underlying physiological causes of anxiety. Adrenal exhaustion, hormonal imbalances, blood sugar fluctuations, anemia and neurotransmitter imbalances are are common underpinnings to anxiety responses.
The dosage of GABA to be used depends on the reason for taking it. To promote sleep, 500 to 1000 mg taken about and hour before bed is recommended. In cases where insomnia is related to anxiety, GABA can be taken with other natural tranquilizers, such as inositol and valerian root. For stress, divided doses throughout the day as needed, i.e. 250 to 500 mg three times per day, or a single dose of 500 to 1000 mg can do wonders for some in blunting stress related tension and anxiety. I have observed excellent tension and anxiety relief benefits by combining inositol with GABA. Inositol enhances serotonin in the brain and may support the inhibitory effects that GABA provides in brain chemistry imbalances. GABA is best absorbed and more effective when taken between meals. A word of caution. In some more sensitive individuals, GABA taken during the day may cause drowsiness, so be careful if driving after taking GABA.
A knock on GABA supplements is that they are not well absorbed in the gut, yet there is little evidence to support that argument. On the contrary, research on GABA uptake in the intestinal tract demonstrates that it is absorbed by a specialized transport mechanism.(6) It is well documented that GABA is a growth hormone potentiator.(7) Without adequate absorption, GABA’s effect on growth hormone would be insignificant or nil.
GABA’s clinical benefits for anxiety or panic disorders, also demonstrates that there is sufficient absorption taking place and that it crosses the blood brain barrier adequately. In studies with GABA and it’s effects on HGH levels, doses of 2 to 18 grams were found to be effective. However, a word of caution as larger dosing of GABA may in some individuals, cause side effects. Paradoxically, GABA in higher doses can exacerbate the very symptoms of anxiety and insomnia that it is supposed to alleviate. Since individuals can vary to their sensitivity to GABA,it is best to start with lower doses and gradually increase to your ideal dose. Tingling and flushing are not uncommon reactions with GABA intake. In a few cases, I have seen mild stomach irritation or nausea. Women who are pregnant or breast feeding and people with liver or kidney disease should not take GABA. Prescription medications for anxiety target GABA receptors in the brain. Individuals who are taking such medications should not use GABA supplements without the advice of a medical professional. Finally, GABA is contra-indicated in the following conditions: Prader-Willi Syndrome (8), Angelman Syndrome (8), encephalopathy (brain disease including dementia) due to liver disease (9), or behavior disorders such as attention deficit hyperactivity disorder-ADHD. (10)
1. American Druggist. Top 200 drugs of 1995. New York, N.Y. Hearst Corp, 1996:18-26.
2. Nicotinamide is a brain constituent with benzodiazepine-like actions. Mohler H, Polc P, Cumin R, et al. Nature 1979;278(5704):563-565.
3. Reductions in the occipital cortex GABA levels in panic disorder detected with 1H-Magnetic Resonance Spectroscopy. Goddard AW, Mason GF, Almai A, Rothman DL, Behar KL, Petroff OAC, Charney DS, Krystal JH (2001). Arch Gen Psychiatry 58: 556-561.
4. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Biofactors. 2006;26(3):201-8.
5. Yoga Asana Sessions Increase Brain GABA Levels: A Pilot Study Streeter CC, Jensen JE, Perlmutter RM, Cabral HJ, et al. J Altern Complement Med. 2007 May;13(4):419-42
6. Interaction of Benzodiazepines with Central Nervous Glycine Receptors: Possible Mechanism of Action Anne B. Young, Stephen R. Zukin, Solomon H. Snyder Proceedings of the National Academy of Sciences of the United States of America, Vol. 71, No. 6 (Jun., 1974), pp. 2246-2250 7. Intestinal absorption pathway of -aminobutyric acid in rat small intestine A. Nácher, A. Polache, M. J. Moll-Navarro, J. M. Plá-Delfina, M. Merino * Biopharmaceutics & Drug Disposition Volume 15, Issue 5 , Pages 359 - 371 8. Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man. Cavagnini F, Invitti C, Pinto M, Maraschini C, Di Landro A, Dubini A, Marelli A. Acta Endocrinol (Copenh). 1980;93(2):149-54. 9. Elevated plasma gamma-aminobutyric acid (GABA) levels in individuals with either Prader-Willi syndrome or Angelman syndrome. Ebert MH, Schmidt DE, Thompson T et al J Neuropsychiatry Clin Neurosci 1997 Winter; 9(1):75-80. 10. Plasma gamma aminobutyric acid concentrations provide evidence of different mechanisms in the pathogenesis of hepatic encephalopathy in acute and chronic liver disease. Levy LJ & Losowsky MS Hepatogastroenterology 1989 Dec; 36(6):494-498.
11. Plasma GABA in children and adolescents with mood, behavior, and comorbid mood and behavior disorders: a preliminary study. Prosser J, Hughes CW, Sheikha S et al J Child Adolesc Psychopharmacol 1997; 7(3):181-199.
Is it true that GABA is a by-product of the KREBS cycle that provides the fuel needed by brain cells? Does this mean that it is virtually impossible for a normal brain to be low on GABA?
Is it also true that GABA is water soluable and therefore cannot normally pass the blood-brain-barrier despite the claims often made?
Do GABA analogues such as the seizure medication gabapentine, which can cross the BBB, work not by interacting with the GABAergic neurons as GABA does, but affect the glutamate system instead?
Is the brain is so efficient at up-taking GABA that it is effectively a built-in mechanism for ensuring that GABA has only very local effects around the synapses from which it is released - i.e. extraneous GABA is sucked up before it can get anywhere near a GABAergic synapse.
Furthermore, to reduce the large quantities of GABA in the brain does the blood-brain-barrier contain a system of efflux transporter proteins that pump this amino acid from extracellular fluid into the blood stream for elimination?
Can you confirm that while people with anxiety or epilepsy are not deficient in GABA, they have fewer/impaired GABA binding sites (receptors)? Therefore, isn't trying to alleviate either of these disorders by increasing the amount of GABA in the brain akin to filling a car's gas tank to fix faulty spark plugs?
Finally, are the benefits of GABA supplements limited to the people that sell them and, possibly, the bacteria living in sewers down which the GABA ends up after being excreted from the body without ever making it into the brain?