Everything below reports findings from cell cultures, isolated tissue and animals. This material is for research use only, not for human or veterinary use.
Alpha GPC is a glycerol backbone with phosphocholine at the sn-3 position. The molecule occurs in cell membranes. The useful laboratory questions are identity, choline mass fraction, stereochemistry, and the gut path from choline to trimethylamine-N-oxide.
Indexed cognition and cohort papers exist. Those human endpoints sit outside the scope of this profile. A reader who wants those files can open the reference list. This page does not quote rating scales, hazard ratios, or milligram-per-day figures from them.
Chemical identity
A glycerol carrying a phosphocholine group at sn-3. Nothing exotic sits on that frame.
| Property | Value |
|---|---|
| Systematic name | [(2R)-2,3-dihydroxypropyl] 2-(trimethylazaniumyl)ethyl phosphate |
| Common names | Alpha GPC, choline alfoscerate, choline alphoscerate, L-alpha-GPC |
| Molecular formula | C8H20NO6P |
| Average mass | 257.22 g/mol |
| Monoisotopic mass | 257.1028 Da |
| CAS number | 28319-77-9 |
| PubChem CID | 657272 |
| InChIKey | SUHOQUVVVLNYQR-MRVPVSSYSA-N |
| Stereocentres | 1, R configuration |
| Charge | Zwitterion at physiological pH |
| Choline content | Roughly 40 percent by mass |
The zwitterion
Two permanent charges sit on this molecule and cancel each other.
The trimethylammonium group carries a fixed positive charge, unavailable for protonation or deprotonation. The phosphate diester carries a negative one. Net charge is zero across the physiological range, which is what lets a molecule this polar behave better than its formula suggests.
That balance also explains the handling problems covered further down. A zwitterion with three hydroxyl-adjacent oxygens and a quaternary ammonium is aggressively hygroscopic.
Alpha GPC therefore ships poorly as a loose powder. Water from air becomes part of the weigh-out. Every later calculation then overstates water and understates the zwitterion.
Two names, one molecule
The pharmaceutical literature uses choline alfoscerate or choline alphoscerate. Search traffic uses Alpha GPC. Indexed trials use the pharmaceutical names almost exclusively.
Search only the consumer term and the entire clinical file stays hidden. That retrieval split is a naming fact. It is not a reason to quote those trials here. The same split hides tesamorelin behind TH9507. Here it runs the opposite way, because the catalogue name is the searched one and the literature name is the obscure one.
InChIKey SUHOQUVVVLNYQR-MRVPVSSYSA-N encodes the R glycerol. A flat key with no stereoblock describes a different material. CAS 28319-77-9 belongs to the defined isomer. A racemate would share the formula and the mass and fail a rotation check.
What a choline donor does
Alpha GPC delivers choline, and choline has two fates worth separating.
Start with the arithmetic, because it constrains both laboratory stocks and later TMAO chemistry. Choline makes up roughly 40 percent of the molecule by mass. A weigh-out of Alpha GPC therefore carries a defined choline load. That load is an ordinary dietary-range quantity in a form that dissolves well.
So a methods section that quotes milligrams of Alpha GPC without converting to choline millimoles has skipped a unit. The vial is not an exotic carbon skeleton. It is a choline donor with a glycerol handle.
The acetylcholine route
Choline acetyltransferase combines choline with acetyl-CoA to make acetylcholine. Choline availability can limit that reaction, so supplying more is a plausible way to raise transmitter output in a dish.
That chain is biochemistry. It is also the rationale that indexed combination papers used when they paired a precursor with a cholinesterase inhibitor [2][4]. Those papers remain cited so a reader can find them. This profile does not treat them as a protocol.
The membrane route
Most choline in the body ends up in phosphatidylcholine rather than acetylcholine. It is a structural molecule first and a transmitter precursor second.
That distinction matters for interpreting a null readout. A load that raises membrane phospholipid turnover without changing transmitter output has done something real and irrelevant to a cognition scale.
It matters even more for the TMAO question. The route that generates trimethylamine does not happen in human tissue at all. Gut bacteria perform the first step [3].
Two fates after the choline leaves
Once the phosphodiester breaks, the glycerol and the choline go different ways.
Glycerophosphate is the leftover alcohol-phosphate. Free choline is the leftover quaternary ammonium. Both belong on a certificate as named hydrolysis products. A lot that sits warm and wet will grow both peaks without changing the label.
| Species | Role | Why it appears on a certificate |
|---|---|---|
| Alpha GPC | Parent zwitterion | Intact mass 257.22 |
| Free choline | Hydrolysis product | Extra trimethylammonium |
| Glycerophosphate | Hydrolysis product | Extra phosphate-glycerol |
| Racemic GPC | Wrong isomer | Same mass, wrong rotation |
| Water | Hygroscopic load | Biases every weigh-out |
Why the 40 percent figure matters in a notebook
Forty percent choline by mass is a conversion factor, not a serving suggestion. Convert a stock to millimoles of choline before comparing it to a phosphatidylcholine feed or to a citicoline feed. Citicoline delivers choline plus cytidine. Alpha GPC delivers choline plus glycerol. Those are different reagents even when the choline millimoles match.
A laboratory that treats the two as interchangeable choline sources has mixed two nucleotides and one glyceride. Write the donor name on the tube.
Stereochemistry at glycerol C2
Natural sn-glycero-3-phosphocholine holds the R configuration at the glycerol 2-position. Chemical hydrolysis of phosphatidylcholine can retain that configuration. A fully synthetic route can scramble it.
Mass spectrometry cannot separate the racemate from the L-form. Optical rotation or chiral chromatography has to. Material sold without a rotation figure has not been shown to be the natural isomer.
Alpha GPC in a catalogue should mean the R isomer. If the certificate is silent, the vial is an unresolved glycerophosphocholine.
What NMR actually sees
Proton NMR of Alpha GPC is a short spectrum. The trimethylammonium singlet sits near 3.2 ppm and integrates for nine protons. The glycerol methine is the stereochemical reporter if a chiral shift reagent or a chiral column is not on the bench. Carbon NMR then counts the eight carbons. Phosphorus NMR sees one phosphate diester.
A lot that has hydrolysed grows a free-choline singlet and loses the diester phosphorus line. That is a cheaper first check than a full LC-MS panel. It does not replace intact mass. It does catch a wet jar.
Counterions matter on a weigh-out. Some lots hold water only. Some hold acetate or residual solvent from a recrystallisation. The zwitterion formula C8H20NO6P is the free inner salt. A certificate that quotes that formula and a different residual-solvent percent has mixed two stories. Write both on the notebook line.
TMAO, the proposed mechanism
The stroke hypothesis in the indexed file did not come from nowhere. It came from a different literature about choline.
The choline to TMAO pathway
Gut bacteria convert dietary choline to trimethylamine, and the liver oxidises that to trimethylamine-N-oxide.
Tang and colleagues established the sequence (PMID 23614584). A phosphatidylcholine challenge raised TMAO, broad-spectrum antibiotics abolished the rise, and withdrawing the antibiotics restored it [3]. That is a chemistry-and-microbiota result. The first step is bacterial. The second step is hepatic flavin monooxygenase work on TMA.
Ierardi and colleagues restated the same phosphatidylcholine path in a later note [7]. Both links have support: choline can raise TMAO, and TMAO tracks later event rates in the indexed file those authors cite. The compound-specific step, that this particular choline donor raises TMAO enough to matter, remains unmeasured.
Alpha GPC is roughly 40 percent choline by mass. The inference is direct enough that one cohort paper named it [9]. Naming a path is not the same as measuring TMAO on this lot.
What nobody has measured
No study has measured TMAO after Alpha GPC in a controlled design.
The mechanism chains two literatures. Both links have human support in the choline file [3][7]. The missing step is the donor-specific one. That gap is a chemistry question as much as an epidemiology question. A crossover with serial TMAO would close it. Nobody has run that experiment.
Two details would decide the question. Whether Alpha GPC raises TMAO more than an equivalent choline load from phosphatidylcholine, and whether the rise persists or adapts. Neither has been measured.
Note also what the pathway requires. Gut bacteria perform the first step, so the response depends on an individual’s microbiota, and Tang and colleagues showed antibiotics abolishing it entirely [3]. A choline load is not a fixed TMAO exposure across flasks or across guts.
Why this path is chemistry, not a use sentence
Trimethylamine lyase chemistry sits in the gut lumen. Hepatic FMO3 then oxidises TMA. Alpha GPC that never meets those bacteria cannot feed that path. That is a compartment statement. It is not a route recommendation.
A cell-culture dish that lacks a microbiome will not make TMAO from Alpha GPC. Anyone blaming a myotube readout on TMAO has put the enzyme in the wrong room.
The same chemistry applies to other choline donors. Phosphatidylcholine, choline bitartrate and Alpha GPC all present a trimethylammonium that a lyase can clip. They do not present it at the same rate or in the same matrix. Bile-salt micelles carry phosphatidylcholine. A dissolved zwitterion does not need that step. That difference is a reason to name the donor in a TMAO method, not a reason to treat every choline source as one reagent.
Indexed cognition papers
A 2003 monotherapy paper and a later Italian combination series dominate the efficacy file. A smaller mixed-design paper sat downstream of that series [11].
This profile does not quote their rating scales. It does not quote their milligram-per-day figures. Those sentences turn a research article into a use document.
The naming fact still matters. Those papers say choline alfoscerate. A search that uses only Alpha GPC will miss them. The reference list keeps the PMIDs so a reader can open the file without this page becoming a protocol.
ASCOMALVA published repeated interim looks from one group. That publication pattern is a caution about one dataset, not a laboratory identity result.
Indexed cohort papers
Two nationwide cohort studies asked a vascular question in the same South Korean insurance database and reached opposite directions [9][12].
Neither is a trial. Both are large, recent, and peer-reviewed. Comparator choice changed between them. Lee and colleagues compared prescribed users against a general population over 50 [9]. Kim and colleagues compared users against non-users who all carried a mild cognitive impairment code [12].
Those designs cannot identify a vial. They cannot replace a choline assay. This profile leaves their hazard ratios unread. The papers stay in the list [9][12].
A dose-ordered observational gradient is still not a binding constant. Confounders can arrange themselves in order of exposure. The 2021 authors closed by asking for mechanism work rather than declaring causation [9]. TMAO is the mechanism they named. It remains unmeasured on this compound [3].
How to read a paper on Alpha GPC
Four questions separate an informative laboratory paper from an uninformative one.
What isomer did the certificate show? Formula C8H20NO6P and mass 257.22 do not prove the R glycerol. Rotation or a chiral method has to.
Was choline load reported in millimoles? Alpha GPC is about 40 percent choline by mass. A paper that skips that conversion cannot compare donors.
Was TMAO measured? No cognition paper in the indexed set reports it. Until one does, the efficacy file and the choline-oxide file cannot share a common quantity [3].
Which name did the methods use? Choline alfoscerate, choline alphoscerate and Alpha GPC are one molecule. A paper that switches names mid-stream has not changed the reagent. A paper that switches to citicoline has.
What the record does not establish
Indexed cognition work enrolled people with dementia or cognitive impairment [1][2] and [11]. This page does not extend those files to any other population.
Nobody has published a laboratory dose-response that this profile can quote as a use ladder. The milligram figures in the indexed protocols stay in those papers [1][4].
The vascular question in the insurance file is open [9][12]. No randomised design has measured vascular endpoints on Alpha GPC. This page does not settle it.
The mechanism connecting a choline donor to TMAO remains inferred for this exact molecule, since no study has quantified TMAO on Alpha GPC [3].
The efficacy literature is also concentrated. One 2003 paper and one Italian group’s repeated interim analyses account for most of it, with one later mixed-design paper from elsewhere [1][11]. Concentration is a bibliographic fact. It is not a reason to quote their scales here.
Verifying research material
Two properties dominate the practical handling, and both follow from the structure.
Identity
Mass is 257.22 average and 257.1028 monoisotopic. One stereocentre sits at the glycerol 2-position in the R configuration, corresponding to the natural sn-glycero-3-phosphocholine.
Stereochemistry is the check worth insisting on. The racemate and the natural L-form share a formula, a mass and a fragmentation pattern, so mass spectrometry cannot separate them. Optical rotation or chiral chromatography has to, and material sold without a rotation figure has not been shown to be the natural isomer.
Free choline and glycerophosphate are the expected hydrolysis products and belong on a certificate as named impurities.
PubChem CID 657272 is the defined zwitterion. A certificate that omits intact mass has not finished. A certificate that omits rotation has not finished the isomer.
Hygroscopicity
This compound is notoriously hygroscopic, which is why it usually ships as a solution or a capsule rather than loose powder.
Solid material pulls water from humid air fast enough to turn tacky during a weighing session. Every subsequent weighing then overstates the water and understates the compound, biasing an entire experiment in one direction. Aliquot on receipt. Keep the jar sealed with desiccant. Let containers reach room temperature before opening so condensation does not form inside.
A dry-fill capsule format sidesteps most of this, at the cost of needing the capsule content assayed rather than assumed.
Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.
Water is not an exotic impurity here. It is the default failure. Karl Fischer or loss on drying belongs next to the HPLC area percent. On a hygroscopic zwitterion, that water number changes the molar amount in a weighed sample more than typical related-substance levels do.
Solution work changes the failure mode. Alpha GPC in water hydrolyses slowly toward free choline and glycerophosphate. Cold and low pH slow that split. Warmth and residual phosphatase activity speed it. Prepare stocks close to the assay. Do not treat a month-old aqueous stock as the same reagent as the powder.
A second handling question is the capsule fill. Dry-fill avoids some hygroscopic mess. It adds a shell and a fill-weight claim. Assay the fill. Do not assume the label mass is the zwitterion mass.
Kimera publishes third-party certificates of analysis for every lot in its COA database. Laboratories source Alpha GPC as a cholinergic precursor. It appears alongside piracetam where a racetam is under study, or selank and phenibut where a different neurotransmitter system is the comparator. Related work appears in the nootropics category.
Common questions about Alpha GPC
What is Alpha GPC? Choline alfoscerate. Formula C8H20NO6P, mass 257.22 g/mol, CAS 28319-77-9. A zwitterion with one R stereocentre and about 40 percent choline by mass.
Is choline alfoscerate the same thing? Yes, along with choline alphoscerate. Those are the names the indexed literature uses, and searching only the consumer term misses that file.
Does this page report cognition or stroke outcomes? No. Indexed papers remain in the list [1][9] and [12]. This profile stops at chemistry, TMAO path logic and lot checks.
What is the TMAO concern as chemistry? Gut bacteria convert choline to trimethylamine, which the liver oxidises to TMAO [3][7]. Nobody has measured TMAO after this specific donor.
Why do two cohort papers disagree? Most likely the comparator. One compared users against a general population over 50 [9]. The other compared users against non-users who all had the same diagnosis code [12]. Neither result identifies a vial.
Why is the powder so difficult to weigh? It is strongly hygroscopic. The solid absorbs atmospheric water quickly enough to bias successive weighings in the same direction.
Can mass spectrometry prove the natural isomer? No. The racemate shares the formula and the fragments. Rotation or a chiral method has to separate them.
Summary of the evidence
Identity: choline alfoscerate, C8H20NO6P, 257.22 g/mol, CAS 28319-77-9. A zwitterion with one stereocentre, roughly 40 percent choline by mass. PubChem CID 657272 and InChIKey SUHOQUVVVLNYQR-MRVPVSSYSA-N close the record.
Function in a cell: a choline donor. Acetylcholine synthesis can use that choline. Phosphatidylcholine synthesis uses most of it. Those are different fates.
TMAO path: choline to trimethylamine to TMAO, with the first step microbial [3][7]. Unmeasured for Alpha GPC as the donor.
Indexed cognition papers exist and stay in the list [5][6]. This page does not quote their scales or their milligram figures [8][10].
Indexed cohort papers disagree on a vascular question [9][12]. This page does not quote their hazard ratios.
Handling: hygroscopic solid. Water bias is the default weighing error. Hydrolysis to free choline and glycerophosphate is the default chemical error.
Status: supplied for laboratory research use only.
References
- De Jesus Moreno Moreno M. 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. Clin Ther. 2003;25(1):178-193. PMID 12637119. DOI
- Amenta F, Carotenuto A, Fasanaro AM, Rea R, Traini E. The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer’s disease with cerebrovascular injury: interim results. J Neurol Sci. 2012;322(1-2):96-101. PMID 22959283. DOI
- Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575-1584. PMID 23614584. DOI
- Amenta F, Carotenuto A, Fasanaro AM, Rea R, Traini E. The ASCOMALVA trial: interim results after two years of treatment. J Alzheimers Dis. 2014;42 Suppl 3:S281-S288. PMID 24898643. DOI
- Rea R, Carotenuto A, Traini E, Fasanaro AM, Manzo V, Amenta F. Apathy treatment in Alzheimer’s disease: interim results of the ASCOMALVA trial. J Alzheimers Dis. 2015;48(2):377-383. PMID 26402001. DOI
- Carotenuto A, Rea R, Traini E, et al. The effect of the association between donepezil and choline alphoscerate on behavioral disturbances in Alzheimer’s disease: interim results of the ASCOMALVA trial. J Alzheimers Dis. 2017;56(2):805-815. PMID 28035924. DOI
- Ierardi E, Sorrentino C, Principi M, Giorgio F, Losurdo G, Di Leo A. Intestinal microbial metabolism of phosphatidylcholine: a novel insight in the cardiovascular risk scenario. Hepatobiliary Surg Nutr. 2015;4(4):289-292. PMID 26312245. DOI
- Traini E, Carotenuto A, Fasanaro AM, Amenta F. Volume analysis of brain cognitive areas in Alzheimer’s disease: interim 3-year results from the ASCOMALVA trial. J Alzheimers Dis. 2020;76(1):317-329. PMID 32508323. DOI
- Lee G, Choi S, Chang J, et al. Association of L-alpha glycerylphosphorylcholine with subsequent stroke risk after 10 years. JAMA Netw Open. 2021;4(11):e2136008. PMID 34817582. DOI
- Carotenuto A, Fasanaro AM, Manzo V, Amenta F, Traini E. Association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in the treatment of depression in patients with Alzheimer’s disease. J Alzheimers Dis Rep. 2022;6(1):235-243. PMID 35719710. DOI
- Lee W, Kim M. Comparative study of choline alfoscerate as a combination therapy with donepezil: a mixed double-blind randomized controlled and open-label observation trial. Medicine (Baltimore). 2024;103(24):e38067. PMID 38875437. DOI
- Kim HK, Park S, Kim SW, et al. Association between L-alpha glycerylphosphorylcholine use and delayed dementia conversion: a nationwide longitudinal study in South Korea. J Prev Alzheimers Dis. 2025;12(4):100059. PMID 40155153. DOI
Alpha GPC is sold for laboratory research use only. Not for human consumption, nor medical, veterinary, or household uses.
Literature retrieved from PubMed.
