Phosphatidylserine: Review of Nootropic Benefits, Side Effects, & Dosage

Updated on March 2, 2024
 by — reviewed by Jason Williams, PhD (Contributor: George Collins / Editor: Yoko Hill)
Overview of Phosphatidylserine's nootropic benefits and its impact on cognitive enhancement.

Phosphatidylserine, commonly abbreviated as PS, is a phospholipid and a crucial component of cell membranes, particularly in the brain. This article delves into the multifaceted role of phosphatidylserine, exploring its benefits, uses, recommended dosage, and potential side effects. 

As an amino acid derivative compound, PS can also play a pivotal role in maintaining cellular functions, including cell membrane integrity and apoptosis, the process of programmed cell death.

The supplementation of phosphatidylserine has garnered attention for its potential to enhance cognitive functions and possibly ameliorate cognitive decline, especially in the elderly.

This review will examine clinical studies and research on PS, focusing on its impact on brain health, mental function, and managing stress levels by influencing cortisol, a key stress hormone.

Furthermore, we will discuss the administration of phosphatidylserine, including the standard dosage and the form of liposome encapsulation for enhanced absorption. We will also share information about phosphatidylserine in brain cells, its effects on memory, and its potential in the treatment of age-related cognitive impairments such as Alzheimer’s disease.

What is Phosphatidylserine?

Phosphatidylserine (PS), a phospholipid, plays a critical role in cell membrane structure and function, particularly within the brain. Phosphatidylserine should not be mistaken for Serine, which is an α-amino acid known for its function in the biosynthesis of proteins.

As an amino acid derivative compound, PS is essential for maintaining the integrity of cell membranes, including brain cells, and facilitates their proper functioning. It’s found in high concentrations in the human brain, underscoring its importance for cognitive functioning, including memory and mental performance.

The effects of phosphatidylserine administration have been studied for its potential benefits in cognitive health, especially in reducing cognitive decline in the elderly. PS supplementation may improve memory and cognitive functions, and some studies suggest its effectiveness in the treatment of age-related cognitive decline, such as Alzheimer’s disease in elderly patients.

In the realm of brain health, phosphatidylserine is known for its role in apoptosis, or programmed cell death, which is vital for the turnover of brain cells and maintaining brain health. Moreover, PS has been linked to the reduction of cortisol, a stress hormone, potentially mitigating the effects of stress on the body and brain.

As for its administration, liposome encapsulation is sometimes used to enhance the absorption of phosphatidylserine in the body. In summary, phosphatidylserine is a key phospholipid with significant roles in brain function and health, showing the potential to mediate cognitive decline and support overall brain function.(1)


  • Improved memory, concentration, and overall increased cognitive function
  • Improved mood and reduction of symptoms of depression
  • Delayed cognitive decline in the elderly
  • Improved athletic performance and reduced muscle soreness


  • PS supplements can be relatively expensive, and the quality may vary between brands
  • More human clinical trials are needed to fully understand the effects and safety of long-term use

Mechanism of Action

Phosphatidylserine is a phospholipid, which includes a group of fatty acids in its complex structure, including linoleic acid, oleic acid, palmitic acid, and stearic acid.(2) The effects of phosphatidylserine therapy help in the maintenance of brain cell structure and is a major component of the cell membrane needed for optimal cognitive health. 

Phosphatidylserine (PS), a crucial component of membrane phospholipids, plays a significant role in various cell survival, especially in brain tissue. The role of PS, or Phosphatidylserine, in the brain is integral to maintaining neuronal health and function.(3)

One of the key mechanisms of action of phosphatidylserine involves apoptosis as well, the programmed cell death essential for the regeneration and health of brain cells. During apoptosis, PS, which is normally located on the inner leaflet of the cell membrane, gets externalized to the outer leaflet of the plasma membrane. 

This externalization of PS on the surface of apoptotic cells plays an important role. It sends a signal for macrophages to begin phagocytosis, thereby clearing out dying cells and preventing inflammation.

This externalization is also involved in the activation of TAM receptors (Tyro3, Axl, and MerTK), which are crucial for the clearance of apoptotic cells and maintaining cellular homeostasis. TAM receptor activation by PS helps in regulating immune responses and in the clearance of apoptotic debris, which is vital for preventing chronic inflammation and autoimmune reactions.

Additionally, PS in the brain is potentially involved in modulating the activity of various cytokines, including tumor necrosis factor (TNF), a key inflammatory mediator. By influencing the activity of such cytokines, PS can potentially mitigate inflammatory responses in the brain, which is beneficial in various neurodegenerative conditions.(4)

In studies, bovine cortex-derived PS has been used to understand these mechanisms. However, due to concerns like mad cow disease, most dietary supplements now use plant-derived PS. The understanding of PS’s role in brain health and its interaction with various cellular components, like TAM receptors and tumor necrosis factor, underscores its importance in neurological health and its potential therapeutic applications in neurodegenerative diseases.

Lastly, phosphatidylserine (PS) has a notable interaction with the cholinergic system in the brain, which is crucial for memory and cognitive processes. The cholinergic system refers to the structure and function of neurons that use acetylcholine as a neurotransmitter. This system is particularly significant in areas of the brain involved in learning, memory, and attention.(5)

PS plays a role in supporting the health and function of cholinergic neurons. It is a key component of cell membranes, including those of nerve cells. By maintaining the integrity and fluidity of these plasma membranes, PS ensures the proper functioning of neuronal cells, including the effective transmission of signals.

Nootropic Benefits of Phosphatidylserine

Phosphatidylserine (PS) is widely recognized for its nootropic benefits, particularly for its ability to provide significant improvement of cognitive functions and brain health. Its role in improving mental capabilities is supported by several studies and clinical trials. 

Here’s an overview of its key nootropic benefits:

1. Enhancing Memory and Cognitive Function

PS has been demonstrated to significantly improve cognitive functions, especially in the elderly. It supports brain cells in maintaining fluidity and facilitating effective communication between neurons.(6)

Phosphatidylserine (PS) is a crucial component of the phospholipid bilayer in cell membranes, playing several important roles in cellular function and signaling. The phospholipid bilayer is a thin polar membrane made of two layers of lipid molecules. These layers are composed of hydrophobic tails and hydrophilic heads.

PS in the bilayer can interact with protein kinases and phosphatases, playing a role in intracellular phospholipase signaling pathways. These interactions can influence a range of cellular functions, from metabolism to cell growth and differentiation.

In the brain, PS is particularly important for the health and function of nerve cells. Its role in the phospholipid bilayer of neurons is critical for maintaining synaptic integrity and facilitating neurotransmission, which is essential for preventing cognitive impairment.

2. Reducing Cognitive Decline in Aging

Results from studies show that phosphatidylserine can be beneficial in the treatment of age-related cognitive decline.(7)Chronic phosphatidylserine treatment seems to improve memory and cognitive function in elderly patients, especially when used in the early stages of treatment of Parkinsonian patients with senile dementia of the Alzheimer type.

Taking phosphatidylserine supplements may include a beneficial increase in the density of the neuronal PS synthase and may reduce the amount of stress hormone cortisol, which can impair cognitive performance. The PS compound also plays an important role in apoptotic cell regulation, ensuring the removal of damaged or aged cells, working as an antibody that is crucial for maintaining healthy brain tissue.

Additionally, phosphatidylserine exposure on the surface of red blood cells, such as platelets, plays a role in the blood clotting process. The externalization of PS on platelets promotes the assembly of clotting enzyme complexes. This makes phosphatidylserine in the treatment of cognitive impairments a very viable option, however, this role is primarily observed in pathological conditions.

3. Supporting Children and Adolescents with ADHD

PS supplementation has shown promise in improving attention and cognitive function in children and adolescents with attention deficit hyperactivity disorder (ADHD).(8) It helps in modulating brain functions, potentially reducing symptoms of ADHD.

4. Reducing Stress Levels

Phosphatidylserine also has neuroprotective properties, which means it can help protect the brain from damage due to stress or other environmental factors.

By influencing cortisol levels, PS can help reduce stress and anxiety, leading to improved mental performance and mood stabilization. Additionally, phosphatidylserine can be used in the treatment of depression to help reduce stress levels, improve mood, and promote better sleep quality. It can also be used to reduce stress on the body after exercise, allowing for improved athletic preformance and reduced muscle soreness.(9)

Studies have demonstrated that PS can even help improve cardiovascular health, as it is an anti-inflammatory and can mediate cholesterol levels.(10)

5. Neuroprotective Effects

Phosphatidylserine provides neuroprotective benefits, possibly due to its role in the inhibition of reactive oxygen species, which can cause oxidative stress and damage to brain cells.(11)

Regular supplementation with PS has been linked to reduced mental fatigue, especially under stress, thereby improving mental clarity and focus.

6. Synergy with Omega-3 Fatty Acids

Both PS and DHA (docosahexaenoic acid) are key components of the phospholipid bilayer of brain cell membranes. DHA is a major omega-3 fatty acid found in the brain, and it helps in maintaining the fluidity and integrity of neuronal membranes.(12) PS, as a phospholipid, also contributes to membrane structure and function.

When omega-3 fatty acids bind to phosphatidylserine, especially docosahexaenoic acid (DHA), the synergy is responsible for PS having an increase in effectiveness when it comes to cognitive enhancement. This combination supports the function of PS in brain health and cognitive function more robustly.

Uses of Phosphatidylserine

Phosphatidylserine is utilized for its numerous benefits in brain health, cognitive function, mood regulation, and athletic performance, with its efficacy often assessed in double-blind placebo-controlled clinical trials.

Here are some of the key uses of phosphatidylserine:

  • Enhancing Cognitive Function: PS has been shown to improve memory, concentration, and the overall cognitive abilities of individuals, particularly in aging populations.
  • Reducing Symptoms of ADHD: In placebo-controlled clinical trials, potentially reducing symptoms of ADHD in children and adults, though this is an area of ongoing research.
  • Alleviating Stress and Anxiety: PS can help lower cortisol levels, a stress hormone, thereby aiding in the reduction of stress and anxiety.
  • Improving Athletic Performance: Some studies suggest that PS can help reduce muscle soreness and improve exercise performance, possibly by affecting the stress response.
  • Treatment of Alzheimer’s Disease and Dementia: PS has been investigated for its potential to slow the progression of Alzheimer’s disease and dementia, with some clinical trials showing promising results.
  • Aiding in Depression Treatment: PS might have a role in improving mood and can be used in the treatment of depression, as indicated in certain studies.
  • Boosting Brain Health in the Elderly: Regular supplementation of PS can help improve the mental function and quality of life in the elderly, potentially delaying cognitive decline.
  • Enhancing Blood Flow to the Brain: PS may help increase blood flow to the brain, thereby improving brain health and function.
  • Modulating Immune Response: Due to its role in cell signaling and membrane function, PS might influence the immune response, which can be beneficial in certain autoimmune conditions.
  • Research Tool: PS antibodies are used in scientific research to study various conditions, including the mechanisms of apoptosis and the behavior of cancer cells.

Where to Buy Phosphatidylserine

When it comes to finding the purest quality concentration of PS to catalyze your brain function and lead you toward optimal cognitive health, our top vendor is

Phosphatidylserine Side Effects and Safety

Phosphatidylserine (PS) is generally considered safe with few side effects, especially when taken at recommended dosages. However, as with any supplement, some individuals may experience adverse effects.

Here’s an overview of the potential side effects of PS:

  • Stomach Upset and Digestive Issues: Some people may experience stomach upset or digestive discomfort.
  • Insomnia: In rare cases, high doses of PS might lead to difficulty sleeping.
  • Headache: A small number of users report headaches after taking PS supplements.
  • Allergic Reactions: Although rare, some individuals might have allergic reactions to PS, particularly if they are allergic to the source of the PS (like soy).

It should be noted that while the FDA (Food and Drug Administration) does not approve dietary supplements, PS is generally recognized as safe.

Phosphatidylserine Dosage

Typical dosages used in clinical studies vary, with a standard dose being around 300 mg per day, or 100 mg PS three times a day. However, the exact dosage and administration of phosphatidylserine can depend on individual needs and medical advice. 

Phosphatidylserine in supplements is often derived from a plant-source, like soy or cabbage, making it a dietary option for those looking to support their cognitive health through supplementation.


Phosphatidylserine is a natural nootropic that can be used to improve mental performance. With the ability to improve memory, focus, and attention, phosphatidylserine is a great choice for those looking to enhance their cognitive performance!

Phosphatidylserine is also known to have a positive effect on mood and stress levels, making it a great option for those looking to manage their cortisol levels. Additionally, phosphatidylserine has been shown to have positive effects on cardiovascular health, making it a great option for those looking to maintain their overall health.

With the wide range of benefits associated with using phosphatidylserine as a nootropic, it is no wonder so many people are choosing it as their go-to supplement for cognitive enhancement.


How long does Phosphatidylserine take to work?

The effects of phosphatidylserine may start to be noticeable within a few weeks of consistent use. However, it varies among individuals and depends on factors such as dosage and overall health.

What is the elimination half-life of phosphatidylserine?

The elimination half-life of phosphatidylserine varies among individuals due to factors such as metabolism and dosage. However, it’s generally expected to be eliminated from the body within 24 hours.

Should you cycle phosphatidylserine?

Cycling phosphatidylserine isn’t typically necessary. It’s a naturally occurring substance in the body and is generally considered safe for long-term use. However, always consult a healthcare provider.

Can I stack phosphatidylserine with other nootropics? 

Yes, phosphatidylserine can be stacked with other nootropics. It’s often combined with substances like Ginkgo Biloba and Bacopa Monnieri. Always check for potential interactions.

How should I store phosphatidylserine?

Phosphatidylserine should be stored in a cool, dry place, away from direct sunlight. Most importantly, keep it out of reach of children.

Sources, Studies, and Scientific Research
  1. Kim, Hee-Yong et al. “Phosphatidylserine in the brain: metabolism and function.” Progress in lipid research vol. 56 (2014): 1-18. doi:10.1016/j.plipres.2014.06.002 ↩
  2. Küllenberg, Daniela et al. “Health effects of dietary phospholipids.” Lipids in health and disease vol. 11 3. 5 Jan. 2012, doi:10.1186/1476-511X-11-3 ↩
  3. Shiratsuchi, A et al. “Essential role of phosphatidylserine externalization in apoptosing cell phagocytosis by macrophages.” Biochemical and biophysical research communications vol. 246,2 (1998): 549-55. doi:10.1006/bbrc.1998.8663 ↩
  4. Khairova, Rushaniya A et al. “A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder.” The international journal of neuropsychopharmacology vol. 12,4 (2009): 561-78. doi:10.1017/S1461145709009924 ↩
  5. Picciotto, Marina R et al. “Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior.” Neuron vol. 76,1 (2012): 116-29. doi:10.1016/j.neuron.2012.08.036 ↩
  6. Kato-Kataoka, Akito et al. “Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints.” Journal of clinical biochemistry and nutrition vol. 47,3 (2010): 246-55. doi:10.3164/jcbn.10-62 ↩
  7. Massaad, Cynthia A, and Eric Klann. “Reactive oxygen species in the regulation of synaptic plasticity and memory.” Antioxidants & redox signaling vol. 14,10 (2011): 2013-54. doi:10.1089/ars.2010.3208 ↩
  8. Hirayama, S et al. “The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.” Journal of human nutrition and dietetics : the official journal of the British Dietetic Association vol. 27 Suppl 2 (2014): 284-91. doi:10.1111/jhn.12090 ↩
  9. Starks, Michael A et al. “The effects of phosphatidylserine on endocrine response to moderate intensity exercise.” Journal of the International Society of Sports Nutrition vol. 5 11. 28 Jul. 2008, doi:10.1186/1550-2783-5-11 ↩
  10. Darabi, Maryam et al. “Phosphatidylserine enhances anti-inflammatory effects of reconstituted HDL in macrophages via distinct intracellular pathways.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 36,5 (2022): e22274. doi:10.1096/fj.201800810R ↩
  11. Mandolesi, Laura et al. “Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits.” Frontiers in psychology vol. 9 509. 27 Apr. 2018, doi:10.3389/fpsyg.2018.00509 ↩
  12. Bradbury, Joanne. “Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain.” Nutrients vol. 3,5 (2011): 529-54. doi:10.3390/nu3050529 ↩