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!

Flower Power: St. John’s Wort’s Drug-Level Effectiveness

St. John’s wort is a small yellow flower, extract of which can be bought inexpensively off-the-shelf in pretty much any pharmacy in most places.

It’s sold and used as a herbal mood-brightener.

Does it work?

Yes! It’s actually very effective. This is really uncontroversial, so we’ll keep it brief.

The main findings of studies are that St. John’s wort not only gives significant benefits over placebo, but also works about as well as prescription anti-depressants:

A systematic review of St. John’s wort for major depressive disorder

They also found that fewer people stop taking it, compared to how many stop taking antidepressants. It’s not known how much of this is because of its inexpensive, freely-accessible nature, and how much might be because it gave them fewer adverse side effects:

Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis

How does it work?

First and foremost, it’s an SSRI—a selective serotonin reuptake inhibitor. Basically, it doesn’t add serotonin, but it makes whatever serotonin you have, last longer. Same as most prescription antidepressants. It also affects adenosine and GABA pathways, which in lay terms, means it promotes feelings of relaxation, in a similar way to many prescription antianxiety medications.

Mechanism of action of St John’s wort in depression: what is known?

Any problems we should know about?

Yes, definitely. To quote directly from the National Center for Complementary and Integrative Health:

St. John’s wort can weaken the effects of many medicines, including crucially important medicines such as:

• Antidepressants
• Birth control pills
• Cyclosporine, which prevents the body from rejecting transplanted organs
• Some heart medications, including digoxin and ivabradine
• Some HIV drugs, including indinavir and nevirapine
• Some cancer medications, including irinotecan and imatinib
• Warfarin, an anticoagulant (blood thinner)
• Certain statins, including simvastatin

Click here for a more comprehensive list of interactions, contraindications, and potential side effects

I’ve read all that, and want to try it!

As ever, we don’t sell it (or anything else), but here’s an example product on Amazon.

Please be safe and do check with your doctor and/or pharmacist, though!