期刊论文详细信息
Lipids in Health and Disease
A 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
David Rutenberg3  Ulla Freitas1  Nadin Franz2  Dominic Vogt2  Juliane Hellhammer2 
[1] Lonza Ltd, Muenchensteinerstr. 38, 4002 Basel, Switzerland;Diagnostic Assessment and Clinical Research Organization (Daacro) GmbH & Co. KG, Science Park Trier, Max-Planck-Str. 22, 54296 Trier, Germany;Lipogen Ltd, P.O.Box 7687, 31078 Haifa, Israel
关键词: TSST;    Stress response;    Chronic stress;    Acute stress;    Cortisol;    PAS;    Stress;    Memree;    Phosphatidic acid;    Phosphatidylserine;   
Others  :  1159967
DOI  :  10.1186/1476-511X-13-121
 received in 2014-05-16, accepted in 2014-07-21,  发布年份 2014
PDF
【 摘 要 】

Background

Supplementation with a phosphatidylserine and phosphatidylserine/ phosphatidic acid complex (PAS) has been observed to normalize stress induced dysregulations of the hypothalamus-pituitary-adrenal axis (HPAA). Prolonged stress first induces a hyper-activation of the HPAA, which then can be followed by a state of hypo-activation.

The aim of this study was to examine effects of an oral supplementation with 400 mg PS & 400 mg PA (PAS 400) per day on the endocrine stress response (ACTH, saliva and serum cortisol) to a psychosocial stressor. A special focus was to analyze subgroups of low versus high chronically stressed subjects as well as to test efficacy of 200 mg PS & 200 mg PA (PAS 200).

Methods

75 healthy male volunteers were enrolled for this double-blind, placebo-controlled study, stratified by chronic stress level, and randomly allocated to one of three study arms (placebo, PAS 200 and PAS 400 per day, respectively). Study supplementation was administered for 42 days for each participant. Chronic stress was measured with the Trier Inventory for Chronic Stress (TICS), and subgroups of high and low chronic stress were differentiated by median values as provided by the TICS authors. A six week period of supplementation was followed by an acute stress test (Trier Social Stress Test - TSST).

Results

Chronic stress levels and other baseline measures did not differ between treatment groups (all p > 0.05). Acute stress was successfully induced by the TSST and resulted in a hyper-responsivity of the HPAA in chronically stressed subjects. Compared to placebo, a supplementation with a daily dose of PAS 400 was effective in normalizing the ACTH (p = 0.010), salivary (p = 0.043) and serum cortisol responses (p = 0.035) to the TSST in chronically high but not in low stressed subjects (all p > 0.05). Compared to placebo, supplementation with PAS 200 did not result in any significant differences in these variables (all p > 0.05). There were no significant effects of supplementation with PAS on heart rate, pulse transit time, or psychological stress response (all p > 0.05).

Conclusion

In chronically stressed subjects, a supplementation with PAS 400 (MemreePlus™) can normalize the hyper-responsivity of the HPAA to an acute stressor.

Trial registration

Trial registration: DRKS-ID: DRKS00005125

【 授权许可】

   
2014 Hellhammer et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150410090726593.pdf 395KB PDF download
Figure 4. 67KB Image download
Figure 3. 29KB Image download
Figure 2. 31KB Image download
Figure 1. 24KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Finan PH, Zautra AJ, Wershba R: The dynamics of emotions in adaptation to stress. In The Handbook of Stress Science: Biology, Psychology, and Health. Edited by Contrada RJ, Baum A. New York: Springer Publishing Company; 2011:209-220.
  • [2]Dallman MF, Hellhammer DH: Regulation of the Hypothalamic-Pituitary-Adrenal Axis, Chronic Stress, and Energy: The Role of Brain Networks. New York: Springer; 2010.
  • [3]Hellhammer DH, Wade S: Endocrine correlates of stress vulnerability. Psychother Psychosom 1993, 60:8-17.
  • [4]Nyuyki KD, Beiderbeck DI, Lukas M, Neumann ID, Reber SO: Chronic subordinate colony housing (CSC) as a model of chronic psychosocial stress in male rats. PLoS One 2012, 7:e52371.
  • [5]Chrousos GP: Stress and disorders of the stress system. Nat Rev Endocrinol 2009, 5:374-381.
  • [6]Heim C, Ehlert U, Hellhammer DH: The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 2000, 25:1-35.
  • [7]Fries E, Hesse J, Hellhammer J, Hellhammer DH: A new view on hypocortisolism. Psychoneuroendocrinology 2005, 30:1010-1016.
  • [8]Schmidt-Reinwald A, Pruessner JC, Hellhammer DH, Federenko I, Rohleder N, Schürmeyer TH, Kirschbaum C: The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm. Life Sci 1999, 64:1653-1660.
  • [9]Pruessner M, Hellhammer DH, Pruessner JC, Lupien SJ: Self-reported depressive symptoms and stress levels in healthy young men: associations with the cortisol response to awakening. Psychosom Med 2003, 65:92-99.
  • [10]Buske-Kirschbaum A, Von Auer K, Krieger S, Weis S, Rauh W, Hellhammer DH: Blunted cortisol responses to psychosocial stress in asthmatic children: a general feature of atopic disease. Psychosom Med 2003, 65:806-810.
  • [11]Kakiashvili T, Leszek J, Rutkowski K: The medical perspective on burnout. International journal of occupational medicine and environmental health. Int J Occup Med Environ Health 2013, 26:401-412.
  • [12]Reber SO, Birkeneder L, Veenema AH, Obermeier F, Falk W, Straub RH, Neumann ID: Adrenal insufficiency and colonic inflammation after a novel chronic psycho-socoial stress paradigm in mice: implications and mechanisms. Endocrinology 2007, 148:670-682.
  • [13]Schult J, Hero T, Hellhammer J: Effects of powdered fertilized eggs on the stress response. Clin Nutr 2010, 29:255-260.
  • [14]Schubert M, Contreras C, Franz N, Hellhammer J: Milk-based phospholipids increase morning cortisol availability and improve memory in chronically stressed men. Nutr Res 2011, 31:413-420.
  • [15]Hellhammer J, Hero T, Franz N, Contreras C, Schubert M: Omega-3 fatty acids administered in phosphatidylserine improved certain aspects of high chronic stress in men. Nutr Res 2012, 32:241-250.
  • [16]Athenstaedt K, Daum G: Phosphatidic acid, a key intermediate in lipid metabolism. Eur J Biochem 1999, 266:1-16.
  • [17]Kooijman EE, Chupin V, De Kruijff B, Burger KN: Modulation of membrane curvature by phosphatidic acid and lysophosphatidic acid. Traffic 2003, 4:162-174.
  • [18]McMahon HT, Gallop JL: Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 2005, 438:590-596.
  • [19]Foster DA: Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells. Biochim Biophys Acta 2009, 1791:949-955.
  • [20]Sergeant S, Waite KA, Heravi J, McPhail LC: Phosphatidic acid regulates tyrosine phosphorylating activity in human neutrophils: enhancement of Fgr activity. J Biol Chem 2000, 276:4737-4746.
  • [21]Adachi M, Horiuchi G, Ikematsu N, Tanaka T, Terao J, Satouchi K, Tokumura A: Intragastrically administered lysophosphatidic acids protect against gastric ulcer in rats under water-immersion restraint stress. Dig Dis Sci 2011, 56:2252-2261.
  • [22]Tanaka T, Horiuchi G, Matsuoka M, Hirano K, Tokumura A, Koike T, Satouchi K: Formation of lysophosphatidic acid, a wound-healing lipid, during digestion of cabbage leaves. Biosci Biotechnol Biochem 2009, 73:1293-1300.
  • [23]Pasiakos SM: Exercise and amino acid anabolic cell signaling and the regulation of skeletal muscle mass. Nutrients 2012, 4:740-758.
  • [24]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, 4:169-178.
  • [25]Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn AD: 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, 29:467-474.
  • [26]Kidd PM: Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. Altern Med Rev 2007, 12:207-227.
  • [27]Hellhammer J, Fries E, Buss C, Engert V, Tuch A, Rutenberg D, Hellhammer DH: Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress 2004, 7:119-126.
  • [28]Hellhammer J, Waladkhani A-R, Hero T, Buss C: Effects of milk phospholipid on memory and psychological stress response. Nutr Res 2010, 112:1124-1137.
  • [29]McDaniel MA, Maier SF, Einstein GO: “Brain-specific” nutrients: a memory cure? Nutrition 2003, 19:957-975.
  • [30]Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D: Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 1990, 52:243-248.
  • [31]Simopoulos AP: Omega-3 fatty acids in inflammation and autoimmune disease. J Am Coll Nutr 2002, 21:495-505.
  • [32]Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R: The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr 2008, 5:1-6.
  • [33]Monteleone P, Maj M, Beinat L, Natale M, Kemali D: Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothamamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol 1992, 41:385-388.
  • [34]Kingsley M: Effects of phosphatidylserine supplementation on execising humans. Sports Med 2006, 36:657-669.
  • [35]Jäger R, Purpura M, Kingsley M: Phospholipids and sports performance. J Int Soc Sports Nutr 2007, 4:1-8.
  • [36]Appleton KM, Rogers PJ, Ness AR: Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials. Nutr Res Rev 2008, 21:13-41.
  • [37]Pandey NR, Sultan K, Twomey E, Sparks DL: Phospholipids block nuclear factor-kappa B and tau phosphorylation and inhibit amyloid-beta secretion in human neuroblastoma cells. Neuroscience 2009, 164:1744-1753.
  • [38]Peet M, Stokes C: Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs 2005, 65:1051-1059.
  • [39]Hibbeln JR: Fish consumption and major depression. Lancet 1998, 351:1213.
  • [40]Hibbeln JR: Depression, Suicide and Deficiencies of Omega-3 Essential Fatty Acids in Modern Diets. In Omega-3 Fatty Acids, the Brain and Retina. Volume 99 edition. Edited by Simopoulos AP, Bazan NG. Basel: Karger; 2009:17-30.
  • [41]Parker G, Gibson N, Brotchie H, Heruc G, Rees A-M, Hadzi-Pavlovic D: Omega-3 fatty acids and mood disorders. Am J Psychiatry 2006, 163:969-978.
  • [42]Küllenberg D, Taylor LA, Schneider M, Massing U: Health effects of dietary phospholipids. Lipids Health Dis 2012, 11:1-16.
  • [43]Schulz P, Schlotz W, Becker P: Das Trierer Inventar zur Erfassung von chronischem Stress-Version 2 (TICS 2)[Trier Inventory for the Assessment of Chronic Stress]. Gottingen, Germany: Hogrefe; 2004.
  • [44]De Boer D, Ring C, Carroll D: Time course and mechanisms of hemoconcentration in response to mental stress. Biol Psychol 2006, 72:318-324.
  • [45]Geddes L, Voelz M, Babbs C, Bourland J, Tacker W: Pulse transit time as an indicator of arterial blood pressure. Psychophysiology 1981, 18:71-74.
  • [46]Vlachopoulos C, Kosmopoulou F, Alexopoulos N, Ioakeimidis N, Siasos G, Stefanadis C: Acute mental stress has a prolonged unfavorable effect on arterial stiffness and wave reflections. Psychosom Med 2006, 68:231-237.
  • [47]Fechir M, Schlereth T, Purat T, Kritzmann S, Geber C, Eberle T, Gamer M, Birklein F: Patterns of sympathetic responses induced by different stress tasks. Open Neurol J 2008, 2:25.
  • [48]Hey S, Gharbi A, Von Haaren B, Walter K, Konig N, Loffler S: Continuous noninvasive pulse transit time measurement for psycho-physiological stress monitoring. eHealth, Telemedicine, and Social Medicine, 2009 eTELEMED’09 International Conference on. IEEE 2009, 113-116.
  • [49]Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH: Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 2003, 28:916-931.
  • [50]Pawlow LA, Jones GE: The impact of abbreviated progressive muscle relaxation on salivary cortisol. Biol Psychol 2002, 60:1-16.
  • [51]Matousek RH, Dobkin PL, Pruessner JC: Cortisol as a marker for improvement in mindfulness-based stress reduction-. Complement Ther Clin Pract 2010, 16:13-19.
  • [52]MacLean CR, Walton KG, Wenneberg SR, Levitsky DK, Mandarino JV, Waziri R, Hillis SL, Schneider RH: Effects of the Transcendental Meditation program on adaptive mechanisms: changes in hormone levels and responses to stress after 4 months of practice. Psychoneuroendocrinology 1997, 22:277-295.
  • [53]Olff M, De Vries GJ, Guzelcan Y, Assies J, Gersons BP: Changes in cortisol and DHEA plasma levels afer psychotherapy for PTSD. Psychoneuroendocrinology 2007, 32:619-626.
  • [54]Bonifazi M, Suman AL, Cambiaggi C, Felici A, Grasso G, Lodi L, Mencarelli M, Muscettola M: Changes in salivary cortisol and corticosteroid receptor-alpha mRNA expression following a 3-week multidisciplinary treatment program in patients with fibromyalgia. Psychoneuroendocrinology 2006, 31:1076-1086.
  • [55]Mommersteeg PM, Keijsers GP, Heijnen CJ, Verbraak MJ, van Doornen LJ: Cortisol deviations in people with burnout before and after psychotherapy: a pilot study. Health Psychol 2006, 25:243-248.
  • [56]Stefanski V: Social stress in laboratory rats: behavior, immune function, and tumor metastasis. Physiol Behav 2001, 73:385-391.
  • [57]Spencer RL, Miller AH, Moday H, McEwen BS, Blanchard RJ, Blanchard DC, Sakai RR: Chronic social stress produces reductions in available splenic type II corticosteroid receptor binding and plasma corticosteroid binding globulin levels. Psychoneuroendocrinology 1996, 21:95-109.
  • [58]Stefanski V: Social stress in laboratory rats: hormonal responses and immune cell distribution. Psychoneuroendocrinology 2000, 25:389-406.
  • [59]Perogamvros I, Ray DW, Trainer PJ: Regulation of cortisol bioavailability–effects on hormone measurement and action. Nat Rev Endocrinol 2012, 8:717-727.
  • [60]Chan WL, Carrell RW, Zhou A, Read RJ: How changes in affinity of corticosteroid-binding globulin modulate free cortisol concentration. J Clin Endocrinol Metab 2013, 98:3315-3322.
  • [61]Moisan M-P: CBG: a cortisol reservoir rather than a transporter. Nat Rev Endocrinol 2013, 9:78.
  • [62]Mavrides N, Nemeroff C: Treatment of depression in cardiovascular disease. Depress Anxiety 2013, 30:328-341.
  • [63]Kirschbaum C, Pirke KM, Hellhammer DH: The ‘Trier Social Stress Test’-a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993, 28:76-81.
  • [64]Hey S, Sghir H: Psycho-physiological stress monitoring using mobile and continous pulse transit time measurement. eTELEMED 2011, The Third International Conference on eHealth, Telemedicine, and Social Medicine 2011, 126-129.
  • [65]Steyer R, Schwenkmezger P, Notz P, Eid M: MDBF: Der Mehrdimensionale Befindlichkeitsfragebogen. Göttingen, Germany: Hogrefe; 1997.
  • [66]Laux L, Glanzmann P, Schaffner P, Spielberger CD: STAI: Das State-Trait-Angstinventar. Göttingen, Germany: Hogrefe; 1981.
  • [67]Hellhammer J, Schubert M: The physiological response to Trier Social Stress Test relates to subjective measures of stress during but not before or after the test. Psychoneuroendocrinology 2012, 37:119-124.
  • [68]Dickerson SS, Kemeny ME: Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull 2004, 130:355-391.
  文献评价指标  
  下载次数:13次 浏览次数:12次