Phosphatidylcholine vs Phosphatidylserine: Which Phospholipid Is Right for You?

Phosphatidylserine is an ingredient you may have seen in nootropics and discussed in biohacking communities as a brain-boosting supplement. Phosphatidylcholine is another major phospholipid that also has brain supportive properties, along with liver, gut, and mitochondrial health. 

So if you’re choosing to supplement, which one is better? As with most questions around how to best support your health and wellbeing, the answer is more nuanced than simply choosing one or the other. The reality is that these two phospholipids work alongside each other on a cellular level, and we need both for optimal cellular function. 

In this article, we’ll discuss the properties, similarities, and differences between phosphatidylcholine and phosphatidylserine, how to best supplement them along with your diet, and how these phospholipids really work best together in the body.

What’s the Difference Between Phosphatidylcholine and Phosphatidylserine?

Phosphatidylserine (PS) is a phospholipid and a component of the cell membrane, just as phosphatidylcholine (PC) is. Supplemental PS is often used to address concerns with memory, age-related mental decline, cognitive issues, and other mental health conditions [1].* 

The brain lipids from which PS was first isolated are called cephalins, substances found in nerve tissue and the brain and spinal cord. PS and its cousin phosphatidylethanolamine (PE) are the primary cephalin components of the inner cell membrane, supported on the opposite side (in the outer cell membrane) by phosphatidylcholine (PC). So one key difference between PC and PS is its location in the structure of cell membrane, but they are both needed to make up the phospholipid bilayer.

Other properties and functions of PS: 

• PS is the most abundant phospholipid in the human brain [2, 3].
• PS is vital to the maintenance of the cell’s internal environment, where it also participates in signal transduction, cell-to-cell communication and cell growth regulation [4].
• PS is important to blood coagulation, where it enhances the activation of prothrombin to thrombin, which is the key molecule in the clotting process [4].

Other properties and functions of PC:

• PC is most abundant phospholipid in our outer cell membranes and mitochondrial membranes [5].
• PC makes up 90% of the phospholipids in the GI mucus layer, protecting the intestinal wall from damage and promoting a healthy gastrointestinal environment [6].
• PC (and choline) is essential for healthy fetal development, especially during the third trimester [7].

Other similarities and differences between PS and PC: 

• Both are phospholipids, a fatty acid with a hydrophilic head and a hydrophobic double tail. 
• We can convert PC to PS in the body, but not the other way around.
• PS is more concentrated in the brain, while PC is abundant in cellular membranes and mitochondrial membranes. So generally, PC is much more widespread in the body, and we need more of it for full body health. 

When needed, PS can be made by exchanging the ethanolamine head of PE with L-serine, the non-essential amino acid important to the biosynthesis of purines and pyrimidines that comprise our DNA. PS can be synthesized from PC as well [8]. 

Ideally, most PS is supplied by the diet, so the energy needed to tap into PE or PC as a reservoir is conserved. Organ meats are a strong source of dietary PS, but muscle meats, eggs, white beans and soy-based proteins also offer a decent supply. But in cases of acute stress on the brain and body, such as from mental illness or traumatic brain injury, supplementing PS is a tempting option.

PC vs. PS: Which One Should You Supplement?

Phosphatidylserine is a powerful phospholipid for brain health and our cell membranes––there’s no doubt about that. But supplementing just PS by itself might not be the best strategy. Part of the reason for this is that PS is integral to the process of apoptosis, programmed cell death. 

As strange as it may seem, cell death occurs for our own good. This activity is programmed into every cell of the body. The process can destroy cells that may harm us, such as those mutated by disease, by the environment, or by other factors. 

Maintaining equilibrium between cell proliferation and cell death in the body is important. With apoptosis, there is cell shrinkage and fragmentation, followed by phagocytosis—engulfment by a scavenger cell. This process allows cell contents to be recycled. 

PS plays a major role in apoptosis when its distribution on the cell’s inner leaflet is disrupted by enzymes that move it to the outer layer [9], thereby signaling the imminent death of the cell and calling for the joint activity of phagocytes to digest the cell [10]. 

Following the transfer of PS to the outer membrane, particular receptors on the surface of macrophages and related scavenger cells start the removal of the apoptotic cell. In this context, PS is definitely an essential component of cellular health. 

However, it might be possible that supplemental PS without its related phospholipid friends could accumulate too much of a good thing. Scientists have questioned whether taking PS as an isolated supplement is worth the possibility of encouraging cell death after levels of PS have exceeded physiological need [11, 12, 13]. Because of its coagulation properties, isolated PS also needs oversight in people taking anticoagulant and antiplatelet medications, such as Coumadin. 

Conversely, endogenous (self-made) PS relies on adequate supplies of folic acid, vitamin B12 and essential fatty acids, including DHA—and it’s almost impossible to overdose on endogenous substances. 

But we don’t need to avoid supplementing PS entirely. It just needs the balance of its fellow phospholipids to ensure that it is used by the body effectively and efficiently.

Phosphatidylcholine Can Supply Phosphatidylserine

Taking supplemental phosphatidylcholine (PC), the number one constituent of the cell membrane, is a prudent measure in the maintenance of overall health, proper liver function, fluidizing the membrane to allow passage of nutrients, providing a reservoir for choline to make acetylcholine, transducing cellular signals an a host of other biological endeavors. 

Taking PC with appropriate PE also allows the body to make the PS it needs and accurately regulate apoptosis.  

To go a step further, taking a phospholipid complex like BodyBio PC supplies four of the major phospholipids (PC, PS, PE, and phosphatidylinositol, PI) in their optimal ratios for the body to utilize wherever the need is greatest.

Working Together to Support Cell Membrane Health

If you’re debating over whether to take a phosphatidylserine or phosphatidylcholine supplement, PC is arguably the better choice due to its greater presence in our cell membranes, as well as the body’s ability to turn PC (and PE) into PS where needed. In this way, PC acts like the mother of the other phospholipids. 

An even better choice is to supplement a combination of phospholipids in their ideal ratios needed in the body. BodyBio PC is a phospholipid complex backed by decades of research into the cellular health benefits of PC and its phospholipid friends.

Read more about phosphatidylcholine and its benefits for whole body health.