Phosphatidylserine (PS), also known as serine phospholipid or diacylglycerophosphatidylserine, is a widely distributed phospholipid typically located in the inner leaflet of cell membranes. As a phospholipid compound belonging to the phosphoglyceride class, it is a component of cell membranes and is involved in a series of membrane functions. Particularly within the human nervous system, it serves as a crucial component of brain cell membranes. It plays a significant regulatory role in various brain functions—especially memory and emotional stability—by influencing cell membrane fluidity and permeability while activating the metabolism and synthesis of multiple enzymes. For instance, human red blood cell membranes contain phosphatidylcholine (19%), sphingomyelin (8%), phosphatidylethanolamine (16%), and phosphatidylserine (10%). Only the latter carries a net negative charge on the cell membrane, contributing to membrane asymmetry. It can also activate tissue plasminogen activator on damaged surfaces. In vivo, it interconverts with phosphatidylcholine and phosphatidylethanolamine. Due to the variability of R1 and R2 groups, phosphatidylserine effectively serves as a general term for a class of compounds.

First isolated and characterized by Jordi Folch in 1942. PS consists of three parts: a hydrophilic glycerol backbone forming the head, and two longer hydrocarbon chains forming the hydrophobic tails. The head comprises three groups: a serine residue linked to a phosphate residue, which in turn connects to the C-3 hydroxyl group of glycerol; the other two hydroxyl groups of glycerol form esters with fatty acids to compose the tails. The fatty acid at the C-2 position of glycerol typically possesses a longer carbon chain and more unsaturated bonds compared to the fatty acid at the C-1 position. Phosphatidylserine (PS) refers to a group of compounds rather than a single component, as the acetyl residue varies significantly depending on the source material used for extraction. PS exhibits amphiphilic properties, meaning it is both hydrophilic and lipophilic. Its structure determines its unique characteristics: the negatively charged head group is hydrophilic (or water-soluble), while the tail composed of fatty acids is lipophilic (or fat-soluble).

The product appears as a white or pale yellow loose powder that emulsifies in water. It is insoluble in ethanol and methanol but soluble in chloroform, diethyl ether, and petroleum ether. Synthetic versions are soluble only in chloroform. When extracted from bovine brain and exposed to air at room temperature, it undergoes approximately 0.5% daily degradation. Natural sources (L-α-Phosphatidyl-L-Serine) are primarily extracted from bovine (or ovine) brain or soybeans. Due to variations in R1 and R2, it is actually a mixture of numerous compounds. For example, the approximate composition of R1 and R2 in bovine brain products is: 16:0, about 1%; 18:0, 40%–41%; 18:1, 28%–30%; 18:3, about 4%; 18:4, about 1%; 20:4, about 1%; 20:5, about 2%; 22:6, 9%–14%. Synthetic products contain numerous isomers, making purification complex. For example, the synthetic product 1,2-Di(hexacosyl)-rac-glycerol-3-phosphate-L-serine, C38H74NO10P, has a molecular weight of 336.0.

Phosphatidylserine (PS) can be synthesized by the human body using serine. It influences chemical signaling in the brain and assists brain cells in storing and retrieving information, making it a crucial nutrient for maintaining normal memory, reaction times, and healthy emotional function.

Primary Benefits

Phosphatidylserine (PS) is hailed as a major emerging “smart nutrient” following choline and the “brain gold” DHA. Experts believe this natural substance helps maintain cell membrane flexibility and enhances the efficiency of neurotransmitters that transmit brain signals, supporting efficient brain function and stimulating brain activation. Specifically, phosphatidylserine offers the following benefits:

(1) Enhances brain function, improves concentration, and boosts memory.

Numerous meta-analyses of phosphatidylserine have emerged in Europe and America. Meta-analysis systematically synthesizes quantitative or qualitative results from multiple independent studies on a specific topic, aiming to provide a more objective synthesis of previous research findings. One analysis examined nine double-blind, placebo-controlled clinical trials involving 1,224 participants. Results demonstrated significant improvements in cognitive and memory parameters following PS supplementation. Undoubtedly, PS supplementation enhances long-term memory, sustained cognitive function, and the ability to speak freely and logically.

With advancing age, phosphatidylserine and other vital brain chemicals gradually diminish, leading to weakened memory and cognitive function. Supplementing with phosphatidylserine increases the number of brain synapses, enhances the fluidity of brain cell membranes, and promotes glucose metabolism within brain cells. This activates brain cells, improves concentration, heightens alertness, and boosts memory. Phosphatidylserine supplements are widely used in Italy, Scandinavia, and other European countries to treat age-related cognitive impairment and memory loss in the elderly.

(2) Enhancing Student Performance.

A double-blind, placebo-controlled study specifically tested PS's effects on alleviating mental stress. Healthy college students received 300 mg of PS daily for 30 consecutive days. Participants completed challenging math tests within timed constraints while their stress responses were monitored. Results showed that students taking phosphatidylserine outperformed the control group in reaction time, confidence, and overall performance, achieving higher test scores. A separate study involving 120 senior high school students at Chongqing Zhongshu Middle School found that after 40 days of taking enhanced phosphatidylserine, participants demonstrated significant improvements in both verbal and non-verbal memory.

(3) Alleviating stress, promoting recovery from mental fatigue, and balancing emotions.

Multiple studies indicate that phosphatidylserine significantly reduces excess stress hormone levels in individuals experiencing work-related tension, alleviating pressure and relieving mental fatigue. It also influences neurotransmitter levels affecting mood within the brain, promoting concentration, alertness, and memory while helping mitigate negative emotions such as depression and discouragement.

(4) Aiding in the repair of brain damage.

As a primary component of brain neurons, phosphatidylserine nourishes and activates various enzymes in the brain. It slows the depletion of neurotransmitters, aids in repairing and renewing damaged brain cells, and helps eliminate harmful substances. It can restore elderly individuals' memory to levels seen 14 years prior. Research indicates that after 12 weeks of phosphatidylserine supplementation, a 66-year-old achieved the memory capacity of a 52-year-old.

Additionally, phosphatidylserine and DHA enhance each other's absorption and protect nerve cells. Adequate phosphatidylserine increases cell membrane fluidity, promoting intellectual development. Together, phosphatidylserine and DHA protect the central nervous system and support fetal brain development.

Research indicates that PS enhances cognitive function primarily by rapidly crossing the blood-brain barrier to enter the brain. There, it relaxes smooth muscle cells in cerebral capillaries, increasing cerebral blood supply. Consequently, many recent stroke-related products utilize PS as an ingredient.

Sources of PS

Phosphatidylserine [4] is a naturally occurring component in foods, including breast milk. It is present in meat and fish, with higher concentrations in brain tissue and organs such as liver and kidneys. Dairy products and vegetables (excluding legumes) contain very little phosphatidylserine.

Changes in modern dietary habits (such as avoiding organ meats), increased awareness of health foods (e.g., low-fat, low-cholesterol options and reduced meat consumption), and food crises (like mad cow disease and foot-and-mouth disease) have led to a significant decline in PS intake. More critically, the natural phospholipid content in industrially produced fats and oils has declined, further reducing the daily PS intake for most individuals. Generally, a diet rich in meat and fish provides approximately 180 mg of PS per day. However, in low-fat diets, daily PS intake may drop to just 100 mg or even below 50 mg. Statistics indicate that the daily PS intake gap between normal consumption and actual requirements ranges from 70–150 mg for the general population, with vegetarians experiencing a particularly severe deficiency gap of 200–250 mg. Given these factors, healthy individuals require daily supplementation of 100–300 mg of pure phosphatidylserine. This is especially crucial for vegetarians, those on low-fat or low-cholesterol diets, and the elderly. Additionally, certain dietary habits can reduce brain phosphatidylserine levels. For instance, insufficient omega-3 fatty acids in the diet lowers brain phosphatidylserine content by 28%, thereby altering biochemical functions in the hippocampus.

Internationally Certified

As a bioactive substance, phospholipids possess unique physicochemical properties and nutritional value. They are widely utilized globally in the food, health supplement, pharmaceutical, and feed industries. Consuming phospholipids can help regulate blood lipids, improve memory, protect the liver, enhance brain function, and delay aging. Phosphatidylserine (PS), a member of the phospholipid family, is the only phospholipid capable of regulating the functional state of key cell membrane proteins and is an essential substance for the human body. Therefore, regular consumption of phosphatidylserine dietary supplements does not impose additional burdens on the body and has been certified by regulatory authorities in numerous countries.

In May 2006, the Korean Food and Drug Administration (KFDA) permitted prominent labeling on PS-enriched products, allowing claims such as “improving negative emotions,” “enhancing memory,” and preventing dementia.

In October 2006, PS (phosphatidylserine) received GRAS (Generally Recognized as Safe) status from the U.S. Food and Drug Administration (FDA). This designation permits PS (phosphatidylserine) to be added as a nutritional fortifier in functional foods such as yogurt, milk powder, bread, and powdered beverages.

PS (phosphatidylserine) is listed in Japan's Ministry of Health, Labour and Welfare (MHLW) catalog of food ingredients (non-pharmaceuticals) and passed individual review as a food additive on February 5, 2010.

PS (phosphatidylserine) was added to the New Resource Food Catalog by the former Ministry of Health of China (now renamed the National Health and Family Planning Commission) on October 21, 2010, permitting its use as a new resource food.

Application Scope

Currently, there are few phosphatidylserine products available on the Chinese market that can be consumed with meals. Common ones include Nature's Bounty Memory Essentials from the United States, GNC Phosphatidylserine, Puritan's Pride Brain Phospholipid PS, Baolimei Algal Oil DHA Softgels with added phosphatidylserine, and Brain Gold Phosphatidylserine DHA Complex Tablets.

Due to the promising efficacy of phosphatidylserine in enhancing children's cognitive development, domestic companies are increasingly incorporating phosphatidylserine into their products. Notable examples include: Children's Milk produced by Chongqing Tianyou Company, Children's Beverage produced by Henan Huahua Niu Company, and Children's Yogurt produced by Xuzhou Lujian Company.

In April 2015, Shijiazhuang Junlebao Dairy pioneered China's first PS-fortified infant formula, establishing a new benchmark for premium children's milk powder.

Experimental Research

Researchers conducted population testing on the memory-enhancing effects of pure milk fortified with phosphatidylserine. (PS raw material at 50% purity was added at a ratio of 0.08% to pure fresh milk, processed into PS milk using ultra-high temperature sterilization.)

Subjects: 120 senior high school students (60 male, 60 female). Results showed significant memory improvement after 40 days of daily 250ml PS milk consumption. High school students receiving 250ml milk fortified with 100mg PS (soy-derived) daily demonstrated markedly enhanced memory after 40 days.

Dr. T.H. Crook of the Memory Assessment Clinics collaborated with Vanderbilt University Medical Center, Stanford University Medical Center, and an Italian pharmaceutical company to conduct a study involving 149 volunteers aged 50 to 75. Participants took either 300mg of phosphatidylserine (PS) daily (divided into three 100mg doses) or a placebo over a 12-week trial period. Assessment tests were conducted before and after the study, with a 4-week follow-up post-intervention. Results showed excellent tolerability of phosphatidylserine. After three weeks of treatment, improvements were observed in naming and recognizing faces, recalling names and faces, and facial recognition. Since these improvements did not remain stable throughout the 12-week study, researchers formed a separate subgroup of 57 participants with more severe memory impairment, averaging 64.3 years of age. Although their performance in recognizing names remained inconsistent, they showed significant improvements in memorizing phone numbers, recalling misplaced objects, sentence recall, and attention during reading, conversation, and task execution after receiving PS treatment. Researchers noted that phosphatidylserine improved this group's performance in recognizing names and faces by an average of 2 points, effectively “turning back the clock” to make them appear 12 years younger. In other words, it restored their cognitive abilities from an average of 64 years old to that of an average 52-year-old. Subsequently, researchers conducted a study involving 51 participants aged 55-85 (average age 71), including a placebo control group. In this randomized, double-blind trial, subjects receiving PS treatment took 300 mg of PS daily for 12 weeks. Results showed improvements in the following areas: (1) remembering distinct names of people who look alike and recalling them during meetings; (2) recalling misplaced items; (3) recalling details of events from the previous day and week. Attention and alertness were also enhanced.

PS (phosphatidylserine) not only nourishes the brains of the elderly but also alleviates physical and mental stress in healthy young adults.

Meta-Analysis

Numerous meta-analyses of PS have emerged in Europe and America. A meta-analysis systematically synthesizes the results of multiple independent studies on a specific issue, either quantitatively or qualitatively, with the primary aim of providing a more objective synthesis of previous research findings. Cenacchietal. analyzed nine double-blind, placebo-controlled clinical trials involving 1,224 participants, using cognitive and memory parameters as indicators. The results showed significant improvements in cognitive and memory parameters after PS supplementation compared to placebo and baseline values. Undoubtedly, PS supplementation enhances long-term memory, sustained cognition, and the ability to speak freely and logically.

Early PS research utilized bovine brain-derived PS (bovine cortical PS). Following the emergence of BSE (mad cow disease) in the UK, all bovine-derived PS studies were discontinued due to safety concerns. In the mid-1990s, the Lucas Meyer Bioactive Substances Division pioneered the extraction of high-purity PS from soybeans through relentless innovation, naming it Leci®-PS. Both animal studies and clinical trials confirmed that soy-derived PS is as effective as bovine PS. In 1998, Crook studied 50 individuals with an average age of 60.5 years who consumed Leci®-PS. After three months, assessments of memory and cognitive parameters revealed not only no difference compared to those taking bovine PS (BC-PS), but Leci®-PS actually yielded superior results.

Phosphatidylserine [3] can reverse age-related memory deficits, demonstrating exceptional efficacy in enhancing learning and name recall. It can restore your ability to remember names to a level comparable to 14 years prior. In other words, after 12 weeks of Leci®-PS supplementation, a 66-year-old can achieve the memory capacity of a 52-year-old.

Phosphatidylserine not only nourishes the elderly brain but also alleviates physical and mental stress in healthy young adults.

A dedicated study tested PS's stress-relieving effects using a double-blind, placebo-controlled trial. Healthy young college students received 300mg of phosphatidylserine daily for 30 consecutive days. Participants completed challenging math tests within timed constraints, with stress responses measured via heart rate and self-reported test anxiety levels. PS users demonstrated superior reaction times, confidence, and performance compared to the control group, and achieved higher test scores.

Additionally, other double-blind studies demonstrated that phosphatidylserine effectively reduces the secretion of stress hormones in young individuals under pressure. Further research examined the effects of PS supplementation on healthy young adults experiencing physical and mental stress. Results indicated PS significantly alleviated stress, markedly improved test subjects' performance, and elevated visual analog scale (VAS) scores (used to evaluate an individual's overall responsiveness). The VAS measures subjects' self-assessment of attention, alertness, and memory during prescribed movements and the General Motor Ability Test (GMAT). PS's function primarily stems from its action on the central nervous system (CNS), enhancing alertness and attention to improve performance.