How to Raise GABA (Gamma-amino-butyric acid) in the Brain by Natural Means

[Answering M.F.’s questions: You recently stressed that I need to increase the levels of GABA in my body to help with my persistent anxiety. Are there natural ways to do this through specific foods or even drinks, such as loose leaf tea (due to its precursor l-theanine)?]

Background: As a general rule, in promoting health I like to stay as close as possible to letting and assisting the body in building its own enzymes, hormones, different substances via its own machinery because of my fear of disrupting the body’s magnificent equilibrium. This fear encompasses different issues of feedback mechanisms, rate limiting steps, dependency issues, etc.

Without further ado: GABA (Gamma-amino-butyric acid) functions in brain tissue as an inhibitory neurotransmitter by altering transmembrane potential differences. Throughout the adult brain, where scientists have mostly studied the roles of glutamate and GABA, it has been established that both amino acids function primarily as signals transmitted between cells. Most of the cells transmitting either glutamate or GABA signals are neurons. After release, GABA diffuses a very short distance and binds to receptor proteins on the surface of the target neuron, which are specialized for sensing either GABA or glutamate via either glutamatergic or GABA receptors. GABA subsequently will be taken up, or transported out by carrier proteins. The uptake process requires energy and involves co-transport of GABA, which is neutral at physiological pH, together with two sodium ions and one chloride ion.[3],[5] The result of GABA stimulation of GABA receptors specifically serves to retard the stimulatory effects of glutamate throughout the brain.

Why is it important for anxiety? All anxiogenic agents act on the GABA-A receptor/chloride ion channel complex, implicating this neurotransmitter system in the pathogenesis of anxiety and panic attacks.[7] As such increasing GABA availability, and or increasing the efficiency/effect of, or sensitivity of GABA receptors should help alleviate the feelings of anxiety.

How to promote its availability: GABA (Gamma-amino-butyric acid) can be formed from glutamic acid in the presence of pyridoxal phosphate[1]  (as a cofactor for glutamic acid decarboxylase – GAD).[2] The pyridoxal phosphate arises from vitamin B6 (pyridoxine). Therefore availability of B6 is necessary. Don't overdo. Too much B6 has neurotoxic effects. 10 mg per day is easily sufficient. Other factors that may promote healthy GABA metabolism would be physiological levels of sodium and chloride (salt), in an ample fluid medium. Practical translation: sufficient salt and water intake. Lyte-Hydrate well.

Valerian raises GAD (glutamic acid decarboxylase) activity[4] which may raise GABA (Gamma-amino-butyric acid) in the neuronal tissues which should have a calming effect. The extract also contains GABA[8] which may have a direct impact on GABA receptors.

Make sure the building block of GABA is available (glutamic acid): All meats, poultry, fish, eggs, dairy products, and kombu are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources.[1]

To my knowledge only certain pharmaceuticals (such as phenobarbitone) function as a GABA receptor modulator which enhances the target function of said receptors.

Theanine: is an amino acid present in green tea which appears to have stimulatory effects and inhibitory effects on glutamic acid. For calming one would desire the inhibitory effect. How it works seems unclear to date (5-28-12). As such I would think it would be okay to use although in this case it is functioning more as a pharmaceutical agent and not as a building block. Theanine is similar in molecular structure to glutamic acid and hence could be ‘pressuring’ glutamic acid and causing it to be more available for transforming into GABA. Here I am theorizing. Then again it could be occupying glutamatergic receptors without causing the usual excitatory activity which glutamic acid usually results in. Here I am theorizing again.

References:

[1] Rodwell VW. Chapter 30. Conversion of Amino Acids to Specialized Products. In: Bender DA, Botham KM, Weil PA, Kennelly PJ, Murray RK, Rodwell VW, eds. Harper's Illustrated Biochemistry. 29th ed. New York: McGraw-Hill; 2011. http://0-www.accessmedicine.com.library.ccf.org

[2] http://en.wikipedia.org/wiki/Glutamate_decarboxylase

[3] GABA as a Neurotransmitter and Neurogenic Signal - eLS - Barker - Wiley Online Library . http://0-onlinelibrary.wiley.com.library.ccf.org/doi/10.1038/npg.els.0000121/full. Accessed 5/13/2012 2012.

[4] R Awad, D Levac, P Cybulska, Z Merali, VL Trudeau, JT Arnason (2007) Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system Can J Physiol Pharmacol 85: 933-942. Doi:10.1139/Y07-083.

[5] Nicotinic Acetylcholine Receptors - eLS - Lindstrom - Wiley Online Library . http://0-onlinelibrary.wiley.com.library.ccf.org/doi/10.1002/9780470015902.a0000245.pub2/full. Accessed 5/20/2012 2012.

[6] Russek, S. J. 2006. γ-Aminobutyric Acid (GABA) Receptors. eLS.

[7] Reus VI. Chapter 391. Mental Disorders. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://0-www.accessmedicine.com.library.ccf.org/content.aspx?aID=9112222. Accessed May 27, 2012.

[8] http://en.wikipedia.org/wiki/Valerian_%28herb%29#Biochemical_composition