Yo! GABA GABA!

The Molecule of Sleep and Relaxation

Currently in the Western, industrialized world it seems we have an epidemic of poor sleep. So much so that physicians specialize in it, there are clinics and medicines and supplements for it, and even skills you can develop to enhance it (sleep hygiene practices). We've removed ourselves from the natural order of things in exchange for technological prowess but alas, like Prometheus we pay a price for our knowledge. Now that cycles of over stimulation and artificial light have disrupted the normal cycles a wakefulness and rest that are native to our biology, we turn back to technology to right the ship.

While I'm no Luddite one issue with relying to heavily on technologies, especially in regards to solving biological problems is that the solutions ignore the underlying complexity and in an effort to help serve to exacerbate the issue. Even in cases where this doesn't happen directly,

With all of this said, I'm certainly aware that my own bias is towards the minimalistic, bare, and zen point of view. Keep this in mind as I present my current ideas on a deeper layer of sleep health and performance.

GABA - The Molecule That Pumps the Brakes

Gamma aminobutyric acid, or GABA, is a compound that modulates neural activity in the body by effecting cellular charge through the manipulation of potassium and calcium channels. GABA is produced in multiple areas of body including the brain (primary) and the gut (secondary). The effect of GABA in general is to decrease the firing of nerves in the body.

GABA levels are on a monitored constant feedback loop in the brain to ensure the right amount of neural activity at the right time. One very interesting fact that brings us back towards our discussion of sleep is that GABA is inhibited by the stress molecule cortisol. In essence chronic stress, which often has a circular relationship with sleep loss, contributes to GABA suppression.

Under acute and semi-acute conditions of alertness this suppression is necessary but long term disruption can contribute to a cycle where the very thing that promotes relaxation gets inhibited. Essentially, the gas pedal of the nervous system gets stuck so long that the brakes stop working.

This is specifically relevant to sleep technology because much of the supplementation and medicine that is used for sleep enhancement is designed to either directly or indirectly enhance GABA (GABAergic) in the brain. Let's look at a few.

GABA Helpers

First and most obviously is the direct supplementation of exogenous GABA. There is some evidence that GABA alone has some positive effect on sleep latency (the time it takes to enter into restorative sleep) as well as REM sleep. With that said there does not seem to be a clear consensus on the potency of the effect(1). What does seem clear is that exogenous GABA is more effective when combined with other supplements such as L-theanine(2), which is up next.

L-theanine is a green tea extract commonly used for its anxiolytic effects (3). While the exact mechanism is still under some investigation there is some evidence that L-theanine bindsand to glutamate, a foundational excitatory chemical and the compound from which GABA originates. The balance between the two is essential for neurological balance and is implicated in many neurological and psychiatric issues including anxiety. Hence why L-theanine has also become a viable supplement option for the suppression of general anxiety.

L-theanine isn't the only herbal source that has some evidence for helping promote GABA. Other herbs such as valerian root, passion flower, and lavender have also shown to be GABAergic (4). A word of calibration. Many of the studies, at least the ones I came across, were done on animals so it's possible that at least in isolation these compounds could have limited effect on humans. With that said, the best evidence I could find for legitimate net effect on humans is when these compounds were used in appropriate tandem with one another.

Another compound worth mentioning here is supplemental magnesium (Mg). Mg is crucial to the synthesis of GABA via its effect on an enzyme (glutamic acid decarboxylase or GAD). Magnesium has been shown to have a relaxation effect on the body and when combined with other GABAergic compounds is a known pathway to improved sleep (5).

One thing to keep in mind with any and all of these compounds is this: they work within the context of your biology, your habits, and your life. These things are supportive aka supplemental to healthy sleep but are not replacements for the behavioral consistency that promotes long term self-regulation of sleep and relaxation. Sleep hygiene, good nutrition, and effective stress management will far outweigh the effects of even the best supplements. With that said, in proper contexts these things can be extremely helpful. If you're not sure what's right for you work with a medical professional or registered dietician who understands these compounds and the chemistry of sleep so that you can use them effectively.

To summarize this section is GABA seems to be a central effector of our ability to relax and fall asleep. Effective sleep supplements seem to most often effect this pathway whether used in isolation or in tandem. Additionally, this powerful neuro-inhibitor has a direct relationship with our larger pathways of autonomic stimulation and relaxation (sympathetic and parasympathetic). The larger environment of stress response therefore leaves an opportunity for the development of skills that support improvements in skills that support restful sleep along with compounds that create a fast track to the net outcome.

What other tools can we use that support even more robust systems for sleep health? What things can we include that are more proximal and even more accessible? Rather than another potential hydra how can we cut off the head of sleep disruption at the root and cauterize the stump so newer and more complicated problems are less likely to grow in their place?

Proximal Strategies For Pumping the Brakes

The parasympathetic aspect of the Autonomic Nervous System (which I've written about many times in this Substack) is the "Rest, Digest, Recover" part of us that down-regulates the body at large. I have come to affectionately refer to this as the "brake pedal". The supplements discussed in the above section for all intents and purposes contribute to the pumping of the brakes but don't necessarily do so directly.

So then what are some tools and skills that we can use to help pump the brakes in general but even more specifically as things that could be executed as part of sleep hygiene rituals to enhance the important molecule of GABA?

First and foremost, breathing. I'd be remiss not to mention this simple and direct pathways to relaxation. Breathing slowly and deeply, especially with a controlled and slow exhale, has been shown to engage the parasympathetic nervous system and promote relaxation. Spending five to ten minutes prior to bed breathing slowly and deeply can be an effective (and free!) way to chill and to teach your body when you want it to chill from the inside out. An easy protocol to start with is one breath every ten seconds. This "resonance breathing" has been shown to engage the relaxation response. Try it as a 3 second inhale, a 2 second pause, and a 5 second exhale. That's not too special and is easy to remember because 3+2=5. You can even do it while you lay in bed!

(*Deep breathing has been shown to improve GABA directly but the improvements can be short lived (6). You have to do it on a regular basis to get the benefits. However, regular breathing exercises can help balance your stress response in general and therefore contribute to a more stable environment for restorative sleep.)

Second, yoga. In a randomized control trial Iyengar Yoga, which focuses on breathing with proper body alignment, was shown to improve GABA compared to walking (7). While it is not sited in this study a reasonable inference is that almost anything that includes breathing combined with low intensity motion is a powerful way to induce relaxation if not GABA directly. While I don't have evidence of any effect on GABA in particular, in my own experience personally and professionally, I have seen things like self-massage prior to bed have measurable positive effect on sleep. Do with that anecdote what you will.

As you unwind these more proximal strategies you'll find that most of the roads lead back to a directed relaxation response in the body and mind. From that healthier, more balanced environment emerges a biochemically balanced system that produces better rest. The cycle gets moved in the opposite direction and is now self-reinforicing towards robustness and longevity.

Counting Sheep

When it comes to the world of sleep supplementation everybody wants to tell you that their stuff is special and the other stuff is crap. That's capitalism at work. The supplements that work, it seems, effective the specific pathway of GABA receptors that help you take a chill pill.

Which ones should you take? Hell, don't know. I don't know you. What I can recommend is to do your research. Does this company actually put the ingredient in that effects the pathway? Do they use fillers? Are there unwanted side effects? *Hint: Third party testing is a good indicator and very few companies do it. 

You can do all that and/or you can use proximal strategies that even if they don't change sleep at all, won't hurt you. Either way you'll be on your way to counting sheep instead of being one.

Sleep well and thanks for reading,

Rob

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References

1. Hepsomali, P., Groeger, J., Nishihira†, J., & Scholey, A. (2020). Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Frontiers in Neuroscience, 14. https://doi.org/10.3389/fnins.2020.00923.

2. Kim, S., Jo, K., Hong, K., Han, S., & Suh, H. (2019). GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharmaceutical Biology, 57, 65 - 73. https://doi.org/10.1080/13880209.2018.1557698.

3. Moreira, S., Neto, W., Lourenço, G., Costa, C., Araújo, S., & Barros, D. (2018). Anxiolytic effects of oral administration of L-Theanine: a revision. Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition. https://doi.org/10.3390/mol2net-04-05543.

4. Bruni, O., Ferini-Strambi, L., Giacomoni, E., & Pellegrino, P. (2021). Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep. Nutrients, 13. https://doi.org/10.3390/nu13020530.

5. Dasdelen, M., Er, S., Kaplan, B., Celik, S., Beker, M., Orhan, C., Tuzcu, M., Şahin, N., Mamedova, H., Sylla, S., Komorowski, J., Ojalvo, S., Şahin, K., & Kılıç, E. (2022). A Novel Theanine Complex, Mg-L-Theanine Improves Sleep Quality via Regulating Brain Electrochemical Activity. Frontiers in Nutrition, 9. https://doi.org/10.3389/fnut.2022.874254.

6. Streeter, C., Gerbarg, P., Brown, R., Scott, T., Nielsen, G., Owen, L., Sakai, O., Sneider, J., Nyer, M., & Silveri, M. (2020). Thalamic Gamma Aminobutyric Acid Level Changes in Major Depressive Disorder After a 12-Week Iyengar Yoga and Coherent Breathing Intervention.. Journal of alternative and complementary medicine. https://doi.org/10.1089/acm.2019.0234.

7. Streeter, C., Whitfield, T., Owen, L., Rein, T., Karri, S., Yakhkind, A., Perlmutter, R., Prescot, A., Renshaw, P., Ciraulo, D., & Jensen, J. (2010). Effects of yoga versus walking on mood, anxiety, and brain GABA levels: a randomized controlled MRS study.. Journal of alternative and complementary medicine, 16 11, 1145-52 . https://doi.org/10.1089/acm.2010.0007.