Phosphatidylserine

While numerous studies have been carried out, it is difficult to compare across studies as the chemical composition of phosphatidylserine has varied widely between trials. Long-term data is also lacking. Our search found: 

• 1 systematic review and meta-analysis of the effect of phosphatidylserine on cognitive function in older adults
• Numerous randomized controlled trials (in young, elderly, or cognitively impaired adults)
• 0 observational studies
• Numerous preclinical studies

The amount of phosphatidylserine in the brain remains mostly constant throughout life, although slight changes have been reported with Alzheimer's disease and aging [1]. It is not clear whether supplements can increase phosphatidylserine brain levels [2]. A 2022 systematic review and meta-analysis found that phosphatidylserine supplementation may have some potential benefit for memory, though it included trials that are difficult to directly compare [3]. Small clinical trials, some of which were included in the meta-analysis, also suggest that phosphatidylserine supplements can yield slight cognitive improvements in adults,  but effects were not large enough to be clinically relevant [4; 5; 6; 7]. Long-term use has not been well-studied, with most trials lasting less than 6 months. Perhaps the biggest challenge is the phosphatidylserine itself: as different sources of phosphatidylserine have different chemical makeups, it is difficult to directly compare the outcomes of many trials.  

For Dementia Patients

Small trials suggested that phosphatidylserine might slightly improve cognition for Alzheimer's patients, but effects were short-lived or detectable only in severely impaired patients [8; 9; 10; 11]. Benefits have not been confirmed in larger trials.

Small clinical trials suggest that phosphatidylserine supplements produce no serious adverse effects for elderly patients, although it may reduce blood pressure or increase body weight [12]. It is possible that phosphatidylserine may increase risk of bleeding. In the past, some phosphatidylserine supplements were derived from cow brain; however, due to theoretical concerns that these supplements could transmit prion disease such as mad cow [13], the only available phosphatidylserine supplements are derived from plant or marine sources. 

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

Phosphatidylserine doses typically range from 80 to 500 mg per day, and can include varying amount of omega-3 fatty acids such as DHA and EPA depending on the source of the phosphatidylserine [3]. The presence of DHA may be important for increasing synthesis of phosphatidylserine in the brain. However, in theory, any phosphatidylserine taken with a separate DHA supplement could have the same effect as DHA-enriched phosphatidylserine because phospholipids may be broken down in the gut before being absorbed [2].

Full scientific report (PDF) on Cognitive Vitality Reports; see also reports for omega-3 fatty acids, including DHA and EPA. 

1. Cunnane SC, Schneider JA, Tangney C et al. (2012) Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis 29, 691-697.
2. Kim HY, Huang BX, Spector AA (2014) Phosphatidylserine in the brain: metabolism and function. Prog Lipid Res 56, 1-18.
3. Kang EY, Cui F, Kim HK et al. (2022) Effect of phosphatidylserine on cognitive function in the elderly: A systematic review and meta-analysis. KOREAN J FOOD SCI TECHNOL 54, 52-58.
4. Cenacchi T, Bertoldin T, Farina C et al. (1993) Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano) 5, 123-133.
5. Vakhapova V, Cohen T, Richter Y et al. (2010) Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial. Dement Geriatr Cogn Disord 29, 467-474.
6. Strike SC, Carlisle A, Gibson EL et al. (2016) A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study. J Gerontol A Biol Sci Med Sci 71, 236-242.
7. Parker AG, Gordon J, Thornton A et al. (2011) The effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exercise. J Int Soc Sports Nutr 8, 16.
8. Heiss WD, Kessler J, Mielke R et al. (1994) Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation. Dementia 5, 88-98.
9. Engel RR, Satzger W, Gunther W et al. (1992) Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur Neuropsychopharmacol 2, 149-155.
10. Crook T, Petrie W, Wells C et al. (1992) Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull 28, 61-66.
11. Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A et al. (1986) Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol Scand 73, 136-140.
12. Vakhapova V, Richter Y, Cohen T et al. (2011) Safety of phosphatidylserine containing omega-3 fatty acids in non-demented elderly: a double-blind placebo-controlled trial followed by an open-label extension. BMC Neurol 11, 79.
13. Requena JR, Kristensson K, Korth C et al. (2016) The Priority position paper: Protecting Europe's food chain from prions. Prion 10, 165-181.