Benefits
Menstrual cycle symptom scores in women
In a double blind trial in 40 women aged 18 to 45 with premenstrual syndrome, 400 mg PS plus 400 mg PA a day for three cycles lowered the total daily symptom score, the main outcome, more than placebo, with a greater drop in physical symptoms. Depressive symptoms and most other scales did not differ significantly. It is one small trial, funded by the maker, with a maker co-author.
Cortisol and ACTH response to a lab stress test
In 75 healthy men, 400 mg PS plus 400 mg PA a day for six weeks brought the cortisol and ACTH rise during a public speaking and math test closer to normal only in men with high chronic stress, not in the group as a whole; half that dose had no effect. Cortisol and ACTH are hormone markers, not a measure of how people feel.
Felt stress during an acute stress test
In an earlier 3 week trial in 80 people, people on 400 mg of the complex reported less distress after a lab stress test while the placebo group reported more; higher doses did not blunt stress hormones. A larger 6 week trial in men found no effect on mood, calmness, anxiety or perceived stress during the same test.
Memory in older adults with memory complaints
In a 3 month trial in older adults with memory complaints, an earlier version of the complex (300 mg PS plus 240 mg PA a day) did not beat placebo on the main memory score; gains were within group or in a subgroup. A 2 month trial in people with Alzheimer's disease, a disease population, reported steadier daily functioning.
PS plus phosphatidic acid compared with PS alone
This complex adds phosphatidic acid to PS, so its results cannot be credited to PS alone, and PS alone results do not transfer to it. No trial compared the complex with plain PS. Plain soy PS did not help memory in a 120 person trial, and its cortisol results after exercise disagree between small trials.
Mechanism of action
Proposed effect on the stress hormone axis
The trial authors propose that PS and PA dampen the hypothalamus pituitary adrenal (HPA) axis response to acute stress, and suggested that a change in corticosteroid binding globulin might explain it. This hypothesis was not tested in the trials, and the hormone changes appeared only in subgroups.
Absorption of PS from the complex
In 8 healthy volunteers given a single dose of the soy PS plus PA material, the PS share of blood phospholipids began rising 30 minutes later, peaked at 90 minutes and returned to baseline by 180 minutes. This shows uptake into blood, not an effect on the brain.
Phospholipids in cell membranes
PS and PA are both phospholipids found in cell membranes, and PA also acts as a signaling lipid in cells. The trial authors propose that taking them may change membrane makeup and function, but no PAS trial measured membrane changes.
Clinical trials
Randomized, double blind, placebo controlled trial of PAS (400 mg PS plus 400 mg PA a day) over one baseline and three treatment menstrual cycles, intake tracked by electronic pill caps; registered DRKS00009005. Run by the contract research institute daacro; funded by Lipogen, and one author (Rutenberg) was a Lipogen employee. (Schmidt et al. 2018, Clin Nutr ESPEN)
40 women aged 18 to 45 with a diagnosis of premenstrual syndrome.
The primary outcome, the Daily Record of Severity of Problems total score, improved more on PAS than placebo (p = 0.001), as did physical symptoms (p = 0.002). Depressive symptoms (p = 0.068) and other scales did not differ, nor did the share of women meeting PMS criteria on a screening tool. Serum cortisol fell slightly on PAS and rose on placebo (p = 0.043); estradiol and progesterone did not change.
Randomized, double blind, placebo controlled trial of PAS 400 (400 mg PS plus 400 mg PA a day) and PAS 200 for 42 days, followed by the Trier Social Stress Test; registered DRKS00005125. The PAS was produced by Lipogen and sold as MemreePlus by Lonza; financed by Lipogen and Lonza, with a Lipogen employee (Rutenberg) and a Lonza employee (Freitas) as authors. (Hellhammer et al. 2014, Lipids Health Dis)
75 healthy men aged 20 to 45, stratified by chronic stress; 72 analyzed.
In the whole group neither dose changed salivary or serum cortisol. In men with high chronic stress, PAS 400 normalized the ACTH (p = 0.010), salivary cortisol (p = 0.043) and serum cortisol (p = 0.035) responses compared with placebo; PAS 200 had no effect. Heart rate, mood and perceived stress did not differ between groups.
Placebo controlled trial, indexed in PubMed as randomized, of 400, 600 or 800 mg PAS a day for 3 weeks, followed by the Trier Social Stress Test. The abstract gives no funding statement; co-author Rutenberg is listed as a Lipogen employee in the group's later papers. (Hellhammer et al. 2004, Stress)
Four groups of 20 people.
400 mg PAS blunted serum ACTH, serum cortisol and salivary cortisol responses to the stress test and did not change heart rate; 600 and 800 mg did not show this effect. Distress rose after the test on placebo but fell on 400 mg PAS. The later 6 week trial did not reproduce an effect on felt stress.
Report of studies run between 1992 and 1999 with L-Telect (100 mg PS plus 80 mg PA per capsule, three a day), described as similar to MemreePlus: a blood level study, a 3 month double blind placebo controlled memory trial and a 2 month randomized double blind placebo controlled trial. Funded by Lipogen; authors were employees of Lipogen, Lonza and a medical writing firm. (Moré et al. 2014, Adv Ther)
72 non-depressed older adults aged 60 to 80 with memory complaints; 96 people with Alzheimer's disease; 8 healthy volunteers for the blood level study.
Memory trial: the primary outcome, change in Wechsler Memory Scale score, did not differ between groups; both groups improved within group, and only a subgroup with higher starting scores differed. Disease trial: daily living scores held steady on PS plus PA and fell on placebo (groups differed at 2 months, p = 0.021), but mental status, emotional state and self-rated condition did not differ.