How Does Phosphatidylserine Support Brain Function?

A Look At The Latest Scientific Literature

We have written about phosphatidylserine at great length on this site. We’ve mentioned it in countless product reviews, and it features in our list of the best ingredients regularly found in natural nootropic supplements. But we’ve never produced a detailed, comprehensive article on phosphatidylserine. 

We’ve never gone in-depth; we’ve explained how it works, sure, but we often only give a rough outline of what it can do, and we focus on its primary function. In the past all mentions of phosphatidylserine will cite one, perhaps two papers at most in support.

Well, it’s about time that changed. 

Below you will find a thorough explanation of what phosphatidylserine is, what it does for brain function, and how it works. We’ll look at the main risks involved with phosphatidylserine supplementation, and whether it is suitable for long-term use. In the end, we’ll take an impartial look at all of these factors and tell you whether we think phosphatidylserine is worth adding to your regular nootropic supplement regimen. 

What Is Phosphatidylserine?

Often abbreviated to simply PS, phosphatidylserine is a glycerophospholipid, but we will just refer to it as a phospholipid for our purposes here.

A phospholipid is just a lipid (fat) usually consisting of a hydrophobic head fatty acid, and two hydrophobic tail fatty acids.

Phospholipids are highly prevalent in the cell membranes of both plants and animals – their hydrophobic nature makes them ideal for this function.

Phosphatidylserine’s structure differs slightly between plants and animals, but it is essentially the same molecule.

It is found in higher or lower concentrations in different foods. The most potent dietary sources of PS for most people are mackerel and herring. The former gives you 480mg per 100g. The only animal tissue that contains more is cow brain, which few people are particularly keen to eat. 

There are lots of plant sources of PS, however. White beans contain over 100mg per 100g. Despite what people tell you, that is way more than what you will get from most animal tissue. 

A common source of phosphatidylserine is soy lecithin. But this is actually phosphatidylcholine from which commercial-grade PS is synthesized. As such, it doesn’t classify as a natural dietary source. Soy beans are actually a poor source of phosphatidylserine. 

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What Does Phosphatidylserine Do?

Like all phospholipids, phosphatidylserine is an absolutely vital structural component of cell membranes. 

Most interestingly from our point of view, it is found in enormous quantities in your brain cell membranes.

For us, this alone counts as a significant cognitive function. 

Without phosphatidylserine, your brain cell membranes couldn’t even form. It is absolutely necessary for the formation of new, and proper maintenance of existing, brain tissue. As your brain function is intimately tied to the physical architecture of your brain, then phosphatidylserine clearly has an incredible and direct influence over cognition. 

This is a well known function of phosphatidylserine. Once you learn that it is a major part of your brain cell membranes, then it is easy to figure out how important it is for brain health and cognitive function. 

But phosphatidylserine has other functions that are just as crucial, if not more crucial. They are just less well known. 

Phosphatidylserine is heavily involved in apoptosis – the process of programmed cell death.

Apoptosis is essentially healthy cellular suicide. You need your older cells to die for new ones to be formed. Ensuring that your cells are performing apoptosis at a proper, healthy rate and at the right time is crucial for your health, longevity, and performance.

In a normal, healthy, functioning cell, phosphatidylserine faces the inside of the cell. It is held there by an enzyme called flippase. 

However, when the cell needs to undergo apoptosis, the enzyme ceases to function. 

This frees up phosphatidylserine. It will move from the inside of the cell to be outward facing. When the phosphatidylserine molecules reach the surface of the membrane, they serve as a signal to your immune cells. Macrophages recognize the phosphatidylserine molecules and immediately begin to engulf the cell. 

Phosphatidylserine therefore acts as the signal to your immune cells to kill off a cell that is no longer functioning healthily. 

That is absolutely incredible. 

We cannot understate the potential power of optimizing your cellular signalling. 

Cell death may sound like a bad thing, but it is imperative for every bodily function. You need to clear out the old to make way for the new.

Phosphotidylserine is the signal that keeps your brain cells turning over at a healthy rate.

Without phosphatidylserine, or without sufficient phosphatidylserine, then you will not be able to destroy unhealthy cells at a rate that is conducive to optimal cognitive function. This hinders your ability to create new brain cells too, which has an enormous impact on your cognitive performance over the long term, not to mention your brain health. 

Once PS has gotten rid of the old cell, it then makes a huge contribution to the new one in the form of a shiny new cell membrane!

It is amazing that so many people focus on phosphatidylserine as a structural component of cellular membranes. 

Many molecules go towards making up bodily tissues.

Very few are involved in cellular signalling in a way similar to phosphatidylserine.

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That has probably convinced most of you to start using phosphatidylserine.

It isn’t too hard to figure out how phosphatidylserine supplementation might benefit cognitive function.

But a lot of the time, things that sound like a no-brainer on paper turn out to be ineffective in practice. They may not be absorbed by the body; they might be destroyed in the gut; they might not cross the blood-brain barrier.

So is phosphatidylserine actually suitable for oral supplementation?

Does it have as big of an impact as we think it will, based on its functions?

Yes and YES!

Let’s not waste any time here. We’re just going to give you some of the best studies currently available and a quick overview of what they state. 

This article, published in Psychopharmacology Bulletin in 1992, looked at PS as a potential treatment for people with Alzheimer’s Disease. The researchers found that “phosphatidylserine may be a promising candidate for study in the early stages of AD.”

The researchers did note that the notable results were present most in people with the lowest degree of cognitive impairment. Their results do not equate to finding a cure. But it seems that PS made a significant difference to cognition for these people.

Another study found that phosphatidylserine supplementation was able to significantly improve memory function in older people struggling with age-related memory loss. The authors state that “there was improvement on both computerized and standard neuropsychological performance tests, and also on clinical global ratings of improvement. The results suggest that the compound may be a promising candidate for treating memory loss in later life.”

Amazingly, these people saw benefits using just 100mg of phosphatidylserine per day. They were already experiencing memory loss and PS seems to have helped either slow its advance or to even help reverse memory function decline (in the short term at least).

A more long-term study was published in the Italian journal Aging in 1993. The authors of this paper looked at the effects of different doses of PS given to geriatric patients with cognitive impairment over a period of 6 months. 

This study is notable in that it used over 490 participants; few dropped out before the 6 month period was over. 

The authors reached a very definitive conclusion about phosphatidylserine’s efficacy as a cognitive enhancer: “Statistically significant improvements in the phosphatidylserine-treated group compared to placebo were observed both in terms of behavioral and cognitive parameters. In addition, clinical evaluation and laboratory tests demonstrated that BC-PS was well tolerated. These results are clinically important since the patients were representative of the geriatric population commonly met in clinical practice.”

This is all pretty conclusive. These kind of studies are plentiful in number. More than one meta-analysis has shown that phosphatidylserine given to people with some sort of cognitive impairment brings about statistically significant improvements in memory function and attention (source). The benefits are lasting. PS is well tolerated, even when used for 6 months or more.

When we see so many studies all pointing to the same conclusion, we’re happy to get excited about a nootropic. 

We have never seen a single shred of evidence to suggest that PS causes side effects.

No long-term health risks have even been hinted at – let alone established. 

Phosphatidylserine is truly an outstanding natural nootropic.

It doesn’t ramp up focus, learning speed and mental energy like cholinergics. Rather, it works quietly in the background, making sure your brain cells are turning over like clockwork, silently guaranteeing optimal long-term brain function. 

A superb addition to any nootropic stack.

References

Tardner, P. 2020. The effects of phosphatidylserine supplementation on memory function in older people: A review of clinical literature. International Journal of Environmental Science & Technology, (online).

Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991 May;41(5):644-9. doi: 10.1212/wnl.41.5.644. PMID: 2027477.

Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano). 1993 Apr;5(2):123-33. doi: 10.1007/BF03324139. PMID: 8323999.

Luke Mercia

Luke is our Editor in Chief. He is the main driving force behind NaturalNootropic.com, and he creates most of our most important content. He is extremely passionate about enhancing human cognition; he has experimented with many different nootropic substances over the years, sometimes with negative results. He wants to help people get more out of performance-enhancing supplements, and he is fascinated by recent advances in longevity research. He can be contacted by email at editor@naturalnootropic.com.