Phosphatidylserine
Soy- or sunflower-derived phosphatidylserine, 300–400 mg/day; the HPA-axis trials used either bovine-cortex PS (no longer sold) or a soy PS + phosphatidic acid complex (PAS) at 400 mg + 400 mg
Early
First results, or a theory about how it works
Four small trials (n=9 to 80, all male) point the same way on cortisol, but the source material differs between them, the dose-response is inverted, and no trial measured sleep, HRV or resting heart rate.
In one very small study of 10 people, the stress hormone released by exercise fell by about a third. Promising, but far too little evidence to count on.
Crossover RCT (n=10, 600 mg/day, 10 days): exercise cortisol AUC −35% and peak cortisol −39% vs placebo (p<0.01); testosterone:cortisol AUC ratio +184% (p=0.02).
Phosphatidylserine is enriched in the inner leaflet of neuronal membranes and appears to restore glucocorticoid-receptor feedback sensitivity at the hypothalamus and pituitary, so a given stressor releases less ACTH and therefore less cortisol.
Chronically stressed people with an exaggerated cortisol response — the 2014 trial found the effect only in the high-chronic-stress subgroup and nothing in low-stress subjects. All the HPA trials were male-only.
What to buy
- ✓Soy- or sunflower-derived phosphatidylserine, 300–400 mg/day; the HPA-axis trials used either bovine-cortex PS (no longer sold) or a soy PS + phosphatidic acid complex (PAS) at 400 mg + 400 mg
- ✓300–400 mg/day of PS; the one trial with a positive TSST result used 400 mg PS plus 400 mg phosphatidic acid, and 600 and 800 mg did not work in that same trial
- ✓Third-party tested (USP, NSF, Informed Sport)
- ✕Proprietary blends that hide the dose per ingredient
- ✕Unstandardised extracts with no active-compound percentage
- · Insomnia and stomach upset are reported above 300 mg/day — an own-goal in a sleep stack if dosed late.
- · Soy-derived product: avoid with soy allergy; sunflower-derived PS is the alternative.
- · Older bovine-cortex PS is off the market over TSE risk; do not source it.
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300 mg per serving is the bottom of the trial range and the most-bought single-ingredient PS. Anything sold as a memory blend hides how much PS you are actually taking.
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400 mg is the dose that moved cortisol in the stress-test trial. Note that 600 and 800 mg did nothing in that same study — more is not better here.
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Sunflower-derived, for anyone avoiding soy. Two capsules give you the 300 mg dose, and it is the highest-rated of the three.
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See all on AmazonEvery result, next to the line that means no effect
Each diamond is a study's best estimate. The thin line shows how sure the study was: the shorter the line, the more certain the result.
- Exercise cortisol AUC% · Crossover RCT 2008, n=10, 600 mg, p<0.01−35.0%[not given]
- Peak exercise cortisol% · Crossover RCT 2008, n=10, 600 mg−39.0%[not given]
- Testosterone:cortisol AUC ratio% · Crossover RCT 2008, n=10, p=0.02+184.0%[not given]
Each unit gets its own scale, so numbers are never mixed on one line. When a study gave no range, we leave it blank instead of inventing one.
4 studies over 22 years
The studies
- 1.Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy menEuropean Journal of Clinical Pharmacology · 1992 · crossover · n = 9
Brain-cortex PS 800 mg/day for 10 days blunted the ACTH (p=0.003) and cortisol (p=0.03) response to exercise stress; growth hormone and prolactin were unaffected.
- 2.The effects of phosphatidylserine on endocrine response to moderate intensity exerciseJournal of the International Society of Sports Nutrition · 2008 · crossover · n = 10
600 mg/day for 10 days cut peak cortisol 39% and cortisol AUC 35% (p<0.01), raised testosterone AUC 37% (p=0.02) and the T:C ratio 184%; growth hormone was unchanged.
- 3.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 studyLipids in Health and Disease · 2014 · rct · n = 72
PAS 400 (400 mg PS + 400 mg PA) for 42 days normalised ACTH (p=0.010), salivary cortisol (p=0.043) and serum cortisol (p=0.035) to acute stress — but only in the chronically high-stressed subgroup. PAS 200 did nothing.
- 4.Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stressStress · 2004 · rct · n = 80
400 mg/day PAS blunted the ACTH and salivary cortisol response to the Trier Social Stress Test, while 600 mg and 800 mg did not — an inverted dose-response that has never been explained or replicated.
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