Phosphatidylserine

Last Updated: January 3, 2024

Phosphatidylserine (PS) is an amino acid derivative that is fat-soluble and found in high amounts in the brain, where it contributes to cognitive functioning. PS has been studied the most for cognition in adults over 50, high chronic stress, and exercise performance, though the effects of PS are inconsistent.

Phosphatidylserine is most often used for

What is phosphatidylserine?

Phosphatidylserine is a major lipid of mammalian cell membranes,[1] comprising 15% of the total phospholipids in the human brain.[2] It was originally extracted from the brains of cattle in the 1990’s,[3] but has since been derived from soy due to safety concerns in regards to Mad Cow Disease.[4][2] PS is sometimes studied alongside the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), since PS is attached to DHA molecules in the brain.[2]

What are phosphatidylserine’s main benefits?

Overall, PS seems to have inconsistent benefits in randomized controlled trials. Slightly more consistent benefits are found in trials examining PS for cognition in adults over aged 50, at dosages of 100–300 mg per day, for 2–6 months.[5][4][6][7] There also might be benefits for perceived stress levels in individuals with high chronic stress, though the effects are inconsistent, and the studies have serious limitations.[8][9][10] PS has also been studied in the context of physical activity, though effects of PS here are even less consistent.[11][12][13][14][15]

What are phosphatidylserine’s main drawbacks?

Many trials examining PS do not comment on adverse events.[11][12][13][14][15][8][10][16] However in the trials that do, there does not appear to be a significantly increased risk of adverse events compared to the control groups. [17][2][7][5]

Randomized controlled trials (RCTs) where PS was given at 300–600 mg per day for 3–6 months in adults over age 50 have not noted significantly increased adverse effects in the PS groups compared to the control groups.[17][2][7][5]

In children with ADHD given PS, there were no major adverse events in the PS groups, though there were some cases of gastrointestinal discomfort.[18] This gastrointestinal discomfort may be minimized by consuming PS with food.[5]

The researchers in 5 RCTs examining PS supplementation in athletes did not comment on adverse events. [11][12][13][14][15] These studies have the advantages of often having high PS dosages (600 mg or 750 mg per day), though PS was given for shorter durations (7 to 10 days).[11][12][13]

In 3 RCTs[8][9][10] examining PS supplementation in participants with chronic stress, only one study commented on adverse event rates; in a study of 60 participants, there were 9 cases of adverse events in the placebo group, and 2 in the PS group.[9]

How does phosphatidylserine work?

PS works by affecting the hypothalamic-pituitary-adrenal (HPA) axis in the brain. This is a pathway where perceived stress causes the hypothalamus to release corticotropin-releasing factor, which causes the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH promotes the release of cortisol from the adrenal glands. PS may work by reducing ACTH and cortisol levels.[8][10]

Supplemental PS can cross the blood brain barrier, where it supports communication of brain cells,[19] and affects memory, learning and language processes.[20]

What else is Phosphatidylserine known as?
Note that Phosphatidylserine is also known as:
  • PS
Phosphatidylserine should not be confused with:
  • Serine
Dosage information

A standard dose of phosphatidylserine (PS) is 100mg, taken 3 times a day to total 300mg daily. This dose seems to be effective as a daily preventative against cognitive decline, and 100mg once daily may provide some degree of benefit (but may be lesser than 300mg).

Studies in children and adolescents for the purpose of attention improvement tend to use 200mg, and a dose of 200-400mg has been used in adult non-elderly humans with success. Animal evidence tends to use a dose correlating to 550mg as well.

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References
  1. ^Mozzi R, Buratta S, Goracci GMetabolism and functions of phosphatidylserine in mammalian brain.Neurochem Res.(2003-Feb)
  2. ^Vakhapova V, Richter Y, Cohen T, Herzog Y, Korczyn ADSafety of phosphatidylserine containing omega-3 fatty acids in non-demented elderly: a double-blind placebo-controlled trial followed by an open-label extension.BMC Neurol.(2011-Jun-28)
  3. ^Crook T, Petrie W, Wells C, Massari DCEffects of phosphatidylserine in Alzheimer's diseasePsychopharmacol Bull.(1992)
  4. ^Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn ADPhosphatidylserine 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)
  5. ^Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn ADPhosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trialDement Geriatr Cogn Disord.(2010)
  6. ^Moré MI, Freitas U, Rutenberg DPositive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer's disease and dementia.Adv Ther.(2014-Dec)
  7. ^Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi GCognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration.Aging (Milano).(1993-Apr)
  8. ^Hellhammer J, Vogt D, Franz N, Freitas U, Rutenberg DA soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study.Lipids Health Dis.(2014-Jul-31)
  9. ^Hellhammer J, Hero T, Franz N, Contreras C, Schubert MOmega-3 fatty acids administered in phosphatidylserine improved certain aspects of high chronic stress in men.Nutr Res.(2012-Apr)
  10. ^Hellhammer J, Fries E, Buss C, Engert V, Tuch A, Rutenberg D, Hellhammer DEffects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stressStress.(2004 Jun)
  11. ^Starks MA, Starks SL, Kingsley M, Purpura M, Jäger RThe effects of phosphatidylserine on endocrine response to moderate intensity exercise.J Int Soc Sports Nutr.(2008-Jul-28)
  12. ^Kingsley MI, Miller M, Kilduff LP, McEneny J, Benton DEffects of phosphatidylserine on exercise capacity during cycling in active malesMed Sci Sports Exerc.(2006 Jan)
  13. ^Kingsley MI, Kilduff LP, McEneny J, Dietzig RE, Benton DPhosphatidylserine supplementation and recovery following downhill runningMed Sci Sports Exerc.(2006 Sep)
  14. ^Wells AJ, Hoffman JR, Gonzalez AM, Stout JR, Fragala MS, Mangine GT, McCormack WP, Jajtner AR, Townsend JR, Robinson EHPhosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans.Nutr Res.(2013-Jun)
  15. ^Parker AG, Gordon J, Thornton A, Byars A, Lubker J, Bartlett M, Byrd M, Oliver J, Simbo S, Rasmussen C, Greenwood M, Kreider RBThe effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exerciseJ Int Soc Sports Nutr.(2011 Oct 21)
  16. ^Alisha Bruton, Joy Nauman, Douglas Hanes, Melissa Gard, Angela SendersPhosphatidylserine for the Treatment of Pediatric Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-AnalysisJ Altern Complement Med.(2021 Feb 4)
  17. ^Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJSafety of soy-derived phosphatidylserine in elderly people.Nutr Neurosci.(2002-Oct)
  18. ^Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman AThe effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extensionEur Psychiatry.(2012 Jul)
  19. ^Vance JE, Steenbergen RMetabolism and functions of phosphatidylserine.Prog Lipid Res.(2005-Jul)
  20. ^Chengxiang Zhang, Qi Hu, Shifen Li, Feifei Dai, Wen Qian, Susan Hewlings, Ting Yan, Yubang WangA Magtein®, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese AdultsNutrients.(2022 Dec 8)
  21. ^Baumeister J, Barthel T, Geiss KR, Weiss MInfluence of phosphatidylserine on cognitive performance and cortical activity after induced stressNutr Neurosci.(2008 Jun)
  22. ^Kennedy DO, Haskell CF, Mauri PL, Scholey ABAcute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserineHum Psychopharmacol.(2007 Jun)
  23. ^Nanci S Guest, Trisha A VanDusseldorp, Michael T Nelson, Jozo Grgic, Brad J Schoenfeld, Nathaniel D M Jenkins, Shawn M Arent, Jose Antonio, Jeffrey R Stout, Eric T Trexler, Abbie E Smith-Ryan, Erica R Goldstein, Douglas S Kalman, Bill I CampbellInternational society of sports nutrition position stand: caffeine and exercise performanceJ Int Soc Sports Nutr.(2021 Jan 2)
  24. ^Schohraya Spahis, Michel Vanasse, Stacey A Bélanger, Parviz Ghadirian, Emilie Grenier, Emile LevyLipid profile, fatty acid composition and pro- and anti-oxidant status in pediatric patients with attention-deficit/hyperactivity disorderProstaglandins Leukot Essent Fatty Acids.(Jul-Aug 2008)
  25. ^Jeffrey A Stanley, Heidi Kipp, Erika Greisenegger, Frank P MacMaster, K Panchalingam, Jay W Pettegrew, Matcheri S Keshavan, Oscar G BuksteinRegionally specific alterations in membrane phospholipids in children with ADHD: An in vivo 31P spectroscopy studyPsychiatry Res.(2006 Dec 1)
  26. ^Suzanne M Czerniak, Elif M Sikoglu, Jean A King, David N Kennedy, Eric Mick, Jean Frazier, Constance M MooreAreas of the brain modulated by single-dose methylphenidate treatment in youth with ADHD during task-based fMRI: a systematic reviewHarv Rev Psychiatry.(2013 May-Jun)
Examine Database References
  1. Reaction Time - Jorissen BL, Brouns F, Van Boxtel MP, Ponds RW, Verhey FR, Jolles J, Riedel WJThe influence of soy-derived phosphatidylserine on cognition in age-associated memory impairmentNutr Neurosci.(2001)
  2. Heart Rate - Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori TSoybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaintsJ Clin Biochem Nutr.(2010 Nov)
  3. Cognition - Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn ADPhosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trialDement Geriatr Cogn Disord.(2010)
  4. Cognitive Decline - Engel RR, Satzger W, Günther W, Kathmann N, Bove D, Gerke S, Münch U, Hippius HDouble-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer typeEur Neuropsychopharmacol.(1992 Jun)
  5. Cognitive Decline - Klinkhammer P, Szelies B, Heiss W.D.Effect of Phosphatidylserine on Cerebral Glucose Metabolism in Alzheimer's DiseaseDementia and Geriatric Cognitive Disorders.()
  6. Cognitive Decline - Crook T, Petrie W, Wells C, Massari DCEffects of phosphatidylserine in Alzheimer's diseasePsychopharmacol Bull.(1992)
  7. Attention - Hirayama S, Terasawa K, Rabeler R, Hirayama T, Inoue T, Tatsumi Y, Purpura M, Jäger RThe effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trialJ Hum Nutr Diet.(2013 Mar 17)
  8. ADHD Symptoms - Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman AThe effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extensionEur Psychiatry.(2012 Jul)
  9. Cortisol - Parker AG, Gordon J, Thornton A, Byars A, Lubker J, Bartlett M, Byrd M, Oliver J, Simbo S, Rasmussen C, Greenwood M, Kreider RBThe effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exerciseJ Int Soc Sports Nutr.(2011 Oct 21)
  10. Stress Signs and Symptoms - Baumeister J, Barthel T, Geiss KR, Weiss MInfluence of phosphatidylserine on cognitive performance and cortical activity after induced stressNutr Neurosci.(2008 Jun)
  11. Exercise-Induced Oxidation - Kingsley MI, Kilduff LP, McEneny J, Dietzig RE, Benton DPhosphatidylserine supplementation and recovery following downhill runningMed Sci Sports Exerc.(2006 Sep)
  12. Memory - Schreiber S, Kampf-Sherf O, Gorfine M, Kelly D, Oppenheim Y, Lerer BAn open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive declineIsr J Psychiatry Relat Sci.(2000)
  13. Fatigue Symptoms - Kingsley MI, Miller M, Kilduff LP, McEneny J, Benton DEffects of phosphatidylserine on exercise capacity during cycling in active malesMed Sci Sports Exerc.(2006 Jan)
  14. Golf Performance Metrics - Ralf Jäger, Martin Purpura, Kurt-Reiner Geiss, Michael Wei, Jochen Baumeister, Francesco Amatulli, Lars Schröder, and Holger HerwegenThe effect of phosphatidylserine on golf performanceJISSN.()
  15. Blood Lactate (Exercise) - Monteleone P, Maj M, Beinat L, Natale M, Kemali DBlunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy menEur J Clin Pharmacol.(1992)