Phosphatidylserine: Benefits, Dosage, Side Effects And Research

Phosphatidylserine (PS) is a phospholipid that forms part of every cell membrane and is especially concentrated in the brain. As a supplement, phosphatidylserine is mainly studied for memory in older adults with age-related memory complaints and, in smaller trials, for blunting the cortisol response to hard exercise. The evidence is real but mixed: the strongest positive trials used PS made from cow brain, while the soy and sunflower PS sold today has a smaller and less consistent research base.

Disclosure: nootropic.org/ may earn a commission from qualifying purchases made through links on this page, including as an Amazon Associate. This never affects which products we recommend. Learn more.

What Is Phosphatidylserine And How Does It Work?

Phosphatidylserine is one of the phospholipids that make up cell membranes. In the brain, it helps form the plasma membranes of neurons, and where it sits in the membrane (inside versus outside) affects cell signaling pathways tied to cell survival, such as Akt, protein kinase C and Raf-1, as well as synaptic communication.^[8]

Most PS in the brain is made locally rather than taken straight from the diet, typically from other DHA-rich phospholipids: phosphatidylcholine and phosphatidylethanolamine.^[8] That is one reason the relationship between swallowing PS and brain PS levels is not straightforward. For a deeper look at how PS relates to its precursor, see our guide to phosphatidylserine vs phosphatidylcholine.

Bovine Vs Soy Vs Sunflower Phosphatidylserine

The source of PS matters more than with most supplements, because the research changed when the raw material changed.

• Bovine-cortex PS was used in most of the early positive trials. It is no longer commercially available because of concerns about mad cow disease (bovine spongiform encephalopathy, or BSE).^[8]
• Soy-derived PS is made from soy lecithin. Its trials have produced mixed results (details below).
• Sunflower-derived PS is made by enzymatically converting sunflower lecithin with L-serine. A sunflower PS ingredient (SunPS) was the subject of an FDA GRAS notice, which also describes how plant sources replaced bovine PS because of BSE contamination concerns.^[10] Sunflower PS is a common pick for people avoiding soy.

Bovine and plant PS differ in their fatty acid tails (the bovine-cortex PS used in the largest trial was described as PS-DHA),^[8] which is one proposed reason the results do not transfer neatly. Treat bovine-era findings as suggestive for modern products, not as proof.

What Does Phosphatidylserine Do? Benefits And Evidence

Here is what the research says for each common use, with an honest rating of evidence strength.

Memory In Older Adults (Evidence: Moderate For Bovine PS, Limited For Plant PS)

The best-known positive trials used bovine PS at 100 mg three times daily. In a randomized, double-blind trial of 149 adults with age-associated memory impairment, 12 weeks of PS improved several memory and performance measures compared with placebo.^[1] The largest trial, a multicenter Italian study of 494 older adults with moderate to severe cognitive decline, reported improvements in memory, learning, motivation and socialization over 3 to 6 months.^[2][8]

Soy PS has a weaker track record:

• A randomized trial of 120 older adults with age-associated memory impairment found no significant differences on any outcome after 12 weeks of 300 or 600 mg/day soy PS.^[3]
• A 6-month Japanese trial of 78 adults aged 50 to 69 with memory complaints found that all groups, including placebo, improved. Only participants with relatively low baseline scores showed memory gains on soy PS (100 or 300 mg/day), mostly in delayed verbal recall.^[4]
• An open-label pilot study of 300 mg/day soy PS reported memory gains over 12 weeks, but it had no placebo group, and all authors were current or former employees of the PS manufacturer.^[5]

Bottom line: PS is a reasonable thing to try for age-related memory complaints, but expect modest effects at best, and know that the strongest data come from a form you cannot buy. For other options, see our guide to the best supplements for memory.

The FDA Qualified Health Claim For Phosphatidylserine

In 2003, FDA issued letters of enforcement discretion for a qualified health claim titled “Phosphatidylserine and Cognitive Dysfunction and Dementia,” and it updated that claim in a November 2004 letter.^[9] A qualified health claim is not an approval; it means FDA will not object to a claim as long as it carries language that reflects how weak the evidence is.

The dementia claim reads “Consumption of PS may reduce the risk of dementia in the elderly,” and it must be paired with the qualifier that “very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of dementia in the elderly.”^[11] According to a later FDA GRAS filing, the claim was allowed for PS from soy lecithin and from bovine cortex, with bovine PS acceptable only from cattle not born, raised or slaughtered in countries where BSE exists.^[11]

Read that qualifier literally. FDA’s own wording signals low confidence, and it is not evidence that PS prevents or treats dementia.

Phosphatidylserine And Cortisol (Evidence: Limited)

Searches for “does phosphatidylserine lower cortisol” usually trace back to a few small exercise studies. In a double-blind crossover trial, 10 healthy men took 600 mg/day of soy PS or placebo for 10 days, then cycled at moderate to high intensity. Peak cortisol was about 39% lower and cortisol area under the curve 35% lower on PS.^[6] The study was tiny, all male and industry-funded, and the authors noted an earlier study at higher exercise intensity found no cortisol effect.^[6]

An independent review from the Alzheimer’s Drug Discovery Foundation describes the cortisol evidence as “varied and very small clinical studies.”^[8] That is a fair summary. There is no good evidence that PS lowers everyday resting cortisol or helps with “adrenal fatigue.”

Phosphatidylserine For Anxiety And Stress (Evidence: Preliminary)

Interest in PS for anxiety follows from the cortisol work, but we found no well-designed trials of PS alone for anxiety symptoms. If stress is your main concern, ingredients such as L-theanine, ashwagandha and rhodiola have more direct human data.

Phosphatidylserine For Sleep: What The Evidence Says

“Phosphatidylserine for sleep” is a popular search, but the evidence is thin. We could not find a published randomized controlled trial that tested PS alone with sleep as its main outcome. The idea is indirect: if PS blunts cortisol, taking it in the evening might help people whose stress keeps them up. That logic rests on the small exercise studies above, not on sleep data.^[6][8] An independent review of PS lists sleep only as an outcome planned for a future trial, not as an established finding.^[8]

Evidence rating: Preliminary. If you want to try it, there is no studied “phosphatidylserine dosage for sleep.” People commonly take one 100 mg dose in the evening, but that is a convention, not a researched protocol.

Exercise And Other Uses (Evidence: Preliminary)

Beyond cortisol, PS has been explored for exercise capacity, attention in children and mood, but the trials are small and scattered. A 2015 review of 127 articles concluded that a number of open-label trials showed promise for cognition, which then led to randomized trials.^[7] There is no credible evidence that PS causes weight loss.

Phosphatidylserine Dosage: What Studies Used

Supplemental doses in the research range from 300 to 800 mg/day, usually split into divided doses and most often given as 100 mg three times daily.^[7]

Purpose	Dose	Duration	Study
Age-associated memory impairment (bovine PS)	100 mg 3x/day (300 mg)	12 weeks	Crook 1991[1]
Cognitive decline in older adults (bovine PS)	100 mg 3x/day (300 mg)	6 months	Cenacchi 1993[2]
Memory complaints (soy PS)	300 or 600 mg/day	12 weeks	Jorissen 2001 (no effect)[3]
Memory complaints (soy PS)	100 or 300 mg/day	6 months	Kato-Kataoka 2010[4]
Cortisol response to exercise (soy PS)	600 mg/day	10 days	Starks 2008[6]

When To Take Phosphatidylserine

The memory trials split the daily dose across meals (100 mg three times a day).^[1][5] PS is a fat-soluble lipid, so taking it with food is sensible. There is no evidence that a specific “best time of day to take phosphatidylserine” changes results. If you are trying it for exercise stress, the cortisol study gave it daily for 10 days before testing, which suggests consistent use matters more than timing.^[6]

Forms And What To Look For In A Phosphatidylserine Supplement

• Source on the label: look for “from sunflower lecithin” or “from soy lecithin.” Bovine PS is not what you are buying.
• PS amount, not “complex” weight: many products list a larger “phosphatidylserine complex” or “phosphatide complex” weight. Check that the label states milligrams of actual PS per serving.
• Softgels or capsules: PS is oily and can oxidize, so sealed softgels and a sensible expiration date are good signs.
• Third-party testing: a certificate of analysis confirms the PS content and checks for contaminants.

Side Effects And Safety: Is Phosphatidylserine Safe?

PS has been well tolerated, with no serious adverse events reported in short trials, though long-term safety data are lacking.^[8] In the 6-month Japanese soy PS trial, no PS-related side effects or changes in blood markers were seen.^[4] In the open-label pilot study, two of 30 participants dropped out with stomach discomfort judged probably related to PS.^[5]

One signal worth knowing about: some trials reported small drops in blood pressure. The open-label soy PS study saw systolic pressure fall by 8.9 mmHg and diastolic by 6.8 mmHg, and a marine PS-DHA extension study reported a 3.1 mmHg drop in diastolic pressure.^[5][8] These findings were unexpected and unconfirmed. People on blood pressure medication should monitor their readings.

Drug Interactions And Who Should Avoid It

Formal drug interaction research on PS is sparse, so the cautious approach is to talk with a pharmacist before using it if you take prescription medication. Specific groups should be careful:

• People taking blood pressure medication, given the blood pressure signals above.^[5]
• People with diagnosed dementia or cognitive impairment, who should not use PS in place of medical evaluation and treatment.
• Pregnant or nursing women and children, because there is no meaningful safety data in these groups.
• People with soy allergy, who should choose sunflower-derived PS.

How Phosphatidylserine Stacks With Other Nootropics

PS is commonly paired with a choline source such as citicoline or alpha-GPC, and with bacopa monnieri for memory-focused stacks. Some people also combine it with omega-3s, since the original bovine PS was DHA-rich. None of these combinations has been tested head-to-head against PS alone, so think of stacking as convenience rather than proven synergy. Our nootropic stacks guide covers how to add ingredients one at a time.

Where To Buy Phosphatidylserine

If you want a study-matched dose, a standalone PS product lets you take 100 mg three times daily. Nootropics Depot sells a 100 mg PS softgel that is third-party tested; buy it through their authorized Amazon store and check that the listing says “Sold by Nootropics Depot.”

Check Nootropics Depot Phosphatidylserine On Amazon

Phosphatidylserine FAQs

What Is Phosphatidylserine Used For?

It is mainly used for age-related memory complaints and, less commonly, to blunt the cortisol response to intense training. The memory evidence is strongest for bovine PS, which is no longer sold.^[8]

Does Phosphatidylserine Lower Cortisol?

In one small crossover study, 600 mg/day of soy PS lowered the cortisol spike after moderate to high intensity cycling by roughly 35% to 39%.^[6] There is no good evidence that it lowers normal resting cortisol.

Does Phosphatidylserine Help You Sleep?

There is no solid evidence. We found no randomized trial testing PS alone for sleep. Any sleep benefit is theoretical and based on the cortisol research.

Is Phosphatidylserine Safe?

Short-term trials of up to 6 months have reported good tolerability, with occasional stomach upset and possible small blood pressure drops. Long-term safety data are limited.^[4][8]

Is Phosphatidylserine 300 Mg Better Than 100 Mg?

Most positive memory trials used 300 mg/day.^[1][2] One soy PS trial found similar results at 100 and 300 mg/day, but only in a subgroup.^[4] If you want to match the research, 300 mg/day is the standard.

Is Phosphatidylserine The Same As Phosphatidylcholine?

No. Both are membrane phospholipids, but phosphatidylcholine is a major dietary choline source, while PS is studied for memory and stress. See our phosphatidylserine vs phosphatidylcholine comparison.

References

1. Crook TH, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41:644-649. PubMed
2. Cenacchi T, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano). 1993;5(2):123-133. PubMed
3. Jorissen BL, et al. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. Nutritional Neuroscience. 2001;4(2):121-134. PubMed
4. Kato-Kataoka A, et al. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. Journal of Clinical Biochemistry and Nutrition. 2010;47(3):246-255. PubMed
5. Richter Y, et al. The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study. Clinical Interventions in Aging. 2013;8:557-563. DOI
6. Starks MA, et al. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. Journal of the International Society of Sports Nutrition. 2008;5:11. PubMed
7. Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015;31(6):781-786. PubMed
8. Alzheimer’s Drug Discovery Foundation. Phosphatidylserine. Cognitive Vitality For Researchers. ADDF
9. U.S. Food and Drug Administration. Qualified Health Claims: Letters of Enforcement Discretion (Phosphatidylserine and Cognitive Dysfunction and Dementia, 2003; updated 2004). FDA
10. U.S. Food and Drug Administration. GRAS Notice 636: Phosphatidylserine derived from sunflower lecithin. 2016. FDA
11. U.S. Food and Drug Administration. GRAS Notice 643: Phosphatidylserine derived from fish. FDA