Phosphatidylserine is a phospholipid component integral to cellular membranes, particularly in the brain. It plays a role in maintaining membrane fluidity, integrity, and functionality.

Literature Review

Oral phosphatidylserine, particularly when sourced from bovine cortex, has shown promise in enhancing attention and memory in individuals experiencing age-related cognitive decline. However, it's not yet clear whether the plant-based versions have the same benefits, or if phosphatidylserine can help in preventing cognitive decline.

Studies involving people with age-related cognitive decline have demonstrated that phosphatidylserine improves various cognitive functions like attention, alertness, verbal fluency, and memory. The dosages commonly used in these studies were 100 mg of bovine- or plant-sourced phosphatidylserine, taken three times daily for up to six months.[i],[ii],[iii],[iv],[v]

While most of the research has been focused on bovine cortex-derived phosphatidylserine, many supplements now use versions derived from soy or cabbage. Preliminary data suggest that plant-sourced phosphatidylserine could also be beneficial for memory in people with age-related memory and cognitive decline.[v]

A particular study involving elderly women complaining of memory loss showed that taking 1-3 capsules daily, which includes soybean-derived phosphatidylserine along with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), modestly improved immediate memory and sustained attention over 15 weeks when compared to a placebo.[vi]

A further analysis of this study indicated that the improvements in cognitive function were most pronounced in patients who had relatively better cognitive performance to begin with.[vii]

Regulatory Perspective: In 2003, the U.S. Food and Drug Administration (FDA) permitted a qualified health claim that consuming phosphatidylserine might reduce the risk of age-related cognitive decline. However, the FDA has determined that there is very little scientific evidence supporting this claim[viii].

Oral intake of phosphatidylserine has been shown to improve both cognitive function and behavioral metrics over a treatment period ranging from 6 to 12 weeks.[ix]

Mechanism of Action

General: Phosphatidylserine is a crucial fat-soluble phospholipid found naturally in humans and is particularly abundant in the brain. It plays essential roles in various cell membrane functions, such as maintaining cellular homeostasis, facilitating signal transmission, and regulating cell growth.[x] Additionally, phosphatidylserine is a part of the mitochondrial membrane, potentially serving as a metabolic reservoir for other phospholipids.[xi] While the human body can synthesize this compound, most of it is obtained exogenously through diet.

Anti-stress effects: Phosphatidylserine is being studied for its potential to mitigate stress induced by exercise and mental tasks. Initial research suggests that it may reduce levels of cortisol and adrenocorticotropin hormone after intense exercise.[xii],[xiii],[xiv] There's also some early evidence that 300 mg of phosphatidylserine per day could improve mood and perceived stress during mentally challenging tests.[xv]

Neurologic effects: The mechanism by which phosphatidylserine benefits conditions like dementia or age-related memory impairment is not fully understood. However, one theory posits that it could help normalize abnormal lipid composition in brain cell membranes, thereby restoring normal neurotransmitter function.[xvi] Phosphatidylserine has been found to increase levels of neurotransmitters like acetylcholine, norepinephrine, serotonin, and dopamine in animal studies and Alzheimer's patients.133

Studies in animal models indicate that the concentration of phosphatidylserine in the brain decreases with age.[xvii] Such research also shows that phosphatidylserine may improve spatial memory and passive avoidance behavior in animals. Moreover, it appears to reduce age-associated losses in neuronal dendrites and the atrophy of cholinergic neurons.135


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[iii]Villardita C, Grioli S, Salmeri G, et al. Multicentre clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration. Clin Trials J 1987;24:84-93.

[iv]Palmieri G, Palmieri R, Inzoli MR, et al. Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration. Clin Trials J 1987;24:73-83.

[v]Schreiber S, Kampf-Sherf O, Gorfine M, et al. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302-7.

[vi]Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geriatr Cogn Disord. 2014;38(1-2):39-45.

[vii]Vakhapova, V., Cohen, T., Richter, Y., Herzog, Y., and Korczyn, A. D. Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial. Dement.Geriatr Cogn Disord 2010;29(5):467-474.

[viii]FDA. Qualified Health Claim: Final Decision Letter - Phosphatidylserine and Cognitive Dysfunction and Dementia. May 2003. Available at: Accessed on March 18, 2020.

[ix]Heiss WD, Kessler J, Mielke R, et al. Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation. Dementia 1994;5:88-98.

[x]Blokland A, Honig W, Brouns F, Jolles J. Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS. Nutrition 1999;15:778-83.

[xi]Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.

[xii]Fahey TD, Pearl MS. The hormonal and perceptive effects of phosphatidylserine administration during two weeks of resistive exercise-induced overtraining. Biol Sport 1998;15:135-44.

[xiii]Monteleone P, Beinat L, Tanzillo C, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 1990;52:243-8.

[xiv]Monteleone P, Maj M, Beinat L, et al. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol 1992;42:385-8.

[xv]Benton D, Donohoe RT, Sillance B, Nabb S. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci 2001;4:169-78.

[xvi]Gatti, C., Cantelmi, M. G., Brunetti, M., Gaiti, A., Calderini, G., and Teolato, S. Effect of chronic treatment with phosphatidyl serine on phospholipase A1 and A2 activities in different brain areas of 4 month and 24 month old rats. Farmaco Sci. 1985;40(7):493-500.

[xvii]Schreiber S, Kampf-Sherf O, Gorfine M, et al. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302-7.