tuneTypical Dose
100–300 mg per day
Fatty Acid
Phosphatidylserine
Phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine)
Evidence TierBWADA NOT PROHIBITED
watchEffect Window
4–12 weeks for cognition. Acute/immediate for cortisol blunting pre-workout.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Phosphatidylserine is a neuronal membrane phospholipid involved in signaling and synaptic function. It is used for memory and attention complaints and for stress-related cognitive performance support.
Trials suggest modest benefits for memory and attention in aging populations and in stress-related cognitive complaints. Some studies report reduced cortisol response to strenuous exercise. Minority evidence includes potential benefit for ADHD symptoms and sports recovery measures. Effects vary by source material, dose, and baseline cognitive status, with smaller effects in healthy young adults.
Structural phospholipid in neuronal membranes that supports neurotransmitter release (dopamine, acetylcholine), brain glucose metabolism, and cellular signaling. Blunts HPA-axis cortisol response to physical and emotional stress.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Mild-to-moderate improvements in memory and word recall in elderly with cognitive complaints (Kato-Kataoka 2010)
- FDA qualified health claim for cognitive dysfunction and dementia
Secondary Outcomes
- Blunts exercise-induced cortisol spike at 600–800 mg (Monteleone 1992)
- Supports neurotransmitter release (dopamine, acetylcholine) via membrane fluidity
Safety
Contraindications and Interactions
Contraindications
- Bovine-derived PS (BSE risk, use soy or sunflower only)
Side effects
- GI upset
- Insomnia at high doses (>300 mg)
Interactions
- Anticoagulants (mild additive effect at high doses)
- Anticholinergics (opposing mechanism)
Avoid if
- Anticoagulant therapy without physician oversight (high-dose PS)
Evidence
Study-level References
phosphatidylserine-SRC-001Double-blind, randomized, placebo-controlled trial.
Sourceopen_in_newKato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr. 2010;47(3):246-255. doi:10.3164/jcbn.10-62. PMID:21103034.
Population: Elderly Japanese adults with memory complaints and mild cognitive impairment.
Dose protocol: Source-listed
Key findings: Six months of supplementation with soy-derived PS significantly improved delayed word recall memory.
Paper content
This 6-month double-blind RCT randomized 78 adults with memory complaints to placebo, 100 mg/day Soy-PS, or 300 mg/day Soy-PS. Across the full sample, neuropsychological scores improved similarly in all groups, which limits any broad claim of large placebo-adjusted benefit. The useful signal was in participants with lower baseline memory performance, where Soy-PS improved delayed verbal recall while placebo did not. Safety markers and vital signs were unchanged, and no Soy-PS-related adverse effects were observed. This is a meaningful but modest memory-support study, not proof of broad cognition enhancement in healthy adults.
phosphatidylserine-SRC-002Systematic review and meta-analysis.
Sourceopen_in_newBruton A, Nauman J, Hanes D, Gard M, Senders A. Phosphatidylserine for the Treatment of Pediatric Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis. J Altern Complement Med. 2021;27(4):312-322. doi:10.1089/acm.2020.0432. PMID:33539192.
Population: Children with ADHD across 3 RCTs (216 participants in the meta-analysis, 344 in the systematic review).
Dose protocol: Phosphatidylserine 200-300 mg/day versus placebo, pooled across 3 RCTs in children with ADHD
Key findings: Statistically significant effect on inattention (ES 0.36, p=0.01). Overall ADHD symptoms and hyperactivity-impulsivity did not reach significance. Evidence quality rated low.
Notes: First meta-analysis specifically evaluating PS for ADHD. Confirms a directional signal for inattention but highlights limitations of the small evidence base.
Paper content
This systematic review and meta-analysis pooled 3 RCTs (n=216) examining phosphatidylserine at 200-300 mg/day for pediatric ADHD. The meta-analysis found a statistically significant small-to-moderate effect on inattention symptoms (ES 0.36, p=0.01), but overall ADHD symptoms (p=0.07) and hyperactivity-impulsivity (p=0.09) did not reach significance. The authors noted that evidence quality is low and additional research is needed. This is the first meta-analysis specifically evaluating PS for ADHD and confirms a directional signal for inattention while highlighting the limitations of the small evidence base.
phosphatidylserine-SRC-003Randomized, placebo-controlled trial, three-arm.
Sourceopen_in_newHellhammer J, Vogt D, Franz N, Freitas U, Rutenberg D. 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;13:121. doi:10.1186/1476-511X-13-121. PMID:25081826.
Population: Healthy male volunteers stratified by chronic stress level.
Dose protocol: PS/PA complex at 200 or 400 mg PS/day for 42 days in healthy men stratified by chronic stress
Key findings: PAS 400 normalized ACTH (p=0.010), salivary cortisol (p=0.043), and serum cortisol (p=0.035) responses to acute stress in chronically stressed men. Lower dose and placebo showed no effect.
Notes: Important direct HPA-axis evidence for PS at a meaningful dose. Effect was specific to chronically stressed individuals, which aligns with the cortisol-blunting application.
Paper content
This three-arm RCT tested two doses of a soy-based PS/PA complex (PAS 200 and PAS 400) versus placebo over 42 days in 75 healthy men stratified by chronic stress levels. The higher dose (400 mg PS + 400 mg PA/day) significantly normalized ACTH, salivary cortisol, and serum cortisol responses to an acute stressor in the chronically stressed subgroup. The lower dose and placebo showed no effect. Heart rate and psychological measures were not significantly affected. This study provides direct HPA-axis evidence for PS at a meaningful dose, specifically in stressed populations where cortisol dysregulation is most relevant.