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

Lipids Health Dis. 2014 Jul 31:13:121. doi: 10.1186/1476-511X-13-121.


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: DRKS-ID: DRKS00005125.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Dietary Supplements
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Middle Aged
  • Phosphatidic Acids / administration & dosage*
  • Phosphatidylserines / administration & dosage*
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • Plant Extracts / administration & dosage*
  • Soybeans / chemistry
  • Stress, Psychological / blood
  • Stress, Psychological / drug therapy*
  • Young Adult


  • Phosphatidic Acids
  • Phosphatidylserines
  • Plant Extracts
  • Adrenocorticotropic Hormone
  • Hydrocortisone

Associated data

  • DRKS/DRKS00005125