Alpha-GPC Research Library: Every Study, Plain English
The Alpha-GPC Research Library is a maintained index of the published science on Alpha-GPC (L-alpha-glycerylphosphorylcholine, also sold and prescribed as choline alfoscerate): 144 studies from 1986 to 2026, organized by outcome, each with a plain-English summary of what it actually showed and a direct link to the original paper on PubMed. Alpha-GPC has lived two lives, as a prescription cognitive-decline drug in parts of Europe and as an over-the-counter supplement in North America, which is why its literature is bigger, older and stranger than most supplement ingredients'.
- Cognition: Clinical Populations (30)
- Cognition: Healthy Adults (5)
- Athletic Performance & Power (5)
- Growth Hormone Response (2)
- Stroke & Brain-Injury Recovery Research (9)
- Safety & Adverse Events (8)
- Pharmacokinetics & Dosing (8)
- Other Clinical Research (9)
- Mechanism, Animal & In Vitro (51)
- Reviews & Landmark Papers (17)
Cognition: Clinical Populations 30 studies
The prescription-era trials: cognitive impairment and dementia-era studies, largely 1990s Italy, in CLINICAL populations. This is where the biggest human numbers live, and it is not evidence about healthy adults.
[Efficacy of choline alfoscerate treatment for subjective cognitive impairment in first-degree relatives of patients with Alzheimer's disease: Results of a comparative 5-year study].
In a 5-year non-randomized Russian comparison of 122 first-degree relatives of Alzheimer's patients with subjective cognitive impairment, repeated 3-month courses of oral choline alfoscerate were followed by improved cognitive scores, while 16.7% of untreated controls converted to mild cognitive impairment.
Reported figure: 96.8% of treated subjects reported marked or moderate improvement; SCI-to-MCI conversion 16.7% in controls by month 60
PMID 42054337 | DOI 10.17116/jnevro202612604292
Effects of choline alfoscerate on cognitive function and quality of life in type 2 diabetes: A double-blind, randomized, placebo-controlled trial.
In 36 type 2 diabetes patients with mild cognitive decrements randomized to choline alfoscerate 1200 mg/day or placebo, the MMSE difference was non-significant at 6 months but reached significance at 12 months, alongside better physical quality-of-life scores.
Reported figure: between-group MMSE difference +1.4 at 6 months (p = 0.059) and +1.7 at 12 months (p < 0.001)
PMID 39703111 | DOI 10.1111/dom.16131
Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea.
In a Korean national cohort of 508,107 patients newly diagnosed with mild cognitive impairment, alpha-GPC users had a lower risk of progressing to Alzheimer's dementia and vascular dementia than non-users, and lower stroke risk among those who did not progress; as an observational study it cannot prove causation.
Reported figure: Alzheimer's dementia HR 0.899 (95% CI 0.882-0.918); vascular dementia HR 0.832 (95% CI 0.801-0.865)
PMID 40155153 | DOI 10.1016/j.tjpad.2025.100059
[Gliatilin in the Treatment of Cognitive Impairments Not Reaching the Level of Dementia: Meta-Analysis and Systematic Review].
A Russian systematic review and meta-analysis of 10 studies of Gliatilin (choline alfoscerate) in vascular or post-traumatic cognitive impairment short of dementia reported a statistically significant treatment effect, strongest for parenteral administration of at least 28 days; the authors note substantial heterogeneity across the included studies.
PMID 41362980 | DOI 10.17116/jnevro202512511186
Comparison of the effects of choline alphoscerate and citicoline in patients with dementia disorders: a systematic review and meta-analysis.
A systematic review and meta-analysis of 3 randomized trials (358 patients with dementia disorders) found choline alphoscerate improved overall clinical condition on the SCAG scale more than citicoline, but with no significant difference between the drugs on memory or word-fluency tests.
Reported figure: SCAG WMD -3.92 (95% CI -7.41 to -0.42) favouring choline alphoscerate; memory and word-fluency differences not significant
PMID 41426989 | DOI 10.3389/fneur.2025.1649661
[Efficacy and safety of choline alfoscerate in the preventive therapy of dementia in elderly patients with Mild Cognitive Impairment: a three-year prospective comparative study].
In a 3-year open comparative Russian study of 100 patients with amnestic mild cognitive impairment randomized to annual courses of choline alfoscerate infusions or no therapy, the treated group showed lower progression of cognitive deficit and a lower conversion rate to dementia.
Reported figure: cognitive-deficit progression 12.2% vs 39.1%; conversion to dementia 8.2% vs 26.1% (p<0.05)
PMID 38696157 | DOI 10.17116/jnevro202412404292
Comparative study of choline alfoscerate as a combination therapy with donepezil: A mixed double-blind randomized controlled and open-label observation trial.
In 119 Korean patients with cognitive decline in a mixed double-blind randomized and open-label design, donepezil plus choline alfoscerate improved MMSE and ADAS-Cog more than donepezil alone or donepezil plus acetyl-L-carnitine/ginkgo over 24 weeks.
Reported figure: ADAS-Cog improved 18.5% with donepezil + choline alfoscerate vs 9.4% with donepezil alone at week 24
PMID 38875437 | DOI 10.1097/MD.0000000000038067
Efficacy and safety of choline alphoscerate for amnestic mild cognitive impairment: a randomized double-blind placebo-controlled trial.
In 100 Korean adults with amnestic mild cognitive impairment, 600 mg/day soy-derived alpha-GPC for 12 weeks improved ADAS-cog significantly more than placebo, with no difference in adverse-event rates.
Reported figure: ADAS-cog decreased (improved) 2.34 points vs placebo after 12 weeks
PMID 39300341 | DOI 10.1186/s12877-024-05366-7
Effect of Choline Alfoscerate on the Progression From Mild Cognitive Impairment to Dementia: Distributed Network Analysis of a Multicenter Korean Database Using a Common Data Model.
In a propensity-matched multicenter Korean common-data-model cohort (3,062 matched pairs of patients with mild cognitive impairment), choline alfoscerate use was not associated with progression to all-cause dementia or Alzheimer's dementia, overall or in any subgroup.
Reported figure: all-cause dementia HR 0.93 (95% CI 0.59-1.26); Alzheimer's dementia HR 1.05 (95% CI 0.51-1.59)
PMID 39512703 | DOI 10.12779/dnd.2024.23.4.202
Effect of choline alfoscerate in older adult patients with dementia: an observational study from the claims data of national health insurance.
In a Korean national claims cohort of 11,463 older adults with dementia, the association between choline alfoscerate use and dementia-progression events was unclear, while users showed roughly 20% lower all-cause mortality; the authors call for further analyses before drawing effectiveness conclusions.
Reported figure: about 20% lower all-cause mortality with exposure; progression association unclear
PMID 39548376 | DOI 10.1186/s12877-024-05531-y
Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis.
A systematic review and meta-analysis of 7 randomized trials and 1 cohort study found alpha-GPC combined with donepezil improved cognition, function and behavior in adult-onset cognitive dysfunction, and alpha-GPC alone outperformed placebo or comparator medications on cognition.
Reported figure: alpha-GPC + donepezil cognition MD 1.72 (95% CI 0.20-3.25); alpha-GPC alone cognition MD 3.50 (95% CI 0.36-6.63)
PMID 36683513 | DOI 10.3233/JAD-221189
Quantitative electroencephalography changes in patients with mild cognitive impairment after choline alphoscerate administration.
In an uncontrolled Korean qEEG study of 33 patients with mild cognitive impairment (20 with follow-up), 2 months of choline alphoscerate 800 mg/day was followed by decreased theta and delta power and increased occipital alpha power, interpreted as a positive electrophysiological shift.
PMID 35714391 | DOI 10.1016/j.jocn.2022.06.006
Association Between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in the Treatment of Depression in Patients with Alzheimer's Disease.
Among 90 ASCOMALVA participants followed 24 months, depressive symptoms were significantly lower with donepezil plus choline alphoscerate 1200 mg/day than with donepezil plus placebo, with the mild-to-moderate cognitive impairment subgroup most responsive.
Reported figure: p < 0.05 for depression scores in favour of the association
PMID 35719710 | DOI 10.3233/ADR-200269
Effectiveness of Nootropics in Combination with Cholinesterase Inhibitors on Cognitive Function in Mild-to-Moderate Dementia: A Study Using Real-World Data.
In Korean real-world records of 583 patients with mild-to-moderate dementia, adding nootropics to cholinesterase inhibitors did not change overall MMSE decline versus cholinesterase inhibitors alone; only the language subscale in Alzheimer's dementia favoured the choline alfoscerate and ginkgo subgroups.
Reported figure: overall MMSE change not significantly different between groups; language subscale F = 7.04, p = 0.001 in AD subgroup
PMID 36012898 | DOI 10.3390/jcm11164661
[Clinical and immunological effects of choline alfoscerate in the treatment of amnestic type Mild Cognitive Impairment].
In an open-label Russian study of 30 patients with amnestic mild cognitive impairment, 3 months of alpha-GPC 1200 mg/day was followed by improved cognitive scores and increased leukocyte elastase activity, proposed as a marker of treatment response; there was no control group.
PMID 36412158 | DOI 10.17116/jnevro202212211259
Efficacy and Safety of the Association of Nimodipine and Choline Alphoscerate in the Treatment of Cognitive Impairment in Patients with Cerebral Small Vessel Disease. The CONIVaD Trial.
In the CONIVaD trial, 62 patients with cerebral small vessel disease and vascular cognitive impairment were randomized to nimodipine plus choline alphoscerate or nimodipine plus placebo for 1 year: no statistically significant differences were found on the primary cognitive outcome or any secondary outcome.
Reported figure: no significant between-group differences; 22% dropout; nimodipine adherence only 15%
PMID 33855653 | DOI 10.1007/s40266-021-00852-8
Volume Analysis of Brain Cognitive Areas in Alzheimer's Disease: Interim 3-Year Results from the ASCOMALVA Trial.
In a 3-year MRI voxel-morphometry analysis of 56 ASCOMALVA participants, adding choline alphoscerate to donepezil was associated with less gray-matter atrophy in frontal and temporal lobes, hippocampus and amygdala than donepezil plus placebo, in parallel with less cognitive decline.
PMID 32508323 | DOI 10.3233/JAD-190623
[Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment].
In an open-label Russian study of 50 elderly patients with amnestic mild cognitive impairment, a 3-month course of choline alfoscerate (Cereton) 1200 mg/day was followed by significant psychometric improvement that partially persisted 7-9 months after treatment; ApoE4 non-carriers responded better on word-recall tests.
PMID 29927403 | DOI 10.17116/jnevro20181185145
P300 latency changes in patients with mild cognitive impairment after taking choline alphoscerate; A preliminary study.
In an uncontrolled Korean study of 27 patients with mild cognitive impairment (17 completed), P300 event-related-potential latency showed no significant change after 3 months of choline alphoscerate, only a non-significant trend toward shortening.
Reported figure: follow-up P300 latencies not significantly changed
PMID 29928709 | DOI 10.1016/j.ensci.2018.04.004
The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial.
In 113 mild/moderate Alzheimer's patients in the ASCOMALVA trial followed 24 months, donepezil plus choline alphoscerate reduced behavioral and psychological symptom severity and caregiver distress versus donepezil alone, with mood symptoms (depression, anxiety, apathy) most improved.
PMID 28035924 | DOI 10.3233/JAD-160675
[Detection of effective treatment of amnestic mild cognitive impairement with cereton by testing of lipids markers].
In 20 elderly Russian patients with amnestic mild cognitive impairment treated with choline alfoscerate (Cereton) 1200 mg/day, plasma phosphatidylcholine rose and expression of ceramide-metabolism genes fell, proposed as lipid markers of treatment response; no untreated comparison group was included.
PMID 28745666 | DOI 10.17116/jnevro20171176121-27
Apathy Treatment in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial.
In 113 mild-moderate Alzheimer's patients in the ASCOMALVA trial, donepezil plus choline alphoscerate lowered apathy scores at 12-24 months and caregiver distress at 6-24 months compared with donepezil alone, independently of cognitive scores.
PMID 26402001 | DOI 10.3233/JAD-141983
The ASCOMALVA (Association between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in Alzheimer's Disease) Trial: interim results after two years of treatment.
At the 2-year interim of the double-blind ASCOMALVA trial in 113 Alzheimer's patients with ischemic brain injury, donepezil plus choline alphoscerate significantly slowed the worsening seen with donepezil alone across cognitive, functional and behavioral measures.
PMID 24898643 | DOI 10.3233/JAD-140150
[The use of cereton in patients with chronic brain ischemia and moderate cognitive impairment].
In an uncontrolled Russian study of 25 patients with chronic brain ischemia and moderate cognitive impairment, intravenous then oral choline alfoscerate (Cereton) for about 3.5 months was followed by clinician-rated moderate or marked improvement in 19 of 25 patients and was well tolerated.
PMID 25726784 | DOI 10.17116/jnevro201411412178-83
[The use of cerepro (choline alfoscerate) in the treatment of outpatients with chronic progressive cerebrovascular disease].
In an uncontrolled Russian study of 90 outpatients with chronic cerebrovascular disease (60 post-stroke), choline alfoscerate (Cerepro) given intravenously then orally for 6 weeks alongside basic therapy was followed by improved coordination, cognitive and emotional measures, with good tolerability.
PMID 22677751
The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim results.
In the first 12 months of the double-blind ASCOMALVA trial (91 of 210 planned Alzheimer's patients with cerebrovascular injury), donepezil plus choline alphoscerate improved MMSE, ADAS-cog, IADL and neuropsychiatric scores compared with donepezil plus placebo, except basic activities of daily living.
PMID 22959283 | DOI 10.1016/j.jns.2012.07.003
[Efficacy and tolerability of choline alphoscerate (cereton) in patients with Parkinson's disease with cognitive disorders].
In a 10-day open randomized Russian comparison in Parkinson's disease with cognitive disorders, intravenous choline alphoscerate (Cereton, 40 patients) produced marked or moderate cognitive improvement more often than piracetam (20 patients) and cognitive worsening less often.
Reported figure: marked/moderate improvement 40% vs 25% (p<0.05); deterioration 5% vs 15% (p<0.05)
PMID 20032953
Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial.
In 261 patients with mild to moderate Alzheimer's dementia, choline alfoscerate 1200 mg/day for 180 days improved ADAS-Cog scores while the placebo group worsened, with consistent improvement across all secondary measures.
Reported figure: ADAS-Cog decreased (improved) 3.20 points at day 180 with choline alfoscerate vs increased (worsened) 2.90 points with placebo; P < 0.001
PMID 12637119 | DOI 10.1016/s0149-2918(03)90023-3
Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer's type.
In 126 patients with probable mild to moderate Alzheimer-type senile dementia, randomized alpha-GPC improved most neuropsychological parameters more than acetyl-L-carnitine (ST200); there was no placebo arm.
PMID 8477148 | DOI 10.2165/00002512-199303020-00006
A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia.
In a 90-day open randomized comparison in 120 patients with mild to moderate vascular dementia, intramuscular alpha-GPC 1 g/day and citicoline 1 g/day both improved symptoms, with statistically higher efficacy for alpha-GPC on most tests; no placebo arm and no blinding.
PMID 1916007 | DOI 10.1177/030006059101900406
Cognition: Healthy Adults 5 studies
What actually exists on memory, focus and cognition in healthy people. Notice how much thinner this section is than the clinical one; that gap is the most misrepresented thing in alpha-GPC marketing.
Vertical Association Between Dietary Total Choline and L-alpha-glycerylphosphorylcholine and the Cognitive Function in Chinese Adults Aged over 55, Result from China Health and Nutrition Survey 1997-2018.
In 7,659 Chinese adults over 55 followed in the China Health and Nutrition Survey, higher dietary intake of total choline and of GPC (average 16.3 mg/day from food) was associated with better global cognition scores; dietary observational data cannot establish causation.
Reported figure: GPC intake beta = 0.073 (95% CI 0.034-0.111, p < 0.001) for global cognition score
PMID 39519545 | DOI 10.3390/nu16213713
Acute Alpha-Glycerylphosphorylcholine Supplementation Enhances Cognitive Performance in Healthy Men.
In a randomized double-blind crossover trial in 20 resistance-trained men, single doses of alpha-GPC (630 mg or 315 mg) improved Stroop test scores versus placebo 60 minutes after ingestion, but showed no significant effect on Flanker or N-Back tests, physical performance, or growth hormone.
Reported figure: Stroop total score change 13.0 vs 5.2 for 630 mg vs placebo (p = 0.013, d = 0.61); no group differences for jumps, bench press throws or growth hormone
PMID 39683633 | DOI 10.3390/nu16234240
Alpha-Glycerylphosphorylcholine Increases Motivation in Healthy Volunteers: A Single-Blind, Randomized, Placebo-Controlled Human Study.
In a single-blind placebo-controlled study in 39 healthy volunteers self-rating emotions for two weeks, alpha-GPC increased self-reported motivation at night versus placebo, with no effect on anxiety.
Reported figure: motivation at night higher in the alpha-GPC group (p < 0.05)
PMID 34207484 | DOI 10.3390/nu13062091
The effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students.
In 19 healthy college students randomized to a multi-ingredient supplement (CRAM: alpha-GPC plus choline bitartrate, phosphatidylserine, caffeine, tyrosine, acetyl-L-carnitine, B-vitamins) or placebo, the blend maintained reaction time and focus after exhaustive exercise acutely, but the effects were not sustained after 4 weeks; effects cannot be attributed to alpha-GPC alone.
Reported figure: reaction time declined with placebo (p = 0.050) but was maintained with the supplement acutely; declines in both groups at 4 weeks
PMID 21156078 | DOI 10.1186/1550-2783-7-39
Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.
In 32 healthy young volunteers randomized to 10 days of oral alpha-GPC or placebo before a scopolamine injection, alpha-GPC pretreatment antagonized the scopolamine-induced impairment of attention and memory.
PMID 2071257
Athletic Performance & Power 5 studies
Power output, strength and exercise studies. Real human trials, mostly small; labeled honestly.
Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial.
In a randomized double-blind crossover in 30 trained male cyclists, 7 days of a blend of BCAAs 8 g, L-citrulline 6 g and alpha-GPC 300 mg increased 20-km time-trial peak power and time to fatigue versus placebo, but not completion time, average power or perceived exertion; the blend design means effects cannot be attributed to alpha-GPC alone.
Reported figure: peak power 354.27 vs 321.67 W (p = .003); time to fatigue 19:49 vs 14:33 min (p = .001)
PMID 37229544 | DOI 10.1080/15502783.2023.2214112
The Effects of Alpha-Glycerylphosphorylcholine on Heart Rate Variability and Hemodynamic Variables Following Sprint Interval Exercise in Overweight and Obese Women.
In a randomized double-blind crossover in 12 overweight or obese women, a single 1000 mg dose of alpha-GPC before sprint interval exercise increased resting heart-rate variability and led to faster recovery of heart-rate variability and blood pressure after exercise than placebo.
Reported figure: HRV and hemodynamic variables recovered faster after alpha-GPC (p < 0.05)
PMID 36235623 | DOI 10.3390/nu14193970
Acute ingestion of neuromuscular enhancement supplements do not improve power output, work capacity, and cognition.
In a randomized crossover in 20 trained college-aged men, a single dose of a blend containing alpha-GPC 500 mg, uridine monophosphate and DHA taken 90 minutes before testing produced no improvement in vertical jump, bench-press repetitions or cognition versus placebo.
Reported figure: no significant difference between supplement and placebo (P > 0.05)
PMID 28222577 | DOI 10.23736/S0022-4707.17.07022-0
Evaluation of the effects of two doses of alpha glycerylphosphorylcholine on physical and psychomotor performance.
In 48 healthy men randomized to 7 days of alpha-GPC 500 mg, alpha-GPC 250 mg, caffeine 200 mg or placebo, there were no differences in isometric strength or psychomotor vigilance; the 250 mg group improved countermovement-jump velocity and power, and the 500 mg group showed significantly depressed serum thyroid-stimulating hormone.
Reported figure: no IMTP/UBIST/PVT differences; CMJ max velocity and power p < 0.05 favouring 250 mg; serum TSH depressed at 500 mg (p < 0.04)
PMID 29042830 | DOI 10.1186/s12970-017-0196-5
The effect of 6 days of alpha glycerylphosphorylcholine on isometric strength.
In a double-blind placebo-controlled crossover in 13 college-aged men, 6 days of alpha-GPC 600 mg/day increased lower-body isometric mid-thigh pull peak force versus placebo, while the upper-body isometric test trended better without reaching significance; a very small study.
Reported figure: mid-thigh pull force change +98.8 N vs -39.0 N for placebo (p = 0.044); upper body p = 0.127
PMID 26582972 | DOI 10.1186/s12970-015-0103-x
Growth Hormone Response 2 studies
Acute GH-response studies. Short-term hormone changes are not the same claim as long-term outcomes.
Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults.
In a double-blind randomized crossover in 8 healthy young men, a single 1000 mg dose of GPC increased plasma growth hormone at 60 minutes and raised free fatty acids and ketone bodies (markers of hepatic fat oxidation) at 120 minutes, while placebo produced no change; acute effects only, in a very small sample.
Reported figure: growth hormone significantly increased 60 min after GPC; no change with placebo
PMID 22673596 | DOI 10.1016/j.nut.2012.02.011
alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects.
In young and elderly volunteers given GHRH with or without alpha-GPC, alpha-GPC potentiated the growth-hormone response to GHRH in both groups, with a more pronounced effect in the elderly; this was an acute hormone-challenge study, not an outcome trial.
PMID 1577400 | DOI 10.1055/s-2007-1003272
Stroke & Brain-Injury Recovery Research 9 studies
Clinical research from the drug era: recovery populations, reported as research history, not as supplement claims.
Effect of Choline Alfoscerate on Cognitive Dysfunction After Mild Traumatic Brain Injury: A Single-Center Prospective Case-Control Study.
In a Korean prospective case-control study of 30 patients with mild traumatic brain injury, the 15 who received choline alfoscerate 800 mg/day for 8 weeks gained more MMSE points than the 15 controls; the choline group also started from lower baseline scores, which limits interpretation.
Reported figure: K-MMSE change +2.5 vs +0.5 points (p = 0.004)
PMID 40353278 | DOI 10.13004/kjnt.2025.21.e17
Choline-Containing Phospholipids in Stroke Treatment: A Systematic Review and Meta-Analysis.
A systematic review and meta-analysis of choline-containing phospholipids in stroke (15 studies, 8357 subjects) found citicoline did not improve neurological function or functional recovery, while choline alphoscerate improved neurological function and functional recovery on the Mathew scale and MMSE; the choline alphoscerate evidence comes largely from open uncontrolled trials.
Reported figure: citicoline NIHSS < 1 OR 1.05 (95% CI 0.87-1.27), not significant; choline alphoscerate outcomes favourable
PMID 37109211 | DOI 10.3390/jcm12082875
[Modern approaches to the diagnostics and treatment of the consequences of traumatic brain injury in children and adolescents].
A Russian article on diagnosing and treating consequences of traumatic brain injury in children and adolescents reports that a double-blind placebo-controlled multicenter randomized trial of choline alfoscerate (Cereton) showed improved cognitive function and clinical condition; the abstract provides no numeric results, so the effect size cannot be assessed from it.
PMID 35758944 | DOI 10.17116/jnevro202212206120
Role of citicoline and choline in the treatment of post-stroke depression: an exploratory study.
In a retrospective cohort of 44 post-stroke depression patients, those treated with nootropics (citicoline or choline alphoscerate) showed only small, statistically non-significant effect sizes for depression and anxiety, while SSRI-treated patients showed large significant improvements.
Reported figure: nootropic depression SRD 0.16 (95% CI -0.17 to 0.46), not significant; SSRI SRD 0.57 (95% CI 0.21-0.79)
PMID 34727752 | DOI 10.1177/03000605211055036
[Efficacy of cereton in acute ischemic stroke: results of the trial SOLNTSE].
In the Russian SOLNTSE trial, 95 patients with acute carotid ischemic stroke received cereton (choline alfoscerate) 1000 mg IV for 10 days plus standard care (50 patients) or standard care alone (45): the cereton group had greater reduction in neurological deficit and higher functional independence at discharge.
Reported figure: NIHSS reduction and Barthel independence better in the cereton group (p < 0.05)
PMID 22677763
[Efficacy of cereton in the acute period of ischemic stroke].
In 40 Russian patients admitted within 24 hours of ischemic stroke, adding cereton (choline alfoscerate) 1000 mg/day IV to basic therapy in 20 patients was followed by faster regression of neurological deficit and better cognitive and functional scores at day 21 than basic therapy alone, with no side effects observed.
Reported figure: NIHSS, Barthel, Rankin, MMSE and clock-drawing improvements p < 0.05 vs control
PMID 19365389
[The use of cereton in the rehabilitation of patients with hemorrhagic stroke].
In 40 Russian patients in late rehabilitation after hemorrhagic stroke randomized to intramuscular cereton (choline alfoscerate) 1000 mg/day for 15 days or placebo, the cereton group had significantly better recovery of cognitive function and improved cerebral blood supply and balance measures.
Reported figure: MMSE and 10-word learning better vs placebo (p < 0.05); rheoencephalographic blood supply increase p = 0.03 vs control
PMID 19894302
[Preliminary evaluation of risk and effectiveness of early choline alphoscerate treatment in craniocerebral injury].
In an uncontrolled Polish series of 23 patients with craniocerebral injury given early choline alphoscerate (intramuscular then oral for 6 weeks), 96% improved by 3 months, 14 returned to independent professional activity, and no treatment complications were observed; one patient died of pneumonia.
Reported figure: improvement in 96% of patients at 3 months
PMID 15174236
alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial.
In an open uncontrolled Italian multicenter trial, 2044 patients with recent stroke or TIA received alpha-GPC intramuscularly for 28 days then orally for 5 months: Mathew and MMSE scores improved significantly and 71% ended with no cognitive decline or forgetfulness, with adverse events in 2.14%; without a control group the improvement cannot be separated from natural recovery.
Reported figure: Mathew Scale +15.9 points in 28 days (p < 0.001); MMSE from 21 to 24.3 (p < 0.001); adverse events 2.14%
PMID 8030842 | DOI 10.1111/j.1749-6632.1994.tb12095.x
Safety & Adverse Events 8 studies
The section most alpha-GPC content hides. Both large Korean cohorts are here, including the one that found increased stroke risk. Read this section first.
Safety of L-alpha-glycerylphosphorylcholine (L-alpha-GPC) from soya phospholipids (lecithin) as a novel food pursuant to Regulation (EU) 2015/2283.
The EFSA Nutrition and Novel Foods Panel concluded that soy-derived L-alpha-GPC as a food supplement at up to 203.7 mg/day does not raise safety concerns for people over 3 years of age, deriving a NOAEL of 1000 mg/kg bodyweight/day from 90-day and teratogenicity studies while noting limitations in the submitted animal data.
Reported figure: NOAEL 1000 mg/kg bw/day; margin of exposure 111 for children over 3 and 345 for adults
PMID 42131868 | DOI 10.2903/j.efsa.2026.10008
Association between L-α-glycerylphosphorylcholine use and risk of kidney cancer: A nationwide representative retrospective cohort study.
In a propensity-matched Korean national cohort (81,970 alpha-GPC users, 409,801 non-users, followed 2011-2024), alpha-GPC use was not associated with kidney cancer risk in any subgroup or lag-time analysis.
Reported figure: adjusted HR 0.95 (95% CI 0.84-1.08)
PMID 42361543 | DOI 10.1016/j.canep.2026.103152
Safety evaluation of alpha-glycerylphosphorylcholine as a novel food.
In a Chinese novel-food safety package (acute, 90-day, teratogenicity and genotoxicity studies in rats), alpha-GPC showed no genotoxicity and no acute toxicity at 10 g/kg; at the highest 90-day dose (2000 mg/kg) females had lower body weight and raised liver enzymes, giving a NOAEL of 1000 mg/kg for female and 2000 mg/kg for male rats.
Reported figure: NOAEL 1000 mg/kg bw (female) and 2000 mg/kg bw (male) over 13 weeks
PMID 39577616 | DOI 10.1016/j.fct.2024.115123
Potential Risk of Choline Alfoscerate on Isoflurane-Induced Toxicity in Primary Human Astrocytes.
In primary human astrocytes exposed to the anesthetic isoflurane, pretreatment with 10 micromolar alpha-GPC decreased cell viability and further suppressed antioxidant gene expression versus isoflurane alone, suggesting alpha-GPC could amplify anesthetic-induced cell damage in this laboratory model.
PMID 37859347 | DOI 10.3340/jkns.2023.0208
Role of Gpcpd1 in intestinal alpha-glycerophosphocholine metabolism and trimethylamine N-oxide production.
In Caco-2 cell and mouse experiments, the intestinal enzyme Gpcpd1 hydrolyzed luminal GPC to choline, and deleting Gpcpd1 in intestinal epithelium partially abolished the rise in blood TMAO after GPC administration, mapping the pathway by which supplemental alpha-GPC raises TMAO.
PMID 39510189 | DOI 10.1016/j.jbc.2024.107965
Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years.
In a Korean national cohort of 12 million adults aged 50+, prescription alpha-GPC users had a 43-46% higher 10-year risk of total stroke than matched non-users, rising in a dose-response manner with longer use; the single most important safety signal in the alpha-GPC literature, though observational data cannot fully exclude confounding by indication.
Reported figure: matched total stroke aHR 1.43 (95% CI 1.41-1.46); ischemic aHR 1.34; hemorrhagic aHR 1.37; dose-response with duration of use
PMID 34817582 | DOI 10.1001/jamanetworkopen.2021.36008
The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis.
In hyperlipidemic Apoe-knockout mice, dietary GPC supplementation promoted atherosclerosis, shifted the gut microbiome toward TMA-producing bacteria, and activated pro-inflammatory signaling in human coronary artery endothelial cells, consistent with conversion of GPC to pro-atherogenic trimethylamine N-oxide (TMAO).
PMID 34948275 | DOI 10.3390/ijms222413477
L-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: a double-edged sword phenomenon.
In neonatal rat cardiac myocytes, 3-hour GPC treatment protected against simulated ischemia-reperfusion cell death, but 24-hour exposure caused significant cell death and increased oxidative stress across a wide concentration range: a double-edged-sword result the authors say warrants comprehensive cardiac safety testing.
PMID 31280435 | DOI 10.1007/s11010-019-03580-1
Pharmacokinetics & Dosing 8 studies
Absorption, bioavailability, half-life, and what doses the studies actually used.
Choline supplementation in preterm infants: effects of four different supplements on choline plasma concentrations.
In 32 enterally fed preterm infants randomized to 48 hours of choline chloride, choline bitartrate, GPC or egg phosphatidylcholine (30 mg/kg/day choline equivalent), all four supplements raised plasma choline to a similar extent, with GPC producing the fastest initial rise.
Reported figure: similar choline AUC (0-54 h) across supplements; GPC fastest at 6 h (p = 0.01)
PMID 41524941 | DOI 10.1007/s00394-025-03865-w
Pharmacokinetics of soy-derived lysophosphatidylcholine compared with that of glycerophosphocholine: a randomized controlled trial.
In 12 healthy men, single doses of soy-derived lysophosphatidylcholine and GPC (matched for choline) both increased plasma choline, and neither significantly elevated plasma TMAO after this single 480 mg dose, with no adverse events.
Reported figure: plasma TMAO not significantly elevated by either supplement (single dose)
PMID 38490741 | DOI 10.1093/bbb/zbae031
Different choline supplement metabolism in adults using deuterium labelling.
In 6 healthy men given four deuterium-labelled choline forms in randomized order, D9-GPC raised plasma D9-choline and D9-betaine quickly, but like the other water-soluble forms produced measurable D9-TMAO, whereas phosphatidylcholine (POPC) produced virtually none, making the phospholipid form preferable if TMAO is a concern.
Reported figure: D9-TMAO formation lower for POPC and phosphorylcholine than for choline chloride and GPC
PMID 36840817 | DOI 10.1007/s00394-023-03121-z
Differential metabolism of choline supplements in adult volunteers.
In 6 healthy men given 550 mg choline equivalents as choline chloride, choline bitartrate, GPC or egg phosphatidylcholine in randomized sequence, all forms raised plasma choline and betaine similarly, but all water-soluble supplements including GPC rapidly increased TMAO whereas egg phosphatidylcholine did not.
Reported figure: no AUC difference in plasma choline between supplements; TMAO increased rapidly after GPC but not after egg-PC
PMID 34287673 | DOI 10.1007/s00394-021-02637-6
Formulation and bioequivalence studies of choline alfoscerate tablet comparing with soft gelatin capsule in healthy male volunteers.
In healthy Korean male volunteers in a randomized two-period crossover, a new choline alfoscerate tablet was bioequivalent to the reference soft gelatin capsule (Gliatilin) after a 1200 mg oral dose, with both formulations well tolerated.
Reported figure: 90% CIs for AUC and Cmax ratios 84.51-111.98% and 83.31-104.10%, within bioequivalence criteria
PMID 31040642 | DOI 10.2147/DDDT.S193424
L-alpha-glycerophosphocholine contributes to meat's enhancement of nonheme iron absorption.
After identifying L-alpha-glycerophosphocholine as the long-sought "meat factor", researchers fed 13 women with low iron stores isotope-labelled vegetarian lasagna: adding GPC increased nonheme iron absorption, comparably to ascorbic acid at the same enhancer-to-iron molar ratio.
Reported figure: iron absorption increased with GPC (P = 0.023) and with ascorbic acid (P = 0.010)
PMID 18424594 | DOI 10.1093/jn/138.5.873
Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-L-alpha-glycerylphosphorylcholine.
In rats given radiolabelled alpha-GPC intravenously or orally, the compound was hydrolyzed in the gut mucosa and its labelled metabolites distributed widely (liver, kidney, lung, spleen and brain), with choline incorporated into brain phospholipids within 24 hours and most radioactivity ultimately exhaled as CO2.
PMID 8243501 | DOI 10.1007/BF03188793
A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers.
In 12 normal volunteers studied on three randomized occasions, a single 1000 mg intramuscular dose of alpha-GPC raised free plasma choline rapidly (peak at 15-30 minutes), with considerably higher levels than the same dose of citicoline.
PMID 1428296
Other Clinical Research 9 studies
The scattered rest of the human literature: eyes, hearing, mood and more. Included because comprehensive means comprehensive.
Choline Alfoscerate in the Treatment of Subthreshold Depression in the Elderly: A Pilot Study (CARTESIO).
In the open-label single-arm CARTESIO pilot in 17 elderly patients with subthreshold depression, 8 weeks of choline alfoscerate 1200 mg/day was followed by significant reductions in depression scores with good tolerability, but no change in cognition or apathy; uncontrolled and hypothesis-generating.
Reported figure: HAMD-17 reduction p < 0.001; GDS-15 p < 0.05
PMID 42278899 | DOI 10.3390/jcm15114037
Potential Impact of Choline Alphoscerate on Depressive Symptoms in Association with Insulin Resistance in Elderly Patients with Type 2 Diabetes.
In a 6-month double-blind trial randomizing 49 older type 2 diabetes patients with mild depressive symptoms to choline alphoscerate 800 mg/day or placebo, depression scores improved in BOTH groups with no between-group difference; only insulin-resistance-related measures (waist circumference, LDL/HDL ratio) favoured choline alphoscerate.
Reported figure: Hamilton depression change: no inter-group difference (p = 0.297); waist-reduction OR 18.28 (95% CI 2.27-461.35)
PMID 40095622 | DOI 10.3390/jcm14051664
Combination Therapy of Choline Alfoscerate With Ginkgo biloba Monotherapy in Age-Related Hearing Loss: Effects and Outcomes.
In a retrospective comparison of presbycusis patients on Ginkgo biloba alone versus Ginkgo plus choline alfoscerate, the combination group showed a slower rate of hearing decline over 15 months of audiometry follow-up.
PMID 38052524 | DOI 10.7874/jao.2023.00192
Alpha-Glycerylphosphorylcholine and D-Panthenol Eye Drops in Patients Undergoing Cataract Surgery.
In 40 cataract-surgery patients, eye drops combining alpha-GPC and D-panthenol (20 patients) improved clinical signs and confocal-microscopy measures of corneal re-epithelialization and nerve repair versus topical hyaluronic acid (20 patients), with good tolerability; a non-randomized comparison.
PMID 35711284 | DOI 10.1155/2022/1951014
Effect of Choline Alphoscerate on the Survival of Glioblastoma Patients: A Retrospective, Single-Center Study.
In a retrospective single-center analysis of 187 IDH-wild-type glioblastoma patients, continuous choline alphoscerate use for at least 12 months was associated with longer overall survival in multivariate analysis; shorter use made no difference, and the authors stress the need for prospective validation.
Reported figure: median OS 38.3 vs 24.0 months (p = 0.004); multivariate HR 0.532 (95% CI 0.314-0.900)
PMID 36294373 | DOI 10.3390/jcm11206052
Supplementary Effect of Choline Alfoscerate on Speech Recognition in Patients With Age-Related Hearing Loss: A Prospective Study in 34 Patients (57 Ears).
In a prospective case-control study of 34 hearing-aid users aged 65-85 with age-related hearing loss, 11 months of choline alfoscerate 800 mg/day improved word recognition scores while controls deteriorated, with no change in pure-tone thresholds, pointing to central speech understanding rather than peripheral hearing.
Reported figure: word recognition +4.2% vs -0.6% in controls (p = 0.035)
PMID 34149400 | DOI 10.3389/fnagi.2021.684519
Effect of Oral Choline Alfoscerate on Patients with Keratoconjunctivitis Sicca.
In a retrospective chart review of 47 dry-eye patients refractory to eyedrops, oral choline alfoscerate was followed by improved tear break-up time and symptom scores, but no change in fluorescein staining or photophobia; uncontrolled data.
Reported figure: TBUT, OSDI and VAS improved (p < 0.05, paired tests)
PMID 32456260 | DOI 10.3390/nu12051526
[Analysis of choline alfoscerate effectiveness in chronic ocular ischemic syndrome].
In 51 Russian patients with chronic ocular ischemic syndrome and cerebrovascular disease, adding choline alphoscerate to standard therapy (26 patients) was followed by faster and more stable improvement in visual acuity, visual fields and retinal light sensitivity than standard therapy alone (25 patients); non-randomized.
PMID 27213801 | DOI 10.17116/oftalma2016132273-76
Stimulation of the cholinergic neurotransmissions enhances the efficacy of vestibular rehabilitation.
In a retrospective series of 42 elderly patients with vestibular deficits and mild vascular cognitive impairment undergoing vestibular rehabilitation, the 22 who also took choline alphoscerate 1200 mg/day achieved better postural control under optokinetic stimulation and better Dynamic Gait Index scores than rehabilitation alone.
Reported figure: p < 0.05 for optokinetic postural control and Dynamic Gait Index vs rehabilitation alone
PMID 20559468
Mechanism, Animal & In Vitro 51 studies
How alpha-GPC behaves in cells and animal models: choline delivery, acetylcholine synthesis, membrane phospholipids. Preclinical by definition.
Neuroprotective Effects of Choline Alfoscerate in Experimental Diabetic Peripheral Neuropathy.
In streptozotocin-diabetic rats with peripheral neuropathy, choline alfoscerate treatment raised paw-withdrawal thresholds (less mechanical hypersensitivity), preserved sciatic nerve structure and lowered serum triglycerides, without lowering blood glucose.
PMID 42515756 | DOI 10.3390/ph19071076
Treatment with soybean lecithin-derived α-GPC (SHCog™) improves scopolamine-induced cognitive declines in mice via regulating cholinergic neurotransmission and enhancing neural plasticity in the hippocampus.
In scopolamine-treated mice, soybean-lecithin-derived alpha-GPC (SHCog, 125 and 250 mg/kg) restored short-term and spatial memory, lowered elevated acetylcholinesterase, raised choline acetyltransferase, and restored hippocampal PSD-95 and BDNF.
PMID 39765138 | DOI 10.1016/j.tice.2024.102705
Taming Microglia in Alzheimer's Disease: Exploring Potential Implications of Choline Alphoscerate via α7 nAChR Modulation.
In BV2 microglial cells exposed to amyloid-beta 1-42, alpha-GPC pretreatment antagonized the inflammatory microglial phenotype by directly activating the alpha-7 nicotinic acetylcholine receptor, evidenced by calcium influx and acetylcholine-like currents.
PMID 38391922 | DOI 10.3390/cells13040309
The Endogenous Metabolite Glycerophosphocholine Promotes Longevity and Fitness in Caenorhabditis elegans.
Endogenous GPC declines in the plasma of ageing humans, and in the nematode C. elegans GPC supplementation extended lifespan, improved exercise capacity during aging, reduced lipofuscin accumulation and inhibited reactive-oxygen-species accumulation without impairing reproduction.
PMID 35208251 | DOI 10.3390/metabo12020177
The effect of choline alphoscerate on non spatial memory and neuronal differentiation in a rat model of dual stress.
In rats exposed to combined noise and restraint stress, oral alpha-GPC 400 mg/kg for 7 days improved non-spatial memory and increased hippocampal ChAT, BDNF and neuroblast expression while reducing IL-1beta, countering stress-induced cognitive impairment.
PMID 35398024 | DOI 10.1016/j.brainres.2022.147900
Beneficial Effects of Choline Alphoscerate on Amyloid-β Neurotoxicity in an In vitro Model of Alzheimer's Disease.
In retinoic-acid-differentiated SH-SY5Y neurons challenged with amyloid-beta 25-35, pretreatment with 100 nM alpha-GPC reduced amyloid-induced toxicity and tau phosphorylation, acting through the NGF/TrkA system and preserving synaptophysin.
PMID 34102970 | DOI 10.2174/1567205018666210608093658
The beneficial effect of glycerophosphocholine to local fat accumulation: a comparative study with phosphatidylcholine and aminophylline.
In 3T3-L1 adipocytes and mice, GPC suppressed adipocyte differentiation, stimulated glycerol release (lipolysis), and subcutaneous GPC injection into the inguinal fat pad reduced fat-pad mass and adipocyte size more than phosphatidylcholine or aminophylline.
Reported figure: 22.3% inhibition of differentiation at 4 mM; two-fold glycerol release at 6 mM
PMID 34187950 | DOI 10.4196/kjpp.2021.25.4.333
Corneal absorption of glycerylphosphorylcholine.
In eye-bank corneas stored cold, GPC from the preservation medium was absorbed into corneal tissue to concentrations far above endogenous levels without detectable metabolic or physical toxicity, and corneas retained transparency, suggesting a possible role for GPC in cryopreservation.
PMID 31962097 | DOI 10.1016/j.exer.2020.107932
Efficacy of Long-Term Feeding of α-Glycerophosphocholine for Aging-Related Phenomena in Old Mice.
In old mice fed GPC long-term, the aging-related decline in expression of long-term-potentiation-related genes was reduced and beta-oxidation gene expression improved, but taste-sensitivity decline was not improved: a mixed result.
PMID 31968334 | DOI 10.1159/000504962
Neuroprotective potential of choline alfoscerate against β-amyloid injury: Involvement of neurotrophic signals.
In in-vitro models of early Alzheimer's disease, choline alfoscerate given before or after beta-amyloid insult reduced apoptotic cell death and preserved neuronal morphology, with activation of neurotrophin survival pathways proposed as the mechanism.
PMID 32343461 | DOI 10.1002/cbin.11369
Anti-diabetic effect of S-adenosylmethionine and α-glycerophosphocholine in KK-A(y) mice.
In diabetic KK-Ay mice, 10 weeks of GPC in drinking water reduced total cholesterol and triglycerides, and GPC combined with S-adenosylmethionine reduced serum glucose, leptin and food intake.
PMID 30582404 | DOI 10.1080/09168451.2018.1559721
The delaying effect of alpha-glycerophosphocholine on senescence, transthyretin deposition, and osteoarthritis in senescence-accelerated mouse prone 8 mice.
In senescence-accelerated SAMP8 mice, GPC in drinking water lowered total senescence scores at 36 weeks, decreased brain deposition of the amyloidogenic protein transthyretin, and reduced knee-joint degeneration.
Reported figure: GPC 0.07 mg/ml in drinking water
PMID 29191088 | DOI 10.1080/09168451.2017.1403883
Late treatment with choline alfoscerate (l-alpha glycerylphosphorylcholine, α-GPC) increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment.
In rats after pilocarpine-induced seizures, alpha-GPC 250 mg/kg/day started 3 weeks post-seizure for 3 weeks improved water-maze cognitive performance, reduced neuronal death and blood-brain-barrier disruption, and increased hippocampal neurogenesis; immediate 1-week treatment showed no neuroprotection.
PMID 27765578 | DOI 10.1016/j.brainres.2016.10.011
Choline and Choline alphoscerate Do Not Modulate Inflammatory Processes in the Rat Brain.
In healthy rats treated for two weeks, neither choline nor choline alphoscerate (GPC 150 mg/kg/day) changed inflammatory cytokines or endothelial adhesion molecules in frontal cortex, hippocampus or cerebellum: a null result showing GPC did not modulate brain inflammatory markers in this model (a 2024 correction to this paper exists).
Reported figure: no effect on IL-1beta, IL-6, TNF-alpha, ICAM-1 or VCAM-1 expression
PMID 28961195 | DOI 10.3390/nu9101084
l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in Zebrafish Embryo Model.
In gamma-irradiated zebrafish embryos, 194 micromolar GPC added 3 hours before irradiation significantly improved survival and reduced morphological distortion, and dampened radiation-induced NF-kB and IL-1beta overexpression.
PMID 27486826 | DOI 10.1089/zeb.2016.1269
Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine.
In rat liver mitochondria and a rat liver ischemia-reperfusion model, GPC improved complex I-linked mitochondrial respiration with lower leak respiration, and GPC administration reduced inflammatory enzyme activities and oxidative and nitrosative stress markers after ischemia-reperfusion.
PMID 27861548 | DOI 10.1371/journal.pone.0166682
Protective effects of L-alpha-glycerylphosphorylcholine on ischaemia-reperfusion-induced inflammatory reactions.
In a rat mesenteric ischemia-reperfusion model, intravenous GPC given before ischemia or before reperfusion attenuated the drop in mesenteric flow, reduced superoxide production, nitrotyrosine and xanthine oxidoreductase activity, and preserved liver ATP.
Reported figure: 16.56 mg/kg i.v.
PMID 24682350 | DOI 10.1007/s00394-014-0691-2
Cerebrovascular and blood-brain barrier morphology in spontaneously hypertensive rats: effect of treatment with choline alphoscerate.
In spontaneously hypertensive rats, 4 weeks of choline alphoscerate 150 mg/kg/day reversed the hypertension-induced increase in the blood-brain-barrier water-channel marker aquaporin-4 and partially countered brain microvessel changes, with no vasodilator effect and mixed effects on endothelial inflammation markers.
PMID 25714975 | DOI 10.2174/1871527314666150225140855
[GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED RATS].
In 24-month-old rats tested in an 8-arm radial maze, a course of Gliatilin (choline alfoscerate) 100 mg/kg significantly improved age-impaired working and reference spatial memory.
PMID 26292506
Effect of lipoic acid and α-glyceryl-phosphoryl-choline on astroglial cell proliferation and differentiation in primary culture.
In primary astroglial cultures, lipoic acid or alpha-GPC alone each up-modulated proliferation and differentiation markers, but the combination of the two showed no additional effect or even down-regulation, an unexpected non-additive interaction.
PMID 24166560 | DOI 10.1002/jnr.23289
L-α-glycerylphosphorylcholine reduces the microcirculatory dysfunction and nicotinamide adenine dinucleotide phosphate-oxidase type 4 induction after partial hepatic ischemia in rats.
In rats with partial hepatic ischemia-reperfusion, GPC 50 mg/kg before reperfusion preserved microvascular perfusion, lowered liver enzyme release, and reduced NOX4 expression, myeloperoxidase activity and HMGB1, without affecting NOX2 or TNF-alpha.
PMID 24636100 | DOI 10.1016/j.jss.2013.12.025
Radio-neuroprotective effect of L-alpha-glycerylphosphorylcholine (GPC) in an experimental rat model.
In rats given 40 Gy hemispheric brain irradiation, 4 months of oral GPC 50 mg/kg markedly decreased the radiation-induced cognitive impairment in the Morris water maze and reduced gliosis, calcification and demyelination on histology.
PMID 24880750 | DOI 10.1007/s11060-014-1489-z
Effects of cholinergic enhancing drugs on cholinergic transporters in the brain and peripheral blood lymphocytes of spontaneously hypertensive rats.
In spontaneously hypertensive rats, 4 weeks of choline alphoscerate increased expression of the choline uptake transporter and especially the vesicular acetylcholine transporter in brain and lymphocytes, consistent with increased acetylcholine synthesis, storage and release, while galantamine had the opposite effect.
PMID 22191561 | DOI 10.2174/156720512799015118
Cholinergic precursors modulate the expression of heme oxigenase-1, p21 during astroglial cell proliferation and differentiation in culture.
In primary astroglial cell cultures, alpha-GPC increased expression of the cell-cycle inhibitor p21 at both culture ages studied and slightly reduced heme oxygenase-1 (significantly only in older cultures), a mixed modulation of proliferation/differentiation markers among the cholinergic precursors tested.
PMID 22956150 | DOI 10.1007/s11064-012-0873-3
Neuroprotective effect of treatment with galantamine and choline alphoscerate on brain microanatomy in spontaneously hypertensive rats.
In spontaneously hypertensive rats, 4 weeks of galantamine or choline alphoscerate each countered brain nerve-cell loss; choline alphoscerate additionally reduced astrogliosis and restored aquaporin-4 expression, and the two drugs together had the broadest neuroprotective effect.
Reported figure: galantamine 3 mg/kg/day; choline alphoscerate 100 mg/kg/day
PMID 19304299 | DOI 10.1016/j.jns.2009.02.349
Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmission.
In rat brain, choline alphoscerate or rivastigmine alone each increased acetylcholine levels and high-affinity choline transporter binding, and their combination increased both dose-dependently, providing the preclinical rationale for precursor-plus-cholinesterase-inhibitor combination trials; plain choline had no effect.
PMID 16297435 | DOI 10.1016/j.mad.2005.09.017
Effect of treatment with choline alphoscerate on hippocampus microanatomy and glial reaction in spontaneously hypertensive rats.
In spontaneously hypertensive rats used as a cerebrovascular-disease model, 8 weeks of choline alphoscerate 100 mg/kg/day countered hippocampal nerve cell loss and astroglial reaction, while an equivalent choline dose as phosphatidylcholine (lecithin) had no effect; neither compound changed blood pressure.
PMID 16989788 | DOI 10.1016/j.brainres.2006.08.068
L-alpha-glycerylphosphorylcholine inhibits the transfer function of phosphatidylinositol transfer protein alpha.
In a biochemical study, glycerophosphocholine inhibited the lipid-transfer function of phosphatidylinositol transfer protein alpha between liposomes, with the inhibition strongest for highly anionic membranes: evidence that the molecule itself can modulate lipid-signaling proteins.
PMID 14729069 | DOI 10.1016/j.bbalip.2003.10.007
L-alpha-glycerylphosphorylcholine enhances the amplitude of the pattern electroretinogram in rhesus monkeys. A pilot study.
In a pilot study in two rhesus monkeys, intramuscular L-alpha-GPC 85 mg/kg increased the amplitude of the pattern electroretinogram within 10-30 minutes, most at low spatial frequencies, suggesting effects on retinal information processing.
PMID 10897800
Evidence for an in vivo and in vitro modulation of endogenous cortical GABA release by alpha-glycerylphosphorylcholine.
In freely moving rats and cortical slices, alpha-GPC increased endogenous cortical GABA release; the effect was blocked by the alpha-1 adrenergic antagonist prazosin, indicating noradrenergic rather than direct cholinergic mediation.
Reported figure: alpha-GPC 30-300 mg/kg i.p. in vivo; 0.4 mM in slices
PMID 8726961 | DOI 10.1007/BF02527751
Effect of L-alpha glycerylphosphorylcholine on muscarinic receptors and membrane microviscosity of aged rat brain.
In aged rats, chronic L-alpha-GPC restored the age-related loss of muscarinic M1 receptors in striatum and hippocampus and partially restored membrane fluidity, while its individual metabolites (choline, glycerophosphate, phosphorylcholine) did not.
PMID 8861196 | DOI 10.1016/0278-5846(95)00313-4
Nucleus basalis magnocellularis lesions decrease histochemically reactive zinc stores in the rat brain: effect of choline alphoscerate treatment.
In rats with unilateral nucleus basalis lesions, choline alphoscerate treatment partially restored the density and pattern of zinc-containing fibres in the fronto-parietal cortex and hippocampal mossy fibres, changes that parallel findings in Alzheimer's disease brains.
PMID 8835182
Muscarinic cholinergic receptors in the hippocampus of aged rats: influence of choline alphoscerate treatment.
In 27-month-old rats, 6 months of choline alphoscerate treatment partially countered the age-related loss of muscarinic M1 receptors in the hippocampus, with no change in M2 receptors.
PMID 7845062 | DOI 10.1016/0047-6374(94)90007-8
Choline acetyltransferase and acetylcholinesterase in the hippocampus of aged rats: sensitivity to choline alphoscerate treatment.
In aged rats, 6 months of choline alphoscerate 100 mg/kg/day did not change biochemical choline acetyltransferase activity in the hippocampus, but partially restored ChAT immunoreactivity and increased acetylcholinesterase reactivity, a mixed result on cholinergic enzyme markers.
PMID 7934207 | DOI 10.1016/0047-6374(94)90097-3
Long term choline alfoscerate treatment counters age-dependent microanatomical changes in rat brain.
In old rats, 6 months of choline alfoscerate 100 mg/kg/day countered the age-dependent loss of nerve cells and silver-stained fibres in the hippocampus and cerebellar cortex, with the hippocampus more responsive.
PMID 7972861 | DOI 10.1016/0278-5846(94)90107-4
Chronic L-alpha-glyceryl-phosphoryl-choline increases inositol phosphate formation in brain slices and neuronal cultures.
Repeated but not single alpha-GPC dosing increased basal inositol monophosphate formation and inositol incorporation into phospholipids in rat hippocampal, cortical and striatal slices and in cultured neurons, suggesting increased phospholipid and phosphoinositide synthesis rather than a single-neurotransmitter effect.
PMID 8190709 | DOI 10.1111/j.1600-0773.1994.tb01082.x
Influence of ipsilateral lesions of the nucleus basalis magnocellularis and of choline alphoscerate treatment on histochemically reactive zinc stores and on the ultrastructure of the rat frontal cortex.
In rats with unilateral nucleus basalis lesions, 4 weeks of choline alphoscerate restored the lesion-induced loss of histochemically reactive zinc stores in the frontal cortex and partially countered degenerative changes in cortical synaptic terminals.
PMID 15374276 | DOI 10.1016/0167-4943(94)00576-1
Effect of ipsilateral lesioning of the nucleus basalis magnocellularis and of L-alpha-glyceryl phosphorylcholine treatment on choline acetyltransferase and acetylcholinesterase in the rat fronto-parietal cortex.
In rats with ibotenic-acid lesions of the nucleus basalis, choline alfoscerate treatment partially restored the lesion-induced loss of choline acetyltransferase and acetylcholinesterase activity in the fronto-parietal cortex.
PMID 8152614 | DOI 10.1016/0304-3940(93)90854-e
PKC translocation in rat brain cortex is promoted in vivo and in vitro by alpha-glycerylphosphorylcholine, a cognition-enhancing drug.
In rat brain cortex, a behaviourally active oral dose of alpha-GPC transiently increased membrane-bound protein kinase C activity in vivo, and alpha-GPC promoted PKC translocation in cortical slices at concentrations as low as 50 nM with a bell-shaped dose-response.
Reported figure: in vivo effect at 600 mg/kg; in vitro effect from 50 nM
PMID 8239301 | DOI 10.1111/j.1749-6632.1993.tb23072.x
Cholinergic neurotransmission in the hippocampus of aged rats: influence of L-alpha-glycerylphosphorylcholine treatment.
In aged rats treated orally from 21 to 27 months, choline alphoscerate partially restored hippocampal ChAT immunoreactivity and acetylcholinesterase reactivity and countered the age-related loss of muscarinic M1 receptors, without affecting M2 receptors.
Reported figure: 100 mg/kg/day from month 21 to 27
PMID 8239302 | DOI 10.1111/j.1749-6632.1993.tb23073.x
Cognition stimulating drugs modulate protein kinase C activity in cerebral cortex and hippocampus of adult rats.
In rat cortex and hippocampus, alpha-GPC (like the nootropic oxiracetam) produced an early increase in membrane-bound protein kinase C activity in vivo and in cortical slices at nanomolar concentrations, supporting PKC activation as a shared mechanism of cognition-enhancing drugs.
PMID 8246681 | DOI 10.1016/0024-3205(93)90490-t
Nerve growth factor receptor immunoreactivity in the cerebellar cortex of aged rats: effect of choline alfoscerate treatment.
In 24-month-old rats, 6 months of choline alfoscerate 100 mg/kg/day increased nerve growth factor receptor immunoreactivity in the cerebellar molecular layer and Purkinje neurons, which declines with age.
PMID 8377526 | DOI 10.1016/0047-6374(93)90076-4
L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat.
In rats, oral alpha-GPC prevented and reversed scopolamine-induced amnesia in passive avoidance and dose-dependently increased hippocampal acetylcholine synthesis and release, with radiolabelled alpha-GPC converted into brain acetylcholine.
Reported figure: maximum effect at 300 mg/kg
PMID 1319912 | DOI 10.1016/0014-2999(92)90392-h
Oral choline alfoscerate counteracts age-dependent loss of mossy fibres in the rat hippocampus.
In rats treated from 18 to 24 months of age, oral choline alfoscerate 100 mg/kg/day preserved hippocampal mossy fibre area and density and left about 7% more dentate granule neurons than in untreated aged controls.
PMID 1340517 | DOI 10.1016/0047-6374(92)90075-o
Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats.
In young and aged rats, alpha-GPC reversed scopolamine-induced amnesia and improved active-avoidance performance, and in tissue experiments enhanced receptor-stimulated phosphatidylinositol signaling and restored potassium-induced calcium responses in aged animals.
PMID 1409797 | DOI 10.1016/0091-3057(92)90650-5
Behavioral effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the rat.
In 24-month-old rats with learning deficits and in rats with kainic-acid lesions of the nucleus basalis, 20 days of alpha-GPC 100 mg/kg improved learning and memory in active and passive avoidance tests.
Reported figure: 100 mg/kg/day for 20 days
PMID 1574535 | DOI 10.1016/0091-3057(92)90124-x
Effect of choline alfoscerate treatment on changes in rat hippocampus mossy fibres induced by monolateral lesioning of the nucleus basalis magnocellularis.
In rats with unilateral nucleus basalis lesions, 4 weeks of oral choline alfoscerate 100 mg/kg/day restored Timm staining of hippocampal mossy fibres and roughly halved the lesion-induced loss and deformation of presynaptic terminals.
Reported figure: presynaptic button loss reduced from about 23% to 12%; impaired buttons from about 40% to 27%
PMID 15374385 | DOI 10.1016/0167-4943(92)90021-u
Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine.
In rats, oral alpha-GPC reversed scopolamine-induced passive-avoidance amnesia with a long-lasting effect (up to 30 hours), partially counteracted the scopolamine-induced fall in hippocampal and cortical acetylcholine, and increased potassium-stimulated acetylcholine release from hippocampal slices.
Reported figure: peak effect at 600 mg/kg intragastrically, 5 h before training
PMID 1662399 | DOI 10.1016/0091-3057(91)90040-9
Age-related structural changes in the rat cerebellar cortex: effect of choline alfoscerate treatment.
In 24-month-old rats, 3 months of choline alfoscerate treatment noticeably reduced the age-related loss of cerebellar Purkinje and granule neurons and restored Nissl body and fibre density toward young-adult values.
PMID 1824122 | DOI 10.1016/0047-6374(91)90015-r
Age-related anatomical changes in the rat hippocampus: retardation by choline alfoscerate treatment.
In aged rats, 3 months of choline alfoscerate treatment counteracted the age-related loss of pyramidal and granule neurons in hippocampal CA1, CA3 and dentate gyrus and slowed the decline of Nissl substance in those neurons.
PMID 15374427 | DOI 10.1016/0167-4943(91)90059-y
Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drug.
In rats, tritium-labelled alpha-GPC reached the brain after injection and oral dosing, and alpha-GPC increased striatal DOPAC content and potassium-stimulated dopamine release, behaving as an indirect cholinomimetic that likely raises choline availability for acetylcholine synthesis.
PMID 3709792
Reviews & Landmark Papers 17 studies
Review articles, pooled analyses, and the papers that defined the field.
[Choline alfoscerate in the treatment of cognitive impairment].
A 2026 Russian review of choline alfoscerate (Cereton) in cognitive impairment summarizing the Russian and international trial base and describing the two-stage injection-then-oral dosing schemes used in Russian practice; written around a single branded product.
PMID 42133414 | DOI 10.17116/jnevro202612604148
A Friend or Foe: Understanding the Physiological Significance, Therapeutic Uses, and Potential Risks of Glycerophosphocholine-A Narrative Review.
A 2026 "friend or foe" narrative review of glycerophosphocholine covering its therapeutic uses in aging-related conditions alongside the growing evidence linking high intake of choline compounds including GPC to TMAO production and atherosclerosis risk, and noting the inconsistencies in the TMAO-harm literature.
PMID 42196986 | DOI 10.3390/nu18101526
L-α-GPC in Cognitive Decline: Mechanisms and Clinical Evidence in Neurodegenerative Disorders.
A 2026 narrative review of L-alpha-GPC in neurodegenerative cognitive decline summarizing mechanisms (cholinergic enhancement, BDNF, alpha-7 nicotinic receptor modulation) and clinical studies, and cautioning that the clinical evidence remains heterogeneous and requires large well-designed RCTs.
PMID 42199923 | DOI 10.2147/NDT.S579603
Nutritional and biological insights into natural α-glycerylphosphoryl derivatives (α-NGPs): a comprehensive review of α-GPA, α-GPC, α-GPE, α-GPI, and α-GPS.
A 2026 review of the natural alpha-glycerylphosphoryl derivative family (alpha-GPC, GPA, GPE, GPI, GPS) covering neurocognitive and growth-hormone effects of alpha-GPC, and raising an "oxidative paradox" in which supraphysiological alpha-GPC intake may induce localized oxidative stress.
PMID 42299118 | DOI 10.1080/10408398.2026.2681928
Unlocking the potential of l-α-glycerylphosphorylcholine in the food industry: From safety approvals to market prospects.
A 2025 review of L-alpha-GPC for the food industry summarizing chemical properties, pharmacology, safety assessments and preparation methods, noting new-food-resource approvals in Canada (2023) and China (2024).
PMID 39898924 | DOI 10.1111/1541-4337.70117
Unlocking the Potential of l-α-Glycerylphosphorylcholine: From Metabolic Pathways to Therapeutic Applications.
A 2025 review of GPC metabolic pathways, pharmacology and safety concluding that GPC alleviates cognitive impairment across multiple conditions and is not genotoxic, while explicitly noting that possible risks of atherosclerosis and stroke await necessary validation.
PMID 40036805 | DOI 10.1093/nutrit/nuaf008
Choline Alphoscerate: A Therapeutic Option for the Management of Subthreshold Depression in the Older Population.
A 2025 review proposing choline alphoscerate as a treatment option for subthreshold depression in older adults based on its cholinergic, dopaminergic and serotonergic actions; written before the CARTESIO pilot and the negative diabetes-depression RCT results.
PMID 40126282 | DOI 10.3390/geriatrics10020032
L-Alpha-Glycerylphosphorylcholine (L-α-GPC): A Comprehensive Review of Its Preparation Techniques and Versatile Biological Effects.
A 2025 comprehensive review of L-alpha-GPC covering preparation techniques and biological effects in animal models and human trials, spanning cognitive dysfunction, cardiometabolic effects, anti-aging and ergogenic uses, and identifying remaining knowledge gaps.
PMID 40556032 | DOI 10.1111/1750-3841.70338
Choline alphoscerate: insights between acquired certainties and future perspectives.
A 2025 review of choline alphoscerate in mild cognitive impairment summarizing established efficacy data in MCI, Alzheimer's and vascular cognitive impairment, emerging evidence on non-cognitive symptoms and sleep, and its neuroprotective effects against beta-amyloid injury (a correction to this article was published in 2026).
PMID 40842650 | DOI 10.3389/fnagi.2025.1613566
Choline supplements: An update.
A 2023 review of choline supplement forms (alpha-GPC, choline bitartrate, lecithin, citicoline) summarizing preclinical and clinical evidence for their use as acetylcholine precursors in memory and cognitive enhancement.
PMID 36950691 | DOI 10.3389/fendo.2023.1148166
Revisiting choline alphoscerate profile: a new, perspective, role in dementia?
A 2013 review of the choline alphoscerate profile concluding the compound showed benefit in patients with cognitive dysfunction in a number of clinical studies and arguing for larger carefully controlled trials, alone and combined with cholinesterase inhibitors.
PMID 23387341 | DOI 10.3109/00207454.2013.765870
Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline- containing phospholipid with a still interesting profile as cognition enhancing agent.
A 2013 review (Traini, Bramanti and Amenta) summarizing choline alphoscerate's preclinical acetylcholine-release and neuroprotection data and clinical improvements in memory and attention in dementia, while acknowledging the size and duration limits of the existing trials.
PMID 24156263 | DOI 10.2174/15672050113106660173
Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.
A 2008 review of acetylcholine synthesis, transport and release as treatment targets, explaining metabolically why free choline and lecithin failed in dementia trials while CDP-choline and choline alphoscerate produced a documented modest cognitive improvement.
PMID 18289004 | DOI 10.2174/092986708783503203
Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?
A 2007 review of cholinergic precursors in vascular cognitive impairment concluding lecithin showed no clear benefit, while CDP-choline and choline alphoscerate showed a documented modest improvement of cognitive dysfunction that cannot be generalized because of small trial sizes.
PMID 17331541 | DOI 10.1016/j.jns.2007.01.043
The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies.
A 2002 review of the cholinergic approach to vascular dementia reporting favourable cognitive effects for citicoline, choline alphoscerate and cholinesterase inhibitors, with choline alphoscerate improving cognition better than citicoline, while urging caution because the controlled trials were small.
PMID 12450245 | DOI 10.1081/ceh-120015346
Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches?
A 2001 review of cholinergic precursors in Alzheimer's disease concluding that choline and lecithin failed in controlled trials, whereas CDP-choline, choline alphoscerate and phosphatidylserine provided a modest cognitive improvement, most pronounced with choline alphoscerate, and calling for larger trials.
PMID 11589920 | DOI 10.1016/s0047-6374(01)00310-4
Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data.
The landmark 2001 pooled analysis of 13 published choline alphoscerate trials totalling 4054 patients: in 10 dementia trials (1570 patients, 854 in controlled trials) the drug improved memory and attention with results superior or equal to active comparators and superior to placebo, while the 3 stroke/TIA trials (2484 patients) were all uncontrolled and need confirmation.
PMID 11589921 | DOI 10.1016/s0047-6374(01)00312-8
- August 2026: library launched. Initial index of 144 studies, 1986 to 2026, including both large Korean safety cohorts.
