Sports Medicine

, Volume 36, Issue 8, pp 657–669 | Cite as

Effects of Phosphatidylserine Supplementation on Exercising Humans

  • Michael KingsleyEmail author
Review Article


Phosphatidylserine (PtdSer) is a ubiquitous phospholipid species that is normally located within the inner leaflet of the cell membrane. PtdSer has been implicated in a myriad of membrane-related functions. As a cofactor for a variety of enzymes, PtdSer is thought to be important in cell excitability and communication. PtdSer has also been shown to regulate a variety of neuroendocrine responses that include the release of acetylcholine, dopamine and noradrenaline. Additionally, PtdSer has been extensively demonstrated to influence tissue responses to inflammation. Finally, PtdSer has the potential to act as an effective antioxidant, especially in response to iron-mediated oxidation.

The majority of the available research that has investigated the effects of PtdSer supplementation on humans has concentrated on memory and cognitive function; patients experiencing some degree of cognitive decline have traditionally been the main focus of investigation. Although investigators have administered PtdSer through intravenous and oral routes, oral supplementation has wider appeal. Indeed, PtdSer is commercially available as an oral supplement intended to improve cognitive function, with recommended doses usually ranging from 100 to 500 mg/day. The main sources that have been used to derive PtdSer for supplements are bovine-cortex (BC-PtdSer) and soy (S-PtdSer); however, due to the possibility of transferring infection through the consumption of prion contaminated brain, S-PtdSer is the preferred supplement for use in humans. Although the pharmacokinetics of PtdSer have not been fully elucidated, it is likely that oral supplementation leads to small but quantifiable increases in the PtdSer content within the cell membrane.

A small number of peer-reviewed full articles exist that investigate the effects of PtdSer supplementation in the exercising human. Early research indicated that oral supplementation with BC-PtdSer 800 mg/day moderated exercise-induced changes to the hypothalamo-pituitary-adrenal axis in untrained participants. Subsequently, this finding was extended to suggest that S-PtdSer 800 mg/day reduced the cortisol response to overtraining during weight training while improving feeling of well-being and decreasing perceived muscle soreness. However, equivocal findings from our laboratory might suggest that the dose required to undertake this neuroendocrine action may vary between participants.

Interestingly, recent findings demonstrating that short-term supplementation with S-PtdSer 750 mg/day improved exercise capacity during high-intensity cycling and tended to increase performance during intermittent running might suggest an innovative application for this supplement. With the findings from the existing body of literature in mind, this article focuses on the potential effects of PtdSer supplementation in humans during and following exercise.


Muscle Damage Bovine Spongiform Encephalopathy Muscle Soreness Creatine Kinase Activity Oral Supplementation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of this manuscript. The views and opinions contained in this review are those of the author alone. The author has no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Folch J, Schneider HA. An amino acid constituent of ox brain cephalin. J Biol Chem 1941; 137: 51–62Google Scholar
  2. 2.
    Blokland A, Honig W, Browns F, et al. 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: 778–783PubMedCrossRefGoogle Scholar
  3. 3.
    Sakai M, Yamatoya H, Kudo S. Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents. J Nutr Sci Vitaminol 1996; 42: 47–54PubMedCrossRefGoogle Scholar
  4. 4.
    Vance JE, Steenbergen R. Metabolism and functions of phosphatidylserine. Prog Lipid Res 2005; 44: 207–234PubMedCrossRefGoogle Scholar
  5. 5.
    Souci SW, Fachmann E, Kraut H. Food composition and nutrition tables. Stuttgart: Medpharm Scientific Publishers, 2000Google Scholar
  6. 6.
    Voelker DR, Frazier JL. Isolation and characterization of a Chinese hamster ovary cell line requiring ethanolamine or phosphatidylserine for growth and exhibiting defective phosphatidylserine synthase activity. J Biol Chem 1986; 261: 1002–1008PubMedGoogle Scholar
  7. 7.
    Suzuki TT, Kanfer JN. Purification and properties of an ethanolamine-serine base exchange enzyme of rat brain microsomes. J Biol Chem 1985; 260: 1394–1399PubMedGoogle Scholar
  8. 8.
    Alves CS, Andreatini R, da Cunha C, et al. Phosphatidylserine reverses reserpine-induced amnesia. Eur J Pharmacol 2000; 404: 161–167PubMedCrossRefGoogle Scholar
  9. 9.
    Suzuki S, Yamatoya H, Sakai M, et al. Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats. J Nutr 2001; 131: 2951–2956PubMedGoogle Scholar
  10. 10.
    Furushiro M, Suzuki S, Shishido Y, et al. Effects of oral administration of soybean lecithin transphosphatidylated phosphatidylserine on impaired learning of passive avoidance in mice. Jpn Pharmacol 1997; 75: 447–450CrossRefGoogle Scholar
  11. 11.
    Drago F, Spadaro F, D’Agata V, et al. Protective action of phosphatidylserine on stress-induced behavioral and autonomic changes in aged rats. Neurobiol Aging 1991; 12: 437–440PubMedCrossRefGoogle Scholar
  12. 12.
    Koutoku T, Takahashi H, Tomonaga S, et al. Central administration of phosphatidylserine attenuates isolation stress-induced behavior in chicks. Nerochem Int 2005; 47: 183–189CrossRefGoogle Scholar
  13. 13.
    Cenacchi T, Bertoldin T, Farina C, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging 1993; 5: 123–133PubMedGoogle Scholar
  14. 14.
    Crook T, Petrie W, Wells C, et al. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull 1992; 28: 61–66PubMedGoogle Scholar
  15. 15.
    Amaducci L, SIDD Group. Phosphatidylserine in the treatment of Alzheimer’s disease: results of a multicenter study. Psychopharmacol Bull 1988; 24: 130–134PubMedGoogle Scholar
  16. 16.
    Soares JC, Gershon S. Advances in the pharmacotherapy of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 1994; 244: 261–271PubMedCrossRefGoogle Scholar
  17. 17.
    Pepeu G, Pepeu IM, Amaducci L. A review of phosphatidylserine pharmacological and clinical effects: is phosphatidylserine a drug for the ageing brain? Pharmacol Res 1996; 33: 73–80PubMedCrossRefGoogle Scholar
  18. 18.
    Toffano G, Bruni A. Pharmacological properties of phospholipid liposomes. Pharmacol Res Commun 1980; 12: 829–845PubMedCrossRefGoogle Scholar
  19. 19.
    Nishijima M, Kuge O, Akamatsu Y. Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells, I: inhibition of de novo phosphatidylserine biosynthesis by exogenous phosphatidylserine and its efficient incorporation. J Biochem Chem 1986; 261: 5784–5789Google Scholar
  20. 20.
    Kuge O, Nishijima M, Akamatsu Y. Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells, II: isolation and characterization of phosphatidylserine auxotrophs. J Biol Chem 1986; 261: 5790–5794PubMedGoogle Scholar
  21. 21.
    Palatini P, Viola G, Bigon E et al. Pharmacokinetic characterization of phosphatidylserine liposomes in the rat. Br J Pharmacol 1991; 102: 345–350PubMedCrossRefGoogle Scholar
  22. 22.
    Heikinheimo L, Somerharju P. Translocation of pyrene-labeled phosphatidylserine from the plasma membrane to mitochondria diminishes systematically with molecular hydrophobicity: implications on the maintenance of high phosphatidylserine content in the inner leaflet of the plasma membrane. Biochem Biophys Acta 2002; 1591: 75–85PubMedCrossRefGoogle Scholar
  23. 23.
    Bruni A, Orlando P, Mietto L, et al. Phospholipid metabolism in rat intestinal mucosa after oral administration of lysophospho-lipids. In: Bazan NG, editor. Neurobiology of essential fatty acids. New York: Plenum Press, 1992: 243–249CrossRefGoogle Scholar
  24. 24.
    Cenacchi T, Baggio C, Palin E. Human tolerability of oral phosphatidylserine assessed through laboratory examinations. Clin Trials J 1987; 21: 125–130Google Scholar
  25. 25.
    Jorissen BL, Brouns F, Van Boxtel MP, et al. Safety of soy-derived phosphatidylserine in elderly people. Nutr Neurosci 2002; 5: 337–343PubMedCrossRefGoogle Scholar
  26. 26.
    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: 385–388PubMedGoogle Scholar
  27. 27.
    Fahey TD, Pearl MS. The hormonal and perceptive effects of phosphatidylserine administration during two weeks of resistive exercise-induced overtraining. Biol Sport 1998; 15: 135–144Google Scholar
  28. 28.
    Monteleone P, Beinat L, Tanzillo C, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 1990; 52: 243–248PubMedCrossRefGoogle Scholar
  29. 29.
    Kingsley M, Miller M, Kilduff LP, et al. Effects of phosphatidylserine on exercise capacity during cycling in active males. Med Sci Sports Exerc 2006; 38: 64–71PubMedCrossRefGoogle Scholar
  30. 30.
    Benton D, Donohoe RT, Sillance B, et al. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci 2001; 4: 169–178PubMedGoogle Scholar
  31. 31.
    Takai Y, Kishimoto A, Iwasa Y, et al. Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids. J Biol Chem 1979; 254: 3692–3695PubMedGoogle Scholar
  32. 32.
    Ghosh S, Xie WQ, Quest AF, et al. The cysteine-rich region of raf-1 kinase contains zinc, translocates to liposomes, and is adjacent to a segment that binds GTP-ras. J Biol Chem 1994; 269: 10000–10007PubMedGoogle Scholar
  33. 33.
    Nagai Y, Aoki J, Sato T, et al. An alternative splicing form of phosphatidylserine-specific phospholipase Al that exhibits lysophosphatidylserine-specific lysophospholipase activity in humans. J Biol Chem 1999; 274: 11053–11059PubMedCrossRefGoogle Scholar
  34. 34.
    Kim HY, Akbar M, Lau A, et al. Inhibition of neuronal apoptosisby docosahexaenoic acid (22:6n-3): role of phosphatidylserine in antiapoptotic effect. J Biol Chem 2000; 275: 35215–35223PubMedCrossRefGoogle Scholar
  35. 35.
    Specht SC, Robinson ID. Stimulation of the (Na++K+)-dependent adenosine triphosphatase by amino acids and phosphatidylserine: chelation of trace metal inhibitors. Arch Biochem Biophys 1973; 154: 314–323PubMedCrossRefGoogle Scholar
  36. 36.
    TsakirisS, Deliconstantinos G. Influence of phosphatidylserine on (Na++K+)-stimulated ATPase and acetylcholinesterase activities in dog brain synaptosomal plasma membranes. Biochem J 1984; 220: 301–307Google Scholar
  37. 37.
    Morrot G, Zachowski A, Devaux PF. Partial purification and characterisation of the human erythrocyte. Am J Physiol 1990; 216: 82–86Google Scholar
  38. 38.
    Sepulveda MR, Mata AM. The interaction of ethanol with reconstituted synaptosomal plasma membrane Ca2+-ATPase. Biochim Biophys Acta 2004; 1665: 75–80PubMedCrossRefGoogle Scholar
  39. 39.
    Bick RI, Buja LM, Van Winkle WB, et al. Membrane asymmetry in isolated canine cardiac sarcoplasmic reticulum: comparison with skeletal muscle sarcoplasmic reticulum. J Membr Biol 1998; 164: 169–175PubMedCrossRefGoogle Scholar
  40. 40.
    Kent-Braun JA. Central and peripheral contributions to muscle fatigue in humans during sustained maximal effort. Eur J Appl Physiol 1999; 80: 57–63CrossRefGoogle Scholar
  41. 41.
    Allen DG. Skeletal muscle function: role of ionic changes in fatigue, damage and disease. Clin Exp Pharmacol Physiol 2004; 31: 485–493PubMedCrossRefGoogle Scholar
  42. 42.
    Giannesini B, Cozzone PJ, Bendahan D. Non-invasive investigations of muscular fatigue: metabolic and electromyographic components. Biochimie 2003; 85: 873–883PubMedCrossRefGoogle Scholar
  43. 43.
    Bruni A, Toffano G, Leon A, et al. Pharmacological effects of phosphatidylserine liposomes. Nature 1976; 260: 331–333PubMedCrossRefGoogle Scholar
  44. 44.
    Toffano G, Leon A, Benvegnu D, et al. Effect of brain cortex phospholipids on catechol-amine content of mouse brain. Pharmacol Res Commun 1976; 8: 581–590PubMedCrossRefGoogle Scholar
  45. 45.
    Bigon E, Boarato E, Bruni A, et al. Pharmacological effects of phosphatidylserine liposomes: regulation of gylcolysis and energy level in brain. Br J Pharmacol 1979; 66: 167–174PubMedCrossRefGoogle Scholar
  46. 46.
    Casamenti F, Mantovani P, Amaducci L, et al. Effect of phosphatidylserine on acetylcholine output from the cerebral cortex of the rat. J Neurochem 1979; 32: 529–533PubMedCrossRefGoogle Scholar
  47. 47.
    Pepeu G, Giovannelli L, Giovannini MG, et al. Effect of phosphatidylserine on cortical acetylcholine release and calcium uptake in adult and aging rats. In: Horrocks LA, Freysz L, Toffano G, editors. Phospholipid research and the nervous system: biochemical and molecular pharmacology. Padova: Liviana Press, 1986: 265–271Google Scholar
  48. 48.
    Casamenti F, Scali C, Pepeu G. Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: a microdialysis study. Eur J Pharmacol 1991; 194: 11–16PubMedCrossRefGoogle Scholar
  49. 49.
    Yamatoya H, Sakai M, Kudo S. The effects of soybean transphosphatidylated phosphatidylserine on cholinergic synaptic functions of mice. Jpn J Pharmacol 2000; 84: 93–96PubMedCrossRefGoogle Scholar
  50. 50.
    Kingsley M, Wadsworth D, Kilduff LP, et al. The effects of phosphatidylserine on oxidative stress following intermittent running. Med Sci Sports Exerc 2005; 37: 1300–1306PubMedCrossRefGoogle Scholar
  51. 51.
    Luger A, Deuster PA, Kyle SB, et al. Acute hypothalamicpituitary-adrenal responses to the stress of treadmill exercise: physiologic adaptations to physical training. N Engl I Med 1987; 316: 1309–1315CrossRefGoogle Scholar
  52. 52.
    Mongar JL, Svec P. The effect of phospholipids on anaphylactic histamine release. Br J Pharmacol 1972; 46: 741–752PubMedCrossRefGoogle Scholar
  53. 53.
    Goth A, Adams HR, Knoohuizen M. Phosphatidylserine: selective enhancer of histamine release. Science 1971; 173: 1034–1035PubMedCrossRefGoogle Scholar
  54. 54.
    Shores AJ, Mongar JL. Modulation of histamine secretion from Concanavalin A-activated rat mast cells by phosphatidyl serine, calcium, cAMP, pH and metabolic inhibitors. Agents Actions 1980; 10: 131–137PubMedCrossRefGoogle Scholar
  55. 55.
    Moodley I, Mongar JL. IgG receptors on the mast cells. Agents Actions 1981; 11: 77–83PubMedCrossRefGoogle Scholar
  56. 56.
    Monastra G, Pege G, Zanoni R, et al. Lysophosphatidylserine-induced activation of mast cells in mice. J Lipid Mediat 1991; 3: 39–50PubMedGoogle Scholar
  57. 57.
    Devaux PF. Static and dynamic lipid asymetry in cell membranes. Biochem 1991; 30: 1163–1173CrossRefGoogle Scholar
  58. 58.
    Tyurina YY, Shvedova AA, Kawai K, et al. Phospholipid signaling in apoptosis: peroxidation and externalization of phophatidylserine. Toxicology 2000; 148: 93–101PubMedCrossRefGoogle Scholar
  59. 59.
    Tanaka Y, Schroit AJ. Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells. J Biol Chem 1983; 258: 11335–11343PubMedGoogle Scholar
  60. 60.
    Gilbreath MJ, Hoover DL, Alving CR, et al. Inhibition of lymphokine-induced macrophage microbicidal activity against Leishmania major by liposomes: characterization of the physi-cochemical requirements for liposome inhibition. J Immunol 1986; 137: 1681–1687PubMedGoogle Scholar
  61. 61.
    Aramaki Y, Matsuno R, Nitta F, et al. Negatively charged liposomes inhibit tyrosine phosphorylation of 41-kDa protein in murine macrophages stimulated with LPS. Biochem Biophys Res Commun 1997; 231: 827–830PubMedCrossRefGoogle Scholar
  62. 62.
    Huynh ML, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-pl secretion and the resolution of inflammation. J Clin Invest 2002; 109: 41–50PubMedGoogle Scholar
  63. 63.
    Ponzin D, Mancini C, Toffano G, et al. Phosphatidylserine-induced modulation of the immune response in mice: effect of intravenous administration. Immunopharmacology 1989; 18: 167–176PubMedCrossRefGoogle Scholar
  64. 64.
    Monastra G, Bruni A. Decreased semm level of tumor necrosis factor in animals treated with lipopolysaccharide and liposomes containing phosphatidylserine. Lymphokine Cytokine Res 1992; 11: 39–43PubMedGoogle Scholar
  65. 65.
    Bruni A, Mietto L, Secchi FE, et al. Lipid mediators of immune reactions: effect of a linked phosphorylserine group. Immunol Lett 1994; 42: 87–90PubMedCrossRefGoogle Scholar
  66. 66.
    Facci L, Cusinato F, Negro A, et al. The immunosuppressant steroid cholesterylphosphoserine inhibits tumour necrosis factor-alpha secretion in vitro and in vivo. Cytokine 2000; 12: 770–773PubMedCrossRefGoogle Scholar
  67. 67.
    Vincent P, Sargueil F, Sturbois-Balcerzak B, et al. Phosphatidylserine increase in rat liver endomembranes during the acute phase response. Biochimie 2001; 83: 957–960PubMedCrossRefGoogle Scholar
  68. 68.
    Hoffmann PR, Kench JA, Vondracek A, et al. Interaction between phosphatidylserine and the phosphatidylserine receptor inhibits immune responses in vivo. J Immunol 2005; 174: 1393–1404PubMedGoogle Scholar
  69. 69.
    Dacaranhe CD, Terao J. A unique antioxidant activity of phosphatidylserine on iron-induced lipid peroxidation of phospholipid bilayers. Lipids 2001; 36: 1105–1110PubMedCrossRefGoogle Scholar
  70. 70.
    Lou P, Gutman RL, Mao FW, et al. Effects of phosphatidylserine on the oxidation of low density lipoprotein. Int J Biochem 1994; 26: 539–545PubMedCrossRefGoogle Scholar
  71. 71.
    Latorraca S, Piersanti P, Tesco G, et al. Effect of phosphatidylserine on free radical susceptibility in human diploid fibroblasts. J Neural Transm 1993; 6: 73–77CrossRefGoogle Scholar
  72. 72.
    Gauvin L, Rejeski WJ. The exercise-induced feeling inventory: development and initial validation. J Sport Exerc Psychol 1993; 15: 403–423Google Scholar
  73. 73.
    Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science 1972; 175: 720–731PubMedCrossRefGoogle Scholar
  74. 74.
    Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 2005; 288: 345–353CrossRefGoogle Scholar
  75. 75.
    Armstrong RB, Warren GL, Warren JA. Mechanisms of exercise-induced muscle fibre injury. Sports Med 1991; 12: 184–207PubMedCrossRefGoogle Scholar
  76. 76.
    Dekkers JC, van Dooran LJP, Kemper HCG. The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage. Sports Med 1996; 21: 213–238PubMedCrossRefGoogle Scholar
  77. 77.
    Feasson L, Stockholm D, Freyssenet D, et al. Molecular adaptations of neuromuscular disease-associated proteins in response to eccentric exercise in human skeletal muscle. J Physiol 2002; 543: 297–306PubMedCrossRefGoogle Scholar
  78. 78.
    Thompson D, Williams C, Kingsley M, et al. Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation. Int J Sports Med 2001; 22: 68–75PubMedCrossRefGoogle Scholar
  79. 79.
    Peake JM, Suzuki K, Wilson G, et al. Exercise-induced muscle damage, plasma cytokines, adn markers of neutrophil activation. Med Sci Sports Exerc 2005; 37: 737–745PubMedCrossRefGoogle Scholar
  80. 80.
    Miller PC, Bailey SP, Barnes ME, et al. The effects of protease supplementation on skeletal muscle function and DOMS following downhill running. J Sports Sci 2004; 22: 365–372PubMedCrossRefGoogle Scholar
  81. 81.
    Friden J, Sjostrom M, Ekblom B. Myofibrillar damage following intense eccentric exercise in man. Int J Sports Med 1983; 4: 170–176PubMedCrossRefGoogle Scholar
  82. 82.
    Tibbits GF, Nagatomo T, Sasaki M, et al. Cardiac sarcolemma: compositional adaptation to exercise. Science 1981; 213: 1271–1273PubMedCrossRefGoogle Scholar
  83. 83.
    Sugden PH, Bogoyevitch MA. Intracellular signalling through protein kinases in the heart. Cardiovasc Res 1995; 30: 478–492PubMedGoogle Scholar
  84. 84.
    Liang MT, Meneses P, Glonek T, et al. Effects of exercise training and anabolic steroids on plantaris and soleus phospholipids: a 31P nuclear magnetic resonance study. Int J Biochem 1993; 25: 337–347PubMedCrossRefGoogle Scholar
  85. 85.
    Gorski J, Zendzian-Piotrowska M, de Jong YF, et al. Effect of endurance training on the phospholipid content of skeletal muscles in the rat. Eur J Appl Physiol 1999; 79: 421–425CrossRefGoogle Scholar
  86. 86.
    Sumikawa K, Mu Z, Inoue T, et al. Changes in erythrocyte membrane phospholipid composition induced by physical training and exercise. Eur J Appl Physiol 1993; 67: 132–137CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Sports ScienceUniversity of Wales SwanseaSwanseaUK

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