Cellular Health
Phosphatidylserine for Cellular Health, Cognitive Function, Cortisol Regulation, and More
PS is a phospholipid in the brain and essential to cell integrity, memory formation, learning, attention, mood regulation, and stress management.
Phosphatidylserine (PS) is a distinctive molecule in the body that significantly impacts cellular signaling. PS has a noticeable impact on our cognitive, endocrine, blood, and cardiovascular systems. PS is also a nutrient, rich in animal products and some plant sources.
I only introduce critical and well-researched nutrients and supplements that might significantly impact our health. Phosphatidylserine is one of them. I introduced many other valuable nutrients, which I linked at the end of this article.
Even though our bodies can create this molecule from food and other phospholipids due to various factors, the optimal amounts might become unavailable. Therefore, I decided to create awareness of this vital phospholipid and nutrient for the health of our cells and tissues.
To make the story readable and digestible, I structured it under eight short sections covering only the critical points. This story is for busy people who can quickly review it in around 10 minutes and understand the value and rationale behind this vital molecule.
First, I’d like to introduce the concept of phospholipids so that the functions, mechanisms, and benefits of phosphatidylserine can make sense to you.
1 — What are phospholipids?
Phospholipids are essential for maintaining cells’ and tissues’ structural and functional integrity. They serve as the main structural components of cell membranes. Therefore, their disruption can cause physical and mental disorders.
Their most critical aspect is maintaining the integrity and fluidity of cell membranes, allowing for the exchange of fluids between cells, and regulating cell signaling processes.
Phospholipids are also essential components of lipoproteins, which I will cover in another article, as they are critical for metabolic health, such as transporting fat molecules and cholesterol in the bloodstream.
Phospholipids have complex chemical structures, but I’d like to simplify them with a brief explanation.
Phospholipids are composed of a glycerol backbone, two fatty acid chains, and a phosphate group, They are essential for the structure and function of cell membranes. Their significant roles are cellular signaling and maintaining fluidity.
Glycerol is a type of alcohol that acts as a backbone in phospholipids. A phosphate group is a molecule comprising a phosphorus atom and four oxygen atoms.
The phosphate group is attached to the glycerol backbone to form part of the molecule’s polar head. This head maintains the structure and stability of cells. Literature classifies them as glycerophospholipids and sphingolipids.
Apart from phosphatidylserine, there are several phospholipids. The well-researched ones are phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, and phosphatidic acid.
2 — What is phosphatidylserine?
Phosphatidylserine (PS) is an abundant phospholipid compound in the brain. PS is an essential component of cell membranes. It can also increase the neurotransmitter acetylcholine.
The most researched aspect of PS is about cognitive processes, such as memory formation, retention, recall, attention, and mood regulation. However, the mechanisms are still debated with some consensus based on growing literature, including clinical studies.
Based on my reviews, PS might increase the availability of neurotransmitters, such as acetylcholine and dopamine, which are involved in learning and memory.
The good news is the body can create PS with some chemical reactions. The balance between phospholipid transfer proteins and phospholipases regulates this process.
In summary, the body can convert it from phosphatidylethanolamine (PE) or phosphatidylcholine, other essential phospholipids. Interestingly, once converted, PS can form other phospholipids and be converted back to PE.
Choline is a precursor for phospholipid synthesis. Therefore, this nutrient plays an indirect role in the production of PS in the brain. I documented the importance of choline deficiency in a previous article based on experience.
We don’t need to know the chemical details, but understanding the functions of PS in the body and addressing deficiencies is critical for cognitive, cardiovascular, neurological, and mental health.
Deficiency is possible because various factors, such as age, stress, and certain health conditions, can impact the body’s ability to synthesize PS.
As we age and are prone to chronic stress, the production of PS decreases. Therefore, supplementation is a viable solution. But first, we need to consider getting it from food.
3 — Foods Containing Phosphatidylserine
Phosphatidylserine is naturally present in mainly animal-based foods such as fish, seafood, animal brains, liver of beef, lamb, chicken, egg yolks, and dairy products like milk, cream, yogurt, and cheese.
PS also exists in plant sources such as cabbage, sunflower, soybeans, and soy-based products like lecithin and tofu.
4 — Critical Functions of Phosphatidylserine
In this section, I summarize the six critical functions of this phospholipid in the body and mind, as the balance of PS can have physiological and psychological effects.
a — Cellular Signaling (Signal Transduction)
PS regulates signal transduction pathways, which play a role in various physiological processes, including cell division, cell growth, cell death, and gene expression.
“Signal transduction” refers to cells receiving, processing, and responding to signals from the external environment. These signals can trigger various cellular responses from hormones, neurotransmitters, and growth factors.
b — Integrity and Fluidity of Cell Membranes
PS is a natural component of cell membranes. It can maintain their integrity and fluidity. These processes are essential for the proper functioning of cells and tissues.
c — Activation of Enzymes and Co-Factors
PS activates the enzyme tyrosine hydroxylase. It is necessary for the synthesis of catecholamines. PS also acts as a co-factor for the activation of protein kinase C.
d— Cognitive Function
PS can regulate neurotransmitter activity. It boosts impaired cholinergic systems. For example, it can increase the excitability of cholinergic interneurons. Therefore, several studies found that it could improve cognitive function and memory. I cover cognitive function in the following sections.
e — Cortisol Regulation and Anti-Inflammatory Effect
PS can regulate cortisol levels in response to increased stress. As PS can lower oxidative stress, it is believed to have anti-inflammatory effects. Literature indicates that phospholipids serve as precursors for essential signaling molecules regulating inflammation and blood pressure.
f — Facilitation of calcium and glucose uptake
PS can facilitate calcium uptake in the central nervous system (CNS). It can also increase glucose uptake in the CNS. Considering its cortisol, calcium, and glucose effects, a 2012 study indicates that PS supplementation can enhance exercise performance by reducing muscle damage due to excessive cortisol levels during overtraining and promoting recovery. I cover the supplementation aspect in the next section.
5 — A Brief Review of PS Supplementation
Research into phosphatidylserine and phosphatidylethanolamine started in the 1800s. You can learn the historical background from this publicly available paper published in the Journal of Lipid Research.
As a dietary ingredient Phosphatidylserine (PS) has evolved over the years. PS used to be extracted from cow brains in the past. However, because of mad cow disease, this source became unsafe. Therefore, soy, cabbage, and sunflower became the new source.
As Dr. Parris M. Kidd documented in the Textbook of Natural Medicine (Fifth Edition) in 2020, some people were skeptical that soy-based PS would work because it had different fatty acid profiles than the bovine cortex PS.
However, several trials have shown soy-based PS to have clinical benefits. Advances in enzyme technology have allowed the production of PS preparations containing omega-3 fatty acids (DHA and EPA). PS is also created from sunflowers.
Overall, the literature indicates that PS products are effective in trials involving children with ADHD and elderly subjects with memory complaints.
Advanced PS preparations from reliable manufacturers are considered safe and well-tolerated. However, there have also been trials that showed that soy-based PS without omega-3 fatty acids could also be effective, suggesting that the headpiece of the PS molecule may be the key to its benefits.
I’d like to briefly introduce the findings of initial clinical studies.
As documented in this review paper, “Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials.
For example, phosphatidylserine with DHA/EPA has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, mainly containing phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles.
In a double-blind trial, Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels.”
Therefore, the authors believe that utilizing DHA and EPA with phospholipids and membrane antioxidants to achieve a triple-cell synergy may further diversify their wide range of clinical applications.
Some studies suggest that supplementing with PS might improve cognitive function in elderly individuals, particularly those with age-related declines in memory and thinking abilities. I cover them in the following sections.
6 — Findings of PS Brain Benefits from the Review of 127 Papers
As there are hundreds of papers on the cognitive function of PS, I decided to introduce one comprehensive review to reflect the findings of many studies.
This review study published in the journal Nutrition aimed to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function.
The authors reviewed many scientific papers published before June 2014. Based on their criteria, they included 127 papers for their assessment.
The results indicated that a large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability.
The authors concluded that “phosphatidylserine (PS) is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission.”
They confirmed that “exogenous PS (300–800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells.”
In terms of benefits, the review confirms that PS supports human cognitive functions, including:
the formation of short-term memory,
the consolidation of long-term memory,
the ability to create new memories,
the ability to retrieve memories,
the ability to learn and recall information, the ability to focus attention and concentrate,
the ability to reason and solve problems, language skills,
and the ability to communicate.
It also supports locomotor functions, especially rapid reactions, and reflexes.
In addition, when I checked the database of Examine.com, I noticed that Phosphatidylserine is linked to 14 conditions and 11 health outcomes. This database requires membership, but you can see the conditions and health outcomes mentioned publicly.
In summary, PS studies include dementia and Alzheimer’s Disease (4 studies), ADHD (2 studies), cognitive impairment (1 study), and Exercise performance, including running, cycling, golf, and aerobic exercise (one study for each), metabolic health (1 study), Mental Resilience, memory improvement, and mood improvement (one study for each).
In summary, those papers’ health outcomes include cognition, memory, reaction time, blood pressure, heart rate, cholesterol, triglycerides, and liver enzymes.
When I checked my research diary on this molecule, I noticed that older studies also mention the mitochondrial impact of PS.
A 2010 study showed that the loss of PS asymmetry is an early indicator of apoptosis and serves as a signal to initiate blood clotting affecting cardiovascular health.
A 2018 study investigated phosphatidylserine as a cancer cell targeting biomarker.
7 — Phosphatidylserine as a Nutraceutical
As defined in this paper, “Nutraceuticals are foods, or compounds within foods, that provide health benefits beyond that of strict nutritional support.”
In Chapter 3, titled “Cognitive Effects of Nutraceuticals,” two scientists investigated phosphatidylserine's potential mechanisms and effects on the cognitive system.
They informed that PS might improve blood lipid levels, reduce the risk of cardiovascular problems, and have anti-inflammatory and anti-oxidative stress properties.
Regarding cognitive effects, the authors mention that PS may boost cholinergic function, which is involved in learning and memory.
They highlighted that this effect had been observed in rats, where treatment with PS restored the release of acetylcholine to levels seen in young rats. However, this effect was only seen in older rats and not in young rats, suggesting that PS may only enhance impaired cholinergic systems.
The authors also mention several biochemical effects of PS, such as activating the enzyme tyrosine hydroxylase necessary for catecholamine synthesis, facilitating calcium uptake in the brain, and increasing glucose uptake in the central nervous system.
PS is also necessary for activating a protein called protein kinase C, which increases nerve cells' excitability in memory and learning.
8 — PS Side Effects and Medication Interactions
I have used 100 mg PS daily, mainly for cognitive function, from reliable manufacturers for over a decade and did not notice any side effects. However, some studies have reported potential side effects of PS supplementation. Therefore, I’d like to highlight them for awareness.
The common side effects mainly relate to gastrointestinal distress manifesting as stomach upsets and diarrhea. Some trials mentioned headaches and insomnia.
In addition, PS might interact with some medications, such as anti-depressants and blood thinners. Since PS can increase acetylcholine, patients on anticholinergic drugs cannot use PS.
There is a debate about the effectiveness of PS for bipolar, and some believe it might worsen the condition. When I check the literature, I found two studies shedding light on the issue.
This paper states, “Individuals with bipolar disorder exhibit alterations in their phospholipid levels. It is unclear whether these alterations are a secondary consequence of the illness or if phospholipids and illness risk overlap genetically.”
However, this study in the Nutrition Journal mentions 100 milligrams of Ps with food to address the deficiency for bipolar patients. As bipolar is a severe mental health condition, it is essential to discuss it with qualified healthcare professionals before considering PS supplementation.
Conclusions and Takeaways
Phospholipids are essential for maintaining the structural and functional integrity of cells and tissues. They serve as the main structural components of cell membranes. Therefore, their disruption might cause severe health issues.
In this post, I focused on phosphatidylserine (PS), an abundant phospholipid compound in the brain. Like other phospholipids, PS is an essential component of cell membranes. It also has neural effects, such as increasing the neurotransmitter acetylcholine, which is essential for cognitive health and performance.
The most researched aspect of PS is about cognitive processes, including memory formation, retention, recall, attention, and mood regulation. However, the mechanisms are still debated with some consensus based on growing literature, including clinical studies.
Even though the body can generate PS, deficiencies are possible due to various factors, especially chronic stress, aging, and cognitive decline. Other health conditions might also cause deficiencies.
Addressing nutritional deficiencies is critical for our health. As this study points out, “the most common nutritional deficiencies seen in mental disorder patients are omega-3 fatty acids, B vitamins, minerals, and amino acids that are precursors to neurotransmitters.”
Eating a well-balanced diet and proactive stress management with restorative sleep and regular exercise is critical to improving cellular health.
Therefore, if we have challenges in these critical lifestyle factors, we must seek timely support from qualified healthcare professionals to improve our conditions.
In summary, significant contributors to the imbalances of neurochemicals are excessive stress, chronic inflammation, neurodegenerative disorders, traumatic brain injury, stroke, brain atrophy, infections, and genetic mutations.
In addition, unknown underlying health conditions might also affect our cellular health. Timely diagnosis and treatments of those conditions with support from professionals are crucial for the quality of life and well-being.
Thank you for reading my perspectives. I wish you a healthy and happy life.
I aim to increase the hormonal intelligence of my readers and write about various hormones and neurotransmitters such as dopamine, serotonin, oxytocin, GABA, acetylcholine, norepinephrine, adrenaline, glutamate, and histamine.
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