Evidence Trace, complete trial record
In plain terms
In plain terms: Phosphatidylserine (PS) shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
Phosphatidylserine (PS)
C
Limited: small, mixed or unreplicated trials
The endpoint this grade is based on: Objectively measured functional outcome, Memory in older adults with memory complaints, graded by form. The positive trials used bovine-cortex phosphatidylserine, which is no longer sold: Grade C, stated for that form. The soy-derived form sold today was tested twice without benefit: Grade D, Route 2. FDA qualified health claim (2003) acknowledges limited and not conclusive evidence.
The evidence as the record states it
BOVINE-CORTEX FORM, no longer sold: Cenacchi et al. (Aging (Milano), 1993; PMID 8323999): 494 patients aged 65 to 93 with moderate to severe cognitive decline, 300 mg a day for 6 months; behavior and memory scores improved against placebo. Crook et al. (Neurology, 1991; PMID 2027477): 149 adults with age-associated memory impairment, 100 mg three times a day for 12 weeks; learning and memory tests improved against placebo, most in those starting lowest. SOY-DERIVED FORM, the one sold: Jorissen et al. (Nutr Neurosci, 2001; PMID 11842880): 120 older adults with age-associated memory impairment, 300 or 600 mg a day for 12 weeks; no difference from placebo on any outcome. Kato-Kataoka et al. (J Clin Biochem Nutr, 2010; PMID 21103034): 78 adults aged 50 to 69 with memory complaints, 100 or 300 mg a day for 6 months; every group including placebo improved, the only gain within a low-baseline subgroup. The letter follows the form: C for the bovine-cortex preparation the positive trials used, D Route 2 for the soy form on the shelf.
PMID 8323999 PMID 2027477 PMID 21103034 PMID 11842880
Evidence by specific use
Memory and cognition in older adults, bovine-cortex phosphatidylserine (no longer sold)
Grade C
Cenacchi et al. (Aging (Milano), 1993; PMID 8323999): 494 patients aged 65 to 93 in 23 Italian units, 300 mg a day for 6 months; behavior and memory scores improved against placebo. Crook et al. (Neurology, 1991; PMID 2027477): 149 adults with age-associated memory impairment, 100 mg three times a day for 12 weeks; learning and memory tests improved against placebo. Two positive trials of a preparation withdrawn from sale after the bovine spongiform encephalopathy era. C rather than B because the rule attaches a B to an obtainable form, and this one is not; the soy form that replaced it is graded on the next row.
PMID 8323999 PMID 2027477
Memory and cognition in older adults, soy-derived phosphatidylserine (the form sold)
Grade D
Jorissen et al. (Nutr Neurosci, 2001; PMID 11842880): 120 older adults with age-associated memory impairment, 300 or 600 mg a day for 12 weeks; no difference from placebo on the primary delayed-recall measures or any secondary outcome. Kato-Kataoka et al. (J Clin Biochem Nutr, 2010; PMID 21103034): 78 adults aged 50 to 69 with memory complaints, 100 or 300 mg a day for 6 months; every group including placebo improved, and the only gain reported is within a low-baseline subgroup. The soy form was tested twice in the population it is sold to and did not separate from placebo: D on Route 2. Aligned with the soy-derived phosphatidylserine protocol, graded D Route 2 in October 2026.
PMID 11842880 PMID 21103034
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What this grade covers and what it does not
Grade C, stated for the bovine-cortex form, which is no longer sold. Two randomized trials of that preparation were positive, Cenacchi et al. (Aging (Milano), 1993; PMID 8323999; 494 patients) and Crook et al. (Neurology, 1991; PMID 2027477; 149 patients), so the evidence for it is replicated; it stays at C rather than B because the written rule attaches a B to a form that can be obtained, and this one cannot. The soy-derived form sold today is graded on its own row: Jorissen et al. (Nutr Neurosci, 2001; PMID 11842880) null on every outcome and Kato-Kataoka et al. (J Clin Biochem Nutr, 2010; PMID 21103034) null between groups, D on Route 2. WHAT THIS GRADE DOES NOT COVER: the product a reader can buy, which carries the D; phosphatidylserine combined with omega-3 fatty acids (Vakhapova et al., Dement Geriatr Cogn Disord, 2010; PMID 20523044), a combination not graded here; sunflower-derived phosphatidylserine, which has no cognition trial; and any population other than older adults with memory complaints or cognitive decline. The review opened October is closed: the record follows the evidence for each form. Decided October 2026 by editor adjudication.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.
How to track whether this is working
The trials measured cognitive and memory performance by repeat assessment, and recorded subjective mental fatigue or stress-related symptoms where relevant.