Phosphatidylserine After 40: Memory, Stress, and Training

Turning 40 rarely changes how hard people want to train, but it often changes how they recover, sleep, and handle stress — and many start noticing small lapses in memory. Phosphatidylserine (PS) is one of the few supplements marketed for both brain health and exercise stress. Our editorial team looked at whether the evidence supports its use in middle-aged, physically active adults.

What phosphatidylserine does in the body

Phosphatidylserine is a phospholipid, one of the building blocks of cell membranes. It is particularly concentrated in the brain, where it sits on the inner layer of nerve cell membranes and helps regulate signaling proteins, neurotransmitter release, and membrane fluidity.

The body can synthesize PS, and food supplies some as well, mainly from organ meats, fish such as mackerel and herring, and to a lesser extent soy and white beans. Typical dietary intake in Western countries is estimated at roughly 100–200 mg per day, and lower in plant-based diets.

With age, changes in membrane composition and lipid metabolism occur in the brain. This observation drove early interest in whether supplemental PS could support cognitive function in older adults.

Today's supplements are made almost entirely from soy or sunflower lecithin. Early studies used PS from bovine brain, which was abandoned in the 1990s over concerns about prion diseases; that distinction matters when reading older research.

Cognitive evidence for people over 40

The best-known study is a 1991 trial by Crook and colleagues in Neurology, which gave 300 mg per day of bovine-derived PS to adults with age-associated memory impairment for 12 weeks. Participants improved on several memory tests compared with placebo, especially those with the most pronounced impairment at baseline.

Later trials using soy-derived PS have produced mixed results. A Japanese study in elderly people with memory complaints reported improvements in memory scores, particularly among those with lower baseline performance, while other studies found little difference from placebo in healthy volunteers.

In 2003 the FDA allowed a qualified health claim for PS, but the wording is notably cautious: it states that very limited and preliminary research suggests PS may reduce the risk of cognitive dysfunction in the elderly, and that the FDA concludes there is little scientific evidence supporting the claim.

For a healthy 45-year-old without memory problems, expectations should be modest. PS is not a "smart drug"; any benefit seems most likely in people who already have some measurable decline.

Stress hormones and exercise recovery

The more intriguing angle for active adults is PS's apparent effect on the stress response. In the early 1990s, Monteleone and colleagues reported that PS blunted the rise in ACTH and cortisol caused by physical stress in healthy men.

A 2008 study by Starks and colleagues in the Journal of the International Society of Sports Nutrition found that 600 mg per day of soy-derived PS for 10 days attenuated the cortisol response to moderate-intensity cycling and improved the testosterone-to-cortisol ratio compared with placebo. Other small trials have looked at perceived soreness, mood, and markers of muscle damage, with mixed findings.

Why does this matter after 40? Recovery capacity tends to decline with age, and many middle-aged athletes balance training with demanding jobs and family life. In theory, modulating the cortisol response could support recovery and sleep, although this has not been convincingly demonstrated in long-term outcome studies.

It is also worth noting that cortisol is not an enemy: it mobilizes energy and controls inflammation. A blunted acute response is not automatically better for adaptation.

Doses and practical use

Doses in published studies fall into two broad bands, depending on the goal:

Practical points for adults over 40 who want to try it:

1. Choose soy- or sunflower-derived PS with the dose of PS itself stated on the label, not just "phospholipid complex."
2. Take it with meals to improve tolerance.
3. Give it at least 6–8 weeks before judging cognitive effects.
4. Track something concrete — sleep quality, perceived recovery, or a simple memory test — rather than relying on vague impressions.
5. Reassess cost versus benefit: PS is relatively expensive per effective dose.

Sunflower-based PS is an option for people who prefer to avoid soy, although most clinical research has used soy-derived material.

Safety and interactions

In clinical trials, PS has been well tolerated at doses up to several hundred milligrams per day. The most frequently reported side effects are mild: gastrointestinal discomfort, and occasionally insomnia when taken at higher doses late in the day.

Because PS may influence blood clotting in theory and has been studied alongside cholinergic agents, people on anticoagulants or medications for dementia should consult their physician before use. Data in pregnancy and breastfeeding are lacking.

As a dietary supplement in the US, PS is regulated under DSHEA and not pre-approved for safety or efficacy. Choosing products verified by independent testing organizations is a sensible precaution.

PS is not prohibited by WADA, and it is not a hormonal agent; its effect on cortisol appears modest and short-term. Tested athletes should still prefer certified products.

Editorial Team Conclusions

Phosphatidylserine is a biologically plausible and generally safe supplement with a modest evidence base. The strongest data apply to older adults with existing memory complaints, not to healthy middle-aged people.

For active adults over 40, the cortisol-related findings are interesting but come from small, short studies. PS might be worth a time-limited trial for someone struggling with training stress, but it is not a substitute for sleep, programming, and nutrition.

Anyone noticing real memory decline should prioritize a medical evaluation: thyroid problems, vitamin B12 deficiency, sleep apnea, and depression are common, treatable causes.

Related reading: our articles on ashwagandha and cortisol, on Bacopa monnieri side effects, and on recovery strategies for masters athletes.

References

1. Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41(5):644–649.
2. Kato-Kataoka A, Sakai M, Ebina R, et al. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr. 2010;47(3):246–255.
3. Monteleone P, Maj M, Beinat L, Natale M, Kemali D. 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, Purpura M, Jäger R. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr. 2008;5:11.
5. Jäger R, Purpura M, Kingsley M. Phospholipids and sports performance. J Int Soc Sports Nutr. 2007;4:5.
6. Kingsley M, Wadsworth D, Kilduff LP, McEneny J, Benton D. Effects of phosphatidylserine on oxidative stress following intermittent running. Med Sci Sports Exerc. 2005;37(8):1300–1306.