Does Phosphatidylserine Increase Choline? Understanding Their Complex Relationship

November 10, 2025 •

4 min read

Scientific research shows that phosphatidylserine (PS) supplementation can boost cholinergic function in the brain, but the relationship with choline is more nuanced than a simple increase. Rather than directly increasing free choline, PS works synergistically with choline-containing compounds and enhances the brain's use of them for neurotransmitter production and cell signaling.

Quick Summary

Phosphatidylserine doesn't directly raise free choline levels. Instead, it supports the metabolic pathways that utilize choline, enhancing neurotransmitter release and cell membrane integrity.

Key Points

Indirect Relationship: Phosphatidylserine (PS) does not directly increase choline levels but supports the metabolic pathways that utilize choline.
Enhances Acetylcholine Release: PS improves neuronal communication by enhancing the release of the neurotransmitter acetylcholine, especially in aged brains.
Optimizes Membrane Function: As a key component of cell membranes, PS increases membrane fluidity, which is crucial for cell signaling and neurotransmitter activity.
Metabolic Recycling: In the liver, PS can be converted back into a precursor of phosphatidylcholine, a storage form of choline, but this is an indirect process.
Supports Receptor Density: Studies show PS can help restore the density of muscarinic cholinergic receptors, improving the brain's response to acetylcholine.
Synergistic Effect: PS works synergistically with choline, optimizing the brain's use of existing choline resources rather than simply adding more.

The Core Connection Between Phospholipids

To understand the dynamic between phosphatidylserine (PS) and choline, it's essential to first recognize their foundational roles as phospholipids, the building blocks of all cell membranes. Both are critical for brain health, but their interaction is metabolic and indirect, not a direct one-way conversion. PS is primarily involved in cell signaling, neurotransmitter release, and maintaining membrane fluidity, while choline is a key precursor for the neurotransmitter acetylcholine (ACh) and the phospholipid phosphatidylcholine (PC).

Choline's Role as a Neurotransmitter Precursor

As an essential nutrient, choline is a required component for the synthesis of acetylcholine, the major neurotransmitter vital for memory, attention, and muscle control. The body obtains choline from diet or by converting phosphatidylcholine (PC) back into choline. However, in the brain, choline is often recycled and used efficiently. A significant portion of the body's choline is incorporated into phosphatidylcholine, the most abundant phospholipid in mammalian membranes.

The Role of Phosphatidylserine in Enhancing Cholinergic Function

While phosphatidylserine doesn't directly increase your body's overall choline supply, it significantly influences the cholinergic system—the network of nerve cells and functions that rely on acetylcholine. Instead of acting as a raw material, PS enhances the efficiency and output of this system through several mechanisms.

Supporting Acetylcholine Release

Studies have shown that chronic phosphatidylserine treatment, particularly in aged subjects or those with cognitive decline, can boost the release of acetylcholine (ACh) from neurons. This effect is distinct from simply providing more choline. PS is believed to accomplish this by increasing membrane fluidity and supporting the processes involved in neurotransmitter release via exocytosis, where synaptic vesicles fuse with the cell membrane to release their contents. Essentially, PS optimizes the cellular machinery that uses choline, rather than manufacturing more choline itself.

Restoring Neurotransmitter Receptor Density

PS has also been shown to help restore the density of muscarinic cholinergic receptors, which tend to decline with age. By ensuring these receptors function correctly, PS further enhances the effectiveness of the acetylcholine that is released, improving overall communication within the brain. This can lead to improvements in memory and cognitive function, which are commonly associated with both PS supplementation and a healthy cholinergic system.

Metabolic Pathways: How PS and Choline Interact

The relationship between phosphatidylserine and choline is governed by intricate cellular biochemistry. The synthesis of PS involves a base-exchange reaction where a choline or ethanolamine head group is exchanged for a serine head group on a pre-existing phospholipid, such as phosphatidylcholine (PC) or phosphatidylethanolamine (PE). This process releases choline (or ethanolamine). Conversely, PS can be decarboxylated in the mitochondria to form PE, which can then be methylated in the liver to form PC, thus recycling choline. The key takeaway is that PS doesn't act as a choline booster but rather as a facilitator of the entire phospholipid and neurotransmitter metabolic cycle.

Comparison Table: Phosphatidylserine vs. Choline


Feature	Phosphatidylserine (PS)	Choline
Primary Role	Membrane fluidity, cell signaling, neurotransmitter release, apoptosis signaling	Precursor for acetylcholine and phosphatidylcholine; methyl donor
Source	Produced in the body; supplemented from soy, cabbage, or bovine sources	Essential nutrient from eggs, liver, fish, and legumes
Mechanism	Optimizes neuronal membrane function, enhances acetylcholine release	Raw material used by neurons for acetylcholine synthesis
Benefit to Cognition	Improves memory, learning, attention, and mood by supporting neuronal communication	Supports memory and cognitive function by providing raw materials for neurotransmitters

Sources and Supplementation

Both phosphatidylserine and choline are vital nutrients found naturally in certain foods. PS is present in organ meats (liver), fish (mackerel, tuna), and soy. Choline is abundant in eggs, meat, fish, and some vegetables. However, dietary intake of PS is typically low, which is why supplements are common. Historically, PS supplements were derived from bovine sources, but due to concerns about mad cow disease, most are now sourced from plants like soy or cabbage. The effects of these different forms appear to be similar, though some older studies used the bovine form.

Conclusion: A Supportive Partnership, Not a Direct Increase

To conclude, the premise that phosphatidylserine directly increases choline is inaccurate. PS and choline are distinct but interdependent compounds critical for brain function. Instead of PS raising choline levels, it enhances the utilization and release of the cholinergic system's key neurotransmitter, acetylcholine. By improving cell membrane fluidity, supporting exocytosis, and potentially restoring receptor density, PS optimizes the brain's existing choline-dependent processes. Taking PS is an effective strategy for supporting cognitive function, but it is complementary to, not a replacement for, a healthy choline intake. Together, they form a powerful partnership for maintaining a sharp and healthy brain. Further information on PS metabolism and function is available from scientific publications, such as articles in the Progress in Lipid Research journal, which detail the biochemical pathways. Source: PMC4258547: Phosphatidylserine in the Brain: Metabolism and Function

Frequently Asked Questions

Phosphatidylserine (PS) is a phospholipid that helps protect and transmit messages between cells in your brain, playing a key role in membrane fluidity, cell signaling, and neurotransmitter release.

PS has been shown to increase the release of acetylcholine, a crucial neurotransmitter, particularly in aged individuals. It does this by optimizing the function of neuronal membranes, not by directly providing more choline.

No. While PS supports the use of choline by the brain, choline is an essential nutrient with its own vital functions, such as building phospholipids and cell membranes. PS complements a healthy choline intake rather than replacing it.

The body can produce its own PS, but it also obtains it in small amounts from foods like fish, soy, and organ meats. PS supplements are derived primarily from soy or cabbage.

The cholinergic system is the network of neurons and functions that rely on acetylcholine as their primary neurotransmitter. It is crucial for processes like memory and attention.

Yes. While older supplements were sourced from bovine brains, most modern PS supplements are derived from plant-based sources like soy lecithin or cabbage due to safety concerns. The effects of plant-based PS are generally considered comparable.

Beyond supporting acetylcholine, PS is associated with improved memory, learning, attention, mood regulation, and a blunting of the stress hormone cortisol.