Phosphatidylserine

What it is

Phosphatidylserine is a phospholipid that forms part of cell membranes, including in the brain, and is naturally present across a wide range of foods. Most commercial phosphatidylserine used in foods and supplements is made from soy by an enzymatic reaction with phospholipase D; earlier products were extracted from bovine brain cortex. EFSA has pointed out that the bovine-cortex and soy-based forms differ in fatty acid composition, so results from one do not automatically transfer to the other. Health Canada estimated mean dietary intake at about 228 mg per day.

What the research says

The evidence is disputed and the older positive results mostly used a form no longer sold. The largest well-controlled trial of soy-derived phosphatidylserine in older people with memory complaints found no significant difference from placebo on any outcome. A later Japanese trial reported improved memory only in a subgroup with lower baseline scores, not in the whole sample. EFSA's expert panel concluded in 2010 that phosphatidylserine was not sufficiently characterised and that no cause-and-effect relationship could be established for the claimed cognitive effects, while the FDA had earlier allowed qualified claims about dementia risk in 2003 and 2004 under enforcement discretion. Health Canada's 2024 safety assessment found soy phosphatidylserine acceptable for supplement use.

Evidence grade: Disputed.

What goes wrong

Bovine-cortex phosphatidylserine, the form used in the early positive trials, was withdrawn because of prion disease concerns. (Source 1)

• Expert review, not systematic, Certainty not rated.
• Size: not applicable - expert summary.
• Who: supplement market.
• How long: not applicable.
• Result: no rate reported; a product-availability consequence of transmissible spongiform encephalopathy risk.
• Funding: Alzheimer's Drug Discovery Foundation, Cognitive Vitality.

Due to concerns for prion disease, PS from bovine cortex is no longer available.

Gastrointestinal complaints are among the more commonly reported adverse events with phosphatidylserine. (Source 1)

• Expert review, not systematic, Certainty not rated.
• Size: not applicable - expert summary; no rates given.
• Who: supplement users.
• How long: not applicable.
• Result: no rate reported in the source.
• Funding: Alzheimer's Drug Discovery Foundation, Cognitive Vitality.

Gastrointestinal complaints appear to be one of the more common adverse events.

Phosphatidylserine may interact with anticoagulants and with anticholinergic drugs. (Source 1)

• Expert review, not systematic, Certainty not rated.
• Size: not applicable - expert summary.
• Who: people taking anticoagulants, glaucoma or Alzheimer's medicines, or facing surgery.
• How long: not applicable.
• Result: no quantified interaction; a mechanistic caution.
• Funding: Alzheimer's Drug Discovery Foundation, Cognitive Vitality.

PS may increase risk of bleeding, and so may interact poorly with anticoagulants, and may be best avoided before surgery.

What the evidence supports

Health Canada's 2024 assessment concluded there was enough information to set conditions under which soy phosphatidylserine is safe as a supplemental ingredient. (Source 2)

• Official position, Certainty not rated.
• Size: not applicable - regulatory safety assessment.
• Who: Canadian supplement users.
• How long: not applicable.
• Result: conditions of safe use established for soy-derived phosphatidylserine as a supplemental ingredient.
• Funding: Health Canada Food Directorate, assessment dated 2024-04-18.

Health Canada's Food Directorate determined there to be sufficient information to establish conditions under which phosphatidylserine (soy) would be safe for use as a supplemental ingredient.

What the evidence does not support

A randomised trial of soy-derived phosphatidylserine in older people meeting criteria for age-associated memory impairment found no effect on memory or any other cognitive outcome. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 120 elderly participants.
• Who: people over 57 years old meeting stringent criteria for age-associated memory impairment.
• How long: 12 weeks of treatment plus a 3-week wash-out, assessed at baseline, 6 and 12 weeks.
• Result: no significant differences in any outcome variable between placebo, 300 mg/day and 600 mg/day groups; no interaction with severity of memory complaints.
• Funding: not stated.

No significant differences were found in any of the outcome variables between the treatment groups.

The authors of that trial concluded soy phosphatidylserine does not affect memory or other cognitive function in older people with memory complaints. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 120 elderly participants.
• Who: people over 57 with age-associated memory impairment.
• How long: 12 weeks plus wash-out.
• Result: null across learning, memory, choice reaction time, planning and attention measures.
• Funding: not stated.

In conclusion, a daily supplement of S-PS does not affect memory or other cognitive functions in older individuals with memory complaints.

EFSA's expert panel concluded that no cause-and-effect relationship could be established between phosphatidylserine and the claimed cognitive and stress effects. (Source 4)

• Official position, Certainty not rated.
• Size: not applicable - scientific opinion on health claims.
• Who: general EU population covered by the claims.
• How long: not applicable.
• Result: claims not substantiated; the constituent judged insufficiently characterised.
• Funding: European Food Safety Authority, Panel on Dietetic Products, Nutrition and Allergies, 2010.

The Panel concludes that a cause and effect relationship cannot be established between the consumption of phosphatidyl serine and the claimed effects considered in this opinion.

Where the evidence is mixed

In a six-month Japanese trial, memory test scores rose to a similar extent in every group including placebo, and the only separation from placebo was a within-group improvement in the subgroup whose baseline scores were relatively low. (Source 5)

• Randomized trial, Low certainty.
• Size: 78 participants.
• Who: elderly Japanese people aged 50 to 69 with mild cognitive impairment and memory complaints.
• How long: 6 months.
• Result: no overall separation from placebo: neuropsychological test scores increased similarly in all groups including placebo; the reported gain was a within-group increase against baseline in the phosphatidylserine arms among subjects with relatively low baseline scores, attributed mostly to delayed verbal recall.
• Funding: not stated on the page fetched; authors are affiliated with a supplement manufacturer, which a reviewer should verify.

Limit of this finding: The headline result is a subgroup defined after the fact by baseline score, and it is a comparison against each group's own starting point rather than against placebo. The paper itself says scores rose similarly in every group including placebo, so this trial does not show that phosphatidylserine beat placebo overall.

Neuropsychological test scores were similarly increased in all groups including placebo group. However, in the subjects with relatively low score at baseline, the memory scores in PS treated groups were significantly increased against the baseline, while those of placebo group remained unchanged.

EFSA's panel stated that bovine brain cortex- and soy-based phosphatidylserine are different substances and, citing FDA (2003), that there is considerable uncertainty in generalising results from one source material to the other. (Source 6)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: not applicable.
• How long: not applicable.
• Result: no effect size; a judgement about transferability of evidence between source materials, attributed by EFSA to FDA, 2003.
• Funding: European Food Safety Authority, 2010.

Bovine brain cortex- and soy-based phosphatidyl serine are different substances and might, therefore, have different biological activities. Thus, there is considerable uncertainty in generalising results from studies done with bovine brain cortex phosphatidyl serine as the test substance to soy-based phosphatidyl serine, and vice versa (FDA, 2003).

The fatty acid composition of soy-derived and bovine-brain-cortex phosphatidylserine differs, a characterisation EFSA reproduced from FDA, 2003 rather than generating itself. (Source 7)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: not applicable.
• How long: not applicable.
• Result: soy phosphatidyl serine 7 % alpha-linolenic acid (n-3) and 47 % linoleic acid (n-6); bovine brain cortex phosphatidyl serine mostly saturated and monounsaturated fatty acids besides 8 % docosahexaenoic acid (n-3) and 2 % arachidonic acid (n-6)
• Funding: European Food Safety Authority, 2010, reporting a characterisation it attributes to FDA, 2003.

Limit of this finding: These fatty acid percentages are not an EFSA measurement. EFSA cites them to FDA, 2003, and a reader should treat them as FDA's characterisation reported by EFSA.

For example, the phosphatidyl serine from soy contains 7 % alpha-linolenic acid (n-3) and 47 % linoleic acid (n-6), while the phosphatidyl serine derived from bovine brain cortex contains mostly saturated and monounsaturated fatty acids besides 8 % docosahexaenoic acid (n-3) and 2 % arachidonic acid (n-6) (FDA, 2003).

The US FDA issued letters of enforcement discretion for qualified health claims linking phosphatidylserine to cognitive dysfunction and dementia in 2003, updated in 2004. (Source 8)

• Official position, Certainty not rated.
• Size: not applicable - regulatory position.
• Who: US food and supplement labelling.
• How long: not applicable.
• Result: no effect size; enforcement discretion for qualified claims, the wording of which we could not retrieve.
• Funding: US Food and Drug Administration, letters dated February 24 2003, May 13 2003 and November 24 2004.

Letter Updating the Phosphatidylserine and Cognitive Function and Dementia Qualified Health Claim

The overall human evidence base for phosphatidylserine consists of small studies, and an expert review says larger rigorous trials are still needed for both efficacy and safety. (Source 1)

• Expert review, not systematic, Certainty not rated.
• Size: not applicable - expert summary.
• Who: older adults and people with cognitive complaints.
• How long: not applicable.
• Result: no pooled estimate.
• Funding: Alzheimer's Drug Discovery Foundation, Cognitive Vitality.

Several small studies have indicated a potential benefit of PS for cognition. However, large, rigorous, updated studies of specific formulations of PS are needed both for efficacy and confirmation of safety.

Where the research disagrees

Whether phosphatidylserine has a substantiated effect on memory and dementia risk

• US Food and Drug Administration, letters of enforcement discretion dated February 24 2003, May 13 2003 and November 24 2004, regulatory position allowing a qualified claim; the letters themselves were unreachable, so the qualifying wording is not quoted here: Letter Updating the Phosphatidylserine and Cognitive Function and Dementia Qualified Health Claim (Source 8)
• EFSA Panel on Dietetic Products, Nutrition and Allergies, 2010, scientific opinion assessing the claim evidence: The Panel concludes that a cause and effect relationship cannot be established between the consumption of phosphatidyl serine and the claimed effects considered in this opinion. (Source 4)

Whether soy phosphatidylserine improves memory in older people

• Jorissen and colleagues, Nutritional Neuroscience 2001, randomised, three-arm, placebo-controlled trial in 120 people: In conclusion, a daily supplement of S-PS does not affect memory or other cognitive functions in older individuals with memory complaints. (Source 3)
• Kato-Kataoka and colleagues, Journal of Clinical Biochemistry and Nutrition 2010, double-blind randomised controlled study in 78 people in which scores rose similarly in all groups including placebo, with the reported effect confined to a baseline-defined subgroup: Neuropsychological test scores were similarly increased in all groups including placebo group. However, in the subjects with relatively low score at baseline, the memory scores in PS treated groups were significantly increased against the baseline, while those of placebo group remained unchanged. (Source 5)

How much

• Reference intake: No RDA, Adequate Intake or other reference intake has been set for phosphatidylserine by any body we located; it is a membrane phospholipid the body makes and also obtains from ordinary food. Health Canada's 2024 assessment cites an estimated mean daily dietary intake of about 228 mg per day, attributed to an industry submission (Degusa Food Ingredients GmbH, 2006). (Source 9)
• Upper limit: No Tolerable Upper Intake Level or ADI has been set. Health Canada's 2024 assessment instead identified a no-observed-adverse-effect level of 960 mg/kg body weight per day in animal toxicology for fish-derived phosphatidylserine, and set conditions of use for the soy-derived ingredient. (Source 10)
• Studied: Soy-derived phosphatidylserine 300 mg/day or 600 mg/day for 12 weeks in people with age-associated memory impairment. (Source 3)
• Studied: Soy-derived phosphatidylserine 100 mg/day or 300 mg/day for 6 months in elderly Japanese people with memory complaints. (Source 5)
• Studied: Health Canada's safety assessment reviewed clinical trials of supplemental phosphatidylserine and reported no significant differences between groups for adverse events, vital signs, or biochemical or hematological parameters. (Source 11)

A common belief, and what the research shows

The belief: The FDA approved phosphatidylserine for memory and dementia, so it must work.

What the research shows: What FDA issued were letters of enforcement discretion for qualified claims, listed on its site as "Letter Updating the Phosphatidylserine and Cognitive Function and Dementia Qualified Health Claim" and dated 2003 and 2004. A qualified claim is not an approval of efficacy. Europe's regulator reached the opposite view five years later: "The Panel concludes that a cause and effect relationship cannot be established between the consumption of phosphatidyl serine and the claimed effects considered in this opinion." The strongest single trial of the soy form was null: "No significant differences were found in any of the outcome variables between the treatment groups." And the early positive research used bovine brain material that is no longer sold, about which EFSA warned, citing FDA (2003), "Thus, there is considerable uncertainty in generalising results from studies done with bovine brain cortex phosphatidyl serine as the test substance to soy-based phosphatidyl serine, and vice versa (FDA, 2003)."

Questions and answers

What is it?

Phosphatidylserine is a phospholipid, one of the fatty molecules that make up cell membranes, and it is naturally present in a wide range of foods. The material in supplements is almost all made from soy lecithin by an enzyme reaction with L-serine. Older supplements used extract of bovine brain cortex, which is chemically different and no longer on the market. (Source 12)

What does it do in the body?

In the body phosphatidylserine is a structural component of cell membranes, including in nerve cells. The idea behind the supplement is that extra phosphatidylserine supports neuronal membrane function and therefore thinking and memory. That is how the trials describe the claim rather than an established mechanism of benefit, and the trial evidence has not borne it out consistently. (Source 3)

Is it good or bad for you?

On safety, regulators are reasonably comfortable: Health Canada concluded in 2024 that conditions of safe use could be set for soy phosphatidylserine, and trials up to 600 mg daily for 12 weeks showed no excess of adverse events. On benefit, the picture is negative to unproven: EFSA found the claims unsubstantiated, and the best-controlled trial in people with memory complaints was null. Reviewers also note gastrointestinal complaints and a theoretical bleeding risk with anticoagulants. (Source 4)

How do you get more of it?

Most people already take in a substantial amount from ordinary food. Health Canada's assessment cites an estimate of about 228 mg a day of mean dietary intake, which comes from an industry submission (Degusa Food Ingredients GmbH, 2006) rather than from a Health Canada measurement, and sits in the same range as the doses used in supplement trials. Supplements studied in trials supplied 100 to 600 mg a day of soy-derived material. (Source 9)

If it is harmful, what reduces it?

This does not really apply. Phosphatidylserine is a normal constituent of your own cell membranes and of everyday foods, so there is nothing to eliminate; the only modifiable part is supplemental intake. Where side effects are reported they are mostly digestive, and expert reviews flag a possible bleeding interaction, which is the context in which stopping a supplement is discussed. (Source 1)

Why might someone be low in it or missing it?

No recognised phosphatidylserine deficiency state exists in the literature we searched. It is synthesised by the body and widely present in food, and neither EFSA nor Health Canada describes a deficiency syndrome or an at-risk group. EFSA's panel in fact said the substance itself is not sufficiently characterised. (Source 6)

We searched: EFSA 2010 scientific opinion on phosphatidyl serine health claims, Health Canada 2024 safety assessment, ADDF Cognitive Vitality review, and searches for phosphatidylserine deficiency in humans; none describes a deficiency state or risk group

Which whole foods contain it or feed it?

Health Canada lists phosphatidylserine as naturally present across many foods, with fish such as mackerel, herring, eel and tuna, along with poultry and other meats, among the notable sources. Soy lecithin is the commercial starting material for supplements rather than a major dietary source in itself. (Source 13)

What happens if you do not have it?

The literature we searched describes no consequence of an absent dietary supply, because there is no described human deficiency. Regulatory assessments treat phosphatidylserine as a normal food constituent with an estimated mean intake of about 228 mg a day, a figure Health Canada attributes to an industry submission, rather than as a nutrient with a defined requirement or deficiency disease. (Source 9)

We searched: EFSA 2010 opinion, Health Canada 2024 supplemental-ingredient safety assessment, ADDF Cognitive Vitality review; none reports a deficiency syndrome or a requirement

How can you test for it?

No validated clinical test of phosphatidylserine status exists in the literature we searched, and no reference range or cut-off is published by the bodies that have assessed it. EFSA's panel went further and said the substance itself is not sufficiently characterised, which is the opposite of a position from which a status test could be defined. (Source 6)

We searched: EFSA 2010 scientific opinion, Health Canada 2024 assessment, ADDF Cognitive Vitality review, and searches for a phosphatidylserine status assay or reference range; nothing found

References

1. Alzheimer's Drug Discovery Foundation, Cognitive Vitality. Phosphatidylserine (supplement). undated (fetched 2026-09-23). Read the source
2. Health Canada, Food Directorate. Summary of Health Canada's safety assessment of phosphatidylserine for use as a supplemental ingredient. 2024. Read the source
3. Nutritional Neuroscience. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. 2001. PMID 11842880, DOI 10.1080/1028415x.2001.11747356. Read the source
4. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), EFSA Journal 2010;8(10):1749. Scientific Opinion on the substantiation of health claims related to phosphatidyl serine (ID 552, 711, 734, 1632, 1927) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. 2010. DOI 10.2903/j.efsa.2010.1749. Read the source
5. Journal of Clinical Biochemistry and Nutrition. Soybean-Derived Phosphatidylserine Improves Memory Function of the Elderly Japanese Subjects with Memory Complaints. 2010. PMID 21103034, DOI 10.3164/jcbn.10-62. Read the source
6. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), EFSA Journal 2010;8(10):1749. Scientific Opinion on the substantiation of health claims related to phosphatidyl serine (ID 552, 711, 734, 1632, 1927) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. 2010. DOI 10.2903/j.efsa.2010.1749. Read the source
7. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), EFSA Journal 2010;8(10):1749. Scientific Opinion on the substantiation of health claims related to phosphatidyl serine (ID 552, 711, 734, 1632, 1927) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. 2010. DOI 10.2903/j.efsa.2010.1749. Read the source
8. US Food and Drug Administration. Qualified Health Claims: Letters of Enforcement Discretion. 2004. Read the source
9. Health Canada, Food Directorate. Summary of Health Canada's safety assessment of phosphatidylserine for use as a supplemental ingredient. 2024. Read the source
10. Health Canada, Food Directorate. Summary of Health Canada's safety assessment of phosphatidylserine for use as a supplemental ingredient. 2024. Read the source
11. Health Canada, Food Directorate. Summary of Health Canada's safety assessment of phosphatidylserine for use as a supplemental ingredient. 2024. Read the source
12. Health Canada, Food Directorate. Summary of Health Canada's safety assessment of phosphatidylserine for use as a supplemental ingredient. 2024. Read the source
13. Health Canada, Food Directorate. Summary of Health Canada's safety assessment of phosphatidylserine for use as a supplemental ingredient. 2024. Read the source