Phosphatidylserine Additional Information
Phosphatidylserine (PS) is a phospholipid (a fat molecule attached to a phosphate) component of the cell membrane, the outer layer of the cell. Although the membrane is the outer layer of cells, phosphatidylserine is the inner layer of the membrane. PS can be found in all cells, and it is the second most abundant phospholipid in the brain.
While your body produces PS naturally, it generally is not in sufficient quantities, especially as we age. (1,2) PS can be obtained from dietary sources such as brains and other organs (heart, spleen, kidney, liver), but not only are theses not found in typical diets, they could create hazardous health issues. There are concerns about pathogens in animal tissues that PS was originally sourced from. Since these concerns, PS is now sourced from soy lecithin. (3)
Soy-derived PS is designated as a Generally Regarded as Safe (GRAS) substance by the FDA. Additionally, the FDA gave a Qualified Health Claim status to PS that “consumption of phosphatidylserine may reduce the risk of dementia and cognitive dysfunction in the elderly”.” (4) However, that claim must be accompanied by the disclaimer “very limited and preliminary scientific research suggest that phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.” (4)
Phosphatidylserine Benefits
PS is beneficial for overall cognition through its different mechanisms at the cellular level. (5,7,8,9) PS levels decrease as we start to age, beginning as early as our 20s, which causes a decrease in concentration, memory, attention, mood, and learning. (11) PS keeps cell membranes fluid and flexible and a decrease in levels hardens the casing.
In addition to brain health and cognition, PS has shown to be beneficial in the following ways that will be discussed further in the “Phosphatidylserine Research” section:
- Reduction in stress (16)
- Improves athletic performance (17)
- Improves mood (18)
- May delay cognitive decline (19)
How to Use Phosphatidylserine
PS is an amino acid fat-soluble compound and therefore needs to be taken with food. PS supplements are found as capsules, softgels, powders, or tablets.
While PS can be found in food sources, it is difficult to obtain in that fashion. The most common dietary PS sources are; bovine brain, chicken heart, pig spleen, pig kidney, or chicken liver. Many of these foods are not found in the normal Western diet which is why supplementation with PS is recommended.
Supplementation of PS from bovine brain is not recommended as it leads to an increase in risk in contracting infectious brain diseases. At one point the primary source for PS, it is now derived from soy-lecithin. PS is commonly stacked with other cognitive enhancers such as choline sources or Uridine, a supplement that increases the synthesis of choline in the brain.
Phosphatidylserine Dosage Instructions
The average recommended dosage of PS is 300mg daily. This is typically split between two 150 mg dosages with meals. Like most dietary supplements, it is recommended to start a lower dosage (150mg) to see what kind of effects you feel from the supplement and then increase doses as needed.
It is not recommended to exceed more than 500mg of PS per day as there have been no studies indicating increasing returns from high doses.
Phosphatidylserine Safety and Side Effects
PS is reported to be a very safe supplement. Previously, PS was sourced from bovine brain which lead to a belief that you could contract Creutzfeldt-Jakob disease (CJD) – the human version of mad cow disease. Although CJD is contracted by consuming neural tissue of other living species, no cases have been reported from PS supplementation.
Presently, PS is commonly sourced from soy lecithin so should be avoided if you have a soy allergy. Not all manufacturers use soy lecithin, so check with your manufacturer prior to supplementation. Supplementation of 600mg of PS for 12 weeks in elderly individuals has shown to be safe with few reported side effects. (20)
As PS is naturally produced by the body, supplementation is typically very well tolerated. The most commonly reported side effects are insomnia or an upset stomach. However, these generally occur at higher than recommended doses.
Additional side effects may occur if you supplement with PS while taking medication for Alzheimer’s. Both of these acts as acetylcholinesterase inhibitors which would increase the amount of acetylcholine in the brain. Too much acetylcholine can lead to headaches, slow heart rate, or low blood pressure.
How Phosphatidylserine Works
While being a part of the cell membrane, PS has shown to upregulate the enzyme (Na+/K+) -stimulated ATPase which drives chemical reactions. (5) This also aids in PS’s mechanism to move solutes across the membrane. As a structural component of the cell membrane, PS can increase cell fluidity and also facilitates the entrance of nutrients and discharge of waste. (7) The fluidity (neuroplasticity) helps neurons form new connections needed for memory formation. (8)
In a similar mechanism, PS downregulated acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine. (5) Since acetylcholine is the neurotransmitter primarily responsible for memory and learning, this leads to PS’s effect on cognition.
PS also acts to activate Protein kinase C (PKC) (6). PKC leads to a multiplicity of functions in modulating membrane structure events, regulation transcription, mediating immune responses, regulating cell growth, and playing a role in learning and memory.
PS has an important role in the formation and sending of signals within neurons. (8) Signaling is brought about by proteins that are activated by PS in ways that are key to both intracellular and extracellular signaling. Extracellularly, PS is vital in triggering blood clotting and for the clearance of apoptotic (dead) cells. (8)
PS has also shown to increase Nerve Growth Factor (NGF). (9) NGF is primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain neurons. This shows potential for PS having a long-term positive impact on the brain.
Another mechanism of PS supplementation is a reduction of adrenocorticotropic hormone (ACTH) following an activity related increase. (10) ACTH regulates the levels of cortisol in your body. Following exercise or other strenuous activity, ACTH levels can spike. Since cortisol is responsible for mood, motivation, and fear, regulating ACTH helps to regulate these emotions.
Phosphatidylserine Research
Improves Cognitive Function (12,13)
18 college aged males participated in a randomized, double-blind, placebo controlled, cross-over study to examine the effects of PS on cognitive function. They were administered 400mg of PS for 14 days and then 14 days of a placebo, or vice versa. Cognitive function was measured by a Serial Subtraction Test (SST).
As a result of PS supplementation, the time needed for a correct calculation on the SST decreased by 20%, or 1.27 seconds. The total amount of errors dropped by 39% while the amount of correct calculations increased by 13%.
A separate study was conducted on 30 elderly volunteers (aged 50-90) who had complaints regarding cognitive impairment. They were administered 300mg of PS for 12 weeks and their cognitive function was measured on the parameters of executive functions and mental flexibility via a computerized battery test and a Rey Auditory Learning Test (Rey-AVLT). There was significant increase in both executive functions and mental flexibility.
These studies demonstrate the possibility of PS improving cognitive function. In addition, both studies were conducted with no adverse side effects to show that PS can be safe on humans in doses up to 400mg.
May Improve Memory (14,15)
A randomized, double-blind study was conducted on 36 children aged 4 to 14 years. These children had attention disorders and poor short-term memory. These children were administered either a placebo or 200mg of PS for 2 months. PS supplementation saw a significant increase in short-term auditory memory and differentiation and reverse differentiation.
A 3-month double-blind, placebo-controlled study was conducted to assess the impact of PS on elderly volunteers with reported memory problems. Their memory was then tested using the Wechsler Memory Scale. The patients who received PS reported a significant improvement in memory compared to those who received a placebo.
Reduction in Stress (16)
PS supplementation has shown to normalize stress induced dysregulations of the hypothalamus-pituitary-adrenal axis (HPAA). Prolonged periods of stress can induce hyper-activation of the HPAA, followed by a state of hypo-activation. A study was conducted to determine the efficacy of PS on the endocrine stress response; ACTH, saliva and serum cortisol.
This study used 75 healthy male volunteers conducted via a double-blind, placebo-controlled methodology where the volunteers either received PS or a placebo for 42 days. Stress was measured utilizing the Trier Inventory for Chronic Stress (TICS). Acute stress was induced by the Trier Social Stress Test (TSST).
PS supplementation was able to normalize ACTH, salivary and serum cortisol responses demonstrating PS’s ability to normalize the hyper-responsivity of the HPAA to an acute stressor.
Improves Athletic Performance (17)
A study was aimed at PS’s effect on athletic endurance following 10 minutes stages of cycling. A group of 14 active males were administered 750mg of PS, or a placebo, daily for ten consecutive days. The stages of cycling were performed at 45%, 55%, 65%, and 85% VO₂max (the maximum rate of oxygen consumption measured during incremental exercise) until exhaustion.
The group that was administered PS saw a significant improvement in exercise time until exhaustion compared to the placebo group. PS supplementation increased time until exhaustion from an average of 7:51 to 9:51 whereas the placebo group went from 8:09 to 8:02. This study was the first to show that PS supplementation may have a benefit on athletic performance by increasing the time until exhaustion.
Improves Mood (18)
A small study was conducted on ten elderly women who had depressive disorders. Mood was measured by The Hamilton Rating Scale for Depression, Gottfries-Bråne-Steen Rating Scale, Nurse’s Observation Scale for Inpatient Evaluation, and the Buschke Selective Reminding Test. Patients were administered a placebo for 15 days, followed by 300mg of PS for 30d days. Mood was measured before and after supplementation of the placebo and PS.
PS supplementation induced consistent improvement of depressive symptoms across the board with minor improvements in behavior and memory also observed.
May Delay Cognitive Decline (19)
There is a correlation between a drop in PS levels and cognitive decline with age. One study aimed to determine if supplementing with PS can curb or delay this cognitive decline. 157 non-dementia, elderly volunteers who had reported cognitive decline was randomized to either receive PS or a placebo for 15 weeks. Cognition was measured on the Rey Auditory Verbal Learning Test, Rey Complex Figure Test, and a computerized cognitive battery. In total, 122 of these volunteers completed the study.
Of those who had completed the study, verbal immediate recall, a strong indicator of cognitive decline associated with aging, was significantly improved in the PS group compared to the placebo group. There was s subset of the volunteers that had relatively good cognitive performance prior to supplementation and they saw a significant improvement in delayed verbal recall and learning abilities.
This study demonstrates that PS supplementation may be effective in general cognitive decline for the elderly with memory complaints.
Phosphatidylserine FAQ
What foods are high in phosphatidylserine?
Animal organs, such as bovine brain, chicken heart, pig spleen, pig kidney, or chicken liver are high in PS.
Does phosphatidylserine help you sleep?
Although not normally mentioned as a potential benefit of PS supplementation, the lowering of elevated cortisol levels more allow a more restful sleep to occur.
Is phosphatidylserine the same as phosphatidylcholine?
Phosphatidylserine is the inner layer of the cell membrane while phosphatidylcholine is the outer layer of the membrane. While both are beneficial for cognitive function and memory, phosphatidylserine aids in increasing attention and processing speed while phosphatidylcholine can increase choline levels.
Is all phosphatidylserine now made from soy?
No, some manufacturers use cabbage or sunflower.
Can you take the entire dose of phosphatidylserine at once?
It is best to split your dosage of PS over the course of the day to maintain appropriate levels.
What is a good stack with phosphatidylserine?
PS is most commonly stacked with other cognitive enhances such as uridine or a choline source for cognitive enhancement.
Cited Sources
- https://www.ncbi.nlm.nih.gov/pubmed/6310426
- https://www.ncbi.nlm.nih.gov/pubmed/6397694
- https://www.ncbi.nlm.nih.gov/pubmed/18846580
- http://wayback.archive-it.org/7993/20171114183737/https://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm072999.htm
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1153623/
- https://www.ncbi.nlm.nih.gov/pubmed/7251589
- https://www.ncbi.nlm.nih.gov/pubmed/24992464
- https://www.ncbi.nlm.nih.gov/pubmed/23775696
- https://www.ncbi.nlm.nih.gov/pubmed/27997532
- https://www.ncbi.nlm.nih.gov/pubmed/2170852
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565322/
- https://www.ncbi.nlm.nih.gov/pubmed/22017963
- https://www.ncbi.nlm.nih.gov/pubmed/23723695
- https://www.ncbi.nlm.nih.gov/pubmed/23495677
- https://www.ncbi.nlm.nih.gov/pubmed/25414047
- https://www.ncbi.nlm.nih.gov/pubmed/25081826
- https://www.ncbi.nlm.nih.gov/pubmed/16394955
- https://www.ncbi.nlm.nih.gov/pubmed/1693032
- https://www.ncbi.nlm.nih.gov/pubmed/20523044/
- https://www.ncbi.nlm.nih.gov/pubmed/12385596
