A Functional Medicine Guide GABA + How To Optimize This Essential Neurotransmitter

A Functional Medicine Guide Gaba + How To Optimize This Essential Neurotransmitter Dr. Will Cole 1

Your mood is controlled by various chemicals located in your brain called neurotransmitters. They control whether we are sad, happy, relaxed, anxious, or depressed. Now that’s power! Each neurotransmitter has its own role in how it affects your mood. In order to feel your best, there has to be a proper balance between every neurotransmitter.

As a functional medicine practitioner, when working to optimize my patient’s brain health, I make sure to look at something called GABA. GABA stands for gamma-amino butyric acid and is your body’s signal to calm down. In anxiety, your brain’s cells get overly excited and boost their activity, much like a child on a sugar high. Certain neurons known as GABAnergic neurons, release GABA in the brain to calm down these hyper neurons.

Your body naturally produces and regulates GABA. However, this process sometimes malfunctions, causing (1) GABA levels to decrease, and anxiety, depression, and insomnia to increase, which is why it is important to know how to increase gaba in the brain. Who could have thought one chemical had so much power?

There is good news though – there are many natural ways to support GABA levels and treat low GABA symptoms. So look no further than my complete guide to GABA.

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What are Symptoms of Low Gaba?

Common low GABA symptoms:

  • Anxiety
  • Depression
  • Insomnia or Poor Sleep
  • Sugar Cravings
  • Substance Addictions or Abuse

While these symptoms are common in those with low GABA they are also common symptoms of other health conditions, and may not always be GABA related. It is important to consult a functional health professional for official diagnosis.

GABA Agonists + Your Brain

To stimulate a molecule it first has to bind to a receptor. These receptor-binding molecules are called agonists. GABA agonists can be produced (2) outside or inside of the body and include drugs as well as naturally occurring substances. So when you start to feel relaxed, just know that your GABA has been stimulated through this agonist-receptor relationship.

The two major GABA receptors are GABAA and GABAB. Activation (3) of GABAA can contribute to relaxation, sedation, lowered anxiety, and even short-term memory trouble. GABAB activation (4) will produce similar effects but on a slightly smaller scale. Modulators of this receptor are important (5) when it comes to relieving depression.

Your brain’s hypothalamus contains one of the highest amounts of GABA receptors. The hypothalamus works to maintain homeostasis in your body by controlling your pituitary gland and nervous system to regulate sleep, appetite, body temperature and HPA-axis function. Hypothalamus-related problems like adrenal fatigue can often be traced back to underlying GABA dysfunctions.

Glutamate is another one of your body’s neurotransmitters. Its main responsibility is to excite and motivate, which is the opposite of GABA. In fact, it is actually a precursor to GABA. Your body automatically converts excess glutamate to GABA to maintain balance (6) and keep you calm. GABA conversion problems lead to high glutamate levels, low GABA levels and increased anxiety and depression.

GABA + Your Microbiome

If you want to increase the ability of these GABA enhancers, you need to give them an environment to thrive in in order to get their job done. Going back to the gut-brain axis, if you are suffering from “leaky brain syndrome” – when your blood-brain barrier (BBB) is destroyed – it won’t matter how many supplements you take or therapies you incorporate.

Occludin and zonulin are the two proteins that control both your gut-lining and blood-brain barrier permeability. Elevated levels indicate leaky gut and leaky brain syndrome. When your brain’s protective barrier is compromised, (29) it activates your brain’s immune cells putting them into protective overdrive which causes a cascade of brain inflammation.

“The cytokine model of cognitive function” is a whole area of research (30) that examines how much inflammation is connected to anxiety, depression, brain fog, and autoimmune brain problems. In fact, inflammation decreases the firing rate (31) of neurons in the frontal lobe of the brain in people with depression. Since the underlying inflammatory response is not addressed it can make many antidepressants ineffective.

This can also decrease your brain’s communication with your gut, impairing your gut function and continuing the inflammation cycle. Research is also looking at the microRNA-155 molecule that is elevated

The Benefits of GABA

The amazing thing about GABA is that it doesn’t just affect your mood. Your body is inextricably connected, making the benefits of this neurotransmitter far-reaching.

  1. GABA + Sleep

Multiple studies have shown that GABA plays an important role in sleep quality. GABA extracts have been linked (7) to better sleep even when caffeine was present in the body.

  1. GABA + Gut Health

Your gut is often referred to as your “second brain.” In fact, your gut and brain were actually formed from the same fetal tissue and continue their connection through your life by the gut-brain axis. It only makes sense that our brain health influences our gut – GABA function included. Your intestinal lining also has its own GABA receptors which help to digest food and regulate (8) gastrointestinal activity by producing gastric acid.

If you need another reason to keep your microbiome healthy, research has shown that certain bacterial strains can produce GABA. For those struggling with inflammatory gut problems, this neurotransmitter is especially important since GABA can actually help regulate pain perception. In one study, (9) rats that were given oral bifidobacterium strains experienced less pain and their GABA production increased.

  1. GABA + Brain Function

Brain-derived neurotrophic factor (BDNF) is a protein that helps (10) the growth and function of neurons. Healthy GABA levels are necessary (11) for increasing BDNF which is important since low BDNF levels are associated (12) with impaired memory and Alzheimer’s.

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GABA supplements

There are certain supplements and herbs that help increase activation of GABA receptors which stimulate activity. Not surprisingly, some of my favorite herbs are adaptogens!

  1. KAVA

This plant contains a psychoactive compound called kavain which has been shown to ease anxiety by stimulating (13) GABAA receptors. Kava performed better than other herbal supplements in various studies and was found (14) to work just as well as benzodiazepines for lowering anxiety.

  1. Valerian root

The active compound valerenic acid has the ability (15) to increase GABA. Many studies have shown (16) valerian root to be helpful in improving sleep quality and duration in those suffering with insomnia. It is also a next-level treatment (17) for anxiety.

  1. Skullcap

This herb is packed with antioxidants. Supplementation has been linked (18) to enhanced neuron health and improved cognitive function.

  1. Ashwagandha

Studies have shown (19) that consistent supplementation can reduce anxiety and stress and can even have a mild sedative effect for those with low GABA.

  1. Lemon balm

One of lemon balm’s many antioxidant properties is rosmarinic acid. It works to increase (20) GABA by inhibiting the 4-aminobutyrate transaminase enzyme which is responsible for contorting GABA to L-glutamine.

  1. Green tea

Anyone who is close to me knows that green tea is my go-to beverage not only for taste, but for its many health benefits. Most of these are connected to its high EGCG (Epigallocatechin gallatate) content which helps to stimulate GABA activity.

Other herbs and supplements that help support GABA include:

Lifestyle Changes To Boost GABA

How to increase GABA in the brain without having to use supplements:

  1. Exercise

If you want to know how to naturally increase GABA, exercise is the go to remedy. Unlike endorphins that surge right after exercise, long-term physical activity has been shown (25) to reduce stress and enhance GABA synthesis.

  1. Meditation

According to research, GABA levels are higher (26) in those who meditate. A consistent meditation practice also lowers cortisol which can inhibit GABA function.

  1. Yoga

One study (27) found that a single yoga session can increase GABA by 27 percent.

  1. The ketogenic diet

High glutamate is associated with epilepsy and seizures which have been shown to be helped by a high-fat, moderate protein, low-carb, ketogenic diet. This diet can increase (28) the GAD enzyme and uses ketones as a precursor to GABA. My book, Ketotarian, is all about a plant-based ketogenic diet.

GABA + Your Microbiome

If you want to increase the ability of these GABA enhancers, you need to give them an environment to thrive in in order to get their job done. Going back to the gut-brain axis, if you are suffering from “leaky brain syndrome” – when your blood-brain barrier (BBB) is destroyed – it won’t matter how many supplements you take or therapies you incorporate.

Occludin and zonulin are the two proteins that control both your gut-lining and blood-brain barrier permeability. Elevated levels indicate leaky gut and leaky brain syndrome. When your brain’s protective barrier is compromised, (29) it activates your brain’s immune cells putting them into protective overdrive which causes a cascade of brain inflammation.

“The cytokine model of cognitive function” is a whole area of research (30) that examines how much inflammation is connected to anxiety, depression, brain fog, and autoimmune brain problems. In fact, inflammation decreases the firing rate (31) of neurons in the frontal lobe of the brain in people with depression. Since the underlying inflammatory response is not addressed it can make many antidepressants ineffective.

This can also decrease your brain’s communication with your gut, impairing your gut function and continuing the inflammation cycle. Research is also looking at the microRNA-155 molecule that is elevated when inflammation is higher. It creates (32) more gaps in the blood-brain barrier which perpetuates further brain inflammation. Talk about a vicious cycle!

Ultimately, it all comes back to the gut. Make sure to support your gut through eliminating gut irritating foods, and incorporating probiotic-rich foods like kimchi and sauerkraut. A functional medicine practitioner can also work with you to come up with a food medicine plan specific to your individual health case. Your brain and mood will thank you!

As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe. 

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References:

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  2. Ator, N. (2005). Contributions of GABAA Receptor Subtype Selectivity to Abuse Liability and Dependence Potential of Pharmacological Treatments for Anxiety and Sleep Disorders. CNS Spectrums, 10(1), 31-39. doi:10.1017/S1092852900009883
  3. Rudolph U, Möhler H. GABA-based therapeutic approaches: GABAA receptor subtype functions. Curr Opin Pharmacol. 2006;6(1):18-23. doi:10.1016/j.coph.2005.10.003
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  5. Cryan JF, Kaupmann K. Don't worry 'B' happy!: a role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci. 2005;26(1):36-43. doi:10.1016/j.tips.2004.11.004
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  7. Mabunga DF, Gonzales EL, Kim HJ, Choung SY. Treatment of GABA from Fermented Rice Germ Ameliorates Caffeine-Induced Sleep Disturbance in Mice. Biomol Ther (Seoul). 2015;23(3):268-274. doi:10.4062/biomolther.2015.022
  8. Auteri M, Zizzo MG, Serio R. Pharmacol. 2015; 93:11-21. GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Res doi:10.1016/j.phrs.2014.12.001
  9. Pokusaeva K, Johnson C, Luk B, et al. GABA-producing Bifidobacterium dentium modalates visceral sensitivity in the intestine. Neurogastroenterol. Motil 2017; 29(1):e12904. doi:10.1111/nmo.12904
  10. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736 doi:10.1146/annurev.neuro.24.1.677
  11. Karl Obrietan, Xiao-Bing Gao, and Anthony N. van den Pol Excitatory Actions of GABA Increase BDNF Expression via a MAPK-CREB-Dependent Mechanism - A Positive Feedback Circuit in Developing Neurons Journal of Neurophysiology. 2002 88:2, 1005-1015
  12. Pirjo Komulainen, Maria Pedersen, Tuomo Hanninen, Halle Bruunsgaard, Timo A. Lakka, Miia Kivipelto, Maija Hassinen, Tuomas H. Rauramaa, Bente K. Pedersen, Rainer Rauramaa BDNF is a novel marker of cognitive function in ageing women: The DR’s EXTRA Study Neurobiology of Learning and Memory Volume 90, Issue 4, November 2008, Pages 596-603 doi:10.1016/j.nlm.2008.07.014
  13. Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl). 1994;116(4):469-474. doi:10.1007/BF02247480
  14. Andre Rex, Eve Morgenstern, Heidrun Fink Anxiolytic-like effects of Kava-Kava in the elevated plus maze test—a comparison with diazepam Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 26, Issue 5, June 2002, Pages 855-860 doi:10.1016/S0278-5846(01)00330-X
  15. Santos MS, Ferreira F, Cunha AP, Carvalho AP, Ribeiro CF, Macedo T. Synaptosomal GABA release as influenced by valerian root extract--involvement of the GABA carrier. Arch Int Pharmacodyn Ther. 1994;327(2):220-231.
  16. Bent S, Padula A, Moore D, Patterson M, Mehling W. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006;119(12):1005-1012. doi:10.1016/j.amjmed.2006.02.026
  17. Miyasaka  LS, Atallah  ÁN, Soares  B. Valerian for anxiety disorders. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD004515. DOI: 10.1002/14651858.CD004515.pub2.
  18. Gasiorowski K, Lamer-Zarawska E, Leszek J, et al. Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration?. CNS Neurol Disord Drug Targets. 2011;10(2):184-191. doi:10.2174/187152711794480384
  19. Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J. Psychol Med. 2012;34(3):255-262. doi:10.4103/0253-7176.106022
  20. Alvin Ibarra, Nicolas Feuillere, Marc Roller, Edith Lesburgere, Daniel Beracochea. Effects of chronic administration of Melissa oficinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in mice Phytomedicine Volume 17, Issue 6, May 2010, Pages 397-403 doi:10.1016/j.phymed.2010.01.012
  21. Gilhotra N, Dhingra D. Thymoquinone produced antianxiety-like effects in mice through modulation of GABA and NO levels. Pharmacol Rep. 2011;63(3):660-669. doi:10.1016/s1734-1140(11)70577-1
  22. Renee E. Granger, Erica L. Campbell, Graham A.R. Johnston (+)- And (−)-borneol: efficacious positive modulators of GABA action at human recombinant α1β2γ2L GABAA receptors Biochemical Pharmacology Volume 69, Issue 7, 1 April 2005, Pages 1101-1111 doi:10.1016/j.bcp.2005.01.002
  23. Sheikh Julfikar HOSSAIN, Hitoshi AOSHIMA, Hirofumi KODA & Yoshinobu KISO (2004) Fragrances in Oolong Tea That Enhance the Response of GABAA Receptors, Bioscience, Biotechnology, and Biochemistry, 68:9, 1842-1848, DOI: 10.1271/bbb.68.1842
  24. Mikhail Alexee, Denise K Grosenbaugh, David D. Mott, Janet L. Fisher The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABAA receptors Neuropharmacology Volume 62, Issue 8, June 2012, Pages 2507-2514 doi:10.1016/j.neuropharm.2012.03.002
  25. Hill, L., Droste, S., Nutt, D., Linthorst, A., & Reul, J. (2010). Voluntary exercise alters GABAA receptor subunit and glutamic acid decarboxylase-67 gene expression in the rat forebrain. Journal of Psychopharmacology, 24(5), 745–756. https://doi.org/10.1177/0269881108096983
  26. Crissa L. Guglietti, Zafiris J. Daskalaksi, Natasha Radhu, Paul B. Fitzgerald, Paul Ritv Meditation-Related Increases in GABAB Modulated Cortical Inhibition Brain Stimulation Volume 6, Issue 3, May 2013, Pages 397-402 doi:10.1016/j.brs.2012.08.005
  27. Yoga Asana Sessions Increase Brain GABA Levels: A Pilot Study
  28. Chris C. Streeter, J. Eric Jensen, Ruth M. Perlmutter, Howard J. Cabral, Hua Tian, Devin B. Terhune, Domenic A. Ciraulo, and Perry F. Renshaw The Journal of Alternative and Complementary Medicine 2007 13:4, 419-42628. 
  29. Yudkoff M, Daikhin Y, Horyn O, Nissim I, Nissim I. Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia. 2008;49 Suppl 8(Suppl 8):73-75. doi:10.1111/j.1528-1167.2008.01841.x
  30. Lu, R., Wang, W., Uzzau, S., Vigorito, R., Zielke, H.R. and Fasano, A. (2000), Affinity Purification and Partial Characterization of the Zonulin/Zonula Occludens Toxin (Zot) Receptor from Human Brain. Journal of Neurochemistry, 74: 320-326. doi:10.1046/j.1471-4159.2000.0740320.x
  31. Perry VH. Contribution of systemic inflammation to chronic neurodegeneration. Acta Neuropathol. 2010;120(3):277-286. doi:10.1007/s00401-010-0722-x
  32. Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression [published correction appears in Prog Neuropsychopharmocol Biol Psychiatry. 2005 May;29(4):637-8]. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(2):201-217. doi:10.1016/j.pnpbp.2004.11.003
  33. Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005; 76(2): 77-98. doi:10.1016/j.pneurobio.2005.06.004

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BY DR. WILL COLE

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Dr. Will Cole, DNM, IFMCP, DC is a leading functional medicine expert who consults people around the globe, starting one of the first functional medicine telehealth centers in the world. Named one of the top 50 functional and integrative doctors in the nation, Dr. Will Cole provides a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. He is also the host of the popular The Art of Being Well podcast and the New York Times bestselling author of Intuitive Fasting, Ketotarian, Gut Feelings, and The Inflammation Spectrum.

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