Phosphatidylserine (PS)

What it is

Phosphatidylserine is a phospholipid, that is, a fat with a water-loving head, from which cell membranes are built. Its proportion is particularly high in the brain. Your body produces it itself, and you also take in small amounts with food, for example via organ meats and soy.

The first products were obtained from bovine brain, abbreviated BC-PS. Because of theoretical concerns that prions, as in mad cow disease, could be transmitted this way, this source was replaced. Today PS comes from soy or from marine animals. This changeover is the most important point for understanding the body of evidence.

How it is supposed to work

For cognition, the idea is that PS supports the function of nerve cell membranes and thus signal transmission. This part of the chain of action comes from cell and animal models; it has not been measured directly in humans.

The stress axis is more tangible. In two placebo-controlled studies with healthy men, PS dampened the release of the stress hormone ACTH and of cortisol during physical exertion. This is an effect that has been measured in humans, albeit in very few participants.

Stress, training and sleep

In sport, PS is taken mainly to limit the rise in cortisol after hard training. The figures on this come from small, short studies. For psychological stress, the picture is more nuanced: a study with 75 men found a normalized stress response only with a combination of PS and phosphatidic acid, only at the higher dose and only in participants with severe chronic stress. The subjective experience of stress did not change. Another study with 60 men who took omega-3 PS for 12 weeks likewise found no effect in the group as a whole, but only in the subgroup with high chronic stress. For psychological stress, PS therefore seems mainly to normalize an overstimulated stress axis, whereas under physical exertion it dampened it even in healthy men.

PS is often recommended for sleep, especially in the evening. A controlled study examining PS alone and sleep quality could not be found in the literature search for this page. The recommendation is a derivation from the cortisol finding, not a finding of its own.

What the studies show

Multicenter study 1993: 494 older patients

Double-blind and placebo-controlled, at 23 clinics in northern Italy. The participants, aged 65 to 93, had moderate to severe cognitive decline and received 300 mg PS from bovine brain daily for 6 months. Behavior and memory tests improved significantly compared with placebo, and the product was well tolerated.

Soy PS 2001: no effect

Jorissen and colleagues gave 120 older people with memory complaints 300 or 600 mg soy PS or placebo for 12 weeks. No difference emerged either in delayed recall of a word list or in any other test. This study is important because it tests the form sold today.

Meta-analysis 2022: 9 studies, 961 participants

Kang and Cui evaluated 5 randomized studies and 4 before-and-after studies without a control group, with 100 to 300 mg daily over 6 weeks to 6 months. They found a positive effect on memory in older adults with cognitive decline and no side effects.

Cortisol study 2008: 10 men, 10 days

In a double-blind crossover study, 10 healthy men took 600 mg PS or placebo for 10 days and then cycled for 15 minutes at increasing intensity. With PS, peak cortisol was 39 % lower and the cortisol area under the curve 35 % lower. An older study with 9 men and PS from bovine brain had found a similar effect.

Stress test 2014: 75 men, 42 days

Hellhammer and colleagues gave 75 healthy men a product made of PS and phosphatidic acid in two doses or placebo for 42 days and then exposed them to a standardized psychosocial stress test. With 400 mg PS plus 400 mg phosphatidic acid, ACTH and cortisol normalized, but only in the participants with severe chronic stress. The lower dose had no effect, and heart rate and perceived stress remained unchanged.

Where the data stop

The central limitation is the change of source. The convincing memory studies from 1991 and 1993 used PS from bovine brain. There are considerably fewer data for soy PS, and the largest direct trial with 120 people found no effect. The meta-analysis by Kang and Cui also mixes randomized studies with uncontrolled before-and-after comparisons. A 2026 network meta-analysis saw an improvement in the dementia screening test MMSE with 100 mg PS, but none in the more precise ADAS-Cog.

For healthy young people who take PS for focus and memory, there are no cognition studies. The cortisol data are based on 9 and 10 participants over 10 days each. In the ADHD finding, only inattention was significant, not the overall symptoms, and the authors rate the evidence as low. Controlled studies on sleep are lacking, as are studies on intake for longer than 6 months.

Status, approval and legal

In the EU, PS from soy phospholipids has been authorized since August 2011 as a novel food ingredient for certain foods such as yogurt drinks, cereal bars and chocolate, and must be labeled as soy phosphatidylserine. In Germany, PS is sold mainly as a dietary supplement. In the US, the FDA has allowed a restricted, so-called qualified health claim on PS and cognitive dysfunction and dementia since 2003, which was updated in 2004. Qualified there means that the evidence is explicitly considered limited. For competitive athletes, the general NADA notice on contamination of dietary supplements applies.

Safety

PS is well tolerated. In a controlled safety study with 120 older people, up to 600 mg soy PS daily over 12 weeks showed no differences from placebo in laboratory values, blood pressure, heart rate or side effects. The large study with PS from bovine brain reported good tolerability over 6 months. A review by the Alzheimer’s Drug Discovery Foundation lists a reduction in blood pressure or weight gain as possible effects. Anyone with a soy allergy should pay attention to the source. There are no data for pregnant and breastfeeding women, and PS has not been studied in controlled trials beyond 6 months.

Sources

• Kang, Cui et al., Korean J Food Sci Technol 2022 – meta-analysis on cognition in old age
• Cenacchi et al., Aging (Milano) 1993 – multicenter study with 494 patients
• Crook et al., Neurology 1991 – age-associated memory impairment
• Jorissen et al., Nutr Neurosci 2001 – soy PS and cognition
• Jorissen et al., Nutr Neurosci 2002 – safety of soy PS
• Starks et al., J Int Soc Sports Nutr 2008 – cortisol under exertion
• Monteleone et al., Eur J Clin Pharmacol 1992 – stress axis in healthy men
• Hellhammer et al., Lipids Health Dis 2014 – PS and phosphatidic acid in chronic stress
• Bruton et al., J Altern Complement Med 2021 – meta-analysis on ADHD
• Implementing Decision 2011/513/EU – soy phosphatidylserine as a novel food ingredient