Effects of Soy Lecithin Phosphatidic Acid and Phosphatidylserine Complex (PAS) on the Endocrine and Psychological Responses to Mental Stress


aNeuropattern, Trier, Germany; bDepartment for Psychobiology, University of Trier, Germany; Lipogen Ltd.,

Haifa, Israel

(Received 7 February 2004; Revised 17 May 2004; In final form 28 May 2004)

Phosphatidylserine, derived from cow brains, has been shown previously to dampen the ACTH and cortisol response to physical stress. Further research investigated the influence of soy lecithin phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. In this study, we investigated the effects of soy lecithin phosphatidic acid and phosphatidylserine complex(PAS) supplementation on pituitary adrenal reactivity (ACTH, cortisol) and on the psychological response (Spielberger State Anxiety Inventory stress subscale) to a mental and emotional stressor. Four groups of 20 subjects were treated for three weeks with daily dosages of either 400 mg PAS, 600 mg PAS, 800 mg PAS, or placebo before exposure to the Trier Social Stress Test (TSST ). Treatment with 400 mg PAS resulted in a pronounced blunting of both serum ACTH and cortisol, and salivary cortisol responses to the TSST, but did not affect heart rate. The effect was not seen with larger doses of PAS. With regard to the psychological response, 400 mg PAS seemed to exert a specific positive effect on emotional responses to the TSST. While the placebo group showed the expected increase in distress after the test, the group treated with 400 mg PAS showed decreased distress. These data provide initial evidence for a selective stress dampening effect of PAS on the pituitary–adrenal axis, suggesting the potential of PAS in the treatment of stress related disorders.



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

Juliane Hellhammer1*, Dominic Vogt1, Nadin Franz1, Ulla Freitas2 and David Rutenberg3


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 of200 mg PS & 200 mg PA (PAS 200).


75 healthy male volunteers were enrolled for this double-blind, placebo-controlled study, stratified bychronic 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 ).


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).


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