A Neurotransmitter Less Talked-About

GABA is taken by many people as a supplement, mostly as a mood modifier, though its health claims go beyond the recreational—and also, we’re of the opinion that mental health is also just health, and if it works, it works. We’ll explore some of the claims and science behind them today…

What is GABA?

GABA stands for gamma-aminobutyric acid, and it’s a neurotransmitter. It’s a lot less talked-about than for example dopamine or serotonin, but it’s very important nonetheless.

We make it ourselves inside our body, and we can also get it from our food, or supplement it, and some drugs will also have an effect on its presence and/or activity in our body.

What foods is it found in?

• Animals, obviously (just like in human brains*)
• Fermented foods (many kinds)
• Yeast
• Tea
• Tomatoes
• Mulberries

For more details, see:

γ-Aminobutyric acid found in fermented foods and beverages: current trends

*However, we do not recommend eating human brains, due to the risk of CJD and prion diseases in general.

What claims are made about it and are they true?

For brevity, we’ll give a little spoiler up-front: all the popular claims for it appear to be valid, though there’s definitely room for a lot more human trials (we skipped over a lot of rodent studies today!).

So we’ll just drop some of its main benefits, and human studies to back those.

Reduction of stress and anxiety

GABA decreases task-related stress and anxiety within 30 minutes of being taken, both in subjective measures (i.e., self-reports) and in objective clinical physiological measures:

Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks

Cognitive enhancement

It’s not a does-everything nootropic like some, but it does have clear benefits to episodic memory:

❝GABA intake might help to distribute limited attentional resources more efficiently, and can specifically improve the identification and ordering of visual events that occur in close temporal succession❞

One of the things that makes this one important is that it also deals with the often-asked question of “does GABA pass the blood-brain barrier”:

❝The present findings do give further credence to the idea that oral ingestion does allow GABA to reach the brain and exert direct effects on cognition, which in the present case were specific to temporal attention.❞

Read more:

Supplementation of gamma-aminobutyric acid (GABA) affects temporal, but not spatial visual attention

Potential for more

We take care to give good quality sources, so the following study comes with a big caveat that it has since been retracted. Why was it retracted, you wonder?

It’s about the sample; they cite “30 healthy adults”, but neglected tp mention that this figure was initially 46. What happened to the other 16 participants is unclear, but given that this was challenged and the challenge not answered, it was sufficient for the journal (Nature) to pull the study, in case of deliberate sample bias.

However! Running the numbers in their results section, a probability of 0.03 is very compelling unless the disappearance of 16 subjects was outright fraudulent (which we regrettably cannot know either way).

Here’s the study (so take it with a pinch of salt, considering the above), and taken at face value, it shows how GABA supplementation improves accurate reactions to fast-moving visual and auditory stimuli:

RETRACTED ARTICLE: γ-Aminobutyric acid (GABA) administration improves action selection processes: a randomised controlled trial

…so, hopefully this experiment will be repeated, without disappearing participants!

The sweet spot

You may be wondering how something that slows a person down (having a relaxing effect) can also speed a person up. This has to do with what it is and isn’t affecting; think of it like a “focus mode” on your computer or other device that greys-out everything else a bit so that you can focus on what you’re doing.

It’s in some ways (by different neurochemical pathways, though) a similar effect to the “relaxed alertness” created by l-theanine supplementation.

There’s also a sweet spot whereby GABA is toning some things down just the right amount, without adversely affecting performance in areas we don’t want slowed down. For the science of this, see:

Too Little and Too Much: Hypoactivation and Disinhibition (Reduced GABAergic Inhibition) of Medial Prefrontal Cortex Cause Attentional Deficits

Is it safe?

GABA is “Generally Recognized As Safe”. However:

• you should speak with your pharmacist if you are taking any medications for blood pressure or epilepsy, as GABA supplementation may cause them to work too well.
• you should absolutely not take GABA with alcohol or opioids as (dose-dependent for all the substances involved, and also depending on your metabolic base rate and other factors) its acute depression of the CNS can mean you relax and slow down too much, and you may find yourself not breathing often enough to sustain life.

Aside from that, it is considered safe up to at least 1g/kg/day*. Given that popular doses are 120–750mg, and most people weigh more than 750g, this is very safe for most people:

United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

Where can I get it?

We don’t sell it, but for your convenience, here’s an example product on Amazon

Enjoy!

PS, we love you. With good reason!

There are nearly 20,000 studies on PS listed on PubMed alone, and its established benefits include:

• significantly improving memory
• potential reversal (!) of neurodegeneration
• reduction of stress activation
• improvement in exercise capacity
• it even helps avoid rejection of medical implants

We’ll explore some of these studies and give an overview of how PS does what it does. Just like the (otherwise unrelated) l-theanine we talked about a couple of weeks ago, it does do a lot of things.

PS = Cow Brain?!

Let’s first address a concern. You may have heard something along the lines of “hey, isn’t PS made from cow brain, and isn’t that Very Bad™ for humans, mad cow disease and all?”. The short answer is:

Firstly: ingesting cow brain tissue is indeed generally considered Very Bad™ for humans, on account of the potential for transmission of Bovine Spongiform Encephalopathy (BSE) resulting in its human equivalent, Creutzfeldt–Jakob Disease (CJD), whose unpleasantries are beyond the scope of this newsletter.

Secondly (and more pleasantly): whilst PS can be derived from bovine brain tissue, most PS supplements these days derive from soy—or sometimes sunflower lecithin. Check labels if unsure.

Using PS to Improve Other Treatments

In the human body, the question of tolerance brings us a paradox (not the tolerance paradox, important as that may also be): we must build and maintain a strong immune system capable of quickly adapting to new things, and then when we need medicines (or even supplements), we need our body to not build tolerance of them, for them to continue having an effect.

So, we’re going to look at a very hot-off-the-press study (Feb 2023), that found PS to “mediate oral tolerance”, which means that it helps things (medications, supplements etc.) that we take orally and want to keep working, keep working.

In the scientists’ own words (we love scientists’ own words because they haven’t been distorted by the popular press)…

❝This immunotherapy has been shown to prevent/reduce immune response against life-saving protein-based therapies, food allergens, autoantigens, and the antigenic viral capsid peptide commonly used in gene therapy, suggesting a broad spectrum of potential clinical applications. Given the good safety profile of PS together with the ease of administration, oral tolerance achieved with PS-based nanoparticles has a very promising therapeutic impact.❞

Nguyen et al, Feb 2023

In other words, to parse those two very long sentences into two shorter bullet points:

• It allows a lot of important treatments to continue working—treatments that the body would otherwise counteract
• It is very safe—and won’t harm the normal function of your immune system at large

This is also very consistent with one of the benefits we mentioned up top—PS helps avoid rejection of implants, something that can be a huge difference to health-related quality of life (HRQoL), never mind sometimes life itself!

What is PS Anyways, and How Does It Work?

Phosphatidylserine is a phospholipid, a kind of lipid, found in cell membranes. More importantly:

It’s a signalling agent, mainly for apoptosis, which in lay terms means: it tells cells when it’s time to die.

Cellular death sounds like a bad thing, but prompt and efficient cellular apoptosis (death) and resultant prompt and efficient autophagy (recycling) reduce the risk of your body making mistakes when creating new cells from old cells.

Think about photocopying:

• Situation A: You have a document, and you want to copy it. If you copy it before it gets messed up, your copy will look almost, if not exactly, like the original. It’ll be super easy to read.
• Situation B: You have a document, and you want to copy it, but you delay doing so for so long that the original is all scuffed and creased and has a coffee stain on it. These unwanted changes will get copied onto the new document, and any copy made of that copy will keep the problems too. It gets worse and worse each time.

So, using this over-simplifier analogy, the speed of ‘copying’ is a major factor in cellular aging. The sooner cells are copied, before something gets damaged, the better the copy will be.

So you really, really want to have enough PS (our bodies make it too, by the way) to signal promptly to a cell when its time is up.

You do not want cells soldiering on until they’re the biological equivalent of that crumpled up, coffee-stained sheet of paper.

Little wonder, then, that PS’ most commonly-sought benefit when it comes to supplementation is to help avoid age-related neurodegeneration (most notably, memory loss)!

Keeping the cells young means keeping the brain young!

PS’s role as a signalling agent doesn’t end there—it also has a lot to say to a wide variety of the body’s immunological cells, helping them know what needs to happen to what. Some things should be immediately eaten and recycled; other things need more extreme measures applied to them first, and yet other things need to be ignored, and so forth.

You can read more about that in Elsevier’s publication if you’re curious 🙂

Wow, what a ride today’s newsletter has been! We started at paracetamoxyfrusebendroneomycin, and got down to the nitty gritty with a bunch of hopefully digestible science!

We love feedback, so please let us know if we’re striking the balance right, and/or if you’d like to see more or less of something—there’s a feedback widget at the bottom of this email!