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Stress Support 101: GABA and L-Theanine: The Fast Acting Stress and Anxiety Antidote

In this 3-part blog series (Stress Support 101, 102, and 103), the Quicksilver Staff addresses a multipronged approach to supporting the body under stress. Stay tuned for each essential tidbit!

These days, we often view stress as a badge of honor—proof that our hectic lives are packed to the brim with work, play, friends, family, exercise, shopping, cooking, and limitless other tasks from laundry to surfing social media and tuning in to 24-hour weather and news.

We’re drinking every last drop of life. We’re making our mark. We’re also sleep deprived and chronically tense. Since 2007, the American Psychological Association has conducted an annual nationwide survey to assess how stressed Americans are. Between August 2016 and January 2017, the overall average reported stress level of Americans rose from 4.8 to 5.1, on a scale where 1 means little or no stress and 10 means a great deal of stress, according to the APA survey.1

We tend to forget that chronic stress isn’t just an irritant, but can pave the way for ill health by altering the responses of the sympathetic nervous system and the adrenal axis, increasing the flow of stress hormones, and upregulating inflammation and free radical damage.2 Yet it’s hard to jump off the merry-go-round of stressors that confront us at every turn.

If we understand the biology of stress—just how it acts on the body—then we can make choices that help us to relax and restore ourselves, including the support of natural aids that gently soothe and replenish our cells, tissues and organs.

The hypothalamic-pituitary-adrenal (HPA) axis is the primary axis of endocrine organs in the body that adapts in response to stress. This system impacts the function of many other biological systems and processes through the hormone cortisol. Chronic stress is linked to chronically elevated levels of salivary cortisol in both children and adults.3 These high levels are associated with reduced immune response, affecting healing and thus prolonging recovery time; delayed growth in children; and increased blood pressure and heart rate in both children and adults.

Sleep difficulties are common with anxiety disorders and are often associated with mental activity or worrying. They lead to a lower cortisol awakening response (CAR) which is a burst of cortisol secretion that occurs about 20-30 minutes after awakening in the morning, and prepares the body for greeting the demands of the day.4

Sleep is a necessity for creatures ranging from fruit flies to humans. It is actually a cleansing process, wherein your brain flushes itself clean, sending waste and toxins out of the cells and bringing in fresh nutrients, which then diffuse back into cells, refreshing and replenishing them.5 While you sleep, your brain detoxifies itself up to ten times faster than when you are awake.6 No wonder good sleep is the foundation of health, while poor sleep raises our risk of stroke, heart attack and even weight gain and weak bones.7

  

Rest & Relax with GABA and L-Theanine

To restore deep and restful sleep, you might turn to a calming amino acid like gamma-amino butyric acid (GABA), which is known as the premier “calm and connect” molecule. Our brain naturally produces it, and it is capable of inhibiting or slowing down nerve impulses, and balancing out our response to stress. Lower GABA concentrations in individuals suffering from post-traumatic stress disorder (PTSD) have been linked to poor sleep quality.8 GABA supplementation has been found to significantly increase calming alpha-wave patterns during stress, and to reduce anxiety levels in humans.9,10 GABA may fine tune our entire neuroendocrine response.11

GABA is found in teas such as pu-erh and foods such as kimchi (where it is a fermentation byproduct).12 For the pure amino acid, liposomal delivery systems have been shown to facilitate transport across the blood brain barrier (BBB) and increase availability of therapeutic agents in the central nervous system.13 It has also been proposed that supplemental GABA may activate receptors in the enteric nervous system (that of the gut), which may be modulated by and signal to the vagus nerve.14 The vagus nerve is the longest cranial nerve in the body. It contains motor and sensory fibers and, because it passes through the neck and thorax to the abdomen, has the widest distribution in the body.

Another calming amino acid, one that enhances GABA’s effect, is L-theanine. It is found naturally in tea.15 After supplementing with L-theanine, brain wave patterns smooth out, much like they do with meditation.16 L-theanine calms without impairing cognitive ability, reduces stress and levels of cortisol (the stress hormone) in saliva, and also lowers blood pressure.17,18 L-theanine has been observed to promote relaxation and reduce stress, possibly by increasing alpha wave activity and by blocking the binding of L-glutamic acid to excitatory glutamate receptors in the central nervous system.19,20

Continuous administration of L-theanine has been shown to increase expression of brain-derived neurotrophic factor (BDNF)21, a protein that increases neural plasticity and promotes neurogenesis, including that of dopaminergic and serotonergic neurons.22 Increased BDNF levels are thought to be a mechanism by which some anti-depressants, supplements, and exercise have a positive impact on anxiety and depression.23,24,25

Supplementation with L-theanine has been shown to have a relaxing effect, reducing heart rate and salivary immunoglobulin A (sIgA) secretion in settings of acute stress.26,27 It also has been shown to reduce anxiety and attenuate blood pressure during a challenging mental task28 and reduce salivary α-amylase activity and subjective experience of stress during mental challenges.29 L-theanine has been shown to improve aspects of sleep quality in boys with attention-deficit/hyperactivity disorder30, and reverse caffeine-induced decreases in slow-wave sleep in animals.31

GABA in combination with L-theanine truly is a ‘busyness’ antidote and produces a very quick and powerful effect. GABA and L-theanine help balance our nervous system, enabling a good night’s deep sleep, and thus supporting optimal health. On their own, oral GABA supplements like capsules or tablets do not easily cross the blood-brain barrier. 32 Hence, a liposomal delivery system for this nutrient combination is key, as it has demonstrated abilities to deliver nutrients through this barrier and into the brain where they are needed.

 


1 Bethune S, Lewin E. Many Americans Stressed about Future of Our Nation, New APA Stress in America™ Survey Reveals. Feb 2017. [cited July 21, 2017] Available at: http://www.apa.org/news/press/releases/2017/02/stressed-nation.aspx

2 Understanding the Stress Response. Updated Feb 2016. [cited July 21, 2017] Available at: http://www.health.harvard.edu/staying-healthy/understanding-the-stress-response

3 Aguilar Cordero MJ, Sánchez López AM, et al. Salivary cortisol as an indicator of physiological stress in children and adults; a systematic review. Nutr Hosp. 2014 May 1;29(5):960-8. View Abstract

4 Hek K, Direk N, Newson RS, et al. Anxiety disorders and salivary cortisol levels in older adults: a population-based study. Psychoneuroendocrinology. 2013;38(2):300–305

5 Iliff JJ, Wang M, Liao Y et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012 Aug 15;4(147):147ra111. View Abstract

6 Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013 Oct 18;342(6156):373-7. View Full Paper

7 He Q, Zhang P, Li G et al. The association between insomnia symptoms and risk of cardio-cerebral vascular events: A meta-analysis of prospective cohort studies. Eur J Prev Cardiol. 2017 Jan 1:2047487317702043. View Full Paper

8 Meyerhoff DJ, Mon A, Metzler T, et al. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep. 2014;37(5):893–900. View Abstract

9 Yoto A, Murao S, Motoki M, et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids. 2012;43(3):1331–1337. View Abstract

10 Abdou AM, Higashiguchi S, Horie K, et al. Relaxation and immunity enhancement effects of gammaaminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201–208. View Abstract

11 Inoue W, Bains JS. Beyond inhibition: GABA synapses tune the neuroendocrine stress axis.Bioessays. 2014 Jun;36(6):561-9 View Abstract

12 Dhakal R, Bajpai VK, Baek KH. Production of gaba (γ – Aminobutyric acid) by microorganisms: a review. Braz J Microbiol. 2012;43(4):1230–1241. View Full Paper

13 Alyautdin R, Khalin I, Nafeeza MI, et al. Nanoscale drug delivery systems and the blood-brain barrier. Int J Nanomedicine. 2014;9:795–811 View Full Paper

14 Boonstra E, de Kleijn R, Colzato LS, et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520. View Full Paper

15 Nobre AC, Rao A, Owen GN. L-Theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17 Suppl 1:167–168. View Abstract

16 Kakuda T, Nozawa A, Unno T, et al Inhibiting effects of Theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93. View Abstract

17 Rogers, PJ, Smith, JE, Heatherley, SV, et al. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and Theanine administered alone and together. Psychopharmacology (Berl) 2008;195(4):569-577. View Abstract

18 White DJ, de Klerk S, Woods W et al. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. Nutrients. 2016 Jan 19;8(1) View Abstract

19 Kakuda T, Nozawa A, Sugimoto A, et al. Inhibition by Theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem. 2002;66(12):2683–2686.

20 Nathan PJ, Lu K, Gray M, et al. The neuropharmacology of L-Theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2):21–30. View Abstract

21 Wakabayashi C, Numakawa T, Ninomiya M, et al. Behavioral and molecular evidence for psychotropic effects in L-Theanine. Psychopharmacology (Berl). 2012;219(4):1099–1109. View Abstract

22 Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004;22(3):123–131. View Abstract

23 Björkholm C, Monteggia LM. BDNF – a key transducer of antidepressant effects. Neuropharmacology. 2016;102:72–79. View Full Paper

24 Hurley LL, Akin F, Fresoye L, et al. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. Behav Brain Res. 2013;239:27–30. View Abstract

25 Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25(6):295–301. View Abstract

26 Lu K, Gray MA, Oliver C, et al. The acute effects of L-Theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol. 2004;19(7):457–465 View Abstract

27 Kimura K, Ozeki M, Juneja LR, et al. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007;74(1):39–45. View Abstract

28 Yoto A, Motoki M, Murao S, et al. Effects of L-Theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012;31:28. View Abstract

29 Unno K, Tanida N, Ishii N, et al. Anti-stress effect of Theanine on students during pharmacy practice: Positive correlation among salivary α-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav. 2013;111:128–135 View Abstract

30 Lyon MR, Kapoor MP, Juneja LR. The effects of L-Theanine (SunTheanine®) on objective sleep quality in boys with attention defcit hyperactivity disorder (ADHD): a randomized, double-blind, placebo controlled clinical trial. Altern Med Rev. 2011;16(4):348–354. View Full Paper

31 Jang HS, Jung JY, Jang IS, et al. L-Theanine partially counteracts caffeine-induced sleep disturbances in rats. Pharmacol Biochem Behav. 2012;101(2):217–221. View Abstract

32 Kakee A, Takanaga H, Terasaki T, et al. Efflux of a suppressive neurotransmitter, GABA, across the blood-brain barrier. J Neurochem. 2001;79(1):110-8.

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