Research library
Phosphatidylserine Research Library
Selected source-linked publications for formulation education, organized by study type, application area, population, summary, and limitations.
Laboratory StudyCell Membrane Biology / Immunology2026
Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells
Gurdap CO, Ragaller F, Muller M, Sjule E, Sych T, Blomén L, Thorén FB, Levental I, Levental KR, Sattentau QJ, Sezgin E
Journal of Cell Science · DOI 10.1242/jcs.264813
- Population
- TMEM30A-knockout immune cell lines (in vitro; live-cell lipid reporter and surface proteome analyses)
- Evidence summary
- This laboratory study deleted TMEM30A, the β-subunit of the P4-ATPase flippases that maintain phosphatidylserine asymmetry, in immune cells and mapped the consequences. Knockout cells showed robust phosphatidylserine externalization together with faster lateral diffusion of membrane constituents, decreased plasma membrane order, and surface proteome changes including increased tetraspanins and CD47; glycocalyx remodeling occurred through ADAM10-dependent shedding of transmembrane mucins. The findings link flippase dysfunction to coordinated lipid, glycan, and protein surface remodeling and to potential sensitization to immune therapy.
- Limitations
- In vitro cell-line model with complete TMEM30A deletion rather than clinically graded loss, so relevance to partial flippase dysfunction in disease is inferred; no animal or human outcomes were tested; the causal ordering between phosphatidylserine externalization and downstream surface changes was not fully resolved.
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Laboratory StudyCell Membrane Biology / Host-Pathogen Biology2026
Parasitophorous vacuole membranes of Toxoplasma gondii and Plasmodium falciparum lack the lipid asymmetry characteristic of host cell plasma membranes
Konishi R, Nakashima Y, Masatani T, Asada M, Hassan H, Fukuda K, Kuriyama S, Nishikawa Y, Kaneko O, Carruthers VB, Fujita A
Biochimica et Biophysica Acta - Biomembranes · DOI 10.1016/j.bbamem.2026.184567
- Population
- Parasitophorous vacuole membranes of Toxoplasma gondii and Plasmodium falciparum analyzed by quick-freeze freeze-fracture replica labeling
- Evidence summary
- Using quantitative quick-freeze freeze-fracture replica labeling, this study measured the transbilayer distribution of phosphatidylserine, phosphatidylethanolamine, and GM3 ganglioside in the parasitophorous vacuole membrane of Toxoplasma gondii and Plasmodium falciparum. In contrast to host plasma membranes, where phosphatidylserine and phosphatidylethanolamine are confined to the cytoplasmic leaflet, all three lipids were symmetrically distributed across both leaflets of the vacuole membrane. The luminal presence of phosphatidylserine may facilitate binding of perforin-like proteins during parasite egress, indicating that the vacuole membrane is profoundly remodeled during infection.
- Limitations
- Laboratory imaging study in cultured parasites; only two apicomplexan species and three lipids were examined; the proposed link between luminal phosphatidylserine and perforin-like protein binding during egress is a mechanistic hypothesis rather than a directly demonstrated interaction.
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Laboratory StudyBiomanufacturing / Enzyme Engineering2026
Combining a chitosan-immobilized phospholipase D with a mixed micelle system for highly efficient synthesis of phosphatidylserine
Liu Z, Wang C, Wu J, Chen M, Zhang Y
Enzyme and Microbial Technology · DOI 10.1016/j.enzmictec.2026.110954
- Population
- In vitro biocatalysis: phospholipase D immobilized on a magnetic chitosan-genipin carrier in a sodium deoxycholate mixed micelle system
- Evidence summary
- This biocatalysis study immobilized phospholipase D on a magnetic chitosan-based carrier crosslinked with genipin and combined it with a sodium deoxycholate mixed micelle system to synthesize phosphatidylserine. The immobilized enzyme achieved an 8.05-fold higher phosphatidylserine conversion rate than free phospholipase D, retained 80% activity after six reuse cycles, and retained 72% activity after 12 days of storage at 4°C, providing an efficient, stable, and recyclable approach to phosphatidylserine production.
- Limitations
- In vitro enzyme reaction system only, without scale-up beyond laboratory conditions; the study reports process metrics rather than biological or clinical outcomes, and results are specific to the tested magnetic carrier, genipin crosslinking, and sodium deoxycholate mixed micelle formulation.
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Human Clinical StudySports Nutrition2026
Football-Specific Performance and Cognitive Fatigue Resistance Following Supplementation with Two Phosphatidylserine Doses Combined with Taurine and Caffeine in Professional Male Football Players: A Randomized, Triple-Masked, Placebo-Controlled Trial
Mizera K, Mazurek D, Martínez-Rodríguez A, Kęska A
Nutrients · DOI 10.3390/nu18162588
- Population
- Professional male football players (97 randomized, four parallel groups)
- Evidence summary
- In this randomized, triple-masked, placebo-controlled trial, 97 professional male football players took placebo, taurine plus caffeine, or the same combination plus 300 or 600 mg/day phosphatidylserine for 14 days. The multi-ingredient conditions showed more favorable baseline-adjusted cognitive, psychomotor, 30 m sprint, and GPS-derived locomotor outcomes than placebo, while the adjusted comparison between the two phosphatidylserine doses was not statistically significant for the registered primary outcome.
- Limitations
- Phosphatidylserine was tested only together with taurine and caffeine, so its independent contribution cannot be isolated. There was no a priori sample-size calculation, some analytical decisions were formalized after unblinding during revision, within-session fatigue-decline indices lacked baseline comparators, the intervention lasted 14 days in professional male football players, and supplement contents were verified from product labels without independent laboratory analysis.
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Laboratory and Animal StudyOncology / Cell Membrane Biology2026
Restricting efferocytosis pathway to CD91 via phosphatidylserine-targeting chimeric protein augments antitumor immune responses
Mizote Y, Nishita H, Hashiba K, Okuma C, Akane S, Minomi K, Tahara H
Molecular Therapy · DOI 10.1016/j.ymthe.2026.05.013
- Population
- Cell culture and murine tumor models
- Evidence summary
- This preclinical study engineered a chimeric protein (PStRAP) that links phosphatidylserine-exposed apoptotic tumor cells to the immunostimulatory phagocytic receptor CD91 instead of tolerogenic phosphatidylserine receptors, and reported increased phagocytosis and cross-priming in vitro plus enhanced antitumor effects when delivered as mRNA lipid nanoparticles alongside a cytotoxic drug in mouse tumor models.
- Limitations
- Evidence comes from cell culture and mouse tumor models only and cannot be extrapolated to humans. Disclosed industry involvement includes patent applications and Nitto Denko Corporation employment for several authors, and the effects are specific to the tested chimeric construct and mRNA/lipid-nanoparticle delivery approach.
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Laboratory and Animal StudyCell Lipid Metabolism / Calcium Signaling2026
Phosphatidylserine synthesis tunes IP3R-mediated ER Ca2+ release via phospholipid homeostasis
Zhou Y, Diao M, Liu Y, He K, Yang X, Ding M, Huang X
Cell Reports · DOI 10.1016/j.celrep.2026.117792
- Population
- Drosophila and mammalian cell models
- Evidence summary
- This laboratory and animal study showed that phosphatidylserine synthesized in the endoplasmic reticulum helps maintain cellular calcium homeostasis: PS deficiency in Drosophila caused mitochondrial damage that was reversed by reducing IP3 receptor-mediated ER calcium release, and mammalian cells with pathological PS levels (deficiency or excess, as modeled in Lenz-Majewski syndrome) displayed abnormal IP3R-mediated ER calcium-release patterns.
- Limitations
- Preclinical Drosophila and mammalian cell models only; the Lenz-Majewski syndrome relevance is based on cellular models rather than clinical data, and the findings do not address dietary phosphatidylserine intake in humans.
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Systematic ReviewCognitive Health / Mental Health2026
The Impact of Citicoline/Phosphatidylserine Supplementation on Cognitive Performance and Executive Functions in Mental Disorders: A Systematic Review of Controlled Trials
Kucuksahin NG, Kaya TT, Halac E, Sut E, Ciray RO
Human Psychopharmacology: Clinical and Experimental · DOI 10.1002/hup.70058
- Population
- Children, adolescents, and adults with ADHD, mood disorders, alcohol and substance use disorders, or schizophrenia (11 controlled trials)
- Evidence summary
- This systematic review of 11 controlled trials (10 randomized, 1 non-randomized) evaluated citicoline and/or phosphatidylserine supplementation, alone or as adjunctive treatment, on cognitive performance in mental disorders. Results were heterogeneous: three ADHD trials reported significant improvements in attention and impulsivity while two found none, and findings were mixed or null in most other diagnostic groups; the authors concluded that current evidence does not support these agents as effective cognitive enhancers in mental disorders.
- Limitations
- Most included trials tested phosphatidylserine together with citicoline, so the independent contribution of phosphatidylserine could not be isolated. The 11 trials were heterogeneous across diagnoses and outcomes, several had high risk of bias, and the search ran through October 2025 without pooled meta-analysis; conclusions should not be generalized to healthy populations or specific finished products.
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Laboratory StudyCell Membrane Biology2026
Phosphatidylserine lipids reduce the adsorption of chondroitin sulphate at the membrane surface
Romano B, Menichetti R, Paracini N, Gutfreund P, Bracco B, Sassi P, Orecchini A, Potestio R, Luchini A
Journal of Colloid and Interface Science · DOI 10.1016/j.jcis.2026.141189
- Population
- Synthetic lipid bilayer model membranes with and without phosphatidylserine, plus molecular dynamics simulations
- Evidence summary
- Combining quartz-crystal microbalance, neutron reflectometry, infrared spectroscopy, and molecular dynamics simulations, this biophysical study found that chondroitin sulphate adsorbs and remains stably attached to phosphatidylcholine-only lipid bilayers through sulphate-choline interactions, while the addition of phosphatidylserine strongly reduces chondroitin sulphate binding at the membrane surface.
- Limitations
- Model-membrane laboratory research on synthetic bilayers without cells, animals, or humans; it does not evaluate dietary phosphatidylserine, and its implications for phosphatidylserine exposure in cancer, apoptosis, or inflammation remain indirect.
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Laboratory and Animal StudyOncology / Cell Lipid Metabolism2026
Targeting Phosphatidylserine Synthesis for Tumor Cell Suppression in Esophageal Squamous Cell Carcinoma and Glioblastoma
Hu Y, Cui Y, Xu Z, Wu D, Yu X
International Journal of Molecular Sciences · DOI 10.3390/ijms27146226
- Population
- Esophageal squamous cell carcinoma and glioblastoma cell lines, mouse tumor models, and pan-cancer transcriptomic datasets
- Evidence summary
- In cancer cell lines and mouse tumor models, pharmacological inhibition of phosphatidylserine synthase 1 (PTDSS1) depleted cellular phosphatidylserine and phosphatidylethanolamine pools, disrupted endoplasmic reticulum homeostasis, and drove a PERK-mediated autophagic response leading to apoptosis, selectively suppressing tumor growth in vitro and in vivo. Pan-cancer transcriptomic analysis linked elevated PTDSS1 expression with reduced overall survival.
- Limitations
- Preclinical tumor biology conducted in cell lines, xenograft models, and transcriptomic datasets; it does not test dietary phosphatidylserine or finished supplements, and whether PTDSS1 inhibition translates to humans is unproven.
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Animal and Laboratory StudyNeuroscience / Cell Membrane Biology2026
Loss of Atp8a2 drives neurodegeneration through the dysregulation of spatiotemporal phosphatidylserine externalization in mature neurons
Schneider A, Merkel AB, Perta N, Ruff L, Ussyshkin N, Zimmer P, Aksan B, Lepeuve A, D’Andrea L, Pelucchi S, Marcello E, Di Marino D, Mauceri D
Cell Death & Disease · DOI 10.1038/s41419-026-09097-y
- Population
- Cultured mature hippocampal neurons and mouse retinal, optic-nerve, and neurodegeneration models
- Evidence summary
- Using cultured neurons and several mouse models, the study associated reduced Atp8a2 expression with altered phosphatidylserine exposure patterns, loss of neuronal structure, and greater vulnerability, while Atp8a2 overexpression produced model-specific protective effects.
- Limitations
- This mechanistic work studied endogenous membrane phosphatidylserine regulation in cell and mouse models, not dietary supplementation or humans. Acute experimental neurotoxicity and model-specific manipulations limit translation to clinical or nutrition outcomes.
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Human Clinical StudyMetabolic and Vascular Research2026
Beneficial vascular effects of oral phosphatidylserine supplementation in type 2 diabetes
McMillan NJ, Augenreich MA, Ramirez-Perez FI, Power G, Burr K, Lateef OM, Nagarajan M, Foote CA, Imkaew N, Jurrissen TJ, Lazo-Fernandez Y, Betancourt-Cortes EE, Ferreira-Santos L, Beltran-Ornelas JH, Manrique-Acevedo C, Martinez-Lemus LA, Padilla J
Journal of Applied Physiology · DOI 10.1152/japplphysiol.00281.2026
- Population
- 34 adults with type 2 diabetes; supporting endothelial-cell, isolated-artery, and db/db mouse models
- Evidence summary
- In a four-week randomized, double-blind, placebo-controlled trial embedded in a broader mechanistic study, adults with type 2 diabetes receiving phosphatidylserine showed changes in leg blood-flow response and load-dependent aortic pulse-wave velocity compared with placebo; supporting cell and diabetic-mouse experiments examined ADAM17 and vascular mechanisms.
- Limitations
- The human sample was small (16 phosphatidylserine and 18 placebo), lasted four weeks, enrolled only adults with type 2 diabetes, and evaluated surrogate vascular measures rather than clinical events. Results are specific to the studied 900 mg/day supplement (about 280 mg/day phosphatidylserine) and do not support treatment claims.
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Laboratory StudyCell Membrane Biology2026
Phosphatidylserine and RhoB connect PI4P and PA metabolism to maintain plasma membrane identity
Huang S, Kim YJ, Cao X, Bumpus TW, Sohn M, Menold MT, Dale RK, Kang JJ, Uematsu S, Gupta S, Qian SB, Yu H, Balla T, Baskin JM
Journal of Cell Biology · DOI 10.1083/jcb.202509213
- Population
- Cultured mammalian cells and biochemical membrane models
- Evidence summary
- In cultured-cell and biochemical experiments, prolonged PI4KA inhibition reduced cellular phosphatidylserine while increasing phospholipase D activity and phosphatidic acid, with RhoB upregulation linked to compensatory membrane and actin changes.
- Limitations
- This is mechanistic laboratory research using pharmacologic and genetic perturbations in cultured systems. It did not test oral phosphatidylserine, finished formulations, whole-animal outcomes, or human health effects.
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Human Clinical StudyCognitive Health2025
The cognitive effects of supplementation with sunflower phosphatidyl serine in healthy children aged 8 to 12 years: a randomized controlled trial
Friling M, Jackson PA, Kennedy D, Dodd F, Smith E, Lavie A, Lopresti A, Ivanir E, Jalanka J
Nutrition Journal · DOI 10.1186/s12937-025-01264-9
- Population
- Healthy children aged 8 to 12 years
- Evidence summary
- This randomized controlled trial reported no significant overall differences on its primary or secondary outcomes, while exploratory subgroup observations were identified for further research.
- Limitations
- The overall outcomes were not significant. Subgroup observations should not be converted into efficacy or medical claims.
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Human Clinical StudyHealthy Aging2025
Effects of a food supplement containing phosphatidylserine on cognitive function in Chinese older adults with mild cognitive impairment: A randomized double-blind, placebo-controlled trial
Duan H, Xu N, Yang T, Wang M, Zhang C, Zhao J, Li Z, Chen Y, Yan J, Zhang M, Li W, Yue Z, Ma F, He R, Huang G
Journal of Affective Disorders · DOI 10.1016/j.jad.2024.09.131
- Population
- Chinese older adults with mild cognitive impairment
- Evidence summary
- The human study reported short-term memory-related findings for a food supplement containing phosphatidylserine in the population studied.
- Limitations
- The study concerns a specific finished supplement and clinical population. Its findings do not establish that a bulk PS ingredient treats cognitive decline.
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Human Clinical StudySports Nutrition2026
Effects of Taurine-, Caffeine-, and Phosphatidylserine-Containing Supplementation Protocols on Physical and Cognitive Performance in Professional Male Football Players
Mizera K, Mizgała-Izworska E, Mizera J, Mackiewicz J
Nutrients · DOI 10.3390/nu18111684
- Population
- Professional male football players
- Evidence summary
- This human exercise study investigated combined supplementation protocols containing taurine, caffeine, and phosphatidylserine in relation to physical and cognitive performance measures.
- Limitations
- The active protocols contained multiple ingredients and different caffeine doses, so the independent contribution of phosphatidylserine cannot be determined.
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Human Clinical StudyCognitive Health2026
Differential cognitive effects of DHA-enriched and standard phosphatidylserine formulations in children with ADHD: a randomized, placebo-controlled trial
Jaicks CCD, Kinter RC
Applied Neuropsychology: Child · DOI 10.1080/21622965.2026.2694486
- Population
- Children with ADHD
- Evidence summary
- The randomized study compared DHA-enriched and standard phosphatidylserine formulations across cognitive measures in the population studied.
- Limitations
- This is research in a diagnosed pediatric population using specific finished formulations. It must not be translated into a disease-treatment claim for a bulk ingredient.
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