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Effects of Phosphatidylserine Supplementation on Exercising Humans

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Abstract

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.

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References

  1. Folch J, Schneider HA. An amino acid constituent of ox brain cephalin. J Biol Chem 1941; 137: 51–62

    CAS  Google Scholar 

  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: 778–783

    Article  PubMed  CAS  Google Scholar 

  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: 47–54

    Article  PubMed  CAS  Google Scholar 

  4. Vance JE, Steenbergen R. Metabolism and functions of phosphatidylserine. Prog Lipid Res 2005; 44: 207–234

    Article  PubMed  CAS  Google Scholar 

  5. Souci SW, Fachmann E, Kraut H. Food composition and nutrition tables. Stuttgart: Medpharm Scientific Publishers, 2000

    Google Scholar 

  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: 1002–1008

    PubMed  CAS  Google Scholar 

  7. Suzuki TT, Kanfer JN. Purification and properties of an ethanolamine-serine base exchange enzyme of rat brain microsomes. J Biol Chem 1985; 260: 1394–1399

    PubMed  CAS  Google Scholar 

  8. Alves CS, Andreatini R, da Cunha C, et al. Phosphatidylserine reverses reserpine-induced amnesia. Eur J Pharmacol 2000; 404: 161–167

    Article  PubMed  CAS  Google Scholar 

  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: 2951–2956

    PubMed  CAS  Google Scholar 

  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: 447–450

    Article  CAS  Google Scholar 

  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: 437–440

    Article  PubMed  CAS  Google Scholar 

  12. Koutoku T, Takahashi H, Tomonaga S, et al. Central administration of phosphatidylserine attenuates isolation stress-induced behavior in chicks. Nerochem Int 2005; 47: 183–189

    Article  CAS  Google Scholar 

  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: 123–133

    PubMed  CAS  Google Scholar 

  14. Crook T, Petrie W, Wells C, et al. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull 1992; 28: 61–66

    PubMed  CAS  Google Scholar 

  15. Amaducci L, SIDD Group. Phosphatidylserine in the treatment of Alzheimer’s disease: results of a multicenter study. Psychopharmacol Bull 1988; 24: 130–134

    PubMed  CAS  Google Scholar 

  16. Soares JC, Gershon S. Advances in the pharmacotherapy of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 1994; 244: 261–271

    Article  PubMed  CAS  Google Scholar 

  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: 73–80

    Article  PubMed  CAS  Google Scholar 

  18. Toffano G, Bruni A. Pharmacological properties of phospholipid liposomes. Pharmacol Res Commun 1980; 12: 829–845

    Article  PubMed  CAS  Google Scholar 

  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: 5784–5789

    CAS  Google Scholar 

  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: 5790–5794

    PubMed  CAS  Google Scholar 

  21. Palatini P, Viola G, Bigon E et al. Pharmacokinetic characterization of phosphatidylserine liposomes in the rat. Br J Pharmacol 1991; 102: 345–350

    Article  PubMed  CAS  Google Scholar 

  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: 75–85

    Article  PubMed  CAS  Google Scholar 

  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: 243–249

    Chapter  Google Scholar 

  24. Cenacchi T, Baggio C, Palin E. Human tolerability of oral phosphatidylserine assessed through laboratory examinations. Clin Trials J 1987; 21: 125–130

    Google Scholar 

  25. Jorissen BL, Brouns F, Van Boxtel MP, et al. Safety of soy-derived phosphatidylserine in elderly people. Nutr Neurosci 2002; 5: 337–343

    Article  PubMed  CAS  Google Scholar 

  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: 385–388

    PubMed  CAS  Google Scholar 

  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: 135–144

    Google Scholar 

  28. Monteleone P, Beinat L, Tanzillo C, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 1990; 52: 243–248

    Article  PubMed  CAS  Google Scholar 

  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: 64–71

    Article  PubMed  CAS  Google Scholar 

  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: 169–178

    PubMed  CAS  Google Scholar 

  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: 3692–3695

    PubMed  CAS  Google Scholar 

  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: 10000–10007

    PubMed  CAS  Google Scholar 

  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: 11053–11059

    Article  PubMed  CAS  Google Scholar 

  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: 35215–35223

    Article  PubMed  CAS  Google Scholar 

  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: 314–323

    Article  PubMed  CAS  Google Scholar 

  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: 301–307

    Google Scholar 

  37. Morrot G, Zachowski A, Devaux PF. Partial purification and characterisation of the human erythrocyte. Am J Physiol 1990; 216: 82–86

    Google Scholar 

  38. Sepulveda MR, Mata AM. The interaction of ethanol with reconstituted synaptosomal plasma membrane Ca2+-ATPase. Biochim Biophys Acta 2004; 1665: 75–80

    Article  PubMed  CAS  Google Scholar 

  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: 169–175

    Article  PubMed  CAS  Google Scholar 

  40. Kent-Braun JA. Central and peripheral contributions to muscle fatigue in humans during sustained maximal effort. Eur J Appl Physiol 1999; 80: 57–63

    Article  CAS  Google Scholar 

  41. Allen DG. Skeletal muscle function: role of ionic changes in fatigue, damage and disease. Clin Exp Pharmacol Physiol 2004; 31: 485–493

    Article  PubMed  CAS  Google Scholar 

  42. Giannesini B, Cozzone PJ, Bendahan D. Non-invasive investigations of muscular fatigue: metabolic and electromyographic components. Biochimie 2003; 85: 873–883

    Article  PubMed  CAS  Google Scholar 

  43. Bruni A, Toffano G, Leon A, et al. Pharmacological effects of phosphatidylserine liposomes. Nature 1976; 260: 331–333

    Article  PubMed  CAS  Google Scholar 

  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: 581–590

    Article  PubMed  CAS  Google Scholar 

  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: 167–174

    Article  PubMed  CAS  Google Scholar 

  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: 529–533

    Article  PubMed  CAS  Google Scholar 

  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: 265–271

    Google Scholar 

  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: 11–16

    Article  PubMed  CAS  Google Scholar 

  49. Yamatoya H, Sakai M, Kudo S. The effects of soybean transphosphatidylated phosphatidylserine on cholinergic synaptic functions of mice. Jpn J Pharmacol 2000; 84: 93–96

    Article  PubMed  CAS  Google Scholar 

  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: 1300–1306

    Article  PubMed  CAS  Google Scholar 

  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: 1309–1315

    Article  CAS  Google Scholar 

  52. Mongar JL, Svec P. The effect of phospholipids on anaphylactic histamine release. Br J Pharmacol 1972; 46: 741–752

    Article  PubMed  CAS  Google Scholar 

  53. Goth A, Adams HR, Knoohuizen M. Phosphatidylserine: selective enhancer of histamine release. Science 1971; 173: 1034–1035

    Article  PubMed  CAS  Google Scholar 

  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: 131–137

    Article  PubMed  CAS  Google Scholar 

  55. Moodley I, Mongar JL. IgG receptors on the mast cells. Agents Actions 1981; 11: 77–83

    Article  PubMed  CAS  Google Scholar 

  56. Monastra G, Pege G, Zanoni R, et al. Lysophosphatidylserine-induced activation of mast cells in mice. J Lipid Mediat 1991; 3: 39–50

    PubMed  CAS  Google Scholar 

  57. Devaux PF. Static and dynamic lipid asymetry in cell membranes. Biochem 1991; 30: 1163–1173

    Article  CAS  Google Scholar 

  58. Tyurina YY, Shvedova AA, Kawai K, et al. Phospholipid signaling in apoptosis: peroxidation and externalization of phophatidylserine. Toxicology 2000; 148: 93–101

    Article  PubMed  CAS  Google Scholar 

  59. Tanaka Y, Schroit AJ. Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells. J Biol Chem 1983; 258: 11335–11343

    PubMed  CAS  Google Scholar 

  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: 1681–1687

    PubMed  CAS  Google Scholar 

  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: 827–830

    Article  PubMed  CAS  Google Scholar 

  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: 41–50

    PubMed  CAS  Google Scholar 

  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: 167–176

    Article  PubMed  CAS  Google Scholar 

  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: 39–43

    PubMed  CAS  Google Scholar 

  65. Bruni A, Mietto L, Secchi FE, et al. Lipid mediators of immune reactions: effect of a linked phosphorylserine group. Immunol Lett 1994; 42: 87–90

    Article  PubMed  CAS  Google Scholar 

  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: 770–773

    Article  PubMed  CAS  Google Scholar 

  67. Vincent P, Sargueil F, Sturbois-Balcerzak B, et al. Phosphatidylserine increase in rat liver endomembranes during the acute phase response. Biochimie 2001; 83: 957–960

    Article  PubMed  CAS  Google Scholar 

  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: 1393–1404

    PubMed  CAS  Google Scholar 

  69. Dacaranhe CD, Terao J. A unique antioxidant activity of phosphatidylserine on iron-induced lipid peroxidation of phospholipid bilayers. Lipids 2001; 36: 1105–1110

    Article  PubMed  CAS  Google Scholar 

  70. Lou P, Gutman RL, Mao FW, et al. Effects of phosphatidylserine on the oxidation of low density lipoprotein. Int J Biochem 1994; 26: 539–545

    Article  PubMed  CAS  Google Scholar 

  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: 73–77

    Article  CAS  Google Scholar 

  72. Gauvin L, Rejeski WJ. The exercise-induced feeling inventory: development and initial validation. J Sport Exerc Psychol 1993; 15: 403–423

    Google Scholar 

  73. Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science 1972; 175: 720–731

    Article  PubMed  CAS  Google Scholar 

  74. Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 2005; 288: 345–353

    Article  Google Scholar 

  75. Armstrong RB, Warren GL, Warren JA. Mechanisms of exercise-induced muscle fibre injury. Sports Med 1991; 12: 184–207

    Article  PubMed  CAS  Google Scholar 

  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: 213–238

    Article  PubMed  CAS  Google Scholar 

  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: 297–306

    Article  PubMed  CAS  Google Scholar 

  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: 68–75

    Article  PubMed  CAS  Google Scholar 

  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: 737–745

    Article  PubMed  CAS  Google Scholar 

  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: 365–372

    Article  PubMed  Google Scholar 

  81. Friden J, Sjostrom M, Ekblom B. Myofibrillar damage following intense eccentric exercise in man. Int J Sports Med 1983; 4: 170–176

    Article  PubMed  CAS  Google Scholar 

  82. Tibbits GF, Nagatomo T, Sasaki M, et al. Cardiac sarcolemma: compositional adaptation to exercise. Science 1981; 213: 1271–1273

    Article  PubMed  CAS  Google Scholar 

  83. Sugden PH, Bogoyevitch MA. Intracellular signalling through protein kinases in the heart. Cardiovasc Res 1995; 30: 478–492

    PubMed  CAS  Google Scholar 

  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: 337–347

    Article  PubMed  CAS  Google Scholar 

  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: 421–425

    Article  CAS  Google Scholar 

  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: 132–137

    Article  CAS  Google Scholar 

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Acknowledgements

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.

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  1. Department of Sports Science, University of Wales Swansea, Vivian Tower, Singleton Park, Swansea, SA2 8PP, UK

    Michael Kingsley

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Kingsley, M. Effects of Phosphatidylserine Supplementation on Exercising Humans. Sports Med 36, 657–669 (2006). https://doi.org/10.2165/00007256-200636080-00003

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