Peptides›Cognitive›Alpha-GPC

Alpha-GPC

/ Cholinergic precursor (small molecule, glycerylphosphorylcholine)

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 257.22 g·mol⁻¹

ALIAS · L-alpha-glycerylphosphorylcholine · Choline alfoscerate · Delecit (trade — Italy) · Gliatilin (trade — Italy) · GPC

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 257.22CLASS · Cholinergic precursor (small molecule, glycerylphosphorylcholine)CATEGORY · Cognitive

Tier 2. Approved in Italy and several other countries as Delecit / Gliatilin (choline alfoscerate) for cognitive disorders following stroke and for adult-onset cognitive decline. Sold as a dietary supplement in the US with no FDA drug approval. Multiple Italian RCTs, including the ASCOMALVA Phase 4 trial in combination with donepezil.

§ B · Mechanism of action

Alpha-GPC is a phospholipid metabolite that crosses the blood-brain barrier and is hydrolysed to free choline and glycerophosphate. The released choline serves as a precursor for acetylcholine synthesis in cholinergic neurons and for membrane phosphatidylcholine biosynthesis. Compared with dietary choline salts, alpha-GPC has been reported to deliver choline to the central nervous system more efficiently in animal pharmacokinetic studies.

§ C · Human clinical evidence

Tier 2. The ASCOMALVA Phase 4 trial (Rea and colleagues, interim 2015) studied alpha-GPC plus donepezil versus donepezil alone in mild-to-moderate Alzheimer disease and reported cognitive, functional, and apathy differences favouring the combination. Earlier Italian trials (De Jesus Moreno Moreno 2003 and others) reported improvement in cognitive measures in mild-to-moderate Alzheimer dementia. The Western evidence base remains modest and concentrated in Italian centres.

§ D · Primary literature

PubMed26402001Rea R et al. — Apathy treatment in Alzheimer's disease: interim results of the ASCOMALVA trial · Journal of Alzheimer's Disease · human-phase-4In ASCOMALVA Phase 4 trial, addition of choline alfoscerate to donepezil was associated with improvements in apathy and cognitive measures versus donepezil alone over 24 months.Limitations: Single-country (Italy) academic trial; relatively modest sample size; manufacturer-affiliated investigators.2015

PubMed12637119De Jesus Moreno Moreno M et al. — 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 · Clinical Therapeutics · human-phase-3-rctCholine alfoscerate 1200 mg/day for 180 days was associated with cognitive measure improvement on ADAS-Cog and MMSE versus placebo in mild-to-moderate Alzheimer disease.Limitations: Single trial; manufacturer-sponsored; not replicated outside the Italian/European literature.2003

§ F · Safety signal

Generally well-tolerated in published trials. Reported adverse events include headache, gastrointestinal upset, and insomnia. A 2021 observational analysis in a Korean health-insurance database (Lee and colleagues) reported an association between long-term alpha-GPC use and stroke incidence, prompting further pharmacovigilance discussion that remains unresolved.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The supportive trial literature is dominated by Italian academic centres and the manufacturer of the European prescription product; independent multinational replication in Alzheimer disease or vascular cognitive impairment is limited. The Korean stroke-association signal is observational and confounded by indication, but it has not been refuted and warrants caution. US supplement-market product identity and purity vary widely.