The History of Phosphatidylserine: How a Supplement Became Popular

Phosphatidylserine, usually shortened to PS, is one of those supplements with a surprisingly long and winding backstory. It began as a curiosity of membrane biochemistry, spent decades as a candidate treatment for age-related memory decline, survived a food-safety scare in the 1990s, and re-emerged as a product marketed to strength athletes and stressed students alike. Tracing that journey helps explain both its appeal and the limits of the evidence behind it.

A molecule of the cell membrane

Phosphatidylserine is a phospholipid — a fat-based molecule with a phosphate head group, in this case attached to the amino acid serine. It is a structural component of every cell membrane in the body, but it is particularly concentrated in the brain, where it makes up a notable share of the phospholipids in nerve cell membranes.

It was first isolated and characterised in the 1940s by the American biochemist Jordi Folch, whose work on brain lipids also gave us the "Folch method" of lipid extraction still used in laboratories today. For decades, PS was of interest mainly to biochemists studying membrane structure.

Later research revealed active roles. PS normally sits on the inner leaflet of the membrane; when it flips to the outer surface, it acts as an "eat me" signal for cells undergoing programmed death. It also helps anchor and activate signalling enzymes such as protein kinase C, and supports neurotransmitter release.

These functions made it a logical candidate for research into ageing brains, where membrane composition and signalling efficiency change over time.

The bovine era and memory research

In the 1980s, Italian researchers and the pharmaceutical industry developed phosphatidylserine extracted from cow brain (bovine cortex PS, or BC-PS). It was tested in older people with memory complaints and early dementia.

Several trials reported modest improvements. The best known, a multicentre Italian study by Cenacchi and colleagues published in 1993, followed nearly 500 elderly patients with cognitive decline for six months and found improvements in behavioural and cognitive scores compared with placebo. Earlier, Crook and colleagues in the US had reported benefits in age-associated memory impairment.

Then came bovine spongiform encephalopathy. The BSE crisis in the UK in the 1990s made any product derived from cattle brain unacceptable, and bovine PS disappeared from the market almost overnight. The research programme was left without its test substance.

This turning point shaped everything that followed, because later products were chemically similar but not identical to the material used in the original trials.

The plant-based revival

Manufacturers responded by producing PS from soy lecithin using an enzyme, phospholipase D, which swaps the head group of plant phospholipids for serine. Later, sunflower lecithin became a popular starting material for allergen-free versions.

Plant-derived PS differs from bovine PS in its fatty acid chains. Brain PS is rich in docosahexaenoic acid (DHA), an omega-3 fatty acid, while soy PS contains mostly linoleic acid. Whether this difference matters for brain effects is debated, and clinical results with soy PS in older adults were less convincing than the bovine trials.

In the US, the Food and Drug Administration permitted qualified health claims in 2003, stating that very limited and preliminary evidence suggests PS may reduce the risk of cognitive dysfunction and dementia in the elderly. The carefully hedged wording itself illustrates the state of the evidence.

In Great Britain and the EU, no health claim for phosphatidylserine has been authorised, so products cannot legally claim to improve memory or reduce stress on their labels.

From the clinic to the gym

The leap into sports nutrition came from research on the stress hormone cortisol. Studies in the early 1990s, using bovine PS given intravenously and then orally, suggested it could blunt the rise in cortisol and ACTH after intense exercise.

Later work with soy PS in trained men produced mixed findings. Some studies reported reduced post-exercise cortisol, improved mood or perceived soreness, and one study found improved performance in golfers' tee-shot accuracy. Others found no meaningful effect on hormones or performance. Doses in these studies typically ranged from 300 to 800 mg per day.

Marketing seized on the cortisol narrative. PS became a staple ingredient in "anti-catabolic", "cortisol control" and sleep or stress formulas, often in amounts far below those used in research.

Why it stayed popular — and what to make of it

Several factors explain PS's lasting presence on supplement shelves:

• a credible biological role in the brain, easy to explain to consumers;
• historical clinical trials, even if conducted with a different form;
• a good safety record at doses up to around 300–600 mg per day in studies;
• its fit with fashionable themes — stress, focus, sleep and "adrenal" health.

Side effects reported in trials are generally mild, such as gastrointestinal upset or insomnia at higher doses. People taking anticoagulants or medicines for dementia should ask a doctor first, as theoretical interactions have been raised.

The honest summary is that PS is a safe supplement with a fascinating history, but modern plant-derived versions have a thinner evidence base than their marketing implies. For athletes, sleep, training load management and adequate carbohydrate remain far more powerful tools for controlling stress hormones.

Anyone curious to try it should look for products that state the actual PS content per serving rather than "phospholipid complex", and keep expectations modest.

Editorial team's conclusions

Phosphatidylserine travelled from biochemistry laboratories to dementia clinics, through the BSE crisis, and into gym supplement blends. Its rise owes as much to history and storytelling as to modern data. The molecule is genuinely important for cell membranes, but the evidence that plant-based PS supplements improve memory, cortisol control or performance in healthy people remains limited and inconsistent.

If the history of supplements interests you, you may also enjoy our pieces on how creatine moved from laboratory curiosity to the most studied sports supplement, what the evidence says about ashwagandha and cortisol, and how omega-3 fatty acids affect the brain.

References

1. Cenacchi T, Bertoldin T, Farina C, 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.
2. Crook TH, Tinklenberg J, Yesavage J, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41(5):644–649.
3. Monteleone P, Maj M, Beinat L, et al. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol. 1992;42(4):385–388.
4. Starks MA, Starks SL, Kingsley M, et al. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr. 2008;5:11.
5. Kingsley M. Effects of phosphatidylserine supplementation on exercising humans. Sports Med. 2006;36(8):657–669.
6. Jorissen BL, Brouns F, Van Boxtel MP, et al. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. Nutr Neurosci. 2001;4(2):121–134.